First published in Great Britain in 2023

by Canongate Books Ltd, 14 High Street, Edinburgh EH1 1TE

canongate.co.uk

This digital edition published in 2023 by Canongate Books

Copyright © Sally Adee, 2023

The right of Sally Adee to be identified as the author of this work has been
asserted by her in accordance with the Copyright, Designs and Patents Act
1988

British Library Cataloguing-in-Publication Data

A catalogue record for this book is available on
request from the British Library.

ISBN 978 1 83885 332 7

Export ISBN 978 1 83885 334 1
eISBN 978 1 83885 333 4
For Ann
 CONTENTS

Introduction

Part 1 – Bioelectricity in the Beginning

1 Artificial vs Animal: Galvani, Volta, and the battle for electricity
2 Spectacular pseudoscience: The fall and rise of bioelectricity

Part 2 – Bioelectricity and the Electrome

3 The electrome and the bioelectric code: How to understand our body’s
electrical language

Part 3 – Bioelectricity in the Brain and Body

4 Electrifying the heart: How we found useful patterns in our electric signals
5 Artificial memories and sensory implants: The hunt for the neural code
6 The healing spark: The mystery of spinal regeneration

Part 4 – Bioelectricity in Birth and Death

7 In the beginning: The electricity that builds and rebuilds you
8 At the end: The electricity that breaks you back down

Part 5 – Bioelectricity in the Future

9 Swapping silicon for squids: Putting the bio into bioelectronics
10 Electrifying ourselves better: New brains and bodies through
electrochemistry
Acknowledgements
Notes
Index
 INTRODUCTION

I was back at the checkpoint. The traffic moved as normal. Bored-looking

soldiers waved through civilians on foot, dusty cars, and rickety trucks full
of livestock and produce.
Then the Humvee in front of the gate blew up.
Out of the eye-searing blast, I made out the figure of a man running at me,
full-speed. He was wearing an explosive vest. I shot him.
A flash of movement to my left revealed a sniper who had just begun to
raise his gun. I got him too.
Now a mass of people – maybe seven? – breached the checkpoint, all of
them with machine guns. I scanned the group to determine who was closest,
who I needed to take out first.
Three more men darted across the roof of a low building that overlooked
the checkpoint. I saw them anyway. Bang-bang-bang.
There weren’t any more after that, only the quiet whistle of the desert
wind. Still I waited, calm and alert, scanning the horizon.
The lights came up and the tech walked in.
‘What’s wrong?’ I asked.
‘Nothing,’ the tech said, surprised. ‘You’re done.’
‘What do you mean, done?’ I was disappointed. I couldn’t have been inside
the simulation for more than three minutes. ‘Can I keep going?’
‘No, it’s over.’
‘How many did I get?’ I asked, as I surrendered my rifle and headgear,
cutting off the flow of electricity that had been coursing through my brain.
She shrugged. ‘All of them.’
I was in a grey office park in southern California, nowhere near any
checkpoint in any conflict. In my hands was an M4 close-combat rifle
modified to fire CO2 cartridges, and while those can pack a bit of a kick, they
don’t do any damage. The people I was firing at were not real; they had been
dreamed up by the programmers of a wall-sized army training simulation.
 What was real was the electrical stimulation device on my head. I had
signed up to have a few milliamps from a 9-volt battery sent through my skull
to test if it would make me a better shot. The scientists’ hypothesis was that
the electrical current would recalibrate a different kind of electricity in my
brain: the naturally occurring bioelectric signals that the nervous system relies
on to communicate. By overpowering these delicate natural streams with an
artificial shock to the executive part of my brain, they hoped to wrench my
mind into a state of alertness and concentration – enough to turn this desk-
slumping journalist into a battle-ready assassin.
Back in 2011, I was a writer and editor for New Scientist. It was a dream job
for which I had recently moved across the ocean. Before that, I reported on
microchips and neurotech for a US-based engineering magazine called IEEE
Spectrum, an inevitable position for someone with my childhood. My dad is a
former radio engineer who filled the basement of our family home with
intriguing contraptions – circuit boards, wires wrapped in candy colours, a
soldering iron – and a fairly comprehensive mid-twentieth-century back
catalogue of a science fiction magazine called Analog. Part of the reason I
became a science writer was to watch the ideas from those old sci-fi stories
undergo metamorphosis into real science.
That would also explain why I was obsessed from the moment I first
caught wind of this mind-boggling military brain-stimulation experiment. I had
seen this technique – known as transcranial direct current stimulation (tDCS)
– bubbling around the science press for a few years. Among other intriguing
results, it seemed to improve everything from treatment-resistant depression
to poor maths skills. This flow of electricity, according to the scientists who
wired me up, might alter the strength of connections between the neurons in
my brain, making them more likely to fire in concert. That natural
synchronisation is the basis of all learning, and speeding it up with an electrical
field would theoretically accelerate the rate at which I could learn a new skill
(in this case, turning me into James Bond).
When I caught my first glimpse of this strange new use for electricity in
2009, it was the stuff of obscure medical trials and secret military projects.
Today, the notion of wearing an electrical stimulator on your head isn’t as
foreign as it seemed back then; it’s certainly the kind of thing you can imagine
someone in Silicon Valley doing for a little extra mental edge, alongside
intermittent fasting or microdosing psilocybin.
But it’s not just about boosting your brainpower with a volt jolt – there are
many other ways electricity is being used to treat the ailments of body and
mind. Take deep brain stimulation, a treatment of last resort for Parkinson’s
disease, in which two electrodes the size and shape of uncooked spaghetti are
slid into the deepest parts of your brain to quiet the disease’s destructive
symptoms. In the wake of its fantastic success, scientists are testing the
treatment on other ailments, including epilepsy, anxiety, obsessive-compulsive
disorder, and obesity. Then there’s the rise of ‘electroceuticals’: these rice-
grain-sized electrical implants, clamped around nerves in the body, supposedly
interrupt their signals, and in rat and pig trials, appeared to reverse diabetes,
hypertension, and asthma. In 2016, outstanding early results in human trials –
in which they seemed to reverse rheumatoid arthritis – convinced Google’s
parent company, Alphabet, to team up with a pharmaceutical multinational on
a £540 million venture to tap into your body’s electrical signals, to try to treat
diseases like Crohn’s and diabetes.1
So when I saw the opportunity to be a guinea pig in a US Defense
Department project, of course I jumped at it, and I wasn’t disappointed: my
own experience with tDCS was transformative. Getting my neurons slapped
around by an electric field instantly sharpened my ability to focus, and by the
transitive property, my sharpshooting skills. It also felt incredible – like
someone had finally hit the off switch on all the distracting negative self-talk
that had, until that moment, been the main provider of my mind’s elevator
music. I was a convert, and I wanted to preach the positive power of electricity
to anyone who would listen.
When my story detailing the experience was published in New Scientist, it
went viral. The timing was perfect: in the early 2010s, Silicon Valley magical
thinking was ascendant and everyone aspired to becoming a Soylent-drinking
productivity goblin. Transhumanists were desperate for new ways to upgrade
their sad meat bodies. Electricity was now poised to join the suite of tools that
could help people override their fundamental human limitations. The article
became a fixture on ‘DIY tDCS’ forums where amateur neuroengineers traded
circuit designs and equipment specs that would let them overclock their brains
in their basements. Media coverage saw promise and peril: the producers of
science podcast Radiolab were intrigued by tDCS’s ability to engineer artificial
zen. The writer and anthropologist Yuval Noah Harari put me into his book
Homo Deus as a cautionary tale, a dire warning of humans trying to engineer
themselves into gods. South Korean documentary filmmakers wanted me to
speculate on whether neurostimulation would transform the human condition.
One interviewer called me the Avon Lady of tDCS.
 Not that I was the first journalist to look into the promise of manipulating
the body’s natural electricity in this way. Since the early 2000s, thousands of
studies – many carried out at prestigious universities like Oxford, Harvard, and
Charité – have pointed to tDCS as a way to improve the mind. A little bit of
electricity enhanced memory, mathematical skills, attention, focus, and
creativity – it had even shown promise for post-traumatic stress disorder and
depression. The data and the headlines had been accumulating for years, but
my gonzo experience took it out of dry clinical stuff and into the ‘it happened
to me!’ category. Seeing dollar signs in the combination of intriguing lab results
and growing public interest, enterprising start-ups quickly began to hawk their
own commercial versions of the brain-enhancing headgear I had road-tested.
These cute wearables, which would set you back a few hundred dollars, had
little in common with the £10,000 gear in the Defense Department’s suitcase.
Nonetheless, they were soon adopted by people looking for any bit of extra
mental edge, including high-level athletes. Before every game, the Golden State
Warriors – a team so unbeatable that it has been accused of ‘ruining basketball’
– wore them in practice sessions to zap their brains into the zone.2 The US
Olympic ski team used headsets in training drills, raising accusations of ‘brain
doping’.3
And then came the inevitable backlash. Sceptics started to wonder if this
was all a bit too good to be true. Curing depression? Better concentration?
Longer memory? Improved algebra? Soon a wave of studies began to debunk
the previous glut of hopeful findings: to prove that the currents involved in
tDCS could have no possible effects on neurons, one group electrically
stimulated a cadaver and concluded that it was pseudoscientific bullshit;
another looked at all the effects across hundreds of tDCS studies – a meta-
analysis – and concluded that if you averaged out all the effects, you’d end up
with nothing.
They had history on their side. The sceptics pointed to 200 years of
electro-foolery, in which quacks claimed that their various electrical belts, rings,
baths and other contraptions could cure everything from perennial ailments
like constipation and cancer to complaints of a more distinctly Victorian
flavour, like the loss of ‘male vigour’ and excessive masturbation. To the
critics, here was proof that the people hawking the benefits of electrical brain
stimulation today had no more science behind them than the charlatans selling
electric penis belts in the 1870s.
A consensus emerged that tDCS was, if not outright quackery, certainly in
the same postcode. Were they right? Had I become the latest victim of the
placebo effect? Had I fallen for reheated, 200-year-old snake oil polished to a
silicon shine?
I had started to wonder about this myself. Still mesmerised by the glow of
that first tDCS nirvana, I had quickly set out to sample the cranial delights
offered at other labs. I found that the experimental psychology department at
Oxford was investigating tDCS’s potential role in boosting mathematical
ability. As this was not, uh, a strong suit, it would be the perfect way to check
my potential placebo bias – a repeat experiment to see just how good electrical
stimulation was.
I swanned into that place expecting virtuosity. I envisioned my hand
casually dancing across a blackboard, populating it with the calibre of
equations you see in Good Will Hunting and A Beautiful Mind. I was excited. But
when I left the lab several gruelling hours later, the closest thing to a light-bulb
moment was the glow of my red face, humiliated by several hours of what had
essentially been a public and very poorly executed exam. While wearing a silly
electrode cap. I had failed to unlock my inner maths genius. Maybe it really all
was bollocks.
But if it was quackery, why did it still seem to work across such a wide
swathe of ailments? Surely all those doctors couldn’t be wrong? At the time I
was seeing medical electricity research everywhere – and not just the
comparatively harmless little tDCS jolts. Invasive stimulators implanted in the
spine were helping paralysed people walk again; implanted in the brain, they
were helping people with untreatable depression get out of bed; implanted in
the vagus nerve they were curing rheumatoid arthritis. What was it about
electricity? What mechanism could it be using to heal the body? I couldn’t get
the question out of my system: what was the relationship between electricity
and biology?
If this technology worked, I had no idea how. So I decided to work it out.
Once I fell properly down this rabbit hole, it took me a decade to climb back
out. I’ve spent the last ten years of my life being electrified by these questions
and their answers – and now I want to pass that jolt onto you.

We Are Electric is about the natural electricity that surges through all our
bodies, and the truly head-spinning ways the world will change if we learn how
to manipulate it. Over the next few hundred pages I will teach you about the
substance that courses through all living things, underpinning their every move
and intention. This natural electrical current predates nervous systems and
even humanity itself; it was coursing through the bodies of our ancestors long
before the first fishy mutants even squelched onto dry land. It is the most
ancient thing about us. It is among the most ancient things about life itself.
My brief foray into professional marksmanship is just one example of the
promise and peril of harnessing our body’s natural electricity. We are
fundamentally electrical creatures, but the full extent of our electrification
would shock you. It is hard to overstate how wholly and utterly your every
movement, perception, and thought are controlled by electrical signals. This is
not the electricity that comes from a battery or the kind that turns on the
lights and powers the dishwasher. That kind of electricity is made of electrons,
which are negatively charged particles flowing in a current.
The human body runs on a very different version: ‘bioelectricity’. Instead
of electrons, these currents are created by the movements of mostly positively
charged ions like potassium, sodium, and calcium. This is how all signals travel
within the brain and between it and every organ in the body via the nervous
system, enabling perception, motion, and cognition. It’s fundamental to our
ability to think and talk and walk and why our knee hurts after a fall, and why
the scraped skin heals. It’s what makes gummy bears taste sour, why we can
pick up a glass of water to wash away the taste, and how we know we were
thirsty in the first place.
The stuff that comes out of your wall socket is created by a power plant.
For the stuff in your body, the power plant is you. Every one of the 40 trillion
cells in your body is its own little battery with its own little voltage: when it’s at
rest, the inside of a cell is (on average) around 70 millivolts more negatively
charged than the extracellular soup outside. To keep it that way, the cell is
constantly shuttling ions in and out of the membrane that surrounds it, always
striving to maintain that -70mv. All of this may sound very petite to you,
somewhat beneath your notice. And, yes, at the scale of our lives, a difference
of 70 millivolts is insignificant; it’s about one thousandth of the amount of
electricity required to power a hearing aid. But from a neuron’s perspective, it
is anything but. When a nerve impulse comes roaring down a nerve fibre,
channels open in the neuron and millions of ions get instantly sucked through
them into and out of the extracellular space, taking all their charge with them.
The electrical field generated by this mass migration of charge works out to
about a million volts per metre, which at that scale would feel like passing an
entire bolt of lightning from one of your outstretched hands to the other. That’s
what it feels like to be every neuron in your body, every moment of your life.
 Biologists have known for a long time that these kinds of bioelectrical
signals are responsible for all communication between the brain and the
nervous system: you can think of them as the telephone wires that help the
brain’s command centre communicate with your muscles to operate your
limbs.
But bioelectricity isn’t confined to our brains. Over the past couple of
decades it has become clear that these signals are pressed into service by every
cell in your body, not just those that govern your perception and motion.
Each of your skin cells has its own voltage, which it combines with
neighbouring cells to generate an electrical field. You can even measure your
skin’s electricity with a voltmeter: just stretch a piece of skin and connect it to
electrodes and the ‘skin battery’ will light up a light bulb. You could power the
same bulb with a prostate battery. Or a breast battery. When that field is
disrupted by injury, you can feel it. That tingling when you bite your tongue or
the inside of your cheek? It’s the wound current, calling to the surrounding
tissue to send help.
Similarly, the cells in your bones are electric. Your teeth are electric. Your
organs are electric – and so is the coat of epithelial tissue that hugs each one.
Blood cells too. Every single one is a microscopic power plant generating a
tiny voltage to communicate within and among themselves.
We used to think those non-nervous-system cells mainly used bioelectric
signalling for trivial janitorial and maintenance tasks – for example, waste
disposal and energy management. But new research is making it increasingly
clear that they do far more. You and I are so much more electric than is
commonly acknowledged.
Recently it has been discovered that electrical signals also send out beacons
as we grow in the womb to guide us into the eventual shape we will take – two
arms, two legs, two ears, a nose. When this signal is interrupted in utero, things
go terribly wrong, so scientists are now working out ways to prevent
physiological birth defects by retuning our electrics. And what we can do for
birth, we can also do for death: cancer cells have their own unusual voltage,
and recent evidence indicates that they use electric signalling to communicate
about their host environment. Disrupting these signals could keep cancer cells
from metastasising.
Nor is this natural electricity confined to us animals – the same signals
have been detected in everything from algae to E. coli. Plants use them to send
messages across far-flung parts of them-selves, warning of predators and
turning on defences. Fungi use them to communicate when their delicate
tendrils have sussed out good sources of food. Bacteria use them to make
decisions about when to grow their communities into antibiotic-resistant
strongholds. Even organisms we haven’t quite figured out how to
taxonomically classify – we shove them into an all-purpose box labelled
‘protists’ – use these electrical communication signals.
I tell you all this to underscore that ‘bioelectricity’ is no mere metaphor, no
elegant stretching of a humdrum biochemical truth. You and I are literally
electric. The basis of all life is electric. When our cellular battery runs out, we
all die.
So what if we learned how to control the switch?

If you still can’t quite get your head around this (or remain suspicious of my
enthusiastic contentions), you are not alone. The entire history of bioelectricity
has been marked – and in some ways defined – by the scepticism levelled at
the researchers from both the physics and biology establishment.
History is filled with tales of the uphill battles biologists faced when trying
to suggest that biological phenomena have electrical underpinnings. Today,
looking at EEG readouts of the brain’s activity is commonplace, but you might
not be aware of the ridicule its inventor, Hans Berger, endured – or that he
ended up dying by suicide in 1941 before he could see how his device changed
the world. Even the most quotidian electrical functions of electricity in the
body were only accepted after a knock-down, drag-out fight; in the 1960s,
Peter Mitchell spent ten years and a great deal of his own money to build his
own lab to convince the scientific establishment that electricity is central to the
way a cell generates energy. (He was one of the few to live long enough to see
his ideas achieve acclaim, receiving the Nobel Prize for Chemistry in 1978.)
Maybe all this scepticism can be traced to the contentious battle that
attended bioelectricity’s origin story. Luigi Galvani’s discovery in the late
eighteenth century that electricity is what lets us move our muscles is perhaps
the original electro-controversy: you may have heard of his experiments
zapping frogs, but you might not know that doubts about his findings started a
scientific war that divided all of Europe. This origin story of bioelectricity
profoundly shaped the way subsequent generations of scientists would
approach the topic, not least by shaping the structure of science itself. As a
result, the scientific knowledge of the electrical underpinnings of life is now
scattered across a wide range of disciplines, many of which think the others are
peddling poppycock.
 Even today, many biologists probably don’t know the whole story of
bioelectricity. In 1995, when Mustafa Djamgoz, a cancer researcher at Imperial
College London, first proposed his theory that electrical signals were involved
in cancer, his colleagues openly dismissed his ideas. Even now, with research
awards piling up around him, Djamgoz frequently finds himself re-explaining
his research – and needing to start from scratch because sometimes the same
concept that elicits a ‘well, obviously’ from one researcher sounds like science
fiction to another.
This reflects a set of calcified notions embedded in the framework of
science: biologists stick to biology, leaving the study of electricity to the
physicists and engineers. They just don’t speak the same language. ‘If you
major in biology, you get maybe half a semester of physics, if that,’ says
another cancer biophysicist, Richard Nuccitelli. ‘You don’t even touch
electrical engineering.’ And forget about computer science. This might seem
like an obvious and unproblematic division of labour, but it means aspiring
PhD students in physics are taught about Tesla and his alternating currents,
but not about the bioelectricity running through their own bodies – and
biology students get neither. This tacit assumption that each field should ‘stay
in their lane’ has been putting limitations both on biology and scientific
advancement for decades. What we need is a new framework to bring the
body’s different electrical parameters under one roof and study them
coherently, together.
Call it the electrome.

The identification of the genome and microbiome proved crucial steps to

understanding the full complexity of biology, but some scientists think it’s now
time to plot the outlines of the ‘electrome’: the electrical dimensions and
properties of cells, the tissues they collaborate to form, and the electrical
forces that are turning out to be involved in every aspect of life. Just as
decoding the genome led us to the rules by which information like eye colour
is encoded in our DNA, bioelectricity researchers predict that decoding the
electrome will help us to decipher our body’s multi-layered communications
systems and give us a way to control them.
Over the past ten to fifteen years, experiments have suggested that not
only can we decrypt this code – we may even be able to learn to write it
ourselves. Researchers are looking for precise ways to flip the circuits inside
our cells that are responsible for everything from healing to regeneration to
memory. When healthy cells turn cancerous, for example, their electrical
signalling changes radically. But restoring these electrical signatures to normal
has kicked tumour cells into reverse, to become healthy once again. Other
experiments indicate that certain patterns of electrical activity in the brain
form specific sensory experiences, and that these may be recorded and
overwritten. This could help create advanced prosthetics that a person can feel
as fully as they can feel the skin they were born with. If cells really do carry
different kinds of messages in their bioelectrical communications, then
cracking their bioelectric code might solve some problems that have remained
unmoved by all the genetic and chemical interventions we’ve thrown at them.
It would be like opening the electrical box and being able to rewire our
systems as we like.
If it were to become possible to manipulate bioelectricity at its source, the
consequences would be staggering. Could we interpret these codes well
enough to fix our biology when it breaks? Some bioelectricity researchers go
as far as to say learning the rules of this software could render our bodies and
minds as programmable as hardware. They’ve mooted all kinds of possibilities:
editing people’s electrical code to increase intelligence; to reprogram
troublesome personalities; to regrow amputated limbs; or to remap the body’s
blueprint altogether. If we are truly electric, then we should all be
programmable at the level of the cell.
But what will happen when we begin to use our knowledge of the
electrome to get better grades instead of cure cancer? The gene-editing
technology CRISPR ushered in a flurry of worries about designer babies, and
our ability to edit the bioelectric code will be much the same. In one study, a
simple tweak to the electrome caused functional eyes to grow on a frog’s butt,
and in another prompted a worm to grow two heads.4 There is a clear
relationship between our electrome and the shape our bodies take – from
frogs to worms to humans – so we need to do much more research before
someone grows themselves a third eye for social media clout.
Bioelectricity research could all too easily be misappropriated by that vague
but undeniable urge to see humans as occupiers of inferior meat bodies that
could only be improved by the addition and substitution of hardware and
software. You know, the idea that someday we’ll pop our consciousness into
the unblemished silicon Heavens of the Cloud. So what limitations should we
place on upgrading or altering humans? Who will govern the rules on
remapping the body’s electrical wiring? What if every country’s department of
defence put their soldiers through the same training I had done in California?
 This book will help you understand bioelectricity, both in the brain and
nervous system where it has traditionally been understood to work, and in the
broader and more unexpected contexts it is now being found. It will illuminate
why we have been applying artificial electricity to tease out how the biological
kind works. You’ll meet the researchers moving beyond artificial electrical
stimulation to build new implants that can talk to our bodies in their own
language – from robots made out of frog cells to new electronic implants
made from shrimp chitin. If we are going to try to manipulate the human
body, the least we can do is manipulate it on its own terms – terms that were
honed by millions of years of evolution, and not with headgear we invented.
We have arrived at a new stage of bioelectricity. ‘With bioelectricity, we are
now at the point where astronomy was when Galileo invented the telescope,’
says Djamgoz, one of the cancer researchers gazing into the unknown. If the
nineteenth century was referred to as the ‘electric century’, the twenty-first
century could go down in history as the bioelectric century.
 PART 1

Bioelectricity in the Beginning

‘Consider: the hero endures; even his downfall
merely foretells his eventual rebirth.’
Rainer Maria Rilke, ‘First Elegy’

N ormally, it’s difficult to muddle together a coherent story out of all the
complex mixtures of culture and history that go into making
something the way it is today. But in the case of the confusion about
bioelectricity, there’s an identifiable chain of causality: a savage battle that
helped split science into the constituent disciplines we see today, pitting
biologists and physicists against one another in a death match that ultimately
determined who gained custody of electricity. Biology lost, physics won, and
the consequences would ripple through the next 200 years of science. This
original schism profoundly shaped the way subsequent generations of
scientists approached the idea of electricity in biology.
 CHAPTER 1

Artificial vs Animal:
Galvani, Volta, and the battle for
electricity

A lessandro Volta was astonished. In his hands he held an early print of a

manuscript whose author claimed to have solved an ancient mystery:
what is the substance that courses through all living things, underpinning their
every move and intention?
The answer: electricity.
Volta – a compactly built striver, prone to high, flamboyant collars, whose
encroachment of thick black hair was engaged in furious battle with his
forehead – felt himself uniquely qualified to evaluate this author’s claims. A
little over a decade earlier, in 1779, he had been elevated to Chair of
Experimental Physics at the University of Pavia, after devising a new tool that
dispensed a ready supply of static shocks. It had seen wide adoption by other
scientists (and foreshadowed the device that would later cement his name in
history), but their smattering of weak plaudits wasn’t enough. Volta wanted
more acclaim. He deserved more acclaim. He had climbed the ranks, toured
the most important scientific centres, and built himself an influential social
network of patrons comprised not just of scientists, but politicians and others
in the top strata of Italian society. He was on the cusp of establishing himself
as one of the global authorities on the controversial, wildly glamorous, and
brand-new study of the mysterious phenomenon of electricity.
Electricity was – is – a force of nature, whose mysteries were then just
beginning to yield to scientific inquiry. No one understood very much at all
about this invisible fluid. It shocked people, it sometimes killed them from the
sky, and it was still very much a matter of debate whether it was the same stuff
electric fish used to stun their prey. Electricity was also just then in the process
of emerging out of the realm of party tricks and ludicrous speculation (a
standard-issue claim was that men with strong electricity could produce sparks
during sexual intercourse). The first rudimentary tools had only recently been
developed to contain this wild stuff for serious scientific investigation and
experimentation. Their inventors were eighteenth-century science’s version of
rock stars. Volta was among them, and had acquired a reputation as a rising
star among the scientists who were decoding the mysteries of electricity into
empirical truths. Some of his fellow physicists were even starting to refer to
him as the ‘Newton of electricity’.1
But now this author, the anatomist Luigi Galvani, claimed to have found a
biological variant.
Galvani was an uptight bumpkin from an Italian state that had only
recently begun to acquire the equipment to bring it up to speed with the
current century. A pious obstetrician whose manuscript was full of
unsophisticated terminology. This person claimed superior knowledge of the
stuff that had confounded the smartest men in philosophy and science?
You can sense in the manuscript that Galvani knew the magnitude of the
claim he was staking. ‘We could never suppose that fortune were to be so
friendly to me, such as to allow us to be perhaps the first in handling, as it
were, the electricity concealed in nerves,’ he wrote in the preface, with a
trepidation that bordered on foreshadowing.2 Indeed, the claim would
eventually rain down ruin.
How could Galvani’s claim – that the body is animated by a kind of
electricity – have been so controversial? To understand why Volta became so
incensed, we need to understand how far biology lagged behind physics in the
late 1700s.
The scientific revolution in Europe had upended scientists’ understanding
of the physical world by tearing down received wisdom and replacing it with
testable laws and predictive equations. Copernicus and Galileo plucked our
planet from the centre of creation and set it into an unremarkable corner of
the cosmos. Kepler discovered the laws governing how the planets moved
around the newly central sun. And from these, Newton deduced the law of
gravity, and extrapolated how things fall down to Earth.
Biology, on the other hand, discovered few new insights of this
magnitude.3 A promising century ended in an impasse for the study of living
things. Microscopes allowed physiologists to examine the minutiae of bacteria,
blood cells, and yeast. Anatomists developed detailed maps of the nerves that
infiltrated every extremity of the body. It was even understood that these
nerves were closely involved in our ability to move our limbs. But how? In the
late 1700s, scientists still knew next to nothing about the mechanism that
allowed humans to walk and talk and wiggle their fingers and toes, to feel or
scratch an itch. How did the immaterial soul direct the motions of the animal
machine? No one had the faintest idea.
To say the seventeenth-century understanding of this phenomenon was
stuck in the dark ages would be an understatement. It had become stuck much
earlier than that – with Claudius Galen, a brilliant physician and philosopher
influential in second-century Rome.4 He kicked off 1,500 years’ worth of
philosophical musings about what was flowing through our bodies to make us
think and move.
Galen’s conjectures were aggregated from centuries of Aristotelian thought
and refined with the help of a host of dissected cadavers. Nerves, he
concluded, are hollow tubes that send man’s will by way of ethereal substances
called pneuma psychikon – ‘animal spirits’ – to be executed in his limbs and
muscles; and that is ‘animal’ not in the zoological sense, but in the sense of
anima, the Latin translation of psyche, the Greek word for vitality. These spirits,
Galen proposed, are produced in a complex series of interactions inside the
body, starting in the liver, distilling in the heart, reacting with inhaled air, and
finally being sent to a staging area in the brain.5 When motion was required,
the brain would function like a hydraulic pump to deploy these animal spirits
into the hollow nerves for distribution to all the body’s feeling and moving
parts. When they flowed thus from brain to muscle, the spirits created
contractions there. When they flowed in the opposite direction, they carried
sensation.
Apart from increasingly baroque refinements, this dogma remained largely
unchallenged for at least the next 1,300 years. Any theoretical advances in the
field came to depend not on experimental probes, but on philosophical
reasoning. For example, in the mid-1600s, René Descartes – the progenitor of
mind–body dualism – conjectured that instead of ‘fire air’ the constitution of
animal spirits was probably closer to a liquid, like water driving machinery.
Medical scientists didn’t fare much better. The Sicilian physiologist and
physicist Alfonso Borelli proposed that rather than being watery, animal spirits
were in fact a highly reactive alkaline ‘marrow’ – in his parlance, Succus nerveus,
or nerve juice – that squeezed out of the nerves at the slightest perturbation.
When this juice reacted with the blood in the muscle, it would cause the
surrounding tissue to boil.
 These interpretations all ran into the same problem – with the invention of
the microscope at the turn of the seventeenth century, it soon became
abundantly clear that nerves could not be hollow. That meant there was no
room for animal spirits or nerve juice to be the substances governing our
limbs. But while these early microscopes were powerful enough to rule out
tubes, they were still too weak to probe nerve structure more precisely. This
left a crucial question unanswerable: how could anything be transported
through a body without the help of tubes? New theories rushed in to fill the
vacuum.
Lack of evidence opened the debate to all comers, from the sublimely
credentialled to the sublimely questionable. Isaac Newton suggested that the
brain’s messages travelled along the nerves by vibration, the way you might
pluck a guitar string. At the other end of the spectrum was the conjecture of a
spa physician in Bath (these were doctors who took up residence at spas, then
at the height of their popularity in England, to prescribe exact drinking and
bathing regimes – for a robust fee, of course): David Kinneir claimed in a 1738
tract that, as the animal spirits were carried in the blood, taking the waters at
the spa would help to unblock the vessels that carried them.6
It’s worth noting that before the nineteenth century, science was a lot less
fussy about its academic boundaries. There was less of a demand back then on
the people who studied the natural world to squeeze themselves into rigid
disciplines, largely because these didn’t yet exist. All that would come later. In
fact, scientists weren’t even called scientists. People who studied the natural
world referred to themselves as natural philosophers, or sometimes
experimental philosophers. The ultimate archetype was Alexander von
Humboldt, who travelled the world studying whatever took his fancy. Men like
him, and Galvani, were free to investigate whatever piqued their interest,
which could (and did) range from bone structure to comparative anatomy to
electricity.
Especially poorly defined were the distinctions between the physical and
life sciences. Cross-field mobility was the norm. Try to categorise people who
studied biology in the eighteenth century and you’d be forced to include
everyone from radical theologians to physicists. One thing was clear, though.
Medics – who were charged with dispensing practical remedies – did not enjoy
high status, owing to an increasing awareness of the gap between their
scientific airs and their actual ability to treat the sick.
A new hope

By the 1800s, we knew little more about our bodies than we had a full
millennium earlier. Meanwhile, the scientific revolution had taken the
understanding of electricity from strength to strength.
Like animal spirits, electrical phenomena had been observed for centuries
without generating great insight. The Ancient Greeks, for example, had
noticed strange stones that seemed to pull metal to them as if by an invisible
force. They had seen that when lightning struck people, it often killed them.
Electric eels were known to deliver a fulsome shock to their prey. Then there
was amber – the insect-trapping resin that also had a strange tendency to
attract bits of dust and fluff, the same way the stones attracted metal. Give the
amber a vigorous little rub, you might get a little zap and see a spark. But
before the seventeenth century, all these observations had not been compiled
into any kind of explanatory framework.
In fact, electricity got its name long before we understood how it was
involved in any of the above. The word was coined in 1600 by William Gilbert,
who – in keeping with what I mentioned earlier about the disciplines –
identified as a physician, physicist, and natural philosopher. He borrowed from
the Ancient Greek word elektron, for amber, owing to that material’s unique
ability to reliably elicit the magic spark.
The scientific revolution vastly upgraded the tools to investigate the
phenomenon. In 1672, Otto von Guericke invented the first device that made
it possible for scientists to generate electricity themselves: an ‘electrostatic
generator’ was a glass globe you could rub with silk to accumulate a small
amount of electrical charge. Touch it and you’d get a zap. (This, incidentally, is
where we get the phrase ‘static electricity’. The globe trapped electricity on its
surface so it wouldn’t go anywhere – it didn’t move. It was in stasis.)
Electrostatic generators allowed the accumulated electricity to be dispelled in
bigger jolts than amber, and that allowed people for the first time to decide
how, when, and where to direct the jolts. More machines followed, some
making it easier to charge the generator by having hand cranks, so your arms
wouldn’t get tired from all that rubbing glass with silk. Bigger glass tubes
yielded stronger jolts. The shock they generated was weak, but it was enough
to start a century of parlour-game science, from the ‘kissing Venus’ – an
electrified woman whose kisses stung gentlemen’s lips with a trivial zap – to
young boys charged up to attract bits of paper and other flotsam as if by
magic.
But all of these generators had the same problem: the very act of touching
these sources of accumulated static electricity released it all in one go (which is
also what’s happened when touching your doorknob zaps you with a sharp
spark of pain). There was no way to store up a large quantity of electricity for
later use.
About a century after the first electrostatic generator, several scientists
separately converged on the idea of a special jar that could siphon the
mysterious invisible substance from a generator and store it for later. To avoid
the thorny question of paternity, the new invention was dubbed the Leyden jar,
an indirect credit to Pieter van Musschenbroek, who did a lot of the early work
in this Dutch city. Scientists competed to see who could concentrate the most
electricity in their jar, because of course they did, and this had exactly the
unfortunate consequences you might expect. When van Musschenbroek
stuffed his Leyden jar to capacity, rather like overpacking a suitcase, it
promptly exploded on him. The shock was enough to send the temporarily
paralysed physicist to bed for two days.
As people got better at stuffing these increasingly capacious vessels to
capacity, Leyden jar demonstrations grew progressively more dramatic, from a
crowd of 200 monks connected by lengths of iron wire and shocked by a
single Leyden jar, to a practical joke in which a specially designed wine glass
was electrified for the amusement of picnic guests (less fun for its unfortunate
target).7 Though high society loved these demonstrations, even they agreed
that electricity was at best a novelty, and no one could quite deduce how this
circus of wonders might prove useful . . . until the mid-1740s, when a Scottish
electric showman called Dr Spencer sent his apparatus to the Philadelphia
residence of a young Benjamin Franklin.8
Franklin is often credited with single-handedly turning the carnival of
electricity into a science. And while it is a bit more complicated than that,
Franklin’s famous kite demonstration did begin the unification process that
proved that different electrical phenomena – lightning, amber, electrostatic
generators – were just different manifestations of the same ethereal substance.
Franklin – famous polymath and politician – was among the vanguard of
investigators trying to develop a grand unified theory of electricity that would
link ‘natural electricity’ (lightning) to the stuff produced by generators and
stuffed into Leyden jars (‘artificial electricity’). He attached a key to a long
string, suspended by a kite, during a lightning storm. If he could charge a
Leyden jar with the proceeds of a lightning storm, his point would be proved.
It was a stupendously dangerous experiment, but it worked so well that kids
are still forced to read about it in school. Upshot: lightning was electricity.
Franklin’s experiment was hugely consequential and helped pave the way
for a new understanding that was formalised into a branch of science, whose
practitioners referred to themselves as electricians. (This word carried a rather
more glamorous connotation back then – you can think of eighteenth-century
electricians as the ‘rocket scientists’ of their day.) What’s more, there was now
an understanding of electricity as an invisible fluid that could be collected in a
jar, cross vast distances, and travel along strings, hollow or not.
What else was electricity? By 1776, people had begun to wonder if this
‘immaterial fluid’ wasn’t germane to those animal spirits everyone had been
wondering about. That year, the notion got its first bit of supporting evidence
when John Walsh experimented with an electric eel.
Walsh was a classic natural philosopher: colonel, MP in the House of
Commons, all-round rich person. He moved in the same circles as Franklin,
who was just starting to cultivate an obsession with electric fish. After their
electrical organs had been described, Franklin became convinced that the
shock the creature delivered was another manifestation of the phenomenon of
electricity, so he convinced Walsh to ‘devote his scientific energies’ (read: a
boatload of his ample fortune) to devising experiments that would prove ‘fish
electricity’ was real.9
The way to do that was to put an electric fish into a dark room and get it
to deliver its jolt – in the hope that doing so would yield a visible spark. That
would be the smoking gun. Incredibly, it seems Walsh was able to do it. Several
historical accounts by people deep in the audience at his 1776 demonstration
reported this convincing evidence that electric eels were, in fact, electric. The
British Evening Post reported ‘vivid flashes’.
While the experiment didn’t provide any direct evidence of a link between
‘fish electricity’ and anything that might be involved in human processes, the
idea was out there nonetheless: a form of electricity might be at work in the
action of nerves and muscles. If an eel could make a spark, perhaps we could
create our own internal sparks.
And that’s how electricity found Luigi Galvani.

The man who wanted to know God’s secret

Historians don’t know very much about Luigi Galvani’s family and youth. We
do know that he was born in 1737 in the Papal State of Bologna, a wealthy and
progressive state of Italy. According to the historian Marco Bresadola, Galvani
was born into a merchant family; his father, Domenico, was a goldsmith on his
fourth wife (Barbara) and second round of children by the time Luigi entered
the world.10 The Galvanis had enough money to send more than one of their
children to obtain a university education, which was not an inconsiderable
expense. But having a scholar in the family was a mark of social standing and
prestige for the merchant classes, so Domenico trotted his kids off to school.
Luigi was initially opposed to this fate. He was a dreamy child who
preferred family life to Bolognese student antics. What he liked most was
spending time in conversation with the monks at a monastery near Bologna,
who were tasked with counselling the dying in their final hours.11 Galvani was
fascinated by the insights the monks brought back from their time with people
at the edge of life and death. There, Galvani also absorbed the values and
ideals of the progressive Catholic Enlightenment, including the reigning Pope’s
theories of ‘public happiness’. Instead of focusing on ritual and splendour, as
many of his predecessors had, the progressive Benedict XIV tried to inspire
his citizens’ devotion by actually improving their lives, which took the form of
civil engineering projects like public drainage, but also improvements to the
education system, including stocking universities with the latest tools, including
electrical ones.12 He redefined faith as charitable action, not competitive
superstition.
This philosophy resonated with the young Galvani, and when he was a
teenager, he asked to join the order. However, his family convinced the monks
to talk him out of it, eager to divert this obviously gifted child onto a more
socially mobile track. So Galvani withdrew his inquiry and instead enrolled at
the University of Bologna to study medicine and philosophy. (He also studied
chemistry, physics, and surgery.) His father was right about his potential –
Galvani would go on to write twenty theses just about the structure,
development, and pathology of bones. After obtaining his doctorate, Galvani
began to research and lecture in anatomy at the university. Though not a
natural extrovert, he was a popular lecturer.13 He was one of the first
professors to enliven his talks with experiments, and his enthusiasm was so
infectious and his teachings so accessible that students from the neighbouring
arts academy often crowded into the room. Galvani was awarded a fast
succession of academic positions and honours at the University of Bologna,
and soon held a concurrent appointment with the Institute of Sciences of
Bologna, one of the first modern experimental institutions in Europe.
 But he would never quite lose sight of the road not taken – according to all
accounts, he remained a devout Catholic to the end of his life. If he couldn’t
devote himself to God in the monastery, he at least wanted to do it in the
laboratory. He lived his principles as best he could, turning his work into an
expression of his devotion. In addition to his post at the university, he became
a practising physician at the local hospital. He gave preferential treatment to
people in extreme poverty – especially women. As an obstetrician, Galvani
nurtured a deep, abiding obsession with creation. More than anything he
wanted to understand the scientific underpinnings of how God had given
humans the spark of life.
Galvani was in the ideal place, at the ideal time. Founded in 1088, not only
was the University of Bologna the oldest university in Europe, it was also the
most progressive and forward-thinking. For example, the university had
recently promoted Laura Bassi, its first female lecturer in experimental physics.
Bassi was a prodigy who taught Newtonian physics from her home laboratory
and established ties with electricians all over the world, including Benjamin
Franklin and Giambattista Beccaria, who were considered the leading electrical
theorists of the time.14 This network ensured the university was at the
vanguard of this important new phenomenon. Unlike some of his
contemporaries, Galvani was in no way scandalised by women in authority or
in the sciences writ large; while no one could attach the anachronistic label of
feminist to him, he was impatient with the idea that it was ‘laughable’ to take
instruction from women. For example, he was nonchalant about his
collaborations with the wax sculptor Anna Morandi, whose exquisite
anatomical models he used to teach his anatomy class,15 even as some
colleagues blanched at the idea that a woman might have anything to teach
them.16 Untouched by such prejudices, Galvani attended many of Bassi’s
lectures, and soon she and her husband, the medicine professor Giuseppe
Veratti, became his mentors.
At the height of his influence, Giambattista Beccaria sent them his
textbook, in which he – like Franklin – was beginning to outline his own grand
unified theory of electricity. Beccaria cautiously explored the idea that perhaps
natural electricity could be present in animals, having read John Walsh’s
explosive new publication detailing the anatomy of electric fish. Bassi and
Veratti began to encourage their protégés to zap animals with Leyden jars,
offering up Bassi’s lab for electrical tests on the hearts, intestines, and nerves
of frogs.
In Bassi’s lab, Galvani grew increasingly obsessed. He began conflating
animal spirits with the electric fluid in his lectures. In one anatomy talk on
causes of death, Galvani claimed it was rooted in the extinction of ‘that most
noble electric fluid on which motion, sensation, blood circulation, life itself
seemed to depend’.17
While many scholars were beginning to converge on this kind of
interpretation, they tiptoed around the conclusion cautiously, loaded as it was
with unscientific associations. The more practical problem was that there was
no experimental way to test the hypothesis. Still, Galvani was transfixed by the
notion that electricity – the stuff in lightning – might be the same mechanism
by which God had given breath to man and all other creatures. He was equally
transfixed by the notion that he could be the first to discover this facet of
God’s beneficence.
So, in 1780, he created a research programme on the role of electricity in
muscular motion, and then set about building a home laboratory that would
allow him to spend more time on these experiments. The lab contained an
electrostatic machine, a Leyden jar, and other more recently invented variants
on this electrical equipment.
From there, he began to experiment on frogs. Why frogs? Their nerves are
easy to locate, their muscle contractions are easy to see, and can continue up to
forty-four hours after the frog has been carved into the grisly configuration
that Galvani referred to as his ‘preparation’. Graphic illustrations of the
amphibian experiments suffuse all of Galvani’s publications. One shows a frog
with its head and midsection almost entirely missing, save for the exposed
gossamer strings of the two crural nerves that still connect its legs to its
spine.18 In others, the frogs are cut in half below the upper limbs, then skinned
and disembowelled. Only their legs remain, joined to each other by a nub of
spine. In another, Galvani and his scientific collaborators, Giovanni Aldini (his
nephew) and Lucia (his wife) stand in his basement lab, surrounded by dozens
of these flayed corpses.
This very particular method of preparing his frogs – from which Galvani
never deviated – was inspired by Lazzaro Spallanzani, one of the most
important naturalists of the time and Galvani’s frequent correspondent.
Spallanzani’s specifications made it extremely easy to distinguish cause and
effect. With everything but nerve stripped away, there could be no confusion
about what happened when you put electricity into a muscle or nerve.
Galvani started his research with a series of experiments designed to help
him understand why electrical current from artificial sources caused muscle
contractions. Applying a zap to a muscle obviously caused the muscle to
twitch, but by what mechanism? At first he simply repeated previous
experiments, touching an electrical contact to various parts of the frog’s body.
To send the electricity from the generator into the specific parts he wanted to
target, he used wires and other metal objects called arcs, connected to the
source of external electricity speared into various parts of the frog.
Usually the results fell in line with his expectations . . . until one day they
didn’t. That day, a frog jumped even though there had been no contact
between it and a generator. Galvani had been touching the exposed crural
nerve of the frog as it lay on its plate. At the same moment, standing about six
feet away, Lucia brought her finger close to the machine, which unexpectedly
elicited a spark. The frog twitched. Galvani was shocked. In the absence of the
usual connections between generator and frog, he could not conceive of any
obvious way the electricity could have been transmitted into the dead animal.
How could it have twitched without any external electricity to animate it?
No existing hypothesis offered any satisfying explanation, and from that
moment on Galvani was ‘inflamed’, as he would later write in his manuscript.19
He began obsessively repeating variations on the experiment, using any
available source of ‘artificial’ electricity – Leyden jars, electrostatic generators –
and moving the frog by turns closer and farther away. The frog jumped every
time.
This led Galvani down a few blind alleys. First he thought there was some
kind of atmospheric electricity in the lab that built up in the frog and was then
released when the frog’s leg was touched. In 1786, Galvani decided to set up a
new experiment to try to get the same result from a different source of
electricity. In a somewhat grotesque echo of Franklin’s lightning investigation,
he set up the experiment that has come to define him in the public
imagination. He hung flayed frogs by hooks from the metal railings of his
terrace, their muscles connected to a long metallic wire pointing skyward as
black clouds gathered and thunder pealed. Sure enough, the distant lightning
had the same effect on the frogs dangling from the metal railing as did the
artificial spark: their legs kicked a zombie can-can. (Decades later, this led to
Galvani’s enduring nickname of ‘frog dance master’.)
He decided that due diligence required him to do the same experiment on
a clear day. Despite it being a sunny day, every now and then, the frogs’ legs
would kick anyway. Galvani checked the sky. No sign of ‘stormy atmospheric
electricity’. Galvani approached the frogs. After watching their contortions for
some time, he began to realise that their jiggles coincided not with storms, but
rather with the movements of the brass hooks clanking against the metal
railing. He walked over to a frog and pressed the hook from which it was
suspended against the railing. The frog’s leg contracted. He let go. The frog’s
leg went slack. He pressed again, and again, and each time he did so, the frog
legs responded as if on command.
The fact that it jumped whenever the hook was manipulated suggested
that there was something inside the frog itself, maybe a kind of lightning all its
own. Or a Leyden jar, as Galvani speculated later. This could change
everything.
Galvani spirited the frogs down to his lab, now seeking escape from any
trace of distant lightning, which was what he assumed was inflaming their
nerves just as the distant spark in his prior experiment had done. He laid one,
still impaled on its hook, onto a metal plate, far from any electrical machine.
The leg jumped. You can feel the tension and excitement in Galvani’s
manifesto as he describes this experiment. There was no possible source of
external electricity – he had removed all of them. This could mean only one
thing: proof that the electrical impulse was coming from inside the animal
itself. Or, as he put it, the mechanism that allows the body to act ‘at the
direction of the soul’. It’s the first time in the document – after pages
cataloguing his many experiments – that he dares to spell out the phrase
‘animal electricity’.20
But he didn’t publish right away. Scientist, Catholic monk, and Galvani
biographer Brother Potamian ascribed this to his solid character: ‘He had not
that intense desire for publicity that causes smaller men to rush into print with
their embryonic discoveries the moment they get their first distant glimpse of
a new truth.’21 It took another half decade before he had satisfied himself that
there could be no other explanation for the phenomenon. In January 1792,
Galvani published his results in a fifty-three-page letter he entitled ‘De viribus
electricitatis in motu musculari’ (‘On the effect of electricity on muscular
motion’). It appeared in Commentarii, the official publication of the Bologna
Institute of Sciences, printed in Latin and disseminated only to a small
circulation. Still, it spread like wildfire. Historians believe Alessandro Volta
obtained an early copy22 – it would explain why he was able to undermine it so
quickly.

The electrician with the ambition

Alessandro Volta’s circumstances were not entirely unlike Galvani’s. He had
grown up in Como, a small city in Lombardy on the shores of Lake Como,
where his family were minor nobility. The Volta money came from land and
property revenues, and Alessandro and his brothers had inherited a fair bit
more from a wealthy relative. The family owned several estates in Como and
Milan.23 Volta could have just enjoyed his money and indulged his curiosity as
an amateur natural philosopher, as was fashionable at the time, but he chafed
at the prospect of an obscure existence of provincial comfort. While he
formally adhered to Catholicism, his first priority was ascension into the ranks
of the natural philosophers, whom he venerated as the heralds of a new
enlightened age. ‘The new age is exploding “blind superstition” and the
people’s deliria of old times,’ he wrote when he was sixteen, in a bombastic
paean to science.24 Echoing the general contempt for theoretical physiology –
with its animal spirits and nervous juices – Volta hailed the physical sciences,
with their testable hypotheses, as ‘the useful sciences’.
In particular, the emerging science of electricity appeared to him a
manifestation of the triumph of the Age of Reason over superstition. In his
view, Franklin’s proof that lightning was an electrical phenomenon, for
example – not caused by ‘the element of fire’ as the ancient superstitions had it
– showed that modern natural philosophers had unquestionably established
their superior understanding of the world. Volta wanted more than anything to
rise to the rank of natural philosopher, but not just an academic ‘letterati’.
Volta coveted the title of electrician.
He devoured the readings of the stars among them: Franklin,
Musschenbroek, and Giambattista Beccaria, who along with Bassi had
introduced Franklin’s ideas to Europe. To infiltrate this eminent clique, Volta
took an unusual approach: he began to write to them. Often. At the time,
addressing leading figures like these without credentials or connections was
considered quite bold. He was only eighteen, and yet was inviting comments
on a juvenile theory of electricity, as if he were a professor casually engaging in
collegial chat with equals. Eventually, he posted his lengthy thesis to Beccaria.
It took Beccaria a year to respond, and when he finally did, the sole
missive was a print of a recent paper, in which he had laid out his latest new
theory of electricity, a tortured derivation based on the friction of different
substances and their respective inclination to ‘give’ or ‘receive’ electric fluid.
However, his hypothesis had been politely ignored by other influential
electricians of the time. This had probably smarted Beccaria enough, but to
then be faced with the gall of a young upstart Volta pointing out that it
disagreed with his own (totally uncredentialled) new theory of electricity would
have been the final straw. After a few more fruitless exchanges, a clearly
affronted Beccaria ‘invited’ Volta to ‘maintain an everlasting silence on the
topic of electricity’.25
Volta gamely turned the subject of subsequent letters to other topics, but
inwardly seethed at the disdain. So when he brought up his theory with
another member of his rapidly growing network of aspirational
correspondents, he was open to any suggestions. Paolo Frisi – who shared
Volta’s generally underwhelmed reaction to Beccaria’s idea – advised Volta
that, rather than trying to engage with him in yet more letters, he should ‘place
as much emphasis on scientific instruments as on controversial theory’.26
By that time, Volta was nurturing a new ambition: to become not just an
electrician but a professor of electrics. For that, he would first need to become
famous. He got to work on a new apparatus that would cement his reputation
by proving his theory about the role of attraction in electricity: the
electrophorus, a new tool that provided a ‘perpetual’ source of electricity.
Perpetual was maybe too strong a word, but in a considerable improvement on
Leyden jars, the electrophorus could deliver 100 zaps before it would need to
be recharged, and you could even use a Leyden jar to recharge it instead of
faffing around with amber and silk. ‘Superb and useful’ were the words
lavished on Volta by Carlo Firmian, his most important political patron at
Pavia. He did not hold back: ‘Doing honour to your Country, and to all of
Italy, Mother of the Sciences and the Arts.’ A few months later, at the age of
thirty-four, Volta was chair of experimental physics at the university, and yet he
still hadn’t attained the level of respect he so longed for.
One reason for this was that two other experimental philosophers had
invented something rather like the electrophorus a few years before, and it
strained credulity to imagine Volta had never heard of it or them. Such
suspicions were not assuaged by the fact that Volta – always more of an
instrument man than a theory man – could never satisfactorily explain how it
worked, or by what laws it was governed. When confronted, he hummed and
hawed about producing a paper – but while he (very slowly) worked on writing
it up, he realised that, actually, he might never need to publish the thing. What
actually mattered was that the invention had already buoyed his reputation as
an electrician. Thanks to the well-connected social and professional network
Volta had fostered, the electrophorus was sent to electricians in cities from
London to Berlin to Vienna. Apart from a few unappeasable dart-throwers,
most other electricians didn’t care about a theory as long as it yielded a tool
that helped them do better science. But while some of those were now calling
him ‘the Newton of electricity’, the dart-throwers never entirely went away,
sneering at his flimsy paper – which he had published despite its continued
lack of convincing explanation27 – and continuing to keep alive the low-key
rumour that he had stolen the credit for the invention of the device. He
couldn’t shake it off for sixteen years, not even through his invention of a truly
game-changing tool, the condensatore. This could detect, not generate,
electricity. It was the most sensitive detector ever built.
Yet still his critics derided him as the inventor of ‘amusants electriques’:
electrical amusements.28 This was the moment that, in 1791, Volta – defensive,
prickly, and a bit piqued – first read a copy of the Commentarii.

Volte-face

Initially, Galvani’s manuscript delighted Volta. Though the electrician should

have been put off by his prejudices against physiologists, when he repeated
Galvani’s experiments for himself, he became convinced. That spring, he
enthused that ‘I have changed my mind [about the idea of animal electricity]
from incredulity to fanaticism’. Immediately, he wrote a paper in response to
Galvani’s manuscript, introducing it in the spring of 1792 as ‘one of the great
and brilliant discoveries, which deserves to be considered defining an era in the
physical and medical sciences’. Concluding his paper, Volta wrote that Galvani
has ‘all the merit and paternity of this great and stupendous discovery’.29
But this full-throated approval would not last. By his next publication, a
mere fourteen days after the first one, Volta’s ardour had cooled
substantially.30 He casually put forward an alternative explanation for the frog-
leg contractions – it was the metals Galvani had used, he said, that were solely
responsible for the electric charge – and accused Galvani of being ignorant of
some fundamental laws of electricity. Volta had seen how materials could
respond to a far-off electrical source without contact being necessary. Perhaps,
he began to wonder, if Galvani had been aware of this law, he would have
correctly identified the material on the hooks as the cause of the contraction
rather than some electricity intrinsic to the frog.
Volta wasn’t the only one who went from hot to cold. The Italian
physician Eusebio Valli visited the French Académie des sciences to
demonstrate Galvani’s experiments there.31 Valli had been among the first to
publish a supporting paper on animal electricity, in which he wrote that
‘Galvani’s discovery’ had robbed him of ‘sleep during several nights’. After
witnessing the demonstrations, the Académie launched a series of replications,
their usual approach for putting promising or controversial research through
its paces.32 It appointed several established scientific authorities to the
commission, among them Charles Coulomb, a French physicist who would go
on to describe the electrostatic force of attraction and repulsion, and whose
name is now synonymous with the standard international unit of electric
charge. However, the commission’s eagerly awaited findings never materialised.
The science historian Christine Blondel points to ‘uncertainty about the
theoretical interpretation’ Galvani lent to his experiments: code for a suspicion
on the committee that Galvani was simply dressing up old superstitions as
nouveau science.33 In any case, the report disappeared and the Académie
remained noncommittal.
Volta had no such reservations – he had done more replications of his
own, and had begun to suspect Galvani was badly misconstruing his own
results. The problem was this: when Volta did the experiments, the frog’s
muscles didn’t always contract. Sometimes they did, sometimes they didn’t, and
Volta thought he saw a pattern emerging. When he connected the frog
elements using a wire made of two different metals (for example tin and
silver), the legs could be trusted to jump. But if he used a wire made of only a
single metal? The frog legs were as likely to twitch as to remain lifeless. This
pattern led Volta to suspect that maybe Galvani was looking at the experiment
backwards – instead of springing from some inherent biological electrical flow
within the frog, maybe the electricity had been entering the frog from outside
all along. Maybe it was something about the metal in the wires that was actually
generating the electricity.
Still stung by the fact his electrophorus had earned him a professorship
but not philosophical acclaim, Volta continued his hunt for a general theory of
electricity to cement his reputation as a brilliant theorist – and thought he had
found it in Galvani’s misconstrued results. Six months after the publication of
Galvani’s ‘De viribus’, Volta published this alternative explanation of the
contractions. First he aggressively debunked Galvani: ‘equating the animal
spirits with the electrical fluid that flows through the nerves is one of those
“plausible and seductive” explanations that have to be withdrawn in the face
of contrary experiments,’ he wrote.34 In his view, the contracting legs actually
demonstrated the power of the ‘dissimilarity of the metals’ in the wire that had
been inserted into the frog. After all, if the reason for the frog’s jerking leg had
simply been unbalanced animal electricity, the composition of the wire that
connected the frog’s limbs should have made no difference to the results. But
it did matter, as Volta’s own experiments showed. To get a sure twitch, you
needed a wire made of ‘two metals that are of different kinds or that are
dissimilar in some other way, such as in hardness, smoothness, shine, etc,’ he
wrote.
Volta hypothesised that contact between any two different metals
automatically generates electricity all by itself. Metals, he said, ‘should be
regarded no longer as simple conductors, but as true motors of electricity, for
with their mere contact they carry it around’.35 As his confidence in this
explanation grew, his language grew more aggressive. ‘There is surely no
reason to assume that a natural, organic electricity is at work here,’ he wrote in
one paper. In an open letter published at the end of the same year, he dropped
the gauntlet. ‘If that is how things are, then what is left of the animal electricity
claimed by Galvani? The entire edifice is in danger of collapsing.’
Many undecided scientists were swayed by these muscular proclamations;
Galvani’s frogs were in hot water. In response, Galvani produced a new
experiment. Volta retaliated with one of his own. And so it went: experiments
and counter-experiments, each designed to prove conclusively that the other
was wrong. Nevertheless, the two (largely) persisted in gentlemanly conduct: as
late as 1797, when the differences in their interpretation of the frog
experiment had become insurmountable, Galvani still emphasised Volta’s
‘erudition’ and ‘depth of wit’, and Volta in turn called Galvani’s experiments
‘very fine’.
The same could not be said of their contemporaries, who had long since
split into bilious factions engaged in proxy combat. Volta’s declarations were
made ‘with the thunder of truth’, according to the physician Giovacchino
Carradori. The chemist Valentino Brugnatelli bombastically announced ‘the
ruinous downfall of Galvani’s theory’ under the ‘repeated attacks of a terrible
adversary’. One of Galvani’s most loyal supporters was his nephew Giovanni
Aldini, who had not only helped with the experiments, but had written some
of the publications himself. He was incensed by what he perceived as the
baseless attacks. ‘If the good repute and integrity of scientific opinion were to
be called into question whenever the slightest doubt was raised, we would
certainly have few or no theories,’ he sniped in a letter to Volta.
As for Galvani himself, he unwaveringly disputed Volta’s characterisation
of his inability to provoke contractions from a single metal: ‘I can assure you
that I obtained the motions not a few times, as Volta claims, but in many,
many experiments, so that in a hundred times the effect had not happened just
once,’ he explained to his old friend Lazzaro Spallanzani. ‘These experiments
have been recently replicated by other people well versed in this sort of thing,
and they never failed.’ The variability, he explained, was largely a consequence
of other researchers using frogs that had been dead for longer than forty-four
hours. In addition, they had not necessarily followed Galvani’s exacting means
of preparation.
By now, so many scientists had joined the cause that Europe started
running out of frogs. ‘Sir, I want frogs,’ Valli admonished a colleague when he
ran out while replicating one of the experiments. ‘You must find them. I will
never pardon you, sir, if you fail to do so’.36
All the while, no one could reach a definitive conclusion on the validity of
the animal electricity that was increasingly being referred to as ‘galvanism’.
After the first French commission of the Académie des sciences ended in
uncertainty, in 1793 the baton passed to the Société philomatique de Paris, an
entity founded with the explicit mission of ‘repeating doubtful or little-known
experiments’. Instead of great physicists, however, the Société had the second
commission run by three amateur scientists.37 Though they seemed less hostile
towards Galvani, again they were unable to offer a definitive verdict on
galvanism.
By then, in 1794, Galvani was ready to claim victory for good. He
understood that if he was to prevail, he would need to prove that it was
possible to obtain contractions without the aid of any metals at all; if he could
get the same dancing-legs result sans wires, Volta would have to concede. So
he did just that: after a gruelling series of variations on the original experiment,
he was finally able to subtract the confounding wire, instead managing – with
an anatomist’s delicate precision – to surgically connect a frog’s muscle directly
to its nerve. The leg jumped.
Here it was at last: irrefutable proof that intrinsic electricity coursed
through animal tissues – its vestiges remaining at least for a while after death –
entirely isolated from any possible external source of metallic electricity. He
had long thought that a muscle was like a Leyden jar, whose spark could be
freed by a conductor – and here was proof that in animal tissue, the nerves
were the conductors. Galvani published. His powerful and loyal friend Lazzaro
Spallanzani lent the weight of his reputation, proclaiming that he had
succeeded in ‘confuting victoriously the objections’.
Now everybody wanted to be a Galvanian. Valli declared victory on behalf
of Galvani, saying that ‘metals possess no secret magic virtue’. Membership
expanded: ‘Thunder of truth’ Carradori abandoned Volta for his rival, as did
‘ruinous downfall’ Brugnatelli. (Indeed, in the wake of the third experiment,
Brugnatelli now claimed he too had obtained movement in his frog ‘without
the help of the metals’.38) Galvani’s relief was almost palpable in a letter to
Spallanzani shortly afterwards, thanking him for the support. ‘It could not be
more courteous and appreciated,’ he wrote. ‘This letter produces a fulsome
calmness in my soul, which was indeed rather restless.’
Galvani and his supporters were convinced that the new results would
finally put an end to the controversy. A rumour even spread that in December
1794 Valli had met Volta in Pavia and ‘converted’ him. The rumour was
unfounded and Volta was furious. Immediately he set about writing a series of
letters to Anton Maria Vassalli, the secretary of the Turin Academy of
Sciences, dissecting Galvani’s latest publication and the social fallout it had
occasioned. ‘These experiments impressed many people, and drew them
towards Galvani’s banners when they had already subscribed, or were going to
subscribe, to my totally different conclusion.’ Volta could not be right if
Galvani was not wrong.
In his letters with Vassalli, Volta set out his riposte. Perhaps, he theorised,
the connection between the muscle and the nerve wasn’t a home run for
‘animal electricity’ after all. Because what if – like metals – different kinds of
tissue also allowed a very thin charge to pass between them as long as they
were sufficiently dissimilar? In other words, maybe nerve and muscle were just
the biological version of tin and silver; their differences, put into contact,
would cause electricity to flow.
This insight inspired him to return to the discovery that had led him to
examine the difference in metals in Galvani’s initial experiments in the first
place: the theory of dissimilar conductors. He decided to broaden his theory of
metallic contact beyond metals. ‘Any time two different conductors are
connected, an action arises, which pushes the electric fluid,’ he announced. As
long as a circuit is closed, and as long as the materials are very different, ‘some
current is constantly excited’. Even meat could be a material that conducts, as
long as it is joined to another kind of meat that is sufficiently dissimilar. Once
again public opinion swung in Volta’s favour.
After months of trying to figure out how to connect two such gossamer
fibres, Galvani suddenly realised what he had to do next: connect two nerves
within the same frog, instead of connecting a muscle to a nerve. He aligned
the cut end of a frog’s left sciatic nerve with its right sciatic nerve and then
aligned the cut end of the right sciatic nerve with its left sciatic nerve. It was
exactly the same kind of tissue within the same animal. No conceivable
difference, metallic or biological. And still: both legs jumped.39
With that, he undercut Volta’s last remaining objection to the idea of an
innate electrical current inside an animal: according to Volta’s own logic, two
nerves, comprised of exactly the same material, should not possibly generate
any charge at all. Which meant there could be no other explanation of the
current being witnessed in the nerves – it had to have a physiological origin.
Galvani sent his manuscript to Spallanzani in 1797, whose response was
unreserved. ‘For [its] novelty, for the importance of its doctrines . . . for the
clarity and brilliance with which it is written, this work appears to me as one of
the most beautiful and valuable of the eighteenth-century Physics,’ he declared.
‘With it, you have erected a building that, because of the firmness of its
foundations, will last for the centuries to come.’ It was a prescient statement.
The series was a fundamental experiment for the foundation of all
electrophysiology. Neither Volta nor the other adversaries of animal electricity
ever bested it.
This should have ended all argument. Galvani should have harvested the
fruits of all his long years of experiments. In a just world, Galvani would have
been showered with awards and honours, and his success would have led to an
enormous boom in electrophysiological research focused on narrowing down
exactly what kind of electricity it was that flowed through the nerves.
But that’s not what happened. Instead, Galvani’s beautiful coup de grâce
went practically unnoticed by the scientific community and was nearly lost for
ever. That’s because Volta was about to unveil his world-changing instrument:
the battery. Volta had been busy turning his expanded general theory of
contact electricity into a physical device. According to the theory, the frog in
Galvani’s original experiments had simply functioned as a damp material that
closed the circuit between two dissimilar metals – a ‘moist conductor’. So why
not create an artificial ‘frog’ but with wet brine instead of the wet frog?
Sure enough, Volta found stacking two discs of different metals, separated
by a cardboard disc soaked in brine and connected at both ends by a wire,
produced a spark. The higher you piled the discs, the bigger the spark. This
cemented Volta’s conviction that Galvani had his hypothesis backwards and
helped him sell his version of the story to other scientists. All Galvani had
really done, Volta claimed, was to create a semi-biological version of his
‘voltaic pile’, in which the brine was replaced by the rather more cumbersome
frog. Remove this overcomplication, and you got a device that was able to
store and release continuous charge – in other words, a rudimentary battery.
The final blow to Galvani’s place in history was delivered not by science,
but by politics. Bologna had succumbed to the French occupation of northern
Italy. Napoleon’s Cisalpine Republic insisted that every university professor
must swear an oath of loyalty to its authority. By 1798, Volta and Spallanzani
had taken the oath, but Galvani was still a holdout.40 He could not bring
himself to make such a concession to an authority that conflicted so heavily
with his social, political, and religious ideals. ‘He did not believe he ought to,
on so serious an occasion, permit himself anything but the clear and precise
expression of his sentiments,’ wrote his first biographer Giuseppe Venturoli, a
fellow professor at the University of Bologna during the galvanism wars, who
had remained an unwavering Galvanian. ‘He also refused to take advantage of
the suggestion that he should modify the oath by some subterfuge that
betrayed his principles.’ The price for his refusal was steep; he was stripped of
all his academic positions, leaving him without income, estate, or purpose.
After lengthy consideration, in 1798, the republican government decided to
overlook the refusal and reinstate him. But the decision came too late: by the
time the word was handed down, he was already dead.
The urgency of finding what he conceived of as God’s ‘breath of life’ had
kept Galvani toiling through countless hours in a lab surrounded by the
corpses of dead frogs, through the heartbreak of his wife’s death, and through
an excruciating public attack on the validity of his scientific discoveries. But a
man has his limits. Luigi Galvani died in his brother’s house in Bologna, poor,
anguished and stripped of his titles, on 4 December 1798.
By the time Volta formalised his victory in 1800 by publicly showcasing his
demonstration of the voltaic pile to the president of the Royal Society of
London, word of the stupendous new invention had spread widely – he had
been writing drafts since 1797, and had certainly shared them with colleagues.
He had thoroughly won the day. The battery invalidated Galvani’s claim to the
existence of animal electricity – not because Volta had proved it, but because
he said so.
Apart from a few stubborn Galvani loyalists like Spallanzani, the voltaic
pile swung the scientific community to his side. ‘Thunder of truth’ Carradori
switched teams one last time to back Volta, along with ‘ruinous downfall’
Brugnatelli.41
With no leader left, the serious study of animal electricity fell away. Neither
Galvani nor his supporters had ever been able to measure animal electricity
with any kind of electrometer. The current was simply too faint to be detected
by the instruments of the day. No instrument had emerged from the ruck of
studies – French and otherwise – that could support the theory of animal
electricity the way the obviously useful voltaic pile had immediately buttressed
Volta’s notion of metallic contact electricity. Volta could prove his theories
with a tool and many use cases. Galvani could not.
One crucial limitation of Galvani’s experiments was that he was never able
to separate the source of animal electricity from its detector – they were both
the frog. No similar confusion plagued Volta’s research. That put Galvani at a
major disadvantage, because it muddled the terms.
So while Volta’s invention of the battery did not itself invalidate any of
Galvani’s theories about animal electricity, it effectively shut down all further
challenge. Volta had changed the terms of the debate, leaving his
contemporaries so dazzled by the device and its potential that they forgot what
the original fight was about. Galvani’s ideas weren’t so much disproved as
abandoned.

The long tail

In the wake of Volta’s perceived victory, Galvani’s theories were shunned by

science for nearly half a century. Galvanism was quickly overrun by quacks and
their most gruesome pseudo-medical treatments. At the same time, the battery
– and the ‘artificial’ electricity it was able to make flow continuously for the
first time – quickly went on to underpin many of the century’s most important
advances in the physical sciences. It allowed Michael Faraday to come up with
the laws of electromagnetism, and in more practical terms, it powered
telegraphs, electric lights, doorbells, and eventually power lines. In the hands of
the physicists, artificial electricity transformed civilisation.
If the Galvani–Volta battle set the stage for the separation of what we
understand today as biology and physics, it was only the beginning. Eventually,
better tools were able to detect the exquisitely faint electrical currents running
through frogs’ legs, but by then it was too late. The idea had been set:
electricity was not for biology. It was for machines, and telegraphs, and
chemical reactions. Not until the following century did research on biological
electricity return to being a legitimate scientific pursuit, and even then, it
returned in a much more circumscribed context.
The historians Marco Bresadola and Marco Piccolino note that outside
Bologna, even two centuries after his death, Galvani’s contribution to science
was still represented mainly as that of a know-nothing anatomist whose
accidental insights helped midwife Volta’s invention of the battery. But the
person who cemented that reputation immediately after Galvani’s death wasn’t
Volta – in fact, it was the last person you might have expected.
 CHAPTER 2

Spectacular pseudoscience:
The fall and rise of bioelectricity

G iovanni Aldini was looking for the perfect body. Not something that
had been dragged out of a grave – it should be as fresh as possible to
minimise the dissipation of its vital powers. It shouldn’t be someone who had
died slowly, from one of the ‘putrefying diseases’ that might contaminate their
humours.1 Not too dismembered, either. The ideal body would be one whose
previous owner had been healthy and intact until the moment of death.
Aldini’s star had been rising in Europe as he demonstrated Galvani’s
experiments on much larger animals than frogs, to often macabre effect. In an
echo of some of the early electricity spectacles – but with a darker twist – he
had recently electrified a decapitated dog to entertain a crowd that included
royalty.2 He was desperate to prove that the animal electricity Galvani had
discovered was present in the same way in all animals – that what was true for
frogs was true for humans. He was willing to use Volta’s battery and any
amount of theatrics to prove it.
Aldini was in the right place at the right time: it was 1803 in the UK, and
the Murder Act had for well over half a century included a provision that
would serve up exactly the corpse he was after. After a convicted killer’s public
hanging, their naked body would be flayed in a public dissection. If that seems
over the top, it was absolutely intended to be – this ‘further terror and peculiar
mark of infamy’ had been added to give would-be murderers just that extra bit
of pause, all the better to prevent ‘the horrid crime’.3 It was unclear whether,
as Aldini would later write, it also better helped them atone for their sins, or
whether there was a more convenient secondary benefit; as there were laws
against digging up corpses, this law provided a steady stream of cadavers to
upskill medical students and lecturers at the Royal College of Surgeons.4 The
fellows there had invited Aldini from Italy to demonstrate the experiments
that had recently made him famous around Europe.5 They were happy to
supply the necessary materials. And so, after the convicted murderer George
Forster was hanged on the gallows at Newgate prison, his body was carried
across town to the Royal College of Surgeons, where Aldini nervously waited.
The room was crowded with luminaries, scientists, and gentlemen standing
elbow to elbow. Assisting Aldini in his efforts would be the rising star Joseph
Carpue, a surgeon and anatomist at the Duke of York’s Hospital who had
extended the invitation, and Mr Pass, the beadle of the Surgeons’ Company,
who was tasked with making sure all proper protocols were followed during a
dissection.6 But the crowds weren’t what had Aldini sweating; he was used to
performing in front of high society.
What was worrying him today was the cold: it was January, and the body
had been left hanging for an hour in temperatures two degrees below freezing.
The chill might stunt the flow of animal electricity through the body, rendering
his experiment a humiliating, public flop. He was putting his faith in the
enormous piles of alternating zinc and copper discs sitting on the slab where
Forster’s corpse was now laid out, ready to dispense their ‘galvanic juices’ into
the dead man’s nervous system.
Aldini moistened the tips of two metal wires attached to either end of the
pile by dipping them into saltwater. When he threaded them gingerly into
Forster’s ears, the results did not disappoint. The dead man’s jaw, according to
a report in The Times, began to quiver: ‘the adjoining muscles were horribly
contorted, and the left eye actually opened’, giving the impression of a ghastly,
lewd wink.7 Over the next several hours, Aldini’s team exposed every nerve
and muscle on the man’s body, from the thorax to the gluteus, for electrical
experimentation.
Forster wasn’t Aldini’s first criminal corpse. He had spent the previous year
in Bologna and Paris perfecting his galvanic technique on the heads and bodies
of other hanged and beheaded convicts, not to mention the scores of lambs,
dogs, oxen, and horses, living and dead, that joined Italy’s population of frogs
on his table. These animal experiments had given him the idea for an especially
dramatic demonstration.
When Aldini plugged one of the wires into the dead man’s rectum, the
convulsions that wracked the corpse were ‘much stronger than in the
preceding experiments’, Aldini wrote. So strong, in fact, ‘as almost to give an
appearance of reanimation’. At this point, according to The Times, ‘some of the
uninformed bystanders actually thought the wretched man was on the eve of
being restored to life’. Some in the audience clapped; others were deeply
disturbed. Mr Pass was so shaken by what he saw on the table that he went
home that night and died.8 As far as Aldini was concerned, the experiment had
been a success.
This spectacular public demonstration begat many copycats, and historians
trace a line from the Forster galvanisation to Mary Shelley’s idea for
Frankenstein. So it may come as a surprise that Aldini didn’t start out with the
goal of titillating vapid royalty by raising the dead. He was pushed down his
path by an altogether more noble impulse: to restore the reputation of his
beloved uncle. But not unlike Dr Frankenstein, his obsession caused him to
reach beyond what science could provide, and eventually turned him into a
mockery. He would become a scientific pariah. Instead of reviving his family’s
legacy as well as decapitated bodies, his experiments would play a major role in
banishing the serious study of animal electricity into a desert of quacks and
mountebanks for the next four decades.

Aldini’s gambit

Aldini’s loyalty to Galvani wasn’t just a matter of family honour. He had also
been his uncle’s closest and most important scientific collaborator. He had
written some of the anatomist’s famous communications himself – some of
the liveliest ripostes between ‘Galvani’ and Volta had actually involved just
Volta and Aldini.9 But after Galvani’s death, few champions remained to take
forward the serious scientific inquiry into animal electricity.
In 1801, Napoleon’s French Académie launched a commission (the fifth in
as many years), offering a prize of 60,000 francs for anyone who could do for
animal electricity what Volta had done for the metallic or artificial variety.10 (In
today’s money, this would have been worth around £860,000.) Generous as it
was, however, the prize went unclaimed. No one was in the position to make
something as consequential as a battery for animal electricity. In addition, the
false perception that acceptance of metallic contact theory and animal
electricity had to be mutually exclusive meant, for many, that because Volta (so
heavily favoured by Napoleon) had been demonstrably right, Galvani must by
definition have been wrong.
 Aldini was desperate to stop this becoming the official received wisdom.
He had understood the scientific foundation his uncle was trying to build, and
he had noted the sleight of hand that undermined it. In particular, Aldini was
still pained that their most triumphant paper – the one Spallanzani had hailed
as ‘one of the most beautiful and valuable of the eighteenth-century Physics’,
in which Galvani had showed up Volta once and for all by successfully proving
that nerve electricity could excite nerve tissue – was already being forgotten.
This was the paper that should have put the lie to Volta’s insistence that the
only reason contractions could be evoked in a dead frog was that some version
of metallic electricity was generated by the meeting of two dissimilar kinds of
meat. Instead, the paper had been buried under the fanfare around the voltaic
pile.
And so, Aldini’s initial investigations after his uncle’s death focused on
buttressing the basic science underlying this experiment, and how it could
advance a deeper understanding of animal electricity. He had assumed the
chair of physics at Bologna in 1798, just before Galvani passed away. This was
a prestigious post from which to carry on his uncle’s work, and Aldini used it
to launch the Galvanic Society of Bologna.
Galvani had experimented almost exclusively on frogs. Aldini’s first
experiments therefore extended his uncle’s investigations into warm-blooded
mammals. His 1804 publication Essai théorique et expérimental sur le galvanisme is
filled with long, repetitive accounts of experiments in which he and his
Galvanic Society collaborators sought to understand ‘intra-animal’
electrification. In one characteristic experiment, he placed several calves’ heads
in an electrically conducting line called a ‘series’, and used the resulting animal
current to violently electrify a dead frog. But when he tried to reverse the
experiment, applying the animal electricity of frog nerves to the decapitated
heads of oxen, he found the results less dramatic and even disappointing. All
these experiments successfully replicated Galvani’s original idea that the same
electrical substance coursed through all animals, but none yielded grand
dramatic outcomes or novel insights.
At some point, it seems to have become clear to Aldini that to maintain
excitement about scientific galvanism, he would need to do what the five
commissions hadn’t been able to: find a way to make his uncle’s discoveries
medically relevant for humans. It was around then that his focus rather quickly
shifted, revealing a sudden new appreciation of the ‘galvanic juices’ dispensed
by Volta’s pile. ‘The battery imagined by Professor Volta gave me the idea of a
cleaner means than any of the ones we have used so far to estimate the action
of the vital forces,’ he recalled in the 1804 Essai.11
It must have been hard for Aldini to hold his nose and use the instrument
of his uncle’s doom, but once he got the hang of it, he was prolific. He used
the pile’s ability to dispense a steady flow of electricity to stage big, dramatic
experiments on dead animals. He inserted wires into their rectal cavities, often
detailing the inevitable violent expulsion of faeces that followed. He also
began to experiment with touching different areas of the animals’ brains, as
well as his own; when he administered a jolt from the pile to his own cranium,
it led to a few days of insomnia but also a strange feeling of elation.
Such experiments fascinated the other members of the Galvanic Society: if
a jolt to the head could make Aldini feel euphoric, what else could it do? They
analysed and repeated these kinds of experiments until they eventually accreted
into new theories about how electrical ministrations could improve ailments.
Most promising were epilepsy, a type of paralysis called chorea, and what was
then called ‘melancholy madness’, which we understand today as treatment-
resistant depression. Now they just needed test subjects.
In 1801, at Sant’Orsola Hospital in Bologna, Aldini found a twenty-seven-
year-old farmer called Luigi Lanzarini who had become catatonic with
melancholy madness and had been declared a lost cause.12 He shaved
Lanzarini’s head and stimulated the man’s scalp with a weak battery. Over the
next month he slowly increased the current, and Lanzarini’s symptoms seemed
to lessen, eventually enough for him to be released into Aldini’s custody. After
about a month, Aldini deemed him well enough to send back home to his
family.
Word of this achievement spread quickly enough that, by 1802, French
scientists founded their own Parisian branch of the Galvanic Society. They
devoted themselves to Aldini’s goal of elevating the reputation of galvanism as
a legitimate pursuit, by any means necessary. Joseph Carpue – the rising-star
surgeon who had assisted in the Forster experiment – reported that a M. La
Grave of the Parisian Galvanic Society had made a voltaic pile out of sixty
layers each of human brain, muscle, and hat material (you read that right)
moistened with salt water.13 Its effect was allegedly ‘decisive’ – generating a
current that provided yet another piece of evidence that animal electricity was
just as relevant and present in human tissues as it was in animal tissues.
It was never entirely possible to extricate galvanism from its associations
with woo and quackery – ‘a couple of [the Galvanic Society’s] members drifted
into “galvanic magic”,’ notes the historian Christine Blondel – but most of the
group’s research was greeted with interest by French and foreign scientific
journals and even encouraged.14 The attention-seeking experiments were
doing their job. Famous French psychiatrists began to consult Aldini about use
of the pile to restore their patients to health.
But by then, Aldini already had his eye on an entirely new patient
population: he started investigating electrification as a way to revive the dead.15
To be clear, his goal was never to stitch together some kind of undead golem –
Aldini was referring to the evidently reversible state of ‘suspended animation’
that followed accidental drowning, apoplexy, or asphyxia.16
Aldini was campaigning to get galvanism – specifically a jolt of electricity
to the head – included in the go-to methods for emergency resuscitation,
which included ammonia and a kind of proto-CPR that involved exhaling into
the lungs of the temporarily deceased. Adding an electric shock to either of
these remedies, Aldini insisted, ‘will produce much greater effect than either of
them separately’. He also began to lobby to have electrification adopted as a
research tool to determine whether someone was truly, irreversibly dead. ‘It
would be desirable to establish by public authority, in all nations, by people
enlightened and able to make the necessary tests to determine whether death is
real or not.’
Of course, it’s well known today that his hunch was correct – electrical
defibrillation can bring a person back from what would have been certain
death. But Aldini’s speculations were not based on any specific mechanism or
evidence. He had no access to any of the information that we take for granted
200 years later: that a meaningful resuscitation is largely determined by
whether or not the patient is brain-dead; that it’s crucial to keep oxygen
moving to the brain; that there is a small window of time after which any
attempt at resuscitation becomes useless. Unfortunately, even the most
fundamental mechanism eluded Aldini – that the organ that should be
stimulated is the heart, not the brain. In fact, he repeatedly and explicitly
refuted the idea that the heart could be affected by electrification at all. His
focus on spectacle over basic science had misled him.17
So it came as no surprise to him that none of his experimental subjects –
human or animal – were ever shocked back to life. Neither was such an
outcome ever his goal for the hanged Forster. ‘Our object here was not to
produce reanimation, merely to obtain a practical knowledge of how far
Galvanism might be employed as an auxiliary to other means in attempts to
revive,’ he wrote in an 1803 account of the experiment. This writing also
provides clues to how he thought galvanisation might act to restore the dead
to life: by ‘re-establishing the muscular powers which have been suspended’, in
addition to preparing the lungs to receive resuscitation.
 However, these were not the promises that got royalty crowding around
his table. It was the extras: the grimaces, the rectal probes, and the unspoken
possibility that, just maybe, one of the malefactors might rise from the dead.
Word had begun to spread of his work on deceased criminals in Bologna in
early 1802.18 He had managed to raise the forearm of a corpse to the height of
eight inches seventy-five minutes after death, ‘after we put in his hand a fairly
considerable weight, such as an iron pincer’. Stimulation of the arm caused the
hand to rise and curl into a position that looked for all the world like an
accusing finger pointing at the assembled audience, several of whom promptly
fainted. His colleagues at the Galvanic Society, Professors Giulio, Vassalli, and
Rossi, quickly repeated these experiments in Turin on three recently
decapitated men.19 It wasn’t long before such demonstrations piqued the
interest of the Royal Humane Society of London, though maybe not for the
reasons you might expect.
These days, a person who identifies as humane might find cause for
concern in the public dissection of dead criminals for entertainment. Not
these officials. They had more pressing concerns, like how to distinguish
between people who were genuinely dead and those who were going to wake
up.20 Before the wide availability and awareness of reliable methods of
resuscitation, burials could be a pretty hasty affair, and more than one
unfortunate had found themselves waking from a comatose or cataleptic state
(or just a deep and drunken sleep) inside a little box under six feet of earth.
Sometimes, their screaming was heard in time. (In one especially grisly case,
this fate befell the same poor woman twice.) ‘A host of facts have repeatedly
shown us that people were rushed to the tomb before death had irrevocably
struck them. Shouldn’t we give our fullest attention to preventing such deadly
events?’ Aldini had written, scandalised by the haunting stories of these
potentially ‘murderous burials’.21 Busy, commercial, and maritime Britain was
seeing a glut of drownings and mining accidents, and so for the Royal Humane
Society, having some way to distinguish the dead from the ‘not actually dead
even though they sure look like it’ was very much at the top of the agenda.
In late 1802, they sponsored Aldini for a long tour of Oxford and London,
and that’s how he came to be in the room with Mr Pass and Mr Forster that
chilly morning. Did he think the man would wake up there on the table?
Certainly not. Did he think the experiment would contribute to better
resuscitations? Sure – but there is little evidence in his writing of any empirical
understanding of how the stimulation might accomplish that. So in some way
he must have understood that what he was doing there that day was to a large
extent more showmanship than science.
 Unfortunately, in trying to preserve what was left of his uncle’s nascent
science, Aldini failed. He did, however, have great success at blurring the line
between ‘legitimate’ galvanism and the unscientific electroquackery that had
begun to proliferate long before Galvani touched his first frog. And the quacks
came marching over it.

Elisha and the quacks

Almost as soon as the Leyden jar was invented in the mid-1740s, people were
convinced its zaps could dispense powerful cures.22 In Italy, its invention
prompted the opening of no fewer than three schools of electrical medicine.
Treatments there varied – some doctors simply shocked their patients and
hoped for the best; others hoped that electrical stimulation would boost
topical medicines’ ability to reach deep beneath the skin. The practice was said
to cure a spectrum of ailments so wide it bordered on the miraculous.
No ailment was spared the intervention of the Leyden jar, including but
not limited to gout, rheumatism, hysteria, headache, toothache, deafness,
blindness, irregular menstruation, diarrhoea, and, as ever, venereal disease.23
By the 1780s, electricity was rumoured to beget miracles, as in the report of a
couple who, after ten years of infertility, ‘regained hope through electricity
thanks to a few turns of the crank and some shocks in the appropriate parts’ –
the Abbé Bertholon, reporting this, ‘demurely did not specify which’.24 It
wasn’t just a continental fad: Britain’s medico-electric quack culture also
thrived, adding ‘weak ligaments’, testicular and urinary conditions, and ague
(that’s ‘the shivers’ to you) to the list of conditions electricity would relieve. It
was hard to beat the electrical apparatus devised in 1781 by the London
medical electrician James Graham, who guaranteed that his electrically
stimulating Celestial Bed, in a special wing of his Temple of Hymen, would
cure sterility and impotence.25 What put this electro-quackery a cut above the
usual sort was that no actual electricity was involved – merely the idea of it, as
Graham figured ‘the fashion of electrical vapours’ would suffice to cure his
patients.26 A night in this contraption would set you back £50, around £9,000
in today’s money,27 but if you still had money burning a hole in your pocket,
you could hit the temple gift shop on your way out for a take-home
aphrodisiac called Electrical Ether. (Given that the temple closed its doors
within two years, ‘homeopathic electricity’ does not seem to have been an
unqualified success.28)
But it was Galvani’s science that would inspire the most brazen of these
quacks: Elisha Perkins. ‘Among the delusions which have succeeded in
imposing on men of education and position, it is pre-eminent,’ wrote Francis
Shepherd, describing ‘Perkinism’ in the Popular Science Monthly in 1883.29
Perkins – who at the time of Galvani’s ‘De viribus’ publication was
practising medicine in Connecticut – had keenly followed accounts of the fight
raging on the Continent, and saw an opportunity in the argument about dual
metals.30 One that could make him rich. In 1796, he unveiled his contribution
to medical galvanism – a pair of sharp-tipped three-inch rods, one iron, one
brass, which he called ‘tractors’. Drag them over your afflicted parts for a few
minutes, and he claimed that you would soon be rid of rheumatism, pain,
inflammation, and even tumours. Perkins’ patented tractors took off in
America among the wealthy and influential. Even George Washington bought
a set for his family, along with Chief Justices Oliver Ellsworth and John
Marshall.31
The Connecticut Medical Society was having precisely none of it. In a
scorching rebuke of Perkins, they began expulsion procedures with a letter
stuffed to the margins with indignation. Castigating Perkins’ inventions as
‘delusive quackery’, they accused him of using the auspices of his Society
membership to spread his ‘mischief ’ to the south and abroad. ‘We consider all
such practices as barefaced imposition, disgraceful to the faculty, and delusive
to the ignorant,’ the Society fulminated. With that, they invited Perkins to
‘answer for his conduct, and render reasons why he should not be expelled
from the Society, for such disgraceful practices’.32
Whatever reasons Perkins may have offered, they failed to sway the
opinion of the Society, which in 1797 expelled him for violating their
prohibitions against nostrums (medical treatments prepared by unqualified
chancers). This goes some way to explaining why Perkins’ son soon took the
family business to the Continent. They were a wild success. In 1798, the Royal
Hospital in Copenhagen officially adopted the tractors for treatment. In
London, the Royal Society ‘accepted’ the tractors and the accompanying book
(there’s always a book), and by 1804, a Perkinean Institution had been
established. Members included fellows of the Royal Society. Soon a hospital
was built whose sole treatment was ‘tractoration’. Testimonials abounded: not
least from bishops and clergymen, whom Perkins had slyly provided with that
most ancient grift: free review samples. ‘I have used the tractors with success
in several cases in my own family,’ wrote one recipient, channelling the logic of
a multilevel marketing scheme. ‘Since experience has proved them, so no
reasoning can change the opinion.’
Over time, galvanism was conscripted into a pre-existing, ever-widening
gyre of pseudoscience that included Franz Mesmer’s animal magnetism,
hypnosis, and electrifying wearables, variously said to be associated with
earthquakes, dowsing, and volcanic activity. The whole line of research was
evidently starting to exasperate the public. In an 1809 poem, Lord Byron
lumped galvanism in with tractors eleven years after Galvani’s death,
apparently channelling the public mood that had started to conflate both:

What varied wonders tempt us as they pass

The cow pox, Tractors, Galvanism and Gas
In turns appear to make the vulgar stare
Till the swollen bubble bursts – and all is air!33

‘A prostitution of galvanism’

In the end, Aldini’s efforts to clear his uncle’s name had the opposite effect.
They created a self-perpetuating spiral that destroyed what was left of
Galvani’s reputation as the father of animal electricity: the more quacks who
co-opted galvanism for their own purposes, the fewer legitimate researchers
were willing to be associated with the relationship between electricity and life;
the less serious research took place, the more ground was ceded to ludicrous
claims. As the years went on, an increasing number of scientists and historians
looking back on the Volta–Galvani feud began to ad lib historical details about
Galvani that confirmed the cynical new perspective on animal electricity – and
his ignorance in believing it to exist. One of the most enduring of these is the
pernicious origin myth that Galvani accidentally bumbled upon the idea of
animal electricity as his wife was preparing a frog for soup using a metal knife,
rather than in a decade-long series of ever more finely honed replications.
At the same time, the sciences were now rapidly beginning to diverge into
their fields, and biology was defining itself as a discipline. Not wanting to make
Galvani’s mistakes, those who pursued the legitimate study of biology recoiled
from electricity and returned to a largely descriptive anatomical and taxonomic
focus, a study of pieces instead of the forces and processes that govern the
whole.
People who studied electricity seriously – the electricians – were desperate
to restore respectability to their endeavours, and that meant separating the
object of their study from vitalistic connotations, and focusing strictly on the
advances being made by chemists and physicists thanks to Volta’s battery.
These multiplied quickly. In 1800, his proto-battery helped scientists
electrolyse water, decomposing it into hydrogen and oxygen. In 1808, an
improved version helped chemists to discover sodium and potassium and
alkaline earth metals. Equations were devised to define the relationships by
which electricity could act on the world. In 1816, the first working prototype
of a telegraph was built in Hammersmith, powered by voltaic piles. The
physicists and engineers had created an electric force field around themselves
that no one could touch, protecting themselves from both the biologists and
the charlatans.
Medical professionals also separated themselves from animal electricity in
due course, even as some of them continued to deploy the artificial electricity
that could zap people’s ailments. In the 1830s, a young doctor called Golding
Bird – after seeing the quacks make money hand over fist – set up ‘electric
baths’ facilities at Guy’s Hospital in London, where he charged his posh
patients a hefty fee to alleviate vague maladies.
But not everyone abandoned the project of building a legitimate discipline
around investigating animal electricity. Behind the scenes, another scientist had
been working to keep its study on life support: Alexander von Humboldt had
reviewed Galvani’s work for the French commission throughout the 1790s,
and had grown to strongly suspect that Volta and Galvani’s theories did not
contradict each other after all, and that Volta had in fact been wrong to
dismiss animal electricity out of hand.34
Humboldt would go on to become chamberlain to the Prussian king and a
leader of the Enlightenment, shaping how we conceive of nature itself as a
single interconnected system. But during the electricity wars he was still in his
early twenties, having recently graduated from university into a position as a
mining inspector. Quickly his polymathic tendencies jumped from geology to
botany to comparative anatomy. When he became aware of the Volta–Galvani
controversy, he set his mind to solving the mystery.
To that end, Humboldt conducted about 4,000 experiments over five
years, several on himself. (His friend Johann Wilhelm Ritter, whom he often
convinced to join him, scrambled his nervous system so much with this type
of self-experimentation that he died at thirty-four.) Of these investigations,
arguably the most shocking was Humboldt’s decision to insert a silver wire
connected to a galvanic pile into his own rectum, an experiment the historian
Stanley Finger calls ‘almost unimaginable’.35 This elicited all the unpleasant
results Aldini had obtained with large animals, but performing the experiment
on himself gave Humboldt the added benefit of first-hand experience. Thus he
gained the insight that the involuntary faecal expulsions were accompanied by
painful abdominal cramps and ‘visual sensations’. Not content to stop there,
he forced the wire further into his anus and found that ‘a bright light appears
before both eyes’. It would be hard to go further to prove one’s dedication to
understanding animal electricity.
In 1800, he undertook a journey to Venezuela for the purposes of
investigating John Walsh’s experiments with live eels, which didn’t tend to
survive the journey out of their native habitats. Using pack animals as bait to
draw out the eels (some of which were five feet long and discharged 700-volt
shocks – enough to stun the horses and mules) he saw for himself the
unambiguous power of animal electricity. After the trip, he began to draw
connections between this kind of powerful defensive biological electricity and
the more quotidian variety that underpinned everyday motion and perception.
In his subsequent writings on electric eels, he concluded, in carefully written
prose, that at some future point ‘it will perhaps be found that, in most animals,
every contraction of the muscular fibre is preceded by a discharge from the
nerve into the muscle; and that the mere simple contact of heterogeneous
substances is a source of life in all organized beings’.36
Instead of adopting Aldini’s strategy of charging ahead with his belief that
Galvani had been right, Humboldt played the long game to bring experimental
physiology back: he encouraged promising young scientists to study animal
electricity. When Humboldt returned to Berlin from his travels in the late
1820s, he became a patron of the up-and-coming physiologist Johannes Müller
and helped install him to lead the anatomy department of the world-beating
university his brother Wilhelm von Humboldt had founded two decades
earlier.37
The electroquacks had so thoroughly discredited the official record of
animal electricity that when the first real evidence of its existence finally
presented itself, even the scientist who rediscovered it didn’t understand quite
what he had found. In 1828, Leopoldo Nobili, a physicist in Florence, was
working on ways to improve the sensitivity of electrometers, which were
becoming increasingly important as they were crucial to the running of
transatlantic telegraph cables. Electricians used them to confirm that current
was flowing and that messages were being delivered. The early versions
suffered from limited accuracy because the earth’s magnetism interfered with
the measurement of the wake of the current. No one could figure out how to
get rid of it.
To do that, you needed a much more sensitive electrometer. (By now, these
were starting to be known as galvanometers, thanks to a sly nod from the
French physicist André-Marie Ampère.) To test that his improved version
really was better, Nobili needed to find the weakest possible current. He
remembered Volta’s assertion that Galvani had witnessed not some special
‘animal electricity’, but nothing more than the vanishingly faint currents
generated from contact between two dissimilar materials. He realised that if his
device could measure something as infinitesimal as the current travelling
through a dead frog, its superiority would be incontestable. Sure enough, his
new meter detected this flow, which he immediately christened ‘corrente di
rana’ (frog current).38 It allowed him to make the first-ever recording of
electrical activity from the neuromuscular preparation. But Nobili did not
actually believe it was intrinsic to the frog – he was still firmly in Volta’s camp.
It was all, he insisted, to do with metals.
It would take another ten years for another scientist to correctly interpret
the significance of what Nobili had measured, and finally put bioelectricity
back on its pedestal.

The frog battery

Carlo Matteucci chopped the last of the frog thighs off its erstwhile owner and
fitted it carefully onto the pile. He had killed ten frogs, removed their thighs,
and carved each into a shape roughly resembling a halved orange – intact on
one side, bisected on the other. He had then stacked these amphibian pieces
atop each other into a biological inversion – some might say perversion – of a
voltaic pile where zinc and copper were replaced with muscle and nerve.
Matteucci had just finished constructing the world’s first battery made
exclusively of frogs.39
When he tested the current, he saw the output: the more thighs he
connected, the more the galvanometer needle was deflected, indicating an
increase in the flow of current. But that wasn’t the end of the experiment.
When he was satisfied that his pile contained enough biological material, he
picked up the wire attached to his biological battery, and delicately touched it
to a separate frog lying limp on a plate nearby – or rather, what was left of it.
Unlike the frog battery, this one had been prepared in the style popularised by
Galvani many years ago: flayed, head and midsection almost entirely missing
save for the two crural nerves that still connected its spine to its legs, which
remained whole. When the wire made contact, the hideous little half-puppet
immediately jerked into the familiar dance. Animal electricity – and animal
electricity alone – had caused a dead frog’s legs to move.
Here, forty years after Galvani’s death, was the first real progress in
electrophysiology since the days of Galvani himself.
Matteucci was another of the promising young scientists who had been
mentored and funded by Humboldt during the decades animal electricity fell
out of favour. Humboldt had been inspired by Matteucci’s enthusiasm for the
promise of an underlying electrical force in the nerves, and had recommended
the young scientist for the professorship he now held at the University of Pisa.
He also defended Matteucci against attempts to discredit his discovery of the
nerve centres torpedo fish used to control their shocks. So when Matteucci
told Humboldt of his frog battery, his patron was so thrilled he immediately
disseminated the paper to his entire social network, including Müller at the
University of Berlin, who pressed Matteucci’s paper into the hands of his eager
young student, Emil du Bois-Reymond.40 Humboldt was – again – a mentor
to this young physiologist. ‘He is studying a matter, the deep natural secret of
muscle movement,’ Humboldt wrote to the German cultural minister in 1849
to secure funding for du Bois-Reymond’s research, ‘with which I, too, was
preoccupied in the earlier half of my life’. When he sparked du Bois-
Reymond’s interest with Matteucci’s experiment, the match caught.
Though he found Matteucci’s grotesque experiment unscientific (‘no one
can feel more deeply than myself how much this examination leaves to be
desired in focus and clarity’), the work du Bois-Reymond did to build on it
over the next two decades would finally resuscitate the long-dead field of
bioelectricity and bring it back under the umbrella of legitimate scientific
inquiry. He was incredibly ambitious and passionate about making his name,
and du Bois-Reymond’s fifty-five-year tenure at the University of Berlin turned
into an attempt to secure his place in history by usurping Galvani as the father
of animal electricity.
He was Galvani’s heir in many ways. His commitment to good science and
rigour was legendary. To characterise and measure the currents in nerves more
precisely, he went to lengths that might be considered obsessive. He spent
years on trial-and-error assembly of his own design for a special galvanometer
sensitive enough to measure the faint electrical current flowing not through
telegraph lines, but through frog muscles and nerves. He acquired so many
frogs his Berlin flat turned into a ‘frog kennel’.41 When severing his frogs’
muscle and nerve fibres, to avoid introducing any accidental source of external
electricity, he would bite them in half instead of using a metal implement. He
nearly blinded himself with his constant exposure to the irritants in frog skin.
Berlin, like Italy decades before, began to run out of frogs. But this tenacity –
inflamed by his determination to refine and take credit for Galvani’s
experiments – paid off.
Using his new galvanometer, du Bois-Reymond was able to see for himself
the distinct electrical disturbance on his meter that accompanied muscle
contractions. The needle on his galvanometer swung whenever the current
passed through the area he measured. Whereas Galvani had only indirectly
detected the electrical impulse travelling through the muscle by the evidence of
a frog’s leg twitch (making the frog the world’s first galvanometer, in a twisted
way), here du Bois-Reymond was directly seeing the animal electricity as it
excited the muscle. The eighty-year-old Humboldt gamely lent himself as a
guinea pig for these studies: even though he was now enough of a big deal to
be taking ‘his daily dinner at the King’s side’, he would roll up his sleeve and
flex until he deflected the needle of du Bois-Reymond’s galvanometer.42
While most researchers greeted the early experiments coldly – the zeitgeist
being still firmly against the idea of thoughts and intentions producing
measurable electricity43 – by the end of the eighteenth century du Bois-
Reymond and his colleagues had successfully established bioelectricity as an
aspect of neurobiology. The notion of electricity running through nerves and
muscles was approaching respectability. A couple of outstanding questions
remained – how did it travel? And why was this electricity so much slower than
the kind that ran down telegraph wires?
But now you could measure it. Du Bois-Reymond and his colleague
Hermann von Helmholtz called this electrical jolt that the nerve sent to
activate the muscle the ‘action current’. Other scientists soon joined the hunt
to characterise it precisely, and while acrimonious fights broke out over many
of the details, the existence of electrical phenomena in the nervous system
became largely accepted. Du Bois-Reymond proved that electricity was
relevant in the human body. Nerves ran on the stuff. He had made von
Humboldt proud and usurped Galvani.44 ‘I have succeeded in restoring to life
in full reality that hundred-year-old dream of the physicist and physiologist, the
identity of the nerve substance with electricity,’ he wrote.45
 At the same time as du Bois-Reymond’s research had resurrected the
legitimacy of biological electricity, there had been new advances in mapping
the brain and the nervous system. As had happened in the past, new tools cast
doubt on old science, and a fresh uncertainty loomed. How could a single
electrical impulse be responsible for such an enormous variety of discrete
sensation and motion? Science at that point conceived of the nervous system
as a vast uninterrupted network of fused strings. The best available metaphor
was plumbing: Rather than being comprised of a bunch of separate cells,
scientists still saw a series of tubes. Except instead of animal spirits, it was now
electricity that coursed through them.
Thanks to better tools – like sensitive galvanometers and Volta’s battery –
and Humboldt, du Bois-Reymond, and Helmholtz’s commitment to the
rigours of the scientific method, the millennia-old mystery of animal spirits
had finally been solved. Animal spirits, the things that carried the brain’s
impulse and intent to the limbs to carry out, and carried back the sensations of
the world outside, were electric. Animal spirits were animal electricity. But
instead of calling it animal electricity, the new term was ‘nervous conduction’.
It meant the same thing; it was just science instead of philosophy. Galvani was
vindicated.
 PART 2

Bioelectricity and the Electrome

‘[A] full understanding of life will come only from
unravelling its computational mechanisms.’
Paul Davies, The Demon in the Machine

D uring the centuries of argument over the existence and nature of the
nervous impulse, sceptics had many reasons to doubt that actual
electricity runs in the animal nervous system. Investigations into the intriguing
powers of electric fish and eels had yielded an obvious source: a giant electrical
organ specialised to store up electrical charge and then dispense it in one big
paralysing zap. No anatomist had yet succeeded at locating anything like that
in a human body. And without a power source, how were we supposed to be
sending electrical current down our nerves? This led to lingering suspicions
that electricity was just an unsatisfying metaphor for the otherwise mysterious
conduction mechanism of nervous signals.
All that changed in the latter years of the twentieth century – when we
found the source. The new technique that aided this discovery caused a step
change in the disciplines of electrophysiology and neuroscience. The
consequent advances were so swift, and so numerous, that science historians
Marco Bresadola and Marco Piccolino call them ‘comparable to that of
quantum mechanics in Max Planck’s day’.1
 CHAPTER 3

The electrome and the bioelectric code:

How to speak our body’s electrical
language

B y the end of the nineteenth century, animal spirits had been rescued
from millennia of airy philosophical conjecture and placed onto the
firm ground of the scientific method. Alexander von Humboldt, Emil du
Bois-Reymond, and Hermann von Helmholtz had vindicated the work for
which Galvani had given his life: what are the animal spirits in our nerves,
these things that animate our every sense and motion? They are electric.
Yet even they could not have anticipated what their foundational tools and
insights would set in motion over the next 150 years. Today, our understanding
of bioelectricity is in the process of another metamorphosis as we begin to
grasp the outlines of the electrome.1
The electrome transcends the bioelectric signals whose outlines Galvani
and du Bois-Reymond glimpsed. Those were the drivers of the nervous
system’s ability to help us sense and move in the world, and today are well-
characterised, thanks to copious investigations that helped establish the
modern discipline of neuroscience. But in the past twenty years or so, a new
picture has been emerging, one that shows with increasing clarity how
instrumental bioelectric signals are beyond the nervous system, and how much
they do in the rest of the body. Just as the genome describes all of the genetic
material in an organism – the DNA that writes the instruction set to build it,
the As, Cs, Ts, and Gs that make up the code this instruction set is written in,
and other elements that control the activity of the genes – a complete
accounting of our electrome would catalogue all the profound ways different
electrical signals shape biology.
 Mapping the electrome would furnish a unique blueprint of the electrical
properties that determine almost every aspect of our life and death. It would
include a profile of the dimensions and properties of our electrics from the
level of organs to cells to the tiny constituents of those cells, including
mitochondria, and to the behaviours of the electrical molecules themselves.
As you saw in the first part of the book, the earliest glimpse of the
electrome came to us courtesy of the electrical activity of nerves and muscles.
‘Animal spirits’ became nervous conduction, and the scientific discipline that
coalesced around its study was neurology. The insights from neurology (and
electrophysiology, the field that united eighteenth-century electricians with
theoretical physiologists) were codified in the 1960s into the formal discipline
that is today known as neuroscience: the study of the animal nervous system.
The twentieth century brought tremendous advances in characterising the
patterns hidden in the electrical activity of the nervous system. We began to
crack the code that explains how it transmits information to and from the
brain. As you’ll see in the next few chapters, almost all of these insights were
delivered by probing the nervous system with metallic electricity. This led us to
discover that artificial electricity could even, to varying degrees of success,
modify our own bioelectricity – and health, thoughts, and behaviour. That was
startling enough, but then, towards the end of the century, we found out how
much deeper the rabbit hole goes.
But before we go any further, we’ll need to establish some of the basics of
neuroscience, so that we can be on the same page about how the nervous
system works and why people were so hot to prod it with artificial electricity.
That’s what this chapter is for. Please join me for a speedrun through 150
years of electrophysiology.

Nervous conduction 101

Figuring out how electrical messages are sent through the body got a lot easier
once we figured out the structure of the brain and spinal cord and the special
cells that enable them to pass communications. These are called nerve cells, or
neurons. All this was established in a series of groundbreaking insights known
as the Neuron Doctrine, which won Camillo Golgi and Santiago ramón y Cajal
a Nobel Prize in 1906. It was the first time we understood how the nervous
system worked. (Before this, as the conversation around animal spirits makes
clear, we thought the nervous system was just a single connected network of
tubes that went from the brain through the whole body, which is why it made
sense that you could fill them with water or hydraulic fluid – and why not
much else about it made any sense.)
What Ramón y Cajal and Golgi figured out (though again via plenty of
backbiting and disagreement) is that the nervous system was composed of
cells – separate special cells that had been coined ‘neurons’ – that could pass
electrical signals from the brain to the nerves and muscles, and back.
No one had ever realised that the nervous system is made of cells, and
that’s because neurons don’t look like your standard cell. Most cells look like a
sphere that got a bit squashed. Not neurons. A neuron has three distinct parts.
It has a cell body (this bit does look like a normal cell), but sprouting from
that cell body in all directions are branching protuberances of different lengths.
These come in two flavours: the first – called dendrites – are very short, and
they bring incoming messages to the cell body. The second – axons – can be
up to a metre long, and their job is to send messages from the cell body to
other neurons or muscles.
While some of the brain’s 86 billion neurons exist only in the brain, a vast
number of them extend down your spine and into your skin, heart, muscles,
eyes, ears, nose, mouth, organs, intestine – in other words, into absolutely
everything in your body – to make it move and feel and much more besides.
The ‘feeling’ neurons that bring sensation and perception into the brain
are part of the ‘afferent system’, which brings you news of the outside world:
the sights, sounds, smells, scratches, and bumps it confers on your body. These
neurons are also called sensory neurons. The ‘moving’ neurons, which bring
your intention down into your body to actuate it, are part of the ‘efferent
system’, which lets you respond to the sensations carried by the afferent
system.
Whether you’re feeling or moving, the signals that are in charge of
transmitting information to and from the brain are sent by way of an electrical
mechanism: the action potential. This was the little needle-moving blip du
Bois-Reymond knew as the action current or nervous impulse. Nerve impulse,
action potential, you might have heard it called a spike – it’s all the same thing:
the small electric signal that relays a message between two neighbouring nerve
cells in the brain, or from nerve to muscle. When a dendrite receives a
message, it passes the signal on to its cell body, which then evaluates whether
to pass that signal on to the axon. If it passes the message on, it zips to the
end of the axon, where it jumps to the next cell’s dendrite. People had started
fighting about whether the nerve signal was electrical or chemical almost from
the moment du Bois-Reymond and Helmholtz started measuring it. But the
fight graduated to near war with the discovery of how the signal hops from
one cell to the next.
This is because that message hits a little speed bump at the end of the
axon. There, it encounters a tiny gap that separates the axon of one cell from
the dendrite of another. This gap is called a synapse, christened the same year
the Neuron Doctrine won its progenitors the Nobel. The discovery of a gap
between cells that were meant to be transmitting an electrical signal revived a
lot of doubts about the still-fragile idea that animal electricity is real and that
the nerve impulse is electric. After all, an electric signal can’t travel over an air
gap in telegraph wires, so why should it be able to do so in the wires of the
nervous system?
In 1921, the discovery of chemicals called neurotransmitters, which float
across the synapse’s gap, only deepened those doubts. That briefly led to a
fight over the nature of the nervous signal between opposing groups of
scientists who called themselves the Soups (team chemistry) and those calling
themselves the Sparks (team electricity).2 It was like science’s own West Side
Story.
In the end – after fierce fights against the Soups’ insistence that no
electrical aspect existed – the Sparks won the day. Their champions were Alan
Hodgkin and Andrew Huxley, two Cambridge University physiologists whose
names may engender a very faint rustling in the back of your brain, in the part
that had to memorise something about their endeavours in school. The reason
their work is canon in the history of science is because they established that
electricity is a crucial arbiter of the nerve impulse. They finally ended all the
nattering between the Soups and the Sparks in the 1950s. Their experiments
showed for the first time, in indisputable detail, exactly how the action
potential is carried down a neuron by electrically charged particles, without
whose electrical properties and activity nothing would happen at all.
Those particles are called ions. Ions are atoms with a positive or negative
charge. The fluid that bathes every one of your cells – there’s a lot of it, and it’s
the reason you always hear that you are 60 per cent water – is teeming with
them. The ions that are dissolved in this so-called ‘extracellular fluid’ bear a
strong resemblance to the constituents of seawater: mostly sodium and
potassium, with smaller amounts of other stuff including calcium, magnesium,
and chloride. Their precise concentrations inside and outside each neuron are
the primary determinants of whether an electrical signal is permitted to pass.
 They got their name from Michael Faraday, in honour of their weird
tendency to move as if of their own accord. It was thanks to Volta’s pile that
he discovered this tendency, in fact. After Volta gave him one of his early
prototype batteries in 1814,3 Faraday used it to devise the principles of the
electric motor and induction, and unify the laws of electricity. But much more
important for our purposes here, it was instrumental to his discovery of the
existence of ions. Faraday would experiment with putting various compounds
into water and passing an electrical current through the water to see what it
would do to them. Compounds are materials composed of a mix of two or
more separate elements: under an electric current, the compound would
dissolve back into the two separate elements that had made it, a bit like a cake
neatly disgorging its sugar and flour. In this metaphor the ‘sugar’ bits, having
segregated themselves out of the mix, would migrate over to the electrode that
was passing the current through the water; meanwhile, the ‘flour’ particles
would congregate at the other electrode.4 Faraday didn’t know what to make
of this back then. What was it that was travelling through the water and
accumulating on his electrodes? In 1834, he christened the mysterious particles
‘ions’, which is about as far as anyone got with them for the next half century.
Then, in the 1880s, the Swedish scientist Svante Arrhenius realised that
ions’ movement was a result of them being pulled by electrical forces – which
made sense, as ions were just atoms that, rather than being neutral, were either
positively or negatively charged. This explained how they wandered through a
solution as if of their own accord. They weren’t doing that at all; rather, the
positive ions had been attracted to the negative pole of the battery, and the
negative ones wanted to get to the positive side. Finally, a clear explanation for
Faraday’s observations.
These properties apply in all solutions – including the biological soup that
bathes the inside and outside of all the cells in all biological tissues. Ions are
the ingredients that keep us alive. If you’ve ever been on an IV drip, you have
ions to thank, and the nineteenth-century physiologist Sydney Ringer, who
figured out the precise recipe of sodium, potassium, and other electrolytes to
flood your vasculature with this facsimile of extracellular fluid. It enabled him
to keep organs from failing even after they had been removed from the body
that previously sustained them. His first experiment was on a frog heart,
which, when placed into his new ‘physiological saline’, was able to keep
beating for several hours normally, sans frog.5 The broth was originally called
Ringer’s solution, and has been monumentally consequential for biology.
But why were ions so important? What was so special about them that we
couldn’t live without them? As the twentieth century dawned, the consensus
slowly emerged that ions could be the main agents in the electrical
transmission of the nervous impulse.
As the Neuron Doctrine was coming into view, here’s what we knew. One:
biochemists had established that positively charged atoms like sodium, and
negatively charged chloride, carried their electrical charge with them wherever
they went. Two: it was also understood – thanks to people like ringer – that
ions populate the spaces inside and outside our cells. And finally, three: we
knew action potentials created electrical activity strong enough to make
galvanometer needles swing as the nervous signal flew past. Together, this was
circumstantial proof that electric charges were moving in the nerve or muscle.
But just as we had had a collection of unconnected facts about animal
electricity in the eighteenth century with no framework to unite them, we
didn’t yet have a way to make sense of all these separate facts about the
nervous system and ions. Not until the 1940s anyway, when a series of
experiments showed exactly how ions were the main agents in the electrical
transmission of the nervous impulse.
Alan Hodgkin and Andrew Huxley knew if they could prove that ion
concentrations changed differently inside and outside a nerve cell during the
course of an action potential, it would prove once and for all that electricity
was involved in the very heart of the generation of the bioelectric signal – as a
causative agent, not just as an echo of some chemical process.6 Again, frogs
met their end – but their nerves were definitely too small for any existing tool
to be able to analyse the ion content inside their membranes. Next, Hodgkin
and Huxley tried crabs. Still too small. Finally, they found an animal with a
nerve big enough to stick an electrode into: the squid.
This creature has a pair of uncommonly large axons – on the order of
millimetres, a thousand times the diameter of anything in a human, earning
them the nickname ‘giant axon’ – as they must send the brain’s ‘run away!’
instructions instantly down a squid’s massive body.7 This left plenty of room
for Hodgkin and Huxley to insert the recording equipment necessary to
monitor the electrical properties of the cell. They wanted to know how these
would change as the nerve fired, and how the ion concentrations would
change, inside and outside the cell, in response. They found a way to stick one
electrode inside, and another outside, and in so doing, for the first time
measured the electrical difference between the inside and the outside of a cell.
That difference was pretty big: the outside of the cell was 70 millivolts higher
than inside when the nerve wasn’t actively firing, just resting.
This number is called the cell’s membrane potential. It measures the
difference between the charged particles inside the membrane and outside it.
Remember how ions are positively or negatively charged atoms? That means
they bring their charge with them wherever they go. A sodium is carrying a
+1, for example. So is potassium. Chloride drags around its -1, and I can’t help
thinking of it as being perpetually low-key ashamed. Fancy calcium poses
conspicuously with its +2. Outside the neurons, a mix of these ions (and their
various charges) congregates in the free space of the extracellular fluid.
Because there’s only so much room in any given neuron, the comparatively
lower population of ions inside them creates a situation where the sum of
charges is lower inside the cell than out. That’s why it’s 70 millivolts lower in
any neuron than in the spaces outside it, and that 70 millivolts is exactly how
the neuron likes it. For that reason, it’s called the ‘resting potential’. It’s the
neuron putting its feet up, conserving its energy.
But when an action potential raced through, Hodgkin and Huxley found
those numbers changed wildly. The charge difference between the inside and
outside of the cell quickly zeroed out, getting less and less pronounced until
there was no difference between the inside and the outside of the cell. (Then,
it kept going just a little bit past zero, until the inside of the cell was
momentarily more positively charged than the soup outside.) But when all the
fuss was done, it always returned to its 70-millivolt happy place.
While all this electrical commotion was underway, Hodgkin and Huxley
also noticed that the different ions did very different things. During the resting
potential, lots of potassium ions were inside the cell. But when the action
potential happened, suddenly it was all sodium in the cell, which belched out a
big wave of potassium. The cell’s return to happiness was accompanied by a
return of all the potassium ions. This phenomenon cascaded down the nerve,
carrying the nerve impulse like a wave. That’s how Hodgkin and Huxley finally
proved that action potentials are unquestionably generated by changes in the
concentration of ions.8 The sodium and potassium were somehow responsible
for the signal travelling down the axon – the electrical charge passed on by the
precisely choreographed comings and goings of these ions.
So there it was: the solution to the mystery of Ringer’s solution. The
reason this precise mix of ions is crucial to keeping a body alive is that they are
what makes the nerve impulse travel down the nerve. Without ions, the
nervous signal couldn’t jump. Then we couldn’t breathe in or out or swallow
and our heart wouldn’t beat.
In 1952, Hodgkin and Huxley published the results of years of work that
showed how sodium and potassium ions swap places in a cell, carrying their
electrical charges in and out, to create the action potential. Revealing the
mechanism of the action potential for the first time netted them the Nobel,
but for Hodgkin the real triumph was the concrete evidence that electricity
was not just a side effect but the cause. As he put it in his Nobel lecture in
1963, ‘the action potential is not just an electrical sign of the impulse, but is
the causal agent in propagation’.9
Their discovery was momentous, and should have set off a coordinated
new quest to understand the information carried by these ions (and for a short
time it did – one report quoted how the oceans around the main research
centres briefly ran out of squid). But the spike in interest was short-lived. Just
when animal electricity should have taken the spotlight once more, a cloud
passed over the sun. No sooner had Hodgkin and Huxley revealed the elusive
mechanism of the nerve impulse, than two other young researchers stole the
show with a discovery deemed far more monumental: the double helix. In
1953, James Watson and Francis Crick – and Rosalind Franklin – unveiled
their discovery of DNA. ‘There are only molecules. Everything else is
sociology,’ Watson pronounced,10 and the importance of bioelectricity was
sidelined by a ‘bigger’ discovery once again, just as it had been after Galvani.
Hodgkin and Huxley had shown that an action potential depends crucially
on a cell holding tight to potassium and expelling sodium. But apart from the
glamour of DNA, the bigger reason the avenue of research they had opened
didn’t continue into humans was because we didn’t have small enough
equipment to peer into the ever tinier nooks and crannies we’d have to explore
to see ions going in and out of a cell and find out how it was happening. As a
result, big questions went unanswered.
A longstanding theory going back to du Bois-Reymond’s time had it that
the cell’s membrane wall would just disappear every so often, becoming
transparent to a bunch of ions, like a curtain being pulled aside.11 But that had
never made much sense – and it made even less sense now in the wake of
Hodgkin and Huxley’s findings. Seeing sodium and potassium swap places like
that made Hodgkin realise the membrane was not just being drawn back like a
curtain. It was actively choosing what to let in and out. But what was the
mechanism? Did neurons have special holes for particular ions?
How did nerve cells know how to only get rid of sodium, while potassium
was untouched? This was especially weird given that potassium is about 16 per
cent smaller than sodium, lending extra mystery to the question of how a cell
could momentarily expel all potassium while allowing in sodium.
During their long years of experimentation, Hodgkin and Huxley
formulated a theory that the ions were entering and exiting through tiny holes
that perforated the membrane like a sieve – maybe some of these holes liked
sodium, and others potassium? People were starting to develop theories and
language about these dynamics – but they didn’t get a name until they were
christened ‘ion channels’.

I am ion man

What exactly is an ion channel, anyway? Since the 1960s, there had been
growing suspicion that these pores were actually proteins that tunnel through
the cell membrane. But no one managed to get any further until the early
1970s, when Erwin Neher, a physicist, and Bert Sakmann, a physiologist, got
their hands on the problem at the Max Planck Institute for Biophysical
Chemistry in Göttingen, West Germany. They reasoned that if those little
holes actually existed, it should be possible to detect the teeny-tiny currents
stirred up as the ions shuttled in and out. But since that’s about a hundred
thousand millionths of the current that powers your toaster, detecting it would
require more sensitive equipment than anything that could be built.
So Neher and Sakmann created a new device that could isolate a little
patch of neuron containing just a few, or maybe even a single one, of these
putative holes. The ions and the holes were still too small to see with the
equipment of the time, but when they were able to record the telltale current
coming out of a single ion pore in a living cell membrane, Neher and Sakmann
proved the holes were actually there. They existed.
What’s more, they figured out how they worked. The shape of these
current pulses made it clear that these little pores could only ever be in one of
two states: all the way open or all the way closed. They were never half ajar.12
And when they were open, boy, were they open. A single open pore let
potassium and sodium ions flood in and out of a cell at a rate ranging from
10,000 to 100,000 ions per millisecond. That is a lot of +1s.
A few years later, in 1978, William Agnew and his team at the California
Institute of Technology (Caltech) finally identified what a sodium channel
actually is: it’s not just a hole in a sieve, it’s a protein.13 And with that insight,
molecular biology went from show-stealing enemy to bioelectricity’s best
friend. That’s because Watson and Crick’s DNA discovery had given scientists
the ability to read any protein’s genetic code – which meant that if you could
isolate and sequence it, you could clone it. And that meant you could start
messing around with ion channels in earnest. You could make cells that only
had shut versions, or open versions, and see what the effect was on an
organism.
In 1986, Masaharu Noda was the first to clone a voltage-gated sodium
channel (this is a kind of sodium channel that opens if it detects a change in
the voltage pressing on the membrane around it).14 Scientists started
synthesising proteins in different shapes and cloning different cells with
different kinds and numbers of ion channels.15 You could create cells with
particular channels edited out altogether. If you were really enterprising, you
might make cells with ‘designer’ Frankenchannels that had been edited
together – and see what happened next. This research soon gave scientists a
full index of all the ion channels – sodium channels, calcium channels, chloride
channels, potassium channels. Never mind the transparent curtain – it was
these proteins that decided which ion was allowed to go where, when.
How did they make these complicated decisions? That puzzle was solved
in 1991 – the same year Neher and Sakmann got their Nobel for kick-starting
this avalanche of research – by the biophysicist Roderick MacKinnon.
Many complex metaphors have been used to describe the incredibly
complicated system MacKinnon uncovered. But I like to think of ion channels
as shape sorters – you know, the toy you give a baby so it can shove different-
shaped pegs into a wooden box through matching holes. Some of the pegs are
round, others are triangular, or squares, or stars. The square holes
accommodate the square pegs, and so on. So, while some holes may be
technically bigger than their non-matching counterparts, they still won’t fit
through. They are incompatible with the dimensions of the channel, and
therefore it remains impenetrable. (It’s actually a little more complicated still,
because the holes in this baby toy shape-shift to accommodate the peg they
like best.)
After MacKinnon completed the picture of the cell membrane, we
understood for the first time the array of interlocking mechanisms that
underpin biological electricity: how the proteins in the membrane work with
ions to generate the action potential, and how everything goes back to square
one again when the action potential has passed. Once we understood ion
channels, we were able to understand the action potential in full.
It is remarkably similar to how you manage an exclusive night club.

In the club
I should mention that the following analogy ignores the entire universe of
complexities inside and outside a cell, focusing only on the place where the
voltage is generated. But after all, this is a book about bioelectricity.
You can therefore think of the cell as a highly micromanaged nightclub.
Ions take the role of the patrons, and the ion channels act as bouncers staffing
VIP access doors. These participants orchestrate the three stages of the action
potential. (My ridiculous ion nightclub piggybacks on a wonderful explanation
in Frances Ashcroft’s The Spark of Life.)

Stage 1 – the resting potential

At rest, when no action potentials are passing through, the nerve cell is in
what’s known as its ‘resting potential’. This was the 70-millivolt difference
Hodgkin and Huxley found. In this state, the inside of the cell is more
negatively charged than the soup in the extracellular space.
Inside our club, the crowd is mostly made up of positively charged
potassium ions, which cram into the tiny space at a concentration fifty times
greater than they mill around outside. Outside the club, a long line of hopefuls
– mainly sodium ions, also carrying a positive charge – press against the doors.
But alas, most of those doors are shut to them. Management has a clear
preference for members of the potassium group – a strict NO SODIUM
ALLOWED policy is in effect. Those sodium ions though, they’re just like us,
so they cram in greater and greater numbers against the doors, wanting to get
in. But management is not messing around. If a bouncer, known as an ion
pump, finds a sodium ion has somehow sneaked in, it is briskly escorted out –
and in a final insult, any three available potassium ions are waved through
security in its place.
As for the potassium ions – well, they’re just like us too. They get tired of
the heaving conditions inside the club and occasionally depart, leaving a
negative charge behind them. There are no barriers to them leaving.
This delicate balancing act of managerial vigilance, the sodium ions’
desperation, the potassium ions’ general standoffishness, and other variables, is
what keeps the cell membrane’s resting potential perpetually hovering at -70
millivolts. (More positively charged sodium ions outside than positively
charged potassium ions inside make the inside negative compared to the
outside.)
Little wonder the cell biologist Robert Campenot describes the state of a
nerve cell before an action potential as being on a hair trigger. All it needs is
an excuse. Any minute change in the equilibrium will pitch it all into chaos.
Before we get to that, though, there’s just one more thing. Those doors
with the bouncers I’ve described so far are not the only doors. There are also
emergency doors: the voltage-gated sodium channels. They bang open if they
sense a change to the carefully maintained resting potential. If the amount of
charge outside the club changes the right amount, then in an instant, all the
potential energy that has thus far been held in delicate suspension is released.16
Which is to say, if the crowd of sodium outside the club gets too rowdy, the
velvet ropes topple, and they start to force themselves into the club. And then
it’s panic at the disco.

Stage 2 – the action potential

Relative to the size of the cell, the membrane potential is massive. The cell
membrane is about 10 nanometres across, and one side of it is 70 millivolts
more negative than the other. If you had the equivalent voltage difference
across your body, it would feel like 10 million volts. That is . . . a lot. An
intense static shock that will make you turn the air blue with swear words
packs about 10,000 volts.
The shock of an action potential is way more intense for our little ion
channel bouncer friends. The emergency doors are flung open. The sodium
ions take advantage of the confusion to rush into the club, triggering a
feedback loop: the bigger the change in membrane potential, the more sodium
channels open and the more sodium ions crowd in – and the more sodium
ions come in, the more the voltage goes positive, the more sodium channels
open, and so on. In an instant, sodium has taken the place by storm.

Step 3 – repolarisation
Now that millions of sodium ions have mobbed this formerly exclusive club,
jostling and crowding the horrified potassium ions, the inside of the cell can
briefly reach 100 millivolts more positive than the outside. Less than a
millisecond later, the potassium channels open and the potassium ions,
disgusted, leave the club en masse.
Inside the club, the mass exodus of potassium ions has returned the cell
membrane to its resting state. But now the customers are all wrong!
Management is desperate to win back the fleeing potassium ions. They lock
the place down again. The bouncers start cracking their knuckles. Most of the
sodium ions leave of their own accord.17 It takes a while to convince the
potassium ions to re-enter the despoiled premises. Eventually, though,
management coaxes them back. Then it’s just a matter of time before the
whole thing happens all over again.
The voltage opens and closes the channels.18 Sodium and potassium
channels that react to the voltage changes mediate the generation of action
potentials, which allow signals to be propagated from one end of a neuron to
another. The same mechanism was ultimately even what controlled the
chemical neurotransmitters. At the very end of the axon, where the action
potential terminates, there’s another set of bouncers: voltage-gated calcium
channels. When the action potential hits, these open, and calcium from the
extracellular saltwater floods into the end of the axon. That releases
neurotransmitters (your familiar serotonins, dopamines, oxytocins) to drift
across the axon terminal and onto the nearby entry point of the dendrite of
the neuron next door. And that sets off the next action potential, and the
whole sequence starts all over again. All these things – chemical and electrical
aspects – are ultimately controlled by the membrane’s voltage, its electrical
status.
And that’s the story of the nerve impulse – the thing that’s responsible for
our every sensation, motion, emotion, and heartbeat. Its electricity is the
central generator. The source of your electricity, and mine, is not a separate
electric organ like the one in an eel, but a self-regenerating mechanism
produced inside the cells themselves, by the exquisitely coordinated dance of
ions through proteins.
The basic mechanism that was in charge of all of this complexity was
startlingly simple. Stack more charged ions on one side of a membrane than
another, and you got an electrical potential. Change the voltage, and you
released all that energy. That’s essentially how a battery works: one side has a
different amount of charge than the other. Nerve and muscle cells, it became
clear, were tiny rechargeable batteries.
Forty trillion batteries

But they were not the only cells that acted like batteries. After it became
possible to properly study ion channels using the tools of molecular biology, it
became clear that ion channels (and the ions they admitted and didn’t) were
also present in every other cell in the body. This was the wake-up call: what
were they doing there? What use did all these other cells have for electrical
properties?
We found out in due course. In 1984, the ion channel physiologist Frances
Ashcroft found that the pancreas, for example, uses a particular potassium ion
channel to issue the electrical commands that precisely synchronise its insulin-
secreting beta cells. (These travel ten times faster than the chemical kind, so it’s
the only way to synchronise that many cells to act in unison.) This potassium
channel needs to be in perfect working order to coordinate the insulin release.
In the early 2000s, Ashcroft and Andrew Hattersley found the mutation that
locked it open – and thereby caused a variant of diabetes.
Insights such as these multiplied and soon transformed medicine. Ion
channel physics emerged as a major biomedical discipline in its own right.
Now scientists had the tools and understanding to investigate how ion
channels in muscle and nerve cells sustained the most basic workings of the
human body. And more importantly, what happened when they didn’t. Most
importantly, they finally had a new tool in the arsenal for manipulating that
electricity more precisely, and it would prove the most consequential tool for
bioelectricity researchers since the invention of the battery.
The first ideas for drugs that could manipulate the electrics came from
neurotoxins. In the 1960s, research on neurotoxins had clarified that many of
these natural poisons affect sodium and potassium balances, throwing into
chaos the delicate mechanisms that make cellular communication possible –
acting like a reverse Ringer’s solution.19 The reason you’re not supposed to eat
puffer fish (unless it has been prepared by someone with an advanced degree
in precision-filleting a puffer fish) is that some of its parts carry a defensive
poison called tetrodotoxin. Get even the tiniest amount of that inside you, and
it can quickly paralyse the muscles that drive everything in your body, including
your lungs, and then you asphyxiate. The exact mechanism of how this works
was unlocked by the improved understanding of ion channels brought by
Neher and Sakmann: tetrodotoxin keeps sodium ions from entering the cell.20
It wedges itself into those channels, blocking the doors, and if there’s no
sodium influx, then there’s no outward potassium stampede, and that prevents
all the rest of the dominoes that cascade into an action potential. Other kinds
of neurotoxins pry open all the doors, which has the same eventual effect: the
cell can’t communicate any signals to other nerves or muscles. No cell can
survive without functional ion channels.
Once researchers realised how nature made neurotoxins – by throwing a
wrench into those all-important ion channels – they realised they could make
their own bespoke neurotoxins to jam shut, or pry open, only the channels of
their choice. (Ashcroft and Hattersley figured out that an existing drug could
close the errant ion channels and reverse this rare form of diabetes.) And that
was the dawn of the age of ion-channel drugs.
Ion channel drugs are a bedrock of modern medicine. They underpin
treatments you get for some snake bites by artificially pumping up the
communication between the nerves and muscles. They underpin drugs for
heart arrhythmias. Now researchers are investigating a whole slew of
movement disorders, epilepsy, migraines, and some rare inherited diseases for
possible mutant ion channels.21 All over biology, ion-channel physics
revolutionised the treatment and conceptualisation of disease and disorder. ‘It
is difficult to exaggerate our misunderstanding of heart action potentials
before we knew about calcium channels,’ wrote one cardiac
electrophysiologist.22
Ion channels are important drug targets, but our understanding of them is
incomplete. We keep finding more unexpected variations of them. One is gap
junctions, which were first noted in the heart but now seem to be in every one
of our trillion cells. A gap junction is a special ion channel that pokes between
two neighbouring cells, creating a sneaky door only they share, like adjoining
hotel rooms. In heart cells, gap junctions synchronise the activity of cells that
need to operate in tandem, but they also festoon the membranes of skin cells,
bone cells, heart cells, and they even occur on blood cells. They are
everywhere. They all talk to each other using these electrical synapses. What on
earth for?
New ion channels aren’t the only surprises. Another recent observation is
the electron current expelled by cancer cells as they make the transition out of
good health.23 On a larger scale, there are also aspects of the nervous system
we didn’t appreciate until the turn of the twenty-first century, when it started
to emerge that the nervous system doesn’t just act on the feeling and moving
bits, but also regulates organ function and the immune system. These are the
kind of insights that are beginning to form the outlines of the electrome.
 Until recently, knowledge of these disparate electrical features of biology
was sequestered in narrow subdisciplines. That’s because the study of
bioelectricity had been increasingly siloed into neuroscience, and in
electrophysiology, which focused a lot on nerves and neuroscience – to the
extent that scientists assumed bioelectrics were only used by nerves.
One of the more astonishing features of the electrome is that animal
electricity is by no means confined to animals. We’re not the only ones with
these ion channels. All the other kingdoms are run on the same stuff.

Electric kingdoms

We had had glimpses of that reality, too, much earlier than we could reasonably
account for it. In 1947, the physiologist Elmer Lund found electric fields
coming off algae.24 He wasn’t alone; these confounding electric emanations
seeped from every other biological surface people thought to measure: Venus
flytraps, frog and human skin, fungi, bacteria, chick embryos, fish eggs, and oat
seedlings.
Reports from disparate fields of study indicate that the electrical signals
used by plants, bacteria, and fungi are all weirdly similar to our own, and the
research is beginning to suggest that they use these signals to very similar
effect. Bacteria use electrical calcium waves to coordinate themselves into
biofilm communities (disrupting these electrical control signals is a hot
research topic in the fight against antibiotic resistance).25 Fungi use them
(among other things) to communicate along their long tendrils whether they’ve
found a nourishing food source or a dud.26 Plants use electricity to activate
chemical defences against predators. The list goes on and on.
We have wondered in the past twenty years, as we discover ever more
similarities between their electrics and ours, why these signals (in bacteria, in
fungi, in protists) are so similar to those in our nervous system. But now a lot
of people are starting to wonder if perhaps we’ve been getting the question
backward: why are we so similar to them, and what does that mean about our
electrics?
All creatures, brains or no, use a collection of similar ions to create
voltages across their cells. We all use these voltages as a basis of
communication. Animals use them to make their nervous systems function as
a command and control centre; other kingdoms use them for signalling and
communications without a nervous system. ‘Flipping the voltage potential is
how, I think, all signalling probably began,’ says Scott Hansen, an
electrophysiologist at the UF Scripps Biomedical Research Institute at the
University of Florida.
And that is raising a wild idea: could we have another communications
system running in parallel to the nervous system? Recent research strongly
suggests our bodies are running at least two – if not more – electrical
communications networks.
Evidence has begun to accumulate that the bioelectricity in the nervous
system – the animating force behind animal spirits – is not the only electrical
communication network used by the animal body. Strange electrical features
and behaviours connect all the cells in our body. Skin, bone, blood, nerve –
any biological cell – put it in a petri dish and apply an electric field, and they all
crawl to the same end of it. It’s as if they can sense the electric field, even
though we don’t yet understand how cells could possibly sense those things.
All we know is that electric fields affect the bioelectric properties of a cell –
any cell, and sometimes whole organs – in a way that can be used to make it
do things it normally wouldn’t.
It is for this reason that some scientists are beginning to think
bioelectricity can be understood as a component of epigenetics – which
describes how the environment can cause changes that alter the way your
genes work without changing the actual DNA. ‘More and more epigenetic
factors which drive the organisation of biological information patterns and
flows are being discovered,’ writes the physicist Paul Davies.27 Bioelectricity is
emerging as a major – if as yet poorly understood – epigenetic factor, he
thinks, providing a powerful way for cells to manage epigenetic information.
But other researchers are finding that it may be more than just another aspect
of epigenetics. The word ‘epigenetic’ means ‘above the genes’. And maybe
electrical signalling functions as a kind of ‘meta-epigenetics’ – one ring to bind
them, if you will. As you will see over the next few chapters, electrical guidance
exerts control over a great many complicated aspects of biology, from how
genes are expressed to whether inflammation will commence in the immune
system.

The bioelectric code

A granular understanding of the electrome, then, could also provide a way to
control the genome almost as easily as we can control our computer hardware
with software. Indeed, the Tufts University researcher Michael Levin is among
those who have found evidence to suggest that the electrical dimensions of life
can exert control over genes, providing a way to hack other systems we
previously thought were too complex to precisely control. Levin suspects that
this deeper understanding of bioelectricity will yield a bioelectric code. This
code is written not in genes but in ions and ion channels. That code controls
the complicated biological processes that formed you in the womb, by
executing a controlled program of cell growth and death. The bioelectric code
is the reason you retain that same shape throughout your entire life; it prunes
your dividing cells so you keep being recognisably you. And if it could be
deciphered and manipulated, it could be used to precisely re-engineer the
human physical form, rescuing it from birth defects and cancer (more on that
in Chapters 7 and 8). If we can profile the electrical properties of biological
tissues in the same way we have profiled its genetic basis – that is, to complete
the human ‘electrome’ – we can crack the human bioelectric code.

When people think about the origin of life, obviously the first thing that
comes to mind is the genetic code. How did DNA and RNA evolve in the first
place, and lead to reproducible life, and all that jazz? There’s a second thing
that should come to mind, but usually doesn’t. How is it that you got a cell
membrane?
The cell membrane is important for a number of reasons. The first is just
practical. All the DNA and RNA in the world, reproducing all the elements, all
the nucleotides and amino acids you could possibly want for life – well, they’d
just float away in a big soup if they didn’t have a container. To do anything
remotely useful with the constituents of life, you need something to hold them
all together. So that was the membrane: the most underappreciated
evolutionary innovation.
But there’s a bigger reason the membrane is so important. As soon as
there’s a membrane, there’s a separation between an inside and an outside. And
since every cell we know about has always contained different kinds of ions,
the second you had a membrane separation, you had a voltage. That’s just
physics. After that, you just needed the proteins to form passages in the
membrane that allowed all those ions to get in and out of the cell.
These ion channels, as a group, are something like three billion years old.
Plants, fungi, animals, the whole lot of us inherited them from our eukaryotic
ancestors. Signalling certainly didn’t start with sodium channels – those only
evolved around the time the first nervous systems did, about 600 million years
ago.28 In 2015, the neurobiologist Harold Zakon published a deep
evolutionary history of ion channels and found most of the same ion channel
families are present all the way back to our last known ancestor.29 Our sodium
channel’s building blocks, Zakon found, were found in the first ion channel,
potassium. In fact, the potassium channel is the little Lego from which most
of the other channels – sodium, calcium and so on – were later formed. ‘The
motif that allows potassium to permeate the channel is very ancient, very
conserved. It’s pretty much the same from bacteria to us,’ Zakon says. ‘We
have it, every cell in our body has it, probably every cell on earth has that gene
for that channel.’
In fact, you can still find that molecular motif of the first ion channels in
bacteria today. Every subsequent channel and pump comes from that ancestral
gene.
The upshot is this: separating and moving ions across membranes is
fundamental to all living things. Nervous systems did not invent it, and we are
still nowhere near understanding the full extent of how nature recruits its
electric potential. Although literally all cell types use this self-generated
electricity, the breathtaking range of functions for which it is instrumental is
utterly underappreciated. It’s certainly not covered in textbooks of
introductory biology, at least not in such a way that would make anyone
actually appreciate the importance of the electrical dimension of life or the
deeper significance. Those elements we all ferry across our membranes –
sodium, calcium, chloride – are fossil stardust. If there are any other cells out
there in the universe, we might share that with them, too. ‘Probably every cell
in the universe,’ Zakon noted.
We knew none of this when we first started to experiment with animal
spirits and found the first hints of what would later become the bioelectric
code. We didn’t know about ion channels or patterns, and the only tools we
had to probe the animal spirits were cousins of Volta’s pile. Which is why the
first glimpse of the electrome came to us courtesy of the electrical activity of
nerves and muscles. This – as you’ll see in the next three chapters – was how
we started to learn that we could use electricity to take control of our hearts,
brains, and central nervous system.
 PART 3

Bioelectricity in the Brain and Body

‘Wonderful as are the laws and phenomena of electricity when
made evident to us in inorganic or dead matter, their interest
can bear scarcely any comparison with that which attaches to
the same force when connected with the nervous system and
with life.’
Michael Faraday, Experimental Researches in Electricity

I n the twentieth century, better tools began to reveal the first hints that
there were patterns in bioelectric signals that might indicate health or
disease. This quickly led to the notion that electrical stimulation could be used
not only to understand the body but to improve it – by overriding the faulty
patterns with healthy ones. We could electrically control ourselves back to
health.
 CHAPTER 4

Electrifying the heart: How we found

useful patterns in our electrical signals

F ew protests had been lodged about the horrific dissection of either

Galvani’s frogs or Aldini’s decapitated prisoners in the quest to
understand animal electricity, but the dog-loving citizens of the UK had their
limits. In 1909, an affronted member of the anti-vivisection lobby arrived at
the House of Commons with a report of an alarming act of scientific cruelty.1
That May, the lobbyist had attended a ‘Converzatione’ – a soirée at which
the scientists of the Royal Society would demonstrate their findings for
members of the public. (The allure of these events, according to one
newspaper, was that ‘for once [scientists] condescend to admit the average
man and woman into their mysteries’.) One such demonstration featured a
scene shocking enough to warrant a hearing before Parliament: a dog had been
restrained by a ‘leather strap with sharp nails wound around his neck’,
according to the anti-vivisectionist’s complaint, ostensibly to keep the poor
creature immobilised while its ‘feet were immersed in glass jars containing salts
in solution, and the jars in turn were connected with wires to galvanometers.
Such a cruel procedure should surely be dealt with under the Cruelty to
Animals Act of 1876?’ the petitioner admonished.2
The grisly description proved somewhat misleading, and it fell to acting
Home Secretary Herbert Gladstone to clear things up.3 Rather than an ill-fated
specimen destined for experiments, he explained that the animal in question
was in fact the scientist’s beloved pet English bulldog, Jimmy. That ‘leather
strap with sharp nails’? Jimmy’s (rather expensive) brass-studded collar. And
finally, Gladstone clarified that the ‘solution’ in which the dog stood – of his
own volition and indeed pretty cheerfully, in keeping with his reputed
‘Churchillian’ demeanour – was saltwater. ‘If my honourable friend had ever
paddled in the sea, he will appreciate fully the sensation obtained thereby from
this simple pleasurable experience,’ he concluded. Nonetheless, with this
harmless demonstration Jimmy the bulldog had just done more for the
advancement of electrophysiology than all of Aldini’s dead prisoners. He – or
rather his owner, the physiologist Augustus Waller – had demonstrated the
world’s first recording of the electrical activity of the heart.4
The ability to listen to electrical signals would soon become a cornerstone
of modern medicine, and not just for the heart, whose previously opaque
processes were about to become a lot more transparent. By the end of the
twentieth century such signals would be discovered radiating from many other
organs, using tools Waller wouldn’t have dreamed of, to gain penetrating
insights into the health and disease of a person’s body and mind to a degree he
would hardly have believed possible.

The telltale heart

In the mid-1880s, Waller realised that if you connected your limbs to an

electrometer, it should be possible to form a circuit through which you could
conduct the heart’s electrical signal and make it legible. (Prior to his
breakthrough, the only way to ‘read’ a heartbeat had been to open the body
and put electrodes directly on the exposed organ – a feat only possible with
more grisly animal experiments and occasionally on people with horrible, yet
medically fortuitous, injuries.)
For Waller, however, recording the electrical activity of the heart remained
something of a party trick. The tracings provided by his set-up were fuzzy and
imprecise, owing to the slow response time of the equipment.5 They couldn’t
tell you much about the heartbeat except that it was there. Indeed, this is how
his guests tended to avail themselves of it at his soirées, where the ladies and
gentlemen in attendance used his contraption to bring solid evidence to their
companions that they were in possession of a beating heart. And what a
contraption it was: the cumbersome set-up required polite company, after
dinner, to remove one shoe and sock, sit in a chair connected to a large
measuring instrument called a capillary galvanometer that looked not unlike a
Victrola cabinet, and dip a bare foot and one hand into two buckets of saline
water. If the unusual set-up made them a bit nervous, Waller would offer to
first demonstrate on Jimmy, who placidly endured the whole thing.
Instead, the Dutch physiologist Willem Einthoven saw the potential that
escaped Waller’s notice. In 1889, at a physiology conference in Switzerland,
Einthoven witnessed a demonstration of the technique by Waller himself. He
soon refined the device to do what Waller’s couldn’t: get tracings precise
enough to read the contours of the signal.6 Over the next decade, steady
technological improvements led to ever more exact recording of the heartbeat,
culminating in 1901 with Einthoven’s particular contribution, the ‘string
galvanometer’. This electrometer was capable of measuring the faintest of the
body’s electrical signals. If you’ll permit a gross oversimplification, its
mechanism was a string, illuminated by an extremely bright light to cast an
exaggerated, enlarged shadow onto a white sheet. You could watch that
shadow vibrate with every beat of a heart. Einthoven refined it further by
including silver-coated quartz strings, moving photographic plates, and
mechanical pen recorders, but my description of the basic mechanism stands.
The only reason Waller or Einthoven were able to pick up these surface
readings from the heart is that the signals, as small as they are, are so incredibly
‘loud’ in combination – loud enough to be picked up by that string
galvanometer. An individual cardiac muscle firing its action potential is a friend
humming quietly next to you; loads of them firing in synchrony is a 100-
person choir harmonising with the organ in the last four glorious chords of
Handel’s Messiah. Only a few places in the body perform Handel’s Messiah:
many heart muscle fibres have to fire together simultaneously to produce the
heart contractions that pump blood around our bodies.
Where Waller’s tracings had been fuzzy and imprecise owing to the slow
response time of the old and busted type of galvanometer he was using,
Einthoven’s better version yielded sawtooth waveforms of such crisp
resolution that it could even tell a healthy heart from a sick one. It was
Einthoven who put a name to these squiggles at the Dutch Medical Meeting of
1893, where he coined the term ‘electrocardiogram’, now best known by its
acronym – ECG.7
The machine he had built to do it, however, was a monster. Waller’s early
iteration was dwarfed by the sheer size and ungainliness of Einthoven’s
creation, which filled two rooms, weighed 600 pounds, and required five
human operators and special cooling equipment8 – not to mention that the
person whose heart was being read now had to immerse two hands along with
the usual foot. But the equipment worked a treat: in the early years of the
twentieth century, Einthoven further formalised Waller’s fuzzy scribbles into
the diagnostically accurate troughs and peaks, within whose characteristic
idiosyncrasies doctors could diagnose heart conditions in hospitals. Clinicians
began to acquire them, including the cardiac electrophysiologist Thomas
Lewis, who in 1908 started using it on his patients at University College
Hospital. With this newfound ability to investigate and describe various heart-
rhythm abnormalities, beginning with atrial fibrillation, Lewis knew he was
laying the foundation for a new field: clinical electrocardiography. The
electrocardiograph enabled medicine to peer into the body as never before,
and over the next decades helped explain exactly how the heart’s electrical
activity was instrumental to its ability to coordinate the flow of blood around
the body.

A pump controlled by electricity

Each pump of blood through the heart is set into motion by a group of cells
that is best understood as the conductor. The group of cells, located in the
upper right part of the heart, is called the sinus node. This conductor
coordinates all the cells of the heart into a precise rhythm that ensures blood
only ever enters one specific kind of chamber and only ever exits another
specific type. Blood enters a set of upper chambers called the atria, and flows
down to the ventricles (the lower chambers), which contract about half a
second later, one ventricle sending its blood to the lungs and the other sending
its blood around the body. This is quite a precise rhythm to orchestrate, and
high stakes! If you do it wrong, the heart can’t coordinate the blood
distribution around the body properly and the body will die. And it all depends
on the electrics.
The conductor kicks off all of this with an action potential, but these are
not the familiar action potentials of the nervous system. That’s because the
muscles of the heart don’t have their own nerves driving them in the same way
that nerves drive skeletal muscle. The heart is all muscle, but it’s an unusual
kind of muscle. It’s a kind of self-determining muscle that moves without you
being in charge of it – as you well know, your heartbeat is not under your
control. With a lot of practice and focus, you can learn to slow it, but you can’t
stop it in the same way you can close your eyes. Rather like nerves, the heart
muscles generate their own action potentials, except without chemical
synapses.
So how does the action potential pass from cell to cell? How is the
conductor’s signal sent to all the muscle cells through the heart? Turns out,
instead of being connected by standard synapses, they’re all connected by
direct, electrical high-speed lines – those gap junctions I referred to in the
previous chapter.9 These adjoining hotel room doors are usually left open so
the signal can instantaneously zap between rooms. Whatever one cell knows or
experiences diffuses immediately through the connecting door for its
neighbour to know or experience instantaneously. This mode of
communication is about ten times faster than a regular chemical synapse
because it does away with neurotransmitters and gaps between cells.
This is how the heartbeat’s rhythm shimmies down from the top of the
organ to the bottom to ensure that the outgoing blood is always pumped just
precisely half a second later than the incoming blood comes in.
It was this synchronised wobble that Waller was picking up. But his early
equipment was too primitive to see the details, which were only made legible
when Einthoven deployed his fancy string. That’s when we got our first look at
those sawtooth-shaped blips that you may know from medical dramas (or if
you’ve ever been hooked up to a heart monitor).
What was much more interesting than seeing the normal heartbeat,
however, was that Einthoven’s crisper readings made it possible to see when
things were not all right with the heartbeat. You could now not only visually
distinguish the signature of a healthy heart from a sick one, you could start to
detect specific ailments – for example, an abnormally slow heartbeat. This
condition, called bradycardia, means the blood can’t deliver enough oxygen to
the brain and other body tissues, so a person with this condition often feels
dizzy or weak, or faints.
Long before we fully understood how all these signals travelled and
worked, people started to use electricity to whip those errant signals into
shape.

The pacemaker takes control

The pacemaker had its origin on an operating table in Prussia in 1878.
Catharina Serafin had just survived a brutal surgery that had removed a
malignant growth but left her beating heart exposed, covered by nothing more
than a thin flap of skin.10 This afforded a rare opportunity for the German
physician Hugo von Ziemssen to mechanically and electrically stimulate her
living heart, which led to the new realisation that it was possible to directly act
on the heart with electricity. Previous investigators like Aldini had thought the
only way to manipulate the heart electrically was by way of the nervous system.
In the course of experimenting on Serafin’s heart, Ziemssen realised that if
you applied periodic pulses of DC current – the same steady flow of electricity
Volta had generated from his pile – that was just a bit faster than the natural
heart rate, the heart would try to keep pace with this artificial metronome.
Here was evidence that you could overwrite a faulty rhythm – or resuscitate a
stalled one – by dubbing an artificial electrical pulse into the place at the top of
the heart where the natural electrical signal originates. But nothing much came
of it. This method only worked when you put the electrode directly onto the
exposed surface of the heart – it didn’t work if you applied the pulse through a
closed chest. And with no one clamouring to open their body to apply electric
shocks, there was no business case.
It took thirty more years for any new medical applications to come of this
understanding. What finally got things going was that the electrification of
America had led to a sharp uptick in accidental electrocutions11 – exactly the
kinds of ‘temporary deaths’ Aldini had been trying to find a way to reverse
more than a century earlier. Now the matter had some urgency. It had been
established that you could restart or correct a heartbeat – the next question
was how to keep it going. Work got underway on a device that could overwrite
the heartbeat continuously. And that device was absolutely terrifying.
It was the size of a small suitcase, weighed 7.2 kilograms – about 16
pounds – and was operated by a hand crank.12 A wire sent the electricity it
generated to a needle that pierced the heart. It worked, but it was a tough sell
to get this into clinical trials. Finding the exact right spot to put the needle was
of paramount importance; if you got it wrong you got a fatal haemorrhage. In
1932, both the device and its creator Albert Hyman were roundly condemned
by the American Medical Association: reports of cardiac resuscitation by such
cardiac injections, they stated, ‘belong with miracles’.13 The scepticism was
part of a hangover from years of experiments like Aldini’s, and ensured that no
American manufacturers were willing to put their reputations on the line to
help Hyman produce his device.
 Nonetheless, by 1950 other physicians, clearly in need and now able to
avail themselves of more advanced materials, developed a different design.
These were not always what you might call an improvement. People had to
wheel them and their tangle of tentacular cables around on a trolley. They
sometimes required power from the wall (more’s the pity if the power went
out, which was not unheard of). Early attempts to figure out how to make
them implantable – the ultimate in portability – needed a better power source
than what was available.

Lightning to the heart

If you think nuclear power would be a bad choice for powering an implant
close to your heart, there are 139 people who would disagree with you.14 In
the 1970s, several manufacturers rolled out pacemaker designs that were
powered by a bit of plutonium. The heat generated as this radioactive isotope
decayed was transformed into electricity that powered the circuits in the
model,15 but don’t worry, they were ‘shielded well enough to deliver very little
radioactivity to the patient’. Battery designs for implantable pacemakers only
got weirder from there, including one that ran on biological electricity not
conceptually dissimilar to Matteucci’s frog thigh battery.16
In 1958, Wilson Greatbatch found an enduring source of power that was
less unsettling than plutonium, with the invention of a pacemaker that used a
lithium ion battery, and there we still are today, for the most part.17 Within a
couple of decades, his invention had been refined into the small, implantable
gadget we understand today as the pacemaker.
The concept is simple enough and the pacemaker is implanted much the
way Hyman did it. Fortunately, no one uses a needle to pierce the heart any
more. Instead, an electrode is surgically implanted on the faulty spot that’s
causing the trouble. The electrode is attached to the pulse generator by a wire
that carries the stimulating electrical charge, conceptually not entirely unlike
the kite string Ben Franklin used to bring lightning down from the sky. Except
instead of atmospheric lightning, this conductor conducts the tiny, contained
lightning from a battery-powered stimulation unit: the pacemaker. These are
improbably tiny now, considering their trolley-top origins – about the size of a
ten-pence piece – and they keep getting smaller.
 The most common use for a pacemaker is to speed up a slow heart rate (as
in bradycardia). The tiny lightning overwrites the heart’s own bioelectricity,
applying miniscule, regular electric shocks to drive the heart at the right rate.
When it reaches the muscle cells in the sinus node (that conductor in
charge of the first domino), the electrical stimulation forcibly changes the
membrane potential of the cell.18 The muscle is depolarised, which opens the
voltage-gated sodium channel, and then triggers the action potential. And then
that sets off all the rest of the cascading actions of the heartbeat.
Some of the most advanced models today don’t just zap; they can listen to
make sure they’re dispensing the right kind of zap at the right time. They sense
the wearer’s heart rhythm so as to modulate it in real time. That ability to
respond to real-time feedback puts the pacemaker in a category known as
closed-loop devices.
After Greatbatch added the lithium ion battery, things happened fast. By
the 1960s, several of the twentieth century’s biggest technological
breakthroughs – plastics, transistors, microchips, batteries – conspired to make
the pacemaker implantable and reliable.19 Engineers and scientists who
adapted it into a working device went on to found a medical device company
called Medtronic. Over the next twenty years, the number of patients with
pacemakers quickly rose from half a dozen to nearly half a million.
In the late 1960s, a neurosurgeon in Wisconsin took Medtronic’s
implantable cardiac pacemaker outside its intended environment for the first
time, repurposing it for his chronic pain patients. It was implanted in the spine
– but that was just the beginning for the pacemaker’s strange journey, which
would soon find a new home in the brain.
So did Waller’s early tracings, for that matter. After first allowing doctors to
diagnose heart conditions in hospitals, and then laying the groundwork for the
first recordings of the activity of the brain, the electrocardiograph became the
basis of much of the electrical imaging that proliferates today to diagnose sleep
and neurological disorders. These advanced brain diagnostics, in turn, opened
the door to the idea that animal electricity is the body’s way of digitising
information so that it can speak to itself in a kind of specialised neural code,
an idea that took root in the twentieth century and has flowered into the
defining idea of neuroscience in the twenty-first. Many are now convinced
that, with these descendants of Waller’s early contraption, we are mere steps
from reading the electrical activity of thoughts – and perhaps unlocking the
secrets of consciousness itself.
 CHAPTER 5

Artificial memories and sensory

implants:
The hunt for the neural code

I n 2016, a Silicon Valley start-up called Kernel emerged from ‘stealth mode’
to publicly announce that they were building a prosthetic memory – a
brain-implantable microchip that would not only help people with traumatic
brain injuries regain their ability to recall information but also eventually help
the rest of us become more intelligent. The possibilities were limitless, if you
believed Kernel’s founder, Bryan Johnson, who had just bet $100 million on
the idea. ‘Could we learn a thousand times faster?’ Johnson said at the time.1
‘Could we choose which memories to keep and which to get rid of ? Could we
have a connection with our computers? If we can mimic the natural function
of the brain, and we can truly work with the neural code, then I posit the
question – what can’t we do?’
If you had been reading the science journals and tech press, you might
have thought Kernel’s plan was airtight. The rate of progress in brain implants
over the previous decade had been astonishing, and Johnson had tapped into a
growing body of apparently promising academic work. He had plucked one of
the world’s most prolific biomedical engineers, Theodore Berger, from the
University of Southern California to lead the project as its chief science
adviser. Berger had been working for twenty years on writing electrical signals
into the neurons of rats and primates. He had just created an algorithm that
could decipher the code sent by one part of the brain to another, and in so
doing had apparently improved several rats’ ability to form short-term
memories.2 Now, with an infusion of Kernel’s cash, it was time for human
trials. The Matrix was upon us.
 Or was it? The belief that the right kind of implants can overwrite our
normal brain activity has become practically an article of faith among the
technocracy. ‘The future of the human race depends upon our ability to learn
how to read and write our neural code,’ wrote Johnson in a subsequent Medium
post.3 But why? And where did it come from, this idea that we’ll soon let
academics and tech companies programme our minds like a PC? The story of
Kernel’s memory chip turns out to be a good parable for the limitations of our
current metaphors for the inner workings of the brain. But to understand the
problem in full requires a brief deep-dive into what people mean when they
speak of the ‘neural code’.

From heartbeat to neural code

The muscles in the heart either respond to a stimulus or they don’t; that much
had been clear to scientists since the 1870s. The rate of a heartbeat can vary
but the beats themselves do not: there are no small or big heartbeats or half
heartbeats. A heart either beats or it doesn’t. Similarly, in early experiments, if
you stimulated a muscle fibre, it either twitched or it didn’t; there seemed to be
no such thing as a half twitch. This was why du Bois-Reymond called it ‘all or
nothing’. For the heart, this binary made sense, because a functioning heart
has one job: it just needs to beat.
But how could nerves and muscles use this same system to transmit more
complicated information to and from the brain? How could they vary the
content of the information they were carrying if all they could do was either
fire or not fire? Nerves and muscles were clearly capable of acting on much
more complex gradients of information. For example, you can choose to flex
your arm either lightly, incompletely, or max out to exhaustion. And we are all
familiar with the feeling of an initial sensation like sitting down in a chair or
putting on a soft jumper, which after a while attenuates so we stop feeling it at
all. Actions and sensations like these are hardly ‘all or nothing’.
To find out whether muscles and nerves were really part of this all-or-
nothing club, at the start of the 1910s the Cambridge University engineer and
electrophysiologist Keith Lucas dispatched the usual complement of frogs. He
was able to confirm that muscle fibres responded only when a stimulus was
strong enough to exceed a certain threshold.
 So all muscles obeyed the same binary rule – they either twitched or they
didn’t. Was the same rule true for nerves? And if it was, how on earth were
they able to deal with complicated information?
Two problems blocked further understanding. The first: wherever you find
them, nerves and muscles are not single wires, but bunched together in cables.
These are a bit like the strands of fine wire ferrying signals along the ocean
floor between continents. The signals aren’t sent in one wire but separately
along individual fibre-optic lines cabled into tight bunches of varying
thickness. Similarly, the nerve ‘cables’ in the body vary in thickness, some
being very thick (like the spinal cord) others consisting of maybe a few tens of
nerves.4 The brain sends the message to the muscle, via the nerve, that it
should contract. So whenever you try to listen to them, you’ll get the din of
loads of different neurons shouting over each other. Isolating an individual
neuron to listen to its monologue was out of the question: first because it was
surgically impossible to unpick a single (live) nerve from its fibre, and second
because an instrument to detect its action potential didn’t exist.
Even when listening to the loudest multi-neuron fibres in concert, you
weren’t listening to their natural conversation. All the way back to Galvani,
every nerve or muscle signal ever measured had been ‘induced’ by artificially
stimulating the nerve to fire by applying an electrical zap. (I guess if we’re
going to stay with this metaphor, this is the equivalent to giving the nerve a
giant static shock and listening to its enraged scream.) This method placed
limits on how much you could learn about how the nervous system really
worked in the wild.
Like any good physicist, the first thing Lucas did was find someone clever
to take over the grunt work in his lab at Trinity College: a young PhD student
in physiology, Edgar Adrian. Adrian’s assignment: find out how the nervous
signal is conducted and whether it also obeyed the same all-or-nothing
principle Lucas had found in muscles.
They started by narrowing down the number of nerves in a muscle fibre
that they had to contend with. Lucas found a muscle in the frog that was
innervated by only ten nerve axons. When he stimulated it with an electrical
zap, he found that the resulting muscle contraction depended on the intensity
of the applied jolt. But that wasn’t true of the individual nerves. They
responded the same no matter the intensity of the electrical jolt: either firing or
not. More stimulation caused more of the nerve fibres to fire, and that was
what changed the amount of muscle contraction. The binary message in
individual nerves never changed.
 Here was solid evidence that nerves obey the same all-or-nothing law as
muscle.5 But the team’s quest was disrupted by the First World War. Lucas left
the lab and joined the Royal Aircraft Factory, putting his engineering skills to
use for the war effort by devising new compasses and bomb sights. While
testing one of these devices in 1916, he died in a mid-air collision. When
Adrian returned to Cambridge after his mentor’s death, his obsession with
Lucas’ question had deepened. How was he going to listen to an individual
nerve impulse? No one had made a machine powerful enough to record the
signals themselves, but could you make something that amplified them
sufficiently for existing machines to record?
During the war, Adrian’s American friend Alexander Forbes worked on
wireless radio receivers, early radar tools, and new devices called vacuum tubes
which could enhance audio signals. The war had made them cheap and easy to
get your hands on. After the war ended, Forbes used them to make a new
amplifier, stuck the thing onto an Einthoven string galvanometer – and voila.
A nerve’s infinitesimal action potential could now be amplified by an
unprecedented factor of fifty, which rose over the next few years to 7,000.6
Such a great device – now if only he could find a way to listen to a nerve
bundle in its natural state, not one that was being artificially jolted into firing
by the application of electrical stimulation. Adrian got himself the blueprints
to build a device of his own, and put in an order for frogs.7
The trick would be finding a scenario where nerve firing was predictable
enough to be caught in situ and recorded. One day, he was recording the
‘resting’ state in a frog muscle. This was intended to provide a silent baseline
against which to compare the natural signals he hoped later to find. The frog
leg was just hanging there, not doing anything and not being stimulated.
Obviously no signal should have been present. And yet, every time he tried to
get a good recording of this baseline resting state, the same annoying,
unaccounted-for noise interfered, the same kind of oscillations that he had got
when actively stimulating the muscle. The interference started to drive him
around the bend, and Adrian laid the frog down on a glass plate – instantly, the
mysterious signal stopped. He picked up the frog, letting its legs dangle once
more. Signal. He put it down. No signal.
That was when Adrian suddenly realised what he was seeing. He
understood the nature of the signal he had been detecting: the nerves attached
to the legs were alerting the central nervous system that they were being
stretched. He had found the signal they used to transmit this complicated
information.
 Now he’d need to find a way to record a single one of these signals as it
travelled along a single nerve. Adrian set to work, and in 1925 he and his
colleague Yngve Zotterman managed to reduce a muscle group to only one
single strip, within which remained only one single muscle, within which
remained only one single nerve. This sensory neuron was tasked with
communicating just one thing: how much the muscle was experiencing the
sensation of stretch. ‘Under strong emotional stress we hurried on,’ Zotterman
wrote, ‘recording the nerve’s response to varying degrees of stimulation.’ The
signal they recorded from the single nerve was a series of clean, steady blips –
the sound of a single, undiluted action potential. The blip was always the same.
It never got bigger or smaller no matter how it was stimulated. The only thing
that ever changed was how frequently it fired. Pull the neuron’s muscle taut,
and the blips became frequent and numerous. Give the muscle slack, and they
slowed. When the muscle was perfectly at rest on the glass plate, there were no
blips at all. Zotterman and Adrian both realised that ‘what we now saw had
never been observed before and that we were discovering a great secret of life,
how the sensory nerves transmit information to the brain’.8 It was a massive
lightbulb moment – they were the first to finally figure out how the brain gets
information from the limbs. They had cracked the code of how these blips tell
the brain useful things about the information in the environment. Stretch:
many frequent blips! Stop stretching: no blips. Something about this encoding
sytem seemed awfully familiar.
The war, with its years of effort that involved breaking code and
intercepting transmissions, had given Adrian a new conceptual lens through
which to understand what he was seeing.9 The mechanism he had found in the
nerve’s information transmission looked like a kind of bioelectric Morse code.
Nerve impulses, and the nervous system in general, had been described in
terms of information communication since the invention of the telegraph in
the previous century. But when Adrian discovered that the nerve impulse was
just a series of variable-in-time brief pulses (Morse code without the dashes),
he was struck by the way this limited signal was able to pass on complex
information (the sensation of stretch). ‘In any one fibre the waves are all of the
same form and the message can only be varied by the changes in the frequency
and duration of the discharge. In fact, the sensory messages are scarcely more
complex than a succession of dots in the Morse code.’10 You can see a similar
change in the language of Zotterman’s accounts. Years later, recounting the
frustration of previous experiments before they were able to isolate that single
neuron, he wrote that ‘it was as if we were tapping a telegraph cable with many
lines simultaneously in transmission. It did not permit any reading of the
code.’11
Adrian’s scientific and popular writings introduced the concepts that began
to define the common perception of the nervous system and, by extension, of
the bioelectric signal and its function: messages, codes, information.
This idea of a code began to bleed from single neurons into the idea of how
whole nerve systems used action potentials to translate the outside world for
interpretation by the brain. Now that there was a code being used by the
peripheral nervous system to send messages to the brain, the next thing
Adrian wanted to understand was how the brain received those signals – how
it translated the Morse code back into a language it could understand. Was the
brain a ‘central station’ that decoded the signals into experience, as Adrian
intimated in the lecture he delivered when accepting the Nobel Prize for this
work? In which case, ‘we could tell what someone was thinking if we could
watch his brain at work’.12
Even before delivering that speech, Adrian had started combing the
literature for any explanation. And while he didn’t find it, he did discover a
possible way to find it: a new machine recently invented by the German
neurology professor Hans Berger. Its findings were of ‘exceptional interest’ to
Adrian, and he and his colleagues were shocked that no one had ever tried to
repeat them.13

Hans Berger’s quest for the brainscript

Almost ten years before Augustus Waller stood his first bulldog in saltwater,
the Manchester physiologist Richard Caton was looking at similar rhythmic
readings he had obtained from putting electrodes on people’s scalps. Unlike
Waller, Caton knew the significance of what he had just found. In the years
since the electrical nature of the action potential was established, speculation
had been growing as to whether the processing machinery in the brain might
have its own electrical signature as well. In 1875, Caton discovered a ‘feeble
current’ emanating even when there was no muscle activity – not in keeping
with scientific consensus of the time, according to which muscle motion
should have been the only thing capable of generating measurable brain
activity. And yet here was Caton’s patient sitting perfectly still, emanating like a
beacon.
Nearly fifty years later, his work was exhumed by Berger, then the director
of the psychiatric clinic at the University of Jena.14 Outwardly, the man was
strict and charmless in the job.15 His heart was elsewhere; he had been toiling
in secret since the 1890s on a project of immense personal significance. It all
went back to an accident he suffered in a military training exercise as a young
man. In 1892, pulling heavy artillery on horseback, Berger was thrown off, his
head landing inches in front of the wheel of an approaching artillery gun. The
cart had stopped at the very last second – by all rights Berger should have
died. When he returned to the barracks that night, shaken by the experience,
he found a telegram from his father asking if he was all right. The reason for
the inquiry: right at the time of his accident, his older sister was overwhelmed
with an inexplicable feeling of panic and pleaded with her father to make sure
nothing had happened to Hans.
Berger couldn’t square the experience with science. What could explain
such an extraordinary coincidence? He could only conclude that the sheer
intensity of his terror had assumed a physical form external to his mind, and
had been transmitted somehow instantaneously to his sister. Berger was
determined to find the psychophysiological basis for mental telepathy.
In 1902, he discovered Caton’s work on detecting the brain’s electrical
currents with an electrometer. After twenty more years of trying to find
commensurate signatures in the brain, he finally got his hands on a string
galvanometer. His first experimental subject was a seventeen-year-old college
student named Zedel, who had been left with a large hole in his skull after the
removal of a brain tumour. Berger attached Zedel’s electrodes to a string
galvanometer he had borrowed from the university hospital, where it was
normally used to do early versions of the ECG. Suddenly, there they were –
electrical tracings like the ones Waller had got from the heart, clear as day, but
this time from the brain. Evidence of electrical brain emanations at last.
But the patterns he picked up from the brain were much more varied,
faint, and noisy than the signals the clinical device had been able to detect
from the heart, and therefore much harder to analyse for coherent motifs.
Berger ordered an even bigger galvanometer. For five obsessive years he
painstakingly tweaked the apparatus to tease out meaningful patterns from all
the other interference that obscured them: the slightest bodily movements, the
heartbeat, and even the pulsations of the brain’s own blood flow.
By 1929, he had developed his new equipment enough to produce
hundreds of recordings from patients with skull defects, epilepsy, dementia,
brain tumours and other disorders, as well as from healthy controls – himself
and his son.16 All showed consistent patterns in the waveforms; they were the
same across many kinds of people. More intriguingly, they changed in similar
ways. Their shape changed when you were paying attention versus when you
had your eyes closed, for example. They changed when someone with epilepsy
was having a seizure. It appeared that the shape of these waves did indeed tell
us something about the internal processes of the brain. Finally, he had amassed
enough proof to convince himself that he had devised a ‘brain mirror’ to
reflect the mental activity of the brain. He called his new tool an
electroencephalogram, and it was the inexact first EEG – a device that could
let you eavesdrop on the electrical activity of the brain. Almost five years after
recording, Berger finally worked up the courage to publish his results.
Perhaps he had been wise to be reticent. The reception was icy, his paper
mostly ignored. Thanks to his secrecy and the dour, uninspired reputation he
hid behind, no one could believe that this little man had found anything
groundbreaking. Many of his German contemporaries openly doubted that the
oscillating waves he claimed to have found even originated in the brain. At a
conference in Paris, while Berger explained the projections of his EEG graphs
in a darkened auditorium, half the audience simply walked out.
Adrian, however, saw potential in Berger’s work. He immediately began to
work on it in his own lab, replicating and expanding it.17 Berger found, for
example, that the resting activity of the brain forms a pattern of wavelets he
named the alpha rhythm, which hums along regularly, reliably producing
between eight to thirteen of these little sawtooths every second. Intense
mental activity changed the rhythm – the faster, more irregular waves he called
beta waves. Adrian publicised Berger’s work widely, going so far as to try to
rechristen the alpha wave ‘the Berger wave’.18 He even staged a demonstration
for the Royal Society in which he took traces of himself thinking in public –
changing the shapes of his own emitted oscillations in real time.19 No bulldogs
were involved.
Reading EEG patterns now began to allow American technicians to
distinguish sleep from waking states, focus from inattention, and even healthy
brains from those with neurological disease.
In Germany, the public imagination was beginning to enter its fever phase,
and in the late 1920s and 1930s, the EEG’s ability to make recordings of the
electrical activity of the human brain began to kindle far-reaching speculations
about the imminent deciphering of the brain – and consequently, the mind. A
German journalist wrote enthusiastically that ‘today the brain writes in secret
code, tomorrow scientists will be able to read neuropsychiatric conditions in it,
and the day after tomorrow, we will write our first authentic letters in
brainscript’.20
This enthusiasm would not last. At some point, the optimistic tone
disappeared, leaving only the worst-case scenarios. A radio programme
investigated the worrying ‘electrophysiological problems of the future’.21
Editorial cartoons captured the attitude of the average German at the time:
one speculated that the addict of the future would be addled by electricity
instead of cocaine and morphine; and another – a brutalist depiction of a
person’s exposed brain irradiated by waves that shone out through his
confused eyes – envisioned brainwashing by a surveillance state. The cartoon’s
caption: ‘Intensification of suggestive forces by the supply of electrical
oscillatory energies into the brain’.22
Then there were the enterprising opportunists who seized on EEG, whose
schtick you’ll find quite familiar by now. Berger’s discovery ushered in a
booming market of quack medical appliances. One buyer asked Berger for
advice on using EEG to assess the temperament of his new horse. The head
of a women’s clinic at Tubingen tried to use EEG to establish neural signatures
of pregnancy.23 Berger was furious about all of it.
Outside Germany, by 1938 the tool was being used all over the world. It
was particularly useful for diagnosing the patterns characteristic of epileptic
seizures, sleep stages, and drug responses. The study of EEG advanced at a
particularly breathtaking speed in the US, where wartime tech and American
open-mindedness was leading to breakthroughs in theory, devices, and
praxis.24 When new EEG labs broke ground at universities, the ceremonies
attracted luminaries from all over the country. But this was not an era known
for the open sharing of scientific knowledge between Germany and other
nations, so Berger had no idea how much his EEG was already changing the
face of neuroscience in the US. He only saw what he fulminatingly called the
‘ballyhoo’ his creation had brought about in his own country. In 1941, just as
Adrian was writing up his letter recommending Berger to the Nobel
committee, the latter, mired in despair and depression, took his own life.
After seventeen years of progress in EEG technology, the field stalled for
another four decades. During this time, we decided that we’d rather send
electricity into the brain than decipher the codes hiding in the natural kind.

How we decided the brain was a computer

At the dawn of the computer age – as engineers began to assemble the very
first room-sized computing machines – those computers were also being built
(and conceived of) as a kind of brain. In 1944, the electronics manufacturer
Western Electric, in a glossy Life magazine ad for its new anti-aircraft guidance
system, declared that ‘this electrical brain – the Computer – thinks of
everything’. The next logical leap was inevitable: if a computer is a kind of
brain . . . might the brain be a kind of computer?
The American neurophysiologist Warren McCulloch entertained that
possibility. He was already familiar with Adrian’s search for the messages
hidden in the nerve’s all-or-nothing firing rates. And now, as he became
familiar with the binary coding that was the basis of computing, he identified a
possible correlation. In computers, the binary choice is between ‘a statement
that is either true or false’: 0 or 1. In the brain, ‘the neuron either fires or it
does not’. Could all-or-nothing neural firing be the brain’s version of binary
code?
The vocabulary in the two disciplines soon overlapped. During the
following years and decades, McCulloch and his colleagues in many disparate
disciplines seeded their descriptions of how the nervous system worked with
electrical engineering terms. Neurology adopted terms like ‘brain circuits’.
Electrophysiology adopted terms like ‘circuit’, ‘feedback’, ‘input’, and ‘output’
into descriptions of how the nervous system worked. Increasingly, the line
blurred between the code you write into a computer to program it, and the
idea that brains were subject to similar governance.
All this intermingling soon bred a formal new school of thought:
cybernetics, an idea that emerged from the Second World War, was seen as a
science of communications and automatic control systems, relevant for both
machines and living things. But for its most ardent disciples, it was also a
means towards mind control. The main idea in cybernetics is that if anything a
human (or any animal) perceives and experiences is just code routed through
the brain by the nervous system’s circuits, you should be able to control a
human mind as surely as you can control a machine. It wasn’t just scientists
who succumbed to the cybernetics craze – this new understanding soon fully
penetrated the zeitgeist. Engineers built robots whose operating systems
purported to model the human brain, and imbued them with consciousness-
like qualities thanks to their ability to ‘perceive light’ or return to their charging
stations of their own accord.25 By the time Norbert Wiener published the
hugely influential book Cybernetics: Or Control and Communications in the Animal
and the Machine in 1948, the idea was already wildly popular and the book
became an international bestseller, despite containing, as the historian of
science Matthew Cobb has pointed out, ‘vast tracts of equations that were
incomprehensible to most readers (and were full of errors)’.26 In other words,
the idea was so compelling, there wasn’t much point in bothering with whether
it was based in fact. The idea that we should be able to drive an animal like a
robot by simply activating specific circuits of neurons was too good to verify.
But with what tools would it be possible to control the human circuitry?
Scientists went back to a tried-and-true method – shocking people. (Even
Edgar Adrian had had a brief dalliance.27 During the First World War, while
finishing his medical studies in London, he and his colleague adapted
‘torpillage’, a kind of electro-therapy popular in France and Germany, to cure
British soldiers of shell shock and get them back to the front as fast as
possible.28 When he realised that soldiers relapsed more often than they
improved, Adrian abandoned the practice in 1917 and returned to the work
that would lead to his Nobel.)
At first, electro-therapists administered jolts of electricity to the whole
brain, with no luck. But what if, instead of blasting a person indiscriminately
with electricity, you targeted the shock at a specific brain circuit? Specific brain
areas were a hot topic. In the 1940s, while looking for parts of the brain
responsible for epileptic seizures, the neurosurgeon Wilder Penfield found a
remarkable clue that there were areas deep in the brain responsible for very
specific experiences and memories. Before cutting out the bits of brain tissue
that generated the epileptic symptoms, Penfield would first locate the problem
area by electrically stimulating several parts of the deep brain. Strange
behaviour would ensue. His patients might suddenly start singing lyrics to a
song they hadn’t heard since they were children; they might say they smelled
some powerful phantom scent. Electrical activation of some brain areas clearly
brought sensations out of the dark closet of the deep brain and into the light
of day.29
Emboldened by these hints about what was encoded in brain circuits,
other scientists opened up people and animals and stuck electrodes into them
for more precise control. Early approaches focused on the brain’s pleasure
centres and reward circuits. This approach had powerful consequences. An
electrode that hit the right spot in a rat’s brain would cause the animal to do
absolutely anything to stimulate itself, including staying awake doing nothing
else for twenty-six hours.30
The discovery of such a control switch in the mammalian brain led to
exactly the kind of ethical trainwrecks you might expect. In the late 1960s, a
patient came to the office of Robert Heath, a psychiatrist at Tulane University
in New Orleans. This patient was desperate to be cured of his homosexuality,
understandable given the cultural attitudes in 1960s Louisiana. By the time the
patient – Heath referred to him as B-19 in his records – sought professional
help, he was suicidal. So Heath implanted his patient with a stimulator with the
view to reorienting his desires towards women. While B-19 controlled the self-
stimulator, Heath instructed him to watch unlimited heterosexual pornography
in the lab.31 Heath reported that ‘B-19 stimulated himself to . . . almost
overwhelming euphoria and elation, and had to be disconnected, despite his
vigorous protests’. After some time, B-19 wanted to try it in the flesh, and
Heath procured a prostitute to visit the lab. The psychiatrist’s clinical
observation: ‘The young lady was cooperative, and it was a very successful
experience.’32 The long-term effects, however, were less conclusive. While B-
19 did go on to have a long-term heterosexual relationship, he never stopped
having sex with men. Simply zapping the human reward circuitry, it seemed,
had its limits. So did the public’s patience for Heath’s work in this area, which
in 1972 was denounced as a ‘Nazi experiment’ by a local magazine, a
judgement that sent his career into a terminal plunge.33 But his work had
already been overshadowed by something much more exciting and media-
friendly: instead of a ‘go’ button, something that stopped.
José Delgado was a Spanish neurophysiologist at Yale University who, in
his formative academic years, explored the neural roots of aggression, pain,
and social behaviour, just as cybernetics was gaining steam. It was under this
framework that he began his research on electrical stimulation in animals. He
was soon expertly building custom microelectronics to implant into the brains
of cats, rhesus monkeys, gibbons, chimpanzees, and bulls.34
In the mid-1960s, Delgado went to a ranch in Córdoba, Spain, to
investigate the areas of the brain where neural activity was related to
aggression. For his experiment, Delgado chose a fighting bull called Cayetano
and another called Lucero. Each weighed well north of 500 pounds.
Delgado inserted a battery-powered electrode into an all-purpose area in
Lucero’s brain that was involved in everything from movement to emotion.
Then he got him angry. When the bull charged, at the last moment Delgado
pressed a button on a radio device that remotely turned on the stimulating
electrode, electrifying Lucero’s caudate nucleus and causing the bull to stop
short.
The grainy photograph depicting the famous experiment has probably
made its rounds through every undergraduate neuroscience seminar in the
world. Delgado cuts an improbable figure in slacks and a professorial V-neck
pullover over a collared shirt, facing down a beast that is charging towards him
in a fenced enclosure. He is holding up something that looks like a portable
radio with an antenna – standing apparently unfazed in front of a bull that
seems to have skidded to a halt so short, its rigid hooves are barely visible
behind a cloud of dust.35
Lucero’s implant did not only stop the bull from charging. If the bull was
eating when Delgado pushed his remote control, he would stop eating. If the
bull was walking, pushing the button would cause him to stop walking. It
seemed that Delgado had found in this brain area something like a universal
‘stop’ button. The sudden transition from rage to peace led The New York Times
to call the experiment a ‘deliberate modification of animal behaviour through
external control of the brain’.36
Delgado continued to explore the control of aggression, passivity, and
social behaviour using implants in humans, chimps, cats, and many other
animals. In 1969, he published a book discussing his experiments and their
implications, called Physical Control of the Mind: Toward a Psychocivilized Society. It
achieved instant notoriety, if only because of its final chapter, in which
Delgado – whose cybernetic ethos had been shaped by five months in a
concentration camp – declared that humanity was on the verge of ‘conquering
the mind’, and should shift its mission from the ancient dictum ‘Know
Thyself ’ to ‘Construct Thyself ’. Used wisely, he insisted, neurotechnology
could help create ‘a less cruel, happier, and better man’.37
No one could propose implanting a stop switch into a human brain for
such speculative reasons. But soon a much more compelling use case
presented itself.

A pacemaker for the brain

It was an otherwise quiet morning in 1982, and a patient named George had
just been admitted into a psychiatry unit with a diagnosis of catatonic
schizophrenia. The designation had been applied not because it fitted, but
because nothing else did. The patient was unresponsive, but he still seemed
alert, a combination outside all the existing frameworks available at the time.
The psychiatrists were sure the patient had a neurological disorder, and the
neurologists were sure the patient had a psychiatric disorder. Eventually, the
chief resident ran to the office of the director of neurology, Joseph Langston.
 Langston set aside his coffee, looked up from that morning’s EEG reports,
and began conducting his own tests and consultations. Initially, he concluded
George exhibited all of the symptoms of advanced Parkinson’s disease, a cruel
neurodegenerative disorder whose iconic symptom is a trembling so violent, a
person can’t so much as hold a cup of water, and which progresses after many
years into a rigid freeze. But Langston knew the diagnosis couldn’t be right for
two reasons. The patient was only in his early forties, which was about twenty
years too young for a diagnosis of Parkinson’s. And instead of manifesting
gradually over the course of years or even decades, his (apparently) end-stage
symptoms had appeared literally overnight.
The mystery only deepened further when they found George’s girlfriend
frozen in the same state despite being even younger – she was only thirty.
Eventually, the team located five more identical cases. It took some sleuthing
and luck, but Langston and the police eventually uncovered the common
factor: each of the patients had recently used heroin – or at least what they
thought was heroin. When Langston’s group got their hands on some samples,
what they found wasn’t heroin at all: the street chemists had mistakenly
synthesised a compound called MPTP. A search through the medical literature
revealed several existing studies on MPTP, and their findings didn’t bode well
for the couple. By destroying an area deep inside the brain called the substantia
nigra, MPTP had been found to create irreversible symptoms that mirrored
Parkinson’s – notably that rigid freeze.
The discovery of that relevant brain area was consequential. During the
1970s, a few neurosurgeons had been experimenting with implanted electrodes
for chronic pain and epilepsy. They drilled open the skull and pushed a
penetrating electrode deep into the grey matter. It was a promising solution to
the big problem that had driven psychosurgery out of business: unlike the
traditional approach of burning or cutting out bothersome bits of the brain,
‘electrical lesions’ were adjustable as well as reversible. If you were applying
too little electricity, you could dial up more; if you were putting in too much,
you could dial it back down.
As they did this, doctors began to notice two patterns among the patients
exhibiting troublesome symptoms: first, the electrical stimulation alone was
sometimes enough to blunt the symptoms. Second, the faster the electrical
stimulation pulsed, the more the patients improved.
These patterns were intriguing, but the electrodes couldn’t be implanted
for take-home care. Like Hyman’s earliest pacemaker, they were hooked up to
an unwieldy external apparatus, a large power source which was connected to
the electrodes that stuck out of the head by wires.38 Moreover, no one had
done any large clinical trials to verify that stimulating some particular brain
area worked for everyone, or if it was just bespoke to the individual patient.
The only assessment of whether it worked at all was the assurance of the
implanting surgeon.39 However, all the growing interest had led Medtronic to
work on adapting their pacemaker to make it suitable for brain implantation.
They sent their experimental devices to specialist centres, and even
trademarked the term DBS (‘deep brain stimulation’). Their devices were still
limited to small, one-off experiments. But that all changed when George’s
revelatory case study made it to the desk of Alim-Louis Benabid at the
University Hospital in Grenoble, and he connected the dots.40
Benabid was among the few psychosurgeons still using implanted
electrodes to identify the correct brain area in advance of psychosurgery. He
had become fascinated with the clear and obvious effects he saw in his
Parkinson’s patients: symptoms would quiet in real time in the operating
theatre. When he grasped the significance of George’s case study, he obtained
Medtronic’s new brain pacemakers and implanted a handful of patients. The
improvements were dramatic. Stopping the faulty neurological code emerging
from that part of the brain settled the trembling, allowing patients to once
again move their limbs as they wished. Medtronic hired Benabid to design
massive trials. Now, instead of unscientific zaps accompanied by an
unconvincing thumbs-up from a clinician, here was a disease with extremely
well-spelled-out symptoms, a relevant brain area, and a robust response to an
already approved medical device.
Medtronic had been desperate to find a way to expand its hugely
successful pacemaker business. In Benabid’s work, they saw a new opportunity.
And in trial after trial they found the same dramatic effects: start the current
flowing through those deep electrodes, and trembling subsided instantly.
People who before the surgery could not hold a cup of tea were now able to
confidently brew themselves a whole pot. EU regulators approved the implant
for Parkinson’s in 1998, and the Food and Drug Administration (FDA)
approved the treatment in the US in 2002. One of the doctors who began
implanting his patients hailed it as ‘providing a new life’. The pacemaker had
moved into the brain and deep brain stimulation was born.
More than 160,000 of these ‘brain pacemakers’ have been implanted to
mitigate the disabling muscle spasms of people with Parkinson’s, essential
tremor, and dystonia.41 As brain surgeries go, it is actually pretty
straightforward. First, drill two holes in the skull. Next, push two metal
electrodes, each about the dimension of dry spaghetti, into the region of the
brain responsible for the symptoms. Finally, snake the wire through the head
and down the neck until it reaches, implanted under the skin near the
collarbone, an object about the size of a stopwatch. That’s the pacemaker! But
now it’s sending a current whose pulse and amplitude, over the following
couple of weeks, a technician will adjust until the symptoms subside.
In big clinical trials with many participants, knowing which brain area to
overwhelm with electricity has allowed surgeons to successfully short-circuit
faulty signals in these broken regions. What other brain areas were amenable
to freezing in this way, to widen the net of conditions controllable by a
pacemaker? Many small trials offered clues to the next big ailment.
In 1999, researchers at the Catholic University of Leuven (KUL) in
Belgium implanted DBS electrodes into an area called the internal capsule in
four people with severe obsessive-compulsive disorder. Symptoms improved
for three.42 More trials on other ailments followed in rapid succession – again
small, investigational studies, often only with ten or fewer participants. But
despite their small size, these trials generated dramatic headlines, as my
colleague Andy Ridgway noted in 2015 in New Scientist .43 DBS allowed a
thirteen-year-old autistic teenager to speak for the first time.44 It freed people
with Tourette’s from bone-breaking physical tics. It allegedly stopped obese
people from overeating and anorexic people from undereating.45 The small
trials proliferated – what else would yield to a brain pacemaker? Anxiety?
Tinnitus? Addiction? Paedophilia?46
Medtronic bet on depression. They weren’t alone in thinking this was
promising. The idea had been germinating since 2001, when neuroscientist
Helen Mayberg had the idea to investigate DBS for intractable depression (the
kind that refuses to budge no matter the treatment). DBS, she told me when I
met her at the International Neuroethics Society symposium in San Diego in
2018,47 ‘seemed to block abnormal brain function in Parkinson’s, so we
wanted to block our own depression-specific area’. Mayberg focused on a
brain region known as Brodmann’s area 25, which has been dubbed the brain’s
‘sadness centre’. Too much activity here, Mayberg and her colleagues thought,
was driving symptoms like negative mood and that characteristic lack of a will
to live. What would happen if you froze those neurons? Four of her first six
patients saw dramatic improvement.48 Twenty more small trials recorded
improvement rates as high as 60 or 70 per cent. ‘People come out of that very
dangerous state, and stay well,’ Mayberg told Ridgway. ‘They just get back on
the bus.’ In other trials all over the world, depression lifted similarly.
After enough such intriguing results had piled up, St. Jude Medical – a
Medtronic rival – took the plunge and bankrolled a major trial. It seemed all
but guaranteed to culminate in the first new commercial application of DBS
since Parkinson’s. Two hundred participants at more than a dozen medical
centres got the implant. The buzz was immense. And then, after six months,
the trial stopped. Gossip spread among industry insiders that it had failed an
FDA futility analysis, meant to make sure spendy trials get kneecapped if they
are clearly wasting time and money. There were stories of terrible side effects
and a suicide attempt.49 The implication – bad for the future of the technology
– was that there was no difference between a placebo and an implant.50
When all the drama and recriminations settled, the story ended up being a
lot weirder and less straightforward than the first reports suggested: as the
journalist David Dobbs concluded in a deeply reported post-mortem analysis
published in The Atlantic in 2018, it appeared to be a case of a treatment that
actually seemed to work being sabotaged by a trial that didn’t. For the people
in whom it worked, it was a gift, yielding immediate results that were so
dramatic as to be nearly magical. ‘What did you do?’ would be the response of
the awake patient, still in the operating room, the moment the stimulator was
turned on. And when that happened, the results were enduring. ‘If you got
better, you stayed better, given continued stimulation,’ Mayberg told several
media outlets in the wake of the trial. The same pattern held true for
obsessive-compulsive disorder: those patients who had responded well in a
brain stimulation trial at the Catholic University of Leuven still had their
obsessive-compulsive disorder under control after fifteen years. ‘It was like
someone spring-cleaned out my brain and took out all the unnecessary
thoughts,’ another participant told Alix Spiegel, host of the National Public
Radio show Invisibilia.51
But it was just not possible to predict who would have a miracle and who
wouldn’t. There were also some strange side effects.52 The deep, ancient areas
of the brain targeted for electrification in depression and Parkinson’s are
involved in much more than motor and mood control. They are implicated in
learning, emotion, and reward – which is to say, addiction. Interfering with
these had unpredictable consequences. This was the case for one Dutch man
being treated for severe obsessive-compulsive disorder, anonymised by his
doctors at the University of Amsterdam as Mr B. His new brain implant had
been working for just a few weeks when he chanced upon a recording of
Johnny Cash’s ‘Ring of Fire’. In the five decades before the twin electrodes
penetrated his deep brain, he had never been especially moved by music – he
was the kind of guy who claimed to like both The Beatles and the Rolling
Stones. The day Johnny Cash’s voice hit his newly electrified pleasure centres,
however, all that changed. From then on, no other music was allowed. Mr B
bought every Johnny Cash CD and DVD he could get his hands on. But when
the electrical stimulator was off, he could not for the life of him recall what
was so important about Johnny Cash.53
Not all side effects were as endearing, though. People with Parkinson’s
implants have reported an increase in impulse control disorders, such as
excessive gambling and hypersexuality.54
This reflects a somewhat uncomfortable open secret about DBS: despite
all the complicated talk about the function of precise areas of the brain, no
one is sure exactly how DBS works.55 As recently as 2018, academic reports
described DBS as an effective but ‘poorly understood’ treatment, even in
Parkinson’s and the other motor diseases it has been approved to treat for
decades.56 ‘If you think of neurons executing the neural code as playing a
melody on a piano,’ says Kip Ludwig, a former director at the US National
Institutes of Health (NIH), ‘then DBS is like playing that piano with a mallet.’
There’s a limit to this approach. Electrifying specific brain areas could
broadly control some maladies, but it was impossible to get truly granular
enough to reliably hit a target as ephemeral as depression. We needed to know
exactly what was happening in the brain’s code as a response to those zaps.
For that, we needed to decipher the neural code.

Reading the neural code

By the 1970s, Francis Crick had grown bored of molecular biology, even
though he’d essentially invented it. He was looking to solve his next great
mystery. If cracking the blueprint for life had been exciting, how about
cracking the secret of consciousness? So in 1977, he left Cambridge for the
Salk Institute in California, where he turned his attention to what he
considered a deeply unpromising approach to neuroscience. He demanded
new ‘theories dealing directly with the processing of information’ and ways to
tie behaviours and actions to the neural firings that accompanied them.
In 1994, he summarised his research in The Astonishing Hypothesis, a slim
volume that would have an explosive impact on neuroscience and philosophy.
‘One may conclude,’ he wrote, ‘that to understand the various forms of
consciousness we need to know their neural correlates’.57 He further argued
that all those things we think or feel or see ‘are, in fact, no more than the
behaviour of a vast assembly of nerve cells and their associated molecules’.58
(He did not address how this was materially different from our identity being
no more than the behaviour of a vast assembly of genes.) The subtitle – The
Scientific Search for the Soul – made clear the book’s ambition.
In the whole two decades before Crick’s book was published, fewer than
ten peer-reviewed scientific papers referred to the term ‘neural code’. After the
release of The Astonishing Hypothesis, however, neuroscientists increasingly
turned their attention to trying to find the neural signatures of a vast array of
behaviours and thoughts. For students of the sensorium, neural code was the
new black.
Not that they knew what the term meant. Even as Crick was writing his
book, the definition of the term was the subject of a contentious spat in
neuroscience. Adrian’s ideas that information could be encoded in the Morse
code dots passed by individual neurons still had its adherents, but now there
was a fresher idea. Brain plasticity – summarised by the axiom ‘neurons that
fire together, wire together’ – became ubiquitous thanks to its succinct
explanation of how different neurons learn to work together as you learn
different skills, from language to ballet. A real neural code couldn’t possibly
focus on the firing of single neurons, representatives of the new guard wrote
in 1997, but had to take into account the way vast collections of different
neurons fired together in synchrony to form a coherent pattern over time and
space.59
It would be one heck of a hard thing to measure. By then, we had begun to
grasp the sheer size of the brain – 86 billion neurons. No tool was, or is (or
possibly will ever be), capable of reading the activity of all those neurons at the
same time. But as the twenty-first century approached, we had options.
The trusty EEG was still in use, a workhorse that had given us the
different waves that could reveal focus and inattention, but also much more.
Scientists spent decades using these readings to advance our understanding of
sleep. Because EEG doesn’t require opening the skull, just some electrodes on
the scalp, scientists were able to obtain a lot of data from a lot of people. The
EEG evolved from its humble origins in Hans Berger’s lab into skullcaps
encrusted with dozens of electrodes that could read subtle variations in the
chorus of the brain’s billions of denizens. That helped drill down into the
brainwaves, and the subsequent discovery of delta and gamma waves (in
addition to Adrian’s alpha and beta) helped researchers identify the different
stages of sleep, yielding the familiar, ever-deeper stages of I–IV and dreaming
sleep. Other work tied characteristic disruptions in these waveforms to sleep
disorders and neurological disorders – even helped identify the location of
brain tumours. Thanks to increasingly powerful computer processing power
and better signal-processing algorithms, EEG could more finely analyse the
brain’s patterns. Depression was correlated with an overabundance of alpha
waves in the EEG. In Parkinson’s disease, there was a paucity of beta waves.
Alzheimer’s patients have been found to have a deficit of high-amplitude
gamma waves. Various research papers reported a rainbow of emotions
correlated to waveforms Berger couldn’t have dreamed of.60
Another tool, electrocorticography (ECoG), could get deeper into the
brain, but it would be amenable to a smaller population. It looked like a mat of
electrodes placed directly onto the exposed folds of the brain, a bit like a doily
on a side table, to record electrical activity from the cortex. It does require
opening the skull, which is why it is rare to obtain these sorts of traces. The
only human volunteers for this kind of brain reading have already had their
skull opened for unrelated investigational purposes. Sometimes these
individuals gave researchers permission to put the mesh on their brains and
read the neural correlates of certain specific thoughts, but it still didn’t let the
researchers get next to any specific neurons.
For that, you needed an invasive brain-penetrating electrode. The first of
these was approved to stick into human brains in the 1990s. It was called the
Utah array, and it looked like a small metal square with ninety-six electrodes
sticking out of it, a bit like a bed of nails for a ladybird. Nestled into brain
folds, it could record the squabbling of many neurons talking to each other, or
hone in on one in particular. But this reading was the most invasive of all: it
required not only opening the skull (or drilling a hole in it), but also jamming
the penetrating electrode through the blood–brain barrier, and running a lead
out of the skull to power and listen to the array. The only subjects on whom it
was considered ethical to test this device were animals – and later, people who
had suffered the kind of irreversible physiological trauma that made this the
last faint hope for the possibility of a research breakthrough that would help
them.
By 2004, the theoretical neuroscientist Christoph Koch – a buddy of
Crick’s who profoundly influenced his ideas about the neural correlates of
consciousness – predicted that thanks to these and other new tools, it would
soon be possible to decipher the workings of the neural code to understand
consciousness, language, and intentionality.
Around the turn of the twenty-first century, the evidence for this
optimistic reading of the future was all around us in media reports. In 1993, an
invasive electrode placed into the cortex of a woman who had been paralysed
by a stroke allowed a computer to determine where exactly on a square of
letters she was focusing her attention. ECoGs detected the electrical signatures
of people thinking in whole words: ‘yes’, ‘no’, ‘hot’, ‘cold’, ‘thirsty’, ‘hungry’,
‘hello’, and ‘goodbye’.61
So it seemed that, in line with Koch’s predictions, you could indeed use the
brain’s electrical signals to peer into people’s minds. By 2022, at least fifty peer-
reviewed papers every year were invoking the term ‘neuron code’. Many of
these papers investigated what actions, thoughts, and feelings could be traced
back to bioelectric signals in the brain.
That raised a new question: if you could read the brain’s state by examining
its electrical signals, what would happen if you changed them? Could you
reprogram the brain?

Writing the neural code

On 22 June 2004, a little metal pincushion was pressed into Matt Nagle’s
motor cortex, specifically, into the region that controlled his dominant left
hand and arm. After he had been paralysed from the neck down in an
accident, the neuroscientist John Donoghue had signed him up for a clinical
trial called BrainGate, and implanted him with a Utah array. Eventually, Nagle
was able to move a computer cursor with just his intentions. If he wanted to
move the cursor to the left, the motor neurons in his brain fired how they
normally would have to control his fingers. The Utah array picked up that
signal, translated it into machine language to control the cursor, and the cursor
moved left. That’s how, in 2005, Nagle beat a Wired magazine reporter at the
computer game Pong.62
Donoghue had much bigger plans. If these signals could drive a robot arm,
why couldn’t researchers find a way to take control of a real arm – namely
Nagle’s own? In 2005, he told Wired that his eventual plan was to ‘hook
BrainGate up to stimulators that can activate muscle tissue, bypassing a
damaged nervous system entirely’.63 It was ambitious and very exciting (if a bit
Frankenstein): instead of trying to heal the spinal cord injury that had
disconnected the limbs from the brain, the BrainGate implant would beam the
electrical signals that drove intent to their intended endpoint directly, and so
reanimate the limbs.
 The idea was called a neural bypass, and within a decade, it was being
demonstrated in a TED talk.64 ‘The idea is to take signals from a certain part
of the brain and reroute them around the injury – whether that injury is to the
brain or the spinal cord – and then reinsert those signals back into the muscles
to allow them to regain movement,’ Chad Bouton told the audience, pacing
the stage like a TV-handsome talk show host. Bouton was the engineer who
had developed the signal processing algorithms for the original BrainGate
project. ‘But we still had not given [our subjects] movement,’ he said,
frustrating his vision of helping people with life-altering spinal injuries to walk
again. When, in 2008, Cyberkinetics, the company that owned BrainGate
failed, Bouton moved to the Feinstein Institute in Manhasset, New York, to
begin work on his neural bypass. Under the auspices of a project funded by the
US Defense Department, he joined a research supergroup with the science
institute Battelle and Ohio State University, and in 2014 they implanted a
computer chip into the motor cortex of a young man named Ian Burkhardt,
who had become quadriplegic after a diving accident.
For Bouton and the others working on restoring fine motor control,
deciphering the neural code was not a matter of counting the action potentials
generated by every nerve the way Edgar Adrian did it. In a brain full of 86
billion neurons, you can’t possibly pick out and analyse the spiking behaviour
of the billion or so involved in every motion. Bouton thought the thing to
focus on instead was how groups of neurons synchronise the timings of their
firing when any particular intention was recorded. He called it a ‘spatio-
temporal’ relationship. After harvesting this pattern, they would re-encode it
into machine language, and this would animate a cuff of electrodes around
Burkhardt’s wrists. Instead of actuating motors on a robot limb (the way
BrainGate had done), each electrode would stimulate tiny swatches of muscle
in his own arm.
It wasn’t exactly the way a brain signal would innervate the muscle, but the
tortured mathematical transformations worked. With the help of the device,
Burkhardt picked up a mug of water and lifted it to his own lips to take a sip.
Ian Burkhardt had become the first person to use a chip to ‘reanimate’ his own
living muscles with the neural code harvested from his own brain.65 The
signals were precise enough to let him play Guitar Hero.66
But Bouton still wasn’t totally satisfied. What good is it to be able to move
if you have no sense of what you’re touching? This was a practical question. ‘It
seems so simple to you and me, but if you have no sense of touch in your
hands, no pressure or slip awareness, you don’t know if your grip is tight
enough,’ Bouton told me when I visited his lab at Feinstein a couple of years
later. Without that grip awareness you’d be just as likely to drop the cup as
suddenly crush it and spill hot coffee all over yourself (and your lack of pain
awareness would make you unaware that you’ve just given yourself second-
degree burns that need a doctor). To avoid this, an implantee must train their
full attention exclusively on gripping that cup from the moment they pick it up
to the moment they let it go. ‘There was one guy with the implant,’ Bouton
said, ‘he could pick stuff up, but as soon as he wanted to do or think about
literally anything else, he’d drop whatever he was holding.’ Imagine if you had
to do that every time you wanted a sip of coffee. And now imagine it’s not a
cup of coffee you’re holding, but your kid’s hand. All these activities of daily
life would be meaningless without sensation. A half measure, thought Bouton.
The sensorimotor cortex, where sensation lives, is right near the motor
area where intention lives. That’s the good news. The bad news was that
writing the correct pattern of electrical spikes into the brain to replicate the
experience of sensation would be a much harder problem than reading existing
signals as they fired.
Almost exactly six months later, a paralysed volunteer called Nathan
Copeland – working with a different research group at the University of
Pittsburgh – lay blindfolded next to a five-fingered robotic arm. Each time a
researcher prodded one of the robot’s ‘fingers’, Copeland identified where on
his own hand he was feeling the touch. ‘Index finger,’ he noted as the
researcher touched the machine’s index finger. ‘Middle finger. Ring finger,’ and
so on, and thus followed a long series of correct localisations.67 In addition to
the usual BrainGate-style motor cortex implants, Copeland had had two
electrode arrays implanted into areas of his brain whose neurons respond to
sensation in the fingers (each implant was about the size of a sesame seed).
Every time the researcher jabbed the robot’s finger, these little seeds sent
electricity patterns into the correct neurons.68
This mechanism interested Theodore Berger (no relation to Hans), but
instead of implanting sensations, his electrodes would spark artificial
memories.

The memory maker

Berger’s goal was to mimic the function of the hippocampus, a part of the
brain where memories are processed and encoded. He had long been working
on a chip that recorded whatever brain pattern corresponded to a behaviour
he liked, then fed it back into the brain using what he called a multiple-
input/multiple-output (MIMO) algorithm to reproduce the behaviour.
He tested MIMO by temporarily damaging a rat’s brain, in a way designed
to specifically block the hippocampus’s ability to write memories, mimicking
the effects of dementia. He had previously recorded the rat successfully doing
a specific task. With the brain damage, the rat now couldn’t repeat the
performance. But when the damaged hippocampus was zapped with the
MIMO patterns recorded earlier, the rat’s performance on the memory task
went back to normal – even though its brain was still damaged.69
Berger believed he had created a prosthetic memory (although many
would dispute that characterisation). He and his co-authors concluded that
‘with sufficient information about the neural coding of memories, a neural
prosthesis can restore and even enhance cognitive processes’. That wasn’t all.
Code taken from any one rat could be zapped into any other rat, which
seemed to suggest that Berger had discovered aspects of a universal code that
governs how all creatures form memories,70 even rhesus monkeys.71 This time,
MIMO was tapped to intervene whenever it looked like a monkey was about
to make a wrong choice. Monkeys that got the ‘right decision’ code stimulation
made better choices 15 per cent of the time. This showed, Berger insisted, that
MIMO was not specific to one particular animal, raising the possibility that
one day when you’re reaching for the fries, your good decision implant could
give you a little ‘salad’ zap.
Berger had long relied on grants from the Defense Advanced Research
Projects Agency (DARPA), widely known as the US military’s mad science
wing, and his research dovetailed nicely with their efforts to understand the
neuroscience of memory and traumatic brain injury (with a view to fixing
those sustained from IEDs and other war injuries). The agency was funding a
prosthetic memory device for implantation in a human brain,72 but both the
timeframe (too short) and the money (not enough) put human trials out of
reach. Enter Bryan Johnson, who had recently pocketed $800 million from
selling his online-payments company to PayPal, and was looking for something
more exciting to invest in.73
When he discovered Berger’s work, Johnson immediately dumped $100
million into the new start-up, Kernel, that would bring the memory chip to
reality. There seemed to be no ceiling to what you could do by tapping the
neural code. If all your senses ultimately boiled down to electrical signals
hitting different areas of the brain, couldn’t you make a memory from scratch
by impersonating those signals?
The engineers said that all they needed was access to more neurons.
Another group of researchers, who said they had transmitted a memory of a
sensation, had used thirty-two electrodes. But Johnson told reporters that the
plan was prosthetic memory implants containing nearly 2,000 electrodes, and
that 5,000 or even 10,000 were achievable. Never to be outdone, SpaceX and
Tesla entrepreneur Elon Musk proposed a brain implant that would read to
and write from thousands of neurons simultaneously. (Not known for modest
goals, Musk advocated using this implant to ‘co-evolve’ with artificial
intelligence.) It seemed like a fairly straightforward, linear progression: the
more neurons you could manipulate, the more precisely you could write the
neural code; the more precisely you could write the neural code, the more
powerful the brain interface. Therefore, if you want to read and write more
neurons, just add electrodes.
However, one does not simply ‘add’ more electrodes (see Chapter 9 for
more on this). Not long after Kernel snapped up Berger, Johnson convinced
Adam Marblestone to leave his post at MIT’s Synthetic Biology lab to become
the company’s chief strategy officer. But when he began to review Berger’s
work and Kernel’s goals, Marblestone and his colleagues saw a potential
problem. First, Berger was working with a device that had a total of sixteen
electrodes, far less than even a Utah array. Second, saying the algorithm had
restored memory might have been an overly generous interpretation of the
experiment, as the tasks were both narrow and basic. ‘To say it meant you
“read the neural code” would be like saying you have cracked language when
you only decoded the words “yes” and “hello”,’ said Marblestone, ‘technically
true but potentially overstated.’
After a failed human experiment, the collaboration fell apart. Still,
Marblestone didn’t think this a reason to be overly cynical. ‘Given that we
don’t yet understand much about the neural code, and the lack of technology
with which to densely read and write,’ he says, ‘we just don’t know yet whether
it’s possible or not.’ But that’s not a statement you can take to investors. After
Johnson realised that there was no way to take what Berger had built and scale
it up to build something anyone could or would buy, Kernel abandoned the
memory chip.
In the end, it was the full appreciation of the hardware problem that drove
Bryan Johnson to rethink his relationship with the neural code. ‘For a while,
Kernel was looking at maybe building a medical device a bit like DBS,’
Marblestone says. ‘But we don’t really know what can be done with DBS-type
devices, beyond Parkinson’s.’
And that explains what happened next: Marblestone advised Johnson to
abandon the idea of writing the neural code, and instead figure out the most
interesting thing that could be done with the brain without opening the skull.
Johnson listened, and Kernel settled on reading brain signals. They started
building something that could measure other signatures of mental activity
while the brain is stimulated, whether by implants or by ketamine – in other
words, the kind of closed-loop device neuroscientist Helen Mayberg was after.
Such a device would be able to listen to the brain’s neural code during and
after zapping or other stimulation, so you knew what had happened in the
brain as a consequence.
A memory chip may not be on the cards, but the neural code has yielded
some dividends for Ian Burkhardt. In 2020, Battelle researchers were able to
use his existing implant to detect residual signals from his sensory nerves and
thereby restore an approximation of sensory feedback.74 ‘It’s huge because I
can know that I’m not going to drop something when I’m using the system,’
Burkhardt told a reporter from MathWorks.75

The future of brain chips

So when can you expect to buy your own exocortex? The Utah array – whose
design has remained largely unchanged since its invention – is the single FDA-
approved device and remains the only game in town for those looking to read
or write the neural code. Just to be clear: it’s approved for research. Not for
you and me. Regulatory hurdles have kept more advanced implants from
advancing enough to crack the language of the brain. Many devices produce
intriguing results in rats (or sometimes monkeys), newspapers go bananas, but
then they stall before hitting the market. Why? The answer is always the same.
There is a huge difference between the hardware that can read complex signals
in lab animals and the kind that you are allowed to experimentally put into the
brain of a human volunteer.
But as a brain–computer interface, this postage stamp-sized miniature
pincushion leaves much to be desired. It can only read signals from at most a
couple of hundred neurons, and only the kind that populate the topmost
millimetre of the brain. And no, you can’t just fill the brain with a whole bunch
of them. Any more than a couple, and the wires that connect the chip to the
signal processing apparatus outside the skull pose an increasingly serious
infection risk. Not to mention the prohibitive amount of data this would
generate – more than can be reasonably stored by today’s machines.76
While dramatic implants like BrainGate got a lot of publicity, after the TV
lights and cameras went away, some participants found their devices stopped
working. After years spent learning to use her implant with a robot arm, Jan
Scheuermann, another tetraplegic volunteer in Donoghue’s experiments at
BrainGate, gradually lost her dexterity, which felt an awful lot like descending
into paralysis for the second time. As the researchers explained to her, this was
due to a predictable immune response.77 It shouldn’t come as a surprise that
the brain experiences a metal pincushion as a foreign invader and mounts a
spirited defence, walling off the implant in a protective sheath. As a result, the
Utah array is unlikely to be the foundation of any future brain chip.
There was once a design that ostensibly addressed this problem – in the
1990s, a neuroscientist named Phil Kennedy designed an alternative to the
Utah array. Instead of 100 pins sticking their noses into the neurons to
eavesdrop on their conversation, his ‘neurotrophic electrode’ worked on the
opposite principle – make them come to you. The electrode was a glass cone
that housed a gold wire impregnated with growth factors and other tempting
treats for neurons. Instead of mounting an immune response, they would grow
into and entwine themselves with the electrode, which in theory should keep
the electrode functioning for years. Oh, and it was wireless.
In 1998, Kennedy put one of these into a Vietnam veteran named Johnny
Ray, who had been rendered unable to move or speak by a stroke; he was fully
aware but locked in. Kennedy’s electrode was able to pick up Johnny Ray’s
brain signals well enough to allow him to move a cursor across a keyboard to
slowly put together words. The media compared Kennedy to Alexander
Graham Bell, but the accolades didn’t last. After another one or two locked-in
subjects didn’t respond as well, and Kennedy couldn’t find new volunteers, the
FDA rescinded approval for the neurotrophic electrode for human volunteers.
Kennedy wouldn’t provide clear data on what kinds of things he was putting in
the electrodes he was implanting into his volunteers. And, now that we had the
Utah array, there was not a lot of urgency. By the 2010s, Kennedy was
desperate. In a last effort to get enough data to convince the FDA to re-
approve his implant, he chose the only patient he could. In 2014, Kennedy
flew to Belize to have his own (banned for human use) electrode implanted
into his own (perfectly healthy) brain by an increasingly nervous neurosurgeon,
for $30,000. The procedure would have been illegal in the US.
Kennedy survived the eleven-and-a-half-hour surgery, and despite a few
scary post-operative days during which his state resembled the locked-in
patients he used to treat, a few years later he seems to have come through the
experience largely intact. Unfortunately, the electrode only stayed in his brain
for a few months before there was a problem. A second surgery excised the
recording and transmission equipment, but not the electrodes – they were in
too deep to safely get out.78
After the stunt, the FDA is unlikely to ever take another look at Kennedy’s
paperwork. Kennedy insists he got good enough data to inform future papers,
and apparently doesn’t have lingering effects from the things that are in his
brain. However, now there are several other new designs in the works –
another electrode called Neuropixels is already being used to record data in
patients undergoing DBS implantation.79 It’s not yet approved but has a
similar design to Kennedy’s neurotrophic electrode, able to record deeper in
the brain. And then there’s neural dust – micron-size piezoelectric sensors that
would be scattered throughout the brain and use reflected sound waves to
capture electrical discharges from nearby neurons.80 The one you have
probably heard of is neural lace, the stuff Elon Musk sewed into a pig using a
robot sewing machine. The most recent entrant is neurograins; salt grain-sized
sprinkles unveiled in 2021 to make a better ECoG.81 They are proliferating,
largely because money has been pouring in. BlackRock, the investment fund
that has financed the neurograins, is on record as stating that they want brain
chips to become more common than pacemakers.82
There are three essential problems facing the further development of brain
interfaces. One that sometimes gets overlooked is that when it comes down to
it we don’t actually understand much about how the brain really works. ‘What
gets forgotten in a lot of these conversations is how little we know about the
brain,’ says Flavio Frohlich, a neuroscientist at the University of North
Carolina. ‘There are very few facts that have been independently verified – I
mean like basic fundamental stuff, including visual processing.’ This is where
the device Johnson pivoted to may help. Kernel is now working on a new kind
of brain-reading headgear – no brain surgery required – that combines the best
of both EEG and fMRI: magnetoencephalography (MEG). This provides a
kind of Google street view for your brain, showing where electrical activity is
happening. MEG used to be feasible only with superconductors, which have to
be cooled with liquid nitrogen, so the machine was about the size of one of
Einthoven’s early ECG contraptions. Johnson’s design uses laser cooling; the
only remaining problem is that like the early galvanometers Nobili was
working to improve, the MEG is overwhelmed by the Earth’s magnetic field.
‘It is wildly bigger than the magnetic field of your brain,’ says Marblestone.
Which is why for now, the helmet looks like a large white plastic mushroom,
Mario Kart by way of Spaceballs. But at least it’s useful.
There’s a lot of open road between current brain implants and any Silicon
Valley applications. Complex and subjective functions like memory would
require reading the output and then manipulating so many neurons, it is
unlikely that we will ever be able to influence them through this method.
There is also the problem of how many pins you can actually stick into
someone’s brain before the brain begins to fight back. This all sounds abstract
until you think about the fate of people like Ian Burkhardt, whose paralysis is
only temporarily abated every time he volunteers to be experimented on in the
lab.83 Jan Scheuermann, the woman who gradually lost her ability to use her
robotic arm, told MIT Technology Review reporter Antonio Regalado that she
once had her care aides put rat ears and a tail on her in a darkly funny nod to
how she sometimes thinks scientists might perceive her.84 Further advances in
brain implants will require many more people like Burkhardt and
Scheuermann.
However, until we have the answers to the first two problems, no
government oversight will responsibly allow trials on large enough groups of
human volunteers to constitute a proper trial. And yet, these are not the
messages that dominate about the future of brain implants. That’s because not
a lot of people feel empowered to call bullshit on the more extreme claims.
Few areas contain subject matter more opaque and that requires more cross-
disciplinary knowledge than neuroengineering. Unscrupulous start-ups
capitalise on the confusion to provide air cover for claims that don’t stand up.
Kernel’s story is a rare exception in that the company followed the science
where it wanted to go, not where they wanted it to go.
And these challenges don’t just apply to the brain.
The neural code is only one aspect of a much larger system of body-wide
bioelectrical signalling.
 CHAPTER 6

The healing spark:

The mystery of spinal regeneration

I n 2007, Brandon Ingram reached out for his walker, cantilevered himself
up from his wheelchair, and, once he had righted himself, began to take
small steps across the carpeted living room. It took great effort and some help,
but he was ultimately able to control his own legs by using his abdominal
muscles.1
This should not have been possible. Five years earlier, Ingram had been
thrown from a car in a highway accident and the injury to his spinal cord was
final. Doctors told him that he would not walk again.
And yet here he was, walking. It was a bit of a technicality, as he still
needed a wheelchair for most things, but he had regained other capacities that
are far more important when you have a spinal injury: shifting his position,
and feeling some sensation. ‘I’m very fortunate,’ Ingram told the Boston Globe.2
His good fortune was that his accident took place just as a new clinical trial
was recruiting spinal injury patients at Purdue University in Indiana. Several
days after his injury, a neurosurgeon placed electrodes between the vertebrae
of his crushed spine, where they emitted an electric field. This field, the
researchers hoped, would coax opposing ends of the severed motor and
sensory nerves in Ingram’s spine to slowly crawl towards each other over the
damaged site and knit themselves back together, allowing the brain’s signals to
flow through once more unimpeded. The implant was removed after a few
months. When the researchers followed up with Ingram and his cohort a year
later, most trial participants reported some improvements.
In 2019 – twelve years after Ingram’s tentative steps – the scientist who
invented the device that mitigated Ingram’s grim prognosis died, and with him,
much of the expertise around the oscillating field stimulator. Though it had
been deemed safe and appeared to do what no other drug or technology had
ever managed, and a larger trial had already been tentatively approved by the
US regulatory authorities, soon after Ingram’s comments to the Globe, the
research stopped cold.3 Only fourteen people have ever benefited from it, and
after years of having its development blocked at every turn, the company
tasked with bringing it into the world went bankrupt. The device was
mothballed.
There are still people who get very upset about the circumstances around
its demise. ‘I think this set back spinal injury research by ten years,’ says James
Cavuoto, who runs the influential industry publication Neurotech Reports.
‘Where would we be today if they hadn’t scared off the researchers and
investors who wanted to pursue this line of research?’ Sidelined by an
establishment that didn’t understand the principles behind its function,
attacked by point-scoring competitors whose animus was more personal than
professional, the oscillating field stimulator, Cavuoto reckons, was simply too
far ahead of its time and too unfamiliar to succeed – too much of a departure
from how people were thinking about interfacing biology and electricity at the
time.
That’s because this implant wasn’t targeting action potentials: it aimed to
harness a more fundamental electrical field, whose existence hadn’t been
officially acknowledged until the 1970s. The same electrical signature is
emitted and used by skin, bones, eyes, by every organ in your body. New
research and tools have begun to shed light on the physiological underpinnings
of this bioelectric field, illuminating its inner workings and medical potential.
The 2020s will bring more devices and techniques designed to manipulate it.
As usual, though, to understand this tale in full, we have to go back (very
briefly!) to the beginning.

Lionel Jaffe’s lab

It all started with those old studies that showed everything produces its own
electric field – brainless organisms like hydroids, algae, oat seedlings. Lionel
Jaffe began trying to unpick the mystery in the 1960s, when few
electrophysiologists wanted to study anything but the nervous system. But
Jaffe, a Harvard-trained botanist with the soul of a physicist, was in pursuit of
bigger, more unifying theories.
A good place to start was with brown algae (that’s marine fucus to you, if
you’re nasty). Fun fact: fucus contains up to eight times more sodium than
cheddar cheese and eleven times more potassium than bananas. Maybe we’ll all
be eating it in the future. But the reason biologists love the stuff is that it’s a
sexual organism that discharges its sperm and eggs directly into seawater
(you’re welcome). That makes it possible to study its entire developmental
procession from day one, without having to navigate any tricky uteruses. The
algae grow differently on one side versus the other, based on which end of
them is exposed to sunlight.
To investigate their electrical characteristics close up, Jaffe got a bunch of
the fucus fronds and put them into a Purdue hot tub to commingle their
efflux. Once he had his new developing embryos, he put them into a neat row
in a narrow tube, shone some light on one end to mimic sunshine, and
checked whether there was any measurable electrical field as the embryos
began to grow. And boy was there. Positive up, negative down. It was like a
battery. Now he needed some smart kids to help him investigate why.
Purdue was one of the premier electrophysiology institutions in the world,
so talent was plentiful. Jaffe decided to poach the most promising students
from the physics department. His first catch was Ken Robinson, who
abandoned vacuum physics after attending his first Jaffe class. He was in awe.
‘He had the most accurate and intuitive understanding of physics and
mathematics of anybody that I ever knew,’ Robinson told me. ‘I was just blown
away’.
Next, Jaffe turned Richard Nuccitelli’s head away from solid state
engineering. ‘Who ever would have thought cells could make electrical
currents?’ he marvels, fifty years on. He left physics and crammed entire
semesters of biology to try to catch up with the rest of his labmates. They
were glad to have him. ‘He was the most gifted technician I have ever laid eyes
on,’ said Robinson. In 1974, Nuccitelli built Jaffe a brand-new electrical
measurement device called a vibrating probe. It was a hundred times more
sensitive and powerful than anything that had come before. With this, the
newly assembled team could start to properly investigate the minuscule
electrical currents that swirled around the surface of fertilised fucus eggs.
These currents were much, much smaller than the ones that make an action
potential go pop. The team christened them ‘physiological currents’. In
addition to being weak, they were also steady: where action potentials oscillate
like strobe lights, the physiological currents shone from the organisms, steady
as a lightbulb.
The field seemed to orient the fucus, enabling it to grow correctly towards
the sun. What would it do for other creatures? Jaffe decided to make his own
weak electric field, being careful to exactly mimic the faint strength of the
physiological fields that emitted from brown algae eggs naturally, and apply it
to other living things.
First up: the spinal neurons of frogs. These had been chosen by Mu-ming
Poo, the biophysicist on the team, in keeping with the centuries-old tradition
that had been inaugurated with Galvani’s preparation. Poo placed the cells into
a petri dish, put them under the physiological field, and watched. A curious
behaviour emerged. As the neuron grew its neurites (the broad name for the
outgrowths of neurons that includes axons and dendrites), they extended more
quickly towards the positive electrode. The neurites just seemed to prefer that
end of the electric field.4
To go back to Faraday’s ions for a minute – it’s not just ions that wander
towards their preferred electrical ‘side’. Turns out, whole cells can wander too.
Jaffe’s group hadn’t been the first to observe this phenomenon – people had
been seeing electrotaxis (the migration of cells under electricity) since the
1920s.5 It genuinely freaked people out. There was simply no plausible
explanation for a bunch of cells crawling around a petri dish chasing an electric
field. People chalked it up to a poorly understood chemical effect and did their
best to ignore it. What was different now, in Jaffe’s lab, was that for the first
time, there was an instrument and new knowledge to study this phenomenon
properly.
The experiments and theories that came out of Jaffe’s lab united a whole
branch of cell electrophysiology, which because it took place outside
neuroscience, had previously been littered across a collection of separate
disciplines. Jaffe’s lab was considered a second home by many of his students.
He was incredibly dedicated to his science and to the scientists who worked
under him. Robinson was inspired by his fearless approach to seeking the
truth. ‘He never let data follow a hypothesis – only the opposite,’ he told me.
‘If you got a result that didn’t match the data, he didn’t get upset about it,’ said
Nuccitelli. ‘He would drop everything and say “we have got to pursue that and
find out what it’s telling us”.’ Mu-ming Poo is now one of the towering giants
of neuroscience, with joint appointments at the University of California
Berkeley and the Chinese Academy of Science. Jaffe’s inner sanctum was his
lab family. Then Richard Borgens came to town.
The Texan

There were some missing years on Richard Borgens’ application to study in

Jaffe’s lab. Jaffe asked about them. Instead of an answer, Borgens handed him
a vinyl record of his band, the Briks.6
Borgens was from Texas, and the only thing bigger than his personality
was his moustache. He liked vintage cars, vintage guns, and amphibians (from
an early age, he had been transfixed by how newts in his father’s aquarium
regrew their legs after the fish bit them off). His path to Purdue was very
different from the high-calibre institutional pipeline that had produced Ken
Robinson and Mu-ming Poo.7 In the late 1960s, he had started an
undergraduate degree at the University of North Texas, where he was soon
diverted by the Denton music scene (most of his bandmates attended Cooke
County Junior College, designated by one teacher a ‘home for the academically
ill’8). He was vocals and lead guitar, and the band’s moody, melodic twang
sufficiently captured the zeitgeist to attract a dedicated fanbase and have a few
songs go national. On weekends, Borgens liked to jam with Stevie Ray
Vaughan’s older brother, or when he wasn’t around, Don Henley. ‘All of us
who followed them thought for sure they were headed for greatness,’ wrote
one fan on a memorial site forty years later. ‘But time, the military, and the war
in Viet Nam [sic], and the general insanity of the time, all saw it another way.’9
Borgens ended up on a brief tour as an army medic and came back with a
different perspective. He quit the band and finished his degree, completed a
masters in biology, and then arrived at Purdue. Borgens recalled walking into
Jaffe’s lab and seeing people doing things he already knew how to do to get a
PhD – ‘Why couldn’t I get a degree doing that kind of thing too?’ Borgens was
the only one in Jaffe’s lab who wasn’t a physicist, but that didn’t bother either
of them.
Like Jaffe, Borgens was too impatient to study parts of a system – he
wanted to understand how they worked as a whole. If his approach to
academia was slightly less buttoned-up than some of his labmates, he won
them over quickly enough. ‘He came across as a hick, you know, but he was
really very smart,’ says Nuccitelli. The two became fast friends when Borgens
found out Nuccitelli played string bass: ‘We wrote a lot of songs together
making fun of the people in our lab.’
But mostly they played with what they could get electrical fields to do.
Borgens liked to call himself an experimental zoologist.10 For a while he was
diverted by a project in which he tried to use electrical fields to grow legs on a
snake. Mu-ming Poo was long gone – he had abandoned electrotaxis in favour
of the more obviously explicable, scientifically acceptable mechanism of using
chemicals rather than electricity to coax neurites around a petri dish. But the
other students in Jaffe’s lab retained their commitment to physiological fields
even after they left Purdue – Robinson going to Connecticut, Nuccitelli to
California, Borgens to a fellowship at Yale. In 1981, Robinson and his student
Laura Hinkle published definitive proof that the cells in the dish were
responding to the electrical field and not any other mysterious chemical
signals.11 They found that it was possible to ‘turn’ the neurites’ growth in any
direction you liked just by re-orienting the field. This worked so well and so
predictably that by continually changing the location of the field source, they
were able to ‘draw’ intricate patterns. They made a game of looking for their
own initials in the axons’ looping scrawls.12
As they were starting to discover this power of manipulation, new
implications arrived: those same electric currents they had measured with the
vibrating probe were also involved in regeneration. They had been shown
leaving the cut ends of amputated amphibian limbs, raising the possibility that
they were causative agents.13 Borgens took the petri dish research from Jaffe’s
lab, and in 1981 extended it into living vertebrates. He started with larval
lampreys.14 What’s unique about these sea creatures is their ability to
spontaneously regenerate their spinal cord if it gets severed. The process
normally takes about four to five months, and during the healing process you
can observe those physiological fields and currents driving out of the injury
just as clearly as du Bois-Reymond measured his own wound current.
Borgens wanted to know if you could amp them up. When he applied an
electric field to the regenerating neurons, he was able to speed up the healing
time by a factor of three. The reason this had worked, and that the electric
field was able to speed up the spinal healing process, is because it had
prevented the severed axons from engaging in a behaviour called die-back.
Die-back is one of the most vexing obstacles to healing any spinal injury,
mammalian or amphibian. When neurons are cut, they initially respond by
shrinking away from the cut edge before beginning the process of regrowing.
If you could prevent the die-back, you could head off a bunch of the other
problems that pile up after a spinal injury.
Dying and injured cells void their toxic internal contents, which
inadvertently kills nearby healthy cells. That brings the macrophages and white
blood cells, charged with tidying up debris and gobbling up foreign bodies,
marching into the injury site. But these cells are not great at portion control;
they invariably overeat and over-stay their welcome, which creates a big fluid-
filled cyst. Then scar tissue begins to form, creating yet another physical
obstruction for any axon thinking about regenerating. As if all that weren’t bad
enough, in adult mammals, injury leaves behind inhibitory molecules that
unambiguously signal that something bad has happened here, do not enter. No
wonder so few vertebrates can regrow a spinal cord.
Borgens had an idea for how to overcome this. He figured if you could get
axons to grow across this territory right away before all the other chaos kicks
off, there was a much better chance of regeneration. Poo had already
established that neurites grow faster when you put them in a DC electric field,
and that they grow toward the cathode. Sure enough: when Borgens applied
the electric field, it acted as a coach and guide. It coaxed the axons to ignore
the normal inhibitory cues that prevent reconnection to their lost other halves.
And this was happening in the complex environment of a living lamprey, not
some petri dish.
In 1982, he returned to Purdue, where he quickly took his lamprey finding
up the ladder into mammals, suturing electrodes to guinea pigs’ severed spinal
columns. The experiment yielded the same results: he found that, again, he
could trace the regeneration of axons across the lesion site. But he ran into a
problem he hadn’t seen in lampreys. Healing in the guinea pigs was sporadic
and depended on whether the cathode was above or below the injury site.
The spinal cord is organised like a two-lane highway. The sensory axons go
up to the brain to deliver sensations. The motor axons come down from the
brain to carry instructions. So, if you put the cathode above the injury site, all
the axons will grow towards it – meaning only the sensory axons will
reconnect across the site. Put the cathode below the site, and only the motor
axons cross. However, Borgens remembered that Robinson had previously
demonstrated in frogs that neurons grow eight times faster towards the
cathode than they do towards the anode. He realised that if he could get his
electric field to strobe instead of shine steady – reversing its polarity back and
forth so the cathode would be on one side of the injury for fifteen minutes,
and then switched to the other side – he might be able to solve the problem.
To everyone’s surprise, it worked: Borgens was able to create a kind of two
steps forward, one step back pattern of progress that eventually coaxed all of
the axon pieces to fuse together. The guinea pigs regained motor and sensory
function.15 He called his new invention the extraspinal oscillating field
stimulator (OFS).
By then, both Borgens and Robinson were back at Purdue, ready to
continue the work begun by their mentor Lionel Jaffe – who had meanwhile
left the university to direct the brand-new National Vibrating Probe Center at
the Woods Hole Marine Biological Lab (and to devote more time to his marine
fucus) – but they had different ideas of how to do so. Borgens had already set
his eye on medical applications. The implications were so obvious. Human
spinal cords don’t heal naturally. But if guinea pig spinal neurons could be
coaxed to regenerate by an applied electric field, it stood to reason that this
technique should help heal the same kinds of devastating injuries in people.
It was a good time to be doing this kind of work. Optimism about spinal
injury research was ascendant after a long period in the doldrums, aided by a
spate of high-profile injuries. Marc Buoniconti, the son of a Super Bowl-
winning Miami Dolphins linebacker, had just been catastrophically injured
playing college football. In 1985, his father helped found the Miami Project to
Cure Paralysis.16 It was one of several influential efforts formed in the US and
Canada to address spinal cord injury, all of which attracted considerable
funding and media attention. It was one of these organisations that invited
Borgens to attend a philanthropic dinner for spinal cord injuries, recalls Debra
Bohnert, the lab’s administrative assistant from 1986 to 2018. ‘He came back
and said, “I can do this, I can figure out how to cause regeneration in the
spinal cord”,’ she says, ‘and that’s what we ended up doing for the rest of his
career.’ His passion clearly impressed the philanthropists he had met at one of
these dinners, because in 1987 one of them, a Canadian millionaire who used a
wheelchair, donated a pile of money to Purdue, earmarked for Borgens. He
used it to establish the Center for Paralysis Research at Purdue’s School of
Veterinary Medicine.
With the new influx of cash, and the upgrade to a whole new building,
Borgens set his eyes on his next target. He wanted to get the OFS into human
trials, but you couldn’t go to the FDA with a guinea pig or rat trial – the
diameter of their spinal cord is an order of magnitude smaller than that of a
human. The effects from an electric field would differ so much as to make the
trials meaningless.
So Borgens settled on dogs. It wasn’t just the better approximation they
offered of human anatomy; he was also interested in them because they
offered a chance to treat real-world injuries. When dogs sustain spinal injuries,
the injuries tend to have a lot in common with the kinds of spinal damage
people face – messy crush injuries, not artificially tidy scalpel incisions made in
a lab. This could be the springboard to a human trial. (Also, it must be said,
Richard Borgens loved dogs.)
So he got in touch with a company that makes assistive devices for
paralysed dogs called Doggy Kart. You may have seen dogs wheeling around
in these – they look like a child’s toy wagon. The dog’s back half is strapped in
while the dog uses its front legs to pull it along. As cheerful as this situation
may look to passers-by, for dogs and their owners, paralysis is a grim situation.
When a dog is paralysed, the owner must manually express the animal’s bowels
and bladder several times a day. A veterinarian will usually recommend
euthanasia.
Bohnert says the centre offered to pay for a dog’s spinal surgery if the
owner would agree to let them implant the stimulator. ‘We also gave them a
wheelchair,’ she says. ‘We just asked them – hey, if your dog gets better, we
want it back.’ The first trial was on twenty-four dogs, thirteen of which were
implanted with a real stimulator.17 (An important note here is that, at this
point, there was no more ability to test whether the neurites had grown the
way Borgens was expecting them to. People’s pet dogs are not lamprey eels –
you can’t kill them after a test and dissect their spines to examine how well the
neurites responded to the electrical stimulation. All you can do is figure out
from the dog’s behaviour whether there have been any meaningful changes.)
After six months, seven of the OFS dogs could walk again, two of them
almost as well as a dog that had never been injured. All the rest regained
control of bowel and bladder and other functions. The gains were
permanent.18
Based on this success, in the early 1990s, they expanded the trial. People
sent their dogs from all over the country to take part. Borgens recruited Scott
Shapiro, a neurosurgeon at Indiana University, to help him implant more OFS
devices in more animals. By 1995, they had treated nearly 300 dogs with spinal
injuries. ‘Without treatment, 90 per cent of these dogs would have been put to
sleep,’ Borgens told the Chicago Tribune.19 ‘We got a lot of carts back,’ says
Bohnert.
Saving dogs from paralysis and euthanasia simply had no PR downside.
These successes were captivating, and Purdue was awash in the warmth of
media attention and money. In 1999, Borgens got a provision written into
Indiana law that committed the state to give half a million dollars to Purdue
each year for spinal injury research.20 The following year, Mari Hulman
George, the chair of the Indianapolis Motor Speedway – if you watched the
Indy 500 between 1997 and 2015, it was her voice you heard bellowing ‘Ladies
and gentlemen, start your engines!’ – added another $2.7 million to the pot.21
There was now enough money to pursue a human trial. Shapiro and Borgens
started the long process of getting approval from the FDA. ‘It took two years
and four volumes of text but we got approval to put ten devices in ten
patients,’ says Shapiro.
 Purdue held a grand, official announcement to kick off the human trial.
Wandering around the stage was a shiny brown pointer mix called Yukon
whose life had been saved four years earlier by Borgens and his team after
being paralysed by a ruptured disc.22 David Geisler, whose family Yukon was
part of, recounted the harrowing circumstances around bringing his beloved
pet to the centre for evaluation to see if he qualified to join the trial, knowing
the outcome if the answer was no. ‘There was a team of people watching me
cry,’ he said. But the OFS came through. ‘I knew he was getting better when
he started wagging his tail,’ said Geisler.23 By the time the human trial was
announced, Yukon was bounding up and down the stairs again. Hope was
thick in the air at the press conference. The event was covered by the Los
Angeles Times.24 The bar had been set high.
Brandon Ingram and the nine other volunteers had been paralysed during
a narrow window less than twenty-one days before starting the treatment. All
their injuries had been catastrophic. Borgens and Shapiro implanted the device
about the size of a cardiac pacemaker and left it there for fifteen weeks. In that
time, they hoped, its oscillations would guide the axons across the injury the
same way as they had been shown to do in lampreys, rats, and guinea pigs. And
they hoped for the same functional and sensory results they had seen in the
dogs.
After the devices were taken out, Borgens and Shapiro then followed the
participants for one year, testing them periodically for what sorts of changes
they perceived. Unfortunately, few reported changes in mobility like Ingram
experienced – but that is far from the only endpoint for spinal surgery. In
surveys, people with spinal injury consistently put regaining the ability to walk
at the bottom of a long list of much more pressing concerns, which include
going to the bathroom independently, regaining sensation, and the ability to
subtly shift position to prevent pressure ulcers. The volunteers regained a mix
of these abilities.
After a year, all but one of the participants had regained enough sensation
to feel their hands and legs. It was mainly light touch and pain, sexual function,
and some proprioception (the body’s sense of its own position). No one
regained bowel and bladder function. This wasn’t a disappointment, as
Borgens never claimed that he’d make people walk again: ‘Richard was very
careful to say to us: “never say we’re going to cure paralysis – just that we will
give some people some function back”,’ Bohnert told me. Two patients –
including Ingram – did recover some lower-extremity function, and both recall
that another of the patients could now lift his legs horizontal to the floor for
the first time since his injury. Most importantly, any ability that had been
regained was there to stay: ‘Their improvements were durable,’ Shapiro says.
The results were impressive enough that the editors of the Journal of
Neurosurgery: Spine put them on the cover in 2005. This was a phase one clinical
trial, which is only for safety, not for efficacy, so the functional improvements
‘didn’t count’. But that was fine – the device had cleared its first hurdle: no
deaths, no infections, and no painful side effects. The OFS had been proven
safe.
Eventually, it would have to pass several more trials in order to be sold. A
device like this is not permitted to be sold on the open market in the US
without explicit regulation by the Food and Drug Administration. If the FDA
doesn’t clear it for use in human beings, you can’t sell it. Period.
Of course, none of the subsequent headlines screamed about the device
having passed a routine safety clearance. ‘Nerve Repair Innovation Gives Man
Hope’ was more like it.25 Ingram’s experience was especially galvanising. He
was able to dress himself, shower, and get in a car on his own, he told
newspapers, which continued to seek him out two years later.26
Based on the safety analysis of the first trial, the FDA approved a second
clinical trial for ten more patients with severe spinal cord injuries.27 This one
would differ from the previous trial in a crucial way: instead of simply ensuring
the device was safe, it would explore how well it actually worked. The most
important way to do that in any scientific study is by equipping some people
with the real device and others with a sham – a pseudo-stimulator that doesn’t
do anything. This placebo control group is the key to any ‘gold standard’ trial.
They provide the crucial contrast to your technique. If there’s a big difference
between their improvement and the better improvement of the people with
the real device, you move on to bigger and bigger trials to determine, to ever
greater precision, whether the effect of your device is real and how big it is.
Neurosurgeon Scott Shapiro methodically went about planning all of these
next steps. He recruited three more neurosurgeons at other medical centres
that had agreed to take part in the next small randomised controlled trial. And
after that, his plan was to approach the NIH to fund a slightly bigger trial of
eighty patients, forty of whom would receive a functional OFS. To Shapiro, the
next steps were clear, and they had to be done in order.
That wasn’t how Borgens saw it. He was getting older, and he had been
carrying out this work now for the better part of twenty-five years. He was
tired of baby steps, and all the publicity and acclaim was making it harder to
think in increments. He wanted something on the market. But the OFS was a
hard sell for big device manufacturers like Medtronic. There was no money to
be made on such a comparatively rare injury. What was even more
unpersuasive to them was that most of these injuries occurred in uninsured
males (more likely to sustain gunshot and diving injuries). Borgens thought he
could manufacture and sell the device to a big, rich company and let them
worry about all the FDA paperwork. So, three months after the paper was
published in the journal, he and some of his colleagues founded a start-up
called Andara Life Sciences and negotiated the intellectual property rights to
the OFS. Within a year, they had found their big, rich company, and it quickly
swooped in and gobbled up Andara.28 The company was Cyberkinetics, the
same outfit that had made BrainGate. Yeah, those guys.
Purdue bathed in the golden light of Borgens’ fame. His research was
raining both state and private money on the school. Mari Hulman George
reached into her foundation’s pockets again for another $6 million. In short
succession, the OFS won a series of major accolades from industry watchers
who eagerly anticipated the day when this first-ever neural regeneration device
would hit the market: it ‘represents a groundbreaking advance in
neurotechnology,’ pronounced James Cavuoto, the editor of Neurotech Business
Report.29 As an investigational device, however, the OFS was still not approved
for sale, and was available only through participation in a clinical study (the
details of which Shapiro was still meticulously working through).
Cyberkinetics, which wanted to start earning money from its latest investment
a lot sooner than that, filed an application for Humanitarian Use Device status
from the FDA, which, if granted, would have let Cyberkinetics sell the device
commercially by late 2007. Borgens and Bohnert were given to understand
that the approval was almost a formality. ‘They told us: oh yeah don’t worry
about that, we know how to deal with the FDA,’ says Bohnert. Cyberkinetics
expected that they would start selling the stimulators the following year.

The apostate

Ken Robinson was worried. He had wondered, reading Borgens and Shapiro’s
paper, what accounted for the decision to choose exactly fifteen minutes
between switching between cathode and anode. But when he poked around in
the references for the justification – he found himself faced with his own
name. This was a big surprise for Robinson, as the paper in question had in no
way addressed this idea. ‘It misrepresented my work,’ he says.
Robinson had never seen any mammalian neurons respond to
physiological fields the way his amphibian neurons did. To get any effects at all
required one or two orders of magnitude higher fields. So Robinson tried to
repeat the experiment in zebrafish. It should have been a formality, a box-
ticking exercise. Instead, his zebrafish neurons were unmoved by any
interaction with the ‘physiologic’ currents. ‘We were stopped cold,’ he says.
‘You could not extrapolate from amphibians to other animals and assume they
were the same, especially mammals. And that caused me to start looking at the
whole picture.’
In 2007, Robinson brought his misgivings to Shapiro in a long letter,
asking whether the team had ever actually directly observed the vaunted
bidirectional growth in any of the frogs. ‘Well, I got no answer whatsoever,’ he
says. Robinson began to worry that the experiments had been unethical. ‘They
just did not have sufficient grounds for doing it.’
How could a scientist make any claims for an intervention when there was
no one in the study who was not receiving the treatment, as was the case for
this safety trial, by design? How could they account for the placebo effect?
There was no way to check the volunteers’ self-reported improvements against
spinal neurite growth – it’s not like you could cut them up for dissection. The
comparison groups Shapiro and Borgens used were case studies from other
experiments unrelated to theirs. Sure, none of the ten subjects were harmed,
but ‘those experiments were unethical even if they didn’t harm anyone,’
Robinson insists. Skipping the necessary foundational work, he says, meant the
design of the stimulator was utterly arbitrary, and this alone rendered the
experiments unethical. Founding a company and selling the device
compounded the offence.
This argument formed the rough gist of a review article, which Robinson
and his colleague Peter Cormie published in 2007, after deeming that they had
waited long enough for a response to their letter.30 It eviscerated Borgens’
work. Its most immediate effect was to alienate Robinson from the rest of
Jaffe’s descendants. The break was so immediate and complete that today,
retired in Oregon, he still refers to himself as ‘the apostate’. This term is
usually reserved for religious acolytes who turn their back on their beliefs. The
acerbic review was the first drop in a hailstorm.
Against expectations, the acquisition by Cyberkinetics had not cleared a
path for trials. In fact, nobody told Shapiro about the acquisition. ‘I was
unaware,’ he says. He had been plugging away at his fastidious roadmap,
having implanted another two patients, and things were going well. ‘All of a
sudden, this company came in, took all my study documents and devices, and
shut me down.’
What no one knew was that, by 2007, Cyberkinetics was near bankruptcy
and desperate for a commercial product. ‘They tried to ram the device through
the FDA on a compassionate use basis on the basis of twelve patients,’ Shapiro
says. ‘I knew that would fail.’ At some point – in addition to failing to grant the
humanitarian exemption – the FDA also appears to have withdrawn its
approval for any more implanted patients in a phase two trial.
But none of this was ever made clear to Borgens. The FDA just dragged
its feet on approvals, in a move that seemed calculated to run out the clock
until no one had any money left, and the project withered and died.
Quick aside for a moment in defense of the FDA: the Food and Drug
Administration might be the most underfunded, overworked, and unfairly
maligned regulatory agency in the US. They are tasked with making sure every
drug and device meets its claims and doesn’t kill people. Business-friendly
political administrations like to starve it of funds, believing that the agency
really enjoys getting in the way of innovation. But when the FDA can’t do its
job properly, you get things like vaginal mesh implant disasters and breast
implants that leak. It’s thanks to the FDA that faulty ventilators were recalled
during the Covid-19 pandemic before they could kill someone.
However, as the oscillating field stimulator was going through its
tribulations, the FDA was very different from the agency it is today, and this
played a part in the device’s demise.
Like James Cavuoto, Jennifer French was frustrated by the way the agency
handled the Andara device’s approval. French, a patient advocate for the FDA,
saw the entire process from the inside. She knows a thing or two about spinal
injuries. In 1998, after a snow-boarding accident permanently damaged her
spine, she became tetraplegic. A year later, French volunteered to become one
of the first people in the world to test a cutting-edge new electrical implant
called the Implanted Neural Prosthesis, which temporarily restores to
paralysed people the ability to stand and move. It does so by injecting pulses
of current into the muscles and nerves through precisely placed electrodes.
Serving as a test pilot for this cutting-edge neuroengineering gave her
unparalleled insight into the gap between what people needed and what
researchers were providing. She quickly became involved in advocating for
people with neurological conditions, specifically to help the agencies tasked
with sorting the promising advances from the snake oil.
 For French, the OFS’s ability to restore sensation had been the most
compelling and statistically significant outcome. Sensation is an absolutely vital
priority for people with spinal injuries. It is crucial to warding off pressure
sores – breaks in the skin. When you can’t feel your skin, these can go
unnoticed and then become infected and turn septic, poisoning the blood.
Sepsis is one of the top two causes of death among people with spinal cord
injury.
However, when it came to evaluating evidence of a product’s efficacy, the
FDA was less interested in what patients in trials had to say about a device’s
impact on their life than in what it considered more ‘objective’ measures,
which is why, in 2007, the measurements the FDA used to evaluate a device
didn’t include sensation. ‘It’s considered a black box,’ she explains. The sort of
evidence they wanted could be evaluated independently by a clinician with a
focus on motor activity. Today, thanks to the advocacy of people like Jen
French, that has changed, and the FDA takes patient-reported outcomes much
more seriously than they used to.
But at the time, this meant that the FDA didn’t really see what the fuss was
about. This device wasn’t really getting people on their feet again, so why rush
through more trials or exemptions? The other issue was that, unlike today, the
agency hadn’t yet established the programmes that help guide companies
through the reams of paperwork necessary to gather the safety and efficacy
data needed for approval. They just sort of let them figure it out for
themselves. Some did; others didn’t.
All the while, Cyberkinetics continued to bank on the exemption, which
kept being promised and delayed, month after month. ‘Back then the FDA
was taking a long time to make decisions,’ says Cavuoto. Even as they passed
over patient reports, they attended to reams of other evidence in their
deliberations. That probably included Robinson’s review. But it would have
certainly included the public statements made by a world-famous neuro-
scientist in a leading newspaper. In 2007, Miguel Nicolelis at Duke was
interviewed about the OFS by the Boston Globe.31 ‘I have nothing good to say
about this company,’ he fumed. ‘I see no solid science behind their latest
attempt to make some quick revenue or save their stock price from collapsing
altogether.’
What did Miguel Nicolelis know about physiological fields? Not much, it
turns out. ‘This had nothing to do with Andara,’ says Cavuoto – it had
everything to do with John Donoghue, one of the founders of Cyberkinetics.
Nicolelis hated Donoghue, he recalls. Both men were pioneers in brain–
computer interfaces, but Donoghue was the media darling who got column
inches in The New York Times, and Nicolelis wasn’t – to his ever-present
consternation. ‘Nicolelis didn’t know anything at all about the technology – all
he knew was that it was John Donoghue’s company.’
After the disparaging comments were published, Cavuoto wrote a pleading
editorial – aimed at the FDA – begging them to not listen to Nicolelis. But it
was too late. Cavuoto reckons the article helped sink the company. ‘The FDA
took their sweet time and [Cyberkinetics] ran out of money, and the investors
pulled the plug. And that was that,’ he says. Then the 2008 recession hit.
Cyberkinetics, Andara, the humanitarian device exemption – all of it was gone.
Fifteen years later, Cavuoto is still sore about the way things went down,
and not just about the device itself. ‘When you forced Cyberkinetics out of
business – which is what the FDA did – you were sending a clear message to
the research and the investment community,’ he says: work on this, and your
career will go nowhere. The effects of its actions, he claims, ripple out more
than a decade later. ‘In my opinion, it set the field back maybe ten years.’

The end of the road

Meanwhile, the Purdue lab could never get their phase two trial properly
underway. ‘The FDA wouldn’t allow it to start,’ says Bohnert. ‘They just kept
requesting more information. We never knew why. I just remember saying to
Richard, “Who did you piss off ?”’ But true to his personality, after all the
setbacks, Borgens still refused to give up. He tried several times to reassemble
what pieces they had left. Both he and Shapiro – and later, his post-doc
Jianming Li – applied herculean efforts to get the OFS restarted or at least
prevent it from being memory-holed. In 2012, Shapiro wrote a post-review
publication to report the OFS results that included the four additional
participants he had managed to cobble together. He published another similar
review in a European journal in 2014, part of the same effort to keep the work
academically relevant.32
But eventually, it was too much even for Borgens. ‘The FDA just buried
him under so much paperwork that he eventually gave up,’ says Ann Rajnicek,
who earned her PhD under Robinson but cut ties after the events. ‘He used to
put his hand up, you know, extend his arm as high as it can go, and he would
say, “I have filled in paperwork, literally this high for the FDA, to try and make
this happen.” And he said, “I just don’t have the will for it any more.”’
Li, now a research professor, tried to take over. He modernised the OFS
electronics and tinkered with optimising the electrode placements. The
technological advances since 2001 offered staggering upgrades: the ability to
alter device settings, new algorithms, control of the device using an app. But
Borgens had already turned his focus away from technology and towards
drugs that could fuse neurons.33
Then, in 2018, he was diagnosed with prostate cancer. That’s when Purdue
cleaned house. Bohnert says one of the deans forced Borgens to retire. The
others in the department who weren’t laid off either retired early or left.
Borgens passed away at the end of 2019.
Even then, Li tried to carry on his old mentor’s work, trying to keep both
the Center for Paralysis research and the OFS alive.34 As the original patent
had expired, Li put together a new patent filing and published some of the
advancements.35 A tentative collaboration with Case Western was on the verge
of testing the new version of OFS in humans. Then Covid struck.
In the chaos, Li was let go and replaced with a new director, who changed
the mission of the centre in a direction that ruled out further work on the
OFS. ‘It was just so sad,’ says Bohnert. ‘He had a way of helping people and
they wouldn’t let it go forward.’ Shapiro retired from Indiana University in
2021. All that remains of Richard Borgens at Purdue is an office door painted
to look like the Texas flag.
Decades later, Andara is a whole garden of what-ifs. Would it have
succeeded if it hadn’t gotten caught up with Cyberkinetics, hadn’t been
torpedoed by the recession? Was Robinson right that Borgens skipped crucial
steps at the beginning that would have made themselves known in later trials?
Or was the idea simply too far ahead of its time?
Here was a device that worked on neurons but had nothing to do with
familiar concepts like the neural code and action potentials. It was a wound-
healing mechanism that used electricity, which didn’t make any sense to
biologists and dredged up old memories of electroquackery. ‘The stuff he was
doing was truly on the cutting edge,’ says Richard Nuccitelli. ‘Trying to
regenerate the spinal cord – guide new growth – that’s something standard
electrophysiologists know nothing about. They aren’t interested in that –
they’re only interested in action potentials’.
Today, spinal stimulation is back in the news.36 But it’s action potentials
that are the focus of these new research efforts, which approach spinal
connectivity from the traditional perspective. Instead of trying to reconnect
severed axons, they apply intense bursts of electricity to any remaining intact
axons in the spinal cord to force them to carry action potentials that drive
motor function. These few remaining undamaged pathways, it turns out, can
exhibit plasticity like that most commonly associated with the brain. This – not
fusing broken neurons back together – seems to be how electricity is popularly
used in spinal injury research now. And there is some success. A handful of
people are walking who, before technological intervention, did not. ‘Maybe if
Andara had been approved, that all would have happened years earlier with
more different approaches,’ Cavuoto grouses. ‘Maybe more people would be
walking around now after spinal injuries.’
Was Borgens’ device actually working on these principles? Or are today’s
devices actually working because some of the fields are reconnecting axons the
way the OFS did? The problem is that there are not a lot of ways to test
whether Borgens was right about exactly what mechanism restored movement
to Brandon Ingram. As with dogs, you can’t cut people open to check.
However, the work emerging from other areas of bioelectricity in the body
could settle that question soon. That’s because it’s becoming clear that Richard
Borgens was tapping into bioelectric properties of cells that are just now
beginning to be understood in full. When it comes to the physiological fields
Borgens’ OFS was recruiting, those were absolutely real, and they are not
unique to cells in the spine. The same electrical properties are common to
every living cell in your body. Borgens might have recruited them in a way that
put the cart before the horse, but it is clear that he was tapping into something
elemental. And as this research finally begins to mature, it is cohering into
theories of how physiological electric fields mend the body whichever way it
breaks down, and how to create new devices to help it do better.
Borgens’ work continues to be replicated in small trials, most recently by a
Slovakian group in 2018, which recreated the OFS precisely. They tested it in
rats, and with the improved imaging and analysis available more than thirty
years after Borgens did his own rat trials, were able to see exactly what the
OFS was doing. Under the guidance of the electric field, the mangled axons
successfully clasped on to their estranged partners over the injury site. We may
not have seen the last of the oscillating field stimulator.
Borgens’ instincts, it turns out, had been right.

All your batteries

In the decades Borgens spent fighting his battle, other researchers rapidly
populated the periodic table of all the other cells that respond to ultra-weak
physiological electric fields.
Colin McCaig set out to build an unassailable body of evidence that nerves
and muscles aligned themselves under a weak electrical field. He realised he
needed to bolster his case for sceptics, and that he could do so by showing
that the so-called ‘physiological field’ did the same thing in other kinds of
bodily tissue. He recruited Ann Rajnicek – Robinson’s estranged protégé – and
Min Zhao, who had studied with China’s top trauma surgeon, to move to
Scotland and join his lab at the University of Aberdeen. Together, they set out
to demonstrate that bioelectricity had profound effects everywhere in the
body. What else could be dragged around by a cathode?
Pretty much anything, as it turned out. The same subtle fields Borgens had
tried to recruit to heal wounded axons – and which Poo had found guiding
those spinal neurites – also coaxed crawling behaviours out of skin cells,
immune cells, macrophages, bone cells, and just about anything else they got
their hands on.
Zhao in particular was shocked by the sheer power these electric fields
could exert. Arriving at McCaig’s lab, he had expected a predictable series of
events to unfold: as usual in science, he would put in some time characterising
yet another interesting factor among so many others, in yet another complex
biological process. Sure, the work would be ‘important’ – but, he suspected,
not thrilling or actually that consequential. It wasn’t going to change the world.
That’s how it normally is in biology; there are too many factors involved to
ever neatly pinpoint the overarching importance of a single one. This was
especially true of wound healing, a farrago of interlocking growth factors,
cytokines, and other contenders: ‘Everyone has their favourite molecule and
they can show that it plays a significant role,’ he says. But when Zhao turned
on the electricity for a healing experiment, the results blew them all out the
water.
Zhao was stunned. A tiny electric field held veto power over the influence
of any other growth factor or gene or anything else people had previously
assumed to account for wound healing.37 The cells did what the electrical
fields told them to do, no matter what else competed for their attention.38
This is the hallmark of an epigenetic variable. ‘That was when I realised we
were working on something far more important than other people, even
myself, had expected,’ Zhao told me.
To his consternation (and McCaig’s and Rajnicek’s), no one else was
interested in their findings. As evidently disruptive as their work was – for
better tissue repair, for understanding of embryonic development, you name it
– among other electrophysiologists it went largely ignored.39 Electricity doesn’t do
that. Many scientists looked at it with the distaste normally reserved for
homeopathy.
The Aberdeen dream team, however, was undaunted. They pressed on.
They had only seen the first glimpses of why these fields were important. The
individual cells shuffling around their petri dishes weren’t the main point.
After all, your body isn’t made of a bunch of individual cells milling about, it’s
made of huge assemblies of them organised into cooperating tissues and
organs. They form four main types of tissue: apart from nervous and muscle
tissue, there’s also connective tissue and epithelial tissue (skin). And the
Aberdeen research promised to answer the longstanding mystery of why
electricity poured from these when they sustained damage.
Your skin is a tightly coordinated collective of billions of cells. It’s
organised into three layers of tissue called epithelium, the outside-facing of
which is called the epidermis. If you’ll permit an oversimplified metaphor, you
can think of your skin as a scaled-up cell membrane, but for your whole body.
That’s especially true from an electrical perspective.
Epithelium generates a voltage across itself. You could interpret it as an ‘all
systems nominal’ signal. When your skin is intact, it generates an electric
potential so that the outer skin surface is always negative with respect to the
inner skin layers.
Where it gets really interesting, though, is what happens when you cut that
skin. You sever the epithelial layers of the epidermis, and when that happens,
all those sodium and potassium ions, which had been travelling nicely through
the neat pathways offered by their gap junctions, leak haphazardly all over the
place. If this were a wire you had cut, you’d be short-circuiting it, meaning
electricity would flow in every direction. The neat avenues for the current are
gone or smashed-up, and so the ions just pour out into every available space.
As I mentioned in the introduction, this is the wound current you can feel
if you bite the inside of your cheek and then touch the bite mark with your
tongue. The tingle is you sensing the voltage. Ken Robinson used to do a
much more dramatic demonstration for his students at Purdue, recalls
Rajnicek. He would take an ammeter and project its dial, resting placidly at 0,
on a screen at the front of the lecture hall. Then, with a flourish, he would
show two beakers of salt solution connected to the meter, and dip his fingers
into the solution, to show that it left the dial unperturbed. For his next step,
‘which I don’t recommend doing today,’ Rajnicek says, Robinson pulled out a
razor blade and nicked his finger, and then dipped the bloody appendage into
the beaker once more. The needle would swoop. ‘You could just see the
current going right up,’ she says. ‘It got gasps from the audience every time.’
All that leaking current creates a field whose influence can be felt across
some distance within the body. This acts like a combination burglar alarm,
compass, and bat signal for surrounding cells. Just as Mu-ming Poo and Ann
Rajnicek used artificially generated electric fields to drag individual cells
around a petri dish, the naturally occurring field created by the wound current
convinces a whole crew of them to migrate to the wound. It guides in and
directs the body’s emergency workers: the keratinocytes and fibroblasts that
rebuild the structure, and the clean-up crew (the macrophages). They all work
together to reseal the epidermis. What’s even cooler? The electric field directs
the cells to the centre of the wound. That’s your natural cathode – the big red
bulls-eye towards which all the migrating helper cells in the body are
marshalled.
This starts the repair process. And as the repairs get underway, the wound
current and its associated electric field begin to fade out. By the time the
wound is healed over, there is no more wound current to detect. This is how it
works in all epithelial cells.
And guess what: your skin is not your only epithelium.
To simplify things even further, think of your skin epithelium as the
electric shrinkwrap around your body that keeps your insides inside you and
your outsides outside you. And just as your whole body is surrounded by the
multi-layered electrical epithelium you call your skin, so are all of your organs
bound by their own individual electric shrinkwrap.
Depending on the organ, the epithelial shrinkwrap is either on the outside
or the inside (technically, if it’s inside, you call it an endothelium, but it’s still
the same stuff). Some organs have both – your heart is wrapped in the stuff
inside and out. It wraps your kidneys and your liver. It lines your mouth, blood
vessels, the hollow parts of every organ such as the lungs, eyes, your urogenital
tract, your digestive tract, your vagina, your prostate. I can’t stress this enough:
it’s everywhere. Its main job, just as a cell’s membrane creates a boundary that
determines what’s allowed in and out, is to determine what goes in and out of
the organ it wraps (with contributions from the circulatory system). And
because both epithelium and endothelium are electric, that means all those
things are batteries too. Every organ in your body has a voltage, and it uses
that voltage. The reason for the heart battery is easy to conceptualise – the
heart literally uses the field to control its beat. ‘It’s an electrical contraction,’
says Nuccitelli. But you also have a kidney battery. You have a boob battery
(the lumen of mammary glands). A prostate battery (looking at you, Alexander
von Humboldt). Everywhere current crosses the epithelium, you get a battery.
The eye battery is probably harder to conceive of, but it’s the coolest one.
The eye has an extra-strong wound current that helps speed up the healing
process in the cornea and the lens when they are injured.40 That’s because the
retinal epithelium is one of the most electrically active tissues in your body: the
reason any of us can see anything at all is because of the electrical currents and
fields that eddy about in its many layers, which 1970s researchers christened
the ‘dark current’.41 While it sounds like a homage to Pink Floyd, its name is
literal: this current only flows in darkness. Turn on the lights, and the sodium
channels snap shut, and a bunch of other signals flip on the colour vision.
So: nerve, muscle, and skin, all confirmed electric. That leaves one last
category – the connective tissues like bones and blood, which bind and
support the others. Are they electric?
Well, you wouldn’t be reading a book called We Are Electric if they weren’t,
so I’ll spare you the suspense.
Bone is electric too. Bone is a piezoelectric material, which means it’s a
tissue that can take one form of energy (the compression of running, say) and
convert it to another. For example, the stress of your footfalls on your bones
makes them grow stronger because the charges bone cells generate in response
to this mechanical activity get translated into electric signals that enhance bone
growth. Bone also emits strong wound currents when it breaks: voltages
appear at fracture sites and help the bone heal its wound.
In short, you can’t talk about a living system without recognising its
electrical component. We are nothing without electricity.
So if the body naturally uses its own electricity to heal wounds, what if we
could learn how to control it the way we had with the pacemaker and deep
brain stimulation?

Playing the field

It was becoming clear that you could disrupt the body’s natural repair
processes just by interfering with the electrics. Researchers in Scotland found
that if they used channel-blocking drugs to inhibit sodium ions, thereby
interrupting the electrical signals sent by the wound current in rats, their
wounds took longer to heal.42
But was the opposite true? Could we also speed up the healing process by
amplifying our body’s natural electricity? A spate of clinical trials over the past
decade increasingly suggests that the answer is yes. Perhaps the most
harrowing kinds of wounds are severe bed sores, which can take months to
years to heal (if they heal at all) and attack tissue, muscle, and bone deep
beneath the skin. Most of the research using electrical stimulation to heal
wounds in humans has been done in these kinds of wounds – like deep brain
stimulation, this is a method of last resort when nothing else seems to help.
After many years of these kinds of experiments, two groups of scientists
conducted meta-analyses and concluded that amplifying the natural wound
current with electrical stimulation almost doubles their healing rate.
Nor was the effect limited to skin; since the 1980s, a growing body of
evidence hinted that the same kind of small electrical currents could accelerate
healing in bone fractures, and some suggested it might even help treat
osteoporosis.43 It helps new blood vessels grow into wounds faster and is also
beginning to be seriously examined for eyes. Electrical stimulation has even
been shown to be effective at aiding skin transplants – it seems to help the
new skin take.
There’s a catch: the results of all these types of experiments have been
broadly positive – but also inconsistent and unpredictable. ‘The problem here
is that it’s not optimised,’ says Mark Messerli, who is working on bioelectric
wound dressings at the University of North Dakota. Because we don’t
understand the mechanism by which the electricity is speeding the healing of
the wound, we can’t do anything targeted to enhance or improve – or even
standardise – the stimulation. And that makes things hard for any doctors
hoping to use electrical stimulation on their patients. ‘To optimise wound
healing, we need to understand how it works.’
Min Zhao was able to vastly advance this understanding in 2006, when he
and the geneticist Josef Penninger undertook the first-ever controlled
experiment aimed at pinning down some of the genes that get switched on by
electric fields on wounds.44 This work was reported widely in the news – it
finally brought electricity into the legible zone of genes. This was some of the
earliest, most robust and tantalising evidence for the epigenetic power of the
electrome.
The next thing to do was find a way to measure the actual electrical field of
human wounds. Existing electrotherapy devices apply current with no insight
as to what effect it has on a person’s own bioelectricity. To change that, you
need a device that can help identify whether a person has an abnormal or
malfunctioning wound current. No tool had ever been capable of measuring
the electric field in the air next to dry mammalian skin – it had always been
done on wet frog skin in the controlled conditions of a lab. In 2011, Richard
Nuccitelli created a non-invasive device that could deal with human skin,
allowing our injury currents to be closely observed. The Dermacorder could
sense whatever the nearest voltage is. Hold it up to the skin and it maps the
voltage on its surface and correlates it with the depth of the wound.45 That
gives you a topographical, three-dimensional electrical map of the wound.
‘This was the first tool a physician could actually hold and use on a person,’
says Rajnicek.
It vastly deepened the understanding of how electricity works in wound
healing. Nuccitelli found a strong correlation between the magnitude of the
wound’s electric field and the progression of the healing – it peaks at injury,
slowly decreases as the wound heals, and returns to undetectable when healing
is complete. More interesting, though, was the relationship between the
strength of a person’s wound current and their ability to heal. People with
weak injury current healed more slowly than those whose injury current was
‘louder’. Most interesting of all: wound current strength wanes with age,
emitting a signal that is only half as strong in people over the age of sixty-five
as it is in those under twenty-five.46
With better measurements came better experimental results. In 2015,
Nuccitelli and Christine Pullar applied electrical stimulation to wounds and,
mapping it with the Dermacorder, were able to coax new blood vessels to
form, accelerating the healing in all their patients.

Electric healing

The idea of accelerated wound healing seems to be reaching a critical mass. In

2020, DARPA gave Zhao and several researchers $16 million to develop a
next-generation wound-healing system. This will not be a sticking plaster like
the kind you use when you nick yourself chopping vegetables. The bandage is
intended to heal major traumatic wounds, so it will recruit bioelectric healing
of multiple kinds of tissues at once – and speed up healing in all of them.
 The first proof of concept has been completed: a device that can maintain
specific voltage gradients in cells by exerting individual control over ion
channels.47 The other device is a wearable electronic tattoo, circuitry made of
electric ink drawn on the epithelium.48 This traces, in a three-dimensional way,
exactly where the wound current travels through the tissue as it heals. Such a
bandage is useful both observationally and diagnostically, as it provides
something like a topographical map in live tissue. The idea is that you could
use it like Google maps to track the exact movements of the wound current’s
various elements in real time. It can also deliver external electrical current with
similar precision. Rather than just beaming an all-purpose electrical field onto
a wound and hoping for the best, it introduces electrical fields in a precise way
that guides them to where they are needed.
Zhao reckons that this electrical conductivity body map is similar for all of
us, a bit like the wiring in every house adhering to common standards. ‘You
can’t just stick your power plug into any random spot on the wall,’ he says.
Richard Borgens was far ahead of his time in trying to harness the radical
implications of what Lionel Jaffe had discovered about the body’s
physiological fields. But in rushing ahead with clinical experiments, he was
trying to skip the steps that are only now possible with better understanding of
bioelectricity’s role in healing and precision tools to map and measure it.
In fact, using a wound-healing perspective may have not been radical
enough for what Borgens was trying to do with broken neurons. He was
focusing on controlling individual cells. In the past decade, an amazing rush of
new research has revealed that you don’t have to micromanage at this level –
there are ways to switch on the body’s dormant control systems to do it all for
you.
If you can figure out the right ion channels to switch on and off, you can
do a heck of a lot more than heal an injured limb. You could just regrow the
whole thing from scratch.
 PART 4

Bioelectricity in Birth and Death

‘We have trillions and trillions and trillions of cells in our
body . . . the genes in your nose and the genes in your eyes and
the genes in your mouth and the genes in your elbow, meaning
the cells in these tissues are all the same. Why do they do so
many different things?’
Mina Bissell

B y the dawn of the twenty-first century, we began to suspect that the

signals encoded in all those moving ions do a lot more than patch up
injuries. The old view that only neurons send messages that govern
communication gradually began to fall away, and a new idea emerged that
perhaps all cells send and receive electrical communications. The same
physiological fields that guide healing also appeared to guide our body’s ability
to mould itself from scratch according to a remarkably consistent blueprint –
and seemed key to cancer’s ability to spread in the body. Understanding this
electrical language could offer the keys to life’s most fundamental questions
and intractable problems – from how we are made to how we are unmade.
 CHAPTER 7

In the beginning:
The electricity that builds and rebuilds
you

Schrödinger’s finger

F or the past decade, Michael Levin’s conference talks and papers have
included a finely detailed line drawing of a little white mouse sitting up
on its hind legs. The expression on its face can only be described as a Mona
Lisa smile.1 Another source of ambiguity is its left foreleg, which is encased in
a small box. The paw in the box may have five fingers, or it might have four.
There are several actual mice in Levin’s lab at Tufts University, and they’re
each wearing one of the little boxes. All have had a single finger amputated.
The box is called a bioreactor, and it is placed on the stump after amputation,
along with something patented to manipulate the electrical communications in
the remaining tissue. It’s possible that one of the boxes contains a once-again
complete set of five fingers. The results are not yet in but this Schrödinger’s
appendage could change the future of an entire scientific field.
‘Regenerative medicine’ is an umbrella term that was only invented about
thirty years ago to cover the wide variety of ways people have tried to replace
what has been lost to trauma or age.2 The discipline was stitched together, a
bit like Frankenstein’s monster, from a disparate collection of other sub-
disciplines that included implant and transplant medicine, prosthetics, and
tissue engineering. What united them all into a coherent framework was the
discovery, and the galvanising promise, of stem cells.
 The reason you’re always hearing about stem cells is because of their
unique ability to turn into many other kinds of cells. They’re a bit like kids:
initially infinitely malleable, but as they mature and grow into their eventual
vocation, they specialise into specific adult roles like muscle or nerve or bone.
When you were a three-to-five-day-old blastocyst, you were all stem cells
(about 150 of them, in fact). By the time you’re an adult, you don’t have many
of them left, and what few you have are mostly generated in your bone
marrow.
When, in 1998, it became possible to derive these magic materials from
human embryos and transform them into any other cell in a lab, it was
suddenly conceivable that we could use them to repair or replace any organ or
body part, instead of what we had done before: swapping in metal or plastic,
or a donated organ that required suppressing the immune system. Whether
they were old, damaged or diseased, soon stem cells would rejuvenate livers,
joints, hearts, kidneys, eyes and anything else you could want.3
Amid controversies (people didn’t like the idea of using foetal tissue as
building blocks for medicine) and new hope (it turned out other cells in the
adult body could be recruited for similar purposes!) the headlines never
stopped. Stem cells would cure neurological disorders. They’d cure lower back
pain. Heck, they’d cure anything. They were biological miracles.
Despite thirty years of dramatic headlines, however, most of these goals
remain perpetually out of reach. ‘There’s no injury, no disease, no anything,
where stem cell therapy is better than the other things we’re doing, after all
these years,’ says Stephen Badylak, who runs the McGowan Institute for
Regenerative Medicine in Pittsburgh. So Levin is trying something completely
different. Instead of trying to micromanage the wildly complicated universe of
molecular and chemical interactions involved in building an appendage out of
individual cells, he thinks it’s possible to instead turn on the bioelectric
switches that shaped that mouse (and all its fingers) in the first place. He’s
banking on the idea that the ability to regrow anything you’ve lost to injury or
illness is not written in your genes, but can be controlled by the electrical
language the body uses to talk to itself about what shape it is. Figure out that
code, and you can just get nature to build you a new one. The first hints of
these electric switches’ existence go back nearly a century, long before we
knew what to do with them.

The spark of life

Had he tried to undertake his experiments today, Harold Saxton Burr would
have been frog-marched straight to HR. But in the 1930s, it was still
conceivable for the director of a Yale biology lab to ask the women who
worked for him to measure their voltages every day and chart them against
their menstrual cycles.
Burr spent his entire career at Yale University’s medical school, where his
prolific publishing record bracketed the mid-twentieth century. His life’s
mission was to understand whether all biological systems exhibit electrical
properties, and if so, why. To catalogue the full extent of biological electrical
activity, he spent thirty years wiring up everything from bacteria to trees to
women, measuring and mapping the subtle forces they emitted. When Burr
started this project, both the EMG (electromyograph – for muscles) and the
ECG (electrocardiograph – for the heart) were already in wide use. But he
wasn’t interested in these loud and obvious rhythms. Hidden among all this
noise, Burr had identified a different signal – a faint electrical signature that
never waxed, never waned, only persisted. He wanted to know more. To pin
down this signal, he first had to spend three years devising a millivoltmeter so
sensitive it made the heartbeat Augustus Waller had managed to detect with
his buckets seem like eavesdropping on a gunshot.4
For his initial investigations, he asked the men in his lab to submit to
voltage readings. Two electrodes were stuck into cups filled with an electrolyte
solution, into which the men would dip their respective index fingers to get a
sense of the difference between the voltage at the two fingers – a bit like what
Ken Robinson did to demonstrate the wound current, but no one had to slice
anything open. Still, Burr’s extremely sensitive voltmeter registered a
difference. ‘Immediately it was clear that there was a voltage gradient between
the two fingers,’ he wrote.5 This steady DC electric field, he realised, was
evidence that the men all carried their own personal electrical polarisation –
one side of our body negative, the other positive. He called it ‘the
electrodynamic field’, or L-field. It was the first evidence that we are a human
battery.
To be sure this signal was real, Burr and his colleagues repeated the
experiment ten times (and with variations to rule out misinterpretations).
When they were satisfied, they began their study in earnest. The men were
instructed to take these measurements every day of every week of every
month. Examining the results, Burr found that he could plot different men’s
field strengths along a spectrum. Some men consistently exhibited robust
voltage gradients as high as 10 millivolts while others barely cleared two, but
an individual man’s field never varied much day to day.
 That was when Burr began to wonder about the women in his lab. Might
their signatures be more variable? He asked them to join the experiment.6 And
sure enough: ‘we found to our astonishment that for 24 hours every month,
there was a large voltage increase’. This coincided – after an ‘examination of
the personal records of the females’ – roughly with the approximate midpoint
of the menstrual cycle, suggesting at once that the rise might be associated
with ovulation.
Even in the 1930s, you couldn’t have taken this experiment much further
with human women, so Burr tested his hypothesis in a rabbit. A rabbit’s
ovulation is predictable: stimulate its cervix, and nine hours later an egg drops.
They did a rather gruesome experiment to be able to read the voltage of the
rabbit’s ovary while simultaneously and directly observing the actual event of
ovulation, opening its abdomen and extruding the fallopian tube.7 ‘To our
delight the moment of rupture of the follicle in the release of the egg was
accompanied by a sharp change in the voltage gradient on the electrical
recorder,’ Burr wrote. ‘The experiment was done enough times that it was
perfectly clear that there could be no question that the electrical change was
associated with the event of ovulation.’8
Replicating this exact experiment on a living, breathing woman would have
been out of the question. However, Burr was able to find a very close proxy: a
young woman who was about to undergo an investigative surgery. She agreed
to let them conduct their study, and so, during the fifty-six hours she spent
waiting for her operation, they continuously measured her with their recording
galvanometer. Burr placed one electrode outside onto her central abdominal
wall, and the other inside, against the wall of her vaginal canal near the cervix,
and watched for changes in the voltage between the two. When the recordings
showed the same spike in voltage gradient that Burr had observed in the
rabbit, the patient was sent immediately to the operating room for the
laparotomy. The ovary was removed as planned, and close examination
revealed a recently ruptured follicle – the sign of ovulation.
To Burr, this was clear confirmation that his findings in the rabbit
translated to women.9 He did a few more studies in this vein10 and soon
caught the eye of Time magazine, which in 1937 reported on ‘an electrical
gadget whose invention may bring Dr. Burr a Nobel Prize’.11 The reporter
described the gadget in loving detail: ‘In a box small enough to be carried
around are four different kinds of electric batteries, a delicate galvanometer,
two radio vacuum tubes, eleven resistors, one grid leak, and four switches.’12
Burr offered to share the wiring diagram with anyone thinking of building one
of his devices for personal use, but cautioned the reporter that it should be
assembled only by ‘an experienced mechanic who is thoroughly familiar with
radio set construction’. But it might be worth your while, as this complicated
device could do something no one else had yet managed: tell you when a
woman’s ovary was about to produce an egg. Time dutifully explained that this
would be a boon for people trying to start a family, but did not end the article
without the delicate acknowledgment that ‘such foreknowledge might guide a
woman’s conduct in case she did not want to have a baby’. Today, we can be a
bit more direct: it could provide birth control.
Meanwhile, Burr’s findings were confirmed in other animals by several
scientists, including the Cornell-trained animal behaviourist Margaret Altmann,
who found the same bioelectric correlates in sows and hens as they went into
heat.13 All this fuss finally drew the attention of John Rock, a prominent
obstetrician and fertility specialist who ran the gynaecological hospital at
Harvard.
Rock got involved because Burr’s hypothesis courted some controversy. At
the time, it was presumed that all women ovulated like little clockwork dollies,
dead centre in the middle of their menstrual cycles – fourteen days before
onset of menses, tick tock, out pops an egg. The data was not grounded in
particularly solid science; it had come from epidemiological studies of veterans
returning home after the First World War, and how fast their wives
subsequently ‘fell pregnant’. These observations had quickly graduated to the
status of generalisable scientific knowledge.
Burr’s findings indicated that while this ‘mid-cycle ovulation’ rule might
have been a good rule of thumb, individual women’s monthly timings could
vary, some quite widely. Indeed, his data suggested that some women ovulate
more than once a month, that others had wildly variable fertile windows (never
the same window in consecutive months), and that consequently it was very
hard to get pregnant solely on the assumption that your fertile window was
centred on fourteen days. On the other hand, it was a great way to get
pregnant when you didn’t want to.
Rock was a Catholic fertility specialist who had pioneered early sperm
freezing and in vitro fertilisation techniques. Quite out of step with the church,
he was strongly in favour of women being in control of their own reproductive
destinies, and would later go on to play a crucial role in the development of
the first birth control pill, (vainly) lobbying the Pope for its acceptance.14 But
in the late 1930s, the only birth control even conditionally regarded as moral
by the Catholic Church was the rhythm method, in which women would track
their past periods to predict the time of the month they were least fertile (it
required an ironclad faith that past performance was a guarantee of future
results). Rock was in charge of a clinic where he taught clients how to use it.
For the rhythm method to be trustworthy, however, the average woman
would need to ovulate at regular intervals; if a woman who actually ovulates on
the twenty-first day of her cycle is only abstaining from sex in the middle of
her cycle, you might accidentally end up with more little Catholics running
around. When Rock saw Burr’s experiments, he quickly set up a number of
measurements in his hospital and completed experiments on ten more women
to confirm Burr’s findings.
Initial findings seemed promising, but Rock changed his mind within a
year. After noting a number of discrepancies in the form of voltage deviations,
he abandoned his investigation. Rock concluded that Burr’s work had been
misguided: there was no way ovulation could be taking place at these random
times so far away from the centre of the menstrual cycle. In his final
publication on the matter, Rock dismissed Burr’s findings about electrical
signals and returned to the view that the deviations were anomalies from an
otherwise reliable norm.15
Despite Rock’s confidence in his own insights into women’s reproductive
machinery, today we know that Burr was right – the rhythm method is bunk.
And later it emerged that some electrical changes are indeed well correlated
with fertility. Chloride ion concentrations, for example, spike right before you
ovulate.16 That is so evident, particularly in the cervical mucus and saliva, that
it has become the basis of an ovulation test which was developed specifically
to check for concentrations of these ions. Examine these fluids under a
microscope and you can literally watch the chloride crystal deposits flowering
into crystalline patterns that resemble ferns.17 These are bona fide indicators
of fertility. (Anecdotally, when a personal friend of Burr’s used his
electrometric method after struggling with infertility, she was able to conceive.
Burr wrote it up as a case study.18)
Burr’s early experiments run rather far afoul of modern workplace norms,
but he was prescient: everything he theorised about bioelectricity in the body
has been validated in the fifty years since he said it.

The electricity of development

Beyond the small flurry of replications undertaken in the 1930s and 1940s, no
one has repeated Burr’s studies of ovulation voltage. So we can’t say with
certainty exactly what signal he was detecting. But we do know, from nearly a
century of other experiments undertaken since, that both eggs and sperm are
electrogenic – living cells that produce electrical activity. A mind-boggling
amount of it.
As both Burr and Lionel Jaffe would have told you, human eggs are far
more difficult to study in their natural environment than the eggs of seaweed
and frogs, which conveniently go through all their reproductive stages outside
a womb. This is why so many studies of animal development have been done
in frogs, and so few in humans.
While they’re still sleeping in their follicle or testis, young eggs (oocytes)
and young sperm (spermatids) don’t emit strong signals. But as they mature,
eggs of all species ramp up their electrical activity.19 Just before an egg gets
ready to drop off the mothership, it starts broadcasting energetically, almost
like someone turned on an electrical switch. (The strength of this signal has
been used to determine which eggs are best to use for IVF.20) Elisabetta Tosti,
a biologist at Stazione Zoologica Anton Dohrn in Naples, found that this ‘on’
signal is carried by a change in the amount and kinds of ions that flow through
the egg’s membrane, causing the egg to become hyper-polarised.
Sperm have a similar electrical on-switch that prepares them to meet the
egg. In the 1980s, studies of sea urchin sperm found them to be teeming with
potassium and chloride channels and the other usual suspects you find in
neurons – and just as in neurons, blocking those channels prevented the sperm
reaching their goal. For example, one of the most important electrical currents
in human sperm is calcium, which confers an extra turbo boost to help it
through the hostile terrain of the reproductive canal.21 Take out the calcium
channel and the sperm wriggles ineptly and goes nowhere. (This mechanism
has been explored as a potential avenue for male birth control.)
Once it actually gets to the egg, you might think the sperm has one job,
but it actually has two. We all learn in school about how it transports the male
genome into the egg. For that to even have a chance of happening, however,
the sperm first needs to hit yet another electrical on-switch on the egg’s
membrane. This one is known as ‘activation’ and, genome or no genome, it’s
crucial for any further development to take place. It differs from the
maturation on-switch in the same way switching on your bedside light is
different from igniting the first stage of a spacecraft. The first touch of sperm
to egg triggers an immense calcium current that smashes across the egg. Now
no other sperm can get in, making it harder for silver-medallist sperm to get
over the finish line.
This process is so consistent that when researchers zap a calcium current
into an egg without sperm present, the egg gets excited and starts turning into
an embryo anyway. That’s right – virgin birth! By artificially mimicking the
(normally) sperm-induced calcium wave, it jumpstarts an egg into dividing
without the sperm or its genome.22 Ethical considerations prevent us finding
out just how far this bootstrapping of the reproductive process would take a
human embryo, but in rabbit eggs it got the embryo about a third of the way
through development. (Fun fact: while not parthenogenesis, the special sauce
in cloning Dolly the sheep, the world’s first cloned mammal, was an electrical
zap that activated the process.23)
The point is this: through all the stages of conception, from egg to
fertilisation, ion channels and the currents they generate play a fundamental
role in the spark of life. But none of this holds a candle to their importance in
influencing the shape we eventually take.

Assembly instructions for one (1) human

A Lego set generally comes with a detailed, step-by-step instruction manual

that leaves little doubt as to how you’ll snap together each successive Lego
piece. It also should give you a good over-view of where any particular piece
fits into the larger blueprint of the final structure you’re assembling.
Making an embryo is much like making a Lego castle: in the same way that
a castle needs turrets and gargoyles and a moat, you need two legs and two
eyes and a heart. Except unlike the Lego Camelot, you don’t come with a
picture on the box of what you’re meant to look like in the end, much less an
instruction manual – and you’re not going to be the one to assemble the
structure. Instead, you’ll sit back and wait for the Lego pieces to organise
themselves. Our cells, our little Lego pieces, assembled themselves. What’s
even more astonishing is that when they got it right, all those cells got it right
in broadly the same ways: we all managed to come out with the characteristic
shape and proportions appropriate to our species (we can all spot a regulation-
issue chicken, frog, mouse, or human shape).
 So how did all our initial progenitor cells know how to organise into us –
forming our eyeballs, legs, fingers and all that in the right place and the right
order? Who gave them the blueprints to check that all those fingers or fins or
beaks weren’t too giant, or too tiny, or of wildly different lengths? Most
important – how did they know when to stop?
Well, you might be thinking: that’s what DNA is for. Not true. You can
search all the As, Ts, Cs, and Gs in your genome, turn ’em upside down and
shake the spare change out of their pockets – you won’t find the instructions
for anatomy. You’ll find plenty of specs – code that tells you about the colour
of hair a baby will have, its skin, its eyes. You’ll find nothing about how many
eyes. There’s no gene for two eyeballs. There’s no gene for ‘the eyeballs need
to go on the front of the head’. There’s also no gene for ‘two arms and two
legs, kind of this far apart’. It’s simply not possible to recover the shape of an
organism solely from reading a printout of its genome.
So if not genes, what does control your shape?
The question had begun to assemble itself in Michael Levin’s head when
he was still a child, wondering how an entire person could be assembled from
an egg. Later, puzzling over the old studies done by Lionel Jaffe and Harold
Saxton Burr, he began to suspect that the ion currents Jaffe had found eddying
around seaweed, and the fields Burr had measured coming off, well, everything
else, might play a crucial and early role in determining a creature’s anatomy.
But where to start with a question that big?
As it happened, Levin needed a topic for his PhD thesis at Harvard
Medical School, and in the early 1990s, there was still one aspect of how
human beings are shaped in the womb that remained a total mystery: how
embryos tell left from right. There had been theories, but never a smoking
gun. For a grad student, this was tempting, low-hanging fruit. So Levin began
to investigate how all those cells, without having brains, nonetheless seemed to
know their left from their right. And make no mistake – their ability to
distinguish left from right during development is critical to our survival. From
the outside we may pull off the illusion of symmetry – two eyes, two ears, two
arms, and two legs, same on one side as we are on the other. But inside, it’s a
different story. You probably know that your heart and stomach lean left, and
that your right side houses your liver, appendix, and pancreas. For about 1 in
20,000 people, this whole image is flipped.24 And that’s absolutely fine! They
don’t usually have health issues (apart from overzealous researchers poking
and prodding them to understand their condition, known as situs inversus).25
However, when just some of the bits are flipped, you have a problem.
Jumbling up the body’s precise internal asymmetry, particularly when it affects
the fastidious plumbing of the heart, is the origin of many congenital heart
defects and other life-threatening syndromes.
Understanding what caused any of this – the correct pattern, the flipped
pattern, the jumbled pattern – was a longstanding, perennially interesting
unsolved mystery. Why does the heart go on the left and not the right? And
how does the body know to develop this way? No one had been able to finger
a specific molecular component, so there was no hint of a genetic cause.
Genes couldn’t be the whole story, anyway. After all, genetic information is not
spatial. The genome can’t tell left from right. It seemed to Levin, from
studying the old ion current papers, that electricity was somehow fundamental
to establishing the polarity of a cell. But how?
Jaffe was far from the only one who had investigated these questions.26
Decades of work catalogued every ion that shuttled in and out of developing
embryos of every species and identified the ion channels that send them
through the zygote and the blastomeres it calves off into as it begins to
diversify into the developing embryo. A funny thing happens to the ions and
ion channels in the cell during this transition: they all mysteriously change.
Some pop into existence, others disappear then reappear, and their currents
wax and wane with those disappearing and reappearing acts.
Another clue to the functional importance of these weird ion events was
what happened when you interfered with them. Disrupting even seemingly
minor sodium currents resulted in a ‘rosette’, which is an abnormal embryo
that ‘appears to have lost its spatial orientation’, noted the Italian biologist
Elisabetta Tosti. She concluded that the currents during and after fertilisation
are crucial for correct embryo development.27 Messing with potassium
currents also led to developmental defects, further evidence that ion
movements are crucial for an embryo. But no one had been able to assemble
this jumble of interesting pieces into a coherent whole.
By the time the twenty-first century got underway, Levin could ask these
questions in his own lab at the Forsyth Institute, at Harvard. How was
electricity setting the polarity of a cell? He and Ken Robinson discovered a
proton pump, another variety of the bouncers we met in Chapter 3. Protons
are hydrogen ions. This bouncer specialised in making sure hydrogen and
potassium were kept in strict ratios. On an unfertilised frog egg, proton pumps
are speckled evenly around the whole surface.
But when Levin and Robinson checked on these pumps after fertilisation,
they found something strange: all the channels started drifting over to one side
of the egg, where they smashed themselves into a tight little clique. No one
had ever seen anything like this. When the pumps gathered on one side of the
egg, it meant hydrogen ions were only able to get in or out of the cell on that
one side. This created a voltage, and it happened really soon after fertilisation,
when the frog embryo consisted of only four cells. Could this be the answer
they were looking for?
When scientists think they have found a causative agent like this, their next
step is to try to figure out an experiment that can disprove their idea. Levin
and Robinson decided to see what would happen if they prevented the proton
pumps from drifting out of perfect symmetry after fertilisation. To do that,
they added extra proton pumps or potassium channels to the developing
embryo to even out their distribution, mimicking the smooth distribution on
an unfertilised egg. If the researchers were right, this evenness would wreak
havoc on the embryo’s ability to discern left from right. And they were correct.
The embryos with the extra proton pumps were all messed up, as likely to have
their hearts on the right as the left. The proton pump was clearly essential to
kicking off the difference between left and right sides.
But it was also changing the membrane voltage. That was weird. As we saw
in Chapter 3, a change in membrane potential is how nerves send action
potentials. But why was a brand-new embryo changing membrane potentials?
What possible use could that be, when it hadn’t even developed nerves yet?
Levin wondered if this voltage was part of the system an embryo used to tell
its constituent cells to become different kinds of tissue. This idea is articulated
by the biologist Mina Bissel: if all our cells have exactly the same genes in
them, then why do some of them do one thing when others do other things?
How do some of them become bone cells and others skin, or nerves?

The ghost frog

In 2003, Dany Spencer Adams was a restless assistant professor of biology on

the tenure track at Smith College in Massachusetts. Having trained in the
biomechanics of developmental biology, she had begun to find her job
unfulfilling. After some sleepless nights, she decided to abandon the prospect
of tenure, and take her chances doing something more interesting.
She saw a job ad for a post-doctoral position looking at left–right
asymmetry. It wouldn’t be a standard career path, but Adams was intrigued
enough to drive to Boston to find out more. Within an hour, Levin offered her
the job, and she knew she was going to take it.
Adams started with the proton pump that Levin and Robinson had found.
Step one was to turn their finding into a tool that could take control of those
ions to tune the membrane voltage of a cell. By tweaking voltages in frog
embryos, she and Levin were able to create situs inversus, that mirror-image
organ condition.
They began to notice that many of these tadpoles didn’t just have inverted
organ patterns – they also had very similar anomalies of the head and face.
There was a clear pattern. This was dramatic evidence for Levin’s hypothesis
that these membrane voltages might be in charge of a whole lot more than
internal asymmetry – what if they were in charge of the whole body?
To go any further, they would need to observe those changing membrane
voltages in a way you could track with the naked eye. But what tool could
allow you to see changing membrane voltages not just in space but over time?
Adams settled on an electro-sensitive dye that was able to turn differences
in voltage into something that was plainly visible, in this case a gradient of
brightness.28 The extremes of the electrical potential were translated into
degrees of luminance, with high voltages represented in bright white, low in
black, and anything between in a balayage of grey. This dye could be infused
into every single cell and track every one of them, even as they divided and
proliferated. They would be able to watch every electrical step of embryo
development.
Remember how I said that neurons rest at about 70 millivolts more
negative inside than the outside? That’s what the textbooks tell you because
that’s true of neurons and many other mature cells – but it’s not true of
embryonic stem cells (the little guys who proliferate during the first stages of
development). Stem cells’ resting voltage is much closer to zero. (That means
the charge inside and outside their cell membrane is about the same, which is
also the voltage of a nerve cell in its ‘panic at the disco’ moment.) But where
that zero moment is only momentary for a nerve, it is the stem cell’s
permanent identity.
Until, that is, it turns into something else. And that role is reflected in a
cell’s electrical potential.29 You already know about the nerve cells’ potential
(-70). Skin cells have the same potential. But bone cells have a higher potential,
a firm and immovable -90. Fat cells are a relatively wobbly -50. What they all
have in common is that they use their ion currents to keep their membrane
voltage at the resting point that defines their cellular identity. A stem cell’s low
potential ensures that it can become any other cell. But once it has become a
bone, nerve or skin cell, it stays there. It gets set in its ways, a bit like us.
With electrosensitive dye, it was possible to watch all these electrical
becomings unfold at the same time, in real time. Different regions of cells lit
up at different times, forming patterns that faded into and out of existence on
the embryo’s surface. Many patches of embryonic cells would be near zero.
But at any given point, some patch might drift up to -30. Another might hit
-50. You could watch each region slowly glow up like Lilliputian cities coming
online. It was beautiful to watch, but it didn’t lend itself to any overarching
theories.
Then, one autumn evening in 2009, after a day of watching these
embryonic glimmers, Adams decided to leave her camera on record for the
whole night. Her expectations were low; these little developing embryos would
probably start wriggling around, leaving her with footage that was blurry and
unusable. But what she found on her return the next morning was a ‘jaw
dropper’.30
On the otherwise featureless, smooth blob of a frog embryo, the
hyperpolarised (negatively charged) areas twinkled brightly against darker areas
of depolarised cells, as they had before. But then, as the froglet continued to
develop, the random bright patterns playing across the dark surface suddenly
cohered into a picture that looked an awful lot like a couple of eyes over a
mouth. And then, sometime after those shimmers had faded, real physical
features began to manifest in their place. Exactly where the electric glow had
presaged eyes, soon there were two actual eyeballs. Precisely in the place where
the pattern had projected the ghost of a mouth, development began on the
real thing.
Soon all kinds of features developed exactly where she had seen their
electrical premonitions. Not only could you match the voltage patch to the
tissue, it perfectly predicted what kind of tissue would form, and its exact
shape. It was stunningly clear: electrical signals appeared to encode the
locations of anatomical features.31
The next question was pretty important – were these signals necessary for a
normal head and face to form? Or were they just irrelevant indicator lights? To
find out, Adams and Levin would need to prove that normal development was
affected if you turned off the electricity. When they disrupted the ions that
were responsible for the predictive patchwork quilt, that’s exactly what
happened: not only did that lead to changes in gene expression, but after
removing the paint-by-numbers pattern indicators, the faces that emerged
from the electrical chaos were deformed.32
 So what exactly were they disrupting? And how was it possible that these
brand-new, unformed cells were able to talk to each other about their voltages,
or what parts to form? How were the membrane voltages spreading from cell
to cell? Well, remember gap junctions? They start to form the moment the
zygote has come together – that first new cell created by fusion of egg and
sperm. Right away, they establish a cellular intranet quite unrelated to the
nervous system, connecting cell to cell to cell.33 Each new cell that cleaves off
is already connected to the cells around it. Long before nerve cells develop
synapses, our non-excitable embryonic cells have another, much faster, more
electrical way of communicating.
Levin had long suspected that these gap junctions were involved in how an
organism decides how to shape itself. In his earliest days of investigating left–
right patterning, he had found that turning off gap junctions also messed up
asymmetry. Later, he and another postdoc, Taisaku Nogi, found gap junctions
were the culprit in the unparalleled regenerative superpowers of a weird little
sea worm called a planarian. This small flat worm can regrow no matter how
finely you chop it – and it only takes about a week to return to fully functional
normalcy. Nogi and Levin realised that gap junctions could explain how re-
patterning information could spread so quickly over thousands of cells.
In two different animals, then, the gap junctions seemed to enable long-
distance messages without a nervous system. In some ways, they were better
than a nervous system. When two cells are connected in this way, each cell has
direct, privileged access to the other’s internal informational universe. What
one cell knows or experiences diffuses immediately through the connecting
door for its neighbour to know or experience too. The effect is close to
telepathy.
It was becoming clear how the whole thing worked: ion currents
controlled the membrane voltage. The membrane voltage determined which
tissue group a cell joined, which determined what kind of tissue it turned into.
Cells changed their identities in line with cues they got from their neighbours,
and the whole process was kicked off electrically.
This was when Levin first began to formulate his theory of the bioelectric
code. The membrane voltage carried information, and the gap junctions
formed the body-wide network – the electrical network that was not the
nervous system – that sent that information around the body.
Levin started to think of the information as taking the form of a code.
That code controls the complicated biological processes that formed you in
the womb, by executing a controlled program of cell growth and death. The
bioelectric code is the reason you retain that same shape throughout your
entire life; it prunes your dividing cells so you keep being recognisably you. It
wasn’t the only important thing – biomechanics, biochemicals, and all the rest
mattered too. But just as the neural code was mooted to govern behaviour and
perception, and the genetic code governs heritable traits, the bioelectric code
was how the body told itself about its form.
But if all that was true, he would need to prove it. He would need to show
that changing those cues could make the cells do something they normally
didn’t. It would have to be something really bonkers.
While messing with a particular potassium channel in a tadpole in 2007,
Adams and Levin and their grad student Sherry Aw inadvertently altered its
bioelectrical signalling, causing it to grow two identical, extra right arms
alongside the original appendage.34 This had been an accident, though – could
they now do it on purpose? Aw hypothesised that ‘for every structure in the
body there is a specific membrane voltage range’ that drove the creation of
that structure.35 They tested that idea in 2011, tweaking the membrane voltage
on a patch of tissue on a developing frog’s gut to mimic the same
hyperpolarised state Adams had seen before eyes formed on the ghost frog. It
worked. An eye grew on the frog’s stomach. They did it again on the tail.
Another eye grew. ‘You can put eyes pretty much anywhere on a frog by
changing the membrane voltage,’ says Adams. ‘It’s like an X marks the spot.’
If it was possible to grow new eyes anywhere on a frog, what could you do
with a human?

Make like a salamander and regenerate

We used to think that only some animals could regenerate themselves: hydras,
salamanders, crabs . . . nothing as interesting as a mammal. But in the
twentieth century, the formal study of regeneration revealed just how
widespread the phenomenon actually is in the animal kingdom.
In nature, there seems to be no theoretical limit to what you can cut off
and expect to get back, if you find the right animal: hydras – tiny freshwater
organisms – can be cut to absolute ribbons, and the little shred will rebuild
itself again into a fully functioning animal. The same is true of that freshwater
flatworm we met before, called the planarian.
 In fact, this is how they reproduce – they tear themselves in half (you
thought you had problems).36 If you had this capability, someone could throw
a segment of your finger into the sea and a week later, it would have grown
into an extra you. You can see for yourself, in fact: chop a hydra in half and the
tail end will sprout a new head and the head end will sprout a new tail.
Sea stars combine the abilities of hydras and planarians. In addition to
being able to regenerate a new body from a severed arm, some species can
regrow their entire central nervous system from scratch. They’ve been known
to tear themselves in half on purpose to start a family,37 and they’ve also been
known to use their own severed leg to beat off their enemies.
Then there are salamanders, which can regenerate a remarkable number of
their tissues and organs, including their limbs, tails, jaws, spinal cords, and
hearts. A frilly red version called an axolotl can heal anything on its body
without scarring, including its brain. Frogs can regenerate entire limbs and tails
(and even eyes) when they are tadpoles, but they lose this ability after their
metamorphosis into a frog.
Same goes for humans – at least until you exit the womb. To riff off a
famous phrase often attributed to Abraham Lincoln: we can regenerate all our
tissues some of the time, and some of our tissues all of the time, but we can’t
regenerate all our tissues all the time. Our regenerative ability follows a
schedule that is strictly dependent on age and body part.
A zygote is the regenerative equivalent of a planarian. Someone could slice
it in two and the two cells would continue developing into identical twins.38
That ability falls off quickly, but a foetus has impressive regenerative ability
even so. Most foetal injuries don’t leave scars, an insight obtained in the late
1980s when foetal surgery became routine.39 After birth, however, the
superpower disappears fast, with one exception. Until between the ages of
seven and eleven (for obvious reasons there hasn’t been a lot of experimental
evidence to pin this down exactly), if you lose the tip of your finger, you’ll
probably regenerate it in full.
This phenomenon is not extensively documented in the scientific literature
– and not for the pinky-decapitating reasons you might think. Ai-Sun Tseng, a
professor at the University of Las Vegas who leads a lab that specialises in
regeneration, recalls describing her work to a class. One of her students ‘totally
lit up. He was like, “Yeah! Look at my fingers!” He grew up in the Philipines
and at some point he’d had four of his fingers chopped off above the knuckle,’
she says. Because he was not yet eleven when it happened, they all grew back
perfectly. But his age wasn’t the only factor. His family had been too poor to
afford a doctor, so they kept the wounds wrapped and wet and clean – and
eventually all four fingers regenerated perfectly, nails and all. By the time Tseng
inspected them decades later, they were indistinguishable from fingers that had
never been maimed. At a conference a few years later, Tseng recounted the
story to a group of colleagues, one of whom was a paediatric surgeon. He
pointed out that, faced with a similar situation, most parents actually refuse to
take advantage of this last vestige of regenerative ability. ‘They’re way too
scared of leaving an open wound,’ he told her. ‘They worry it’ll get infected.’
So they ask the surgeon to suture together the surrounding skin, which
protects the wound with fibrous scar tissue that forecloses any hope of the
finger regenerating according to its potential. ‘Part of the reason we know
about childhood regeneration at all is because of children in developing or
poorer countries without healthcare,’ she recalls him telling her.
Our regeneration schedule is age-dependent – but it also depends on the
body part. The liver renews about once every two months. Your intestinal
lining sheds completely and renews again every seven days; what you eat next
Saturday will be processed by a completely different set of cells than the ones
working on today’s breakfast.40 A small population of stem cells in your lungs
regularly undergo cell division. Even the lens of your eye regenerates. As you
age, however, all these tissues lose their ability to rise from the dead,
exemplified by the skin, whose outer layer renews every fourteen days while
you’re in your teens, but slows to twenty-eight or even forty-two days by late
midlife. And of course, most of our tissue doesn’t do it at all. Cut off a nose or
a hand and they stay gone.
But why, when we obviously carry the genetic instructions for
regenerating? Why can children regrow a fingertip but not a nose? Over the
past couple of decades, the consensus across multiple disciplines has become
that this latent ability actually lurks in every animal – and with it, our ability to
regrow lost limbs or regenerate other organs. But how to unlock it? Once
again, we turn to electricity.

Hacking the body map

Lionel Jaffe had found big differences between the electrical currents emitted
by animals that regenerate limbs and the ones that just put a scar on a wound
and call it a day.41 In the early 2000s, Betty Sisken at the University of
Kentucky painstakingly copied the exact qualities of the electrical fields that
had been observed in regenerating animals and inscribed these onto the tissues
of animals that don’t regenerate. After amputation, a range of her animals –
including amphibians, chick embryos, and rats – began to form limb buds.
These had complex tissues like cartilage, vasculature, all the things you need
for a functioning limb.42 But alas, not an actual functional limb. Then Ai-Sun
Tseng, who at the time was part of Levin’s lab, manipulated the membrane
voltages with ion-channel tweaks, and now we were cooking with gas.
She and Levin had been kicking around an idea – instead of
micromanaging the process of regeneration, could it be possible to tweak the
bioelectrics to kickstart the development processes that had built these
appendages in the first place? Tseng started looking for ion channels that
might be amenable to tweaking. She discovered one kind of sodium channel
that was crucial to regeneration. Better yet, an ion-channel drug had already
been developed that could act on these. Called Monensin, it was able to ferry
extra sodium into a cell. Tseng had a hunch that flooding the cell with sodium
– mimicking the electrical differences Jaffe had identified all those years ago –
might restart regeneration in an animal that normally doesn’t: a tadpole. Not
only did it work, it worked shockingly quickly. Soaking for a single hour in the
sodium channel drug bath drove eight days’ worth of tail regeneration. When
she told Levin about it, even he was sceptical. An hour seemed so short. But
Tseng had been right. That little soak was enough to give the cells the idea, he
says: ‘Grow back whatever belongs there.’43
This was literally what he had envisioned being possible with the
bioelectric code. Tseng had shown that all the persnickety chemical gradients,
transcriptional networks, and force cues needed to orchestrate individual cells
into complicated tissues could be harnessed with a comparatively simple set of
electrical instructions. The genes were hardware, and they could be controlled
by manipulating ion flows – the instructions from the software. Tseng and
Levin soon published the seminal paper introducing their new idea: ‘Cracking
the bioelectric code’.44
Subsequent research has yielded multi-limbed frogs and other evidence of
bioelectricity’s role in regeneration. Among the most startling of these, it was
possible to use bioelectric interventions to make planarians that had been
chopped in half grow a second head instead of a tail. And as the press loves
nothing more than a mutant, all the resulting media attention translated to
money. First, DARPA came calling with enough money to build the little
regenerative boxes that are now on the mice in Levin’s lab. They’ve extended
out to frogs, too, growing a new leg on an adult frog. The new leg wasn’t
perfect, but it worked – the frog used it to swim around, and after a few
months it even regrew toes. In 2016, Microsoft billionaire Paul Allen added
nearly $10 million to Levin’s coffers.
The open question now: when will it jump to humans?

Electrifying regenerative medicine

Stephen Badylak heads up one of the largest projects on regeneration yet

undertaken. It involves fifteen different investigators from multiple disciplines
at eight separate institutions, and is funded by the US Army (which, if you
want to be cynical about it, is uniquely incentivised to help heal the soldiers it
has thrown into the geopolitical shredder). The goal is systems that can
comprehensively understand the physiologic state of injuries, at every level
from gene expression to mechanical properties, and then alter those states so
the healing mimics development rather than default scar tissue formation. ‘Star
Wars-type stuff,’ Badylak says. He is convinced that bioelectricity will play a
role.
Bioelectricity researchers are considered the weird kids at the regenerative
medicine table. Their paradigm is not entirely in step with early twenty-first-
century science, which is heavily focused on genetics as the primary driver of
human physiology. Every newspaper article about Levin’s work includes a
quote from some nonplussed geneticist mouthing a variation of ‘well, I guess
we’ll see’. Most of the excitement is still focused on traditional avenues like
tissue engineering and genetics, which are informing most of the human trials
and work on lab-grown organs. Against this backdrop, work like Levin’s can
raise some eyebrows.
When Levin’s team started publicising their experiments a little over a
decade ago, many biologists were openly hostile to the notion. Today, things
are beginning to shift, as more traditional researchers start to delve into the
specific relationship between bioelectric patterning and the genes it turns on
or off. For example, Christiane Nüsslein-Volhard, who in 1995 won a Nobel
for her work on genetic control of early embryonic development, is now
among those investigating the electrical dimensions that seem to influence
how zebrafish get their stripes.45
 It should be said: regenerative medicine could certainly use the help.
Organ transplants require an often lifelong regimen of immune-suppressing
drugs to stop the body rejecting the new organ, which has its own health
consequences. Metal replacement parts can become loose with time,
engineered tissue scaffolds become inflamed, and artificial skin has no sweat
glands or hair follicles.
In a perfect world, all these problems would have been solved by those
famous stem cells. But despite the media hurrah, they have been a bit of a
disappointment. The challenge has been how to stimulate them to become the
cells you want them to be, and get them to go where they are needed, and
keep them there in their new shape. Currently, most of the research on how to
do that focuses on biochemical control. But we haven’t had much luck with
anything on the wish list: identifying, growing, inducing, or safely delivering
stem cells to the appropriate target. In fact, it’s rather unpredictable what will
happen to stem cells once they get into your body.
This is why stem cells are regulated as an experimental drug, and the
problem is highlighted by some fairly grisly anecdotes. One woman who had
olfactory stem cells injected to heal her spine after a car accident ended up
growing the precursor to a nose in her spine.46 Another patient, who had stem
cells injected in order to rejuvenate her face, ended up growing bones in her
eyelids that were so big they clicked whenever she opened or closed her eyes
(‘a sharp sound, like a tiny castanet snapping shut’).47 After they started to
interfere with her ability to open her eyes, she had an operation to remove the
bones, though there is no guarantee more stem cells are not waiting in the
wings with more castanets. Then there are the three women permanently
blinded by a poorly controlled, poorly designed trial that harvested cells from
their body fat to improve their vision.48 Such examples are among the reasons
stem cells for regeneration are banned on US soil, though of course they thrive
in shady clinics, leading to regular warnings issued by regulators and other
authorities about the ‘Wild West’ of private therapies.49
But bioelectric medicine could offer a way out of this cul-de-sac.
Preliminary work by Sarah Sundelacruz – a former protégé of Levin who was
immediately snapped up into private industry – suggests you could tweak stem
cells’ bioelectrical parameters to influence their eventual identity. More
recently, Sundelacruz showed that you could even analyse stem cells’
bioelectric profiles to determine if they were any good at keeping their shape,
or if they would revert into a kind of cell you didn’t want – perhaps staving off
the fate of the lady with the clicking eyes. This approach can even be used to
guide stem cells into the specific physical locations where they are needed: Min
Zhao’s team have used electrical stimulation to guide stem cells to grow into
replacement neurons in brain-damaged areas, which has been nearly
impossible before.50
But what happens when the bioelectric signals that shape cellular identity
go wrong? The consequences can be deadly.
 CHAPTER 8

At the end:
The electricity that breaks you back
down

The wound that does not heal

I n the late 1940s, the zoologist Sylvan Meryl Rose toiled in his lab at Smith
College, creating cancer chimeras. He would cultivate rapidly growing
kidney tumours in frogs, excise them from their hosts, and then carefully graft
the growths onto the legs of salamanders, tucking them just under the skin.
(As we learned in the prior chapter, except for some brief periods during
development, frogs can’t regenerate, but salamanders can regrow whole limbs.)
After the tumour transplant, the poor salamanders usually died of the resultant
malignancies, with one exception: if Rose cut off the leg onto which he had
grafted the tumour, precisely bisecting the implanted tumour, the animal
regrew its leg, every time. The regenerating limb bud conscripted what was left
of the tumour, transforming its cancerous cells into the normal cellular
building blocks of biological tissue.1 The regenerating leg essentially absorbed
the cancer.
His experiment was among the first to identify the strange link between
regeneration and cancer, but it was not the last.2 Among the strangest of these
is the discovery of the naked mole rat’s trifecta of superpowers: not only does
this rodent rarely get cancer, it seems to heal without scarring3 – and it defies
known biological laws of aging.4 These animals can live up to thirty years in
captivity (a standard non-naked, non-mole rat clocks in at about a year). Naked
mole rats had been known for a long time to be almost totally impervious to
tumours, but in 2018 it emerged that they don’t die of old age the way other
mammals do. Emerging evidence also suggests that they can heal better than
other mammals.
This odd story is one of many strange links between healing wounds,
regeneration, and cancer. We have known since before Jaffe and Borgens that
differences in bioelectric signalling are a critical component of both wound
healing and limb regeneration – but instead of creating more of what we
needed, what if it could also create more of what we don’t? It would be a long
time, however, before the proper study of the complicated relationship
between electricity and cancer could be undertaken. The first scientists who
tried to investigate the electricity of cancer faced an uphill journey, thanks to
the a long parade of Victorian con artists who had poisoned the well with their
electrical cancer cures.

An indicator light for cancer

Around the time Sylvan Rose was chopping off salamander legs, Harold
Saxton Burr and his colleagues got a visit from Louis Langman, an obstetrician
at Bellevue Hospital in Manhattan. Langman hoped Burr’s electrical ovulation-
detecting technique might help bolster his success rates at artificial
insemination, as one has to be ovulating for the procedure to work.5 Burr –
having just emerged from his bruising fight with Catholic doctor John Rock
over the electrical signals in ovulation – was happy to help and instructed
Langman on proper use of the device. It turned out well; electrometric
measures improved the rate at which Langman was able to help women
conceive. But it soon became clear that this wasn’t the sole reason he had
approached Burr. What he really wanted to know was if this technique might
also help him identify cancers in his clients’ reproductive systems.
Burr was in. He enthusiastically sent one of his contraptions back with
Langman to his wards, where, in an initial group of 100 women, he strapped
one electrode to the lower abdomen above the pubis, and the other either on
or alongside the cervix.6 Women whose troubles turned out to be caused by
ovarian cysts or other non-cancerous medical issues almost always had a
positive reading. Women with malignant tumours, however, showed an
electrical ‘marked negativity’ of the cervical region every time.7 Langman
confirmed their diagnosis with a pathological examination. Cancerous tissues,
it appeared, emitted an unmistakable electrical signature.
Langman repeated the technique in about a thousand women to see
whether his results stood up. They did: 102 of his patients exhibited the
characteristic voltage reversals. When Langman operated on them, he
confirmed that 95 of the 102 had cancer.8 Even more remarkably, often the
masses had not even progressed to the point where the symptoms would have
driven them to visit the doctor, never mind obtain a correct diagnosis. After
removing these cancers, the electrical polarity shown on the electrometer
would normally flip back to a ‘healthy’ positive indicator – but it did not
always. When it stayed negative, Burr and Langman suspected that this
indicated that they either hadn’t got it all, or the cells had metastasised.
Somewhere in the body, a cancerous mass was still sending its nefarious
signals.
What struck them as especially strange was that the electrode inside the
genital tract did not have to be placed directly on, or even particularly near to,
the malignant tissue for the anomaly to be detectable. It was like a distress
signal was being sent over distances through the body’s healthy tissue.
It’s hard to evaluate any of these experiments nearly eighty years after the
fact. But to all appearances, it sure seems like a potentially reliable, non-
surgical way to detect malignancy was discovered in the 1940s – and then got
memory-holed. Langman and Burr were happy to acknowledge that ‘the
method employed in this study is obviously an adjunct to other diagnostic
procedures, and in no sense should be considered as a substitute for them’.9
However, it was something – and they wrote rather plaintively that they hoped
others would refine this fledgling technique to aid early diagnosis. In his
memoir, published twenty-five years later, Burr noted with evident
disappointment that no one ever followed up their literature or did any
replications.
In hindsight, it’s quite easy to see why. No one had any idea what could
possibly account for a voltage difference in cancerous tissue. Langman and
Burr’s findings were poorly understood, and like most bioelectrical phenomena
outside neuroscience, were ignored. And then, of course, four short years later,
studies of electrical signals in biology became moot with James Watson and
Francis Crick’s announcement that they had discovered the double helix
structure of DNA. Oncology began to reorganise itself around genes. Not
long after DNA was determined to be the sole arbiter of inheritance, it
became canon that anything that damaged DNA and caused mutations in it
may also cause cancer. In the 1970s and 1980s, a vigorous search for the
abnormal genes ensued.10 It was not a good time to go against the grain of
science.

‘A story that sounds almost like science fiction’

In the 1940s, while Langman and Burr had been investigating the
electrometric cancer diagnostic techniques, Björn Nordenström was furrowing
his eyebrows, puzzling over the subtle anomalies he kept finding in the X-rays
of his lung and breast cancer patients. As a diagnostic radiologist at the
Karolinska Institute in Stockholm, he had used X-ray imaging to inspect the
blood vessels inside lung cancer tissues. It was during these examinations that
he started to wonder about the persistent and puzzling irregularities that kept
showing up in his images.11
The images in the X-rays looked like spiky flares around the tumours and
lesions.12 Colleagues dismissed these as artifacts of the imaging method, but
that explanation didn’t satisfy Nordenström. By 1983, he had devised a theory.
Like Burr and Langman, Nordenström had found mysterious electrical
differences between normal tissue and tumours, and concluded that these were
the result of differences in the way ions flowed around them, thereby the
source of the flares he had found, which he named ‘corona structures’. He
believed that both coronas and the flow of ions that caused them were part of
a body-wide electrical circulatory system that existed alongside our traditional
vasculature, like an additional blood stream. This system transported the ions
in our ‘conductive media and cables’ (including the blood) like little weather
systems in coherent circuits around the body. Our electrical circulatory system
was not only as complex as the circulation of the blood, but also similarly
implicated in all the body’s other physiological activities. But because it was
invisible, until now we had missed it.
Controversially, instead of publishing this hypothesis as a series of small
articles in highly ranked journals, which is the way scientific theories are
typically disseminated, Nordenström decided to skip all that. In 1983, he self-
published the whole thing in the form of a book – an oversized, 358-page
colossus which he named Biologically Closed Electric Circuits: Clinical, Experimental
and Theoretical Evidence for an Additional Circulatory System.13 No publisher would
touch it.
Some researchers would, though. The book’s introduction sported not one
but three forewords – and a preface – from four scientists willing to stake their
reputation on this unusual idea. ‘I feel little need for lengthy considerations of
its scientific merit,’ harrumphed Universite d’Aix-Marseille biochemist Jacques
Hauton with unsatirisable French bof-ery. ‘Its full importance is today
impossible to appreciate,’ he continued, representing ‘no less than a major
point in the evolution of our understanding of biologic science.’14 The other
contributors were similarly dazzled.
It had only been seven years since the first ion channel had been observed
ferrying sodium in and out of cellular nightclubs. In the eyes of science, that’s
a millisecond, so the idea of bioelectricity in cancer was inconceivable. ‘The
theory sounds flawed,’ a National Cancer Institute deputy director, Gregory
Curt, told the Los Angeles Times in 1986. ‘Based on what we know about cancer
biology, there is no evidence that changing electrical fields have any impact on
a tumor.’15
Nordenström, however, had already started treating patients using the
principles of his biologically closed electrical circuits to (he claimed) interrupt
the electrical signals that promoted cancer. He would place a positively charged
electrode needle into the tumour and another negatively charged one into
healthy tissue, and send ten volts of direct current through the tissue for
several hours. This was repeated until the tumour began to shrink.
Nordenström told the Los Angeles Times that the patients on whom he was
experimenting ‘have been rejected by surgeons and other physicians as having
cancer too advanced to be treated’.16 Between 1978 and 1981, he treated
twenty such hopeless cases. Thirteen died despite his interventions. But
Nordenström insisted that many of the tumours shrank and even disappeared.
A short description of those first twenty cases appeared in 1984 in the Journal
of Bioelectricity.17 He insisted that he had been too busy to publish detailed
accounts in mainstream journals – and, in a move that was sure to make him
no friends, told the Los Angeles Times that what he was doing was too complex
for many of his colleagues to comprehend. ‘People say it’s controversial
because it’s another way to say they don’t understand.’
Here, surely, was the pseudoscience trifecta: a theory completely out of
step with current scientific thinking; a standoffish refusal to publish in
appropriate venues; and insistence on treatment being administered before the
method has been properly validated. Nordenström was showing all the
hallmarks of being a quack. And yet! Very smart researchers just couldn’t
agree. ‘It doesn’t follow the usual medical logic but it fits in with a number of
scientific facts in many disciplines,’ Morton Glickman told the Los Angeles
Times.18 It had taken Glickman, a radiology professor at Yale School of
Medicine, a full year to inch his way through the migraine-inducing
explanations of the biologically closed electrical circuits. He had come out the
other side a believer. ‘My feeling is there is a very good chance that it will [turn
out to be] true,’ he said.
While Western science held its nose, Nordenström’s mentions of unseen
forces travelling around the body piqued considerable interest in the People’s
Republic of China. In 1987, he was invited to Beijing to demonstrate his
technique at the Ministry of Public Health.19 There’s not much information
about that meeting, but afterwards the ministry wasted no time in mounting an
aggressive education campaign to get Nordenström’s technique taught at
hospitals. Between 1988 and 1993, forty-two courses were convened to teach
Nordenström’s methods, attended by 1,336 doctors from 969 hospitals.20 By
1993, they had treated nearly 5,000 patients. By 2012, the technique had
treated over 10,000 malignant and benign tumours.21
The media was sceptical, if not hopeful. On 21 October 1988, the highly
regarded TV news programme 20/20 ran a segment about a surprising new
approach to cancer.22 ‘Reporting on exciting medical breakthroughs is a role
20/20 has carried out for years,’ host Barbara Walters prefaced, before
describing the vetting process the show goes through ‘to make sure we don’t
give credence to frauds’. It was an unusual bit of deflection from an otherwise
impeccably confident anchor. She then went on to introduce ‘a story that
sounds almost like science fiction. It involves the theory that electricity plays a
very major role in the human body. It could revolutionise medical science. It
might even provide a new way of treating cancer.’
So what do we make of this? As Walters’ unease reveals, it can be really
difficult in the moment to distinguish the quack from the revolutionary, but
clarity tends to set in within a couple of decades. Not so with Nordenström.
He disappeared. He may have moved to China to continue his work, and by
one arcane account he died in 2006.23 Several of the researchers who staked
their careers on his claims have also passed away. Most people have forgotten
him . . . but only most. Some of the researchers I interviewed have quietly
squirrelled away copies of his book, which are a rare find. They were kind
enough to send me photocopies of certain sections, because like Glickman
they believe – off the record – he will be vindicated.
 Whatever you make of his theory – if you can understand it – there were
some basics we didn’t comprehend then which have since been put on solid
foundations. One of these is that ion channels are present in all cells. Their
activity determines the membrane voltage of the cell and the tissue, and
thereby the behaviour of these cells and tissues. Even cancer.

Cancer? There’s an ion channel for that

Mustafa Djamgoz was in the middle of his third pint down at the pub when he
got the overwhelming urge to put a cancer cell into a patch clamp. He had
never heard of either Burr or Nordenström. He wasn’t even a cancer
researcher (yet) – at the time, he was a neurobiologist at Imperial College
London. It was the early 1990s and he had met up with some of his old
colleagues one evening after a conference to knock a couple back.
They were pondering cancer’s electrical behaviour and getting nowhere
when Djamgoz, who had spent his life studying ion channels, had his eureka
moment. ‘Suddenly this big penny dropped in my mind: “My God, no one has
looked at electrical signals in cancer cells!”’ He asked his friends for some cells
and got to work. Djamgoz didn’t know it at the time, but he was about to
embark on the most complicated and frustrating seven years of his career.
Good thing, then, that he was no stranger to complexity and frustration.
Djamgoz grew up in Cyprus, whose Greek and Turkish residents have long
been engaged in various territorial feuds. The island seethed under British
colonial rule from 1878 to 1960, so when Djamgoz was born, every corner of
his neighbourhood was still festooned with characteristic British red telephone
and post boxes. Throughout his childhood he dreamed of attending Imperial
College, and as a teenager taught himself to build a radio transmitter from
scratch. He would shock himself up to fifty times a day in the process – and
not always by accident, as he was quickly developing a fascination with the way
electricity is interpreted by human biology. This unusual child was soon lured
from sunny Cyprus by a scholarship to study physics at a soggy boarding
school in Kent, a springboard to Imperial. The university had an established
reputation in visual psychophysics, the branch of vision research that probes
the way animals transform physical stimuli like photons into our subjective
sensory experience of the world, like the colour blue. Djamgoz built an
electrophysiology lab for his mentor from scratch, down to the amplifiers, and
in return received his doctorate.
He spent the next two decades studying the electrophysiological response
of the retina. ‘The retina is a beautiful model of the central nervous system,’ he
says. ‘You peel it out of the eye, you put electrodes in, you flash lights and you
can see all those individual cells responding.’ He still remembers the first time
he stuck an electrode into a retinal cell and flashed a red light at it. The cell
obliged immediately, flopping down into a state of flabby depolarisation, its
inner voltage becoming the same as its surrounding milieu, letting ions drift in
and out of the cell as they please. Then he flashed it some blue, and the cell
responded in the opposite direction, hyperpolarising – re-establishing the big
electrical difference between its inside and outside, which meant the ion
movements were once again tightly controlled. ‘This one cell knew the colour
it was seeing,’ he marvels. ‘And you knew because you could see the potential
on the oscilloscope just go up and down.’
Djamgoz was doing these experiments in the mid-1990s, at the dawn of
scientific investigation into adult synaptic plasticity – the idea that the brain’s
ability to change its connections doesn’t end with childhood, but persists into
later life.24 Indeed, Djamgoz’s work provided evidence for the idea, using the
retina as his model to assemble proof that adult retinal cells can change their
connections and adapt to different conditions. The work earned him a
professorship in neurobiology, and that’s where he likely would have spent the
rest of his career if it hadn’t been for that fateful night at the pub.
Now cancer seized his attention. One of his interlocutors from that
evening gave him a batch of cells from prostate tumours in rats. Back in his
lab, Djamgoz subjected these to the same electrophysiological prodding usually
reserved for the retina. He found them teeming with electrical activity – but
not the kind he was used to seeing in healthy cells.
It had long been known that as healthy cells turn cancerous, they de-
differentiate: this means that they leave behind their prior identities as bone or
skin or muscle cells, and return to a primordial state resembling that of a stem
cell. But unlike stem cells, which often dutifully transform into new identities
and go where they are needed, cancer cells refuse to ‘grow up’. They simply
drift, proliferating and consuming madly, never contributing to the society of
healthy cells around them. This de-differentiation was reflected perfectly in the
electrical activity Djamgoz observed in the cancer cells. The cancer cells had
traded their strongly negative electrical identities (-70mV) for the permanently
depolarised ‘zero’ existence of a perpetual stem cell. (This observation of his
was not unique, but in line with decades of previous observations.)
 But that wasn’t the only electrical artifact that grabbed his attention. They
were doing something else too, something far more perplexing. These
depolarised cancer cells were somehow . . . spiking. ‘These were bog standard
action potentials,’ says Djamgoz – but what business did these cells have with
action potentials? These cells came from gut or skin cells, not nerve cells. And
yet, the aggressive cancer cells had somehow gained this ability to spike like a
neuron during their transformation from healthy cells. But the spikes they sent
were not the dependable, decisive spikes of nervous signalling. They were
much more chaotic than that, waving and flickering and exhibiting an
incoherent pattern Djamgoz had previously seen only in epileptic episodes.
What were these weird action potentials doing in cancer cells?
Djamgoz knew they were unmistakably the work of a voltagegated sodium
channel, the same family of sodium channels that lets nerves send action
potentials. No one had ever investigated whether changes in these ion
channels’ behaviour could be related to a cell’s transformation into cancer.
Could these aberrant spiking channels be the reason tumours became
aggressive and metastasised? This was the question Djamgoz asked in his first
paper. He and his colleagues submitted it to Nature, the premier science
journal in the UK. It was rejected instantly by editors who dismissed the
observations as an epiphenomenon. But Djamgoz and his co-authors
eventually managed to present their work at an obscure urinary-tract
conference. It was enough to get their paper published in a minor but
respectable journal.25 It was 1993, and Mustafa Djamgoz was done with
neurobiology. The retina was out. Djamgoz only had eyes for cancer.
The next seven years were spent on what Djamgoz calls a charm offensive:
publishing a barrage of incremental advances, climbing up the ladder of minor
journals to arrive at middling journals, and talking to anyone who would listen
about electrophysiology, bioelectricity, and basic physiology. An ever-
increasing list of diseases were being accounted for by pathological mutations
of the various ion channels – including cystic fibrosis, epilepsy, heart
arrhythmias, and even gastrointestinal diseases – why should cancer be
exempt? ‘Your electricity is what helps you get up and move around,’ he
remembers shouting at his oncology associates. ‘Well, it helps cancer cells get
up and move around too!’ He continued to harangue his colleagues as he
worked to build a careful foundation to understand the precise role these
channels played in metastasis.
The broad consensus on cancer is that it results from abnormal expression
of genes – or at least, a cell’s initial flip from healthy to cancerous is usually
chalked up to genetic defects and mutations. However, that is not what ends
up killing you. It’s widely accepted that most cancer deaths happen when the
cells invade the rest of the body.26 This incursion is facilitated by a repertoire
of basic cell behaviours in which ion channels are known to be crucial:
moving, multiplying, attaching, and more. It is not always possible to look at
the genes in someone’s prostate tumour and conclude from the DNA whether
that tumour will sit there not bothering anyone, or whether it will start
roaming around your body. But Djamgoz and his team were starting to
wonder if maybe there was a clue in the action potentials. Could their spikiness
correlate with the aggressiveness of the cancer? That would be a hugely
valuable diagnostic tool.
By the turn of the century, people stopped dismissing these ideas. Other
researchers had already been making the connection between ion channels and
cancer, notably the Italian pathologist Annarosa Arcangeli, who had spent
decades at the vanguard of linking cancer’s electricity to specific genes.27 At
the University of Florence, she established the cancer-causing relevance of a
gene called hERG, which is already familiar to many biologists in an electrical
context: the ion channel it encodes plays a well-known role in coordinating
your heartbeat by controlling its potassium current.28 Arcangeli and Djamgoz
were careful and talented scientists, and as more researchers began to join their
investigation, overwhelming evidence accumulated that ion channels were key
players in cancer progression.29 Suddenly it wasn’t just an interesting academic
finding or even a new diagnostic: here was a promising avenue for new
treatments.
Ion channel drugs were now a plausible way forward for cancer treatment.
About 20 per cent of drugs on the market target ion channels in some way,
variously blocking them or prying them open.30 If ion channels were turning
out to be important in letting cancer proliferate, could blocking the right one
help stop it? Could one of the existing ion channel drugs hold the key to
stopping these aggressive cancers?
There was just one problem: the property Djamgoz identified as making
cancer more aggressive was controlled by the same voltage-gated sodium
channels in charge of the action potential. You couldn’t block them. Sure, you
might stop a person’s cancer metastasising, but you’d also stop their nervous
system; bad news for their heart and their brain.
This is one of the hardest, most bedevilling problems in cancer treatment:
finding some unique target that exists exclusively in a cancer cell but that will
not also mess up a normal, healthy cell. ‘There’s a huge history in cancer of
people identifying some property of cancer cells,’ Mel Greaves told me. ‘But
when you dig deeper, you often find those properties are not cancer-specific at
all; it is only that cancer cells are exploiting a perfectly normal property.’
Greaves, at the Institute of Cancer Research in London, is cancer-research
royalty – he received a knighthood in 2018 for his investigations into what
triggers leukaemia in children.31 This is the guy journalists call when they want
to know if something is legit in oncology.
But Djamgoz dug deeper. When he did, he found that the guilty cells were
using a special type of ion channel that normally only existed in the cells of
developing foetuses. There, they supercharged cell multiplication and the other
processes needed to quickly form a whole human from nothing. By the time a
baby is born, though, this turbo version should have been shut down, deleted,
and replaced with the normal, ‘adult’ version of the channel, the one that only
does approved activities like sending action potentials.
Djamgoz’s prostate cancer cells were teeming with these pre-birth ion
channels, which he called an ‘embryonic splice variant’. Something had woken
them up again as the previously healthy tissue turned cancerous.
Now that Djamgoz knew how the aggressive splice variant differed from
the normal and life-sustaining regular sodium channel, he had a target whose
removal would not harm normal bodily operations. Over the next few years,
he searched for the same variant in other metastatic cancers, trawling through
biopsies from human cancer patients, and reliably found his splice variants (or
their counterparts) in colon, skin, ovarian, and prostate malignancies.32 This
time, it did not take much convincing to get a grant from Cancer Research UK
to work on an antibody to specifically inhibit these variants.
Mustafa Djamgoz and Annarosa Arcangeli are no longer struggling to get
people to accept their ideas. More than two decades after Djamgoz’s ion
channel was dismissed as a coincidence, the field exploring ion channels and
cancer has exploded.33 Researchers around the world34 are busy digging for
hidden treasure in that big catalogue of existing drugs.35 What’s more, sodium
and potassium channels are no longer the only game in town. People are also
looking at chloride and calcium. The picture that is emerging is of many
different types of channels all working together in complicated synchrony, like
an orchestra, as Djamgoz put it in a 2018 interview. The sodium channel
‘could be the lead violinist, but to be able to create the full symphony we must
understand the other players as well’.36 For example, Arcangeli’s hERG
channel is now an object of great interest among pharmaceutical companies.
At a roundtable of Bioelectricity editors in 2019, she predicted that novel
therapies targeting ion channels would be a future cancer treatment.37
Djamgoz has his own company now, and they were starting to put
together a human clinical trial when – as with so much science – the pandemic
put everything on ice. Neither this nor the fact that he is not a clinical
oncologist have stopped forlorn people from calling him at all hours of the
day. ‘They are desperate,’ he says. People diagnosed with cancer need new
options.

A new ally in the war on cancer

The efficacy of the most common treatments depends on the cancer being
caught early, while it is still a tumour sheltering in place. Once the cancer has
spread its tendrils elsewhere into the body, survival rates start to go down. Mel
Greaves outlined his theory explaining why in the journal BMC Biology in 2018:
successfully destroy a tumour with radiation or chemotherapy, and in theory,
you’ve won. If no cells remain, for the moment, you are cancer-free. However,
should even a single cell survive, then by definition, it is now immune to
anything you threw at the tumour before. That cell is the mother of your
future tumour, and as it proliferates, all its progeny will be equipped with that
same resistance. (The same logic governs drug resistance.38) And there’s
evidence that this new batch of cells will be not only more tenacious, but more
aggressive than the original tumour. ‘We are battling natural selection, one of
the fundamental laws of the universe,’ Charles Swanton, an oncologist at the
Francis Crick Institute in London, told New Scientist.39
To start working out the new battle plan, in 2013 Mel Greaves set up the
Centre for the Study of Evolution in Cancer. He gave a talk at London’s
Science Media Centre, where he floated a new idea to address the resistance
problem: for some advanced cancers – particularly in older patients – instead
of hunting down every last cancer cell in the aim for a cure, perhaps we should
approach it more like a chronic disease. ‘Most cancers hit people when they
are past the age of sixty,’ he explained to me, recounting the talk he gave there.
‘If you treat cancer as a chronic disease, and keep it from becoming aggressive,
you might get ten or twenty more good years.’ This would be a vast
improvement over the mere months some treatments add to people’s lives in
pursuit of curing their late-stage cancer (not to mention the impoverishing
expense, and the toxic medications that more often destroy their quality of life
than their cancer). Not everyone was convinced. ‘I got a lot of hassle for that,’
he recalled in our conversation. An editor from The Times told him that it was
the worst idea he had ever heard. The published responses were similarly
unkind. ‘Let’s stop trying to cure cancer, says cancer professor,’ sneered the
Daily Telegraph.
But time has been on Greaves’s side. A lot of scientists today agree: catch
it early, but if you can’t, ‘control is a much more realistic objective’.
Genomics has revolutionised cancer treatments and has vastly enhanced
our in-depth understanding of cancer. It has yielded powerful new diagnostic
and therapeutic tools that have been incredibly effective in some cases,
including a game-changing treatment for adult leukaemia.
But there is a gulf between these successes and the contention that cancer
is a disease of the genome. ‘Cancer is not purely a disease of the genome, just
like evolution is not just about genes,’ Greaves says. A cell can change many of
its attributes on the fly, in response to its environment, in a way that their
genomes can’t fully account for. ‘So saying it’s all genomics is wrong,’ Greaves
told me.
So the question is: if the electrome affects cancer, what can we do with
that information?

Detecting the electrics

In the decades since Harold Saxton Burr and Louis Langman first suggested
using cancer’s electric properties to detect it, many research efforts have
discovered that you can use bioelectric properties to distinguish cancer cells
from their healthy counterparts, owing to the way they disrupt the flow of
electrical currents through the body. This was an unfamiliar concept when
Burr and Langman were doing their work, but is now widely known as
bioimpedance.40 You might recognise the word from those fancy scales they
have at gyms and spas that measure body composition (though most people
who use them are primarily interested in the precise ratio of body fat to muscle
they reveal). These work on the principle that current can’t travel through fat
cells – fat having a higher ‘impedance’ – but can travel through lean tissue like
muscle. Cancer also has its own bioelectric signature.
When removing a cancerous tumour from any area of the body, the
surgeon’s goal in the operating theatre is to leave nothing behind. But she is
cutting blind, unable to see the difference between cancerous and healthy
tissue. While imaging techniques and other technologies give a location and
map of the mass, when it comes to the actual act of cutting tumour out of
flesh, it’s highly educated guesswork. To raise the odds that the whole mass is
cleanly removed, the surgeon aims to carve out not just the tumour but also a
generous rind of normal tissue around it, often several centimetres’ worth.
After surgery, that carved-out lump of flesh is sent to a pathologist. The
pathologist examines it – specifically, the rim of healthy flesh around the
tumour, which is known as the surgical ‘margin’ – to be sure that margin is
clear of any cancer cells. The problem is that the results can take several days
to come back, and if the analysis finds a positive margin – cancer cells are
present in the rind – it will mean the patient needs a second or third surgery,
and more treatments to augment them.41
Several new technologies, in various stages of clinical trials, aim to help
surgeons get the whole tumour the first time. One promising candidate,
ClearEdge, developed by a start-up in San Francisco, used bioimpedance for
breast cancer margin detection. It integrated the technology into a device
called a ‘margin probe’. This is used by the surgeon while the patient is still
under anaesthesia, after the surgery, to measure the bioelectric properties of
the area around the tumour that has just been removed. A ‘traffic light’
bioimpedance map helps the surgeon see where she missed a spot: red for
cancer, yellow for uncertain, green for clear. It was clinically evaluated in
several hospitals in the UK. In 2016, surgeons at the University of Edinburgh
Medical School and Western General Hospital, in Edinburgh, successfully used
the device to identify cancer in areas around the excision and reported that it
can reduce the need for repeat surgeries.42 It compared favourably to existing,
more time-consuming ways of testing for cancer.
So, where’s ClearEdge? Why haven’t you heard of it? Mike Dixon, one of
the surgeons who trialled the device, told me that while the technology was
easy to use and its results were pretty good, the follow-up studies never
happened. ‘The company was reliant on venture funding,’ he said. ‘The
technology sounds great,’ he says, but so have many other margin probes that
their team has been involved with. Some proved too elaborate, others not
accurate enough, and some just disappeared.
Dany Spencer Adams is working on a way to make an affordable, accurate
version that she says anyone can use, based on the same kind of bioelectric dye
that helped her visualise the ghostly frog face. It tattles on the peculiar
electricity of cancer cells in a different way – by lighting them up according to
their membrane voltage, so cancer cells appear to be a different colour than
healthy cells. They don’t do this in a live, open patient though – they do it with
the mass they’ve already removed, and a very fancy piece of blotting paper.
After excising the tumour, a surgeon will press this special paper to the margin
of the mass to transfer the cells, put the paper in the dye, photograph it, and
upload the results to a computer program. Within ten minutes, you have a heat
map of the entire surgical margin – a paint-by-numbers landscape that tells you
where you missed a spot. If they did, they can go back in while the patient is
still on the table.
That’s the idea, anyway. After testing it in many cells in petri dishes, and
watching the voltage dye cause the cancer cells to light up dramatically, testing
has begun on live tissue with promising results. However, it’s not available yet.
Clinical trials are always expensive, and sometimes investor goals can work
against new devices, when cashing out of your start-up is more important than
making it into a surgeon’s hands. We’re therefore still a way off this new wave
of bioelectric diagnostics making it into the operating theatre, where it could
make surgery for cancer much more effective and reduce recurrence, not to
mention the trauma and infection risk that comes from more surgeries.
Further out, it may become possible to check your cancer’s bioelectric
properties to find out whether you even need surgery to take the tumour out
at all. Remember, genetic defects may have caused the initial cancer, but
whether it grows or goes on walkabout is up to your body’s bioelectrics. Not
all tumours are aggressive – some are slow, and may go away on their own. In
an as yet unpublished study, Djamgoz and his colleagues have collected more
evidence that their sodium channel could in and of itself be a diagnostic
marker for a cancer’s aggression levels.43 When his channels whip up ion
currents, survival rates drop, he told an ion channel modulation symposium in
2019. This could help people make difficult treatment decisions, for example
when evaluating the need for radical and life-altering surgeries and other
treatments. ‘We have never seen metastasis where the channel was not present,’
he told me. Djamgoz’s sodium-channel findings are also opening up some
really unexpected new options for how we might treat the cancer we find.

Communications blackout

To prevent seizures, some people with epilepsy take drugs that close the
sodium channels that spark abnormal action potentials in nerves. This calms
the electrically overactive brain action potentials, making them less likely to
cascade. Such drugs don’t just treat epilepsy symptoms; they have a wide range
of uses, such as for heart arrhythmias and some types of antidepressants.44
A little over a decade ago, anecdotes at clinics and occasional reports to
the FDA began to hint that people who took these sodium-channel-blocking
drugs seemed to have a lower risk of getting some kinds of cancer, and were
more likely to survive if they did get it.45 According to follow-up reviews,
those kinds of epilepsy drugs seemed to be associated with lower incidences of
colorectal cancer, lung cancer, gastric cancer, and blood cancers.46 (To be clear:
these are early signs, not smoking guns. None of this is enough data for
anyone to start taking anti-epileptic drugs if they’re not needed!)
The very preliminary story of these sodium-channel-blocker drugs,
however, happens to fit very neatly into Djamgoz’s theory. Added to this
mosaic, Djamgoz’s research suggests a mechanism for the mystery of how the
sodium channel blockers might be keeping cancer at bay. The erratic action
potentials sent by his splice variant create a way for the tumour cells to
establish contact with each other and the cells in the immediate vicinity. ‘They
are communicating with each other,’ he says. Blocking them would block this
communication.
These trials are all in their earliest days, but if they pan out, there’s good
news: the process to approve these drugs to treat cancer could be very short.
Djamgoz, Huang, and Arcangeli are among many researchers repurposing the
troves of existing ion-channel drugs to keep cancer cells from communicating
and acting on their environment. One big draw of repurposing existing ion-
channel drugs is that you don’t have to start from scratch with drug
development – which can take decades – and that can dramatically accelerate
how soon you see them in the clinic.
If such drugs can remove a cancer’s ability to metastasise, Djamgoz thinks
you can turn the disease into a chronic and manageable condition – exactly in
line with Greaves’s position that cancer should be treated as a chronic illness.
‘We advocate “living with cancer”, rather like we can live chronically with
diabetes and the AIDS virus,’ Djamgoz said in his 2018 interview. ‘Living with
cancer means suppressing metastasis, since this is the main cause of death in
cancer patients.’47
But ion-channel drugs could do even more than that. Some very early
studies have raised the possibility that, just as Sylvan Rose’s regenerating
animals were able to hit the undo button on a growing tumour, messing with
the right bioelectric parameters could help us do the same.
The society of cells

In the last few years, an unambiguous general consensus has emerged that the
solution to the cancer problem likely resides in new theories of cancer. In
1999, Ana Soto and Carlos Sonnenschein at Tufts University School of
Medicine suggested exactly such a novel paradigm: what if we started looking
at cancer not as a breakdown of individual cells but as a breakdown of cellular
society? When individual cells get together, they form tissue, and that tissue is
a kind of society. Proliferation is a cell’s default state, they argued. So cancer is
not sparked by one rogue cell gone wrong so much as a failure of the local
environment to keep the cell’s ‘natural instincts’ in check.
Cancer, in this view, becomes a disorder of organisation in the human
body rather than a defect of individual cells. It was a beguiling metaphor,
especially as it squared so well with the way cancer cells stop contributing to
the body and decide to live on their own radically individualistic terms. Nor
was it as radical a supposition as it first appeared.
A spate of more recent work has begun to more closely examine the
significance of non-genetic factors on cancer’s spread: things like tensile forces
and biomechanics in the micro-environment, and their contribution to a
tumour’s ability to expand and invade its surroundings. In 2013, researchers at
Memorial Sloan Kettering Cancer Center in New York wrote that ‘many
studies have shown that the microenvironment is capable of normalizing
tumor cells’, that re-education of the cells around the tumour, rather than
trying to get rid of them, ‘may be an effective strategy for treating cancer.’48 In
other words, the healthy cells around the tumour are just as important as the
tumour in determining whether the thing can spread. It’s not just the cells
themselves but something in their environment (the society) that is falling
down on the job of regulating their behaviour.
In particular, the evidence has recently started to point to the importance
of the bioelectric signals that cells use to process information. The same kinds
of weak electrical fields that coaxed healthy cells to crawl across a petri dish
have also convinced cells from brain, prostate, and lung tumours to make the
trek.49 Such fields, of course, also exist inside the body – they’re the
consequence of the currents swirling around the cytoplasm and the membrane
voltage of all our cells.
To sum it all up, the interactions between cancer cells and the surrounding
bioelectric fields are increasingly recognised as an overlooked but crucial
aspect of how cells make decisions based on the state of their neighbours. In
this framework, cancer can be viewed as a failure of communication – a fault
in the field of information that coordinates individual cells’ ability to be part of
a normal living system.
So if that’s the case, is it possible to re-establish the communication
protocols? This is fairly unconventional thinking when it comes to cancer, and
yet has a growing number of adherents.50 But as we get a better view of the
varied roles bioelectric signals play in cancer, new possibilities are emerging.
The new suite of tools enabled by a focus on the bioelectricity of cancer could
lead to earlier diagnosis, its transformation into a chronic disease – and maybe
even a way to convince cancer cells to hit the ‘undo’ button.
If you recall, the cell’s membrane voltage is closely related to (and can
determine) its identity, from stem to fat to bone.51 Manipulating this voltage
made many remarkable changes to an organism: like that eye made to grow on
a frog’s butt. Well, it turns out the same factor that could sculpt an eye on a
frog’s butt could also tamp down a cell’s will to become cancerous.
If the body’s ‘societal’ control over its cells is mediated by the signal of
membrane voltage, then a good way to test this bold theory would be to see if,
simply by changing the electrical voltage of a cell, you could cause a healthy
cell to turn cancerous, or convince a cancerous cell to return to a healthy state.
Those were precisely the experiments researchers undertook at Michael
Levin’s lab at Tufts University in 2012. If bioelectric signalling was an
important part of how cells communicate to work on pattern and coherence,
they reasoned, and cancer represented a break in this multicellular contract,
then interfering with cells’ ability to send bioelectric signals should lead to
cancer. After Levin’s doctoral student Maria Lobikin depolarised normal cells,
the depolarised cells began to act malignant.52 It was evidence that
bioelectricity is the informational glue that holds big multicellular structures
together. Membrane voltage was ‘an epigenetic initiator of widespread
metastatic behavior in the absence of a centralized tumor,’ she and her co-
authors wrote.
The next year, another member of Levin’s team, Brook Chernet, went a
step further: could you use membrane voltage alone to predict whether cells
would become cancerous? They tested the hypothesis on frog embryos that
had been laced with human cancer genes to cause them to form tumours.
Using the same fluorescent voltage-reporter dye that Dany Spencer Adams
had used to watch the electrical development of the frog face, they were able
to observe depolarised membrane potential in the tumours. And just as Adams
had been able to predict facial features, the electric signal change just by itself
could predict which cells would turn cancerous.53 This experiment, they wrote,
not only implicated bioelectric signalling in tumour formation, but suggested
new approaches for anti-cancer therapies. That’s because when they
repolarised (and strengthened) the low-voltage cancerous membrane, the cells
stayed connected to the society and ignored their own mutated genes’ efforts
to turn them cancerous. In other words, Chernet and Levin reduced the
number of tumours just by repolarising the depolarised cancer cells.54 Chalk
up another win for the bioelectric code.
By 2016, Chernet could not only stop new tumours from forming – he
was able to ‘reprogramme’ existing ones back into normal tissue in tadpoles.
Their tumours were advanced: they had already spread and formed their own
blood supply. But when Chernet used light-activated channels (a technique
known as optogenetics) to modulate the cells’ resting potential, they stopped
acting like cancer. ‘You can turn on the light . . . and the tumor goes away,’
Adams, who was one of the co-authors of the paper, told Reuters.55
Electrically reminding the cells of their role in the rest of the tissue, Levin told
me, appeared to snap them out of their midlife crisis and help them re-enter
the society of cells. Bioelectricity overrides genetics. As these and other
experiments showed, the voltage changes were not merely a sign of cancer.
They controlled it.56
This is all fascinating, but it, too, is an extremely long way from your
doctor’s consulting room. Like all the recent results on bioelectricity, those in
cancer are still early. Tadpoles are really, really not like us. Furthermore,
repeating some of the experiments has flagged inconsistencies.57 There’s a lot
left to do.
Like regeneration, however, it offers a very tantalising prize: a control
switch for more complicated biological processes. ‘The electrical
communication amongst cells is really important for tumour suppression,’
Levin says. What’s more, this control switch might also be amenable to existing
pharmacological interventions. Like Djamgoz and Arcangeli, Levin is also
looking at ion-channel drugs.58

In a little under a century, bioelectric signals in cancer have gone from an

overlooked curiosity to suspicious quackery to a promising way to improve
cancer detection and treatment. The more recent investigations have
illuminated why Burr and Langman were right: cancer has characteristic
electrical signatures that can be used to detect it. Indeed, these signatures may
be just the beginning.
Nordenström may have been onto something when he tried to disrupt
tumours with electricity back in the 1940s. There’s now a flourishing and
rapidly advancing line of research into destroying tumours with nanosecond
pulses of cold plasma that are more precise and powerful than anything he had
access to in his day.59 This newfound ability to harness room-temperature
lightning for medical purposes is fast changing the way we treat tumours, says
Jose Lopez, who directs the plasma physics program at the US National
Science Foundation. This is yet another bioelectric intervention to watch in the
next ten years.
Many devices and technologies are now being recruited to interface with
the body’s electricity for regeneration, wound healing, and cancer treatment,
and they join ion-channel blockers as the new vanguard of medicines.
But that’s now. There are things in the pipeline that look nothing like these
tools. They won’t be made of metal. They will interface with us on a much
deeper level. And they will likely be made of the stuff we find in the natural
world, which runs on the same electrical programming as we do.
 PART 5

Bioelectricity in the Future

‘We have been promised a future of chrome, but what if the
future is fleshy?’
Christina Agapakis

T he bioelectric code is only one of several facets we are beginning to

discover about the electrome. All of them suggest that successfully
engaging with our natural electricity won’t be about control and manipulation
so much as it will require interacting with it on its own terms. Understanding
the full breadth of the electrome will also require much more than just a
command of ion channels or an understanding of the nervous system. It will
require a huge interdisciplinary effort and a critical look at how the structure
of today’s science itself can limit scientific understanding. It will also require a
rethink of the materials that we use to interact with our electrics. Maybe it will
even lead to a new way to think about the drugs we take and their effects on
the electrome. It will be, in other words, revolutionary.
 CHAPTER 9

Swapping silicon for squids:

Putting the bio into bioelectronics

F rogs have been through a lot over these past 200 years of
electrophysiology, from Galvani’s grotesque puppeteering to Matteucci’s
body horror power source. But no one could have anticipated the next role
they would play in the quest to unite biology and electricity. In 2020, frogs
became the raw material for a class of organism that had never before existed
in the evolutionary history of the world.
Well, their cells did anyway. A few thousand of them were scraped off frog
embryos and then reconstituted into groups of roughly 2,000. Under some
cleverly programmed tutelage, the clumps began to cooperate, moving and
acting of their own accord, becoming – in the verbiage of their creators –
‘xenobots’, literally ‘frog’ (from Xenopus) ‘robots’. This wasn’t the average
person’s idea of a robot, but neither were these frogs, not any more. They did
not have brains or nervous systems so their ability to move and decide was
outside the traditional accounting for how animals do this. They didn’t have
mouths or stomachs so they couldn’t eat. No reproductive organs meant they
couldn’t make more. Joshua Bongard, the University of Vermont roboticist
who had helped create them, called them the only thing he could: ‘these are
novel living machines’.1
Wait – roboticist? Why is a roboticist creating frog cell bots?
Robotics is changing. Where they used to be thought of as hard-edged
appliances that occasionally (as in The Terminator) take on biological forms,
now the line is blurring between biology and robotics as we learn more about
both. After all, a robot is a programmable device that can manage information
– and a cell is turning out to be that too. The xenobots’ creators speculate that
the tiny organisms might someday deliver drugs into targeted areas of the
body, scrape plaque out of arteries, or clean up plastic waste in oceans. But
perhaps the most important thing they offer is a rare glimpse into the possible
future of the materials we use for robotics, electronics – and implants.
For years, researchers have toiled to find new and better ways to interface
with our nervous system, but have been thwarted by the mechanical, chemical,
and electrical properties of existing devices and their fundamental mismatch
with our brains. Compared to the signals they are tasked with manipulating,
these metal devices are rigid and bulky. ‘It’s like playing the piano with a
mallet,’ Andrew Jackson complained when I went to his neural interfaces lab at
Newcastle University to get a better understanding of the future of brain
implants. (His phrasing echoes Kip Ludwig’s on deep brain stimulation – two
researchers using this phrase is an interesting coincidence; if a third uses it, I
might cry conspiracy.)
For the past decade or more, the limitations of metal devices have
motivated an enormous project to create squishier, stretchier, more
biocompatible materials that let our bodies electrically communicate with the
foreign bodies inserted into them. This trend extends from tissue engineering
to robots, which are increasingly being augmented by, or made entirely out of,
synthetic materials such as hydrogel, a squishy polymer that is popular for soft
robotics.2 In the future, such nano-gloop-bots will supposedly swim through
our bodies, making adjustments to errant tissues.3
As we gain a better understanding of the electrical instructions of biology
itself, a sizeable contingent of scientists is beginning to wonder if the ultimate
biocompatible material isn’t just . . . literal biology. That’s why researchers are
now studying the properties of sea creatures, frogs, and fungi for their
programmability and biological compatibility.

The rise and fall of electroceuticals

Around ten years ago, an astonishing breakthrough was reported in Wired

magazine, and from there quickly raced through the rest of the media. The
neurosurgeon Kevin Tracey had used an electrical implant in a research
subject’s neck to zap the vagus nerve, an enormous treelike projection of nerve
bundles whose branches extend to and from the brain through a vast amount
of the body. Electrically stimulating it had dialled back the excruciating
symptoms of the patient’s rheumatoid arthritis, an immune disorder with
which he had suffered for years.4 It was an extraordinary story: before the
treatment the subject had been so debilitated, he couldn’t play with his
children, but the electrical stimulation was so effective he could return to
work, throw his kids around, and even resume his favourite game, ping pong.
(This turned out to be too much of a good thing – he overdid it and ended up
giving himself a ping pong injury.5)
Rheumatoid arthritis was far from the only immune system problem this
intervention promised to treat without drugs or side effects: asthma, diabetes,
hypertension, and chronic pain were also promising targets. ‘I think this is the
industry that will replace the drug industry,’ Tracey told the New York Times
journalist Michael Behar.6 Soon, science magazines and newspapers teemed
with the catchy new portmanteau that described this merger of electricity and
pharmaceutical: the era of ‘electroceuticals’, it seemed, was upon us.
What so bewitched those of us in the science press, however, was not only
the promise of transcending drugs. It was the elegance of the new mechanism:
you didn’t have to mess with drugs and side effects, you just flipped a switch
and the body would do the rest. That is, he had recently discovered that the
nervous system could control a lot more than our motor nerves. It might be
able to control inflammation and the immune system. He believed the circuit
he had identified was only the first of many ways we would find the vagus
nerve entangled with our every organ and cavity, and thereby able to govern
any number of their functions. The immune response had previously been
considered beyond the reach of the nervous system’s control architecture – we
simply didn’t realise nerves went there or did that. But now the list of ailments
targeted for electroceutical intervention expanded to include chronic
obstructive pulmonary disease (COPD), other heart conditions, and
gastrointestinal diseases. They just needed the wiring diagram.
To find it, the global pharma giant GlaxoSmithKline set up a $1 million
prize. The endgame, they explained to me in 2016, would consist of rice-sized
electrical implants that would sit on specific control branches of the vagus
nerve, monitoring messages as they flashed through on their way between
brain and viscera: muting some, amplifying others, and generally recording the
electrical activity within to catch problems and quickly fix them. It sounded
like an NSA wiretap, but for your health. By then, Google’s life sciences arm
Verily had also become keen, and the two superpowers spun off a new
supergroup, a venture they christened – remarkably – Galvani Biosciences.
Early pilot studies confirmed the potential of the approach, with one group
finding that the correct series of electrical impulses to the right nerve bundle
could reverse diabetes in mice.
Surmounting the remaining technical hurdles ‘might take 10 years’, Kris
Famm, head of GSK’s bioelectronics research and development unit, told
Behar at the New York Times. But looking a decade out, he told a CNBC
reporter a year later, ‘we should have a number of tiny devices that will be
treating conditions we use molecular medicines for today’ heralding this ‘new
class of new therapies’. All I can tell you is, in tech, beware the ten-year
horizon.
After that, electroceutical chat went very, very quiet. (Part of that story
concerns a patenting misfire.) Nobody has rice-sized implants routing their
nervous signals around the body. Galvani Biosciences is still plugging away, but
with replication results that don’t make any headlines.
Now, part of this is just the inevitable rollercoaster of the hype cycle. First,
you get a big splashy announcement of a new possibility and everyone is very
excited. Then the grind of basic research sets in, and there’s a long trough of
disillusionment because the new hot devices aren’t ready immediately.
Eventually, positive results start to emerge from the long tail of clinical
research, and slowly the once-hyped revolution is integrated into routine care
at your doctor’s office, and fades into the background of everyday life. And in
fact there are signs that this is starting to happen – in 2022 Galvani put the
first autoimmune disorder device into a clinical trial.7
So maybe electroceuticals are tracing this classic innovation curve. But
even after they go through trials, they will face many of the same factors that
have been putting the brakes on DBS’s ability to perform miracles.
Sticking a pin into the 100,000 fibres of the vagus nerve is unsurprisingly
turning out to be much more complicated than initial reports promised, with
similar uncertainties and unexpected side effects.8 Several of these are
catalogued in a 2018 book The Danger Within Us, written by a former
emergency room physician associate named Jeanne Lenzer, who turned to
investigative journalism after witnessing the life-altering consequences of the
first generation of these implants – these were nothing like the rice grains
envisioned by Galvani, but big pacemaker-like devices that had been implanted
before there was much understanding of how stimulating the vagus nerve
worked to ameliorate symptoms of drug-resistant epilepsy. Lenzer’s book
shone a particular spotlight on this technique, approved by the FDA long
before Kevin Tracey found it might influence immune function. For one of
Lenzer’s patients, the intervention devastated his cardiac function.9
 The metal implants we use to stimulate the nervous system simply don’t
play well with the nervous system.

The trouble with implants

To interact with the electrical signals of the body, either by reading or writing
them, you need to use an electrical device. In the brain and heart, implants like
pacemakers and deep brain stimulators have traditionally been made from
materials deployed in the semiconductor industry, like silicon or metals that
control the flow of electricity, among them platinum and gold.
But (unfortunately) your body isn’t made of gold. There’s no love lost
between these kinds of implants and biology, which is likely to mount a
healthy campaign of resistance to the invader. That is especially true with brain
implants, which create an inflammatory defence response in brains. You can’t
blame the brain, because during insertion, ‘the microelectrode tears blood
vessels, mechanically damages the membrane of neuronal and [other] cells, and
breaches the blood brain barrier’, per the authors of a widely cited 2019 study
of ways to calm the resulting inflammatory response.10 Things don’t get much
better from there.
For people who have no other options – some of whose stories I told in
Chapter 5 – an electrode can alleviate acute symptoms. But there are trade-offs
and problems. For one thing, metals tend to be the wrong thing to stick in a
brain. The two materials have a mismatched Young’s modulus, which is a way
of quantifying a material’s ‘bend or break’ quotient. For the brain, the Young’s
modulus describes not just its give but also its ability to deform and then
return to its prior shape. Say you had a bowl of jelly, and you stuck a pencil
into it, and carried it around your house. Initially, you’d see no gaps between
the jelly and the pencil: they’re in perfect contact and the join looks seamless.
But after a bit of walking around, you would soon see the jelly de-adhere from
the pencil. Worse for the wobbly dessert, apart from the big gaps between jelly
and pencil, there would start to be some indirect structural damage in the jelly
caused by the destabilising effects of the intrusion – sideways clefts that split
off from the pencil gap. The jelly starts to lose its structural integrity.
You don’t want any of this happening to your brain. Once neurons die,
they don’t regenerate. To try and protect them, the brain relies on supporting
characters called glia. They are traditionally considered fighters and janitors
that help defend and protect the neurons in their care and keep them running
optimally. After an electrode implant, these cells flood in to try to seal the rest
of the brain off against the wound made by the rigid, bulky electrode and the
dead neurons. To protect the brain’s integrity, they envelop the implant in a
thick sheath of proteins and cells. This creates a spatial and mechanical barrier
that, as it grows thicker, mutes any electrical signals the electrode can both
send and receive. Over time, the signals will degrade in crispness and the
implant will eventually stop working entirely. At that point it will have to be
replaced, which requires yet another brain surgery, another implant, more dead
neurons, and more angry glia.
Meanwhile, things aren’t going too great for the pencil in our extended
metaphor, either. Being sealed off from the electrical signals is not the only
trouble for the implant. Biology is hostile to things like silicon and metal.
Instead of a harmless tasty flavour, imagine your jelly is a corrosive brine of
salt and vinegar. That pencil may look okay for a while, but leave it in the
mixture long enough and it will start to take some damage – all right for a £1
pencil, less so for your extremely expensive, sensitive, experimental electrode.
Engineers test implant materials for longevity by bathing the devices in
warm salt water for a few weeks to try to recapitulate a couple of years in the
environment of a human body.11 But we have little idea what would happen to
an implant you want in your head for thirty years, as the scope for testing is
limited; mice only live for, at most, three to five years.
Are you thinking about those so-called telepathic AI-brain implants a little
differently now?
There’s an enormous research effort to mitigate these problems, with
many projects at various stages of maturity. Different rules will apply for
neural implants, tissue engineering, and materials for wound healing. But
broadly there are two rules, Chris Bettinger tells me, and he knows these rules,
because his laboratory at Carnegie Mellon University in Pittsburgh works on
creating the materials that need to obey them: ‘The main ways to make an
implant that evades the immune response is either make it very small or
camouflage it.’
The first rule explains why there has been an enormous effort to make
everything at the nanoscale. Tiny wires or grains will be so infinitesimal, so the
theory goes, that the brain won’t notice the interloper and therefore won’t
mount an immune response. The problem with that is that you can only do so
much listening or talking with a tiny device. The smaller the electrodes get, the
less suited they will be to recording from the brain due to basic physics.12
You’d have to make up for it by putting in many, many tiny devices. And then
your brain will probably notice, and you’re back to square one with an immune
response.
The other option addresses the problem a bit more elegantly: cover the
electrical interloper in something the body mistakes for familiar. Many people
are trying to come up with a material the body is happy to see hanging out
inside its environment and use it to disguise the silicon or metal beneath.13
The winning material needs to be able to conduct electricity without messing
with your brain’s structure or otherwise catching the attention of the glia. But
what material conducts electrons apart from metals? Well, as it turns out,
plastics.
We used to think polymers were insulators – and they are, which is why
they are used for, well, insulation. But in 1977, Alan J. Heeger, Alan G.
MacDiarmid, and Hideki Shirakawa found out that some kinds of plastic can
conduct a current when they discovered a synthetic polymer called
polyacetylene. Their fabrication of this ‘conductive plastic’ with metallic-like
electroactivity was a major breakthrough in the field – in 2000, it earned the
trio the Nobel in chemistry.14 It’s to them we owe the existence of flat-screen
TVs and anti-static coatings and all kinds of trappings of modern life. Their
discovery also kicked off a new field of research called organic electronics, and
twenty-five types of conductive polymers have been developed since.
One major goal for organic electronics has been to solve the Young’s
constant problem and thereby create ever squishier, more flexible electronics.
Some organic semiconductors fit the bill, and one that is getting a lot of
attention right now has an unspeakable name typical of the genre: poly(3,4-
ethylenedioxythiophene). The material (nickname PEDOT) is so promising it
even found its way into the Independent: ‘Scientists have discovered a ground-
breaking bio-synthetic material that they claim can be used to merge artificial
intelligence with the human brain,’ they reported in 2020. ‘The breakthrough is
a major step towards integrating electronics with the body to create part
human, part robotic “cyborg” beings’.15
And PEDOT is indeed nice – squishy, stable, and kinder to cells. But is it
going to help you become a cyborg? Kip Ludwig, ever jaundiced after his many
years in the industry, can contain his enthusiasm: ‘This is not a game-changer
by any stretch.’ Though PEDOT has been approved for devices like catheters,
like the other polymers vying to usher in our cyborg future, PEDOT has some
obstacles to overcome before the FDA or other bodies will let you pop it in
someone’s brain. Yes, it may be the least offensive implant material we have
ever made, and yes, it conducts electrons with the best of the rigid metal
implants. There’s just one problem: we don’t speak electron.

Lost in translation

‘There’s a fundamental asymmetry between the devices that drive our

information economy and the tissues in the nervous system,’ Bettinger told
The Verge in 2018.16 ‘Your cell phone and your computer use electrons and
pass them back and forth as the fundamental unit of information. Neurons,
though, use ions like sodium and potassium. This matters because, to make a
simple analogy, that means you need to translate the language.’
‘One of the misnomers within the field actually is that I’m injecting current
through these electrodes,’ explains Kip Ludwig. ‘Not if I’m doing it right, I
don’t.’ The electrons that travel down a platinum or titanium wire to the
implant never make it into your brain tissue. Instead, they line up on the
electrode. This produces a negative charge, which pulls ions from the neurons
around it. ‘If I pull enough ions away from the tissue, I cause voltage-gated ion
channels to open,’ says Ludwig. That can – but doesn’t always – make a nerve
fire an action potential. Get nerves to fire. That’s it – that’s your only move.17
It may seem counterintuitive: the nervous system runs on action potentials,
so why wouldn’t it work to just try to write our own action potentials on top of
the brain’s own ones? The problem is that our attempts to write action
potentials can be incredibly ham-fisted, says Ludwig.18 They don’t always do
what we think they do. For one thing, our tools are nowhere near precise
enough to hit only the exact neurons we are trying to stimulate. So the implant
sits in the middle of a bunch of different cells, sweeping up and activating
unrelated neurons with its electric field. Remember how I said glia were
traditionally considered the brain’s janitorial staff ? Well, more recently it
emerged that they also do some information processing – and our clumsy
electrodes will fire them too, to unknown effects. ‘It’s like pulling the stopper
on your bathtub and only trying to move one of three toy boats in the
bathwater,’ says Ludwig. And even if we do manage to hit the neurons we’re
trying to, there’s no guarantee that the stimulation is hitting it in the correct
location.
 To bring electroceuticals into medicine, we really need better techniques to
talk to cells. If the electron-to-ion language barrier is an obstacle to talking to
neurons, it’s an absolute non-starter for cells that don’t use action potentials,
like the ones that we are trying to target with next-generation electrical
interventions, including skin cells, bone cells, and the rest. If we want to
control the membrane voltage of cancer cells to coax them back to normal
behaviour; if we want to nudge the wound current in skin or bone cells; if we
want to control the fate of a stem cell – none of that is achievable with our
one and only tool of making a nerve fire an action potential. We need a bigger
toolkit. Luckily, this is the objective for a fast-growing area of research looking
to make devices, computing elements, and wiring that can talk to ions in their
native tongue.
Several research groups are working on ‘mixed conduction’, a project
whose goal is devices that can speak bioelectricity. It relies heavily on plastics
and advanced polymers with long names that often include punctuation and
numbers. If the goal is a DBS electrode you can keep in the brain for more
than ten years, these materials will need to safely interact with the body’s native
tissues for much longer than they do now. And that search is far from over.
People are understandably beginning to wonder: why not just skip the
middle man and actually make this stuff out of biological materials instead of
manufacturing polymers? Why not learn how nature does it?19
It’s been tried before. In the 1970s, there was a flurry of interest in using
coral for bone grafts instead of autografts.20 Instead of a traumatic double-
surgery to harvest the necessary bone tissue from a different part of the body,
coral implants acted as a scaffold to let the body’s new bone cells grow into
and form the new bone. Coral is naturally osteoconductive, which means new
bone cells happily slide onto it and find it an agreeable place to proliferate. It’s
also biodegradable: after the bone grew onto it, the coral was gradually
absorbed, metabolised, and then excreted by the body. Steady improvements
have produced few inflammatory responses or complications. Now there are
several companies growing specialised coral for bone grafts and implants.21
After the success of coral, people began to take a closer look at marine
sources for biomaterials. This field is now rapidly evolving – thanks to new
processing methods which have made it possible to harvest a lot of useful
materials from what used to be just marine waste, the last decade has seen an
increasing number of biomaterials that originate from marine organisms.22
These include replacement sources for gelatin (snails), collagen (jellyfish), and
keratin (sponges), marine sources of which are plentiful, biocompatible, and
biodegradable. And not just inside the body – one reason interest in these has
spiked is the effort to move away from polluting synthetic plastic materials.
Apart from all the other benefits of marine-derived dupes, they’re also able
to conduct an ion current. That was what Marco Rolandi was thinking about
in 2010 when he and his colleagues at the University of Washington built a
transistor out of a piece of squid.

The squid redux

A transistor is a little piece of silicon in your laptop that can switch on or off
the electrical current flowing through it. I don’t want to talk about transistors
any more than I have to, so please trust me that it is the fundamental unit of
modern computing, and that billions of these little guys are stuffed into your
laptop and your phone and all your other digital electronics, and they are
responsible for the astonishing capabilities of these machines.
Rolandi’s transistor looked nothing like the highly sophisticated, exquisitely
etched devices that sit in your laptop. It was neither processed nor exquisite,
just a few soggy-looking nanofibres of chitosan, a material derived from squid
pen, which is a vestigial internal hard bit descended from the animal’s ancestral
mollusc shell. It’s soft and pliable enough that a brain implant would likely
cause minimal scarring, but that wasn’t its main advantage. The appeal of this
transistor was that, unlike the fancy semiconductors that act as gatehouses for
electron currents, this one was able to control the flow of protons.
So why are we so excited about protons?
You might remember from Chapter 7, protons are just hydrogen ions.
Researchers understand them well, because their contributions to the reactions
that make energy in the cell have been studied to death.23 Protons are also the
main component that determines the acidity inside and outside cells. These are
among the most thoroughly picked-over mechanisms in biology.24 So far, so
boring, if I can be frank.
Here’s something about protons that is not boring: they are able to control
the membrane voltage of a cell, and thereby control sodium and potassium
and voltage, and thereby cell identity, during regeneration and cancer. ‘It
doesn’t matter which ions or ion channels you use as long as you can control
the voltage,’ says Dany Spencer Adams. ‘What’s important is the bioelectric
state they create.’ Protons were the easiest to use. You just had to borrow a
gene from yeast to make them. Adams and Levin used this insight to create
that mirror-image organ condition in frog embryos.
Controlling the flow of protons would do something that has not been
possible – combine the effectiveness of drugs with the local precision of
electrical zaps. If you could make an electrical device that could manipulate the
proton gradients the way they were altered to make frogs regenerate – but in a
more tailored way than a drug could – well, then you’d have a whole new
option for bioelectric medicine, a best of both worlds to combine the power of
ion-channel drugs and electroceuticals.
Actually, the more you learn about protons, the easier it is to understand
what Rolandi found so compelling about a device that could control their flow.
If you can manipulate protons in a cell, it becomes possible to do precision
tweaks of cellular electricity without involving electrons – or other ions. ‘It’s
really easy to use,’ Adams says. ‘A proton pump is nothing fancy – it’s just a
single protein.’ That means it is easy to get into the body. After isolating these
proteins from yeast, Adams then simply injected them into the frog embryos.
‘[The proton pump] assembles itself.’ That current changed the concentration
of protons in the cells, which changed the membrane voltage, which then
changed the identity of the cells. Soon, in Adams’ experiment, the once-non-
regenerating cells agreed to start regenerating again. The reverse was also true:
she was able to stop a regenerating frog from being able to do so by poisoning
one of its hydrogen pumps to keep it from working. ‘But it doesn’t matter how
you inject those protons or control them,’ she says. ‘The only thing that
matters is the voltage.’
In the decade or so since he first made that early smudge of chitosan,
Rolandi has honed his device and made many more. And he’s not alone.
Biological materials from cephalopods are an increasingly attractive research
area in general. Chitosan, for example, turns out to be much better at
absorbing large amounts of blood than traditional bandages, so it is widely
used in wound dressings for military applications.
But it’s their electrical properties that have drawn researchers to look more
closely at various parts of the squid. The chitosan from its pen conducts not
just protons, but other ions as well. A reflective protein in squid skin called –
of course – reflectin is also a conductor of protons. Even the ink that jets
defensively out of a squid contains eumelanin, which is capable of mixed
conduction.25
As these properties came to light, more people started tinkering with the
materials to see whether they could make a device that could control a non-
electron current. Alon Gorodetsky, a chemical engineer at the University of
California Irvine, has concluded that reflectin conducts protons fast enough to
make it a plausible material for a proton-based protonic transistor – just as the
transistor is the basic unit of computation that makes the current flow in your
electronic devices, a proton transistor might make ions flow instead.26
Gorodetsky and his group have also been testing materials from arthropods,
and they think these will form the next generation of biocompatible proton-
conducting materials and protonic devices.27 They may even be the basis of
edible batteries, which could also be useful for implants.28
But for all the advances in the field since his first foray into squidtronics,
Rolandi has moved away from cephalopods. ‘We gravitated towards the
biomaterial routes at the beginning,’ he told me, huffing through an early
morning hike near the University of California’s idyllic Santa Cruz campus,
where he is now the chair of the engineering department. ‘Back then, my
thinking hadn’t really crystallised yet.’ More than a decade after his first foray
into biological electronics, he’s agnostic about what kind of material he uses.
The real prize, he realised, was the ability – by any means – to control protons.
Rolandi started making proton devices to tweak cellular currents out of
silver chloride and palladium. The upshot was that protons might be a stopgap
until we can figure out how to interface with individual ions and individual
channels, and offer a more precise interaction and control than electrons
provide. A 2017 paper Rolandi wrote landed on Michael Levin’s desk, and he
got in touch. He knew exactly what he wanted to do with such a capability.
Levin had found that a cell’s fate (bone, neuron, fat, etc.) is tied to their
membrane voltage, as we’ve discussed. Fat cells tended to be around -50
millivolts with respect to the extracellular fluid. Bone cells were the most
polarised, at -90. Skin and neurons hovered in the middle around -70. He had
also seen that stem cells were nearly at 0, and as their membrane polarised so
did their identity develop in accordance with the amount. Now he wanted to
tune a stem cell’s voltage himself and thereby control its destiny. If you could
reliably drive it to become a fat cell, or a bone cell, or a neuron, this would be
proof that electricity could be used as a control system for a dizzying amount
of genetic and chemical processes.
But how could he keep a living cell in a constant state for enough time that
it would differentiate into something new – probably hours, possibly days?
The problem with cells is that they are homeostatic – if something perturbs
their voltage, they will quickly rebalance. In the body, that problem is solved
because the microenvironment around the cell exerts constant regulatory
signalling. No existing tool in an electrophysiologist’s repertoire was capable of
mimicking this.
Then DARPA swooped in to help. It has a long history of investing heavily
in research to advance, for example, new directions in prosthetic limbs and
neuroprosthetics. Around the time Rolandi met Levin, DARPA also developed
an interest in bioelectricity, thanks to the arrival of a new program manager
called Paul Sheehan, who had been deeply influenced by Rolandi’s proton
transistor. (In the course of a previous appointment at the US Naval Research
Laboratory, Sheehan had used proton pumps to design colour-changing
bioelectronic devices, based on squid camouflage.29)
Now that he had a purse at DARPA, Sheehan gave Rolandi and Levin
money for their stem cell fate project. With the money, Rolandi and Levin
brought Marcella Gomez onboard. Gomez is a mathematical and systems
biologist at Santa Cruz with a background in control theory and cybernetics.
She knows her way around mathematical tools that can drive biology and
realised what they needed was a machine learning system that could monitor
the constantly changing voltage of the cells and act on it in real time. So she
made one.
The team put stem cells into an array with a device of Rolandi’s design,
which injected a proton current around the cell to drive its membrane voltage
up. Whenever a cell would engage any of its channels to try to get back to a
more comfortable voltage, Gomez’s AI would notice and inject more proton
current. It was able to consistently keep the membrane voltage of living stem
cells 10 millivolts higher than the cell’s usual depolarised baseline. In 2020, the
trio published the results of Gomez’s remarkable new tool, which had
managed to continuously impose the artificial voltage for ten hours. No one
had ever done that before.
As they were working out how to extend that voltage window so that they
could watch the stem cell differentiate, however, funding ran out.
But that turned out to be okay, because by then, they had given Sheehan all
the evidence he needed to launch the much bigger project he had been
planning. At the beginning of 2020, DARPA launched the $16 million BETR
(Bioelectronics for Tissue Regeneration) programme – a pretty hefty chunk of
money even by DARPA standards – whose goal is a radically expedited healing
process for wounds.30 This has not been possible with traditional electronics
(or anything else, for that matter). While individual studies on electrical
stimulation for healing have sometimes had promising results, no one could
ever give you a specific recipe for how to make it work every time in every
patient. Sheehan had seen enough of the research to suspect that speaking to
the body in its own language might be the way out of the impasse. ‘I wanted to
pivot to bioelectricity mediated by ions, instead of just a voltage,’ he told me.
‘Right now, it is very challenging to go from electrical to biochemical signals
and vice versa. That’s what this programme is trying to do.’ He wants to
improve every aspect of wound healing, from better sensors and actuators to
creating better models of how healing actually works.
There are so many things we don’t know about wounds, and this is why no
one has come up with advances to make them heal better or faster. One
problem is that every wound is different. Sheehan ticked off the list for me.
‘The edge of a wound is different from the centre. A cut on your foot heals at
a different rate than a cut on your face. Young people heal faster than old
people.’
Rolandi’s group is using bioelectronics to control different aspects of
wound regeneration. Instead of just applying an electric field and hoping for
general improvements, the idea is to be specific. The team monitors specific
wound processes (like the inflammation stage) with sensors. Gomez’s
algorithms then process information from these sensors into actionable items,
for example to deliver ions or an electric field to the wound to calm
macrophages faster in a bid to accelerate the healing process. They couldn’t get
that granular without more diverse tools at their disposal. ‘Otherwise it would
be like, great, you’ve detected all this stuff, and you have this very complicated
algorithm, and now all you can do with the information is shoot an electron at
it,’ says Rolandi. ‘That’s just not going to cut it.’
But just as the stem cell project was for Sheehan a stepping stone to the
BETR project, so is BETR a step to something bigger. ‘Wound healing is a
great initial problem to go after,’ he said. ‘But if you look across the board,
there are many different places in medicine where you want to have control
over the delivery of a drug compound.’ One oft-cited example is delivering
specifically targeted medicines to a tumour, but a generic interface could also
choose the time of delivery not just the place. Any oncologist will tell you that
they wish cancer medications could be administered to their patients at night
when they’re asleep, because that is when the body is regenerating. What’s
more, during this resting period, some non-cancerous tissues that are most
sensitive to drugs are not dividing – administering noxious drugs then would
help reduce some of the adverse consequences. But of course you can’t
administer these drugs in the middle of the night. The doctors and nurses and
office managers are asleep too.
Hence Sheehan’s next goal: ‘What we really need is a generic interface with
biology that would enable us to deliver biological information into the body,’
he told me. ‘Cytokines, hormones, chemokines. Having a generic device that
could deliver those therapies would be like having a twenty-four-hour doctor
right there,’ says Sheehan. Or for wounds, it would act as a twenty-four-hour
surgeon on call. As it happens, that was one of the selling points of the
xenobots.

Frog robots and fungus computers

When Michael Levin first started dismantling the frog embryos, he wanted to
understand what happens to living cells when they are freed from the
constraints of the electrical signals sent by their bioelectric environment. You
remember from Chapter 7 that he and a coterie of other scientists believe that
these cues are a crucial authority that instructs cells which shape to assume
and where, and that this guidance is crucial to whether those cells cooperate in
their trillions to properly form us in the womb.
But how do you put that idea to the test? ‘The xenobots were a way of
asking: here are a bunch of cells, how do they specify what they should be
building, in the absence of any guidance?’ Levin told me. ‘The big picture is
not about having robots made of frog cells, or in fact, robots made of any
cells. The idea here is that we need to understand how collections of
competent agents work together towards large goals.’ That would have
obvious corollaries in regenerative medicine: how do cells get together and
agree on building something large, like an organ, or in fact, the whole body? It
might also yield insights into why and under what circumstances cells opt for
an ‘every man for himself ’ approach to become cancerous.
‘Everything in my lab focuses on this idea of how many become one,’ he
says. ‘How is it that lots of small competent agents get together to have a
single unified cognitive system that has a goal state?’ If we understand how
that works, then rebuilding organs, reprogramming tumours, fixing birth
defects, and reversing aging really does just become a matter of programming.
‘Everything boils down to the question of convincing cells to build one thing
rather than whatever they’re currently doing,’ he says.
So he decided to see what the cells would do in the absence of the cues.
He and his collaborators scraped a few thousand cells off a frog embryo. Then
they put them into a completely different, neutral environment and waited to
see what they would make of their newfound independence. The cells had a
lot of options. They could have just died. All the cells could have struck out on
their own. They could have formed themselves into a single layered ‘skin’ that
lay in a flat plane like a cell culture.
They did none of that.
Instead, a few thousand of them got together and made something new.
Somehow, they agreed among themselves to glom together into a new
architecture, little discrete balls. Then each of them grew cilia, which in itself
wasn’t unusual. These little hairs grow on the outer surface of normally
developing embryos to move the mucus around the body and keep it clean –
what was unusual was how they put them to use. ‘These cells basically
repurposed that genetically encoded hardware,’ Levin says. Now, instead of
using their cilia to move the mucus, they used them to move themselves –
even though they didn’t have any nervous system to either conjure intent or
act on that intent. Nonetheless, with their new equipment in place, they started
coasting around. ‘We have these amazing videos of the little clumps moving
around. Sometimes they formed little groups, interacted in various
configurations, they even went through a maze.’
And even though they were just clumps of cells with no brain or nervous
system, they even seemed to have preferences. When Levin cut them nearly in
half, they regenerated, always seeming to favour reconstituting themselves into
the little spherical shapes they had originally assumed, if a ball of 2,000 frog
cells can be said to prefer something. Xenobots indeed. ‘These are neither a
traditional robot nor a known species of animal. It’s a new class of artifact: a
living, programmable organism,’ said Joshua Bongard, the roboticist on the
team.
So far, the only thing that is strictly programmable about them is their
shape and their lifespan. The xenobots don’t have digestive systems and so
their cells are instantiated with a little yolk sac containing a fixed amount of
fuel. When that runs out, they die. That does seem to be the main advantage
of using living systems as robots – living systems die, which rules out the
horror scenario of xenobots overrunning the world.
Or maybe not. By the end of 2021, they had been programmed to
reproduce.31 They had not built themselves novel sex organs – instead, they
used their Pacman-like mouths to scoop up cells into groups of roughly the
same size as themselves, which then themselves aggregated into new lifeforms.
They made new creatures like themselves. It was a method of reproduction
that was new to the evolutionary history of the planet. Nearly five years into
working on the creatures, Levin is unequivocal: they are alive – ‘under any
reasonable definition of life’. No wonder ethicists began to worry. ‘Is this as
much of a Pandora’s Box as it sounds?’ wrote two of them not long after the
self-reproduction study was published, raising a range of possible adverse
consequences and wondering whether science needed more limits placed on it
to avoid them.32 ‘Although xenobots are not currently made from human
embryos or stem cells, it is conceivable they could be,’ they wrote.
Andrew Adamatzky thinks biology is the inevitable future of implants, but
where others are working with frogs and squids, his money is on fungus.
Adamatzky is a professor of unconventional computing at the University of
the West of England, where he has created a computer model of the mycelial
electrical activity and encoded the spikes into logical functions, a bit like
AND/OR functions transistors are able to create in traditional computing.33
Once we have these for the body, why not for the environment?
The future is not diving to the bottom of a reef to source some coral for
your hip. The future is to understand the properties of biomaterials that make
them good interfaces, and then make a steady supply of them, tuned to the
properties that can best interface with the body – synthetic coral, synthetic
squid pen, to ensure a steady supply of materials whose quality is as unerring
as the silicon crystals that now make semiconductor wafers.
While we wait for the new ion-channel drugs, the new trials, and the
biological implants (none of which are guaranteed to be with us in ten years),
there is another option for electroceuticals: non-invasive wearables that can do
it all from outside the skin.
 CHAPTER 10

Electrifying ourselves better: New

brains and bodies through
electrochemistry

M ike Weisend plucked two bespoke electrodes from their nest of

protective foam: these were the large daisy-shaped discs that would
channel the electricity through my brain. He asked me to hold one to my right
temple as he strapped it to my head with gauze. Then he squirted a large gloop
of the green liquid into the cut-outs. He explained that the daisy at my temple
– and the other at my arm – would pass a harmless amount of current through
my skull.
We walked into a windowless grey office that the lab’s decorators had done
their level best to turn into a military theatre of operations. At one end was a
mound of sandbags, piled up about shoulder height. Resting against it was a
big M4 rifle: a model often used for close combat. I shouldered it. Against a
wall about ten feet in front of the sandbags was a projection of a training
simulation called DARWARS Ambush!
I was there to try an experimental technology called transcranial direct
current stimulation (tDCS for short). I had first encountered the idea at a
military conference put on by DARPA, the division of the US military that has
birthed world-changing breakthrough technology like the internet, GPS, and
lasers. (Their conference has since been discontinued, probably because it
allowed nosy journalists like me to find scientists who were accelerating
soldiers’ learning by zapping their brains with an electrical current.) There, I
had learned about a new technique they were using to speed up sniper training,
using bursts of electricity administered to the cranium. They were guarding
this programme so closely that it took four years of pleading with DARPA
before they would agree to so much as a twenty-minute follow-up call. Little
wonder, given their results: ‘For soldiers who are learning marksmanship,
we’ve been able to cut the time it takes to get them from novice to expert in
half,’ the programme manager told me on that phone call. They had achieved
similar results for languages and physics.
Did I really want to take these remarkable results at their word? What I
really needed was someone who could tell me what it was like, and they
wouldn’t let me meet any of the soldiers from the trials. ‘Can I try it?’ I
ventured.
A short pause, and then there was an intake of breath as if he was about to
talk. ‘I’ll sign any waiver you need me to sign,’ I pre-empted, already
intoxicated by visions of my own electrically mediated virtuosity.
Another pause, this one longer and definitely with the speaker-phone
muted. ‘You’d need to come to California—’
‘Okay!’ I said, before he could finish the sentence.
About a month later, I was on my way to the US west coast. In the fast
run-up to this experiment, and my general excitement, I had made some poor
judgement calls. The first was scheduling the meeting the morning after an
eleven-hour flight from London to California, at the wrong time and in the
wrong direction for sleep. Then there was the drive up and down the
mountains where I had decided to stay with a friend to save New Scientist the
hundred dollars for the hotel room. It turns out the LA mountains are a lot
higher that you’d expect. Thanks to jetlag and altitude sickness, I hadn’t
managed to sleep in more than thirty-minute chunks since I’d boarded the
plane. Fuelled by dangerous amounts of coffee, I drove down the sickening
decline in the pre-dawn blackness, crying a little bit and shrilly repeating the
mantra, ‘Great, I guess this is how I die!’ And that was before I hit the traffic.
By the time I arrived to meet the team, I was too busy berating myself to
consider how I was going to approach the challenge that lay ahead. Four years
of chasing this story across two jobs, a transatlantic and transcontinental flight
– and I hadn’t bothered to allow any time to prepare my brain for a
neuroscience experiment? I would have got a better story just by transcribing
the DARPA interview I had conducted from my desk chair in London. I
quaked silently with self-directed rage.
Michael Weisend’s waist-length fall of salt-and-pepper hair didn’t increase
my confidence. Weisend, a neuroscientist who at the time was with the
University of New Mexico, had been kind enough to fly to California that
morning to demonstrate his electrical apparatus. He took me into a small
room where I found a bulky suitcase whose foam-padded insides nestled
around an assortment of wires, a squeezy bottle full of ominous neon green
liquid, and a beige box festooned with switches and dials, which housed a 9-
volt battery. Weisend chortled as he unpacked the ingredients. ‘Can you
imagine getting this stuff past airport security?’
After Weisend had finished attaching the electrodes to my body, he tucked
the chunky rig into the back of my bra. ‘You’re all set,’ he said. It was time to
go to war.
It started easily enough, with some electricity-free target practice, during
which I familiarised myself with the weight and heft of the modified gun. I
found myself in a simulated desert, no sound but whistling wind, facing a row
of roughly humanoid metal targets. Whenever I hit one, the bullet ricocheted
off with a satisfyingly realistic ping. A series of these scenes followed. I did all
right despite the fatigue.
Weisend came back in. ‘Okay, now we’re going to see if we can make this
as realistic as possible,’ he said, fiddling with the box behind me – he meant he
was going to try to approximate the control and sham condition on a clinical
trial. That would require me having no idea whether or not the electricity was
on, so that I wouldn’t get messed around by the placebo effect. ‘I’m going to
come in a bunch of times, but I’m not going to tell you when I turn the
electricity on.’ This wouldn’t have passed a review, but then I wasn’t actually
participating in a clinical trial. This was an anecdote, and I was a tourist.
He left, and the quiet dunes and targets dissolved. I became a sniper at a
checkpoint. More specifically: I became a terrible sniper. I was a nervous wreck
even before anything happened. My eyes flickered back and forth manically
between the building and the incoming cars. Any minute now something
would happen, but I didn’t know what.
It was almost a relief when the bomb went off. As the white blast faded, a
man ran at me wearing an explosive vest. You may recall the rest from the
introduction of this book. The simulation faded out in a grey mist.
The tech came in and reset my rifle, and I re-spawned once more into the
checkpoint. This time I knew what was coming, and was prepared for the first
bomber. I also managed to dispatch the shooters on the roof, but after the
second bomber came at me, suddenly dozens came running impossibly fast
from several directions at once. Grey mist.
I can’t remember how many more times I went through it – three?
Twenty? All I know is that every session seemed interminable, and by the time
the lights came up the last time, I just wanted it to stop.
I was also beginning to wonder if the whole thing was a scam. Recently
published experiments showed tDCS-enhanced training increased a sniper’s
ability to detect a threat by a factor of 2.3, but I wasn’t seeing any of those
results. After all, there is a long history of defence contractors in the US
overinterpreting – or sometimes downright falsifying – their research for eager
government procurement officers. I was getting steadily more resentful,
dreading the drive back through the traffic, reeling with fatigue.
Weisend came in and fiddled with the device again. I tasted metal, a bit like
I’d just licked the tab on an aluminium can. This was it – even though I wasn’t
supposed to know the sham experiment from the real, my permanent dental
retainer had given it away. Despite my earlier scepticism, I was suddenly
excited. I waited for my Matrix moment. Any minute, new information would
rain into my mind like 1990s-movie code hieroglyphics, filling me with the
sudden ability to comprehend the physics of shooting. But that still didn’t
happen. There was only the metallic taste. I sighed heavily and resigned myself
to another humiliating in-game death.
‘I’ll see you in a little while,’ Weisend said, and left. The lights went down
again. And without much fanfare, I calmly dispatched all comers in a session
that felt like it took three minutes, though Weisend (and the tech, and several
wall clocks) would assure me that it was twenty.
‘How many did I get?’ I asked the tech when the lights came up. You know
the rest.
The question I began asking myself back then, and that has continued to
drive me since: how is it possible that an electrical current that lights up your
laptop can manipulate the delicate natural electricity that makes the body run,
to such staggering effect? And when can I get a device of my own? And
should any of us be able to do this?
After the experiment, I developed a particular obsession with question
number two. I remember being at a work social function a few months later,
and surprised myself by welling up as I recounted the experience to one of my
colleagues. It went beyond the experience in the lab itself. It was the drive back
from the lab – I wove calmly in and out of traffic, and driving was so pleasant,
where it’s more often a white-knuckle gritted-teeth affair for me. It was the
following three days, over the course of which I approached incoming
problems exactly the way I had approached those fake assailants: calmly,
without panic, without the complicated ritual where I first needed to dredge
up the lifelong list of my own failures and genuflect before my own
worthlessness. That bottomless font had suddenly dried up. And that meant all
of a sudden, life was so much easier. Who knew you could just, like, do stuff
without first performing the elaborate dance of psychological self-
recrimination?
 And how the fuck, excuse my language, had a little electrical zap done all
of that?
One theory had been that this was a non-invasive way to boost alpha
oscillations. These, as you might recall from Chapter 5, were discovered by
Hans Berger. For the better part of a century, the oscillations he identified
were thought to be epiphenomena, mere ‘exhaust fumes’ of the brain: they
could tell you simple things like whether the engine was running, and even
sometimes dispensed limited information about its condition. For example, in
the 1930s studying oscillations with EEG helped Alfred Loomis advance the
study of sleep science. The now common idea that sleep happens in stages like
REM and non-REM would be inconceivable without these different telltale
waveforms to tell them apart.
A handful of animal experiments had suggested you could technically alter
brainwaves but without the invasive precision of a penetrating implant, you
couldn’t target specific functions, and there wasn’t a use case for doing so in a
human, even if you could get approval.
That all changed in 2000, when two neurologists at the University of
Göttingen in Germany, Walter Paulus and Michael Nitsche, published a paper
describing a new technique called transcranial direct current stimulation. With
tDCS, it was possible to alter the rhythms of the oscillations without brain
surgery – and see if changing the rhythms would change a person’s behaviour
or mental state. It was relatively easy and safe: strap two electrodes to a
volunteer’s head, position them over the brain areas of interest, and set a very
mild current flowing (anywhere between 1 and 2 milliamps). In 2003, Paulus’s
team published an experiment that seemed to show that tDCS could boost
cognitive performance, accelerating people’s ability to learn a random sequence
of keystrokes on a computer keyboard.1 ‘It was like giving a small cup of
coffee to a relatively focal part of your brain,’ one of his co-authors told New
Scientist.2
That’s when tDCS exploded. Now everyone was on the hunt for ways to
improve the brain with this easy new tool. A year later, Lisa Marshall at the
University of Lübeck sharpened people’s memories by boosting the size of a
kind of squiggle called a sleep spindle with short bursts of tDCS, as they
slept.3 The next morning, they could better recall word pairs they learned the
previous day than people who hadn’t had their brains sleep-zapped. Other
researchers jumped to replicate this and other mental boosts. At universities
like Oxford, Harvard, and Charité, a little bit of electricity enhanced memory,
mathematical skills, attention and focus, and creativity. By 2010, thousands of
papers had been published, purporting to show the effects of electrification on
memory and cognition.
Here’s the problem. It did not do that for everyone. It didn’t even reliably
do it for me. As I mentioned in the introduction, while tDCS worked a treat
for sharp-shooting, it didn’t touch my mathematical deficiencies.
Extraordinary claims require extraordinary proof. It began to emerge that
many of the studies whose dramatic results had been so widely reported didn’t
even have ordinary proof. They had been drastically underpowered, with
participant numbers straining credulity in the low single digits. Some had no
control group at all – science’s mortal sin. It wasn’t just the badly done science
that was posing a problem for tDCS. Even the good studies were under siege,
because there was no firm consensus about how exactly tDCS was supposed
to be creating all these effects. Meanwhile, a number of the people who had
purchased one of the many new home tDCS kits began to complain that they
had no effect.
Then a couple of studies were published that raised the question of
whether tDCS was a giant scam. In one somewhat gruesome experiment, New
York University researchers tested the effects of the standard tDCS dose – the
same 2 milliamps I had experienced in California – on a cadaver. That dose
didn’t even send enough electricity through the skull to show up in the brain,
they said: 90 per cent dribbled away into other parts of the body, including the
skin of the scalp. How could something like that have any effects on
cognition? Even the researcher who had done the DARPA protocol on me
was sympathetic to the naysayers. ‘For every good study, there are an equal
number that throw shit at a wall to see if it sticks,’ he told me.
Indeed, by 2016, what had started out as a way to probe the functional role
of oscillations had turned into a full-blown putative panacea. You name it,
someone had got a grant to zap it out of someone. ‘Here is a list of everything
tDCS is supposed to work for,’ declared Vincent Walsh of the University
College London’s Institute of Cognitive Neuroscience at a tDCS summit,
before enumerating a list that included schizophrenia, eating disorders,
depression, migraine, epilepsy, pain, MS, addictive behaviour, poor reasoning,
and autism, and stretched from there into the double digits.4 ‘Do me a favour .
. .’ he said, voice dripping with the finest British vinegar. He was certainly not
alone in being reminded of the post-Galvani era of electroquackery.
This was happening because it had not taken long for the focus to shift
from oscillations to the tool to manipulate them – and somewhere along the
way, the oscillations themselves got lost in the shuffle. Silicon Valley, too, had
interest in ‘overclocking’ the brain and funded development into alpha wave-
boosting technologies – and a tidal wave of gadgets emerged for home use,
none of which seemed to actually work. The overfocus on tDCS (Did it work?
Did it change the brain? Were action potentials being generated?) obscured the
point of using the tool in the first place, which was to see if brain-wide
oscillations – not individual action potentials in individual brain areas – could
be altered to have behavioural consequences.
As the tDCS controversy died down, other approaches to boosting alpha
oscillations renewed the focus on oscillations and whether they were
functional. Transcranial magnetic stimulation (being zapped by a giant
magnet), deep brain stimulation, and transcranial alternating current
stimulation (which wasn’t galvanic current but a fast series of pulses that
switch really quickly from negative to positive current flow) painted a vast new
picture about oscillations: not only could they tell you deep realities about
what was going on in the brain, but changing them could change the related
behaviour.
For all his vinegar, Walsh is not even a kneejerk tDCS sceptic – he has
contributed his own studies to the canon. What made him (and Kip Ludwig,
and many others) so grumpy about tDCS is how credulously small studies
were being reported to, and in, the press. Some of them were barely more
credible than my (completely unreliable) gonzo stunt. And yet, people didn’t
get to read about the fact that the studies didn’t have proper control and only
five subjects. They read about their promise and saw the device was non-
invasive and thought that was equivalent to not having any risks. So, many of
them decided to make one for themselves. Reddit has a board dedicated to
overclocking your brain, where they offer circuit diagrams and other
instructions. I sympathise. Full disclosure, I ended up buying a brain stimulator
myself (I don’t have the talent to make one). I still couldn’t tell you
conclusively whether it’s placebo or not. I only use it when my brain comes at
me with the List.
Lucky me – some people who built their own rigs suffered dire
consequences, blinding and burning themselves trying to replicate the exact
parameters that would effectively stimulate their brains. Enough that a group
of neuroscientists published an open letter begging them to stop.5

Déjà vu all over again

Over the past few years, more tDCS studies have proliferated. Like all
bioelectric treatments, it works or doesn’t based on the tiniest and most
unpredictable factors. There are dozens of variables to account for when
designing the experiments. You even have to account for variability in skull
thickness! (Insert joke here.) Some people get lucky and happen to have the
right kind of parameters to go with the electrical stimulation they’re given.
That seems to have been the case for me, as I inferred several years later
after a chance conversation with a researcher who studies the effects of tDCS
on depression. When I told her that my negative self-talk had been cleared
away like so much San Francisco morning fog by the electricity, she lit up. She
said she had identified a population of depressed people whose disease
manifests in this exact kind of castigating self-talk, where you just spend all
your energy on dragging yourself. Their symptoms were particularly lifted by
the intervention. But like Helen Mayberg’s deep brain stimulation quest in
Chapter 5, she was still figuring out how to discern responders from non-
responders.
The study of brain stimulation is not broken – it’s just really, really hard,
like science in general.6 There’s no conspiracy in science to get bad results past
peer reviewers; it’s just that any one single study can run into loads of
problems – not enough funding for sufficient numbers of trial participants,
researcher bias, non-standardised equipment, stimulation strengths – there are
so many parameters, you hardly know where to start.
But a clinical trial always has to start with some low number of patients (so
as to use few resources, which are supposed to be saved for the big final trial).
That’s standard. Their size makes them more prone to bias, though. That
doesn’t mean the early data from small trials is worthless, former NIH director
Kip Ludwig explains – it’s eventually supposed to feed into the big definitive
study that can tell you a big definitive result.
The trouble is we’ve forgotten that those early studies aren’t evidence – all
the shortcomings I mentioned above lead to a statistical scenario in which you
are quite likely to get a ‘false positive’ that your intervention works great (when
in reality it doesn’t). This is unfortunately what wound up happening with
Ivermectin and Hydroxychloroquine to treat Covid, where people who aren’t
scientists put too much stock into an early study or two, with too few patients
and flawed experimental designs. The later, more definitive, more resource-
intensive studies later revealed those early results to be a fluke. But by then the
misinformation was out there.
We might go through another round of this game of promise-and-
recrimination quite soon. Like tDCS, electroceuticals have gone non-invasive.
The therapy is now called ‘vagus nerve stimulation technology’, or VNS. It’s
getting a large infusion of cash from Silicon Valley and is all over social media,
but hasn’t quite taken the form that was predicted ten years ago. Instead of
supporting penetrating implants, most investors are backing non-invasive
wearable technologies that try to affect the nerve from atop unbroken skin,
such as little earbuds that stimulate the vagus as it climbs from the depths of
the body to nearly breach the surface of the skin at a spot just inside the ear.
Once again, it’s being mooted to help with focus, anxiety, depression . . . By
now you know the rest. Similar to tDCS, for each study that shows a hint of an
effect in a small number of patients – some of which aren’t very well done –
there is another study showing it doesn’t work.7
If we want to understand our electrome well enough to manipulate it
precisely with noninvasive gadgets, the first step is huge trials with invasive
technology that can conclusively show how the technology interfaces with our
bioelectricity.
This raises the question: who is going to let you open their brain to get
that data? Every tool and scrap of knowledge we have assembled about the
body’s electrical dimensions so far has been given by people for whom
enrolling in one of these studies is an option of last resort – from Catharina
Serafin’s heartbeat to Matt Nagle’s work with BrainGate to VNS pioneers.
Cancer cures, limb regrowth, reversing birth defects, neural upgrades, immune
modulation – that healthy people will use to upgrade themselves in the future
– rest on the next generation of test pilots.

The test pilots

Around the time she was trying to steer the FDA onto the right track with the
oscillating field stimulator, Jennifer French founded Neurotech Network, a
neurotechnology advocacy group that helps people with neurological injuries
find assistive technology that can help them in their specific circumstance.
‘Technology can become a great equaliser,’ she says. ‘It gives people choices.’
However, often people who design neurotechnologies can focus on the
kind of evidence that will moisten the eyes of people who are like them, at the
expense of things that will help the actual people who need the technology.
French understands why they do it. ‘Getting people walking again is sexy,’ she
says. Behind the scenes, after the media attention has died down, the
researchers will quietly file the grants that contain the sorts of priorities that
are actually important to people who have a spinal injury: pain, and bowel and
bladder control. ‘Addressing the true needs of this population doesn’t sell in
the media.’
Instead, the public message remains on what the disability studies scholar
Stella Young calls ‘inspiration porn’, and it has wide-reaching consequences.8
For example, those research videos of paralysed people walking make the
rounds on social media and in the traditional media. Shorn of their context –
which they often are, because you know how the internet works – they give
people a deeply skewed picture of what is possible if they get injured.
‘Every time one of those news stories comes out – Hey, we’ve cured spinal
cord injury, we have people up and walking! – that leaves a false impression,’ French
says. ‘Then the advocacy groups get tons of phone calls from people living
with the condition, asking “When can I get the cure?”’ It is not of course a
cure, and it falls to groups like hers to bring people down from the hype. The
media hype is destructive in more ways than one.
The misperception it seeds also makes it hard for people to have a clear
picture of what capabilities actually exist. This makes it difficult to objectively
evaluate whether to enrol in a trial.
When Phil Kennedy underwent voluntary, extremely risky (and potentially
unethical) surgery on himself, he was widely hailed in the tech press as a self-
sacrificing hero of science. And yet, with a few exceptions, the coverage of the
volunteers in clinical trials has little of this veneration. ‘The people who test
neurotechnology are test pilots every bit as much as Chuck Yeager or Buzz
Aldrin,’ French says. Just as those men risked their lives to expand science’s
understanding of the sound barrier and space flight, people who volunteer to
test new neurotechnologies should be understood as daredevils working – at
great risk to themselves – to take science into new frontiers.
Yeager and Aldrin (and Kennedy) knew the risks inside out before they
undertook their experimental flights. But there are no standards for how
clinicians should communicate expectations to people who volunteer for trials.
As many people join trials of new invasive experimental neurotechnology for
altruistic reasons as they do hoping this trial ends up being the cure or an aid.
Sometimes a volunteer comes into a trial desperate, their head filled with
misleading ideas from the ‘inspiration porn’. French is exasperated by this
because the people who join clinical trials are not guinea pigs, and should not
be condescended to or tantalised with false hope.
 Making someone a test pilot is only ethically possible when that person has
the full picture of everything that could go wrong, and precisely managed
expectations of what the technology can and can’t do. Right now, that kind of
transparency is not enforced. ‘We need to be really clear with people about
what this can do for them personally,’ French says. But there are no standards
clinicians must adhere to when advising their trial volunteers.
For one thing, anyone who designs bioelectric interfaces should look at the
ethical history of medical implants. We know about the grisly history of people
having implants against their will – but what about explants? A few people had
their experimental implants removed against their will after the companies that
made them went broke. I spent a few hours at a neuroscience conference a
couple of years ago talking through these issues with Frederic Gilbert, a
neuroscientist and philosopher at the University of Tasmania who studies
explantation.
Gilbert points in particular to a major ethical issue – potential trial
participants are often not told the whole story about the future of their
devices. A study from Rice University and Baylor College of Medicine found
that potential study participants are generally soft-shoed when it comes to
what will happen to their implants after a trial has concluded.
A typical case would involve a person with a treatment-resistant disease
that was robbing her of her quality of life. Maybe she could no longer drive or
work. As a last resort, she would join a clinical trial of an implant that
promised to change all of that. The implant would work. Soon she could drive,
make plans, and regain the fairly predictable life most of us take for granted.
But her implant was an experimental device, and when the neurotech start-
up that had implanted her found their device did not work for everyone in the
trial, the company collapsed into bankruptcy. The insolvent company could no
longer support their devices, so they needed them back. That meant another
brain surgery to remove the investigational device. She was unprepared to
return to life before the implant. She did not consent to having the device
removed, or to the brain surgery. ‘How are you supposed to recover these
devices?’ Gilbert asked me. ‘Do you hunt these people down? It becomes like
something out of Blade Runner.’9
When radical new medical technologies are successful, the tech press
reports breathlessly on paralysed people who can eat grapes, or trial results
that unlock another thing brain implants could ameliorate. But what happens
when the trials are over? The tech press is a little harder to locate.
You might be wondering: why can’t these devices stay in? Usually it’s
because they need long-term tech support a failed start-up won’t be able to
provide. Stimulator batteries need to be changed, or stimulation frequencies
adjusted. There needs to be someone in charge of medical check-ups for
people with implants bedded down in their grey matter. In rare cases, this is
possible – if the person in charge of your clinical trial happens to be Helen
Mayberg. You could call Mayberg the doyenne of DBS – after a long and
prestigious career at Emory University, the Icahn School of Medicine at New
York’s Mount Sinai Hospital created a new Center for Advanced Circuit
Therapeutics just so she could run it. When you implant patients, she says, you
own them. ‘Not in the sense that you can do what you want with them – it’s
the opposite,’ she says. You now bear a lifelong responsibility to them.
Mayberg is passionate about this and has clawed her way to letting her
participants keep their depression-busting DBS implants after a trial. But she is
also a big, powerful name in neuroscience with a lot of credentials to back her
up, institutional firepower at her behest, and university funding.
Hank Greely, a law professor at Stanford and an expert on ethics in
biosciences, thinks the answer is that before any neuro-engineering or
bioelectricity researchers run any kind of trial, the companies or universities
behind them should be forced to invest in something like a bond – ‘a common
fund that allows people to keep their devices, have them maintained and
repaired, and their batteries replaced,’ he says. ‘These people are not rats. You
don’t implant them, grab your data, and get rid of them.’
Today, French lends her expertise to several neuroethics panels and patient
advocacy panels, including the National Institutes of Health, the BRAIN
initiative, and the Institute for Electrical and Electronics Engineers, which is
working on a framework for neuroethics around medical devices and
neurotechnology devices. All the new standards aim to ensure full disclosure
for the volunteers who are trialling deep brain stimulation, spinal stimulators,
and other next-generation neurotech. This is part of the larger neuro-rights
initiative that is gaining traction, most recently having been written into law in
Chile in 2021.10

Don’t mess with the electrics

More volunteers, who are better informed, will accelerate our understanding of
neural implants, electroceuticals and other kinds of electrical intervention. But
electrical stimulation is not the only way we are impacting our normal
bioelectric functions.
We’re starting to look for future electro-drugs in the ion-channel drugs we
have been using for decades. They are ion-channel manipulators, capable of
either blocking them, prying them open, or otherwise messing with their state.
As we saw in Chapters 7 and 8, a more complete understanding of their
significance in bioelectric signalling is driving new research into how these
drugs could be repurposed for cancer therapies and regenerative medicine. But
it also opens up a more unsettling question: if we’re already taking so many of
these drugs, do we have a complete understanding of what they have been
doing to our electrome? Should we start figuring it out?
We started using drugs that acted on our ion channels long before we
actually knew about ion channels. We used them because they worked – we
figured out how they worked later.
In some, bioelectric side effects are already well understood. Most epilepsy
drugs, for example, are acknowledged to cause a range of birth abnormalities if
taken during pregnancy. As it turns out, this is because of how they muck with
our bioelectricity. Many of them suppress overactive sodium or calcium
channels, but while this helps to calm the relevant neurons and stop seizures,
increasing evidence suggests it may also disrupt the ion-channel
communications necessary to correctly pattern a foetal structure. In one
medication, the severity of the potential consequences – a significant risk of
lifelong learning and cognitive disabilities, and physical anomalies – have led to
restricting the medicine’s use in people who can get pregnant, during peak
reproductive age.
Epileptic drugs are far from the only ones with wide-ranging effects on
ion channels – and yet there has been little research into how others might
mess with the complex ways ion channels are involved in development. Like
Kip Ludwig, Emily Bates works on the nitty-gritty details of bioelectricity, but
she does it as a developmental biologist at the University of Colorado School
of Medicine. Bates had long wondered what other drugs can screw up the ion
channels and thereby result in birth defects.
A quick caveat before I go on. It’s very, very early days for some of this
research. Talk of medical effects on development is often tinged with a
particular strain of prim authoritarianism. When you’re pregnant, you aren’t
‘allowed’ to do much of anything without conjuring stern words of concern. I
would be mortified if my book were used as yet another cudgel to shame
someone at a point in their lives when everything is already quite unsettling
enough. This is why it is so important to fund research that lets us know what
is safe for a developing foetus.
Bates decided to focus on drugs for which a robust body of research
already existed, to demonstrate their ill effects on pregnancy. Smoking, for
example, has been widely shown to ‘increase the risk of health problems for
developing babies, including preterm birth, and low birth weight’, confirms the
Centre for Disease Control, along with being firmly linked to birth defects of
the mouth and lip, like cleft palate. But it has been hard to tease out which of
the 7,000 ingredients in cigarettes is the culprit, as they contain such a vast
assortment of chemicals – including ammonia and lead – many of which are
implicated in cancer. This is part of the reason vaping has been quietly
accepted as a harm reduction campaign – it’s the nicotine without all the rest
of the stuff.11 Maybe nicotine in this form is still not great, and it’s not quite
doctor-recommended, but it’s no shock that smokers will often switch to
vaping when they become pregnant. And if they vape already, they may not try
to quit when they find they are pregnant. Either way, vaping nicotine often
results in a higher dose.12
Does foetal nicotine exposure cause birth defects? Bates exposed pregnant
mice to pure nicotine by putting them into a vaping chamber (essentially a
giant walk-in bong) and found that the newborns still had several characteristic
developmental problems: they had shorter bones, notably of the humerus and
femurs (correlated with shorter stature in humans), and the nicotine exposure
had altered their lung development.13 So nicotine was not the innocent
bystander here, as it was clearly causing these defects. So vapes, which provide
nicotine, are bad for a developing baby.
It’s not yet possible to neatly tie these physical effects to a mechanism. But
there’s a lot of other research whose pieces fit intriguingly well with the new
data to form a compelling picture. It’s well established, for example, that
nicotine binds and blocks a potassium channel that’s known as ‘inwardly
rectifying’ – that is, it keeps the concentrations in the cell at the cell’s ‘happy
place’, because the potassium channel’s job is to allow more potassium ions to
enter the cell than leave the cell. Bates has spent her career on this one
channel. Alcohol, it is turning out from early evidence in her lab, may affect it
as well, which may be a culprit for the birth defects associated with foetal
alcohol syndrome.
Anaesthesia also does weird things to ion channels in ways we aren’t quite
across yet. It’s not just during pregnancy that drugs might affect bioelectric
signalling. If you’ve ever had general anaesthesia, there’s a small chance you
may be at higher risk of developing cancer later in life,14 or maybe memory
problems.15 There are even cases where people appear to be under but are not,
or present lingering, mysterious PTSD-like symptoms.16 But we don’t know,
because we actually don’t know exactly how anaesthesia does what it does.
Well, we do know some things. ‘We know what it does to neurons,’ says Patrick
Purdon, a professor of anaesthesia at Harvard. It makes them fire in ways that
are completely different from normal physiological processes, in some cases
shutting down all firing entirely for seconds at a time. The result of this is that
complete gone-ness, more complete than any sleep. We might know the
neurons stop – but we don’t have a molecular explanation for how they do.
Or to be blunt, how they turn back on again. ‘The amazing thing about
general anaesthesia is that any of us ever come back from it the same person as
who went in,’ says Michael Levin. Not everyone does. Some people have
hallucinations. Those little immortal worms, the planarians, when you give
them anaesthesia (and cut off their heads), regrow a head – of another species.
Even bacteria respond to anaesthesia.
It’s not just drugs that can catch our ion channels by surprise. In 2019, a
fifty-four-year-old construction worker collapsed and died even though he was
reported to be in perfectly good health. A year later, the New England Journal of
Medicine published an investigation into the strange case.17 In the three weeks
before he died, the man had eaten one to two large bags of liquorice a day,
every day. At Massachusetts General Hospital, where doctors spent twenty-
four hours trying to save him after his collapse, it became evident that his
heart rhythm had been irreversibly destabilised. It turns out that liquorice’s
active ingredient, glycyrrhizin, mimics a process the body uses when it needs
to retain sodium and shake off potassium. His potassium channels were
gasping for ions, but there weren’t any. Without these ions to regulate the
sodium–potassium balance of the heart’s cells, his heart was incapable of firing
regular action potentials. He hadn’t been the first to have this experience.
Enough similar incidents had piled up by 2012 to occasion a review article
entitled ‘Licorice Abuse’, whose authors darkly warned that liquorice was ‘not
just a candy’. They urged the US Food and Drug Administration to regulate
the ‘substance’ and create public health messages around its health hazards.18
Five years later, the Food and Drug Administration partly obliged, issuing a
stark warning about the dangers of liquorice in time for Halloween. Black
licorice, they asked, trick or treat?
Quite the tangential mashup I have assembled here. But I’m trying to paint
a picture of all the unexpected ways we can unwittingly affect our electrome. I
hope I am making the case for a more holistic understanding of our bioelectric
dimensions. Unfortunately, so far there has been a lot of resistance to that.
One good example was the reaction to Bates’s research.

Institutional silos

The paper shouldn’t have been controversial. It was only a review, and a pretty
dry one at that. It’s not that contentious to point out that bioelectricity seems
to play important roles in development, even though the mechanism by which
it does so remains unclear. So Bates and her co-author put together an
overview of the various mechanisms and theories that have been proposed to
account for bioelectrical involvement in foetal development. They sent this
draft article to a journal, which distributed it to several other scientists, as is
standard practice in peer review in order to publish any paper in a respected
scientific journal. The journal editor passed the feedback to Bates, along with a
breezy instruction to ‘address’ it. Bates made the mistake of reading the
document right before she went to bed.
Some of the responses were scathing in a way that seemed out of all
proportion with the paper they were commenting on. No one was talking
about methodological flaws or accusing her of fraudulent data. They were
simply scathing about the whole field. Phrases like ‘the mythology of the
membrane voltage’ suffused the commentary. The fatal blow seemed to be
Bates’s mention of the bioelectric code.
It wasn’t the first time I heard about one of these dismissive, excoriating
reviews – Ann Rajnicek (who had worked with Borgens) had told me about a
grant application turned down crisply with the single query, ‘Does anyone
really believe this shit any more?’ But as a science journalist, I know that
bruising peer review is just part of the game. As I spoke to more researchers,
however, I noticed a pattern.19 People didn’t ‘believe’ Laura Hinkle had
enacted electrotaxis on cells. Nor did they believe Dany Adams. Or Ai-Sun
Tseng. ‘No one has ever said they don’t believe our data,’ another bioelectricity
researcher told me. ‘They just don’t want to hear it.’ Now here was Bates with
another variation on the theme. The common factor seemed to be that critics
weren’t taking issue with any particulars. Rather, they were issuing sweeping
statements, contemptuous dismissals larded with emotion and belief language.
While critics often couldn’t point to specific problems with the science or
processes in the publications, they kept using phrases like ‘I don’t believe it’.
That’s literally what a colleague told Michael Levin at a conference: ‘I haven’t
read the papers and I don’t need to. I don’t believe it.’
But what is it they don’t believe? That depends on who is doing the
disbelieving. Levin is often invited to give talks across a wide range of
disciplines, from developmental biology departments to NeurIPs, the biggest
AI conference in the world. ‘Someone always gets pissed off,’ he said to me.
‘What they get pissed off about depends on which department I’m in.’
Contentions that are received as obvious by a neuroscientist are sacrilege for a
molecular geneticist. It’s no grand conspiracy driving scepticism around
bioelectricity’s relevance outside the nervous system, though. It’s merely
education.
Jose Lopez at the National Science Foundation thinks we need new ways
to start communicating across these ever-separating disciplines. ‘We need a
new department, and we need polymaths. Not the kind we used to have – that
ship has sailed. People like Alexander von Humboldt and Galvani were alive at
a time when it was still possible to know everything in science. Now a scientist
can spend their entire career on one mutation in one gene that causes one
variant of this rare disease.’ Stephen Badylak agrees that in the field of
medicine, many remain in silo.
A compelling new alternative is getting underway right now, exemplified at
MIT’s Department of Biological Engineering, where you can get a PhD in
being a polymath: students in this department are specifically trained to talk
across disciplines and focus in on the vocabulary and concepts needed to
bridge the chasms between them. They are encouraged to think in a systems
biology way about how information is flowing, rather than viewing
information as discrete chunks.

‘It’s so weird that we don’t teach this’

Emily Bates got through four years of developmental biology in her

undergraduate curriculum at the University of Utah without ever once hearing
the term ‘ion channel’. Then she went on to her doctoral work in neuroscience
at Harvard, and though ion channels now entered her vocabulary, she never
learned about them having any function outside the nervous system. ‘Of
course I knew that they worked for muscle function and also for pancreatic
beta cell function,’ she says, but throughout her many years in undergraduate
and graduate education ‘my perception was that ion channels were studied in
neuroscience and that they weren’t really studied in other tissues’. She was
floored when she learned – entirely by happenstance – that channelopathies
could cause developmental defects that affect the body’s shape and patterning.
‘I was kind of shocked by that,’ she says. ‘It’s so weird that we don’t teach this.’
But she was fascinated by the idea, and so began to work on ion channels
in development. But she didn’t have any direction. There was no one in her
department to guide her. ‘I thought I was alone, studying this weird thing no
one cared about.’ She didn’t even know what terms to put into her literature
searches. ‘I was in kind of a black box.’
After the paper was published, she got an email from Michael Levin, who
sent her some of his work and introduced her to other people working on
similar research. Levin became a hub. Bates started going to conferences and
quickly got plugged into a network of other researchers who were looking at
her channels too. ‘Before Michael Levin reached out, I felt like I was just kind
of this weird anomaly working on this.’
So no wonder her reviewers were so affronted. To be fair, they had
probably never been made aware of ion channels either. ‘It is actually quite
difficult to find reviewers with appropriate expertise that agree on anything,’
Levin said in 2018, during a roundtable meeting held by the editors founding
the new journal Bioelectricity. ‘Trying to get reviewers who see the big picture
beyond their individual silos has definitely been a challenge.’ The new journal
is part of a movement to make bioelectricity an umbrella discipline in its own
right, encompassing the wide range of relevant biological phenomena from
developmental biology to AI. The research into bioelectricity, if this project is
to succeed, needs to begin to resemble the natural philosophy that prevailed
when Galvani made his momentous discoveries. ‘Since when does nature have
departments?’ Levin likes to tell people. However, I can’t think of a
straightforward alternative to dividing science into disciplinary departments.
This separation is part of a modern view of biology that, paradoxically,
may be limiting its reach. ‘Biology today is intensely focused on the molecules
of life and particularly on the genes that specify their structures and functions,’
wrote Franklin Harold in his 2017 book To Make the World Intelligible.
But this has limited how we can understand life. One reason bioelectric
mechanisms have been so tricky to find – no doubt contributing to
bioelectricity’s unfair association with quackery – is that the tools to watch
these minute and ephemeral processes only became conceivable a few decades
ago.
Before that – and even now – looking at live cells has been the exception,
not the rule. The majority of scientific discoveries about our biology came
from dissecting dead tissues. In a kind of ‘shoot first, ask questions later’
approach, most biological investigations have first killed the cells, then poked
around in the goo for the relevant characteristics. And while this has been an
excellent way of taxonomising all the different parts of a cell, dead cells don’t
do any electric signalling, which has made it virtually impossible to learn about
any of the electrical processes that go on in living cells and tissues. Which, in
turn, has made it pretty hard to figure out how the electrics affect the other
stuff. Looking at cells in this way, writes Paul Davies, is akin to ‘[trying] to
understand how a computer works by studying only the electronics inside it’
instead of looking at how these components trade information.20 People like
Galvani and Aldini got lucky that some bioelectric phenomena remain open to
investigation for a day or two after death, but in living animals it’s been
incredibly difficult to observe the flow of electrical currents and change in
voltage in real time.
And this is why I am so confident that we are in the bioelectric century.
Because the tools that let us look at living cells are advancing at astonishing
speed. Just one example is the voltage dye Dany Adams used, which was only
developed in the early 2000s. But today, many different labs are using many
different approaches to this same kind of technique – making bioelectric
parameters observable to the naked eye – and new discoveries are piling up by
the day. In 2019, Adam Cohen at Harvard used a fluorescent dye to answer a
question that had been bothering him about how cells and tissues transition
from their stem identity of a zero voltage to their final electrical identities.
Cohen was curious: as an embryo develops, does its voltage glide smoothly
from 0 to 70 like a slider, going through all the numbers in between? Or does
it snap directly from 0 to 70?
It turned out it was the latter, and that meant that’s how entire tissues
assume their identity as well: they jump right from stem to bone, not stopping
anywhere else along the way. All those cells that are connected by gap
junctions transitioned from stem 0 to final state the way ice crystallises out of
water.21
There are many new tools in development now that will let us look at
living systems in all their electrical complexity in this way, rather than
stagnating in the ‘reductionist fervour’ Paul Davies decries in his book.22
 These will allow us to begin building the full picture of our electrome.
Defining the term in 2016, the Dutch biologist Arnold de Loof described ‘the
totality of all ionic currents of any living entity, from the cellular to the
organismal level.’ We’ll need to map all our ion channels and gap junctions and
figure out how changing cellular voltages can affect cells and tissues. We’ll
need a visceral nerve atlas to understand how the nervous system controls
organ function. I’ve described much of this work in the book but there’s a lot
more I didn’t have space for. The biophysicist Alexis Pietak has already started
developing a tool that can unpick the staggering complexities of how cell
voltage leads to cellular identity: a software package called BETSE (the
Bioelectric Tissue Simulation Engine) allows people like Michael Levin to
simulate how bioelectric signals will propagate in virtual tissue.23 The dream is
that all these tools and the insights they unlock will usher in a future of
interfaces that work with – and possibly improve – biology on its own terms.
For the past half century, that honour has gone to machines and engineers
who promise a future of all-knowing artificial intelligence, cyborg upgrades to
what some have taken to dismissing as our inferior ‘meat bodies’, and a
transhumanist deep future in which all biological matter has upgraded to
silicon. But recently, the shine has begun to come off AI as we realise just how
limited silicon intelligence really is. Existing materials can’t even manage hip
implants that last longer than ten years – so how are we meant to have a
permanent telepathic neural device attached to our brain? The research now
underway in bioelectricity suggests that, rather than grasping for silicon and
electron replacements to biology, the answers to an upgraded future might lie
in biology itself.
Many of the early pioneers of bioelectricity have been redeemed after
being initially ignored or derided. This is true not only of Galvani but also of
Harold Saxton Burr, whose predictions about cancer and development have
been validated with time, just as Galvani was right about the spark of life.
Burr’s individual ideas seem to have been broadly right – but in his book
published in 1974, he also tied these experiments into a bigger hypothesis. He
posited that the day biology investigates forces instead of only studying
particles, it will undergo a conceptual leap to rival the importance of splitting
the atom for physics.
But there’s a final question. What then?
When we learned about the microbiome, we learned that we could
improve it by eating kimchi and lots of greens. Learning about the electrome
isn’t going to yield similar self-help just yet.
 Hacking our memories or overclocking ourselves into infinite productivity
is still quite a way off, and I hope my book has explained sufficiently why that’s
the case. And I hope I’ve convinced you that it’s actually not the right
approach anyway.
Think of it from my perspective. Did tDCS help me overcome an
impairment – the constant self-recriminations – or would its regular
application constitute an unfair advantage? I’m sure castigating inner voices are
hardly a unique feature of my brainscape.
A lot of ink has been spilled asking where you draw the line between
medical intervention and cosmetic enhancement. People raise this question all
the time about all kinds of cognitive (and other cosmetic) enhancement, but
no one ever seems to come up with a good answer. That’s probably because
it’s actually a question that gets more unsettling the closer you peer at it.
Because of course the more people adopt any particular enhancement, the
more pressure they will exert on the people around them – and on themselves!
– to keep up lest they get left behind, and the more unaugmented normalcy is
transformed, by process of inertia, into a deficiency. The blame isn’t on any
one individual – this is a classic tragedy of the commons.
Particularly in sport, this conversation has been very germane. Discussing
tDCS in sport with Outside magazine, Thomas Murray, president emeritus of
the Hastings Centre bioethics research institute, told the reporter Alex
Hutchinson that ‘once an effective technology gets adopted in a sport, it
becomes tyrannical. You have to use it.’ Hutchinson made the dire and
completely correct observation that ‘if the pros start brain-zapping, don’t kid
yourself that it won’t trickle down to college, high school, and even the
weekend warriors.’ Once you start this game, you can never stop.
So my final exhortation for you, the person who has made it all the way to
the end of my book, is this: when you see someone trying to sell you this stuff,
ask who will benefit. Why is someone trying to sell it to you? Is it really for
you? Beyond the basic ‘were the trials any good?’ scepticism, ask what will
happen next. Is this something that will alleviate your suffering? Or will it just
kick the can down the road because eventually your new normal will become
the new sub-standard, making way for the next piece of enhancing kit? The
answer to that question is very different if the intervention is a treatment for
cancer versus a way to be a better hustle goblin at your workplace.
In fact, I would love to take this whole idea of the body as an inferior meat
puppet to be augmented with metal and absolutely launch it into the sun.
Cybernetics keeps dangling the seductive illusion that we can ascend beyond
the grubby world of human biology in our cyborg future – cajoled into correct
action and good health (and maximum productivity, of course) by the electrical
takeover of a couple of relevant nerve terminals.
The study of the electrome shouldn’t serve these masters. Doing the
research that led to this book turned my head exactly 180 degrees from this
view. Rather than being a collection of inferior meat bodies, biology becomes
more astounding the more you learn about it – and fractally complicated too,
as the more you learn, the more you realise you don’t understand. We are
electrical machines whose full dimensions we have not even yet dreamed of.
But as is evident from the MIT programme, academia is waking up to the
interconnectedness, and different fields are starting to talk to each other more
to explore this electric future. That is where we will start to see the next great
steps in bioelectricity.
The real excitement of the field hews closer to the excitement around
cosmology – a better understanding of our place in the universe and in nature.
Already, some of the findings are upending some conventional wisdom. I
honestly can’t wait to see what else we find in the next decade.
 ACKNOWLEDGEMENTS

T here’s a joke that first-time book authors thank every person they have
ever met and I will be no exception. First, thanks to Simon Thorogood
for taking a chance on this! To Mollie Wiesenfeld and Georgia Frances King
for executing the most enormous trust fall. To Carrie Plitt for seeing the
outlines of the book long before I ever did.
I cannot get over the generosity of the scientists and researchers who
answered my emails and phone and zoom queries. They spent hours with me
through Covid lockdowns and electoral chaos to explain wildly difficult
concepts, talk me through controversial history, and help me keep my focus.
Alphabetically: Dany Adams patiently read draft after draft, and sent diagrams
and markups, and ironed out my misunderstandings. Debra Bohnert, thank
you so much for our wonderful conversation – I hope the story does the man
justice. Robert Campenot fielded my first terrified questions with grace and
good humour. Edward Farmer, thank you for reading many drafts of chapters
that were cut! I promise you will see them again. Flavio Frohlich, our
conversations unlocked an entire chapter. Franklin Harold, thank you for
giving me the most wonderful quote that had to be cut out of the final version
of the book (I will never not laugh about the vibrating probe at Wood’s Hole,
and I’m not sorry). Andrew Jackson, thank you for making me start thinking
seriously about ions. Nancy Kopell, thank you for an unforgettable
conversation. Michael Levin: thank you for four years of tirelessly answering
questions, sending papers, reading drafts, sending more papers, reading more
drafts, et cetera ad infinitum. Jianming Li, thank you for making me
understand the hair-raisingly difficult mechanics of die-back and for the many
hours on the phone. Kip Ludwig, thank you for sending more papers than a
single human could read in one lifetime, and for ‘fast email answers’ that went
on for multiple pages. Marco Piccolino, thank you for helping me figure out
where to start, and then making sure I ended up at the right end – thank you
in particular for sending me your amazing book. Ann Rajnicek, thank you for
giving me the oral history of Lionel Jaffe’s lab, but most of all for telling me
about Richard Borgens. Ken Robinson spent ages on the phone with me to
explain how the spinal stimulator did (and did not) work. Nigel Wallbridge, for
all the time spent explaining the bioelectric CANBUS system. Harold Zakon
and Min Zhao, thank you for explaining, respectively, ion channel motifs and
galvanotaxis.
Phone calls can’t do everything. I also trudged through some difficult
reading to try to understand the complicated history of how neuroscience
integrated electricity. Some books offered the keys that unlocked these papers
and historical documents. Among these, three stand out for their clarity and
explanatory power: Matthew Cobb’s book The Idea of the Brain was an
invaluable resource. So were Robert Campenot’s Animal Electricity, and Frances
Ashcroft’s Spark of Life. For anyone in whom my book sparked a curiosity
about the history of science of the brain and nervous system, I urge them to
drop everything and read these books.
To the people who read my early drafts, I am indebted to you forever:
Richard Panek, thank you so much for your inestimable help with my first,
unreadable attempts at ‘history of science’. Lowri Daniels and Michele Kogon,
you are rock stars – thank you for ensuring my facts were actually facts. David
Robson, Clare Wilson, Richard Fisher, thanks for patiently listening to my
spittle-flecked terror. Darryl Rambo, Lorri Lofvers and Joyce Wong, for being
a steadfast lifeboat of calm in turbulent years. Sumit Paul-Choudhury, Hal
Hodson and Will Heaven, thank you for the life-saving powers of Voltron, and
for enduring my endless yammering without exiting the chat (well, thanks to
two of you anyway). Sarita Bhatt: for understanding the subtext. Cristina
Calotta – I can’t thank you enough for the endless stream of requests for
GDPR articles I couldn’t access from their US websites or a library during
Covid. Soren, Cassie, Erin, Mike – you’re the constellations in the firmament.
Ann, you’re the North Star.
Dad, you got me curious about all the things there are to know in the
world – no good deed goes unpunished, so now you have to read this whole
book. Mom, you made sure I had a sceptical head on my shoulders while I fell
down every rabbit hole. And Nick and Daisy and Charlie: thank you for
enduring the late nights, the caffeine jitters, the endless illegible notes about
the neural code scrawled on random pieces of paper (and sometimes on
important mail), the mood rollercoasters. Thank you for your encouragement,
your grace, your patience, and your love.
 NOTES

Introduction

1 Condliffe, Jamie. ‘Glaxo and Verily Join Forces to Treat Disease By Hacking Your Nervous System’,
MIT Technology Review, 1 August 2016.
<https://www.technologyreview.com/2016/08/01/158574/glaxo-and-verily-join-forces-to-treat-
disease-by-hacking-your-nervous-
system/https://www.technologyreview.com/2016/08/01/158574/glaxo-and-verily-join-forces-to-
treat-disease-by-hacking-your-nervous-system/>
2 Hutchinson, Alex. ‘For the Golden State Warriors, Brain Zapping Could Provide an Edge’, The New
Yorker, 15 June 2016. <https://www.newyorker.com/tech/annals-of-technology/for-the-golden-
state-warriors-brain-zapping-could-provide-an-edge>
3 Reardon, Sarah. ‘“Brain doping” may improve athletes’ performance’. Nature 531 (2016), pp. 283–4
4 Blackiston, Douglas J., and Micheal Levin. ‘Ectopic eyes outside the head in Xenopus tadpoles
provide sensory data for light-mediated learning’. Journal of Experimental Biology 216 (2013), pp. 1031–
40; Durant, Fallon, Junji Morokuma, Christopher Fields, Katherine Williams, Dany Spencer Adams,
and Michael Levin. ‘Long-Term, Stochastic Editing of Regenerative Anatomy via Targeting
Endogenous Bioelectric Gradients’. Biophysical Journal, vol. 112, no. 10 (2017), pp. 2231–43

Part 1: Bioelectricity in the Beginning

Chapter 1: Artificial vs Animal

1 Pancaldi, Giuliano. Volta: Science and Culture in the Age of Enlightenment. Princeton, NJ: Princeton
University Press, 2005, p. 111
2 Galvani, Luigi. Commentary on the Effects of Electricity on Muscular Motion. Trans. Margaret Glover Foley.
Norwalk, CN: Burndy Library, 1953, p. 79
3 Pancaldi, Volta, p. 54; and Morus, Iwan Rhys. Frankenstein’s Children: Electricity, Exhibition, and
Experiment in Early-Nineteenth-Century London. Princeton, NJ: Princeton University Press, 1998, p. 232
4 Needham, Dorothy. Machina Carnis: The Biochemistry of Muscular Contraction in its Historical Development.
Cambridge: Cambridge University Press, 1971, pp. 1–26
5 Needham, Machina Carnis, p. 7
6 Kinneir, David. ‘A New Essay on the Nerves, and the Doctrine of the Animal Spirits Rationally
Considered’. London, 1738, pp. 21 and 66–7
<https://archive.org/details/b30525068/page/n5/mode/2up>
7 O’Reilly, Michael Francis, and James J. Walsh. Makers of Electricity. New York: Fordham University
Press, 1909, p. 81
8 Cohen, I. Bernard. Benjamin Franklin’s Science. Cambridge, MA: Harvard University Press, 1990, p. 42
9 Finger, Stanley, and Marco Piccolino. The Shocking History of Electric Fishes. Oxford: Oxford University
Press, 2011, pp. 282–5
10 Bresadola, Marco, and Marco Piccolino. Shocking Frogs: Galvani, Volta, and the Electric Origins of
Neuroscience. Oxford: Oxford University Press, 2013, p. 27
11 Bergin, William. ‘Aloisio (Luigi) Galvani (1737–1798) and Some Other Catholic Electricians’. In: Sir
Bertram Windle (ed.), Twelve Catholic Men of Science. London: Catholic Truth Society, 1912, pp. 69–87
12 Bresadola & Piccolino, Shocking Frogs, p. 27
13 O’Reilly & Walsh, Makers of Electricity, p. 152; and Bergin, ‘Aloisio (Luigi) Galvani’, p. 75
14 Cavazza, Marta. ‘Laura Bassi and Giuseppe Veratti: an electric couple during the Enlightenment’.
Institut d’Estudis Catalans, Vol. 5, no. 1 (2009), pp. 115–24 (pp. 119–21)
15 Messbarger, R. M. The Lady Anatomist: The Life and Work of Anna Morandi Manzolini. Chicago:
University of Chicago Press, 2010, p. 157
16 Frize, Monique. Laura Bassi and Science in 18th-Century Europe. Berlin/Heidelberg: Springer, 2013; see
also Messbarger, The Lady Anatomist, pp. 171–3
17 Foccaccia, Miriam, and Raffaella Simili. ‘Luigi Galvani, Physician, Surgeon, Physicist: From Animal
Electricity to Electro-Physiology’. In: Harry Whitaker, C. U. M. Smith and Stanley Finger (eds),
Brain, Mind and Medicine: Essays in Eighteenth-Century Neuroscience Boston: Springer, 2007, pp. 145–58
(p. 154)
18 Bresadola & Piccolino, Shocking Frogs, p. 76
19 Bresadola & Piccolino, Shocking Frogs, p. 89
20 Bresadola & Piccolino, Shocking Frogs, p. 122
21 O’Reilly & Walsh, Makers of Electricity, p. 133 3
22 See Bernardi, W. ‘The controversy on animal electricity in eighteenth-century Italy. Galvani, Volta
and others’. In: F. Bevilacqua and L. Fregonese (eds), Nuova Voltiana: Studies on Volta and His Times
Vol. 1. Milan: Hoepli, 2000, pp. 101–12 (p. 102). A translation is available at
<http://www.edumed.org.br/cursos/neurociencia/controversy-bernardi.pdf; and Bresadola &
Piccolino, Shocking Frogs, p. 143, among others
23 Pancaldi, Volta, pp. 14–15
24 Pancaldi, Volta, p. 20
25 Pancaldi, Volta, p. 31
26 Pancaldi, Volta, p. 91
27 Pancaldi, Volta, p. 111
28 Pancaldi, Volta, p. 111
29 Bresadola & Piccolino, Shocking Frogs, p. 152
30 Bresadola & Piccolino, Shocking Frogs, pp. 143–4
31 Bernardi, ‘The controversy’, pp. 104–5
32 Material about the French commissions from Blondel, Christine. ‘Animal Electricity in Paris: From
Initial Support, to Its Discredit and Eventual Rehabilitation’. In: Marco Bresadola and Giuliano
Pancaldi (eds), Luigi Galvani International Workshop, 1998, pp. 187–204
33 Blondel, ‘Animal Electricity’, p. 189
34 Volta, Alessandro. ‘Memoria seconda sull’elettricita animale’ (14 May 1792). Quoted in: Pera,
Marcello. The Ambiguous Frog. Trans. Jonathan Mandelbaum. Princeton, NJ: Princeton University
Press, 1992, p. 106
35 Unless otherwise referenced, the quotes from the rash of scientific papers in this section have been
taken from Bresadola & Piccolino, Shocking Frogs and Pera, The Ambiguous Frog
36 Ashcroft, Frances. The Spark of Life. London: Penguin, 2013, p. 24
37 Blondel, ‘Animal Electricity’, p. 190
38 Bernardi, ‘The controversy’, p. 107 (fn. 26)
39 Robert Campenot provides a clear and straightforward description of this experiment. Campenot,
Robert. Animal Electricity. Cambridge, MA: Harvard University Press, 2016, p. 40
40 Bernardi, ‘The controversy’, p. 103
41 Bernardi, ‘The controversy’, p. 107

Chapter 2: Spectacular pseudoscience

1 Aldini, Giovanni. Essai théorique et expérimental sur le galvanisme, avec une série d’expériences. Faites en présence
des commissaires de l’Institut National de France, et en divers amphithéâtres Anatomiques de Londres. Paris:
Fournier Fils, 1804. Available via the Smithsonian Libraries archive at <https://library.si.edu/digital-
library/book/essaitheyorique00aldi>
2 Some sources suggest Queen Charlotte and her son, the Prince of Wales, attended but it may have
been the younger prince, Augustus Frederick, who Aldini later dedicated a book to. It seems clear
that there was at least one royal present.
3 Tarlow, Sarah, and Emma Battell Lowman. Harnessing the Power of the Criminal Corpse. London:
Palgrave Macmillan, 2018, pp. 87–114
4 McDonald, Helen. ‘Galvanising George Foster, 1803’, The University of Melbourne Archives and
Special Collections. <https://library.unimelb.edu.au/asc/whats-on/exhibitions/dark-
imaginings/gothicresearch/galvanising-george-foster,-1803>
5 Morus, Iwan Rhys. Frankenstein’s Children: Electricity, Exhibition, and Experiment in Early-Nineteenth-
Century London. Princeton, NJ: Princeton University Press,1998, p. 128
6 Sleigh, Charlotte. ‘Life, Death and Galvanism’. Studies in History and Philosophy of Science Part C: Studies
in History and Philosophy of Biological and Biomedical Sciences, vol. 29, no. 2 (1998), pp. 219–48 (p. 223)
7 There are many accounts of this experiment – mine is drawn mainly from Morus, Iwan Rhys.
Shocking Bodies: Life, Death & Electricity in Victorian England. Stroud: The History Press, 2011, pp. 34–
7. Other sources are Aldini’s personal account and the Newgate Calendar, 22 January 1803, p. 3
8 Sleigh, ‘Life, Death and Galvanism’, p. 224
9 Parent, André. ‘Giovanni Aldini: From Animal Electricity to Human Brain Stimulation’, Canadian
Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques, vol. 31, no. 4 (2004), pp. 576–
84 (p. 578)
10 Blondel, Christine. ‘Animal Electricity in Paris: From Initial Support, to Its Discredit and Eventual
Rehabilitation’. In: Marco Bresadola and Giuliano Pancaldi (eds), Luigi Galvani International Workshop,
1998, pp. 187–204 (pp. 194–5)
11 Aldini, ‘Essai Théorique’, p. vi
12 Aldini’s most detailed account of such a treatment concerns Luigi Lanzarini.
13 Carpue, Joseph. ‘An Introduction to Electricity and Galvanism; with Cases, Shewing Their Effects in
the Cure of Diseases’. London: A. Phillips, 1803, p. 86
<https://wellcomecollection.org/works/bzaj37cs/items?canvas=100>
14 Blondel, ‘Animal Electricity’, p. 197
15 Aldini, John [sic]. ‘General Views on the Application of Galvanism to Medical Purposes, Principally
in Cases of Suspended Animation’. London: Royal Society, 1819, p. 37. When publishing abroad,
Aldini had the habit of changing his first name. In the UK he anglicised to John, and in France he
became Jean.
16 Parent, ‘Giovanni Aldini’, p. 581
17 Vassalli-Eandi said in August 1802 that Aldini ‘has been obliged to acknowledge that he had not
been able to get any contractions from the heart using the electro motor of Volta’.
18 Aldini, ‘Essai Théorique’, p. 195
19 Giulio, C. ‘Report presented to the Class of the Exact Sciences of the Academy of Turin, 15th
August 1802, in Regard to the Galvanic Experiments Made by C. Vassali-Eandi, Giulio and Rossi on
the 10th and 14th of the same Month, on the Head and Trunk of three Men a short Time after their
Decapitation’. The Philosophical Magazine, vol. 15, no. 57 (1803), pp. 39–41
20 Morus, Iwan. ‘The Victorians Bequeathed Us Their Idea of an Electric Future’. Aeon, 8 August 2016
21 Aldini, ‘Essai Théorique’, p. 143–4
22 This section draws heavily from: Bertucci, Paola. ‘Therapeutic Attractions: Early Applications of
Electricity to the Art of Healing’. In: Harry Whitaker, C. U. M. Smith, and Stanley Finger (eds),
Brain, Mind, and Medicine: Essays in Eighteenth-Century Neuroscience. Boston: Springer, 2007, pp. 271–83;
Pera, Marcello, The Ambiguous Frog. Trans. Jonathan Mandelbaum. Princeton, NJ: Princeton
University Press, 1992; and several unbeatable details from Iwan Rhys Morus’s Frankenstein’s Children
23 Pera, The Ambiguous Frog, pp. 18–25
24 Pera, The Ambiguous Frog, p. 22
25 Ashcroft, Frances. The Spark of Life. London: Penguin, 2013, pp. 290–1
26 Bertucci, ‘Therapeutic Attractions’, p. 281
27 Calculated on 23 May 2022 using the CPI Inflation Calculator.
<https://www.officialdata.org/uk/inflation>
28 Bertucci, ‘Therapeutic Attractions’, p. 281
29 Shepherd, Francis John. ‘Medical Quacks and Quackeries’, Popular Science Monthly, vol. 23 (June
1883), p. 152
30 Morus, Shocking Bodies, p. 35
31 Ochs, Sidney. A History of Nerve Functions: From Animal Spirits to Molecular Mechanisms. Cambridge:
Cambridge University Press, 2004, p. 117
32 Miller, William Snow. ‘Elisha Perkins and His Metallic Tractors’. Yale Journal of Biology and Medicine,
vol. 8, no. 1 (1935), pp. 41–57 (p. 44)
33 Lord Byron. ‘English Bards and Scotch Reviewers’. Quoted in: Miller, ‘Elisha Perkins’, p. 52
34 Finger, Stanley, Marco Piccolino, and Frank W. Stahnisch. ‘Alexander von Humboldt: Galvanism,
Animal Electricity, and Self-Experimentation Part 2: The Electric Eel, Animal Electricity, and Later
Years’. Journal of the History of the Neurosciences, vol. 22, no. 4 (2013), pp. 327–52 (p. 343)
35 Finger, Stanley, and Marco Piccolino. The Shocking History of Electric Fishes. Oxford: Oxford University
Press, 2011, p. 11
36 Finger et al., ‘Alexander von Humboldt’, p. 343
37 Otis, Laura. Müller’s Lab. Oxford: Oxford University Press, 2007 p. 11; see also Finger et al.,
‘Alexander von Humboldt’, p. 345
38 A picture can be seen at ‘Nobili’s large astatic galvanometer’, Museo Galileo Virtual Museum
<https://catalogue.museogalileo.it/object/NobilisLargeAstaticGalvanometer.html>
39 Verkhratsky, Alexei, and Parpura, Vladimir. ‘History of Electrophysiology and the Patch Clamp’. In:
Marzia Martina and Stefano Taverna (eds), Methods in Molecular Biology. New York: Humana Press,
2014, pp. 1–19 (p. 7). However, much of the detail about Nobili and Matteucci’s experiments comes
from Otis’s Müller’s Lab.
40 Cobb, Matthew. The Idea of the Brain: A History. London: Profile Books, 2020, p. 71
41 Finger et al., ‘Alexander von Humboldt’, p. 347 and Otis, p. 90
42 Emil du Bois-Reymond in an 1849 letter to fellow experimental physiologist Carl Ludwig,
reproduced on p. 347 of: Finger et al., ‘Alexander von Humboldt’.
43 Finger & Piccolino, The Shocking History of Electric Fishes, p. 369
44 Bresadola, Marco, and Marco Piccolino. Shocking Frogs: Galvani, Volta, and the Electric Origins of
Neuroscience. Oxford: Oxford University Press, 2013, p. 21
45 Finkelstein, Gabriel. ‘Emil du Bois-Reymond vs Ludimar Hermann’. Comptes rendus biologies, vol. 329,
5-6 (2006), pp. 340-7 doi:10.1016/j.crvi.2006.03.005
 Part 2: Bioelectricity and the Electrome

1 Bresadola, Marco, and Marco Piccolino. Shocking Frogs: Galvani, Volta, and the Electric Origins of
Neuroscience. Oxford: Oxford University Press, 2013, p. 13

Chapter 3: The electrome and the bioelectric code

1 The first mention of the word ‘electrome’ can be found in an obscure 2016 paper written by the
Belgian biologist Arnold de Loof (‘The cell’s self-generated “electrome”: The biophysical essence of
the immaterial dimension of Life?’, Communicative & Integrative Biology, vol. 9,5, e1197446). This
definition did not break into wider circulation. Even before its publication, however, other
bioelectricity researchers, including Michael Levin and Min Zhao, had begun to use the word. Zhao,
in particular, has reviewed a few manuscripts using that term ‘without [consistent] definition, and
clarification. It is an evolving understanding’. The purpose of this book is to pin the word down like
a butterfly behind glass.
2 Valenstein, Elliot. The War of the Soups and the Sparks: The Discovery of Neurotransmitters and the Dispute
over how Nerves Communicate. New York: Columbia University Press, 2005, pp. 121–34
3 James, Frank. ‘Davy, Faraday, and Italian Science’. Report presented at the IX National Conference
of ‘History and Foundations of Chemistry’ (Modena, 25–27 October 2001), pp. 149–58
<https://media.accademiaxl.it/memorie/S5-VXXV-P1-2-2001/James149-158.pdf> Accessed 22
February 2021
4 Faraday, Michael. Experimental Researches in Electricity – Volume 1 [1832]. London: Richard and John
Edward Taylor, 1849. Available at <https://www.gutenberg.org/files/14986/14986-h/14986-
h.htm>
5 Ringer, Sydney, and E. A. Morshead. ‘The Influence on the Afferent Nerves of the Frog’s Leg from
the Local Application of the Chlorides, Bromides, and Iodides of Potassium, Ammonium, and
Sodium’. Journal of Anatomy and Physiology 12 (October 1877), pp. 58–72
6 Campenot, Robert, Animal Electricity. Cambridge, MA: Harvard University Press, 2016, p. 114
7 McCormick, David A. ‘Membrane Potential and Action Potential’. In: Larry Squire et al. (eds),
Fundamental Neuroscience. Oxford: Academic Press, 2013, pp. 93–116 (p. 93)
8 Hodgkin, Alan, and Andrew F. Huxley. ‘A quantitative description of membrane current and its
application to conduction and excitation in nerve’. The Journal of Physiology, vol. 117, no. 4 (1952), pp.
500–44
9 Bresadola, Marco, and Marco Piccolino. Shocking Frogs: Galvani, Volta, and the Electric Origins of
Neuroscience. Oxford: Oxford University Press, 2013, p. 294
10 Ramachandran, Vilayanur S. ‘The Astonishing Francis Crick’. Francis Crick memorial lecture
delivered at the Centre for the Philosophical Foundations of Science in New Delhi, India, 17
October 2004. <http://cbc.ucsd.edu/The_Astonishing_Francis_Crick.htm>
11 Schuetze, Stephen. ‘The Discovery of the Action Potential’. Trends in Neurosciences 6 (1983), pp. 164–
8. See also Lombard, Jonathan, ‘Once upon a time the cell membranes: 175 years of cell boundary
research’. Biology Direct, vol. 9, no. 32, pp. 1–35; and Finger, Stanley, and Marco Piccolino. The
Shocking History of Electric Fishes. Oxford: Oxford University Press, 2011, p. 402
12 Campenot, Animal Electricity, pp. 210–11
13 Agnew, William, et al. ‘Purification of the Tetrodotoxin-Binding Component Associated with the
Voltage-Sensitive Sodium Channel from Electrophorus Electricus Electroplax Membranes’.
Proceedings of the National Academy of Sciences, vol. 75, no. 6 (1978), pp. 2606–10.
14 Noda, Masaharu, et al. ‘Expression of Functional Sodium Channels from Cloned CDNA’. Nature,
vol. 322, no. 6082 (1986), pp. 826–8.
15 Brenowitz, Stephan, et al. ‘Ion Channels: History, Diversity, and Impact’. Cold Spring Harbor Protocols
7 (2017), loc. pdb.top092288
<http://cshprotocols.cshlp.org/content/2017/7/pdb.top092288.long#sec-3>
16 McCormick, ‘Membrane Potential and Action Potential’, p. 103
17 Ashcroft, Frances. The Spark of Life. London: Penguin, 2013, p. 69
18 McCormick, David A. ‘Membrane Potential and Action Potential’. In: John H. Byrne, and James L.
Roberts (eds), From Molecules to Networks: An Introduction to Cellular and Molecular Neuroscience.
Amsterdam/Boston: Academic Press, 2nd edition, 2009, pp. 133–58 (p. 151)
19 Ashcroft, The Spark of Life, p. 49 and pp. 87–9
20 Barhanin, Jacques, et al. ‘New scorpion toxins with a very high affinity for Na+ channels.
Biochemical characterization and use for the purification of Na+ channels’. Journal de Physiologie, vol.
79, no. 4 (1984), pp. 304–8
21 Kullmann, Dimitri M. ‘The Neuronal Channelopathies’. Brain, vol. 125, no. 6 (2002), pp. 1177–95
22 Fozzard, Harry. ‘Cardiac Sodium and Calcium Channels: A History of Excitatory Currents’.
Cardiovascular Research, vol. 55, no. 1 (2002), pp. 1–8
23 Sherman, Harry G., et al. ‘Mechanistic insight into heterogeneity of trans-plasma membrane electron
transport in cancer cell types’. Biochimica et Biophysica Acta – Bioenergetics, 1860/8 (2019), pp. 628–39
24 Lund, Elmer. Bioelectric Fields and Growth. Austin: University of Texas Press, 1947
25 Prindle A, Liu J, Asally M, Ly S, Garcia-Ojalvo J, Süel GM. ‘Ion channels enable electrical
communication in bacterial communities’. Nature. (2015) Nov 5;527(7576):59-63. doi:
10.1038/nature15709. Epub 2015 Oct 21. PMID: 26503040; PMCID: PMC4890463
26 Brand, Alexandra et al. ‘Hyphal Orientation of Candida albicans Is Regulated by a Calcium-
Dependent Mechanism’. Current Biology, 17, (2007), pp. 347–352
27 Davies, Paul. The Demon in the Machine. London: Allen Lane, 2019, p. 110
28 Anderson, Paul A., and Robert M. Greenberg. ‘Phylogeny of ion channels: clues to structure and
function’. Comparative Biochemistry and Physiology Part B: Biochemistry and Molecular Biology, vol. 129, no. 1
(2001), pp. 17–28. doi: 10.1016/s1096-4959(01)00376-1
29 Liebeskind, B. J., D. M. Hillis, and H. H. Zakon. ‘Convergence of ion channel genome content in
early animal evolution’. Proceedings of the National Academies of Science 112 (2015), E846–E851

Part 3: Bioelectricity in the Brain and Body

Chapter 4: Electrifying the heart

1 Besterman, Edwin, and Creese, Richard. ‘Waller – pioneer of electrocardiography’. British Heart
Journal, vol. 42, no. 1 (1979), pp. 61–4 (p. 63)
2 Acierno, Louis. ‘Augustus Desire Waller’. Clinical Cardiology, vol. 23, no. 4 (2000), pp. 307–9 (p. 308)
3 Harrington, Kat. ‘Heavy browed savants unbend’. Royal Society blogs, 14 July 2016. Retrieved from
the Internet Archive 21 September 2021
<https://web.archive.org/web/20191024235429/http://blogs.royalsociety.org/history-of-
science/2016/07/04/heavy-browed/>
4 Waller, Augustus D. ‘A Demonstration on Man of Electromotive Changes accompanying the Heart’s
Beat’. The Journal of Physiology, vol. 8 (1887), pp. 229–34
5 Campenot, Robert. Animal Electricity. Cambridge, MA: Harvard University Press, 2016, p. 269
6 Burchell, Howard. ‘A Centennial Note on Waller and the First Human Electrocardiogram’. The
American Journal of Cardiology, vol. 59, no. 9 (1987), pp. 979–83 (p. 979)
7 AlGhatrif, Majd, and Joseph Lindsay. ‘A Brief Review: History to Understand Fundamentals of
Electrocardiography’. Journal of Community Hospital Internal Medicine Perspectives, vol. 2 no. 1 (2012), loc.
14383
8 Ashcroft, Frances. The Spark of Life. London: Penguin, 2013, p. 146
9 Campenot, Animal Electricity, pp. 272–4
10 Aquilina, Oscar. ‘A brief history of cardiac pacing’. Images in Paediatric Cardiology, vol. 8, no. 2 (April
2006), pp. 17–81 (Fig. 16)
11 Rowbottom, Margaret, and Charles Susskind. Electricity and Medicine: History of Their Interaction.
London: Macmillan, 1984, p. 248
12 Rowbottom & Susskind, Electricity and Medicine, p. 249
13 Rowbottom & Susskind, Electricity and Medicine, p. 249
14 Emery, Gene. ‘Nuclear pacemaker still energized after 34 years’, Reuters, 19 December 2007
<https://www.reuters.com/article/us-heart-pacemaker-idUSN1960427320071219>
15 Norman, J. C. et al. ‘Implantable nuclear-powered cardiac pacemakers’. New England Journal of
Medicine, vol. 283, no. 22 (1970), pp. 1203–6. doi: 10.1056/NEJM197011262832206
16 Roy, O. Z., and R. W. Wehnert. ‘Keeping the heart alive with a biological battery’. Electronics, vol. 39,
no. 6 (1966), pp. 105–7. Also see: <https://link.springer.com/article/10.1007/BF02629834>
17 Greatbatch, Wilson. The Making of the Pacemaker: Celebrating a Lifesaving Invention. Amherst:
Prometheus Books, 2000, p. 23
18 Tashiro, Hiroyuki, et al. ‘Direct Neural Interface’. In: Marko B. Popovic (ed.), Biomechatronics. Oxford:
Academic Press, 2019, pp. 139–74
19 Greatbatch, The Making of the Pacemaker, p. 23

Chapter 5: Artificial memories and sensory implants

1 Hamzelou, Jessica. ‘$100 million project to make intelligence-boosting brain implant’, New Scientist,
20 October 2016 <https://www.newscientist.com/article/2109868-100-million-project-to-make-
intelligence-boosting-brain-implant/>
2 McKelvey, Cynthia. ‘The Neuroscientist Who’s Building a Better Memory for Humans’, Wired, 1
December 2016 <https://www.wired.com/2016/12/neuroscientist-whos-building-better-memory-
humans/>
3 Johnson, Bryan. ‘The Urgency of Cognitive Improvement’, Medium, 14 June 2017
<https://medium.com/future-literacy/the-urgency-of-cognitive-improvement-72f5043ca1fc>
4 Campenot, Robert, Animal Electricity. Cambridge, MA: Harvard University Press, 2016, pp. 110–11
5 Finger, Stanley. Minds Behind the Brain. Oxford: Oxford University Press, 2005, pp 243–7. See also
Ashcroft, Frances. The Spark of Life. London: Penguin, 2013, ch. 3
6 Garson, Justin. ‘The Birth of Information in the Brain: Edgar Adrian and the Vacuum Tube’. Science
in Context, vol. 28, no. 1 (2015), pp. 31–52 (pp. 40–2)
7 Finger, Minds, p. 249
8 Finger, Minds, p. 250
9 Finger, Minds, p. 250
10 Garson, ‘The Birth’, p. 46
11 Finger, Minds, p. 250
12 Adrian, E. D. The Physical Background of Perception. Quoted in Cobb, Matthew. The Idea of the Brain: A
History. London: Profile Books, 2020, p. 186
13 Borck, Cornelius. ‘Recording the Brain at Work: The Visible, the Readable, and the Invisible in
Electroencephalography’. Journal of the History of the Neurosciences 17 (2008), pp. 367–79 (p. 371)
14 Millett, David. ‘Hans Berger: From Psychic Energy to the EEG’. Perspectives in Biology and Medicine,
vol. 44, no. 4 (2001), pp. 522–42 (p. 523)
15 Ginzberg, quoted in Millet, ‘Hans Berger’, p. 524
16 Millet, ‘Hans Berger’, p. 537
17 Cobb, The Idea of the Brain, p. 170
18 Millet, ‘Hans Berger’, p. 539
19 Borck, ‘Recording’, p. 369
20 Borck, ‘Recording’, p. 368
21 Borck, Cornelius, and Ann M. Hentschel. Brainwaves: A Cultural History of Electroencephalography.
London: Routledge, 2018, p. 110
22 Borck & Hentschel, Brainwaves, p. 109
23 Borck & Hentschel, Brainwaves, p. 115
24 Collura, Thomas. ‘History and Evolution of Electroencephalo-graphic Instruments and Techniques’.
Journal of Clinical Neurophysiology, vol. 10, no. 4 (1993), pp. 476–504 (p. 498)
25 Marsh, Allison. ‘Meet the Roomba’s Ancestor: The Cybernetic Tortoise’, IEEE Spectrum, 28
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26 Cobb, The Idea of the Brain, p. 190
27 Hodgkin, Alan. ‘Edgar Douglas Adrian, Baron Adrian of Cambridge. 30 November 1889–4 August
1977’. Biographical Memoirs of Fellows of the Royal Society 25 (1979), pp. 1–73 (p. 19)
28 Tatu, Laurent. ‘Edgar Adrian (1889–1977) and Shell Shock Electrotherapy: A Forgotten History?’.
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29 Underwood, Emil. ‘A Sense of Self ’. Science, vol. 372, no. 6547 (2021), pp. 1142–5 (pp. 1142–3)
30 Olds, James. ‘Pleasure Centers in the Brain’. Scientific American, vol. 195 (1956), pp. 105–17; Olds,
James. ‘Self-Stimulation of the Brain’. Science 127 (1958), pp. 315–24
31 Moan, Charles, and Robert G. Heath. ‘Septal Stimulation for the Initiation of Heterosexual Behavior
in a Homosexual Male’. In: Wolpe, Joseph, and Leo J. Reyna (eds), Behavior Therapy in Psychiatric
Practice. New York: Pergamon Press, 1976, pp. 109–16
32 Giordano, James (ed.). Neurotechnology. Boca Raton: CRC Press, 2012, p. 151
33 Frank, Lone. ‘Maverick or monster? The controversial pioneer of brain zapping’, New Scientist, 27
March 2018 <https://www.newscientist.com/article/mg23731710-700-maverick-or-monster-the-
controversial-pioneer-of-brain-zapping/>
34 Blackwell, Barry. ‘José Manuel Rodriguez Delgado’. Neuropsychopharmacology, vol. 37, no. 13 (2012),
pp. 2883–4.
35 The photo has been widely reproduced, but can be found in Marzullo, Timothy. ‘The Missing
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29–35
36 Osmundsen, John. ‘Matador with a radio stops wired bull: modified behavior in animals subject of
brain study’, New York Times, 17 May 1965
37 Horgan, John. ‘Tribute to José Delgado, Legendary and Slightly Scary Pioneer of Mind Control’.
Scientific American, 25 September 2017
38 Gardner, John. ‘A History of Deep Brain Stimulation: Technological Innovation and the Role of
Clinical Assessment Tools’. Social Studies of Science, vol. 43, no. 5 (2013), pp. 707–28 (p. 710)
39 Schwalb, Jason M., and Clement Hamani. ‘The History and Future of Deep Brain Stimulation’.
Neurotherapeutics, vol. 5, no. 1 (2008), pp. 3–13
40 Gardner, ‘A History’, p. 719
41 Lozano, A. M., N. Lipsman, H. Bergman, et al. ‘Deep brain stimulation: current challenges and
future directions’. Nature Reviews Neurology 15 (2019), pp. 148–60
<https://www.nature.com/articles/s41582-018-0128-2>
 Nuttin, Bart et al. ‘Electrical Stimulation in Anterior Limbs of Internal Capsules in Patients with
42 Obsessive-Compulsive Disorder’. The Lancet, vol. 354, no. 9189 (1999), p. 1526
43 Ridgway, Andy. ‘Deep brain stimulation: A wonder treatment pushed too far?’, New Scientist, 21
October 2015 <https://www.newscientist.com/article/mg22830440-500-deep-brain-stimulation-a-
wonder-treatment-pushed-too-far/>
44 Sturm, V., et al. ‘DBS in the basolateral amygdala improves symptoms of autism and related self-
injurious behavior: a case report and hypothesis on the pathogenesis of the disorder’. Frontiers in
Neuroscience, vol. 6, no. 341 (2013), doi: 10.3389/fnhum.2012.00341
45 Formolo, D. A., et al. ‘Deep Brain Stimulation for Obesity: A Review and Future Directions’.
Frontiers in Neuroscience, vol. 13, no. 323 (2019), doi: 10.3389/fnins.2019.00323; Wu, H., et al. ‘Deep-
brain stimulation for anorexia nervosa’. World Neurosurgery 80 (2013), doi:
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46 Baguley, David, et al. ‘Tinnitus’. The Lancet, vol. 382, no. 9904 (2013), pp. 1600–7; Luigjes, J., van den
Brink, W., Feenstra, M., et al. ‘Deep brain stimulation in addiction: a review of potential brain
targets’. Molecular Psychiatry 17 (2012), pp. 572–83 <https://doi.org/10.1038/mp.2011.114>; Fuss, J.,
et al. ‘Deep brain stimulation to reduce sexual drive’. Journal of Psychiatry and Neuroscience, vol. 40, no. 6
(2015) pp. 429–31
47 Satellite meeting of Society for Neuroscience, San Diego, 2018. Mayberg also spoke about it at the
Brain & Behaviour Research Foundation: ‘Deep Brain Stimulation for Treatment-Resistant
Depression: A Progress Report’, Brain & Behaviour Research Foundation YouTube channel, 16
October 2019 <https://www.youtube.com/watch?v=X86wBj1tjiA>
48 Mayberg, Helen, et al. ‘Deep Brain Stimulation for Treatment-Resistant Depression’. Neuron, vol. 45,
no. 5 (2005), pp. 651–60
49 Dobbs, David. ‘Why Deep-Brain Stimulation for Depression Didn’t Pass Clinical Trials’, The Atlantic,
17 April 2018 <https://www.theatlantic.com/science/archive/2018/04/zapping-peoples-brains-
didnt-cure-their-depression-until-it-did/558032/>
50 ‘BROADEN Trial of DBS for Treatment-Resistant Depression No Better than Sham’, The
Neurocritic blog, 10 October 2017 <https://neurocritic.blogspot.com/2017/10/broaden-trial-of-
dbs-for-treatment.html>
51 ‘The Remote Control Brain’, Invisibilia, NPR, first broadcast 29 March 2019
<https://www.npr.org/2019/03/28/707639854/the-remote-control-brain>
52 Cyron, Donatus. ‘Mental Side Effects of Deep Brain Stimulation (DBS) for Movement Disorders:
The Futility of Denial’. Frontiers in Integrative Neuroscience 10 (2016), pp. 1–4
<https://www.frontiersin.org/articles/10.3389/fnint.2016.00017/full>
53 Mantione, Mariska, et al. ‘A Case of Musical Preference for Johnny Cash Following Deep Brain
Stimulation of the Nucleus Accumbens’. Frontiers in Behavioral Neuroscience, vol. 8, no. 152 (2014), doi:
10.3389/fnbeh.2014.00152
54 Florin, Esther, et al. ‘Subthalamic Stimulation Modulates Self-Estimation of Patients with
Parkinson’s Disease and Induces Risk-Seeking Behaviour’. Brain, vol. 136, no. 11 (2013), pp. 3271–
81.
55 Shen, Helen H., ‘Can Deep Brain Stimulation Find Success beyond Parkinson’s Disease?’. Proceedings
of the National Academy of Sciences, vol. 116, no. 11 (2019), pp. 4764–6
56 Müller, Eli J., and Peter A. Robinson. ‘Quantitative Theory of Deep Brain Stimulation of the
Subthalamic Nucleus for the Suppression of Pathological Rhythms in Parkinson’s Disease’, ed. by
Saad Jbabdi, PLOS Computational Biology, vol. 14, no. 5 (2018), e1006217. See also Kisely, Steve, et al.
‘A Systematic Review and Meta-Analysis of Deep Brain Stimulation for Depression’. Depression and
Anxiety, vol. 35, no. 5 (2018), pp. 468–80
57 Crick, Francis. The Astonishing Hypothesis: The Scientific Search for the Soul. New York: Scribner; London:
Maxwell Macmillan International, 1994, p. 10, see also pp. 182-4
58 Crick, The Astonishing Hypothesis, p. 3. For more on consciousness, a wonderful resource is Chapter 15
of Matthew Cobb’s The Idea of the Brain
59 Gerstner, Wulfram, et al. ‘Neural Codes: Firing Rates and Beyond’. Proceedings of the National Academy
of Sciences, vol. 94, no. 24 (1997), pp. 12740–1
<https://www.pnas.org/doi/epdf/10.1073/pnas.94.24.12740>
60 See Buzsöki, Gyárgy. Rhythms of the Brain, New York: Oxford University Press, 2011
61 Kellis, Spencer, et al. ‘Decoding Spoken Words Using Local Field Potentials Recorded from the
Cortical Surface’. Journal of Neural Engineering, vol. 7, no. 5 (2010), 056007
62 Martin, Richard. ‘Mind Control’, Wired, 1 March 2005 <https://www.wired.com/2005/03/brain-
3/>
63 Martin, ‘Mind Control’, 2005
64 Bouton, Chad. ‘Reconnecting a paralyzed man’s brain to his body through technology’, TEDx Talks
YouTube channel, 25 November 2014 <https://www.youtube.com/watch?v=BPI7XWPSbS4>
65 Bouton, C., Shaikhouni, A., Annetta, N., et al. ‘Restoring cortical control of functional movement in
a human with quadriplegia’. Nature 533 (2016), pp. 247–50 <https://doi.org/10.1038/nature17435>
66 Geddes, Linda. ‘First paralysed person to be “reanimated” offers neuroscience insights’, Nature, 13
April 2016 <https://doi.org/10.1038/nature.2016.19749>
67 Geddes, Linda. ‘Pioneering brain implant restores paralysed man’s sense of touch’, Nature, 13
October 2016 <https://doi.org/10.1038/nature.2016>
68 Flesher, S. N., et al. ‘Intracortical microstimulation of human somatosensory cortex’. Science
Translational Medicine. vol. 8, no. 361 (2016), doi: 10.1126/scitranslmed.aaf8083
69 Berger, T. W., et al. ‘A cortical neural prosthesis for restoring and enhancing memory’. Journal of
Neural Engineering, vol. 8, no. 4 (2011), doi: 10.1088/1741-2560/8/4/046017
70 Frank, Loren. ‘How to Make an Implant That Improves the Brain’, MIT Technology Review, 9 May
2013 <https://www.technologyreview.com/2013/05/09/178498/how-to-make-a-cognitive-
neuroprosthetic/>
71 Hampson, Robert E., et al. ‘Facilitation and Restoration of Cognitive Function in Primate Prefrontal
Cortex by a Neuroprosthesis That Utilizes Minicolumn-Specific Neural Firing’. Journal of Neural
Engineering, vol. 9, no. 5 (2012), 056012
72 Strickland, Eliza. ‘DARPA Project Starts Building Human Memory Prosthetics’, IEEE Spectrum, 27
August 2014 <https://spectrum.ieee.org/darpa-project-starts-building-human-memory-
prosthetics>
73 McKelvey, ‘The Neuroscientist’, 2016
74 Ganzer, Patrick, et al. ‘Restoring the Sense of Touch Using a Sensorimotor Demultiplexing Neural
Interface’. Cell, vol. 181, no. 4 (2020) pp. 763–73
75 ‘Reconnecting the Brain After Paralysis Using Machine Learning’, Medium, 21 September 2020
<https://medium.com/mathworks/reconnecting-the-brain-after-paralysis-using-machine-learning-
1a134c622c5d>
76 Bryan, Carla, and Ivan Rios (eds). Brain–machine Interfaces: Uses and Developments. New York: Novinka,
2018
77 Chad Bouton is working on the solution to the ‘take home’ problem. Bouton, Chad. ‘Brain Implants
and Wearables Let Paralyzed People Move Again’, IEEE Spectrum, 26 January 2021
<https://spectrum.ieee.org/brain-implants-and-wearables-let-paralyzed-people-move-again>
78 Engber, Daniel. ‘The Neurologist Who Hacked His Brain – And Almost Lost His Mind’. Wired, 26
January 2016
79 Jun, James J., et al. ‘Fully Integrated Silicon Probes for High-Density Recording of Neural Activity’.
Nature, vol. 551, no. 7679 (2017), pp. 232–6
80 Strickland, Eliza. ‘4 Steps to Turn “Neural Dust” Into a Medical Reality’, IEEE Spectrum, 21
October 2016 <https://spectrum.ieee.org/4-steps-to-turn-neural-dust-into-a-medical-reality>
81 Lee, Jihun, et al. ‘Neural Recording and Stimulation Using Wireless Networks of Microimplants’.
Nature Electronics, vol. 4, no. 8 (2021), pp. 604–14
82 ‘Brain chips will become “more common than pacemakers”, says investor, as startup raises $10m’,
The Stack, 19 May 2021 <https://thestack.technology/blackrock-neurotech-brain-machine-
interfaces-peter-thiel/>
83 Ghose, Carrie. ‘Ohio State researcher says Battelle brain-computer interface for paralysis could save
$7B in annual home-care costs’, Columbus Business First, 10 October 2019
<https://www.bizjournals.com/columbus/news/2019/10/10/ohio-state-researcher-saysbattelle-
brain-computer.html>
84 Regalado, Antonio. ‘Thought Experiment’, MIT Technology Review, 17 June 2014
<https://www.technologyreview.com/2014/06/17/172276/the-thought-experiment/>

Chapter 6: The healing spark

1 Bowen, Chuck. ‘Nerve Repair Innovation Gives Man Hope’, Spinal Cord Injury Information Pages,
4 July 2007 <https://www.sci-info-pages.com/news/2007/07/nerve-repair-innovation-gives-man-
hope/>
2 Wallack, Todd. ‘Sense of urgency for spinal device’, Boston Globe. 18 September 2007
<http://archive.boston.com/business/globe/articles/2007/09/18/sense_of_urgency_for_spinal_d
evice/>
3 Per Debra Bohnert, Richard Borgens’ lab assistant from 1986 to 2019, in a telephone interview with
the author.
4 Jaffe, L. F., and M.-m. Poo. ‘Neurites grow faster towards the cathode than the anode in a steady
field’. Journal of Experimental Zoology 209 (1979), pp. 115–28
5 Ingvar, Sven. ‘Reaction of cells to the galvanic current in tissue cultures’. Experimental Biology and
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6 Bishop, Chris. ‘The Briks of Denton and Dallas TX’, Garage Hangover, 18 October 2007
<https://garagehangover.com/briks-denton-dallas/>
7 Pithoud, Kelsey. ‘Ex-rocker turns to research’, The Purdue Exponent, 17 September 2003
<https://web.archive.org/web/20151216205707/https://www.purdueexponent.org/campus/article
_73f34375-9059-5273-b6a8-8d9577c74b5d.html>
8 Bishop, ‘The Briks’, 2007
9 Comment by Johnny Young on Bishop, ‘The Briks’, 2007. 25 January 2019 at 11.33 a.m.
10 Kolsti, Nancy. ‘This is . . . Spinal Research’, The North Texan Online, Fall 2001
<https://northtexan.unt.edu/archives/f01/spinal.htm>
11 Hinkle, Laura, et al. ‘The direction of growth of differentiating neurones and myoblasts from frog
embryos in an applied electric field’. The Journal of Physiology, 314 (1981), pp. 121–35
12 McCaig, Colin. ‘Epithelial Physiology, Ovarian Follicles, Nerve Growth Cones, Vibrating Probes,
Wound Healing, and Cluster Headache: Staggering Steps on a Route Map to Bioelectricity’.
Bioelectricity, vol. 2, no. 4 (2020), pp. 411–17 (p. 412)
13 Borgens, Richard, et al. ‘Bioelectricity and Regeneration’. BioScience, vol. 29, no. 8 (1979), pp. 468–74
14 Borgens, Richard, et al. ‘Large and persistent electrical currents enter the transected lamprey spinal
cord’. Proceedings of the National Academy of Sciences, vol. 77, no. 2 (1980), pp. 1209–13
15 Borgens, Richard B., Andrew R. Blight and M. E. McGinnis. ‘Behavioral Recovery Induced by
Applied Electric Fields After Spinal Cord Hemisection in Guinea Pig’. Science, vol. 238, no. 4825
(1987), pp. 366–9
16 Kleitman, Naomi. ‘Under one roof: the Miami Project to Cure Paralysis model for spinal cord injury
research’. Neuroscientist, vol. 7, no. 3 (2001), pp. 192–201
 Borgens, Richard B., et al. ‘Effects of Applied Electric Fields on Clinical Cases of Complete
17
Paraplegia in Dogs’. Restorative Neurology and Neuroscience, vol. 5, no.5-6 (1993), pp. 305–22
18 ‘Electrical stimulation helps dogs with spinal injuries’, Purdue News, 21 July 1993
<https://www.purdue.edu/uns/html3month/1990-95/930721.Borgens.dogstudy.html>
19 Orr, Richard. ‘Research On Dogs’ Spinal Cord Injuries May Lead To Help For Humans’, Chicago
Tribune, 20 November 1995 <https://www.chicagotribune.com/news/ct-xpm-1995-11-20-
9511200137-story.html>
20 ‘Purdue/IU partnership in paralysis research’, Purdue News Service, 28 July 1999
<https://www.purdue.edu/uns/html4ever/1999/990730.Borgens.institute.html>
21 ‘Human Trial for Spinal Injury Treatment Launched by Purdue, IU’, Purdue News Service,
December 2000 <https://www.purdue.edu/uns/html4ever/001120.Borgens.SpinalTrial.html>
22 Callahan, Rick. ‘Two universities launch clinical trial for paralysis patients’, Middletown Press, 12
December 2000 <https://www.middletownpress.com/news/article/Two-universities-launch-
clinical-trial-for-11940807.php>
23 This quote is taken from an edition of Purdue School of Veterinary Medicine’s self-published
newsletter seen by the author: ‘Tales from the Vet Clinic: Yukon overcomes his chilling ordeal!’,
Synapses, Fall 2020
24 ‘Device to Aid Paralysis Victims to Get Test’, Los Angeles Times, 13 December 2000
25 Bowen, C. ‘Nerve Repair Innovation Gives Man Hope’, Indianapolis Star, 4 July 2007
<http://www.indystar.com/apps/pbcs.dll/article?
AID=/20070703/BUSINESS/707030350/1003/BUSINESS>
26 ravn, Karen. ‘In spinal research, pets lead the way’, Los Angeles Times, 9 April 2007
<https://www.latimes.com/archives/la-xpm-2007-apr-09-he-labside9-story.html>
27 ‘Implanted device offers new sensation’, The Engineer, 11 January 2005
<https://www.theengineer.co.uk/implanted-device-offers-new-sensation/>
28 ‘Cyberkinetics to acquire Andara Life Science for $4.5M’, Boston Business Journal, 13 February 2006
<https://www.bizjournals.com/boston/blog/mass-high-tech/2006/02/cyberkinetics-to-acquire-
andara-life-science.html>
29 Cyberkinetics press release, 28 September 2006
<https://www.purdue.edu/uns/html3month/2006/060928CyberkineticsAward.pdf>
30 Robinson, Kenneth, and Peter Cormie. ‘Electric Field Effects on Human Spinal Injury: Is There a
Basis in the In Vitro Studies?’. Developmental Neurobiology, vol. 68, no. 2 (2008), pp. 274–80
31 Wallack, ‘Sense of urgency’, 2007
32 Shapiro, Scott. ‘A Review of Oscillating Field Stimulation to Treat Human Spinal Cord Injury’. World
Neurosurgery, vol. 81/5–6 (2014), pp. 830–5
33 Bowman, Lee. ‘Study on dogs yields hope in human paralysis treatment’, Seattle Post-Intelligencer, 3
August 2004
34 Li, Jianming. ‘Oscillating Field Electrical Stimulator (OFS) for Regeneration of the Spinal Cord’,
2017 entry to the Create the Future Design Contest
<https://contest.techbriefs.com/2017/entries/medical/8251>
35 Li, Jianming. ‘Weak Direct Current (DC) Electric Fields as a Therapy for Spinal Cord Injuries:
Review and Advancement of the Oscillating Field Stimulator (OFS)’. Neurosurgical Review, vol. 42, no.
4 (2019), pp. 825–34
36 Willyard, Cassandra. ‘How a Revolutionary Technique Got People with Spinal-Cord Injuries Back on
Their Feet’. Nature, vol. 572, no. 7767 (2019), pp. 20–5
37 Even chemical and physical factors like contact inhibition release and population pressure.
38 McCaig, Colin D., et al. ‘Controlling Cell Behavior Electrically: Current Views and Future Potential’.
Physiological Reviews, vol. 85, no. 3 (2005), pp. 943–78
39 ‘Direct-current (DC) electric fields are present in all developing and regenerating animal tissues, yet
their existence and potential impact on tissue repair and development are largely ignored,’ they wrote
 in ‘Controlling Cell Behavior Electrically’.
40 Reid, Brian, et al. ‘Wound Healing in Rat Cornea: The Role of Electric Currents’. The FASEB Journal,
vol. 19, no. 3 (2005), pp. 379–86
41 Hagins, W.A., et al. ‘Dark Current and Photocurrent in Retinal Rods’. Biophysical Journal, vol. 10, no. 5
(1970), pp. 380–412
42 Song, Bing, et al. ‘Electrical Cues Regulate the Orientation and Frequency of Cell Division and the
Rate of Wound Healing in Vivo’. Proceedings of the National Academy of Sciences, vol. 99, no. 21 (2002),
pp. 13577–82
43 Leppik, Liudmila, et al. ‘Electrical Stimulation in Bone Tissue Engineering Treatments’. European
Journal of Trauma and Emergency Surgery, vol. 46, no. 2 (2020), pp. 231–44
44 Zhao, Min, et al. ‘Electrical Signals Control Wound Healing through Phosphatidylinositol-3-OH
Kinase-γ and PTEN’. Nature, vol. 442, no. 7101 (2006), pp. 457–60.
45 See National Institutes for Health, ‘A Clinical Trial of Dermacorder for Detecting Malignant Skin
Lesions’, 17 November 2009 <https://clinicaltrials.gov/ct2/show/NCT01014819>
46 Nuccitelli, R., et al. ‘The electric field near human skin wounds declines with age and provides a
noninvasive indicator of wound healing’. Wound Repair and Regeneration, vol. 19, no. 5 (2011), pp. 645–
55
47 Stephens, Tim. ‘Bioelectronic device achieves unprecedented control of cell membrane voltage’, UC
Santa Cruz News Center, 24 September 2020
<https://news.ucsc.edu/2020/09/bioelectronics.html>
48 Ershad, F., A. Thukral., J. Yue, et al. ‘Ultra-conformal drawn-on-skin electronics for multifunctional
motion artifact-free sensing and point-of-care treatment’. Nature Communications, vol. 11, no. 3823
(2020), doi: https://doi.org/10.1038/s41467-020-17619-1

Part 4: Bioelectricity in Birth and Death

Chapter 7: In the beginning

1 Levin, Michael. ‘What Bodies Think About: Bioelectric Computation Beyond the Nervous System as
Inspiration for New Machine Learning Platforms’. The Thirty-second Annual Conference on
Neural Information Processing Systems (NIPS). Palais des Congrès de Montréal, Montréal, Canada.
4 December 2018, slide 49
<https://media.neurips.cc/Conferences/NIPS2018/Slides/Levin_bioelectric_computation.pdf>;
see also Pullar, Christine E. (ed.). The Physiology of Bioelectricity in Development, Tissue Regeneration and
Cancer. Boca Raton: CRC Press, 2011, p. 69
2 Sampogna, Gianluca, et al. ‘Regenerative Medicine: Historical Roots and Potential Strategies in
Modern Medicine’. Journal of Microscopy and Ultrastructure, vol. 3, no. 3 (2015), pp. 101–7 (p. 101)
3 Power, Carl, and John E. J. Rasko. ‘The stem cell revolution isn’t what you think it is’, New Scientist,
29 September 2021 <https://www.newscientist.com/article/mg25133542-600-the-stem-cell-
revolution-isnt-what-you-think-it-is>
4 Burr, Harold Saxton, et al. ‘A Vacuum Tube Micro-Voltmeter for the Measurement of Bio-Electric
Phenomena’. The Yale Journal of Biology and Medicine, vol. 9, no. 1 (1936), pp. 65–76. It is pictured on
the journal’s website alongside the article:
<https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2601500/figure/F1/>
5 Burr, Harold Saxton. Blueprint for Immortality: The Electric Patterns of Life. Essex: Neville Spearman
Publishers, 1972, p. 48
6 Burr, Harold Saxton, L. K. Musselman, Dorothy Barton, and Naomi B. Kelly. ‘Bio-Electric
Correlates of Human Ovulation’. The Yale Journal of Biology and Medicine, vol. 10, no. 2 (1937), pp. 155–
60
7 Burr, Harold Saxton, R. T. Hill, and E. Allen. ‘Detection of Ovulation in the Intact Rabbit’.
Proceedings of the Society for Experimental Biology and Medicine, vol. 33, no. 1 (1935), pp. 109–11
8 Burr, Blueprint, p. 50
9 Burr, Blueprint, p. 51
10 Langman, Louis, and H. S. Burr. ‘Electrometric Timing of Human Ovulation’. American Journal of
Obstetrics and Gynecology, vol. 44, no. 2 (1942), pp. 223–9
11 ‘Medicine: Yale Proof ’, Time, 11 October 1937
<http://content.time.com/time/subscriber/article/0,33009,770949-1,00.html>
12 There is a diagram on p. 156 of Burr et al., ‘Bio-Electric Correlates’.
<https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2601785/?page=2>
13 Altmann, Margaret. ‘Interrelations of the Sex Cycle and the Behavior of the Sow’. Journal of
Comparative Psychology, vol. 31, no. 3 (1941), pp. 481–98
14 ‘Dr. John Rock (1890–1984)’, PBS American Experience
<https://www.pbs.org/wgbh/americanexperience/features/pill-dr-john-rock-1890-1984/>
15 Snodgrass, James, et al. ‘The Validity Of “Ovulation Potentials”’. American Journal of Physiology – Legacy
Content, vol. 140, no. 3 (1943), pp. 394–415
16 Su, Hsiu-Wei, et al. ‘Detection of Ovulation, a Review of Currently Available Methods’. Bioengineering
& Translational Medicine, vol. 2, no. 3 (2017), pp. 238–46
17 Herzberg, M., et al. ‘The Cyclic Variation of Sodium Chloride Content in the Mucus of the Cervix
Uteri’. Fertility and Sterility, vol. 15, no. 6 (1964), pp. 684–94
18 Burr, Harold Saxton, and L. K. Musselman. ‘Bio-Electric Phenomena Associated with
Menstruation’. The Yale Journal of Biology and Medicine, vol. 9, no. 2 (1936), pp. 155–8
19 Tosti, Elisabetta. ‘Electrical Events during Gamete Maturation and Fertilization in Animals and
Humans’. Human Reproduction Update, vol. 10, no. 1 (2004), pp. 53–65
20 Van Blerkom, J. ‘Domains of High-Polarized and Low-Polarized Mitochondria May Occur in Mouse
and Human Oocytes and Early Embryos’. Human Reproduction, vol. 17, no. 2 (2002), pp. 393–406
21 Trebichalská, Zuzana and Zuzana Holubcová. ‘Perfect Date—the Review of Current Research into
Molecular Bases of Mammalian Fertilization’. Journal of Assisted Reproduction and Genetics, vol. 37, no. 2
(2020), pp. 243–56
22 Stein, Paula, et al. ‘Modulators of Calcium Signalling at Fertilization’. Open Biology, vol. 10, no. 7
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23 Campbell, Keith H., et al. ‘Sheep cloned by nuclear transfer from a cultured cell line’. Nature, vol.
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24 Zimmer, Carl. ‘Growing Left, Growing Right’, The New York Times, 3 June 2013
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25 Some have problems with breathing normally and fertility.
26 See Nuccitelli, Richard, Ionic Currents In Development. New York: International Society of
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28 Adams, Dany S., and Michael Levin. ‘General Principles for Measuring Resting Membrane Potential
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29 Cone, Clarence, and Charlotte M. Cone. ‘Induction of Mitosis in Mature Neurons in Central
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31 Vandenberg, Laura N., et al. ‘V-ATPase-Dependent Ectodermal Voltage and Ph Regionalization Are
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32 Adams, Dany Spencer, et al. ‘Bioelectric Signalling via Potassium Channels: A Mechanism for
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33 Moody, William J., et al. ‘Development of ion channels in early embryos’. Journal of Neurobiology 22
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34 Rovner, Sophie. ‘Recipes for Limb Renewal’, Chemical & Engineering News, 2 August 2010
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35 Pai, Vaibhav P., et al. ‘Transmembrane Voltage Potential Controls Embryonic Eye Patterning in
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37 Hall, Danielle. ‘Brittle Star Splits’, Smithsonian Ocean, January 2020 <https://ocean.si.edu/ocean-
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38 Levin, Michael. ‘Reading and Writing the Morphogenetic Code: Foundational White Paper of the
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39 Kolata, Gina. ‘Surgery on Fetuses Reveals They Heal Without Scars’, The New York Times, 16 August
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42 Sisken, Betty. ‘Enhancement of Nerve Regeneration by Selected Electromagnetic Signals’. In: Marko
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44 Tseng, Ai-sun, and Michael Levin. ‘Cracking the bioelectric code: Probing endogenous ionic controls
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46 Dlouhy, Brian J., et al. ‘Autograft-Derived Spinal Cord Mass Following Olfactory Mucosal Cell
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47 Jabr, Ferris. ‘In the Flesh: The Embedded Dangers of Untested Stem Cell Cosmetics’, Scientific
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48 Aldhous, Peter. ‘An Experiment That Blinded Three Women Unearths the Murky World of Stem
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became-a-wild-west-for-dodgy-treatments/>
50 Feng J. F., et al. ‘Electrical Guidance of Human Stem Cells in the Rat Brain’. Stem Cell Reports, vol. 9,
no. 1 (2017), pp. 177–89

Chapter 8: At the end

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26 Reported ubiquitously, including in Pullar, Christine E. (ed.). The Physiology of Bioelectricity in
Development, Tissue Regeneration and Cancer. Boca Raton: CRC Press, 2011, p. 271
27 Arcangeli, Annarosa, and Andrea Becchetti. ‘New Trends in Cancer Therapy: Targeting Ion
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29 Kunzelmann, 2005; Fiske, et al, 2006; Stuhmer, et al, 2006; Prevarskaya, et al, 2010; Becchetti, 2011;
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30 Santos, Rita, et al. ‘A comprehensive map of molecular drug targets’. Nature Reviews Drug Discovery,
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31 McKie, Robin. ‘For 30 years I’ve been obsessed by why children get leukaemia. Now we have an
answer’, The Guardian, 30 December 2018
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protection-against-disease>
32 Djamgoz, Mustafa, S. P. Fraser, and W. J. Brackenbury. (2019). ‘In Vivo Evidence for Voltage-Gated
Sodium Channel Expression in Carcinomas and Potentiation of Metastasis’. Cancers, vol. 11, no. 11
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33 Leanza, Luigi, Antonella Managò, Mario Zoratti, Erich Gulbins, and Ildiko Szabo. ‘Pharmacological
targeting of ion channels for cancer therapy: In vivo evidences’. Biochimica et Biophysica Acta (BBA) –
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34 In 2019, a Chinese multicentre preclinical trial tested an antibody that was effective against
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35 Lang, F., and C. Stournaras. ‘Ion channels in cancer: future perspectives and clinical potential’.
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36 ‘An interview with Professor Mustafa Djamgoz’, External Speaker Series presentation, Metrion
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37 ‘The Bioelectricity Revolution: A Discussion Among the Founding Associate Editors’. Bioelectricity,
vol. 1, no. 1 (2019), pp. 8–15
38 Greaves, Mel. ‘Nothing in cancer makes sense except . . .’. BMC Biology, vol. 16, no. 22 (2018)
39 Wilson, Clare. ‘The secret to killing cancer may lie in its deadly power to evolve’, New Scientist, 4
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40 Hope, Tyna, and Siân Iles. ‘Technology review: The use of electrical impedance scanning in the
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41 Wilke, Lee, et al. ‘Repeat surgery after breast conservation for the treatment of stage 0 to II breast
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42 Dixon, J. Michael, et al. ‘Intra-operative assessment of excised breast tumour margins using
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43 Djamgoz, Mustafa. ‘In vivo evidence for expression of voltage-gated sodium channels in cancer and
potentiation of metastasis’, Sophion Bioscience YouTube channel, 18 July 2019
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44 Dokken, Kaylinn, and Patrick Fairley. ‘Sodium Channel Blocker Toxicity’ [Updated 30 April 2022].
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45 Reddy, Jay P., et al. ‘Antiepileptic drug use improves overall survival in breast cancer patients with
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46 Takada, Mitsutaka, et al. ‘Inverse Association between Sodium Channel-Blocking Antiepileptic Drug
Use and Cancer: Data Mining of Spontaneous Reporting and Claims Databases’. International Journal
of Medical Sciences, vol. 13, no. 1 (2016), pp. 48–59, doi: 10.7150/ijms.13834
47 ‘An interview with Professor Mustafa Djamgoz’, External Speaker Series presentation, Metrion
BioSciences, Cambridge 2018
48 Quail, Daniela F., and Johanna A. Joyce. ‘Microenvironmental regulation of tumor progression and
metastasis’. Nature Medicine, vol. 19, no. 11 (2013), pp. 1423–37, doi: 10.1038/nm.3394
49 Zhu, Kan, et al. ‘Electric Fields at Breast Cancer and Cancer Cell Collective Galvanotaxis’. Scientific
Reports, vol. 10, no. 1 (2020), article 8712
50 Wapner, Jessica. ‘A New Theory on Cancer: What We Know About How It Starts Could All Be
Wrong’, Newsweek, 17 July 2017 <https://www.newsweek.com/2017/07/28/cancer-evolution-cells-
637632.html>; see also Davies, Paul. ‘A new theory of cancer’, The Monthly, November 2018
<https://www.themonthly.com.au/issue/2018/november/1540990800/paul-davies/new-theory-
cancer#mtr>
51 Silver, Brian, and Celeste Nelson. ‘The Bioelectric Code: Reprogramming Cancer and Aging From
the Interface of Mechanical and Chemical Microenvironments’. Frontiers in Cell and Developmental
Biology, vol. 6, no. 21 (2018)
52 Lobikin, Maria, Brook Chernet, Daniel Lobo, and Michael Levin. ‘Resting potential, oncogene-
induced tumorigenesis, and metastasis: the bioelectric basis of cancer in vivo’. Physical Biology, vol. 9,
no. 6 (2012), loc. 065002. doi: 10.1088/1478-3975/9/6/065002
53 Chernet, Brook, and Michael Levin. ‘Endogenous Voltage Potentials and the Microenvironment:
Bioelectric Signals that Reveal, Induce and Normalize Cancer’. Journal of Clinical and Experimental
Oncology, Suppl. 1:S1-002 (2013), doi: 10.4172/2324-9110
54 Chernet & Levin, ‘Endogenous’
55 Gruber, Ben. ‘Battling cancer with light’, Reuters, 26 April 2016
<https://www.reuters.com/article/us-science-cancer-optogenetics-idUSKCN0XN1u9>
56 Chernet, Brook, and Michael Levin. ‘Transmembrane voltage potential is an essential cellular
parameter for the detection and control of tumor development in a Xenopus model’. Disease Models
& Mechanisms, vol. 6, no. 3 (2013), pp. 595–607, doi: 10.1242/dmm.010835
57 Silver & Nelson, ‘The Bioelectric Code’
58 Tuszynski, Jack, Tatiana Tilli, and Michael Levin. ‘Ion Channel and Neurotransmitter Modulators as
Electroceutical Approaches to the Control of Cancer’. Current Pharmaceutical Design, vol. 23, no. 32
 (2017), pp. 4827–41
59 Schlegel, Jürgen, et al. ‘Plasma in cancer treatment’, Clinical Plasma Medicine, vol. 1, no. 2 (2013), pp.
2–7

Part 5: Bioelectricity in the Future

Chapter 9: Swapping silicon for squids

1 Brown, Joshua. ‘Team Builds the First Living Robots’, The University of Vermont, 13 January 2020
<https://www.uvm.edu/news/story/team-builds-first-living-robots>
2 Lee, Y., et al. ‘Hydrogel soft robotics’. Materials Today Physics 15 (2020)
<https://doi.org/10.1016/j.mtphys.2020.100258>
3 Thubagere, Anupama, et al. ‘A Cargo-Sorting DNA Robot’. Science, vol. 357, article 6356 (2017),
eaan6558
4 Solon, Olivia. ‘Electroceuticals: swapping drugs for devices’, Wired, 28 May 2013
<https://www.wired.co.uk/article/electroceuticals>
5 Geddes, Linda. ‘Healing spark: Hack body electricity to replace drugs’, New Scientist, 19 February
2014 <https://www.newscientist.com/article/mg22129570-500-healing-spark-hack-body-electricity-
to-replace-drugs/>
6 Behar, Michael. ‘Can the nervous system be hacked?’, The New York Times, 23 May 2014
<https://www.nytimes.com/2014/05/25/magazine/can-the-nervous-system-be-hacked.html>
7 Mullard, Asher. ‘Electroceuticals jolt into the clinic, sparking autoimmune opportunities’. Nature
Reviews Drug Discovery 21 (2022), pp. 330–1
8 Hoffman, Henry, and Harold Norman Schnitzlein. ‘The Numbers of Nerve Fibers in the Vagus
Nerve of Man’. The Anatomical Record, vol. 139, no. 3 (1961), pp. 429–35
9 Davies, Dave. ‘Are Implanted Medical Devices Creating a “Danger Within Us”?’, NPR, 17 January
2018 <https://www.npr.org/2018/01/17/578562873/are-implanted-medical-devices-creating-a-
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10 Golabchi, Asiyeh, et al. ‘Zwitterionic Polymer/Polydopamine Coating Reduce Acute Inflammatory
Tissue Responses to Neural Implants’. Biomaterials 225 (2019), 119519
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11 Leber, Moritz, et al. ‘Advances in Penetrating Multichannel Microelectrodes Based on the Utah Array
Platform’. In: Xiaoxiang Zheng (ed.), Neural Interface: Frontiers and Applications. Singapore: Springer,
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12 Yin, Pengfei, et al. ‘Advanced Metallic and Polymeric Coatings for Neural Interfacing: Structures,
Properties and Tissue Responses’. Polymers, vol. 13, no. 16 (2021), article 2834
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13 Aregueta-Robles, U. A., et al. ‘Organic electrode coatings for next-generation neural interfaces’.
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14 ‘The Nobel Prize in Chemistry 2000’, NobelPrize.org
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15 Cuthbertson, Anthony. ‘Material Found by Scientists “Could Merge AI with Human Brain”’, The
Independent, 17 August 2020 <https://www.independent.co.uk/tech/artificial-intelligence-brain-
computer-cyborg-elon-musk-neuralink-a9673261.html>
16 Chen, Angela. ‘Why It’s so Hard to Develop the Right Material for Brain Implants’, The Verge, 30
May 2018 <https://www.theverge.com/2018/5/30/17408852/brain-implant-materials-
neuroscience-health-chris-bettinger>
 Technically, there are also ways to inhibit action potentials, but that just means stimulating inhibitory
17 neurons – which are the kinds of neurons that make other neurons not fire. But it’s still the same
mechanism.
18 Some companies try to understand how the body has interpreted the action potential by implanting
even more electrodes to listen to the ensuing signals. But that carries additional surgical risk, and it’s
certainly not happening in humans.
19 Casella, Alena, et al. ‘Endogenous Electric Signaling as a Blueprint for Conductive Materials in
Tissue Engineering’. Bioelectricity, vol. 3, no. 1 (2021), pp. 27–41
20 Demers, Caroline, et al. ‘Natural Coral Exoskeleton as a Bone Graft Substitute: A Review’. Bio-
Medical Materials and Engineering, vol. 12, no. 1 (2002), pp. 15–35
21 Israel-based OkCoral and CoreBone grow coral on a special diet to make it especially suitable to
grafting.
22 Wan, Mei-chen, et al. ‘Biomaterials from the Sea: Future Building Blocks for Biomedical
Applications’. Bioactive Materials, vol. 6, no. 12 (2021), pp. 4255–85
23 DeCoursey, Thomas. ‘Voltage-Gated Proton Channels and Other Proton Transfer Pathways’.
Physiological Reviews, vol. 83, no. 2 (2003) pp. 475–579, doi: 10.1152/physrev.00028.2002
24 Lane, Nick. ‘Why Are Cells Powered by Proton Gradients?’. Nature Education, vol. 3, no. 9 (2010), p.
18
25 Kautz, Rylan, et al. ‘Cephalopod-Derived Biopolymers for Ionic and Protonic Transistors’. Advanced
Materials, vol. 30, no. 19 (2018), loc. 1704917
26 Ordinario, David, et al. ‘Bulk protonic conductivity in a cephalopod structural protein’. Nature
Chemistry, vol. 6, no. 7 (2014), pp. 596–602
27 Strakosas, Xenofon, et al. ‘Taking Electrons out of Bioelectronics: From Bioprotonic Transistors to
Ion Channels’. Advanced Science, vol. 4, no. 7 (2017), loc. 1600527
28 Kim, Young Jo, et al. ‘Self-Deployable Current Sources Fabricated from Edible Materials’. Journal of
Materials Chemistry B 31 (2013), p. 3781, doi: 10.1039/C3TB20183J
29 Ordinario, David, et al. ‘Protochromic Devices from a Cephalopod Structural Protein’. Advanced
Optical Materials, vol. 5, no. 20 (2017), loc. 1600751
30 Sheehan, Paul. ‘Bioelectronics for Tissue Regeneration’. Defense Advanced Projects Research
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31 Kriegman, Sam, et al, ‘Kinematic Self-Replication in Reconfigurable Organisms’. Proceedings of the
National Academy of Sciences, vol. 118, no. 49 (2021), loc. e2112672118
<https://doi.org/10.1073/pnas.2112672118>
32 Coghlan, Simon and Kobi Leins. ‘Will self-replicating “xenobots” cure diseases, yield new
bioweapons, or simply turn the whole world into grey goo?’, The Conversation, 9 December 2021
<https://theconversation.com/will-self-replicating-xenobots-cure-diseases-yield-new-bioweapons-
or-simply-turn-the-whole-world-into-grey-goo-173244>
33 Adamatzky, Andrew, et al. ‘Fungal Electronics’. Biosystems 212 (2021), loc. 104588, doi:
10.1016/j.biosystems.2021.104588

Chapter 10: Electrifying ourselves better

1 Nitsche, Michael A., et al. ‘Facilitation of Implicit Motor Learning by Weak Transcranial Direct
Current Stimulation of the Primary Motor Cortex in the Human’. Journal of Cognitive Neuroscience, vol.
15, no. 4 (2003), pp. 619–26, doi: https://doi.org/10.1162/089892903321662994
2 Trivedi, Bijal. ‘Electrify your mind – literally’, New Scientist, 11 April 2006
<https://www.newscientist.com/article/mg19025471-100-electrify-your-mind-literally/>
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3
sleep improves declarative memory’. The Journal of Neuroscience vol. 24, no. 44 (2004), pp. 9985–92,
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4 Walsh, Professor Vincent. ‘Cognitive Effects of TDC at Summit on Transcranial Direct Current
Stimulation (tDCS) at the UC-Davis Center for Mind & Brain’, UC Davis YouTube channel, 8
October 2013 <https://www.youtube.com/watch?v=9fz7r8VDV4o>. The relevant section of the
lecture begins around fourteen minutes in.
5 Wurzman, Rachel et al. ‘An open letter concerning do-it-yourself users of transcranial direct current
stimulation’. Annals of Neurology, vol 80, Issue 1. July 2016
6 Aschwanden, Christie. ‘Science isn’t broken: It’s just a hell of a lot harder than we give it credit for’,
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7 Verma, N., et al. ‘Auricular Vagus Neuromodulation – A Systematic Review on Quality of Evidence
and Clinical Effects’. Frontiers in Neuroscience 15 (2021), article 664740
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8 Young, Stella. ‘I’m not your inspiration, thank you very much.’ TED, June 2014,
www.ted.com/talks/stella_young_i_m_not_your_inspiration_thank_you_very_much/
9 Source is interview with the author at the International Neuroethics Society meeting, 2 November
2018. The issues are also explored in Drew, Liam. ‘The ethics of brain–computer interfaces’. Nature.
24 July 2019 <https://www.nature.com/articles/d41586-019-02214-2>
10 Strickland, Eliza. ‘Worldwide Campaign For Neurorights Notches Its First Win’, IEEE Spectrum, 18
December 2021 <https://spec-trum.ieee.org/neurotech-neurorights>
11 Coghlan, Andy. ‘Vaping really isn’t as harmful for your cells as smoking’, New Scientist, 4 January 2016
<https://www.newscientist.com/article/dn28723-vaping-really-isnt-as-harmful-for-your-cells-as-
smoking/>
12 ‘Committee on the Review of the Health Effects of Electronic Nicotine Delivery Systems and
Others’. In: Kathleen Stratton, Leslie Y. Kwan, and David L. Eaton (eds), Public Health Consequences of
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13 Moehn, Kayla,Yunus Ozekin, and Emily Bates. ‘Investigating the Effects of Vaping and Nicotine’s
Block of Kir2.1 on Humerus and Digital Development in Embryonic Mice’. FASEB Journal, vol. 36,
no. S1 (2022) <https://doi.org/10.1096/fasebj.2022.36.S1.R2578>
14 Benzonana, Laura, et al. ‘Isoflurane, a Commonly Used Volatile Anesthetic, Enhances Renal Cancer
Growth and Malignant Potential via the Hypoxia-Inducible Factor Cellular Signaling Pathway In
Vitro’. Anesthesiology, vol. 119, no. 3 (2013), pp. 593–605
15 Jiang, Jue, and Hong Jiang. ‘Effect of the Inhaled Anesthetics Isoflurane, Sevoflurane and
Desflurane on the Neuropathogenesis of Alzheimer’s Disease (Review)’. Molecular Medicine Reports,
vol. 12, no. 1 (2015), pp. 3–12
16 Robson, David. ‘This is what it’s like waking up during surgery’, Mosaic, 12 March 2019
<https://mosaicscience.com/story/anaesthesia-anesthesia-awake-awareness-surgery-operation-or-
paralysed/>
17 Edelman, Elazer, et al. ‘Case 30-2020: A 54-Year-Old Man with Sudden Cardiac Arrest’. New England
Journal of Medicine, vol. 383, no. 13 (2020), pp. 1263–75
18 Hesham, R. Omar, et al. ‘Licorice Abuse: Time to Send a Warning Message’. Therapeutic Advances in
Endocrinology and Metabolism, vol. 3, no. 4 (2012), pp. 125–38
19 Actually, I noticed two patterns: most of the scientists who got hit with the most scathing criticism
were women. The men sometimes didn’t recall any trouble at all.
20 Davies, Paul. The Demon in the Machine. London: Allen Lane, 2019,, p. 86
21 McNamara, H. M., et al. ‘Bioelectrical domain walls in homogeneous tissues’. Nature Physics 16
(2020), pp. 357–64 <https://doi.org/10.1038/s41567-019-0765-4>
22 Davies, The Demon in the Machine, pp. 82–3
23 Pietak, A., and Levin, M. ‘Exploring Instructive Physiological Signaling with the Bioelectric Tissue
Simulation Engine’. Frontiers in Bioengineering and Biotechnology, vol. 4, article 55 (2016), doi:
10.3389/fbioe.2016.00055
 INDEX

Académie des sciences (France) ref1, ref2, ref3

action potential ref1, ref2, ref3, ref4
and cancer ref1, ref2, ref3
and the heart ref1, ref2, ref3
and implants ref1
and the spine ref1
Adamatzky, Andrew ref1
Adams, Dany Spencer ref1, ref2, ref3, ref4, ref5, ref6
and cancer treatments ref1, ref2, ref3
and protons ref1, ref2
Adrian, Edgar ref1, ref2, ref3, ref4, ref5
and Berger ref1, ref2
afferent system ref1
aggression ref1
Agnew, William ref1
AI (artificial intelligence) ref1
alcohol ref1
Aldini, Giovanni ref1, ref2, ref3, ref4, ref5
and Galvani ref1
and resuscitation ref1
algae ref1, ref2
alkaline earth metals ref1
Allen, Paul ref1
alpha waves ref1
Altmann, Margaret ref1
Alzheimer’s disease ref1
amber ref1, ref2, ref3
Ampère, André-Marie ref1
amputation ref1
anaesthesia ref1
Ancient Greece ref1
Andara ref1, ref2, ref3, ref4, ref5
animal electricity ref1, ref2, ref3, ref4, ref5
and the brain ref1
and ovulation ref1, ref2
and regeneration ref1, ref2
and the spine ref1, ref2
 see also dogs; frogs
animal spirits (pneuma psychikon) ref1, ref2, ref3
anti-vivisectionism ref1
Arcangeli, Annarosa ref1, ref2, ref3
Arrhenius, Svante ref1
arthropods ref1
artificial electricity see batteries
Ashcroft, Frances ref1, ref2
The Spark of Life ref1
atria ref1
autism ref1, ref2
Aw, Sherry ref1
axons ref1, ref2, ref3, ref4, ref5

bacteria ref1, ref2, ref3, ref4

Badylak, Stephen ref1, ref2, ref3
Bassi, Laura ref1, ref2
Bates, Emily ref1, ref2, ref3, ref4
batteries ref1, ref2, ref3, ref4, ref5
and Aldini ref1
and frogs ref1
and pacemakers ref1
Beccaria, Giambattista ref1, ref2
bed sores ref1
Benabid, Alim-Louis ref1
Benedict XIV, Pope ref1
Berger, Hans ref1, ref2, ref3, ref4
Berger, Theodore ref1, ref2, ref3
beta waves ref1
BETR programme ref1
BETSE (Bioelectric Tissue Simulation Engine) ref1
Bettinger, Chris ref1
biocompatible materials ref1
bioelectric code ref1, ref2, ref3
Bioelectricity (journal) ref1
bioimpedance ref1
biology ref1, ref2, ref3
bioreactor ref1
Bird, Golding ref1
birth control ref1, ref2
birth defects ref1, ref2
Bissel, Mina ref1
Blondel, Christine ref1, ref2
blood ref1, ref2, ref3, ref4
Bohnert, Debra ref1, ref2, ref3, ref4, ref5, ref6
Bologna see University of Bologna
bones ref1, ref2, ref3, ref4, ref5
and coral grafts ref1
and healing ref1
Bongard, Joshua ref1, ref2
Borelli, Alfonso ref1
Borgens, Richard ref1, ref2, ref3, ref4, ref5, ref6, ref7
Bouton, Chad ref1
bradycardia ref1, ref2
brain, the ref1, ref2, ref3, ref4, ref5
and chips ref1
and computing ref1
and ECG ref1
and electro-therapy ref1
and implants ref1, ref2, ref3, ref4, ref5
and neurons ref1
and tumours ref1, ref2, ref3
see also DBS; memory; neural code; tDCS
BrainGate ref1, ref2
Bresadola, Marco ref1, ref2, ref3
Brugnatelli, Valentino ref1, ref2, ref3
Buoniconti, Marc ref1
Burkhardt, Ian ref1, ref2, ref3
Burr, Harold Saxton ref1, ref2, ref3, ref4, ref5, ref6
Byron, Lord ref1

calcium ref1, ref2, ref3, ref4

and cancer ref1
and channels ref1, ref2, ref3
and sperm ref1, ref2
Campenot, Robert ref1
cancer ref1, ref2, ref3, ref4
and ion channels ref1, ref2, ref3, ref4
and regeneration ref1
and treatment ref1, ref2, ref3
Carpue, Joseph ref1, ref2
Carradori, Giovacchino ref1, ref2, ref3
Catholicism ref1, ref2, ref3, ref4
Caton, Richard ref1
Cavuoto, James ref1, ref2, ref3
Celestial Bed ref1
cell membrane ref1, ref2, ref3, ref4
cephalopods see squid
Chernet, Brook ref1
children ref1
chitosan ref1, ref2
chloride ref1, ref2, ref3, ref4
and cancer ref1
and ovulation ref1
and sperm ref1
cilia ref1
ClearEdge ref1
cloning ref1
Cobb, Matthew ref1
coding ref1, ref2, ref3
 and bioelectric ref1, ref2, ref3
and neural ref1, ref2
Cohen, Adam ref1
collagen ref1
computers ref1
Connecticut Medical Society ref1
consciousness ref1, ref2
Copeland, Nathan ref1
Copernicus, Nicolaus ref1
coral ref1
Cormie, Peter ref1
corpses ref1, ref2
Coulomb, Charles ref1
Covid-19 pandemic ref1, ref2, ref3, ref4
Crick, Francis ref1, ref2, ref3, ref4
The Astonishing Hypothesis: The Scientific Search for the Soul ref1
CRISPR ref1
Curt, Gregory ref1
Cyberkinetics ref1, ref2, ref3
cybernetics ref1, ref2

DARPA (Defense Advanced Research Project Agency) ref1, ref2, ref3, ref4
and regeneration ref1
and tDCS ref1
Davies, Paul ref1, ref2
DBS (‘deep brain stimulation’) ref1, ref2, ref3, ref4, ref5
De Loof , Arnold ref1
death ref1, ref2; see also corpses
defibrilation ref1
Delgado, José ref1
dementia ref1, ref2, ref3
dendrites ref1
depression ref1, ref2, ref3, ref4, ref5
and DBS ref1
and tDCS ref1
Dermacorder ref1, ref2
Descartes, René ref1
diabetes ref1, ref2, ref3
die-back ref1
Dixon, Mike ref1
Djamgoz, Mustafa ref1, ref2, ref3, ref4
DNA ref1, ref2, ref3, ref4
Dobbs, David ref1
dogs ref1, ref2
Donoghue, John ref1, ref2, ref3
drugs see medicine
Du Bois-Reymond, Emil ref1, ref2, ref3, ref4

eating disorders ref1

ECG (electrocardiogram) ref1, ref2, ref3, ref4
ECoG (electrocorticography) ref1, ref2
EEG (electroencephalogram) ref1, ref2, ref3, ref4
efferent system ref1
eggs ref1
Einthoven, Willem ref1, ref2
electric fields ref1
electric fish ref1, ref2, ref3, ref4
electricity ref1, ref2, ref3
and algae ref1
and the brain ref1
and embryos ref1
and Galvani ref1, ref2, ref3, ref4
and the heart ref1
and medical care ref1, ref2
and regeneration ref1
and resuscitation ref1, ref2
and skin ref1, ref2
and sperm ref1
and the spine ref1
and Volta ref1, ref2, ref3
and wound-healing ref1, ref2
see also animal electricity; ions; voltage readings
electro-therapy ref1
electrocardiography ref1
electroceuticals ref1, ref2, ref3
electromagnetism ref1
electrome ref1, ref2, ref3
electrometers ref1
electrophorus ref1, ref2
electrophysiology ref1, ref2, ref3
electrostatic generators ref1, ref2, ref3
Ellsworth, Oliver ref1
embryos ref1, ref2, ref3, ref4
and regeneration ref1
and stem cells ref1
see also birth defects
EMG (electromyograph) ref1
endothelium ref1
epigenetics ref1
epilepsy ref1, ref2, ref3, ref4, ref5
and drugs ref1, ref2
epithelium ref1
Essai théorique et expérimental sur le galvanism (Aldini) ref1
eyes ref1, ref2, ref3

Famm, Kris ref1

Faraday, Michael ref1, ref2
fat cells ref1, ref2
FDA (Food and Drug Administration) ref1, ref2, ref3, ref4, ref5
and spinal injury ref1, ref2, ref3, ref4, ref5
fertility ref1, ref2
Finger, Stanley ref1
Firmian, Carlo ref1
First World War ref1, ref2, ref3
Forbes, Alexander ref1
Forster, George ref1, ref2, ref3
Franklin, Benjamin ref1, ref2, ref3, ref4
Franklin, Rosalind ref1
French, Jennifer ref1, ref2, ref3
Frisi, Paolo ref1
frogs ref1, ref2, ref3, ref4
and du Bois-Reymond ref1
and embryos ref1, ref2
and Matteucci ref1
and neural code ref1, ref2, ref3
and proton pumps ref1, ref2
and regeneration ref1, ref2
and robotics ref1, ref2
and spinal neurons ref1, ref2
and tumours ref1, ref2
Frohlich, Flavio ref1
fucus ref1
fungi ref1, ref2

Galen, Claudius ref1

Galileo Galilei ref1
Galvani, Luigi ref1, ref2, ref3, ref4, ref5, ref6, ref7
and Aldini ref1
and Humboldt ref1
Galvanic Society ref1, ref2, ref3, ref4
galvanism ref1, ref2
galvanometers ref1, ref2, ref3; see also string galvanometers
gamma waves ref1
gap junctions ref1, ref2, ref3
Geisler, David ref1
gelatin ref1
genome ref1, ref2, ref3, ref4, ref5
George, Mari Hulman ref1, ref2
Gilbert, Frederic ref1
Gilbert, William ref1
Gladstone, Herbert ref1
GlaxoSmithKline (GSK) ref1
glia ref1, ref2, ref3
Glickman, Morton ref1, ref2
Golgi, Camillo ref1
Gomez, Marcella ref1, ref2
Gorodetsky, Alon ref1
Graham, James ref1
Greatbatch, Wilson ref1, ref2
Greaves, Mel ref1, ref2
Greely, Hank ref1
Guericke, Otto von ref1

Hansen, Scott ref1

Harari, Yuval Noah: Homo Deus ref1
Harold, Franklin: To Make the World Intelligible ref1
Hattersley, Andrew ref1, ref2
Hauton, Jacques ref1
healing ref1, ref2, ref3, ref4
heart ref1, ref2, ref3, ref4
and pacemakers ref1
Heath, Robert ref1
Heeger, Alan J. ref1
Helmholtz, Hermann von ref1, ref2, ref3, ref4
hERG channel ref1, ref2
Hinkle, Laura ref1, ref2
Hodgkin, Alan ref1, ref2, ref3
homosexuality ref1
Humboldt, Alexander von ref1, ref2, ref3, ref4, ref5, ref6
Hutchinson, Alex ref1
Huxley, Andrew ref1, ref2, ref3
hydras ref1
hydrogel ref1
hydrogen ref1, ref2
Hyman, Albert ref1, ref2

Implanted Neural Prosthesis ref1

implants ref1, ref2
Ingram, Brandon ref1, ref2, ref3, ref4
ions ref1, ref2, ref3
and cancer ref1, ref2, ref3, ref4
and channels ref1, ref2
and chitosan ref1
and drugs ref1
and embryos ref1
and implants ref1

Jackson, Andrew ref1

Jaffe, Lionel ref1, ref2, ref3, ref4, ref5, ref6
and regeneration ref1
Johnson, Bryan ref1, ref2, ref3

Kennedy, Phil ref1, ref2

Kepler, Johannes ref1
keratin ref1
Kernel ref1, ref2, ref3, ref4
Kinneir, David ref1
Koch, Christoph ref1
Langman, Louis ref1, ref2
Langston, Joseph ref1
Lanzarini, Luigi ref1
left–right assymetry ref1, ref2, ref3
Lenzer, Jeanne: The Danger Within Us ref1
Levin, Michael ref1, ref2, ref3, ref4, ref5
and anaesthesia ref1
and cancer treatment ref1, ref2
and embryos ref1, ref2, ref3
and protons ref1
and regeneration ref1
and reviewers ref1, ref2, ref3
and stem cells ref1
and xenobots ref1, ref2
Lewis, Thomas ref1
Leyden jars ref1, ref2, ref3, ref4, ref5
Li, Jianming ref1, ref2
lightning ref1, ref2, ref3, ref4
liquorice ref1
liver ref1
Lobikin, Maria ref1
Loomis, Alfred ref1
Lopez, Jose ref1, ref2
Lucas, Keith ref1, ref2
Ludwig, Kip ref1, ref2, ref3, ref4
Lund, Elmer ref1

McCaig, Colin ref1

McCulloch, Warren ref1
MacDiarmid, Alan G. ref1
MacKinnon, Roderick ref1
Marblestone, Adam ref1, ref2
margin probes ref1
marine organisms ref1
Marshall, John ref1
Marshall, Lisa ref1
Matteucci, Carlo ref1
Mayberg, Helen ref1, ref2, ref3, ref4
medicine ref1, ref2, ref3, ref4
and cancer ref1
and ion channels ref1, ref2, ref3, ref4
and sodium-channel-blockers ref1
see also regenerative medicine
medics ref1
Medtronic ref1, ref2, ref3, ref4
MEG (magnetoencephalography) ref1
membrane potential ref1, ref2, ref3
membrane voltage ref1, ref2, ref3, ref4, ref5, ref6
and cancer ref1, ref2
and stem cells ref1
memory ref1, ref2, ref3, ref4
Mesmer, Franz ref1
Messerli, Mark ref1
metals ref1, ref2, ref3, ref4
and implants ref1, ref2
microscopes ref1, ref2
MIMO (multiple-input/multiple-output) algorithm ref1
Mitchell, Peter ref1
mixed conduction ref1
mole rats ref1
Morandi, Anna ref1
MPTP ref1
Müller, Johannes ref1, ref2
Murder Act (1803) ref1
Murray, Thomas ref1
muscle contraction ref1, ref2, ref3, ref4, ref5
and corpses ref1
and du Bois-Reymond ref1
and neural code ref1
Musk, Elon ref1, ref2

Nagle, Matt ref1, ref2

Napoleon Bonaparte ref1, ref2
natural philosophy ref1, ref2
Neher, Erwin ref1, ref2, ref3
nerve impulse ref1, ref2, ref3, ref4, ref5
nervous system ref1, ref2, ref3, ref4
and du Bois-Reymond ref1
and electroceuticals ref1
and ions ref1, ref2
and neurons ref1
neural bypass ref1
neural code ref1, ref2, ref3
neural dust ref1
neural lace ref1
neurograins ref1
neurons ref1, ref2, ref3, ref4, ref5
Neuropixels ref1
neurostimulation ref1, ref2, ref3
neurotechnology ref1
neurotoxins ref1
neurotransmitters ref1, ref2
Newton, Isaac ref1, ref2
Nicolelis, Miguel ref1
nicotine ref1
Nitsche, Michael ref1
Nobili, Leopoldo ref1
Noda, Masaharu ref1
Nogi, Taisaku ref1
Nordenström, Björn ref1, ref2
Nuccitelli, Richard ref1, ref2, ref3, ref4, ref5
and skin ref1, ref2, ref3
Nüsslein-Volhard, Christiane ref1

obsessive-compulsive disorder ref1, ref2, ref3, ref4

OFS (oscillating field stimulator) ref1, ref2, ref3, ref4
organic electronics ref1
organs ref1, ref2, ref3
ovulation ref1, ref2
oxygen ref1

pacemakers ref1, ref2, ref3

pancreas ref1
paralysis see spinal injury
Parkinson’s disease ref1, ref2, ref3, ref4, ref5
Paulus, Walter ref1
PEDOT ref1
Penfield, Wilder ref1
Penninger, Josef ref1
Perkins, Elisha ref1
philosophy ref1
physics ref1, ref2
physiological currents ref1, ref2
Piccolino, Marco ref1, ref2
Pietak, Alexis ref1
placebo effect ref1, ref2, ref3, ref4, ref5
planarians ref1, ref2, ref3, ref4
plants ref1, ref2
plastics ref1, ref2
polyacetylene ref1
polymers ref1, ref2, ref3
Poo, Mu-ming ref1, ref2, ref3, ref4, ref5
Potamian, Brother ref1
potassium ref1, ref2, ref3
and action potential ref1, ref2, ref3
and cancer ref1
and channels ref1, ref2, ref3, ref4
and embryos ref1, ref2, ref3
and nicotine ref1
and sperm ref1
pregnancy ref1
prosthetics ref1
protein ref1, ref2
protists ref1, ref2
protons ref1, ref2, ref3, ref4
pseudoscience ref1
Pullar, Christine ref1
Purdon, Patrick ref1
quackery ref1, ref2

Rajnicek, Ann ref1, ref2, ref3, ref4, ref5

Ramón y Cajal, Santiago ref1
rats ref1
Ray, Johnny ref1
reflectin ref1
regeneration ref1, ref2, ref3, ref4
and cancer ref1, ref2
regenerative medicine ref1, ref2, ref3
religion ref1, ref2, ref3, ref4
repolarisation ref1
resting potential ref1, ref2
resuscitation ref1, ref2, ref3
reviewers ref1
rheumatoid arthritis ref1
Ridgway, Andy ref1
Ringer, Sydney ref1, ref2
Ritter, Johann Wilhelm ref1
RNA ref1
Robinson, Ken ref1, ref2, ref3, ref4, ref5, ref6
and embryos ref1
robotics ref1, ref2
Rock, John ref1, ref2
Rolandi, Marco ref1, ref2, ref3, ref4, ref5
Rose, Sylvan Meryl ref1
Royal College of Surgeons (London) ref1
Royal Humane Society (London) ref1
Royal Society (London) ref1, ref2, ref3, ref4

Sakmann, Bert ref1, ref2, ref3

salamanders ref1, ref2
Scheuermann, Jan ref1, ref2
scientific revolution ref1
sea stars ref1
Second World War ref1
sensorimotor cortex ref1
Serafin, Catharina ref1, ref2
Shapiro, Scott ref1, ref2, ref3, ref4, ref5
Sheehan, Paul ref1, ref2, ref3
Shelley, Mary: Frankenstein ref1
Shirakawa, Hideki ref1
shocks see electro-therapy
sinus node ref1, ref2
Sisken, Betty ref1
skin ref1, ref2, ref3, ref4, ref5, ref6
sleep ref1, ref2, ref3
smoking ref1
Société philomatique de Paris ref1
sodium ref1, ref2, ref3
 and action potential ref1, ref2, ref3
and cancer ref1, ref2, ref3, ref4
and channels ref1, ref2, ref3
Sonnenschein, Carlos ref1
Soto, Ana ref1
Soups ref1
Spallanzani, Lazzaro ref1, ref2, ref3, ref4, ref5, ref6
and Aldini ref1
Sparks ref1
sperm ref1
spinal injury ref1, ref2, ref3, ref4
sport ref1, ref2
squid ref1, ref2, ref3
static electricity ref1
stem cells ref1, ref2, ref3, ref4, ref5
string galvanometers ref1, ref2, ref3, ref4
Sundelacruz, Sarah ref1
surgery ref1
Swanton, Francis ref1
synapse ref1, ref2
synaptic plasticity ref1

tDCS (transcranial direct current stimulation) ref1, ref2, ref3, ref4, ref5, ref6
teeth ref1
telegraphs ref1, ref2, ref3
telepathy ref1
tetrodotoxin ref1
torpillage ref1
Tosti, Elisabetta ref1, ref2
Tourette’s syndrome ref1
Tracey, Kevin ref1
tractors ref1
transistors ref1, ref2
trial volunteers ref1
Tseng, Ai-Sun ref1, ref2, ref3

University of Bologna ref1, ref2, ref3

Utah array ref1, ref2, ref3

vagus nerve ref1, ref2, ref3, ref4

Valli, Eusebio ref1, ref2, ref3
Van Musschenbroek, Pieter ref1, ref2
Vassalli, Anton Maria ref1
ventricles ref1
Venturoli, Giuseppe ref1
Veratti, Giuseppe ref1
Volta, Alessandro ref1, ref2, ref3, ref4, ref5
and Faraday ref1
and Galvani ref1, ref2
 and Humboldt ref1
voltage readings ref1, ref2, ref3;
see also membrane voltage

Waller, Augustus ref1, ref2, ref3, ref4, ref5

Walsh, John ref1, ref2, ref3
Walsh, Vincent ref1
Walters, Barbara ref1
Washington, George ref1
Watson, James ref1, ref2, ref3
Weisend, Mike ref1, ref2, ref3, ref4
Wiener, Norbert: Cybernetics: Or Control and Communications in the Animal and the Machine ref1
women ref1, ref2, ref3, ref4
wounds ref1, ref2, ref3, ref4, ref5, ref6
and chitosan ref1
and types ref1

xenobots ref1, ref2

yeast ref1
Young, Stella ref1

Zakon, Harold ref1, ref2

Zhao, Min ref1, ref2, ref3, ref4, ref5
Ziemssen, Hugo von ref1
Zotterman, Yngve ref1
 

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