Pearson Edexcel GCE

Biology

Advanced
Unit 5: Energy, Exercise and Coordination
June 2016
Scientific Article for use with Question 7

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Scientific article for use with Question 7

Factory of Life
1. Quietly, on the top floor of a nondescript commercial building overlooking Boston Harbor, the
future is being born.
2. Rows of young scientists tap intently in front of computer monitors, their concentration unbroken
even as the occasional plane from Logan Airport buzzes by. Stateoftheart lab equipment hums
away in the background. This office, in Bostons Marine Industrial Park, is what Californias Silicon
Valley was four decades ago the vanguard of an industry that will change your life.
3. Just as researchers from Stanford provided the brains behind the semiconductor revolution, so are
MIT and Harvard fueling the next big transformation. Students and faculty cross the Charles River
not to build computer chips, but to reengineer life itself.
4. Take Reshma Shetty, one of the young minds at work in the eighthfloor biological production
facility. After receiving her doctorate at MIT in 2008, she, like many new graduates, decided she
wanted to make her mark on the world. She got together with four colleagues, including her Ph.D.
adviser Tom Knight, to establish a company that aims to make biology easy to engineer.
5. Place an order with Ginkgo BioWorks and its researchers will make an organism to do whatever
you want. Need to suck carbon dioxide out of the atmosphere? They can engineer the insides of a
bacterium to do just that. Want clean, biologically based fuels to replace petroleum taken from the
ground? Company scientists will design a microbe to poop those out.
6. Ginkgo is, in essence, a 21st century factory of life. The researchers working there specialize in
synthetic biology, a field that seeks to build living things from the ground up. After envisioning
what they want new organisms to do, Ginkgo biologists actually grow vials full of redesigned cells.
Were going from the place we used to be, in doing science and studying the natural world, to a
place where were now going to be able to engineer and manipulate it, says Shetty.
7. Synthetic biology was born a little more than a decade ago, an offshoot of traditional genetic
engineering but distinct in its ambitions, precision and mindset.
8. Instead of randomly tweaking the genetic blueprints of living organisms and then working
backward to identify a cell with a desirable trait, the new field offered the power of designing and
building cells with novel functions. Its pioneers dreamed of making armies of organisms that could
produce alternative fuels, churn out drugs to battle disease or fill every stomach on the planet by
squeezing more food out of each crop acre.
9. Now, synthetic biologists have laid the groundwork for that radical new future, by building biologys
version of Silicon Valley. One research team has created a new and more complex set of biological
building blocks that snap together like Legos, bringing largescale production of engineered
organisms closer to reality. Other scientists have hooked those parts up in a complex living analog
of an electrical circuit and programmed it, much like programming a computer. Researchers are
now writing code to make cells do things never before thought possible, like hunt down and kill
cancer cells.
10. This is not just oh, were going to go build something thats able to make pieces of DNA better,
says Knight, one of the fields top visionaries. This is were going to go create a technology
infrastructure in the same way that the semiconductor infrastructure was developed.

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From scratch
11. In its early years, synthetic biology had a less practical, more daring public image. In part that was
because of the involvement of J. Craig Venter, the motorcycleriding, globehopping, highprofile
iconoclast of modern biology. In the 1990s he led a private effort to decipher the human genetic
instruction manual, or genome, that competed with a publicly funded effort. More recently, he
sailed his yacht around the world, scooping up water samples every 200 nautical miles to see what
microbes were there.
12. Venter also decided that he wanted to synthesize a living organism from scratch. Such a feat would
involve stitching together a creatures entire genome. DNAs double helix is made of chains of
paired molecules abbreviated as A, T, G and C; long stretches of these letters make up genes, the
basic units of heredity. Genes contain the information needed to make proteins, which perform
thelions share of work in a cell.
13. Commercial biotechnology companies can easily
synthesize short strands of DNA, but putting
those together into a full genome is an entirely
different matter. So Venter turned to a set of
bacteria known as Mycoplasma, which have some
of the shortest known genomes (one species has
just 580,000 pairs of genetic letters, compared
with the 3 billion pairs in the human genome).

Little big players

To carry out their synthetic feats, biologists
typically turn to microbes that have short
genetic instruction books and reproduce
quickly. Organisms worthy of note include,
clockwise from top left, Saccharomyces cerevisiae,
Salmonella, Mycoplasma genitalium and
Escherichia coli.

14. Venters team took commercially made strands of

DNA, then joined them together in his lab using
reactive enzymes. After many such steps, the
scientists succeeded in fabricating the genome
of one Mycoplasma species. The team then
inserted the synthetic genome into a second
species (which had had its own DNA removed),
booting it up. The resulting organism, dubbed
Synthia, essentially cribbed labmade DNA to
run itself.
15. Headlines predictably exploded. Life had been made from scratch sort of. Many synthetic
biologists werent nearly as excited about Venters achievement as the media suggested. These
critics point out that his group had simply built an organism to run off a program that already
existed in nature; the team didnt engineer Synthia to do anything new. The crucial difference in
todays synthetic biology, scientists say, is the ability to customize organisms from the start.
16. Were at the beginning of being able to design life in the way that we want, says Pamela Silver,
a biologist at Harvard Medical School and Harvards Wyss Institute for Biologically Inspired
Engineering.
By design
17. Engineering new forms of life starts with setting up a biological assembly line, the living equivalent
of a transportation innovation. Synthetic biologists aim to reinvent biology in the same way Henry
Ford revolutionized automobile manufacturing. Instead of installing standardized spark plugs or
carburetors as a car moves down the line, the scientists tuck brandnew biological parts into the
body of a bacterium.

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18. To do so, researchers first have to identify distinct, easily defined parts within a cell biological
versions of wheels, hoods, dashboards, engines and so on. Such parts need to be useful in any
design, like a power steering pump that works on both a Taurus and a Focus. The parts also need
to be standardized so that those made at one factory work with those made at another.
19. Drew Endy, a synthetic biology pioneer at Stanford, likes to tell the story of William Sellers, who in
1864 argued for the standardization of nuts and bolts so that a wrench made in WilkesBarre would
fit a nut made in Nashville. Until then mechanics had been working with custombuilt hardware.
In a lecture at Philadelphias Franklin Institute, Sellers called for the country to adopt his new screw
design. The standardized, easily measurable shape of its threads would also apply to nuts and
bolts, allowing industry to develop a cheap and profitable way to mass manufacture machine shop
hardware. Industry agreed, and within just a few years the Sellers screw took off.
20. Similarly, scientists are now compiling their own list of biological parts like the Sellers screw. Most
parts are stretches of genetic material, much shorter than a gene, that trigger some particular
process to turn on or off. A part known as a promoter, for instance, starts the conversion of DNA
information into its counterpart, the RNA molecule, while a terminator part stops the action. Many
of the parts are proteins known as transcription factors, which hook onto DNA to help control how
cells work and respond to their environment.
21. Scientists make parts by building a stretch of DNA or RNA known to perform a desired job, then
adding a standardized string of letters at the beginning and the end to identify it as a part. They
then insert the whole thing into a circular strand of DNA until they need it. In 2003, MIT biologists
started keeping a formal inventory of these biological parts. Many are added by students who
spend summers working on a synthetic biology competition, the International Genetically
Engineered Machine contest, or iGEM. Today the list of parts tops 20,000.
Building complexity
Redesigning organisms to do peoples bidding requires biological parts that can mix and match to create
genetic circuits. Like electrical circuits, these genetic versions perform a useful task or computation and can
be combined into more complex systems.
Biological parts
Protein-coding sequences are stretches of
DNA that hold the recipe for building a
protein.

Protein-coding
sequence
Promoter

Promoters turn on the process that creates a

counterpart RNA molecule from DNA, and
ultimately a protein.
Terminators turn off the process that creates
a counterpart RNA molecule from DNA.
Protein domains are portions of a protein
sequence that can act independently. The
domains may influence a proteins functions
and characteristics.
Plasmids are rings of DNA molecules that can
be copied independently from chromosomal
DNA.

Promoter
Promoter

Protein-coding
sequence

Protein-coding
sequence

In this circuit, two promoters turn on the

transcription of two protein-coding sequences.
The resulting products need to join together
before another promoter can turn on another
sequence, leading to an output product. The
circuit is only on when both of the promoters
are active.

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22. Even that roster is too small for some. In his office at Boston University, bioengineer James Collins
practically bounces in his chair as he complains about the quality and quantity of most parts. We
just dont have enough parts to do what wed like, he says. If you survey the original parts out
there, we usually use only a dozen or so.
23. Collins wants more. Most synthetic transcription factors are designed after versions found in bacteria
like Escherichia coli. Collins team recently looked instead at yeast cells. Yeast are more complex
than bacteria; if engineers could build more parts inspired by yeast, they could use those to create
more advanced designs. Working with colleagues including MITs Timothy Lu, Collins developed a
system to make new transcription factors, and made 19 new ones to start with. Instead of relying
on this small number of things arrived at in nature, we now have a very nice platform that allows
you to ramp up and create transcription factors by design, in large numbers, Collins says. The work
appeared last August in Cell.
Cells wired up
24. Once synthetic biologists have enough parts to work with, the next question is what to do with
them. Here, bioengineers take their cue from electrical engineers. Individual biological parts are
like the transistors, resistors and capacitors that electrical engineers connect together with wires
to create a circuit through which current flows. Circuits can then be connected together on a
semiconductor chip to perform computing tasks.
25. Biologists first reported making synthetic genetic circuits in 2000, when two E.coli papers appeared
in the same issue of Nature. In one, a team led by Collins announced the first artificial toggle switch
in bacteria; the scientists designed two promoters to interact and drive gene activity if prompted
by one molecular signal, and to stop when prompted again.
26. In the second paper, Stanislas Leibler and Michael Elowitz, then at Princeton, described a synthetic
timing switch, in which three genes inhibited one another in sequence, their activity cycling
regularly.
27. These first papers were necessarily
clumsy attempts to emulate what
nature does effortlessly. But with
genetic circuits that accomplished
particular tasks, researchers could
go one step further: They could
connect those circuits with other
components, just as electrical
engineers do on a computer
chip, and program the whole
contraption to perform an even
more elaborate job.

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Solving hunger
Synthetic biology may help farmers feed
more people. For millennia, crops have
been bred with an eye toward improved
harvests. Later, genetic manipulations
upped plant yields and made crops
more resilient against drought and other
hazards. Now, scientists are looking at
tweaking photosynthesis. You dont need
to increase the biomass of plants by that
much to solve the food problems across
the world, says Harvards Pamela Silver.
One idea is that new enzymes could boost
the amount of energy that plants can
extract from the sun. Another suggests
there might be a totally different way to
pull usable carbon from the atmosphere.
In the April2012 Applied and Environmental Microbiology,
Silver and colleagues reported engineering a bacterium to
churn out up to 200percent of its initial cellular mass as sugar.
The work could be used to develop plants that produce more
food per harvest.
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28. Across the Charles River from Ginkgo, on the second floor of a gleaming biotechnology building,
sits one major hub where biological parts are being turned into sophisticated machinery. This is
MITs synthetic biology center. Being MIT, it is full of engineers with novel and creative ways to
think about programming even when that programming involves DNAbased circuits rather than
electrical ones.
29. One such tinkerer is Christopher Voigt, whose round face and easygoing manner belie the fact
that he commands living organisms to do his bidding. Voigt, a former computer programmer, got
into synthetic biology because he saw it as the last frontier. Being able to write a language that
programs E.coli to perform a set of operations is the most challenging problem, he says.
30. At first, it wasnt clear that the dream of programming life would be possible. For most of the 2000s,
synthetic biology fought a reputation as being not much more than a bag of parlor tricks. Students
working on iGEM teams designed cute proofofprinciple projects, like engineering E.coli to darken
in bacterial photographs or to smell like wintergreen or banana. It seemed that scientists were
connecting and reconnecting biological parts, but not in any kind of profound or truly useful way.
31. That paradigm is now beginning to shift, Voigt says, as researchers develop more reliable parts and,
crucially, many more ways in which to wire them together. Instead of using the same few parts
andcircuits over and over again, programmers like him now have far more sophisticated designs.
Were getting to an inflection point, he says. Finally.
32. Last year, for instance, Voigts research group reported recreating the main pathway through which
bacteria convert atmospheric nitrogen to ammonia. By replacing natural parts with synthetic ones,
the scientists essentially adapted the genetic programming guiding the job. The system involved
94 biological parts a scale of engineering unheard of until recently, Voigt says.
33. Going one step further to original design, Voigt and his colleagues recently built the largest
synthetic genetic circuit to date, described in Nature in November. It involves four sensors, each of
which can detect a particular input from the environment. One sensor may detect oxygen levels in
a cell, for example, while a second sniffs for glucose. Combining those inputs and others prompts
the cell to decide whether to take a particular action.
Making energy
An early hope for synthetic biology was that it could wean society off
fossil fuels. Engineering microbes to churn out hydrocarbons would
presumably be a lot cleaner and more climate-friendly than extracting
and burning coal and oil. Since 2000, the U.S. Department of Energy
has poured millions of dollars into funding synthetic biology biofuels
research, such as new types of algae to secrete biodiesel or other
engineered fuels that dont have to be pumped from the ground.
Sofar, progress has been limited.

34. Voigt and his colleagues hope to use these types of circuits in industrial fermentation vats, so that
bacteria inside the vats can sense multiple ways in which the environment changes and adjust
activity accordingly. Some of the very basic circuits are already used in biotechnology, to turn on
the production of protein as much as you possibly can, says Voigt. But if youre trying to make
materials or chemicals like natural products, that requires a lot more sophistication in terms of
timing when things happen.

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35. Put enough circuits together and program them in the right way, and synthetic biology may soon
become a lot more personal. Just as the earliest clunky computers eventually gave way to the
iPhone in your back pocket, designer cells might one day become an everyday part of your life.
They might even course through your veins if Ron Weiss has his way.
36. Weiss works just down the hallway from Voigt at MIT. He began his graduate student career in
typical fashion, using computer programs to simulate biological changes in a developing embryo.
But then something clicked in his brain. I remember the day when I thought, let me flip this around,
he says. Lets look at what I know in computing and understand how I can program biology. Then
his advisers told him he was too close to getting his Ph.D. to start going down such crazy paths.
37. Weiss wasnt going to drop his doctoral quest, but he walked over to Knights office and asked to
join the budding synthetic biology research group there instead. After many 16hour days teaching
himself how to string together DNA, Weiss changed his focus from engineering to synthetic biology.
38. Now, in a sort of biological hit job, Weiss team has
engineered assassin cells to track down and annihilate
cancerous cells. The scientists, including Yaakov
Benenson formerly of Harvard and now at ETH Zrich,
programmed a synthetic circuit that can sense levels
of chemicals often found in cancer cells. The circuit
also includes a kill switch, a synthetic version of a gene
carrying information that can make other cells commit
suicide.
39. Cells carrying this circuit search for cells that are
turning cancerous. Once there, the assassin cells flip
the kill switch and cause the cancerous ones to off
themselves.
40. In a 2011 Science paper, Weiss team showed that this
killer circuit could work in human cells in a lab dish.
But theres a long way to go before it could treat cancer
in people. Scientists need to find a way to deliver the
assassin payload into the body. We need something
like a virus that would go into cells and then compute
whether each cell is cancerous or not, Weiss says. His
team is now working to harness a virus that could be
used to test the idea in mice. If it works, doctors might
eventually be able to inject assassin circuitry into a
person suffering from cancer.

Treating patients
One of the most obvious
goals of synthetic biology
is to make people healthier.
Engineering new drugs,
or designing cells that can
target disease inside the
body, has been a goal of the
field from the start. An early
success involved creating
a bioengineered version
of a drug to fight malaria.
Researchers managed to engineer a
species of yeast to produce large amounts
of a chemical precursor to the antimalarial
drug artemisinin, typically harvested from
the wormwood tree of east Asia. The
pharmaceutical company Sanofi is now
working to bring the process to market. In
another take on better health, engineered
human cells could locate and eliminate
cancerous cells by tricking the evildoers
into committing suicide. Though the
technique has been demonstrated in a lab
dish, it is still far from tackling cancer in
real human patients.

41. Weiss also has his eye on fighting several other important diseases. Diabetes, for instance, can
require a person to regularly inject insulin, but Weiss thinks that engineered cells might be able to
do that job from within the body. In early theoretical work, his team showed how synthetic gene
circuits could steer stem cells to develop into insulinproducing cells. Adding synthetic switches
could nudge the insulin production process in one direction or another as needed, the team
reported last July in PLOS Computational Biology. The cells could reproduce over and over again,
and then die when no longer needed.

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Picking up the pace

42. A medical breakthrough was, in fact, one of synthetic biologys first major industrial successes:
a bioengineered version of artemisinin, a malariafighting drug that once had to be laboriously
and expensively harvested from the wormwood tree of east Asia. In 2006, researchers from the
University of California, Berkeley and Amyris Biotechnologies in Emeryville, Calif., reported that they
had engineered bakers yeast to churn out a crucial precursor to the drug. The scientists teamed
up with the pharmaceutical company Sanofi to scale up the process and make the drug in its
laboratories. Sanofi is in the early stages of shipping the first commercial artemisinin made using
synthetic biology.
Reviews give green light, encourage caution
Engineering life is not the sort of thing you can do quietly.
Ever since biologists first started piecing together genetic components, ethicists have pondered the
implications. Could an artificial form of life turn out to have unexpected consequences, like invading the
environment or otherwise running amok? And what about bioterrorists who might want to get their hands
on synthetic bugs and put them to nefarious uses?
A March 2012 report from friends of the earth, the international center for technology assessment, and
the ETC Group nongovernment organizations that have worked against genetically modified organisms,
among other causes calls synthetic biology an extreme form of genetic engineering that is developing
rapidly with little oversight or regulation despite carrying vast uncertainty. Not since the 1990s birth of
nanotechnology, the engineering of the very small, has a new technology elicited suchire.
Nearly every major safety review of synthetic biology, though, has given the field a cautious green light.
A2010 government review, requested by President Obama after Craig Venter booted up a cell with a
synthetic genome, suggested there was no need to create a new government body to oversee synthetic
biology research. Rather, the reports authors promoted the idea of prudent vigilance paying attention
to whats happening in the field without regulating it out of existence from the start. With these
unprecedented achievements comes an obligation to consider carefully both the promise and potential
perils that they could realize, the report said.
The Woodrow Wilson international center for Scholars in Washington, D.C., has also started a scorecard
for tracking public discussions about synthetic biology. An update last July found that many U.S. federal
agencies had begun taking steps to learn more about the field, as recommended by the presidential report.
Still, the center says, more work is needed. Alexandra Witze

43. Researchers havent been as successful with another of synthetic biologys lofty original goals to
help solve the energy crisis. One early and muchtouted promise was that scientists could insert
synthetic genes into an organisms DNA to make it secrete biodiesel or other petroleum alternatives.
Some companies, including Ginkgo, are still working on this challenge. But many of the highest
profile projects, like those that engineered algae to pump out biofuels, simply havent panned
out. In most cases, fuel made by synthetically altered organisms cant compete economically with
regular petroleum products.
44. Most synthetic biologists see this setback as a bump in the road rather than a major derailment for
the field. Harvards Silver, for instance, has shifted from working on synthetic biology approaches
for cleanburning hydrogen fuel to new ways to reengineer photosynthesis within plants.
45. Once a molecular biologist, Silver shifted to synthetic biology in the early 2000s so that she could
tackle scientific questions no one else could. The idea of building with biology struck me as very
exciting, she says. Today she oversees one of the largest and most productive synthetic biology
research teams, a warren of lab benches and graduate students on Harvard Meds campus in
Boston. Among other efforts, she has developed synthetic genetic counting devices, to keep track
of exposures to things like radiation within a cell.
46. For Silver, synthetic biology is all about accelerating the pace of practical advances. Biology needs
to move faster so that people cheer when something great happens, she says.
Bibliography
Factory of Life, Science News January 12, 2013, www.sciencenews.org, p2328
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