Gene editing

and
agrifood systems
Gene editing
and
agrifood systems

Food and Agriculture Organization of the United Nations

Rome, 2022
Required citation:
FAO. 2022. Gene editing and agrifood systems. Rome. https://doi.org/10.4060/cc3579en

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Contents

Foreword...............................................................................................................................v
Acknowledgements............................................................................................................. vii
Abbreviations and acronyms............................................................................................. viii
Executive summary...............................................................................................................x

1 Introduction.........................................................................................................1
2 Advances in plant and animal breeding.................................................................3
Summary.........................................................................................................................3
A brief history of plant and animal breeding......................................................................3
Principles of gene editing.................................................................................................5
Some illustrative applications of gene editing....................................................................5
Disease resistance in plants................................................................................................. 6
Herbicide tolerance............................................................................................................... 6
Agronomically important traits........................................................................................... 10
Quality traits........................................................................................................................ 10
Quantitative trait regulation................................................................................................ 11
Crop domestication............................................................................................................ 11
Livestock............................................................................................................................. 12
Aquaculture......................................................................................................................... 12
Microorganisms.................................................................................................................. 12

3 Gpotential
 ene editing
hazards, benefits and impacts on the environment and society..............13
Summary.......................................................................................................................13
Gene editing and human hunger......................................................................................13
Gene editing and human health.......................................................................................15
Allergenicity........................................................................................................................ 15
Toxicity ............................................................................................................................... 15
Composition analysis......................................................................................................... 16
Gene editing and the environment...................................................................................16
Issues associated with gene-edited plants........................................................................ 17
Issues associated with gene-edited animals ..................................................................... 18
Gene editing and animal welfare.....................................................................................19
Gene editing, socioeconomic impact and distribution of benefits.....................................19
Economic impact at farm household level......................................................................... 21
Economic impact at input market level.............................................................................. 22
Differentiated markets........................................................................................................ 22
Societal factors and public acceptance............................................................................. 22
Gene editing and fundamental ethical considerations......................................................25

4 G overnance and regulation.................................................................................28

Summary.......................................................................................................................28
Sanitary and phytosanitary regulations............................................................................28
A timeline of national approaches...................................................................................29

iii
 Multilateral instruments.................................................................................................33
Cartagena Protocol............................................................................................................. 33
Codex Alimentarius Guidelines........................................................................................... 34
The International Plant Protection Convention................................................................... 35
The Organisation for Economic Co-operation and Development....................................... 35
Other key issues............................................................................................................35
Identification....................................................................................................................... 35
Off-target changes and unintended insertions................................................................... 36
Property, access and benefit sharing...............................................................................36
Access and benefit sharing................................................................................................. 36
Intellectual property............................................................................................................ 37
Gene-edited products considerations................................................................................. 37
Patents and gene-editing methods..................................................................................... 38
Economic interventions..................................................................................................38
Innovation funding.............................................................................................................. 38
Trade interventions............................................................................................................. 38

5 Roles of the private and public sectors and transformative partnerships...............39

Summary.......................................................................................................................39
Public sector.................................................................................................................39
Private sector ...............................................................................................................40
Intellectual property considerations................................................................................42
Public-private and transformative partnerships................................................................42
Identifying and managing conflicts of interest in public-private partnerships.....................43

6 The way forward................................................................................................45

References........................................................................................................48

Appendices
Appendix A....................................................................................................................64

Appendix B.1a
Case study – Powdery mildew resistance........................................................................69
Appendix B.1b
Case study – PRRSV-resistant pigs.................................................................................70
Appendix B.1c
Case study – CRISPR-Cas9 and fish................................................................................71

iv
Foreword

The promise of CRISPR for food security

When my colleagues and I first described CRISPR genome editing in 2012, my
thoughts about its potential impact focused on human health. The genetic mutation
that causes sickle cell disease, for example, had long been known, but we had
no way to address it until the discovery of CRISPR technology. Over time, it has
become increasingly clear to me that the agricultural and environmental applications
of CRISPR hold the potential for the most widespread impact. Genetic diseases, as
unfortunately common as they are, do not touch everyone the way agriculture does.
Everyone must eat.

In the decade since CRISPR genome editing emerged, scientists have developed a
toolkit to tackle the most pressing issues facing humanity and the planet. With the
capacity to precisely edit the genomes of crop plants, we can alter nutritional content
to combat malnutrition, remove toxins from staple foods like cassava, increase yields
to fight hunger, and improve pest resistance, reducing the need for agrochemical
inputs. Edited products could also introduce adaptations to address drought and flood
resistance, increase biodiversity, and help to capture more carbon, restoring farm
soils and improving the fertility of marginal lands. The benefit of CRISPR extends
beyond the development of products. As a research tool it can be used to conduct
genetic screens, unlocking new biological pathways and expanding our knowledge of
the genome and the functional impact of mutations, all of which provide us with new
options for future applications.

It is important that we understand our place in history, both the challenges we face
today, and ones we have overcome in the past. In late 2022, the number of humans
on the planet surpassed 8 billion. The Earth is being stretched for resources as we
strive to provide for the needs of humanity, while simultaneously reducing our impact
on the global climate. Technologies have helped us through challenging times before.
Starting in the 1960s, the Green Revolution reduced global hunger and poverty, but
it also brought new challenges and unexpected consequences, including overuse
of agrochemicals and monocropping. How can we learn from history to anticipate
problems that may arise and take pre-emptive action to ensure positive outcomes for
all? Growing anthropogenic pressures on the planet necessitate that we consider all
technological options that could sustain human life and preserve the environment.
This report provides the international community with guideposts for areas we must
address as the first genome edited agricultural products make their way to farmers’
fields and our tables.

One area of particular concern for me has been ensuring the equitable distribution
of benefits. In the past, high regulatory burdens on agricultural technologies had
the effect of consolidating the most sophisticated tools in the hands of a few large
companies. This impacted the types of products developed, prices, and global
access, and individual farmers have not shared equally in the benefits. Beyond its
ease of use, its precision, the reduced cost and shortened timeline for development,
CRISPR stands out as a powerful democratizing tool which can be used by scientists
globally. I envision a distributed model of crop development in which local scientists
can address issues of suitability of crops to agroecological contexts, distribution of
benefits, access to genetic resources and sovereignty. In addition, local scientists
understand and share the values of their neighbours and have the trust of their
communities. This approach has the added benefit of supporting a diversity of crops,
particularly neglected varieties, with potentially outsized impacts on malnutrition and
hunger. Driven by this goal, the institute that I founded, the Innovative Genomics
Institute, in partnership with the African Union and African Plant Breeding Academy,
launched an African CRISPR course to equip local researchers with the necessary
skills to develop their own genome edited varieties. By partnering with CGIAR and

v
NARS scientists we can further advance breeding of crops critical to feeding much of
the world’s population like cassava, sorghum, millet and banana.

Around the world, governments have taken a practical approach towards regulation:
in cases where changes made via genome editing are synonymous with changes that
could have been made using conventional breeding, products undergo similar safety
assessments. For edits that lead to insertions of DNA, governments can rely on over
three decades’ worth of experience in transgenics. This clear regulatory approach has
spurred investment by academic and public-sector developers who now have a path
to product approvals.

Any review of genome editing technology should be accompanied by a discussion

on ethics. Valid concerns have been raised over the desire for an unaltered natural
environment, maintenance of ancient germplasm, as well as animal rights, and
cultures around the world will have questions about how the technology might
comply or conflict with religious beliefs. Platforms for societal engagement are
much needed to facilitate discussions on ethics, and to educate the public on the
technology. Individuals should have the ability to choose products that meet their
needs and adhere to their belief systems. A consumer of the future may choose an
edited variety because they prioritize sustainability, animal welfare, have allergies, or
prefer the taste. A farmer of the future may choose to grow an edited crop because
it preserves a favoured variety while making it more resilient to a changing climate,
or because it increases yield, or captures carbon from the atmosphere. A successful
path to the future is one that includes informed choice.

It is my hope that this report will serve as a guiding document for those seeking to
responsibly and equitably deploy genome editing technologies. All of human health
depends on agriculture. It has been just over 10 years since CRISPR genome editing
emerged as a tool; now it is time to wield it wisely.

Jennifer A. Doudna

Professor, University of California Berkeley and

Founder of the Innovative Genomics Institute,
United States of America

vi
Acknowledgements

This Issue Paper was developed by a team of co-authors with oversight from the
FAO Chief Scientist Office. The text was subjected to multiple phases of review
followed by revision, involving the Chief Scientist Office, FAO Task Force on emerging
biotechnologies and external peer reviewers.

Writing team:
Caixia Gao,1 Enoch Kikulwe,2 Jennifer Kuzma,3 Martin Lema,4 Preetmoninder Lidder,5
Jonathan Robinson,5 Justus Wessler6 and Kevin Zhao1 

The commitment and dedication of the members of the FAO Task Force on emerging
biotechnologies is deeply appreciated – their valuable inputs and feedback contributed
to the development, review and finalization of this issue paper.

The following external experts are gratefully acknowledged for contributing their

time and expertise during the peer review of this document:

Margaret Karembu (ISAAA-AfriCenter, Kenya), Elspeth MacRae (Bioeconomy Futures,

New Zealand), Anne Ingeborg Myhr (NORCE, Norway), Peter Thygesen (Office of the
Gene Technology Regulator, Australia), Eliane Ubalijoro (Future Earth, Canada) and Ren
Wang (Chinese Academy of Agricultural Sciences, China).

Please note that reviews and suggestions provided by the external experts do not
constitute an endorsement, and the named reviewers should not be understood to
agree with everything in the paper.

Special thanks go to Ludovica Mei (FAO) for production coordination, Max Kardung
(Wageningen University & Research) for liaising and coordinating with the co-authors
and Adriana Brunetti (FAO) for the design and final layout of the publication.

1
Institute of Genetics and Developmental Biology of the Chinese Academy of Sciences
2
Alliance of Bioversity International and CIAT
3
North Carolina State University
4
National University of Quilmes
5
Food and Agriculture Organization of the United Nations (FAO)
6
Wageningen University & Research

vii
Abbreviations and acronyms

ABE adenine base editors

African swine fever
ASF 
Association of International Research and Development Centers for
AIRCA 
Agriculture
Animal and Plant Health Inspection Service (United States of America)
APHIS 
Bacillus thuringiensis
Bt 
Codex Alimentarius Commission
CAC 
Convention on Biological Diversity
CBD 
cytosine base editors
CBE 
International Center for Tropical Agriculture
CIAT 
Court of Justice of the European Union
CJEU 
Cartagena Protocol on Biosafety
CPB 
clustered regularly interspaced short palindromic repeats
CRISPR 
classical swine fever
CSF 
National Technical Biosafety Commission (Brazil)
CTNBio 
DNA deoxyribonucleic acid
double-strand break
DSB 
European Court of Justice
ECJ 
Environmental Protection Authority (New Zealand)
EPA 
Environmental Protection Agency (United States of America)
EPA 
Food and Agriculture Organization of the United Nations
FAO 
United States Food and Drug Administration
FDA 
Food Standards Australia-New Zealand
FSANZ 
gamma-aminobutyric acid
GABA 
green fluorescent protein
GFP 
greenhouse gas
GHG 
genetically modified
GM 
genetically modified organism
GMO 
homology directed repair
HDR 
high-income countries
HICs 
homologous recombination
HR 
International Atomic Energy Agency
IAEA 
International Panel for Biodiversity and Environmental Services
IPBES 
Agricultural Institute (Colombia)
ICA 
International Center for Biosaline Agriculture
ICBA 
International Centre for Insect Physiology and Ecology
icipe 
Intellectual Property
IP 
Intergovernmental Panel on Climate Change
IPCC 
International Plant Protection Convention
IPPC 
Intellectual Property Rights
IPR 
International Service for the Acquisition of Agri-biotech Applications
ISAAA 
International Treaty on Plant Genetic Resources for Food and Agriculture
ITPGRFA 

viii
 low- and middle-income countries
LMICs 
living modified organism
LMO 
Ministry of Agriculture, Forestry, and Fisheries (Japan)
MAFF 
Ministry of Agriculture and Rural Affairs (China)
MARA 
Ministry of Health, Labour and Welfare (Japan)
MHLW 
microhomology-mediated end joining
MMEJ 
Ministry of Environment (Japan)
MoE 
North American Free Trade Agreement
NAFTA 
national agricultural research systems
NARS 
United States National Academies of Science, Engineering and Medicine
NASEM 
National Biosafety Management Agency (Nigeria)
NBMA 
National Biosafety Authority (Kenya)
NBA 
new breeding technique
NBT 
National Committee on Biosafety (Philippines)
NCPB 
non-governmental organization
NGO 
NHEJ non-homologous end joining
NORCE Norwegian Resource Centre
oligonucleotide-directed mutagenesis
ODM 
Organisation for Economic Co-operation and Development
OECD 
open reading frame
ORF 
Plant Breeding Innovations (Philippines)
PBI 
Patent Law Treaty
PLT 
porcine reproductive and respiratory syndrome
PRRS 
porcine reproductive and respiratory syndrome virus
PRRSV 
research and development
R&D 
ribonucleic acid
RNA 
Agriculture and Livestock Service (Chile)
SAG 
Sustainable Development Goal
SDG 
Honduran National Service of Agrifood Health and Safety
SENSA 
site-directed nuclease
SDN 
transcription activator-like
TAL 
transcription activator-like effector
TALE 
transcription activator-like effector nucleases
TALENS 
Agreement on Trade-Related Aspects of Intellectual Property Rights
TRIPS 
International Union for the Protection of New Varieties of Plants
UPOV 
United States Agency for International Development
USAID 
United States Department of Agriculture
USDA 
whole genome sequencing
WGS 
World Health Organisation
WHO 
World Intellectual Property Organization
WIPO 
World Trade Organization
WTO 
zinc finger nuclease
ZFN 

ix
Executive summary

Many of the agrifood systems that feed the world are severely impacted by global
warming, extreme weather events, degradation of land and water resources, conflict,
pandemics and demographic shifts. The effects have been particularly felt by the most
vulnerable communities and individuals, many of whom depend on agriculture for
their livelihoods. Disruptions to global agrifood systems have resulted in widespread
hunger, malnutrition and inequality. Elimination of hunger and improvement in nutrition
will require major transformations of agrifood systems in many parts of the world.
Innovative applications of science and technology will play significant roles in the
necessary transformations. Gene-editing technology, including CRISPR (clustered
regularly interspaced short palindromic repeats), represents one of the most recent
advances in genetics and its application to plant and animal breeding, and is set to
contribute to improvements in many aspects of agricultural production. It has the
potential to help satisfy the increasing global demand for food and agricultural products.

This science- and evidence-based Issue Paper on gene editing and agrifood systems
presents a balanced discussion of the most pertinent aspects of gene editing,
including the consequences for human hunger, human health, food safety, effects on
the environment, animal welfare, socioeconomic impact and distribution of benefits.
Intrinsic ethical concerns and issues of governance and regulation are addressed, and
the roles of the public and private sectors, alone and in partnership, are summarized.
Various scenarios are also presented for how gene editing might be used in the
future to help transform agrifood systems.

Plant and animal breeding began through the mechanisms of natural selection and
was directed and hastened through the activities of ancient agriculturalists, who, with
no knowledge of the mechanisms of heredity, guided the processes of domestication
through their selections of superior crops and animals. Scientific breeding, relying on
knowledge of genetics and statistics, is only little over a century old and represented
an improvement in speed and precision. Gene editing is the latest advance in this
continuum, further increasing precision in crop and livestock breeding. CRISPR-Cas,
for example, enables parts of a genome to be targeted precisely and cut. Insertions
and deletions of genetic material at the cut site allow a germline to be developed that
will result in a plant or animal expressing desired traits. Applications of gene editing
are discussed in terms of their merits and demerits for various traits introduced into
crops, livestock and fish that enhance production.

Gene editing has the potential to improve food security, nutrition and environmental
sustainability but issues of safety must be considered. Identification of potential
problems associated with new products is important to ensure their secure and
sustainable use and satisfy consumers. The environment, biodiversity and human
health could be negatively influenced by release of gene-edited products and
therefore regulation must be enacted. Considerable information has been gained
from previous experiences with transgenic plants and animals that is relevant to gene
editing and its products. Gene editing can be inherently more precise than other
methods used to date, which could reduce the likelihood of any harmful effects on
human health and the environment.

The economic impact of gene editing will be determined by availability of products,

particularly seeds, to small-scale producers, especially in low- and middle-income
countries. It is possible that gene editing could reduce farm management costs, but
impact at the household level will depend on numerous additional factors, many of
which will be situation specific. Social and ethical concerns, including public trust in
scientists and developers will be important, as will considerations of risk and benefit
distributions, and questions about naturalness and differing cultural values. Intrinsic

x
ethical concerns and animal welfare will also have to be considered when developing
and deploying gene-edited products.

Governance aspects of gene-edited products include sanitary and phytosanitary

regulations. To date, there has been a variety of approaches taken by national bodies,
differing markedly in stringency. While many treat gene-edited products similarly to
products derived from genetic modification, others do not. This has consequences for
international trade and commerce. Governments must focus on taking a well thought
out regulatory approach that attempts international harmonization to the extent
possible. Following establishment of national regulatory protocols, other governance
issues can be tackled, including trade impacts, intellectual property attributions and
facilitation of access and distribution. At the multilateral level, the range of governance
aspects can be addressed through various specialized mechanisms and bodies.

Gene editing research takes place in the private and public sectors, but their
objectives and incentives can differ. The private sector generally prioritizes marketable
products and profits, whereas the public sector is often less constrained and allows
greater academic freedom. Issues of ownership of technologies and products,
including those from gene editing, are seldom straightforward. Intellectual property
considerations are as relevant to gene-editing procedures and products as they
are to other technologies. However, many of the aspirations of public and private
organizations are compatible, and collaboration between the two sectors is possible
and can be beneficial. The principal issue is to ensure that those for whom gene-
editing technologies and products offer a solution to current constraints can afford
and access them.

Gene editing is not a stand-alone technology and is not the only solution for the
problems currently faced by agrifood systems. It should be integrated into plant
and animal breeding systems and used alongside other improved practices and
technologies. The products of gene editing should be available to those that need
them most, and the crops and livestock that are important to small-scale producers
living in vulnerable environments must receive the attention they merit. As the
Nobel Laureate Jennifer Doudna said, “One risk that is often overlooked is the real
possibility that some of the advances we make in genome editing will benefit a small
fraction of society. With new technologies this is often the case at first, so we have
to consciously work from the start to make new cures and agricultural tools that are
accessible and affordable.”
Previous modifications to agrifood systems, including the Green Revolution, have
not necessarily been easy, and not without trade-offs, but innovative applications
of science and technology have regularly resulted in substantial improvements in
productivity. Gene editing may represent a further step towards the transformation of
agrifood systems so that they can withstand better the current pressures and those
they will face to an even greater extent in the future. It is important that interventions
involving application of gene editing result in developments that are appropriate and
sustainable and that are effective within the limits set by the environment.

FAO is ready to play a leading role in this important area of scientific and technological
advance by providing a neutral forum for constructive dialogue and exchange of
knowledge and by promoting discussion on the applications of gene editing to
agriculture and food production.

xi
1 Introduction
Humans have had a binding relationship with The number of people without access to a healthy
the natural world that has endured for over one diet rose significantly from 2019, reaching almost
hundred millennia. As omnivores, with a plant- and 3.1 billion in 2020, reflecting the impacts of rising
meat-based diet, this special relationship has been, consumer food prices caused by various forces,
and continues to be, one of mutual dependence particularly the COVID-19 pandemic. An estimated
for food and feed. However, the relationship 45 million children under the age of five suffered
extends beyond diet to include all aspects of the from wasting, increasing risk of child mortality
environment in which plants and animals exist. appreciably. In addition, 149 million children under
Without plants, crop plants in particular, humankind the age of five suffered from stunted growth and
cannot survive. Because of the special relationship, development due to lack of essential nutrients in
new technologies that impinge on agriculture stir their diets, while 39 million were overweight.
vigorous debate. Gene editing is among the most
recent technologies to do such. To satisfy the global demand for food and agricultural
products by 2050, FAO has projected that agricultural
Currently, agrifood systems, which ultimately feed output will need to increase by between 40 and
the global population, are facing unprecedented 53 percent, compared with a 2012 baseline value
pressures. While agrifood systems have always (FAO, 2018). Other estimates indicate that to feed
been vulnerable to biotic and abiotic stresses, 9.7 billion people in 2050, crop production needs
especially, but not exclusively, changeable weather to increase by 56 percent compared with a 2010
patterns, the combined effects of climate change, baseline value, while demand for animal-based foods
degradation of land and water resources, conflict, is anticipated to increase by nearly 70 percent (World
pandemics and demographic shifts, have exacted Resources Institute, 2019).
a severe toll on many of the most vulnerable
producers and consumers. The result has been Food production currently accounts for about half of
widespread hunger, malnutrition and inequality, all habitable land (UNEP, 2019), while approximately
and systems of production, often traditional, and a third of agricultural land is degraded (FAO and
frequently in marginal areas, no longer function ITPS, 2015). Soil erosion exceeds soil formation
efficiently and often fail completely. The effects rate despite soil productivity having increased
have been felt in both terrestrial and aquatic in many parts of the world (IPCC, 2019). While
environments. water-use efficiency has improved, agriculture still
accounts for 70 percent of freshwater withdrawals
Over recent decades, global food production worldwide and is the primary source of nutrient
steadily increased, life expectancy improved, runoff; 3.2 billion people live in agricultural areas
hunger was in decline, infant and child mortality with severe water shortages or scarcity (FAO,
rates fell, and global poverty levels contracted. 2020). Agrifood systems rely on soil and water
However, past progress is now threatened. The and there is competition for these resources with
world is not on track to meet the Sustainable sectors outside agriculture.
Development Goals (SDGs). To meet the goals set
by SDG 2, zero hunger and improved nutrition, will The world is not on course to meet the
require major transformations of agrifood systems requirements set by the Paris Agreement. Current
in many parts of the world. Millions of people are agrifood systems are responsible for 34 percent
now being pushed into acute poverty and food of total anthropogenic greenhouse gas (GHG)
insecurity. As many as 828 million people were emissions (Crippa et al., 2021). These directly,
affected by hunger in 2021 – 46 million people and negatively, affect climate and amplify risks
more than a year earlier and 150 million more than associated with biodiversity loss and other
in 2019 (FAO, IFAD, UNICEF, WFP and WHO, 2022). issues. Extreme weather events are expected to
In 2021, acute food insecurity reached a new high, increase in frequency and severity and increasing
193 million people experienced crisis levels or temperatures will change distribution and
worse, an increase of 40 million over the previous acuteness of pests and diseases. Changing rainfall
high recorded in 2020 (WFP, 2020). patterns will result in droughts and flooding, both

1
Introduction

being detrimental to agricultural production. The traits in neglected and underutilized crop species.
rural poor, especially those in low- and middle- Gene editing can play a role in enhancing nutritional
income countries (LMICs), are disproportionately composition of crops and improving efficiency of
affected by climate change because their feed conversion and reduction in methane and
livelihoods largely depend on agriculture. nitrogen emissions in livestock. In addition, gene
Biodiversity is also severely threatened, with editing is used to develop microorganisms for
nearly a million species at risk of extinction (IPBES, precision fermentation to produce food ingredients,
2019). Many components at genetic, species and additives and biopolymers.
ecosystem levels that provide vital services to
agrifood systems are in decline. This Issue Paper on gene editing is science- and
evidence-based and is forward-looking. It is not
The evolution of humankind and agrifood systems intended to be an exhaustive review or a meta-
has been one of adaptation and change. Problems analysis. Gene editing regarding microorganisms
have been solved in numerous ways, including is not discussed. The paper takes a broad and
moving to more productive environments, interdisciplinary approach, which is necessary
changing management practices, developing new because application of gene editing, as with any
techniques, etc. Early agriculturalists built on the technology, involves balancing benefits, costs and
results of evolutionary forces by selecting seeds of uncertainties. These are discussed in terms of
the best crops, and superior animals, to perpetuate consequences for human hunger, human health,
their production. They were unaware that they food safety, effects on the environment, animal
were exploiting naturally occurring mutations welfare, socioeconomic impact and distribution
that conferred favourable traits on their crops and of benefits. Intrinsic ethical concerns are also
livestock. Long before the mechanisms of heredity addressed. The gene-editing technology is outlined,
were established in the nineteenth century, and a brief history of plant and animal breeding is
farmers practised plant and animal breeding to presented. Issues of governance and regulation are
increase production. The development of genetics addressed and the roles of the public and private
as a scientific discipline formalized the breeding sectors, alone and in partnership, summarized.
processes and increased their precision. The Finally, various scenarios are suggested for how
principles were applied to numerous key crops and this new technology might be used in the future to
domestic animal species to great effect. Further improve agrifood systems.
application of results from research in biology
and statistics continued to feed into breeding The methodological approach followed for the
processes, all the while increasing precision. Issue Paper drew on robust scientific knowledge
Understanding of genetics at the molecular level, summarized by the authors. The major issues to
including whole genome sequencing, provided be addressed were identified by the authors and
breeders with more refined tools, which increased an FAO Task Force on emerging biotechnologies.
the efficiency of generating adapted plant and To secure a high-quality product, external experts
animal germplasm. This step represented even reviewed the paper. This represented a double
greater precision and efficiency. check to ensure that important issues were not
overlooked.
Gene-editing/genome-editing technologies,
including CRISPR (clustered regularly interspaced This Issue Paper attempts to discuss the most
short palindromic repeats), represent one of the important topics associated with gene editing,
latest advances in genetics and its application to considering FAO’s vision of a world free from
plant and animal breeding. Gene editing allows hunger and malnutrition, where food and agriculture
modification of a genome more precisely than contribute to improving the living standards of
other forms of breeding. Gene editing can reduce all, especially the poorest, in an economically,
the breeding time needed to produce a new variety socially and environmentally sustainable manner.
or breed and reduce research and development In keeping with FAO’s role as providing a neutral
costs. Gene editing also represents an opportunity forum for constructive dialogue and exchange of
to address a range of difficult problems, including knowledge, this Issue Paper addresses the merits
those associated with developing durable and demerits of gene editing. It does not take a
resistances to diseases, pests and abiotic stresses. side in the discussion and neither advocates nor
It also offers new options for developing adapted provides recommendations.

2
2 Advances in plant and animal breeding
SUMMARY
Plants and animals evolved under conditions of A brief history of plant and animal breeding
natural selection acting on spontaneous mutations.
Mutations, the building blocks of evolution, Plant and animal breeding build on the results of
determine which individuals survive and which natural selection, the forces that fuel evolution.
do not, favourable mutations being retained The building blocks of evolution are spontaneous
and perpetuated. Mutations and chromosomal mutations, changes in an individual’s DNA
crossovers provide the diversity on which natural, (deoxyribonucleic acid). Mutations can be molecular
and more recently artificial, selection acts. The changes or the losses or duplications of molecular
advent of settled agriculture represented a time material. Hybridization among individuals with
of increased directional selection, the ancient different mutations creates the diversity on which
agriculturalists choosing seeds of the best plants natural selection, and more recently artificial
to sow in subsequent seasons. Crops were selection, acts.
domesticated through continuous rounds of
selection among wild species. Likewise, the best Wild cereal grains were being harvested and ground
individuals among livestock animals were retained in the Jordan Valley over 20 000 years ago, and
for breeding purposes. Increases in crop and similar relatively sophisticated management of food
livestock production were achieved without any plants took place in other parts of the world. Early
understanding of the underlying mechanisms of agriculturalists had no understanding of genetics
heredity. Understanding of how traits are under and yet unwittingly they selected among plants and
genetic control came about in the mid-nineteenth animals, leading to domestication of some amenable
century and this information was applied to species by 12 000 years ago. Such unintentional,
breeding better crops and livestock. Important traits and later deliberate, selection represent the
were demonstrated to be under the control of single cornerstone of plant and animal breeding. Desirable
genes in some cases and multiple genes in others. plant traits that were consciously selected
With the development of genetical and statistical included upright habit and non-shattering heads
understanding, plant and animal breeding became in cereals, and docility in animals, but many other
more precise and more efficient. Elucidation of the traits valuable to farmers were maintained, and
molecular mechanisms of gene action added further undesirable ones removed. Tremendous progress
precision and provided breeders with additional was made over thousands of years in the absence
tools. Gene-editing technologies represent the of any understanding of the mechanism of heredity.
latest step in this continuum, potentially increasing However, it was established, albeit unknowingly,
precision in breeding crops and livestock. The that breeding progress could only be made if there
technologies, including CRISPR-Cas, enable specific was variation in a population and screening and
areas of a genome to be targeted precisely and cut. selection for traits could be practised within and
Insertions and deletions of genetic material at the among those populations.
cut site alter protein production, ultimately allowing
a germline to be developed that will result in a plant Understanding the genetic mechanism of heredity
or animal expressing sought-after traits. Applications came about through the work of Gregor Mendel in
of gene editing are discussed for traits introduced the mid-nineteenth century that was rediscovered
into plants and animals. in 1900 (Stenseth, Andersson and Hoekstra,
2022). Plant breeding from thereon assumed
scientific status and became more precise.
Scientific breeding replaced empirical breeding,
which for several hundred years had relied in trial-
and-error approaches. Selection among progeny
of deliberately hybridized parents or those with
induced mutations replaced mass screening of
progeny from largely random populations from
open pollinations or spontaneous mutations. As
more became known about genetic control of

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Advances in plant and animal breeding

traits, it was realized that many important traits whom lost their farmland, resulting in considerable
were controlled not by simply inherited single rural-urban migration (Ponting, 2007). Large-scale
genes but by gene complexes, polygenes. This adoption and intensified production of single
is referred to as quantitative genetics. Research crops (monocropping), using fertilizer- and water-
in genetics and statistics furnished breeders intensive methods, had far-reaching agricultural
with tools to help them manipulate both types of and environmental impacts, including lowered
inheritance. Biometrical genetics represented a groundwater tables, soil and water pollution
mathematical approach to breeding and allowed and increased greenhouse gas emissions
increased precision in operations. (Foley et al., 2011).

The aim of plant and animal breeders is to use With developments in the understanding of genetic
variation to produce modified, improved, varieties. processes at the molecular level, plant and animal
This relies on exploiting variation, which can either breeders were supplied with a range of new tools
exist naturally or be induced. Existing variation can to aid their work. This heralded the era of genomics;
include breeding lines, cultivars, landraces and wild entire genomes being sequenced. Now breeders
relatives. Induced variation comprises mutations were able to select for variation at the molecular
and wide crosses. Mutations can be induced level. Selection was no longer confined to selecting
using chemicals or radiation, while wide crosses among phenotypes, what the material looked or
can be sexual or somatic, and hybrids can also be behaved like, but at the genotype level, which gene
developed within or between species and genera. sequences were present or absent. One of the
tools this work supplied was transgenesis, whereby
The application of science to plant breeding led to plant, animal, prokaryote and synthetic genes
major advances in cereal production in the 1960s. could be manipulated to express desired traits in
Wheat and rice varieties had genes for dwarfism adapted material. Gene cloning and recombinant
bred into them that altered their harvest indices and DNA technology, genetic engineering, became
meant that more resources were directed to the widely used in plant and animal breeding, and
grain, and they did not lodge when supplied, often particularly in associated research. This suite of new
under irrigation, with relatively large applications of technologies represented a further advance but
fertilizer. The new high-yielding varieties, through created extensive and impassioned debate, which
shuttle breeding, also had daylength insensitivity continues, on the extrinsic merits and demerits of
bred into them. The agrifood systems of many the technology, the risk of creating an oligopoly and
countries were changed because of the Green control of the global agrifood system, regulatory
Revolution technologies, particularly those of and Intellectual Property Rights (IPR) ramifications
Mexico and India (Pingali, 2012). In those countries and on its biosafety and ethics.
yields rose (Gollin, Hansen and Wingender, 2021),
hunger was averted (von Der Goltz et al., 2020), Gene-editing technologies represent the latest step
incomes rose, pressure on land diminished towards increasing precision in breeding crops and
(Stevenson et al., 2013) and infant mortality livestock and are a natural sequel to genomic and
declined (Bharadwaj et al., 2020). The advances transgenic technologies. Technologies, including
made were not, however, solely attributable to CRISPR-Cas, enable specific areas of a genome
plant breeding efforts; new agronomic practices to be targeted precisely and cut. Insertions and
were required, including increased irrigation and deletions of genetic material at the cut site alter
agrochemical use. Nonetheless, the breeding protein production, ultimately allowing a germline
component has been calculated to account for to be developed that will result in a plant or animal
about 20 percent of yield growth between 1960 expressing sought-after traits. Foreign genes need
and 1980 and approaching 50 percent of the yield not necessarily be inserted into a host genome,
increase between 1980 and 2000 (Evenson and there are protocols for removing foreign material
Gollin, 2003; Qaim, 2016). under some circumstances. As with all new
technologies, there is discussion of the benefits,
The Green Revolution was not entirely positive, risks and consequences from a range of viewpoints,
it did have some negative socioeconomic and which will be addressed in this Issue Paper.
environmental consequences, partially offsetting
the productivity gains. These included increased Figure 1 summarizes developments in plant
indebtedness of small-scale producers, some of breeding technologies, from conventional crossing

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 Gene editing and agrifood systems

Figure 1 Developments in plant breeding technologies

to gene editing, indicating the time saving the same as for the SDN-1 protocol. SDN-3 also
represented by gene editing over other approaches. relies on foreign donor DNA that is inserted into the
cut site. However, unlike SDN-2, which elicits small,
Principles of gene editing precise changes, SDN-3 can insert large fragments
of DNA, including entire genes. SDN-3 is also,
Gene-editing approaches rely on distinct protein- depending on circumstance, inefficient and there
DNA interactions to target specific areas of the are newer, more precise, gene-editing technologies
genome. Various protocols can be used. The available, such as base editing. Fundamentally
discovery and engineering of CRISPR has simplified SDN-1, SDN-2 and SDN-3 respectively effect DNA
the process of rapidly and efficiently targeting disruption, DNA correction and DNA insertion.
protein domains in areas of interest in a genome
(Doudna and Sternberg, 2017). The gene-editing Site-directed small mutations can also be achieved
process comprises two components, targeting a by oligonucleotide-directed mutagenesis (ODM).
DNA site of interest in the nucleus of a living cell ODM uses a short stretch of nucleic acid, which
and editing it. Endogenous cellular DNA replication has a homologous sequence to the target site, but
and repair secures the editing event. which contains a point or small mutation. This type
of gene editing is, therefore, comparable with SDN-
Site-directed nuclease (SDN) gene editing 2 (Sprink et al., 2016).
involves the use of different DNA-cutting enzymes
(nucleases) that cut DNA at fixed locations using A detailed description of some of the gene-editing
various DNA binding systems. After the cut is technologies is provided in Appendix A and site-
made, cellular DNA repair mechanisms recognize directed nuclease are summarized in Box 1.
the cut and repair the damage, using one of two
pathways that are naturally present in cells. SDN-1 Some illustrative applications of gene editing
relies on the endogenous capacity to repair breaks
in DNA. Insertions and deletions around the cut site Gene-editing technologies can be used in practical
change protein synthesis mechanisms so that a plant and animal breeding to make some of the
targeted protein can be knocked out, its expression component processes more efficient and more
terminated. SDN-2 uses a foreign donor nucleic acid precise. They are also of considerable use in
template to perform a precise edit at the cut site, research to generate information in support of plant
which is incorporated into the host genome. The and animal breeding. Although many gene-edited
process is inefficient however and the result is often organisms have been created or are in the pipeline,

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 Advances in plant and animal breeding

Box 1 Site-directed nucleases

SDN-1: Techniques using site-directed nucleases with homologous recombination (HR). SDN-2 generates
the objective of generating localized random base changes spanning few base pairs in genetic elements
pair changes, deletions or short random insertions (promoters, coding sequences, etc.) that pre-exist in
(indels), as a result of error in the cell gene repair the host genome.
mechanism based on non-homologous end joining
(NHEJ). No exogenous DNA repair template is used SDN-3: Techniques using site-directed nucleases with
in these applications. the objective of generating a localized pre-defined
insertion/deletion/replacement of entire genetic
SDN-2: Techniques using site-directed nucleases elements (promoters, coding sequences, etc.), or
with the objective of generating a localized pre- entire genes, because of co-introducing a large DNA
defined point mutation or deletion/addition, because molecule to be inserted in the target area. DNA
of co-introducing a repair DNA molecule that is molecule may or may not be homologous to the
homologous to the targeted area and is expected targeted area, and its insertion can take place either
to act as a repair template. Repairing is achieved by by HR or by NHEJ.

very few have been commercialized to date. subsequently identified a critical additional wheat
Gene-edited products that have already entered genome edit that increases wheat yields and
the market include a gamma-aminobutyric acid rescues any negative pleiotropic growth defects
enriched tomato, two CRISPR edited fish in Japan, resulting from the MLO knockout (Li et al., 2022)
and soybean with improved fatty acid composition (see Appendix B.1a).
in the United States of America (Waltz, 2022).
Rice blast disease reduces rice yields worldwide.
Table 1 provides an overview of applications of Gene editing a critical site in the rice genome
gene-editing technologies in agrifood systems. enables generation of new rice varieties with
durable rice blast resistance (Wang et al., 2016).
Disease resistance in plants Bacterial blight also reduces rice yields. A small,
Host plant resistance to pathogens is controlled targeted deletion edit in the rice genome results in
by various genetic mechanisms. One mechanism, superior improved resistance (Oliva et al., 2019).
involving so-termed S genes, controls resistance to
powdery mildew (MLO resistance), a disease that These are just three examples of many where
infects a broad range of crops, including wheat and gene editing has the potential to improve disease
barley. Fifty years ago, Ethiopian barley landraces resistance in crop plants to a range of pathogens
collected in the 1930s were identified as MLO and pathogen types.
resistant and the resistance did not conform to the
classic gene-for-gene system (Jørgensen, 1992). Herbicide tolerance
Induced mutation was used to develop mlo genes Herbicide tolerance in crops is an important
for barley effective against all isolates of the trait, particularly in intensive agrifood systems.
pathogen. Powdery mildew isolates with elevated Transgenic breeding for herbicide tolerance relied
MLO aggressiveness were produced in barley that heavily on the introduction of herbicide tolerance
were not found in nature. genes from bacteria and various plant species into
major crops such as maize and soybean. Gene-
Natural mutations that decrease the levels of editing approaches can also be applied to develop
the MLO protein were identified in barley, which new crop varieties with dependable herbicide
render those barley cultivars resistant to powdery tolerance. Unlike transgenic breeding, gene editing
mildew disease. Researchers demonstrated that can be used to edit host plant genomes directly,
the use of SDN technologies, which are used for without introducing extraneous DNA. Precise
gene editing, can knock out three copies of the editing, including base editing and prime editing,
MLO gene in wheat to develop resistance (Wang can target specific amino acid sequences in genes
et al., 2014). Subsequent studies established that of interest and thereby confer tolerance. These
simply knocking out the gene in wheat resulted technologies demonstrate the capacity to develop
in decreased crop yields, however. Research new plant varieties rapidly by targeting key areas

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Table 1 Applications of gene editing technologies in agrifood systems

Species Trait Research organization Sources

Improved food and feed quality

Camelina Improved fatty acid composition Department of Plant Sciences and Plant Pathology, Montana [1]
State University, Bozeman, MT 59717, USA
Lettuce Increased vitamin C content State Key Laboratory of Plant Cell and Chromosome [2]
Engineering, Center for Genome Editing, Institute of
Genetics and Developmental Biology, Chinese Academy of
Sciences, Beijing, China
Oilseed rape Improved fatty acid composition National Key Laboratory of Crop Genetic Improvement, [3]
Huazhong Agricultural University, Wuhan, China
Potato Reduced acrylamide formation Cellectis plant sciences Inc., New Brighton, MN, USA [4]
Soybean Improved fatty acid composition Calyxt, Roseville, MN, USA [5]
Tomato High content of γ-aminobutyric Sanatech Minato-ku, Tokyo, Japan & University of Tsukuba, [6]
acid (GABA) Ibaraki, Japan
Wheat Low gluten content Instituto de Agricultura Sostenible (IAS-CSIC), Córdoba, Spain [7]
Wageningen University, Wageningen, Netherlands [8]
Wild tomato De novo domestication – High Several universities from Brazil, Germany and the USA [9]
antioxidant content
Brewer’s Flavour improvement in Centre of Microbial and Plant Genetics, Leuven, Belgium [10]
yeast fermented beverages

Improved agronomic properties

Alfalfa High yield National Institute of Agricultural Technology, Argentina [11]
Banana Fungus protection Queensland University of Technology, Brisbane, Australia [12]
Protection against bacterial wilt, International Institute of Tropical Agriculture, Nigeria [13]
fusarium wilt and banana streak
virus
Protection against bunchy top virus Agricultural Research Council, Pretoria, South Africa [14]
Cacao Protection against fungal disease Pennsylvania State University, USA [15]
Cassava Reduced cyanide levels University of California, Berkeley, CA, USA [16], [17]

Virus resistance
Cherry Virus resistance Department of Horticulture, Plant Biotechnology Resource [18]
and Outreach Center, Michigan State University, East
Lansing, MI, USA
Citrus Protection against citrus canker Chinese Academy of Sciences, China [19]
Cucumber Protection against multiple Department of Plant Pathology and Weed Research, ARO, [20]
viruses Volcani Center, Bet-Dagan, Israel
Flax Herbicide tolerance Cibus, San Diego, CA, USA [21]
Grapevine Drought tolerance Stellenbosch University, Stellenbosch, South Africa [14]
Maize Fungus resistance DuPont Pioneer, Johnston, IA, USA [22]
Oilseed Rape Herbicide tolerance Key Laboratory of Plant Functional Genomics of the Ministry [23]
of Education, Yangzhou University, Yangzhou China
Potato and Disease-resistant varieties Russian Academy of Sciences, Russian Federation [24]
sugar beet
Rice Salt tolerance National Institute for Plant Biotechnology, New Delhi, India [25]
Fungus protection Department of Genetics, Development & Cell Biology, Iowa [26]
State University, Ames, Iowa, USA
Salt tolerance Key Laboratory of Rice Genetic Breeding of Anhui Province, [27]
Rice Research Institute, Anhui Academy of Agricultural
Sciences, Hefei, 230031, China

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 Advances in plant and animal breeding

Species Trait Research organization Sources

Sorghum Increased protein content University of Queensland, Queensland, Australia [28]

Striga resistance Kenyatta University, Kenya [41]

Soybean Nematode resistance Evogene, Rehovot, Israel & TMG, Cambé, Brazil [29]
Tomato Bacterial resistance Department of Plant and Microbial Biology, University of [30]
California, Berkeley, USA
Provitamin D3 enhanced John Innes Centre, Norwich, United Kingdom [40]
Wheat Fungus protection State Key Laboratory of Plant Cell and Chromosome [31]
Engineering, Institute of Genetics and Developmental
Biology, Chinese Academy of Sciences, Beijing, China
Applications in animal breeding
Chicken Protected against avian leukosis Czech Academy of Sciences, Prague, Czech Republic [32]
virus
Dairy cattle Hypoallergenic milk National Institute of Agricultural Technology, Argentina [33]
Polled Recombinetics, St. Paul, Minnesota, USA [38]
Fish (tiger Increased growth Regional Fish Institute, Kyoto, Japan & Kyoto University, [34]
puffer and red Japan & Kindai University, Japan
sea bream)
Goat High-yielding cashmere goats State Key Laboratory of Reproductive Regulation & Breeding [39]
of Grassland Livestock, Inner Mongolia University, Hohhot,
010000, China
Salmon Sterility and disease resistance Norwegian Institute of Marine Research, Bergen, Norway [35]
Swine Double muscled Seoul National University, Seoul, Republic of Korea [39]
Increased tolerance to cold Chinese Academy of Sciences, Beijing, China. [36]
temperatures and leaner meat
Protection against swine fever Roslin Institute, Edinburgh, United Kingdom [37]

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[37] C RISPR immunizes pigs against PRRS—deadly viral disease that costs $600 million annually. 2019. https://geneticliteracyproject.
org/2019/06/26/podcast-crispr-immunizes-pigs-against-prrs-deadly-viral-disease-that-costs-600-million-annually/
[38] C arlson, D.F., Lancto, C.A., Zang, B., Kim, E.-S., Walton, M. et al. 2016. Production of hornless dairy cattle from genome-edited cell lines.
Nature Biotechnology, 34: 479–481. https://www.nature.com/articles/nbt.3560
[39] L i, X., Fei, H., Xiao, H., Hui, W., Bai, D., Wang, X., Liang, H., Cang, M., Liu, D. 2019. Generation of Tβ4 knock-in Cashmere goat using
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[40] L i, J., Scarano, A., Mora Gonzalez, N., D’Orso, F., Yue, Y., Nemeth, K., Saalbach, G., Hill, L., Oliveira Martins, C., Moran, R., Santino, A. &
Martin, C. 2022. Biofortified tomatoes provide a new route to vitamin D sufficiency. Nature Plants. https://doi.org/10.1038/s41477-022-
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[41] M allu, T.S., Mutinda, S., Githiri, S.M., Odeny, D. & Runo, S. 2021. New pre-attachment Striga resistant sorghum adapted to African agro-
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Advances in plant and animal breeding

of the host genome (Zhang et al., 2020; Liu et al., The glutenin gene family in wheat has numerous
2020; Li et al., 2016; Gao, 2021). members. Because many proteins are implicated
in the production of prolamins, it is not possible to
Gene editing is also a viable technology for leverage traditional breeding approaches to develop
screening plant populations. Large RNA (ribonucleic wheat varieties with reduced levels of prolamin.
acid) libraries have been employed to screen Application of gene-editing technologies, however,
for desired traits based on a variety of known could result in the simultaneous edit of 35 genes in
mutations in particular genes and associated the wheat gluten family, producing transgene-free
phenotypes. Such a targeted gene-editing high- cultivars that could significantly reduce immune
throughput screening approach enabled the reactivity (Sánchez-León et al., 2017).
discovery of new mutations conferring desirable
and durable herbicide tolerance in a variety of crops Wheat is mostly used as a raw material to
(Li et al., 2020). The methods can continue to be produce foods, including bread, that require
developed to screen for other useful traits. high temperatures during preparation. High-
temperature baking of wheat converts the small
Agronomically important traits endogenous molecule asparagine into acrylamide,
Nitrogen use efficiency is a crucial element in which is known to be associated with increased
crop production, affecting plant growth and yield. cancer risks. The genes encoding the asparagine
The status of nitrogen fertilizer use efficiency has biosynthesis pathway were identified and it was
important economic consequences for small- hypothesized that a genetic perturbation of this
scale producers because fertilizer represents pathway would reduce acrylamide levels produced
a considerable investment. Rice mutants with during baking. Genetic knockout of the asparagine
impaired physiological functions were developed synthetase gene in wheat resulted in a near
that were more nitrogen use efficient than the complete reduction in levels of asparagine, which
original varieties (Wang et al., 2018). In addition, greatly improves wheat’s nutritional profile (Raffan
through targeted gene editing, specific wheat et al., 2021).
genes were targeted and knocked out to produce
new varieties with significantly enhanced nitrogen Vegetable oils are an important global commodity,
use efficiency (Zhang et al., 2021). However, wheat and their nutritional profiles greatly affect human
yields are determined by numerous aspects of the health (Ghodsi and Nosrati, 2020). Soybean
plant’s physiology. The TaGW7 wheat gene has a oil is produced in large volumes for human
rice homolog that influences grain weight and size. consumption, but its properties include low levels
A genetic knockout of the gene in wheat resulted of monounsaturated oleic acid. The protein encoded
in new bread wheat varieties with larger, heavier by the gene for fatty acid desaturase 2 (FAD2)
kernels (Wang et al., 2019). converts oleic acid to polyunsaturated linoleic acid.
Through targeted gene editing to knock out this
Soil salinity, which causes salt stress, is a frequent gene, new soybean varieties are being developed
barrier to crop production. A single knockout of a with substantially increased levels of oleic acid (Al
gene controlling a specific protein’s production in Amin et al., 2019) and low levels of linoleic acid.
tomatoes generated new tomato varieties with This builds on the work of Demorest et al. (2016),
enhanced tolerance to salt under experimental who developed a soybean line with low levels of
conditions (Tran et al., 2021). Furthermore, trans-fatty acids. A higher consumption of oleic
upregulation of a maize gene (ARGOS8) enhances acid significantly reduces the risk of cardiovascular
drought tolerance in the crop. Using targeted disease in humans (Kris-Etherton et al., 1999).
insertion technologies, the upregulated ARGOS8 Premium high-quality gene-edited soybean oil
gene was incorporated into the genome and in field became available in the United States of America
trials the improved variants had enhanced yields in 2019 (Tome, 2021). Targeted mutagenesis, using
under drought stress conditions (Shi et al., 2017). CRISPR-Cas9, was also used to develop a health-
promoting tomato, Sicilian Rouge, with high levels
Quality traits of gamma-aminobutyric acid (GABA) (Nonaka
The presence of prolamin, a glutenin, in wheat et al., 2017), which is sold in Japan for general
causes the autoimmune disease celiac, which consumption (Waltz, 2021). In 2023, nutrient-
affects between 1 in 170 to 1 in 100 individuals enriched mustard leaf will become available in the
on a global basis (Fasano and Catassi, 2012). United States of America (Smith, 2021).

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 Gene editing and agrifood systems

Potatoes are an important food source for people potato, cassava and banana. Although sixteen cases
around the world, but they do not store well. To of use of CRISPR-Cas9 were listed for tomato, and
extend the storage life of potatoes and enable twenty-one for rice, carrot, eggplant, camelina, apple
year-round consumption, many growers use cold and grape were also listed.
storage. However, sugars accumulate when
potatoes are exposed to low temperatures. Crop domestication
These, in turn, are transformed into acrylamide The genetic base of some crops is narrow.
when processed at high temperatures. The Exploiting the genetic diversity of wild crop
genetic knockout of the vacuolar invertase gene relatives can furnish new and useful genetic traits,
(Vlnv) substantially decreases levels of sugars which can be introgressed into elite varieties.
accumulated in cold-stored potatoes and thereby However, making and managing wide crosses is
extends their storage life (Zhu et al., 2014). difficult and resource demanding.

Quantitative trait regulation A supplementary approach might be to

Numerous agronomically important traits are domesticate wild crop relatives directly to produce
controlled quantitatively, by polygenes, and cannot commercial cultivars. Traditional domestication
be edited through simple genetic knockouts. processes are slow, requiring millennia, as
To modify such traits requires changes in the evolution progresses through gradual accumulation
expression levels of several genes, rather than of spontaneous mutations. Making such genetic
simply switching a single gene on or off. Gene- changes to crop relatives using established
editing technologies can edit cis-regulatory genetic technologies is impractical, if not impossible.
elements to fine-tune expression levels and However, expanding knowledge of the genetics of
expression patterns of multiple genes (Rodríguez- crop domestication has enabled exploration of the
Leal et al., 2017; Zhang et al., 2018a; Xing et al., use of gene-editing technologies to speed up the
2020). Cis-regulatory genetic elements are regions domestication process.
of DNA located near targeted genes. Edited
mutations alter expression levels or patterns of the CRISPR-Cas technology was employed to edit
targeted gene. Editing such regions for specific multiple domestication-related genes in wild tomato
tomato genes produces a variety of growth forms simultaneously (Li et al., 2018). Specifically, partial
and canopy architectures, enhancing genetic domestication of the wild tomato allowed creation
diversity (Rodríguez-Leal et al., 2017) and generating of new varieties suitable for current field production,
useful germplasm for future breeding efforts. comparable with currently grown elite tomato
varieties. The newly domesticated wild tomatoes
A further level of protein expression regulation maintain their highly desired stress resistances.
is governed by the translation levels of genes.
The manipulation of open reading frames (ORFs) In addition to the domestication of wild tomato,
located near a primary coding sequence has a a recent study described potential de novo
major effect on gene expression (Zhang et al., domestication of wild rice to obtain new commercial
2018a; Xing et al., 2020). Through incorporation rice varieties. Wild rice, in comparison with widely
or removal of nearby ORFs, a suite of expression grown elite rice varieties, has broad genetic
levels for specific genes can be generated. Using diversity. Wild rice is characterized by its large
this approach, new varieties of lettuce with biomass and strong environmental adaptability.
various levels of vitamin C and new varieties of Using multiplex gene editing, researchers improved
strawberries with various levels of sugar have been six agronomic traits, including seed shattering, awn
developed (Zhang et al., 2018a; Xing et al., 2020). length, plant height, grain length, stem thickness
and heading date in wild rice (Yu et al., 2021).
Kumar et al. (2022) reviewed the developments
to date on gene editing of a broad range of crops In addition to wild crop relatives, many currently
with respect to nutrient enrichment. This included important crops have not been exhaustively
enrichment for vitamin A, vitamin E, iron and zinc. domesticated. So termed orphan crops and
They summarized over seventy cases of quality neglected and under-utilized species have not been
improvements in more than twenty crops, including exploited to their full potential. Many are adapted
several crops typically grown by smallholder farmers, to harsh environments and conditions, with the
such as sorghum, groundnut, pomegranate, sweet potential to grow on marginal land, unsuitable

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Advances in plant and animal breeding

for standard crop cultivation. Application of gene pigs is a further application of gene-editing
editing has been explored to increase the utility of technology. Applications in the poultry industry
orphan crops such as sorghum, millet, cowpea and include resistance to avian leukosis virus (Koslová
quinoa (Gao, 2021). et al., 2018). Honey bees resistant to the parasitic
Varroa mite are also being researched with gene-
Livestock editing technologies (Mondet et al., 2020).
Gene-editing technologies have been used to
produce numerous new lines in pigs, cattle, Aquaculture
sheep and goats. The gene-edited individuals Two commercial applications of CRISPR in fish have
can potentially be used as bioreactors (Liu been developed in Japan (see Appendix B.1c). Both
et al., 2013), disease models (Tan et al., 2013), studies leveraged the knockout of a single gene
founder animals for genetic lines with enhanced to increase overall size. The leptin receptor gene
productivity (Proudfoot et al., 2015) and organ in tiger puffer was knocked out, which increased
donors (Hauschild et al., 2011; Li et al., 2015). Gene appetite and consequently weight of the fish. Red
editing was successfully applied to pig zygotes sea bream had its myostatin protein knocked out,
to produce live gene-edited pigs (Lillico et al., which because of suppressed muscle growth
2013). Others modified the genome of Holstein– allowed the fish to grow larger while consuming
Friesian cattle, thereby engineering a heritable the same amount of food (Ohama et al., 2020).
genome modification that facilitated resistance to
tuberculosis (Wu et al., 2015). Microorganisms
Although not a focus of this Issue Paper, gene
Applications to livestock production include editing has been used to develop microorganisms
polled cattle, porcine reproductive and respiratory to control some plant pests and diseases,
syndrome (PRRS) virus-resistant pigs (see Appendix improve soil status, and to help in food processing
B.1b); pigs with improved resistance to African (Wesseler et al., 2022). Examples of applications of
swine fever (ASF); sheep, goats, and cattle with such engineered microorganisms include resistance
increased lean muscle yield; thermotolerant cattle to plant pathogens (Glandorf, 2019), bioremediation
with the slick trait, and sheep with increased wool of soils and biostimulants such as products that
length and yield. Other examples include cows and enhance nitrogen fixation and nutrient up-take
goats with changed milk composition. A transgenic (Gosal, Kaur and Kaur, 2020), and alternatives
calf was produced whose milk contained no protein to current plant protection agrochemicals
β-lactoglobulin, a major milk allergen. An application (Scheepmaker et al., 2016). In the food industry as
in pets produced mini-pigs (Cyranoski, 2015) and well as in the forest industry and related bio-based
faster running beagles (Brinegar et al., 2017). industries, gene editing is used to produce new
bacteria and enzymes, for instance new enzymes
Cows with increased resistance to tuberculosis can increase the fermentation efficiency in food
have been researched using gene-editing processing (Deckers et al., 2020). New bacteria
technologies (Van Eenennaam et al., 2021). Wu and enzymes are also important for developing
et al. (2015) added the mouse gene SP110 to a plant-based alternatives to meat and cellular meat
specific location in the bovine genome and created and play an important role in processing biological
transgenic cattle with increased resistance to resources for the development of bioeconomy
tuberculosis. Classical swine fever (CSF) is another products such as biochemicals as alternatives to
devastating disease, leading to large economic those based on fossil fuels (Clomburg, Crumbley
losses in the pig industry, and CSF-virus resistant and Gonzalez, 2017).

12
3 Gon enetheediting – potential hazards, benefits and impacts
environment and society
SUMMARY
Gene editing has the potential to transform agrifood Gene editing represents an advance in technology
systems and improve food security, nutrition and that has the potential to transform some aspects
environmental sustainability, but for gene-edited of the world’s agrifood systems for the better.
food items, as for conventionally produced foods, However, as with all technological advances, in
there are potential hazards. Identifying potential addition to the perceived benefits of gene editing
hazards and assessing the corresponding risks prior there are potential hazards associated with specific
to commercialization of new products is important processes of production. Some of the risks can be
to ensure their safe and sustainable use, as well anticipated, but there might also be unintended
as assuage public concerns. Potential impact consequences that will need to be managed.
categories include effects on the environment, Although the consequences of introducing gene
biodiversity and human health in terms of food editing into agricultural processes are likely to be
safety and nutrition. Suitable methods for assessing complex and interrelated, some elemental divisions
gene-edited products will be important to ensure can be made. One of the prime questions concerns
the safety of gene-edited products while not placing whether gene editing has the capacity to relieve
an onerous regulatory burden on small developers global hunger, albeit partially. It is also relevant
and innovators. The economic impact of gene to ask whether human health will be impacted
editing depends on the extent to which gene-edited positively through consumption of gene-edited food
products become available to small-scale producers, and whether the environment will change in terms
especially in LMICs, and those further down the of ecosystem stability because of introducing gene-
supply chain. Gene editing also has the potential editing technologies. Gene editing, for specific
to reduce expenditures on crop protection and traits that may be introduced in livestock, could also
decrease labour demand. A potential positive impact raise questions about animal welfare. Moreover, if
at the farm-household level will depend on input benefits of gene editing are realized, and agrifood
quality, including that of seeds. There are social and systems are transformed, how will the benefits
ethical concerns associated with gene editing that be distributed? The discussion of these issues will
are influenced by trust in scientists and developers, include both practical and ethical considerations,
concerns about risk and benefit distributions, and and answers to key questions are unlikely to be
questions about naturalness and differing cultural straightforward. At the same time, these issues do
values. These issues, including intrinsic ethical not differ from those associated with established
concerns and animal welfare, will have to be breeding methods, including mutation breeding and
considered when deploying gene-edited products. transgenesis.

Gene editing and human hunger

Food shortages are not the sole cause of hunger.

Hunger and poverty are inextricably linked, and the
causes of poverty are many, including inequitable
income distribution, population pressure,
compromised health, inadequate education and
issues surrounding land tenure. Hunger and
malnutrition are determined by both the amount
of food available for consumption and its quality.
Whether and where gene editing can have an
impact is the point at issue.

Experience with transgenic crops has, at times,

been controversial. An in-depth review of crop
yield data by the United States National Academies
of Science, Engineering and Medicine (NASEM)
established no overall increase in the rate of yield

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Gene editing – potential hazards, benefits and impacts on the environment and society

gain attributable to genetically modified (GM) crops high population growth rate and political instability,
through 2015, although some GM crops and traits, where plant breeding efforts, for example, are
in specific environments, were associated with unlikely to reach their potential.
yield gains (e.g. Bt crops under pest pressure)
(NASEM 2016a). Others suggested that GM crops The issue of malnutrition is not the same as that of
contributed to food safety and improved income of hunger. If the problem is one of an unbalanced diet,
smallholder farmers (ISAAA, 2019). rather that one of total calorie intake, gene editing
could make major contributions. For example,
Yield improvements using gene editing might progress has been made, using traditional and
be possible but are likely only to be for specific modern biotechnological techniques in the field of
crops and traits under specific environmental biofortification. The provision of adequate levels
conditions. However, engineering more complex of essential dietary elements, including minerals,
traits that address yield gains, such as improved by boosting their levels in traditional host plants,
photosynthesis and stress tolerance, might be or by introducing them into non-traditional hosts,
achievable with gene editing (Matres et al., 2021). can have a significant impact on malnutrition. Gene
Gene-edited crops show promise for positive local editing might be used to obviate the sometimes
effects on hunger if they are integrated into small- long breeding processes that HarvestPlus,1 for
scale agrifood systems, many of which are based example, has used to produce nutrient-enriched
on neglected and underutilized species, and not crops. Kumar et al. (2022) published an extensive
necessarily on the major crops that are likely to be list of instances where CRISPR-Cas9 has been
the prime recipients of gene-editing attention. used to improve the quality of a range of crops,
including cereals, vegetables and fruits. They
Gene editing undoubtedly is a more precise provided information on how gene editing has been
technology than previous induced mutagenesis and used to boost the content of vitamins A and E, iron
genetic engineering techniques, and some of the and zinc in various crops in an attempt to tackle
safety issues surrounding introduction of foreign problems of malnutrition.
genes into organisms are no longer valid. However,
what effect gene editing can have when food Gene editing also has potential for developing
distribution represents a major challenge is open orphan crops and neglected and underutilized
to debate, especially given that food production is species to boost food and nutritional security,
often less of an issue than its equitable distribution agrobiodiversity and improve livelihoods. Such
and access. crops are unlikely to be attractive to the private
sector because they are predominantly grown by
Gene editing represents a tool for scientists and poor smallholder farmers in the more marginal
breeders, making their work more efficient and environments. Consequently, funding research
effective. It might mean that response to disease on these crops can be scarce and the private
and pest epidemics can be hastened over current sector usually would not regard them as a priority
relatively time-consuming processes. Useful work for investment. There are however possibilities
has been done on gene editing and powdery for organizations such as CGIAR (formerly the
mildew resistance, but this represents just one of Consultative Group on International Agricultural
many serious crop diseases that merit attention. Research), AIRCA centres (Association of
If gene editing were to contribute significantly to International Research and Development Centers
developing disease and pest tolerant germplasm, it for Agriculture) such as ICBA (International Center
would be an ongoing process because resistances for Biosaline Agriculture) and icipe (International
are overcome through evolution and adaptation Centre for Insect Physiology and Ecology), and
of the pests and pathogens to the engineered NARS (national agricultural research systems) to
resistances. Tan et al. (2020) provided a detailed develop public goods that are unattractive to the
technical account of how gene editing might aid private sector.
plant breeding. However, the environment sets
natural limits on production, and climate change, Gene-editing technologies are constantly
with accompanying extreme weather events, evolving, providing even more precise tools for
makes crop and animal production particularly researchers and breeders. The causes of hunger
challenging. It is also the case that food shortages
frequently occur in areas of significant poverty, 1 https://www.ifpri.org/program/harvestplus

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 Gene editing and agrifood systems

and malnutrition go well beyond anything that crossed allergenicity associated with introduced
gene-editing applications can solve, and alone, novel proteins could potentially arise in SDN-3
gene editing is unlikely to make a significant impact applications. In contrast, for SDN-1/2 the allergy-
on hunger and malnutrition. However, used in related potential risk might be a rise in endogenous
conjunction with other available tools, it is set to allergens, an outcome that is also possible with
make a significant contribution to transformation of mutants obtained using techniques such as
agrifood systems. radiation, chemical mutagenesis or somaclonal
variation, especially if the host crop is a known
Gene editing and human health source of food allergens.

Many direct effects of gene editing on human Traditional allergenicity assessment for intentionally
health are likely to take place through medical introduced proteins (transgenics and SDN-3) has
interventions. In agrifood systems, food safety relied on several methods, including bioinformatic
can be a major issue in terms of human health analysis, looking for sequence homology to known
considerations. While biofortification itself was allergens and by using a threshold homology
largely regarded as beneficial and humanitarian, the (Fernandez et al., 2021). Such methods are better
introduction of foreign genes into plants, and some suited for detecting potential cross-reactivity with
animals, often raised questions. There were fears an existing allergy to other foods. Complementary
about potential adverse effects from consumption methods, used in combination with bioinformatics
of transgenic food products. The debates about to assess the possibility of de novo allergenicity
the benefits of genetically engineered foods were of introduced proteins, include thermal and
taking place at a time when organic farming was protease digestibility. Only in cases where the new
being mooted by some as a viable alternative protein comes from an organism known to cause
to high-tech farming. This was regarded by allergies, or when there is a positive match in the
many as representing a conflict between a bioinformatic analysis, is another study warranted
natural and a synthetic approach to agricultural using IgE binding of sera from people with known
production (Rausser, Simon and Ameden, 2000). allergies to a protein (Su, Ezhuthachan and Ponda,
However, there are, and have always been, 2020).
negative effects of agriculture on human health,
including occupational health, from direct use of In the case of SDN-1/2 gene-edited crops for which
agrochemicals to the indirect impact of agricultural the host is a known source of food allergens,
practices on the environment. A necessary allergenicity due to upregulation (increase) in the
discussion is one of whether an intervention, in expression of allergens may require a complete
this case gene editing, represents an advance over genetic characterization of the unintended changes
current practices or not. and quantitation of endogenous allergens in the
whole food, in the same way as it should be
Potential food safety hazards of agricultural required for mutants obtained using any other
products, including those conventionally produced, techniques where upregulation of allergens is also
includes both toxicity and allergenicity of elements a similar possibility.
in the food. Changes in the levels of toxins,
allergens and nutrients, as well as mutations, can Toxicity
occur naturally. Gene-edited foods are no exception, For SDN-1/2 gene editing, upregulation of
and unintended effects and off-target mutation can endogenous toxicants is possible because it
occur (NASEM, 2016a). Genetically modified crops has occurred occasionally with new varieties
have been assessed on a comparative basis with obtained by spontaneous or induced mutation
their conventional or non-GM counterparts (Kok (for example in potato and celery). However, for
et al., 2008) and as a broad category, marketed GM other mutagenesis-based techniques, the breeder
crops were determined to be as safe to eat as their typically ignores the mutation leading to the new
conventionally bred comparators (NASEM, 2016a). trait and the existence of potential off-target
mutations. Conversely, gene editing offers more
Allergenicity insight that might help breeders discard potentially
SDN-3 can be used for the expression of novel risky mutants more reliably compared with
proteins intentionally to create a transgenic previous techniques.
organism. As with other transgenic crops, new or

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Gene editing – potential hazards, benefits and impacts on the environment and society

For SDN3-based transgenesis, current methods pigs to be reared without neomycin so evolution
applied to assess the potential toxicity of novel of bacterial resistance to that class of antibiotics
proteins in foods derived from recombinant- would be reduced and human health would not
DNA organisms likely will continue to be applied. be put at risk (FDA, 2020). For the thermotolerant
Countries have applied these robust and reliable cattle, during the FDA review, WGS generated
methods following Codex Alimentarius Guidelines evidence of unintended mutations in the genomic
for three decades. sequences from gene editing. However, through
comparative bioinformatic analysis, these were
Composition analysis determined not to result in changes to protein
Off-target edits and unintended DNA insertions expression or impact the safety of the food relative
with SDN-1 and SDN-2 modifications can occur to its conventional counterparts. The necessity
and this should be considered for assessing the for whole-food feeding studies to assess first
safety implications of food products (Lema, 2021). generation GM crop safety has been contested
Although the intended modification might be (Devos et al., 2016; EuropaBio, 2018; Kuiper,
safe and may even already be present in the food Kok and Davies, 2013; Schiemann, Steinberg,
supply, unintended insertions or off-target edits and Salles, 2014), and improved guidelines for
might change the food’s composition regarding the conduct of such GM food studies have been
nutrients, toxins or allergens. With the advent developed (Schmidt et al., 2016). Alternatively,
of cheaper and more efficient DNA sequencing, changes in endogenous toxins or allergens
whole genome sequencing (WGS), in addition to arising from unintended edits or epigenetic
bioinformatic approaches, has been suggested effects in gene-edited crops may be assessed
to detect and assess changes in gene-edited using a component-by-component compositional
foods (NASEM, 2016a; Lema, 2021). For example, approach, which requires prior knowledge of which
during and after the regulatory review of the polled compounds to test for.
gene-edited cattle, WGS detected the insertion
of transgenic antibiotic markers (Young et al., Gene editing and the environment
2020; Carlson et al., 2016). Hahn and Nekrasov
(2019) suggested that the most important factor Settled agriculture, including commercial fishing,
for reducing CRISPR-Cas off-targeting in plants is has continuously changed the environment. As
careful selection of target sequences, which can be the global population increased and agriculture
helped by using various software tools. spread, much of the environment changed from its
initial unmanaged state to one of being intensively
There are several reviews on gene-edited managed. The transition from a natural environment
foods done by regulatory agencies that present to an agricultural environment has been taking
substantial equivalence data relevant to safety. place over millennia because the environment is
For example, substance equivalence data were the most valuable resource of humankind. Both
presented to the United States Food and Drug extensive and intensive farming have had marked
Administration (FDA) for a high-oleic acid soybean impacts on a range of ecosystems, and the effects
(edited using transcription activator-like effector have been exacerbated by changes in climate,
nucleases, TALENs), for a reduced alpha-gal sugar particularly increasing temperatures and erratic
pig (edited using older transposon methods), and rainfall patterns. Many agrifood systems have been
for thermotolerant cattle (edited using CRISPR) degraded and others are no longer sustainable
(FDA, 2019; FDA, 2020; FDA, 2022). For each, it and are unable to feed those populations reliant
was not deemed necessary to conduct feeding on them. There are intrinsic concerns for the
trials on the entire gene-edited food using animals environment, with which humans have a personal
or humans, and although some differences were relationship, and concerns that in many instances
noted, employing compositional assessment, in degradation and disappearance of key ecosystems
comparison with conventional food counterparts will result in famine and migration.
they were determined not to be important
for nutrition or safety. One exception was the While there are legitimate concerns about the
transgene that was integrated into the GalSafe introduction or removal of specific genes in
pig (a transgenic animal) for neomycin antibiotic organisms to increase production or ameliorate
resistance, which was determined to be a potential a situation, there is a long history of introduction
microbial food safety hazard. This required the of entire genomes into new environments.

16
 Gene editing and agrifood systems

Various countries have been plagued by the not required long-term environmental field trials.
introduction of alien species that have wreaked However, this is not necessarily an obstacle
serious environmental damage. Moreover, while for policymaking or safety assessment, given
crop plants seldom represent an environmental the equivalence of final products with products
hazard because they are not adapted to an off-farm of conventional and transgenic breeding.
environment, the same is not true of domesticated Therefore, instead of speculative literature on
livestock, which are often able to thrive off-farm the potential impacts of gene-edited products in
and do considerable damage to the natural and agriculture and the environment, it is instructive to
managed environment. Some of the world’s consider the experience on transgenic products
worst weeds are also introductions (May, 1981) and conventional varieties generated using
and while the importance of such introductions is mutagenesis for anticipating the range of potential
acknowledged, they usually do not attract the same impacts. This approach has been supported by
level of attention and discussion as the introduction several scientific bodies, risks being dependent on
or deletion of fractions of entire crop genomes that the characteristics of the product, rather than the
are to be consumed as food. process by which it was produced, and that the
general categories of risk will be the same in kind
Gene-edited organisms and products in food, for gene editing, conventionally bred and transgenic
agriculture and the environment raise equivalent products (NASEM, 2016a; NASEM, 2017).
concerns about environmental and ecosystem
impacts as transgenic (for SDN-3) and conventionally Issues associated with gene-edited plants
bred (for SDN-1/2) crops (NASEM, 2016a; NASEM, Risks from the introgression of genes from
2017). Potential risks can stem from the introduced genetically modified crops into wild relatives is an
traits or through the editing processes (Eckerstorfer area of concern for both GM, gene-edited crops,
et al., 2021). Types of risk include, but are not limited conventionally bred varieties and varieties bred
to, toxicity to non-target species in ecosystems, using mutagenesis. Generally, gene flow can
increased weediness after genetic introgression, reduce the differences between populations and
invasiveness of the gene-edited organism itself, and decrease diversity within a population, thus broadly
changes to water, land, and energy use that may impacting biodiversity (Tsatsakis et al., 2017). Gene
accompany deployment of gene-edited organisms introgression into wild relatives may also pose
(NASEM, 2016a; NASEM, 2017). Factors influencing more direct risks, depending on the introduced
the assessment of the potential risk to ecosystems trait. For example, several varieties of spontaneous/
from gene-editing products will depend on what somaclonal/chemical mutagenesis, gene-edited
the product replaces, its management, the host and GM herbicide-tolerant crops were cleared from
environment and socioeconomic context. The regulation in the United States of America and
magnitude of the risks from gene-edited products elsewhere (USDA, 2022). They included not only
will depend on the product’s characteristics, use and commodity and food crops, but also grasses able
management in the environment, and the features to cross pollinate with neighbouring wild relatives.
of the ecosystem into which it is placed. Potential Herbicide-resistant weeds have arisen from the
risks of gene-edited products, first generation GM use of GM and conventionally bred herbicide-
products, and conventionally bred products inevitably tolerant crops due to overuse of the companion
vary on a case-by-case or product-by-product herbicide, and herbicide-tolerant crops such as
basis. Their relative risks cannot be placed in broad creeping bentgrass and rice have cross pollinated
categories because the products are of numerous with wild relatives, transferring herbicide resistance
types (NASEM, 2016a; NASEM, 2017) However, in genes, and increasing the potential for increased
principle, it can be anticipated that SDN-1/2 products weediness under selective pressure (Zapiola and
have the same risk scopes as earlier mutation- Mallory-Smith, 2017; Tsatsakis et al., 2017). Indirect
based breeding, including natural mutations, while agroecosystem impacts have stemmed from
SDN-3 has the same potential risk scope as earlier unintended migration of herbicide-tolerant GM
transgenesis-based breeding methods. grass pollen over long distances in the northwest
United States of America, and the resulting
Environmental studies on gene-edited organisms herbicide-tolerant weeds have invaded irrigation
in their intended sites of use are scarce because systems and caused management problems for
few gene-edited products have entered the farmers (Rosen, 2018).
market, and regulatory approval processes have

17
Gene editing – potential hazards, benefits and impacts on the environment and society

For several years after the introduction of herbicide- in ecosystems) could theoretically pose risks to
tolerant crops, less toxic herbicides, and in some ecosystems should they escape or be deployed
areas reduced application of herbicides, occurred. in unmanaged situations. However, there is
However, the level of toxicity, as measured considerable experience with the selection of new
by active ingredient from herbicide use with animal breeds having spontaneous mutations that
first generation herbicide-tolerant crops, was did not confer increased invasive potential. For
sometimes lower in comparison with similar instance, the double muscle, slick and hornless
production systems that did not rely on herbicide- traits in cattle, which are currently being obtained
tolerant crops (NASEM, 2016a). Moreover, again through SDN-1/2 gene editing, have been
the adoption of herbicide-tolerant crops often selected in the past from spontaneous mutations
accompanied the adoption of reduced tillage and there is considerable experience that these
systems, with concomitant benefits to soil health mutations did not increase invasiveness.
(Frisvold, Boor and Reeves 2009). However, the
evolution of herbicide-tolerant weeds following In the case of SDN3-edited animals, prior
extensive use of GM and conventionally bred experience with GM animals may be relevant. For
herbicide-tolerant crops, prompted the return example, there has been concern in the case of GM
to more toxic herbicides with potential negative salmon modified to grow faster than non-modified
health outcomes for farmers, in addition to more salmon (Devlin et al., 2010; Devlin, Sundström and
severe weed management challenges (Bonny, Leggatt, 2015), but the developer later showed
2016). In contrast, the rate of development of that a faster growth rate constituted a fitness
herbicide tolerance has not changed substantially disadvantage (FDA, 2015). There is also the potential
for GM crops, including maize, while it has for for hybridization of farmed GM salmon with wild
soybean and cotton (Kniss, 2018). Regardless of salmon, should they escape from their controlled
such inconsistencies, improved crop management environments and enter nearby waters containing
and better communication of good management native salmon (Devlin, Sundström and Leggatt,
practices would help. Lessons learned from GM 2015; Wringe et al., 2018). GM salmon have mainly
crops will help with management of gene-edited been farmed at inland facilities, although some
crops, many of which are likely to be herbicide contained growth is occurring near shores where
tolerant (Bonny, 2016). there are wild salmon populations (Tutton, 2021).
CRISPR-based gene-editing methods are being
Invasiveness of gene-edited plants is of potential explored for bioconfinement of farmed salmon so
concern. For example, abiotic stress traits such that they cannot reproduce should they escape
as drought and heat tolerance, may theoretically from containment facilities (germ-cell free farmed
confer a fitness advantage that could increase salmon) (Wargelius et al., 2016).
invasive potential in the environment, regardless
of the trait engineered through gene editing, other More recently, transgenic pet fish containing
mutagenesis techniques or transgenesis. Yet, this green fluorescent protein (GFP) escaped into open
is not valid in most cases because domesticated bodies of water (Magalhães, Brito and Silva, 2022).
plants are unlikely to become invasive as they The consequences of that escape have not been
cannot grow outside of a carefully managed assessed, but the invader could directly affect local
farming environment (Smýkal et al., 2018), with species by competing for food (Magalhães, Brito
the exception of few (Tsatsakis et al., 2017). and Silva, 2022; Moutinho, 2022), although this
However, some gene-edited crops in development, possibility is unlikely to be much different from the
and cleared through United States of America escape of wild-type, non-fluorescent pet fish of the
regulation, including grasses, pennycress and same species.
canola (USDA, 2022), have wild relatives and can
persist in the environment. For these, increased Overall, it is not possible to predict ecosystem
stress tolerance from gene editing may be a impacts from introduction of gene-edited animals
concern regarding invasiveness or weediness. or the extent of introgression of their genes.
However, this might not solely be an issue relevant
Issues associated with gene-edited animals to gene-edited animals – many corresponding traits
Invasiveness of gene-edited animals in special can be derived by conventional breeding, but may
cases involving traits increasing their fitness require more time (Van Eenennaam et al., 2021).
(ability to survive, reproduce, feed and persist There is the potential for escaped gene-edited

18
 Gene editing and agrifood systems

animals to be innocuous or detrimental, and studies to improve animal welfare by eliminating the need
on anticipating risks are complex given the various for painful dehorning of young cattle (Carlson et al.,
ecological endpoints that need to be considered 2016). CRISPR prime editing was also successfully
(Van Eenennaam et al., 2021). Gene-edited animals used in the Republic of Korea to correct a single
may present potential environmental risks similarly mutation linked to hip dysplasia in two Labrador
to first generation transgenic animals, depending dogs (Kim et al., 2022), and they, like the fish
on the modified trait, the environmental context, (Magalhães, Brito and Silva, 2022), contain the
and other related or non-related species in the added GFP gene. While, apparently successful, the
ecosystem. Nevertheless, the reported cases of procedure has attracted discussion about the ethics
invasive species can be mainly traced back to an of the procedure and the unknowns, particularly
introduction via international trade and/or travel and unintended consequences. However, the method
not via gene editing or other breeding protocols could have potential in correcting for genetically
(CBD, 2021). determined disorders in livestock. Another positive
example of SDN for animal welfare involves the
Gene drive organisms are briefly discussed in potential use of gene drives. Gene drives are
Box 2. being developed to eradicate invasive rodents
by impacting their fertility, and this may reduce
Gene editing and animal welfare suffering to the rodents by substituting for chemical
anti-coagulants that kill through internal bleeding
Regarding non-human animals and the impacts (Leitschuh et al., 2018). With respect to animal
of gene editing, views on ethical status are of welfare, Schultz-Bergin (2018) asked whether
particular importance, especially considerations of CRISPR is an ethical game-changer, concluding
animal pain and suffering (Thompson and Hannah, that it does have the potential to directly improve
2008). One position is that prospective human animal welfare, for example through introduction of
benefits cannot justify harming animals, whereas disease resistance.
other positions view animals as subjugated, being
of extrinsic value and solely providing for the needs Gene editing, socioeconomic impact and
of humankind (de Graeff et al., 2019). Regardless, distribution of benefits
the amount of suffering of or relief provided to
animals will vary depending on the gene-editing Introduction of gene-editing technologies will have
application and production methods used. It is, far-reaching implications for agrifood and social
moreover, not solely a case of making a gene- systems in terms of its potential for improving
editing intervention, the research that leads to and securing production of food. The extent of
the intervention must be considered. The use of the impact is, to date, speculative and it remains
animals in research has long been controversial and to be seen whether expectations can be lived up
centres on the extent to which animals register to. It is certain, however, that the benefits that
pain, the rights of animals and whether the rights accrue from gene-editing applications will be
of humans and the benefits that accrue from distributed among various parties, although not
animal research outweigh the suffering induced necessarily inclusively. World hunger, malnutrition
during experimentation. Justifying animal research and poverty are invariably located in areas where
has always been contentious but were gene agrifood systems are under most pressure and
editing able to reduce or remove the pain suffered where agriculture is most fragile and vulnerable.
by animals during research, or to contribute to Many of these areas are within LMICs. Questions
reducing the requirements for animal research, that about whether small-scale producers are likely
would represent a positive contribution. to benefit from introduction of gene-edited crops
and livestock or whether it will be the richer, large-
The early days of animal biotechnology often scale farmers, are key to the discussion. Costs
incorporated cloning steps, and deformities in of production, ownership of technologies and
offspring were relatively common. However, gene- materials, dependencies and market control are all
editing processes could represent an improvement part of the discussion. Within the limits set by the
in this regard. For example, in the case of the polled environment, it is possible that food production and
gene-edited cattle, only a single mild abnormality food quality will be improved through application of
was associated with the offspring (Young et al., gene-editing technologies, but if the costs outweigh
2020): the application of gene editing was designed the benefits, the technology may not be adopted.

19
 Gene editing – potential hazards, benefits and impacts on the environment and society

Box 2 Gene drive organisms

Another application of SDNs termed gene drive, protect valued populations (population modification)
differing from gene editing, is currently being (NASEM, 2016b; Devos et al., 2022).
developed (NASEM, 2016b). Although gene drive
organisms have yet to be deployed, a few are Hayes et al. (2018) summarized the categories of
under development to decrease unwanted species potential hazard pathways and adverse ecological
in wild ecosystems. For example, to eliminate consequences from gene drive organisms at three
unwanted pest populations, invasive species and levels – molecular, population, and ecosystem – as
disease-carrying organisms. Gene drive systems, well as according to their impacts on target organism
often based on CRISPR-Cas 9 and the introduction capacities to spread disease, survive, reproduce
of cargo transgenes, allow an edited gene on or spread, on non-target organism survival, and on
one chromosome to copy itself into its partner ecosystem services. For example, potential risks from
chromosome during cell division and meiosis. Thus, gene drive organisms for population suppression
inheritance with each generation is biased towards include the risks stemming from introgression of the
100 percent, rather than 50 percent. Cargo genes, suppression gene into desirable, related species in
conferring any trait that can be genetically linked ecosystems (Romeis et al., 2020; Devos et al., 2022;
to an engineered gene drive system, can, with Hayes et al., 2018). If so, the population of a desired
some fitness cost, spread through the population species could collapse, which might cause additional
with the gene drive (Bier, 2022). Cargo genes can ecosystem disruption. For example, gene drives in
be designed that confer desirable traits, including the fruit-fly Drosophila suzukii were developed to
disease resistance, or harmful traits causing suppress the population and protect fruit crops. If
population decline (for example, by killing females). the population is indiscriminately reduced, it may
In the latter case, theoretically, the release of few be necessary to assess if significant indirect food-
individuals with gene drives could cause an entire web effects could occur because of the intended
population to decline or collapse (given full population large-scale reduction in population (Romeis et al.,
mixing and mating) (Esvelt and Gemmell, 2017). If 2020). More direct effects could occur from the
the gene drive works, most offspring will inherit the introgression of the suppression gene into related
engineered gene unless the gene drive is designed to species that may be beneficial to ecosystems
be self-limiting (Champer, Buchman and Akbari, 2016; (Romeis et al., 2020). Hybridization or horizontal
NASEM, 2016b). CRISPR transgenes must remain in gene transfer (e.g. through transposable elements)
the final product to propagate the gene drive. could also have an impact if the hybridized species
exhibited increased damage potential or if it had
Given short generation times and random mating decreased fitness that led to a decline in important
across distances, the release of few individuals ecosystem services (e.g. via reduction in food source
with gene drive systems designed for population for predators of the hybrid) (Romeis et al., 2020).
suppression could, theoretically, cause substantial
perturbations in a population. However, the gene Overall, impacts of open release gene drive
drive scientific community is also working on gene organisms in agrifood systems, including whether
drives that are geographically limited (that target the gene drive works as intended, are difficult to
genetic sequences associated with specific areas), predict from laboratory or field-cage trials (NASEM,
self-limited, or threshold based, as well as ways 2016b; Kuzma, 2019; Kuzma, 2020; Romeis et al.,
to reverse the spread of gene drives by exploiting 2020; Devos et al., 2022). Scientific organizations and
molecular mechanisms (reversal drives) (Esvelt et al., research communities have called for a stepwise,
2014; Bier, 2022; Chenurri, Adelman and Myles, tiered process for field release of gene drive
2022). In such cases, the organism is not designed organisms and biosafety and biosecurity protocols
to spread throughout the population but could be to provide sufficient attention to risk issues prior
limited in terms of area or spread. Gene drives are to open release (Akbari et al., 2015; James et al.,
being developed not only for eradicating agricultural 2018; NASEM, 2016b). Some risks can potentially be
pests (population suppression) (Romeis et al., 2020; mitigated using molecular or geographic methods
NASEM, 2016b; Devos et al., 2022) but also to add (Bier, 2022; Min et al., 2018; Kuzma, 2020).
beneficial genes, such as immunizing genes, to

20
 Gene editing and agrifood systems

Economic impact at farm household level the importance of secondary pests was recorded
The economic impact of gene-editing technologies with the control of the cotton-bollworm in China
depends on how widely distributed the (Wesseler, Scatasta and Hadji Fall, 2011), while
technologies become and which sectors of the wide use of Bt cotton resulted in the overall
society will benefit from their deployment. Small- regional suppression of the cotton bollworm,
scale producers in LMICs, in general, might be not only benefitting Bt cotton farmers but also
expected to benefit relatively more than those benefitting those not cultivating Bt cotton. Similar
farming more intensively in HICs (Wesseler, 2019). effects could be expected for pest control using
Intensive farming requires that pests and diseases gene-edited crops.
are managed using a range of plant protection
methods. A change in farming methods, possibly A change in labour demand stemming from gene-
incorporating gene-edited products, would not edited crop deployment can be expected at two
be expected to increase crop yield, it would levels. The labour demand for crop protection,
simply represent a substitution of one method such as weeding and pesticide application, would
for another (Wesseler, 2019), but could be more be expected to decline, reducing female and child
environmentally beneficial and reduce expenditure household labour. The decline in labour needed for
on pesticides, that is, reduce food costs. However, weeding would benefit female household labour
the relative benefits of gene editing to LMICs (Haggblade et al., 2017). The decline in labour used
over HICs will only be determined on a case-by- for pesticide applications has been linked with
case basis and will depend on which technologies improvements in health (Mancini, 2006; Rola and
are incentivized, developed and marketed, and Pingali, 1993). In the case of Bt crops, there is
their costs and accessibility. The benefits will significant evidence for improved health outcomes
also depend on the type of farming, for example, for farmers from reduced chemical pesticide use
aquaculture farms, urban and vertical farming, and (Kouser and Qaim, 2011) and there are spin-offs
small-scale versus large-scale farming. for improved environmental health. Herbicide-
tolerant crops produced through first generation
In LMICs, where fewer purchased inputs are GM technologies reduced the time farmers and
used than in HICs, gene editing has the potential farm workers spent on weed control, thus freeing
to increase yields substantially. One of the up their resources of time and finance, in addition
prime examples of the application of transgenic to providing direct economic gains (Brookes and
technologies is the introduction of insect-resistant Barfoot, 2018a; 2020). Furthermore, according to
cotton in China (Pray et al., 2001) and India (Qaim some estimates, both Bt and herbicide-tolerant
and Zilberman, 2003). If seeds improved using crops led to the application reduced application
gene editing that provide resistance to pests and of chemical pesticides from 1996 to 2016 in many
diseases become available in HICs and LMICs, instances (Brookes and Barfoot, 2018b; 2020). The
small-scale producers in LMICs can be expected expected increases in crop yield did result in an
to get enhanced yields (Wesseler, 2019). A yield increase in labour for harvesting. Such increases
increase would be expected to boost farm- are often for a short period of time, during peak
household income. Nevertheless, increases in season, and require hiring additional labour, with
yield often increase aggregate product supply, potentially positive effects on local labour markets.
reducing output prices. The prices for seeds
often increase as well, while other input costs Indirect health benefits can be expected as more
might be lower, including those for pesticides and food becomes increasingly available and as
fertilizers. Moreover, the economic benefit from household incomes increase. Increases in staple
technological change might only be temporary, as crop consumption would have positive health
has previously been the case (Wesseler, Jongeneel effects, especially if containing higher levels of
and Purnhagen, 2019). micronutrients and minerals such as beta-carotene,
iron and zinc (HarvestPlus, 2017). An increase in
Disease and pest-resistant crops are expected to micronutrient supply has been demonstrated to
reduce crop protection expenditures and related have long-lasting positive effects on human health
labour demand, but seed prices often increase (Fogel et al., 1994).
(Klümper and Qaim, 2014). The demand for fertilizer
at the farm level increases because of an expected The expected increase in better nutrition and
increase in crop yields and profits. An increase in higher income at the household level would have

21
Gene editing – potential hazards, benefits and impacts on the environment and society

positive social implications for those households. editing in agriculture can contribute to achieving
Women and children are the main beneficiaries the SDGs and, particularly if permitted for use in
of better food supply, strengthening their position organic agriculture. If the technology were not to be
within the household (Global Nutrition Report, allowed in organic agriculture, only for non-organic
2021). However, cases have been reported where agriculture, the yield gap and the differences in
non-beneficiaries have attempted to undermine gross margin would be expected to favour non-
implementation of better food supply for women organic agriculture and to strengthen the incentives
and children (Zingwe, Manja and Chirwa, 2021). for non-organic agriculture production. The Court
Access to gene-edited crops could widen the of Justice of the European Union (CJEU), in June
economic gap between those who have access 2018, ruled that organisms developed by gene
and those who do not (Klümper and Qaim, 2014). editing were to be GMOs (genetically modified
Importantly, for reaping the benefits, improved organisms) and not exempted from regulatory
crops varieties need to fit into the farming systems, oversight (Purnhagen et al., 2018). This implies
which is often overlooked (Schnurr and Dowd- that gene editing cannot be used in organic
Uribe, 2021). Furthermore, nutritional benefits can agriculture and that countries that export organic
be substantial at household level (Van Der Straeten food products to the European Union must
et al., 2020) and have often not been included differentiate their markets if they choose a different
explicitly in ex ante studies. legal definition. Tracking and tracing gene-edited
products for export represents a challenge (Smith,
Economic impact at input market level Wesseler and Zilberman, 2021). The cultivation of
The potentially positive impact of gene-edited crops gene-edited crops, as for cultivation of transgenic
at the farm-household level depends on the quality crops, might also generate discrimination against
of seeds and other inputs. Maintenance of seed those cultivating the crop at the local level in the
quality has been a problem for seed-based plant case of differentiated markets. Farm households in
pest and disease control options. The effectiveness Germany are concerned about social discrimination
of insect and herbicide resistance largely depends if they cultivate transgenic crops (Venus et al.,
on seed quality. Markets for stealth seeds (Herring, 2016). In those regions where gene-edited crops
2009) and fake herbicides (Haggblade, Diarra and are legally treated like transgenic crops, such as
Traoré, 2022) were recorded in cases where the in the European Union, similar responses can be
technologies were highly appreciated by farmers. expected. Kalaitzandonakes, Phillips and Wesseler
Gene-edited crop seeds, in this case, could be (2016) include several examples from different parts
expected to face the same problem as for any of the world.
improved seed – the quality and control of seed
systems and other inputs for crop production will Societal factors and public acceptance
be very important. The first generation GM crops were associated
primarily with intensive agriculture, which
Improved seeds, in general, are more expensive impacted farming, social and political systems
than standard seeds. The additional costs need to and concentrated on conventional agriculture
be compensated for by higher revenues. Access and larger corporations (e.g. Clapp and Ruder,
to improved seeds might become a problem for 2020). Concerns have been raised about the
cash-constrained farmers. Financial markets will be lack of biotechnology applications for small-scale
important to allow farmers to borrow so that inputs producers and developing countries (Stone, 2010)
can be purchased. This not only applies to access to and increased corporatization of university and
gene-edited crop seeds, but it is also important for public-sector research in developed countries like
other inputs such as fertilizers. the United States of America (Welsh and Glenna,
2006; Glenna et al., 2007). National policies have
Differentiated markets often favoured industrial agriculture, to which the
The application of gene editing to crop and animal first generation GM crops are linked, and those
production can, in principle, have effects on policies impacted social systems. For example, Fox
different markets. Seeds are often the target of and Haight (2010) documented the flow of subsidies
gene-editing applications, which could be used in in Mexico away from smallholders to large-scale
non-organic agricultural production and in organic producers in the wake of NAFTA (North American
production if not regarded as being transgenic. Free Trade Agreement). The impacts of agricultural
Purnhagen et al. (2018) argued that using gene policies in Mexico in the aftermath of NAFTA

22
 Gene editing and agrifood systems

led to 20 percent of Mexico’s farmers leaving are mixed as to whether the public and interested
agriculture and depopulation of rural communities groups can distinguish among first generation
(Zahniser and Coyle, 2004). Although GM crops transgenic approaches and gene editing in
are not directly responsible for the impacts, they forming their attitudes and opinions. For example,
exert global influence (ISAAA, 2019). In 2020, in a recent public perception study comparing
the President of Mexico banned all imports and gene-edited with GM and conventional foods,
approvals of GM maize, citing the need to safeguard respondents viewed CRISPR and GM food similarly
food security, sovereignty, native maize, the milpa and substantially less positively than conventional
system, Mexico’s biocultural wealth, smallholder food (Shew et al., 2018). Other studies established
communities, and the gastronomic heritage that consumers may be more willing to accept
and health of Mexicans (President of the United cisgenic crops (genetic changes introduced from
Mexican States, 2020). Prior to this decree, Mexico the same species, such as those produced by
had been one of the world’s largest importers of some gene-editing technologies) than transgenic
GM maize and soybean (USDA, 2021). It is unclear, crops, but less willing to accept cisgenic crops
however, how this decree applies to policies in in comparison with conventionally bred crops
Mexico regarding gene-edited crops because the (De Marchi et al., 2019; Edenbrandt, Gamborg
policies are still evolving (Kuiken and Kuzma, 2021; and Thorsen, 2018). However, certain benefits
Turnbull, Lillemo and Hvoslef-Eide, 2021). associated with cisgenic and gene-edited foods can
outweigh negative perceptions among consumers.
To date, gene-edited crops are more diverse For example, only a subset of consumers
regarding varieties and traits in comparison rejected cisgenic and transgenic crops under any
with first generation GM crops, and so are the circumstance (typically less than 20 percent), and
institutions developing them (i.e. more public other groups chose them based on health, safety
organizations and smaller companies). Many and nutritional benefits, irrespective of whether
larger multinational corporations are involved in they were cisgenic or transgenic (Yue, Zhao and
gene-edited crop development and regulatory Kuzma, 2015; Siegrist, 2008; De Marchi et al., 2019;
approval (Whelan, Gutti and Lema, 2020; George Edenbrandt, Gamborg and Thorsen, 2018; Busch
et al., 2022; USDA, 2022) and there is a continued et al., 2022).
focus on herbicide tolerance in commodity crops
and sale of companion herbicides, mainly aimed Specific-interest groups are likely to remain opposed
at larger farming enterprises (Zhang et al., 2018a; to GM and gene-edited foods based on their value
Clapp and Ruder, 2019; USDA, 2022). However, systems regarding agriculture, food, ecosystems
there are signs that there is more interest in and nature (Zilberman, Rausser and Wesseler,
developing gene-edited crops with a much broader 2023). For example, there are ongoing tensions in
range of improved traits than solely herbicide rural communities between conventional agriculture
and specific pest tolerances. Furthermore, there and agroecological approaches to farming (Rissing,
remain significant barriers to smaller developers 2021). In some cases, the use of GM crops has
and farmers posed by patents and ownership led to divisions among conventional farmers and
issues with CRISPR technologies and gene-edited organic or non-GM farmers and conflicts over fears
seeds (de Wit, 2020). Although a range of traits of cross contamination (seed, pollen and chemical
to improve the environment and social good are drift from companion herbicides) and lost organic
on the horizon, gene-edited crops for enhanced and international markets (Venus et al., 2016; Gupta,
sustainability face significant financial barriers 2018; Paull, 2019). Depending on legalities, one
for development and use (Jordan et al., 2022). group of farmers, organic or non-organic, must
Moreover, the cost of regulatory approvals, if gene- bear a higher level of responsibility than another
edited crops are subject to the same regulatory but often without significant impact on economic
requirements as GM crops, would also likely be efficiency (Beckmann, Soregaroli and Wesseler,
prohibitive for small commodities. 2010). The use of minimum distance requirements
as part of coexistence policies discriminates
Prior conflicts over cultural values, food and against smaller farms (Beckmann, Soregaroli and
agriculture associated with first generation GM Wesseler, 2010). Organic farmers in the United
crops may also play out in the development of States of America bear responsibility for buffer
gene-edited crops despite greater diversity of zones to distance themselves from conventional
actors and crop varieties. Public perception studies and GM agriculture, testing for GM presence, and

23
Gene editing – potential hazards, benefits and impacts on the environment and society

assuring that their products are GM-free or that animals (Ahmad et al., 2021). Despite purported
GM contamination is lower that than the specified marginal risks of gene-edited organisms to the
threshold. Some have suggested that policies environment, human health and the economy
should compensate organic farmers if eventually (Lassoued et al., 2019), current biotechnology
they suffer losses (Paull, 2019; Azadi, Taube and regulations and advocacy groups have mixed views
Taheri, 2018). The issues are likely to persist for on the adoption of gene editing, and this could
gene editing in some regions of the world. For have an impact on public perception and social
example, in the United States of America, the acceptability (Helliwell, Hartley and Pearce, 2019).
National Organic Standards Board has excluded
gene-edited products from being certified as organic Public attitudes to first generation GM crops have
(USDA, 2019). With growing consumer demand in depended on a variety of factors that are likely to
the United States of America for organic and non- apply to gene-edited crops. Some survey results
GM labelled foods (Castellari et al., 2018; Hartmann show that the less respondents knew about the
Group, 2018), tensions between organic and non- technology the more they were opposed to it
GM farmers and those industries that supply gene- (Fernbach et al., 2019). However, other surveys
edited and GM crops are likely to persist. of public attitudes to GM crops showed that
consumer knowledge has a modest to no effect
Cultural concerns among Indigenous Peoples on public acceptance and that consumers with
have also been documented with the use of greater familiarity are often more concerned with
first generation GM crops. For example, Native GM foods, going against the “deficit model” (Rose
Hawaiians objected to the patenting and genetic et al., 2019). Thus, factors other than knowledge
modification of taro (kalo), a crop of significant seem to be more important regarding public
religious and cultural significance (Gupta, 2018). perception of GM crops. The factors include trust
Similarly, regarding quinoa, Andean farmers took in scientists and governments to manage risk,
issue with American agronomists over twenty the legitimacy of decision-making processes,
years ago when they patented a male sterile line respect for diverse cultural values and world
of a Bolivian cultivar of the crop (RAFI, 1997), views, and public ability to control exposure to
considering it biopiracy. Indigenous Peoples risk or make choices about technological products
may view gene editing similarly, with objections (Siegrist, Connor and Keller, 2012; Yue, Zhao
centring largely around sovereignty, ownership and Kuzma, 2015; Kuzma, 2017). Furthermore,
and preservation of natural heritage being less general surveys that address specific traits,
violated by genetic modification, including gene crops and products indicate a differentiated
editing. However, indigenous concerns have also picture. Presentation of the product, ordering of
intersected with economic and non-GM production information, and other survey designs have an
concerns. In Yucatan, the local smallholder impact on the results (Huffman and McCluskey,
economy has relied on honey production, and 2020), as well as consideration of the specific
Mayan producers had their markets to the benefits provided by GM crops (Yue et al., 2015).
European Union threatened by contamination
with GM soybean pollen (Gómez González, 2016). Mandatory labelling, providing simple explanations
Mayan communities formed alliances with other on the use of genetic engineering, led to reduced
groups that were hostile to GM soybean, including opposition to the technology (Kolodinsky and Lusk,
organic farmers and NGOs (non-governmental 2018). Yet, labelling could lead to avoidance of
organizations), to oppose cultivation of GM soybean gene-edited crops by food companies, small-scale
(Gómez González, 2016). producers and trade-dependent LMICs. Therefore,
labelling rules should be framed in a harmonized
There is considerable public concern about the global system based on transparent science-based
potential environmental and human health risks of consideration of risks, in which new traits in food
CRISPR-edited crops and animals, which are mainly would be included in a label if they represented
fuelled by social, religious and ethical viewpoints a fundamental change in the composition of the
(Ahmad et al., 2021; Kato-Nitta et al., 2021). Other food; production method would not be a mandatory
concerns are due to issues relating to limited labelling requirement. Following the introduction
understanding of science, low trust in developers of mandatory food disclosure labelling, an analysis
and regulations and inadequate communication of market behaviour and consumer purchases in
about risks and benefits of gene-edited plants and the United States of America showed that sales of

24
 Gene editing and agrifood systems

genetically engineered soup products decreased by Nkott and Temple, 2021). However, much of the
5.9 percent, sales of non-GMO labelled products social science literature on risk perception and on
increased by 2.5. percent, and sales of organic attitudes to GM food shows that public acceptance
products increased by 1.7 percent (Fan, Stevens is influenced by a range of factors, including
and Thomas, 2022). Public perception and social perception of naturalness, trust, risk-benefit
acceptance can substantially impact how the food distribution, purpose of the product, cultural values
industry responds. The introduction of transgenic and features of the technology such as whether it
wheat in the United States of America and Canada is controllable and fully understood (Siegrist, 2008;
was blocked by concerns expressed about access Siegrist, Connor and Keller, 2012; Frewer et al., 2013;
to European markets (Kalaitzandonakes, Phillips and Scott et al., 2018; Kuzma, 2017; Rose et al., 2019).
Wesseler, 2016). A voluntary market has emerged
for GM-free labelled food products in the United Gene editing and fundamental ethical
States of America and the European Union, taking considerations
heed of public demand (Castellari et al., 2018).
Ethics and transgenics have been extensively
Globally, perceptions of gene editing differ based reviewed (Robinson, 1999: Ubalua, 2009;
on prevailing situations. McConnachie et al. (2019) Gregorowius, Lindemann-Matthies and
established that 66 percent of respondents to a Huppenbauer, 2012) and while technologies have
survey would consume products made from cattle evolved, the ethical considerations discussed
polled using gene editing. The perception that previously have largely remained similar. Ethical
farmers had an obligation to reduce animal pain and considerations concern all aspects of the
suffering through gene editing played a significant potential impacts and consequences of the new
role in their willingness to consume gene-edited technology, in terms of moral imperatives to make
products from polled cattle (Smith, 2021). improvements over current situations related to
human hunger, human health, the environment,
Social acceptance of gene-edited organisms is also societal impacts and distribution of benefits. These
driven by how the perceived benefits meet the considerations are often referred to as extrinsic
needs of communities and possibly by concerns concerns, but there are also intrinsic concerns that
over power changes, particularly those removing must be taken account of. These address aspects
power from farmers. Woźniak, Tyczewska and of what is right and wrong, issues of theology
Twardowski (2020) reported that the critical issue in and what constitutes naturalness and respect for
acceptance of gene editing relates to its application nature. As with GM products, the opinions on
and not the technology itself, and applications products of gene editing are in many instances
aimed at prevention or treatment of diseases, likely not to be based on scientifically established
prevention of disabilities and organ transplantation facts but on value judgements. This is also the
received the highest support at the expense of case for risk assessment, which is not merely an
gene-editing interventions aimed at improving crop objective technical matter, but depends on opinions
and livestock production. For instance, Busch et al. and definitions.
(2022) reported that respondents in Canada, Japan,
the United States of America, Germany and Italy Ethical aspects associated with the application
viewed the application of gene editing for disease of gene editing in agrifood systems span the
resistance in humans to be most favourable, fields of environmental ethics, bioethics, animal
followed by disease resistance in plants and lastly ethics, technological ethics and food ethics,
in animals. They viewed improvements in livestock as well as medical ethics if the product has
for product quality and quantity as least desirable. applications to health and medicine in addition to
food and agriculture (e.g. GalSafe pig). Different
Some authors expect that social acceptance of paradigms of ethical analysis that have been used
gene-edited organisms necessitates strengthening to examine this include utilitarian approaches
seed systems through the operationalization of (weighing benefits versus costs, also known as
regulatory structures and upgrading stakeholder consequentialist ethics), principle-based ethics
knowledge of genetic engineering, analysing the (deontological), virtue-based ethics, care ethics and
effects of the edited variety on biodiversity and soil duty-based ethics. Most ethical issues associated
nitrogen dynamics, and strengthening the technical with GM and gene-edited food and agricultural
and human capacities of the biosafety body (Nlend applications are not unique to the technology,

25
Gene editing – potential hazards, benefits and impacts on the environment and society

applying to many technologies linked to agrifood a more diverse sample of the public, experts and
systems (Thompson and Hannah, 2008). stakeholders in assessing engineered products
for procedural justice, so that the normative
It can be argued that failure to use technology to commitments of a few powerful groups (often
address a serious problem, such as one relating to technology developers and regulators) do not
food security, is morally wrong, but another view is dominate decision-making (Kuzma and Besley,
that applying a technology is not morally justifiable 2008; Meghani, 2014; Meghani and Kuzma, 2011;
if it involves undue risks, violating the principle of Meghani and Kuzma, 2018; Kuzma, 2019). This
non-maleficence. Other concerns like autonomy, also depends on who has the right to decide and
informed consent, rights of animals, privacy, equity that decision-making procedures derived from the
and social justice, distribution of risks or benefits, constitution of the respective jurisdiction should not
and procedural justice are not typically considered be overruled and undermine democracy (Purnhagen
in formal oversight systems or decision-making for and Wesseler, 2020).
GMOs. These ethical issues, as well as the societal
issues, have been subordinated in governance Uncertainty in determining the risks associated with
systems for gene editing (Helliwell, Hartley and GM food and agricultural products also represents
Pearce, 2019). There is an apparent paucity of a potential conflict between libertarian ethics and
policy spaces for public consideration of the ethical utilitarian ethics (Thompson and Hannah, 2008).
and normative questions associated with first The former proposes that individuals have inviolable
generation GM and gene-edited crops (Thompson, rights to be shielded from harm caused by others,
2003; Kuzma, 2021). even if the risk is extremely low (which is also
related to non-maleficence, a bioethics principle),
Ethical issues intersect with socioeconomic and whereas utilitarian ethics considers the benefit-risk
political issues from social justice and commercial balance to a population while allowing for potential
competition viewpoints. The empirical evidence risks to a few (Thompson and Hannah, 2008).
shows that in many cases smaller farms benefitted Rights to know and choose via food labelling of
from GM crops, most welfare gains did materialize gene-edited and GM products may reconcile the
down the supply chain and technology developers two ethical approaches by placing the responsibility
share was about 25 percent or less (Falck-Zepeda, on the consumer (Thompson and Hannah, 2008).
Traxler and Nelson, 2000; Qaim, 2009). However, Arguments in favour of GM and gene-edited food
there are concerns over power and control of labelling have also been made using bioethical
the food supply, the lack of market penetration principle-based approaches (deontological) of
of biotechnologies for poorer or smaller farmers, autonomy and informed consent (Kuzma and
and the transfer of ownership and sovereignty Besley, 2008). Transparency is required in this case,
to companies (Thompson and Hannah, 2008). yet currently, in the United States of America and
Social justice concerns also relate to the ability of several other countries, most gene-edited foods
cultural groups to choose whether GM crops are do not require labelling and little information about
used in their communities, such as the examples them is publicly available (Kuzma and Grieger, 2020).
concerning Indigenous Peoples and their rejection
of GM technologies in sacred, culturally significant, More fundamental ethical considerations about
or economically important agricultural crops. animal gene editing are that it could violate the
Procedural justice suggests that those most dignity of animals, prevent them from living
affected by GM crops should have a voice and according to their instincts, or affect their behaviour
choice in decision-making about using them (Kuzma to the point that they lose their essence and
and Besley, 2008). purpose (de Graeff et al., 2019). However, given
the criticisms of modern animal husbandry,
It has been indicated that although risk assessment regardless of genetic engineering or gene editing,
is informed by science, it involves normative domesticated animal dignity has already been
judgements, such as interpretation of uncertainty, severely contravened. Kato-Nitta et al. (2021)
deciding where safety thresholds lie, and reported that the Japanese were more concerned
determining which endpoints of risks or benefits about gene-edited livestock than gene-edited
are of most worthy of consideration (Thompson, vegetables. More respondents signalled acceptance
2003; Thompson, 2018; Kuzma, 2019). Therefore, of gene-edited vegetables but not gene-edited
it has been argued for having mechanisms include livestock, those with higher science literacy levels

26
 Gene editing and agrifood systems

ranking gene-edited vegetables higher than those world as other organisms. Moreover, except for
with lower levels. However, they remained anti- anthropogenic climate change effects, there have
gene editing when it came to livestock. This could always been natural disasters and serious diseases
be because humans consider animals to be of and genetic disorders, which dispel the concept
intrinsic value, gene editing possibly negatively of benevolent nature. For some, moral objections
affecting their welfare if traits leading to disease arise from humans assuming the role of a deity
are introduced. De-animalization would occur were by intentionally changing the genomes of plants
natural traits to be knocked out, and humanization if and animals and going against natural processes
non-human primates were altered to mimic humans that purportedly maintain a balance within species
(European Commission, 2021). and ecosystems. Counterarguments to this
position note that gene editing may simply mimic
A representative EUROBAROMETER survey natural processes (especially SDN-1 and SDN-2 in
(European Commission, 2010) conducted among comparison with transgenesis). Hybridization is also
European Union citizens on moral delegation far more common in nature than is generally realized.
for decision-making asked respondents for their Furthermore, humans have interfered extensively
governance preferences using a 2x2 matrix on in breeding systems for millennia, and more lately
synthetic biology and animal cloning. Both are through conventional breeding (Bartkowski et al.,
applications of modern biotechnology that largely 2018). In addition, the holistic argument that all
benefit from the CRISPR-Cas technology (Doudna organisms are part of a finely balanced environment,
and Sternberg, 2017). Results showed most the disturbance of which is disrespectful, ultimately
respondents preferred decisions to be made based is reproving of all technological interventions,
on scientific evidence from experts. The results also not just those in agriculture and not solely those
showed that more than a third of the respondents concerned with gene editing.
preferred decisions to be made based on moral
and ethical issues, but as these are often based on If there is a moral obligation to provide the
personal value judgements, there is likely to have most deserving communities with gene-editing
been considerable disparity within that group. technologies and products, the new crops and
livestock are unlikely to represent a panacea.
At the most fundamental level, some ethical Maybe the best that can be hoped for is that
objections to GM and gene editing arise from moral conflicts among welfare ethics, business ethics
positions on the intrinsic worth of unviolated nature and environmental ethics can be resolved, and the
(Bartkowski et al., 2018), while what constitutes adverse effects of current production practices
nature is not necessarily obvious or agreed on. It can be reduced, and present-day inequities can
is not even universally accepted that naturalness be addressed. In this way progress can be made
is fundamentally good. There are various views in transforming agrifood systems for the better.
(Ducarme and Couvet, 2020), but if natural excludes Through continued research and provision of
anything that humankind has had a hand in, this information, public concerns about gene editing
would rule out most things as being natural – might be mitigated and those most in need of the
humans are, after all, as much a part of the natural benefits of the new technology might receive them.

27
4 G overnance and regulation
SUMMARY
Arguably the most important governance aspect Sanitary and phytosanitary regulations
of the products generated by gene editing is
sanitary and phytosanitary regulation. Science- Regulators have considered how to manage gene-
based measures to safeguard human health and edited products in agrifood systems for more than
biodiversity must be balanced against economic and a decade. Because gene-editing techniques use
social considerations. To date governments have recombinant-DNA techniques in direct or indirect
not adopted a coordinated approach to regulating ways, in most cases it is questioned whether the
gene-edited products. Governments must focus on products should be regulated in the same way as
establishing a clear and rational regulatory approach, transgenic organisms (and derived products).
seeking international harmonization to the extent
possible. Only after domestic regulatory protocols Most national regulatory systems subject
are established can policymakers adequately transgenic crops to regulations for genetically
address other governance issues, such as trade modified organisms (GMOs) or living modified
impacts, fostering innovation, intellectual property organisms (LMOs). The leading multilateral
attributions, and access and distribution. In contrast, references for these regulatory systems are:
at the multilateral level the diverse governance
aspects may be dealt with in different specialized a) The Cartagena Protocol on Biosafety (CPB)
fora, and simultaneous discussions, when under the Convention on Biological Diversity
necessary, will be possible. (CBD), which is based on the concept of LMOs.
b) Specific Codex Alimentarius Guidelines, based
on the concept of recombinant-DNA plant/
animal/microorganism.

However, gene editing can involve different types

of intervention in the genome, from transgenesis
and cisgenesis to simple mutations consisting of
deletions or changes of a few nucleotides in the
genomic DNA. Regulatory experts usually classify
this array of techniques into SDN-1, SDN-2 and
SDN-3 types.

It is generally agreed that SDN-3 interventions,

especially when DNA from other species is used,
are categorized as GMO, LMO, and recombinant-
DNA organisms (Sprink et al., 2016). This results
from insertion of foreign DNA into a host
genome, which is recognized to generate a “novel
combination of genetic material” (term used in
the Cartagena Protocol LMO definition, which
later inspired many GMO definitions in national
regulations). However, at the other extreme of
this classification, SDN-1 interventions do not
involve, if properly executed, a DNA insertion. They
damage the DNA at a target site, and then permit
natural cellular repair. Such repair mechanisms
can fail at a low frequency, resulting in nucleotide
deletions or small random changes and insertions.
Such an intervention is very similar, in its general
mechanism and possible results, to breeding based
on induced chemical or radiological mutagenesis.

28
 Gene editing and agrifood systems

Because of the differences in classification, there are by potential risk factors, such as DNA sequences
differing views on appropriate regulatory treatment from plant pests being in the final product.
of the three gene-editing categories (Sprink et al.,
2020). Some argue that SDN-1 derived products Over time, USDA-APHIS has analysed numerous
do not meet the legal definitions of an LMO/GMO, case-by-case consultations regarding gene-edited
or the concept of a recombinant-DNA organism, products. In most cases, the product was not
because they lack insertion of foreign DNA into a considered to be governed by the regulatory
genome. Conversely, others consider that SDN-1 section applying to genetically engineered plants.
products do meet the specific definitions used in The criteria underlying the case-by-case decisions
their national definitions of GMOs; or focus instead were recently refined and finally incorporated
on encompassing them under regulations designed into the Code of Federal Regulations (7 CFR Part
for “modern biotechnology” because of the 340) in 2020. They are now embedded as a set
involvement of recombinant DNA at some juncture. of explicit regulatory exclusions comprising (a)
A third approach is based on the techniques not genetic changes resulting from the cellular repair
having been developed when national biosafety laws of a targeted DNA break in the absence of an
and international agreements and guidance were externally provided repair template, (b) targeted
elaborated. In this instance a regulatory update is single base pair substitutions, (c) the introduction
required to accommodate the products (Eriksson or reconstruction of a gene already present in the
et al., 2019). Qaim (2020) suggested that a trait- plant’s gene pool, and (d) other cases where the
based regulatory approach would represent an modifications are like those that could be achieved
improvement over product-based regulation of crops. through conventional breeding.
This suggestion was reiterated by Gould et al. (2022).
With regard to food safety assessments, foods
Figure 2 represents a summary of many of from gene-edited plants can be submitted to a
the issues and organizations concerned with voluntary pre-market consultation by FDA, and
governance and regulation of gene-edited in 2019 FDA completed its first review on food
organisms and products. from a gene edited soybean. Conversely, the
regulatory standing of gene-edited animals is
A timeline of national approaches different because the FDA proposed an oversight
approach closely following its policy for genetically-
This section summarizes development of the global engineered animals, which fall under their
regulatory situation for gene-edited organisms for jurisdiction for “new animal drugs” and go through
agrifood systems over time, up to July 2022. a mandatory pre-market approval process.

A New Zealand research institute requested the The Environmental Protection Agency (EPA)
Environmental Protection Authority (EPA) determine is currently considering how to regulate gene-
how gene-edited organisms were to be regulated. edited crops under their pesticide authorities if
Initially, the New Zealand EPA compared the use the gene-edited crop contains “plant-incorporated
of SDNs with chemical mutagenesis. Mutagenesis protectants”. The EPA has asserted regulatory
is included in a list of techniques excluded from jurisdiction over GMO plants with incorporated
regulation as GMOs. Therefore, the EPA interpreted pesticidal proteins or genetic changes.
that mutagenesis using SDNs was excluded.
However, that decision was challenged in the High In 2015, the Argentina Ministry of Agriculture,
Court that same year. The court concluded that the Livestock and Fisheries issued Resolution
list of exempted techniques in the regulation is of 176/2015, which introduced a procedure for
a closed kind and the applicable law would require classifying products from new breeding techniques
modification to include gene editing. (including gene-edited organisms) as GMOs or
not. The procedure is based on the definition of
In 2014, the United States Department of an LMO from the Cartagena Protocol. According
Agriculture (USDA) Animal and Plant Health to this definition, an LMO (GMO in the Argentine
Inspection Service (APHIS) considered whether to domestic regulations) “possesses a novel
allow sowing of gene-edited crops on a case-by- combination of genetic material obtained through
case basis. The current biosafety regulation is not the use of modern biotechnology.” This resolution
based on a product/process definition; it is triggered does not create a new product category or special

29
Governance and regulation

Figure 2 Issues and organizations concerned with governance and regulation of gene-edited organisms
and products

Cartagena Protocol Human

occupational
exposure
Environmental
biosafety of
living organisms Oral toxicity Other concerns
Impact on and
animal health allergenicity
International
Plant Protection Toxicity & Food and feed
Convention allergenicity of safety of derived
Other biosafety novel proteins products
SANITARY AND concerns
PHYTOSANITARY
PROTECTION
Socioeconomic Sanitary and
effects phytosanitary
measures

Access, property
and benefit sharing
Trade
interventions
National
Access to genetic techno-
resources and Intellectual development
benefit sharing property of biotech policies
Declaration inventions and
of genetic plant varieties Funding to
resources research and
origin in innovation
patents
Nagoya Protocol

SOCIOTECHNICAL &
ECONOMIC POLICIES

regulatory treatment. Subsequently, several gene- new plant breeding techniques (including gene
edited plant and animal lines developed for food editing). The main attributes of the document were
and agriculture were classified as non-GMO. In coincident with the Argentine case described.
almost every case, the decision was taken because Since then, SAG has received applications to
the resulting organism was not considered to clarify the status of some gene-edited plant lines
possess a novel combination of genetic material. developed for food and agriculture, most of which
In 2018, Argentina presented a joint statement have been classified as non-GMO.
to the World Trade Organization (WTO) on behalf
of a country coalition, which highlighted the The Israel Plant Protection Services Administration
potential benefits of applying gene editing to food published a decision by the National Committee for
and agriculture (G/SPS/GEN/1699). It also stated Transgenic Plants, establishing that the progeny
that governments should avoid arbitrary and of gene-edited plants will not be subject to GMO
unjustifiable distinctions between gene-edited regulations when foreign DNA sequences are not
organisms and those obtained using other breeding incorporated into the plant genome. This decision,
methods. however, only applied to field trials.

In 2017, the Agriculture and Livestock Service In 2018, the National Technical Biosafety
(SAG) of Chile issued an official clarification on Commission of Brazil (CTNBio) issued its
the applicability of its previous Resolution no. Resolution 16/2018. The main features of the
1523/2001 for propagation material developed by document are coincident with the Argentine

30
 Gene editing and agrifood systems

and Chilean approaches, but the Brazilian a proposal for a legal framework for plants obtained
legislation includes lists of techniques and genetic using targeted mutagenesis and cisgenesis and
interventions that are not considered to produce a their food and feed products and a road map was
GMO. CTNBio has also received several petitions developed for improving the current legislation
to clarify the regulatory standing of specific plant on gene editing. A proposal by the European
lines and animal breeds derived from gene editing, Commission is expect in the second quarter of
the results of which are routinely published in the 2023 to be discussed by the European Council,
official gazette. the European Parliament and the European
Commission, the so-termed trilogues.
Colombia notified the WTO of its Agricultural
Institute (ICA) Resolution no. 29299/2018 “Setting The Switzerland Federal Council confirmed, in
out the applicable procedure for crops where any response to a parliamentary interpellation, that gene-
stages over the plant-breeding process incorporate edited organisms fall under the definition of GMOs
innovative phyto-improvement techniques through according to the national Gene Technology Act.
modern biotechnology and the final product does
not contain any foreign genetic material.” Its text In 2019, Australia amended its GMO regulation
is like that of the Argentine Resolution 176/2015. Law to take account of gene editing. The
Since then, ICA has processed several petitions amendment expanded the list of “organisms that
for gene-edited rice and maize lines, which were are not GMOs” to include those (i.e. SDN-1).
ultimately classified as non-GMO.
In its Environmental Code regulations, Ecuador
The European Court of Justice (ECJ) ruled that clarified that organisms not possessing
mutagenesis induced by gene editing produces recombinant or foreign DNA are excluded from
GMOs according to the GMO definition used GMO biosafety regulations.
in the European Union regulations. According
to the ECJ ruling, all organisms obtained by Guatemala and Honduras signed their bilateral
mutagenesis (regardless of the technique used) are Resolution no. 60/2019, where both countries
GMOs according to the European Union Directive agreed to harmonize their GMO regulations,
2001/18/EC, but those derived from mutagenesis linked with broader policies establishing a
techniques, which have conventionally been used common market. That resolution settled criteria for
repeatedly, and have a long safety record, are distinguishing which gene-edited products should
exempted from the regulation. During the years be treated as GMOs and which as conventional
that preceded the ruling, several Member States new varieties in both countries. The criteria were
of the European Union received applications and later implemented domestically by the Honduran
inquiries from developers regarding field trials with National Service of Agrifood Health and Safety
gene-edited crops. As a result, advisory bodies and (SENASA) in its regulation 8/2019 and by the
competent authorities of some countries (including Guatemala Ministry of Agriculture, Livestock, and
Belgium, Finland, Germany, Ireland, Netherlands, Foodstuff through its Agreement no. 271/2019.
Spain, Sweden, and the United Kingdom of Great The implementing regulations are based on a
Britain and Northern Ireland) indicated that field specific definition for “novel combination of genetic
trials with certain gene-edited products were not material”, and the final product characteristics
subject to the GMO legislation. While decisions compared with conventional breeding products.
on field trials are taken at the national level, the They also pay special attention to harmonization
commercial authorization process for GMOs with other countries.
(including food safety assessment) is a centralized
procedure. Authorization granted therein applies to Nigeria aamended its National Biosafety
the entire European Union. Therefore, the European Management Agency (NBMA) Act to include
Commission asked the Member States to withhold emerging agricultural biotechnologies. The
from providing interpretations, awaiting clarification amendment defines gene editing as “a type of
at the European Union level. That clarification genetic engineering in which DNA is inserted,
arrived with the ECJ ruling. In 2022, the European deleted, modified or replaced in the genome of a
Commission launched a public consultation on living organism.” Subsequently, in 2020, the NBMA
“Legislation for plants produced by certain new published detailed guidelines for gene editing
genomic techniques” to seek stakeholder views on regulation. When the gene-edited product does

31
Governance and regulation

not have a novel combination of genetic material, a Regarding feeds derived from gene-edited plants,
non-GMO regulatory classification is applied. the MAFF guidelines are closely aligned with
the approach taken by MHLW over foodstuffs.
The Ministry of Agriculture and Livestock of A locally developed gene-edited tomato with
Paraguay published Resolution no. 565/2019, increased gamma-aminobutyric acid content (for
which approves a form for “Prior consultation health benefits) was the first product to receive
for products obtained through new breeding confirmation of non-GMO status. Other products
techniques.” It is very similar to its analogue in followed, including a gene-edited sea bream in
the Argentine regulation, while at the same time which CRISPR technology was used to knock out
containing a list of techniques like the Brazilian the myostatin gene. It was also developed by a
regulation. The Paraguay National Commission on start-up incubated by a local university. Both the
Agricultural and Forestry Biosafety is responsible tomato and the fish became commercially available
for analysing applications using this form, although to the public in 2021.
no case has been presented yet.
In 2021, Health Canada determined that a high
In the Philippines, the National Committee on amylopectin starch (“waxy” phenotype) maize
Biosafety (NCBP) issued a resolution for the obtained using an SDN1 technique was not a novel
regulation of Plant Breeding Innovations (PBIs), food product, and therefore did not require pre-
including gene-edited plants, where, once again, market safety assessment as a novel food. The
products are regulated as GMO or not based on rationale for this decision was that the product had
the concept of “novel combination of genetic the same phenotype as pre-existing commercial
material.” The regulations define the latter as “a maize varieties with a similar spontaneous mutation
resultant genetic combination in a living organism and had a history of safe use as food. However, the
that is not possible through conventional breeding.” following year, a gene-edited high oleic soybean
Consequently, the Department of Agriculture was determined to be a novel food, and hence
drafted its rules and procedures to determine the was subject to a food safety assessment based on
regulatory status of PBI products, which were WHO/FAO expert consultations. Furthermore, in
subjected to stakeholder consultations. 2022, Health Canada published a scientific opinion
on the regulation of gene-edited plant products. It
In Japan, the Ministry of Environment (MoE) stated that novel food products from any breeding
and the Ministry of Health, Labour and Welfare technique that might represent a food safety hazard
(MHLW) published procedures and guidelines to would require a food safety assessment, to be
clarify when their GMO regulations apply to gene- done according to domestic guidance based on the
edited products. Later in 2020, the Ministry of Codex Guidance framework for safety assessments
Agriculture, Forestry, and Fisheries (MAFF) also of foods derived from biotechnology.
published implementing guidelines on the same
topic. The MoE criteria centre on determining In 2021, South Africa legally defined a GMO as “an
if products fall outside the scope of the LMO organism, the genes or genetic material of which
definition in the applicable law, which is based on has been modified in a way that does not occur
the Cartagena Protocol. It also clarifies that plants naturally through mating or natural recombination
that (a) do not have integrations of “extracellularly or both”. Based on that definition, the Executive
processed nucleic acids”, or (b) only incorporated Council of the GMO Act (administered by the
genetic material that comes from the same or Department of Agriculture, Land Reform and Rural
sexually compatible species, are both excluded. Development) concluded that the risk assessment
Conversely, MHLW criteria state that foods derived framework for GMOs would also apply to NBTs
from gene-edited plants presenting the same level (new breeding techniques) and modified its
of risk as those from conventional breeding are application forms accordingly to allow a tiered
not subject to the GMO food safety assessment assessment approach.
process. The MHLW criteria for identifying products
that do not require a GMO safety assessment In 2022 in China, the Ministry of Agriculture and
include (a) absence of foreign DNA in the final Rural Affairs (MARA) issued guidelines for safety
product and (b) changes induced by a site-directed evaluation of gene-edited plants for agricultural
enzyme that result in deletions, substitutions, or use. The guidelines apply to gene-edited plants
spontaneous insertion of one or more nucleotides. into which no exogenous genes are introduced,

32
 Gene editing and agrifood systems

with differential treatments according to risk levels. Food Standards Australia-New Zealand (FSANZ) is
For those gene-edited plants whose traits do no performing an ongoing review of how the binational
elicit food or environmental risks, the guidelines Food Standards Code applies to foods derived
establish a simplified registration procedure with from NBTs. This includes a proposal to amend the
respect to transgenic plants. binational food code with definitions for “gene
technology” and “new breeding techniques”.
The Ministry of Environment, Forest and Climate Norway is currently following the European Union
Change of India issued its Memorandum authorization procedures. However, after public
F12013/3/2020-CS-III exempting gene-edited plants surveys and parliamentary debates, the Norwegian
falling into the categories of SDN-1 and SDN-2, Biotechnology Advisory Board presented
which are free from introduction of exogenous recommendations for regulating GMOs, including
DNA, from the rules that apply to genetically exempting or expediting the safety assessment
engineered organisms. This was done following of gene-edited organisms. Although the United
recommendations from the Ministry of Science Kingdom officially left the European Union in 2020,
and Technology, and after requesting public all the relevant European Union regulations were
comments to inform on future policies on gene retained. However, after a parliamentary debate
editing. Previously, draft guidelines for regulation on gene editing, the Department for Environment,
and risk assessment were released, comprising Food and Rural Affairs set up a public consultation
both agricultural and human health applications. The for updating the regulation of genetic technologies.
guidelines proposed a tiered approach to product The government response to the consultation
groups based on risk. Minor DNA edits were results included an announcement to bring forward
identified as posing a low risk, while large or foreign new legislation that would amend the GMO
DNA insertions were considered to pose higher definition, excluding organisms having genetic
risks. The document makes extensive reference to changes that could occur naturally or be achieved
off-target effects. through traditional breeding.

Kenya’s National Biosafety Authority (NBA) Multilateral instruments

published its gene-editing guidelines, aimed at
steering the approach to take while submitting Cartagena Protocol
and reviewing applications for research, trials and The Cartagena Protocol on Biosafety is an
commercial release of gene-edited products. The international treaty governing the transboundary
main feature of the guidelines is the provision for movements of LMOs. It is a supplementary
early consultation to determine the regulatory agreement to the Convention on Biological
pathway to be adopted, in view of the different Diversity, and it entered into force in 2003. It
potential outcomes of gene-editing techniques, currently has 173 parties, most of which base
depending on the case. Prior to publishing national regulations on the language used in the
the guidelines, the NBA had reviewed several Protocol.
applications using new breeding techniques in
contained facilities (biosafety laboratories and The CPB contains provisions regarding the
greenhouses). procedure for the first transboundary movement
of an LMO into a country, including the risk
In addition, many other countries worldwide are assessment of its potential adverse effects on the
currently conducting policy-making processes conservation and sustainable use of biodiversity. It
to develop regulatory criteria for gene editing also considers risks to human health.
applied to agriculture. In some cases, the content
of the processes is recorded in publicly available Two definitions in particular under the Protocol
documents. Such is the case for The Costa Rica serve as a paramount reference to regulators on
State Phytosanitary Service, which recently establishing if this treaty and related domestic
proposed a draft national legal framework for legislations apply to gene-edited organisms:
new plant breeding techniques. It comprises a
procedure to define whether a crop derived using 1. Living Modified Organism is any living
gene-editing techniques is an LMO or not, in line organism that possesses a novel combination
with other Latin American countries. of genetic material obtained by modern
biotechnology.

33
Governance and regulation

2. Modern biotechnology means the application Codex comprises some general food guidelines
of a) In vitro nucleic acid techniques, including and others that apply to specific foods, including
recombinant deoxyribonucleic acid (DNA) “foods derived from modern biotechnology”.
and direct injection of nucleic acid into cells, For this purpose, Codex adopted the definition
or b) Fusion of cells beyond the taxonomic of Modern Biotechnology from the CPB. In
family that overcome natural physiological contrast, the “Living Modified Organism” concept
reproductive or recombination barriers and that from the CPB is not used in Codex guidelines.
are not techniques used in traditional breeding Instead, the guidelines refer to “foods derived
and selection. from recombinant-DNA plants, animals, or
microorganisms”, without providing a definition.
Parties to the CPB and its parent agreement,
the CBD, hold periodic meetings to negotiate Codex guidelines for foods derived from modern
implementation aspects of the treaties. Gene biotechnology were published several years before
editing began to be discussed in the concurrent governments began considering the regulation
meetings that took place in Sharm El-Sheik, Egypt, of gene editing and have not been reopened to
in 2018. Two decisions of the parties arising from discussion afterwards. However, the guidelines
those meetings explicitly refer to gene editing: are widely used worldwide and have proven
robust and valid for new developments in modern
1. Decision on horizon scanning (CBD): “{…} biotechnology and recombinant-DNA organisms.
new technological developments in synthetic
biology … including … concrete applications Codex guidelines that apply to foods derived from
of genome editing if they relate to synthetic modern biotechnology include:
biology”.
Guidelines on food safety assessment, providing
2. Decision on Risk Assessment (CPB): “Calls overarching principles on the risk analysis of foods
for broad international cooperation {…} in derived from modern biotechnology and detailed
assessing the potential adverse effects … from guidance for the safety assessment of foods
LMOs produced through new developments derived from recombinant-DNA plants, animals, and
in modern biotechnology, including LMOs microorganisms. Specifically, they are the Principles
developed through genome editing {…}“. for the Risk Analysis of Foods Derived from Modern
Biotechnology (CXG 4+003) and the Guidelines for
The language in the decisions recognizes that some the Conduct of Food Safety Assessment of Foods
development of gene editing could be considered Derived from recombinant-DNA Plants (CXG 45-
LMOs and/or synthetic biology.2 However, it 2003), Animals (CXG 68-2008), and Microorganisms
recognizes that some other applications may not. (CXG 46-2003). The three latter guidelines state
that, while they were designed for foods derived
Codex Alimentarius Guidelines from recombinant-DNA organisms, the approach
The Codex Alimentarius (Codex) is a collection of they describe could generally be applied to foods
standards, guidelines and codes of practice for derived from organisms that have been altered by
foodstuffs. It is elaborated by the Codex Alimentarius other techniques.
Commission (CAC), which is an intergovernmental
body with more than 180 members. CAC is the Guidelines on labelling comprise the Compilation
central component of the Joint FAO/WHO Food of Codex Texts Relevant to Labelling of Foods
Standards Programme, fully established by FAO Derived from Modern Biotechnology (CAC/GL
and WHO in 1963 to protect consumer health and 76-2011), providing guidance from earlier Codex
promote fair practices in food trade. texts of broad application, which are also relevant
to the labelling of foods derived from modern
biotechnology.

2 Current operative definition of synthetic biology in CBD negotiations is Guidelines on analytic methods, include the
“a further development and new dimension of modern biotechnology Guidelines on Performance Criteria and Validation
that combines science, technology and engineering to facilitate and of Methods for Detection, Identification and
accelerate the understanding, design, redesign, manufacture and/
or modification of genetic materials, living organisms and biological
Quantification of Specific DNA Sequences and
systems.” Specific Proteins in Foods (CAC/GL 74-2010). These

34
 Gene editing and agrifood systems

guidelines provide information on criteria for the The Organisation for Economic Co-operation and
validation of food analysis methods involving the Development
detection, identification, and quantification of The Organisation for Economic Co-operation
specific DNA sequences and specific proteins of and Development (OECD) and its member
interest that may be present in foods, including countries have been addressing issues related to
those foods containing materials derived from biotechnology since 1982. Its Working Party on
modern biotechnology. The guidelines apply to Harmonisation in Biotechnology and the Working
a wide range of biomarkers in foods, including Party for the Safety of Novel Foods and Feeds
the detection of foods derived from modern focus on environmental and food safety issues,
biotechnology and food speciation. It is clear respectively. Their guidance documents usually
now that the methods of analysis based on provide complementary and more detailed content
DNA sequences covered by the guidelines are on the issues covered more broadly by the
applicable to detect foods derived from gene-edited multilateral fora mentioned earlier. Different OECD
organisms, from SDN-1, SDN-2 and SDN3 if the areas also cover other relevant governance issues.
analyst has information on the exact change made New topics often arise faster in the OECD than in
to the DNA sequence of the organism. the Cartagena Protocol or Codex, which was also
the case for gene editing. The OECD has already
Other general guidelines. There are many other organized a workshop focused on the agricultural
Codex guidelines of general applicability that may applications of this technology and its procedures
apply to foods derived from gene-edited organisms, constitute a valuable source of information for
regardless of their regulatory classification. regulators. Additionally, the OECD regularly
These include the Guidelines on the Judgement publishes regulatory updates at the country level,
of Equivalence of Sanitary Measures Associated compiling reports by its member countries.
with Food Inspection and Certification Systems
(CXG 53-2003), which is helpful when countries Other key issues
have different classification systems or regulatory
approaches for gene-edited products. The Principles Identification
and Guidelines for the Exchange of Information A seemingly simple but fundamental issue has not
between Importing and Exporting Countries to been resolved for gene-edited products: a universal
Support the Trade in Food (CXG 89-2016) may help nomenclature. Currently, the same product
to facilitate communication to clarify the presence is often presented under dissimilar (technical
of the products in international shipments. or commercial) names according to different
Finally, the Guidelines for use of Nutrition and governments, in technical publications and more
Health Claims (CAC/GL 23-1997) may be used in with important implications for international trade
connection with leading cases of gene-edited crops (Punt and Wesseler, 2016).
intended to provide health and nutritional benefits.
For the transboundary movement of living
The International Plant Protection Convention organisms, derived products and food speciation,
The International Plant Protection Convention sworn statements, databases, and governmental
(IPPC) provides a system of standards and exchanges are based on standardized scientific
procedures for identifying pests that threaten names (binomial nomenclature) when referring
plant health, assessing their risk, and determining to the species that features in a product. For GM
the strength of measures to be used against their plants to date, the OECD Unique Identifier for
introduction and spread. Under the IPPC, most Transgenic Plants is the internationally recognized
countries have established regulatory organizations denomination for regulatory and technical
experienced in assessing and managing the purposes. Therefore, for gene-edited organisms
risk of pests that threaten plant health. Albeit of that are transgenic plants, the OECD identifiers are
broader scope, IPPC risk analysis and management applied. However, some governments may consider
systems are appropriate for assessing and an SDN-1 mutant not to be a transgenic plant, but
managing, if necessary, the direct or indirect risks still require that the developer use an internationally
of pests to cultivated and wild flora and plant recognizable identification code. In this regard, it is
products that may be presented by LMOs and interesting to consider the FAO/IAEA (International
products of modern biotechnology. Atomic Energy Agency) database on plant mutants.
This database currently registers mutants obtained

35
Governance and regulation

using radiation, chemical mutagens, and the market. It also involves varieties obtained by any
biotechnology-based mutagenesis technique of breeding method. Because gene editing enables
somaclonal variation. direct editing of genes in elite breeding lines or
commercial varieties and eliminates the need for
Off-target changes and unintended insertions backcrossing to introgress a trait from a non-elite
Gene-editing techniques aim to target genomic or wild relative trait donor (Pixley et al., 2022), it
locations precisely and effectively generate a reduces the need for access to, and utilization of
desired sequence change. However, they can genetic resources in breeding, which are regulated
occasionally lead to unintended results, including by access and benefit-sharing frameworks.
off-target changes and unintentional DNA
insertions (see section 2). Off-target changes Two paramount international agreements currently
in genomic DNA sequences may occur if the assist countries in the governance of access and
target sequence (or a similar one) is also present benefit-sharing in agriculture. The International
elsewhere in the genome. An off-target change in Treaty on Plant Genetic Resources for Food and
the DNA sequence of the host organism, in turn, Agriculture (ITPGRFA) and the Nagoya Protocol
may or may not lead to a significant difference in on Access to Genetic Resources and the Fair and
phenotype or safety. The off-target issue is new to Equitable Sharing of Benefits Arising from their
SDN techniques. Therefore, it was not anticipated Utilization to the Convention on Biological Diversity.
in existing international guidance, and scientific The ITPGRFA objectives are the conservation and
literature to date presents a plethora of diverging sustainable use of all designated plant genetic
results that may confuse regulators in the absence resources for food and agriculture, as well as
of standardized criteria to address the topic. promoting fair and equitable sharing of the benefits
arising from their use.
On the other hand, unintentional DNA insertions
result from nucleic acid fragments incorporating into The ITPGRFA entered into force in 2004. It aims
the host cell, purposely or not, during a gene-editing to establish a global system to provide farmers,
procedure. Even gene-editing techniques conceived plant breeders and scientists with access to plant
as “DNA-free” have resulted in the integration genetic materials, ensuring that recipients share
of foreign DNA inadvertently introduced in small benefits they derive from using those genetic
amounts. The insertions can occur anywhere in the materials with the countries of origin. The treaty
genome, not only off/on target sites. prevents the recipients of genetic resources
from claiming intellectual property rights over
The issue of searching for unintentional DNA those resources in the form they were received
insertions is not new in the safety assessment of and ensures that access to genetic resources
transgenic and GM organisms. However, regarding already protected by international property rights
gene-edited organisms, it may have an additional is consistent with international and national laws.
significance for certain countries when deciding if a The ITPGRFA aims to enable a global pool of
particular gene-edited organism is to be regulated genetic resources from 64 crops, which account for
as a GMO or not (Eriksson et al., 2019; Lema, 2021). 80 percent of all plant-derived foods, to be available
to potential users among the 150 State parties to
Property, access and benefit sharing the treaty under standard terms and conditions
that, on the one hand, facilitate access to samples
Governance of property, access and benefit of genetic material for research and breeding and,
distribution in connection with plant varieties, on the other, ensure the equitable sharing of the
animal breeds, and microbial strains is governed by monetary and non-monetary benefits resulting
various international treaties. from research and breeding.

Access and benefit sharing The Nagoya Protocol is a supplementary agreement

Over recent decades, there has been intense to the CBD. It aims at sharing the benefits arising
general debate over the access to genetic from the utilization of genetic resources from all
resources and the sharing of benefits derived from biodiversity fairly and equitably, contributing to the
their utilization. This includes not only the use of conservation and sustainable use of biodiversity.
plant varieties, animal breeds, and microbial strains The Nagoya Protocol also covers traditional
unmodified and as they were found in nature or the knowledge associated with genetic resources

36
 Gene editing and agrifood systems

and the benefits arising from its utilization. It is New plant varieties are protected either by patents
important to highlight that “utilization” in this treaty and/or sui generis systems, depending on each
is understood to include research and development country´s criteria. The multilateral agreements used
on the genetic or biochemical composition as a reference for establishing national protection
of genetic resources, as well as subsequent frameworks are the acts of the International Union
applications and commercialization. Benefits may for the Protection of New Varieties of Plants (UPOV).
be monetary or non-monetary, such as royalties Some national regulations are updated to the
and the sharing of research results. The Protocol (latest) 1991 Act, while others still have rules in line
entered into force in 2014 and currently has 138 with the act prior to 1978. This discrepancy leads
State parties. It aims to foster a transparent, fair to a significantly different treatment of key issues
and predictable legal framework for international like protection of essentially derived varieties and
access to local genetic resources. Its provisions the impact of breeders’ and farmers’ rights on the
aim to help ensure benefit-sharing when genetic subsequent use of a variety after the initial seed
resources leave the country, provide incentives to purchase (Rapela, 2019; Yu and Chung, 2021).
conserve and sustainably use genetic resources,
and enhance biodiversity’s contribution to food Gene-edited products considerations
security and human well-being. To date, gene-editing applications for agrifood
systems have not made a significant appearance
The constituencies of these two agreements are in the meetings of the parties discussing the
currently discussing the access and benefit-sharing implementation of these treaties, and there are
obligations using “digital sequence information” very few references in the specialized literature.
without recourse to the physical genetic materials. However, new varieties/breeds/strains obtained
using traditional breeding methods and GMOs
Intellectual property have been extensively discussed, with numerous
The World Intellectual Property Organization study cases and ad hoc national guidelines being
(WIPO) administers several treaties on intellectual produced.
property, including the Patent Law Treaty (PLT),
which entered into force in 2005. Additionally, the Attending to scientific and (sanitary) regulatory
Agreement on Trade-Related Aspects of Intellectual considerations, gene-edited products may be
Property Rights (TRIPS Agreement), which considered either GMOs or, in some countries,
entered into force in 1995 under the WTO, is also equivalent to mutant breeds obtained by other
of great significance. However, these multilateral means. Therefore, prima facie, gene editing may
instruments do not provide standards for the not result in opening a significant new chapter
patentability of specific technology fields. In this in the governance of intellectual property and
regard, certain biotechnology developments have genetic resources because gene-edited products
been particularly challenging, facing different criteria could be accommodated by rules applied to pre-
depending on national context. existing product categories. For instance, the
patentability or variety registration of an SDN-1
Factors that led to questioning patentability in mutant maize line obtained by CRISPR could be
several cases included inventions incorporated into the same as applied previously to a new variety
self-replicating entities (such as seeds), patenting obtained by radiation breeding. In addition, if the
of DNA sequences (and other biological elements) breeder mutated a pre-existing variety owned
that can be found in nature, the sufficiency of by another developer, the relative rights of the
disclosure on processes not fully understood by original developer and the mutation breeder could
biologists, replicability of processes incorporating be solved as already customary in that specific
a random factor (such as earlier mutagenesis country for essentially derived varieties (Graff and
methods), and outcomes perceived to be contrary Sherkow, 2020). Moreover, suppose the base
to morality or regulations (such as those impacting genetic resources used by the breeder fall under
on animal welfare). The patenting of gene-editing the access and benefit-sharing systems mentioned.
technology has also been criticized for having the In that case, the breeder may have obligations
potential to increase monopoly power, disrupting regarding disclosure of the resource origin,
the market for animal and plant breeding (Then, mutually agreed terms with the resource provider,
Bauer-Panskus and Tippe, 2021). and sharing of derived benefits. However, once
again, there may be no significant difference in the

37
Governance and regulation

obligations, or how they would be implemented, change (Trigo et al., 2021). Consequently, several
as if the mutation were obtained using radiation, governments have announced public funding to
chemicals, somaclonal variation, or spontaneous support the development of gene-edited products
mutation. Similarly, a transgenic plant (and derived for food and agriculture. Synthetic biology is often
foods and other products) obtained through an considered in bioeconomy sources (Gomez San
SDN-3 gene-editing procedure may or may not be Juan and Bogdanski, 2021), and gene editing in
protected using the same criteria that a country various national bioeconomy strategies. However,
had developed for transgenic organisms to date. an appropriate regulatory framework is more
fundamental to fostering gene-editing innovations
Patents and gene-editing methods than the availability of governmental subsidies
In contrast to the patenting of organisms and (Wesseler et al., 2022). This is especially relevant
derived products, where gene editing is not for developing countries with little to invest, and
expected to introduce significant issues, the for international agencies that may offer funding
patenting of the gene-editing methods has already to foster gene-editing innovations (Smith et al.,
raised attention (Gehrke, 2019). This mainly 2021). Additionally, the importance of sustainability
focuses on the different players who struggle to criteria in investments is growing rapidly. Among
own the technology, their license agreements, the bioeconomy indicators used by different
innovations to obtain new patents, etc. Some sources, gene editing provides information on the
research organizations have already announced quality and the safety of a bioeconomy product
that they will, under certain conditions, make the (Bracco et al., 2019).
patents they own freely available. This includes
the Broad Institute (Graff and Sherkow, 2020) and Trade interventions
Wageningen University (Sikkema, 2021). Many of In the past, trans-Atlantic asymmetries in the
the patents enter licencing agreements as with the use and regulation of certain biotechnologies
rapid development in RDN technologies, developers have been linked with actual or potential trade
often having to rely on patents owned by other disruptions and disputes, as in the case of
organizations where cross-licensing of patents veterinary hormones, GMOs and animal clones
have become common (Schenkelaars et al., 2011). (Smith, Wesseler and Zilberman, 2021). A similar
Moreover, in certain countries, the randomness situation may be developing with gene-edited
of mutation breeding and of (transgenic) organisms. Specifically, a developer may obtain
transformation events have been considered an approval for cultivation in a certain country, but not
obstacle to their protection by patents. However, get approval for food import in another because of
SDN-1/2/3 can achieve the same results with asynchronous approvals or differential regulatory
less or no randomness, which may increase their treatment. Differential labelling rules may be also a
acceptability by patent offices (Rapela, 2019; Graff significant asymmetry (Punt and Wesseler, 2016).
and Sherkow, 2020). Moreover, declarations have been presented to the
WTO, in which certain governments pledge others
Economic interventions to cooperate, to avoid situations that could lead to
a different regulatory treatment across geographies
Innovation funding (Pixley et al., 2022). Differential regulatory
Innovative breeding techniques, including gene treatment can lead to potential trade disruptions,
editing, are recognized as an emerging area of the mere possibility of which could hamper
bioeconomy research, for example to increase plant development of gene-edited products, as has
carbon sequestration and help mitigate climate already occurred with GMOs (Smith et al., 2021).

38
5 Rtransformative
 oles of the private and public sectors and
partnerships
SUMMARY
Both the private and public sectors engage in Gene-edited organisms and products have been
agricultural research, although focus and incentives researched in both the private and public sectors
can differ. Private sector research is generally and some ground-breaking discoveries have been
more directed to products that are marketable, made in each (Tramper and Zhu, 2011). Frequently,
and consequently profit-making, whereas public the private sector is involved in the final stages
sector research is often less constrained and allows of the development process, translating research
greater academic freedom. Issues of ownership of into a marketable product (Barrett et al., 2022).
technologies and products can be problematic, and This often relies, however, on work done in the
the motives of private enterprise have sometimes public sector, including that done in universities
been questioned. However, many of the aspirations and research institutes, and can engender public-
of public and private organizations are compatible private partnerships (Rausser, Simon and Ameden,
and collaboration between the two sectors can be 2000). This can take place at an informal level, as
beneficial. reported for CGIAR, where researchers customarily
exchange germplasm among colleagues (Louafi
and Welch, 2021), contributing to substantial gains
from research (Alston, Pardey and Rao, 2022).
Consequently, gene editing represents a potential
transformative technological breakthrough, and it
is important for all stakeholders, including local and
international researchers, policymakers and the
public, to understand the innovation trajectories,
who finances them, who bears the risks and
rewards of innovation, and for whom technologies
are ultimately developed (Fajardo-Ortiz et al., 2022).

An important responsibility assigned to the public

sector in many countries is oversight of safety
protocols arising from developments in plant and
animal breeding, shaping markets and shouldering
the risks of early transformative research
investment (Fajardo-Ortiz et al., 2022). Numerous
countries have agencies that assess food safety
and biosafety aspects of new products. This
requires collaboration with the private sector and
sharing of information. The collaboration with the
private sector and the role and tasks of the public
and private sectors for ensuring food and biosafety
has frequently been controversial.

Public sector

Much of the innovative work underpinning the

advances made in modern biotechnology has been
done by scientists working in the public sector,
public sector funding being instrumental in important
areas of research. Informal exchange among
scientists in conferences, writing joint papers, and
discussing and reviewing research of colleagues
has contributed significantly to the development of
gene-editing organisms and products (Doudna and

39
Roles of the private and public sectors and transformative partnerships

Sternberg, 2017; Heimann, 2018). Those involved have been tested and breached (Mallapaty, 2022).
also reported on the importance of academic Inevitably, public sector researchers have sometimes
freedom, the significance of funding, and the become victims of the controversies associated with
possibilities to draw on human capital. GMO and gene-editing technologies (Dubock, 2014;
Robinson, 2022).
Early on, public sector researchers involved in
developing gene-editing technologies recognized Private sector
the societal challenges their research would face. To
address the challenges, Jennifer Doudna, the Nobel Private sector research has played an important role
laureate, organized meetings following the example in modern biotechnology development. However,
that had been set by the Asilomar conferences private sector research is targeted more towards
(following the creation of synthetic DNA molecules product development than towards scientific
using rDNA technology) where ethical and advance. It is generally the case that private sector
legal issues stemming from gene editing were funding is more focussed than that of the public
discussed. The discussions not only included public sector.
sector scientists but also involved regulators,
representatives from academies of science and The private sector plays an important role in
others, and resulted in funding guidelines that developing products for markets, with the main
public and private sector researchers comply incentive to generate profitable products. For
with to receive public sector research funding. the products to be profitable however, as they
Examples include the funding requirements under have been for seeds of improved varieties for
the European Union Horizon Europe programme,3 instance, prices and sales must be acceptable.
the Dutch Top Sectoren funding,4 and United States One of the important benefits of gene editing and
Agency for International Development (USAID) CRISPR-Cas systems is the substantial reduction
funding.5 Private sector research funding is often in research costs for developing new products in
sought, larger research projects needing to draw on comparison with using traditional, time-consuming,
support from a variety of sources. Ultimately, the methods. Employing gene editing, the time needed
funder setting the highest standards is the one the to develop a new crop with improved traits is
research project must comply with. reduced considerably. Some scientists consider
this to be a democratization of science because
The public sector has established both an informal more researchers have the possibility to conduct
and a formal system governing the safety of research and develop products with new traits.
gene-editing research (see section 4). The safety Researchers in countries where budgets are tighter
standards governing the application of rDNA could benefit relatively more with decreasing
technologies were summarized in the Blue Book returns to scale. Nevertheless, the democratization
of the OECD (OECD, 1986) and set the safety of science does not solely depend on simplifying
standards that are followed by many countries gene-editing processes and discussion continues
(Schiemann, 2006). The initiative supported by about the motives of big business.
OECD was a follow-up to the Asilomar conference,
where guidelines for laboratory work were Investment costs include not only the costs
established. The safety standards are regularly of conducting the research, but also the costs
updated and cover the latest developments in for getting a product on to the market. This has
modern biotechnology. implications for the market structure of the plant
breeding sector (Deconinck, 2020; Wesseler,
Nevertheless, the public sector research system and Jongeneel and Purnhagen, 2019). Often larger plant
its incentive apparatus for professional advancement breeding companies are only able to shoulder the
has resulted in deception in some cases, investment costs, increasing their market share
researchers having fabricated data (van den Belt and over time. The profits a company can make depend
Keulartz, 2007). In other cases, ethical boundaries on the extent of the market: being able to market
seeds to farmers of a country where there are large
3 https://research-and-innovation.ec.europa.eu/funding/funding- areas of uniform environment, and relatively many
opportunities/funding-programmes-and-open-calls/horizon-europe_en farmers, is much more attractive than attempting to
4 https://www.topsectoren.nl/ provide to a smaller, niche clientele. It is moreover,
5 https://www.usaid.gov/work-usaid/find-a-funding-opportunity from the private sector point of view, much more

40
 Gene editing and agrifood systems

economically sound to develop technologies, of the owner. The owner gains monopoly power
and provide products from their application, to over the product for a set time. Patents, however,
major crops such as wheat, maize and rice, than are increasingly being replaced by trade secrets
to attempt the same for minor crops, which are, that rely on getting to market fast, with exclusive
axiomatically, grown over smaller areas. The rights to the technology (Lassoued et al., 2021).
differences in market size and related investment Concerns have been raised that this will allow seed
costs for adopting gene-editing technologies also and pesticide companies to exploit farmers by
explain why not all plant breeding companies favour charging high prices. Empirical studies investigating
changes in legislation that would lower market entry the distribution of rents from improved seeds in
costs (Wesseler, Jongeneel and Purnhagen, 2019). the United States of America show that farmers
gained more than 50 percent of the rents while
Differences in the approval costs are often country- about 30 percent went to the technology provider,
specific and can have a substantial effect on and the remaining part to consumers and
investment incentives (Wesseler et al., 2022). others (Falck-Zepeda, Traxler and Nelson, 2000).
This explains why the private sector has keen Furthermore, pricing power was shown to be
interest in the regulation of gene-edited products. limited by the alternative technologies available
If gene-edited crops are GMOs in the European for crop production. Farmers have the option to
Union, which they currently are, they must follow buy the improved seeds (Weaver and Wesseler,
the approval processes for GMOs, and related 2004). Such situations characterize countries where
labelling and tracking and tracing rules apply. the institutional environment secures property
Many authors have concluded that this will make rights and law enforcement is well established,
cultivation of gene-edited crops almost impossible preventing elites from exploiting their powers.
in the European Union and imports of gene-edited It does not necessarily hold for all countries
crops very expensive (Purnhagen and Wesseler, (Acemoglu and Robinson, 2019).
2020; Nationale Akademie der Wissenschaften
Leopoldina, Deutsche Forschungsgemeinschaft Some previous experiences regarding the role of
und Union der Deutschen Akademien der private companies in developing seeds of high
Wissenschaften, 2019). The European Union has yielding crops could be informative for how gene-
recognized the problem and has set a process in editing technologies might impact farmers. Pray
motion for revising the regulations for gene-edited et al. (1991), with reference to private sector seeds
organisms (European Parliament, 2021). Several for India, said that there is “widespread belief that
other countries have also adjusted, or are in the small-farmer subsistence agriculture in developing
process of adjusting, their regulatory frameworks countries cannot sustain a commercial private
with the expectation of stimulating investments in breeding industry for food crops.” At that time, the
gene editing (see section 4). private seed sector (comprising 17 major companies)
spent as much on research and development as
This investment perspective does not exclude the Government of India, but the privately produced
the possibility that individuals and companies crop varieties were higher yielding than those
in the private sector are solely driven by profit produced by the public sector because the private
motivation. Many private sector companies are sector research was more carefully directed. He
concerned with delivering products that provide suggested that artificially low prices of public sector
societal benefits, such as better nutrition or health, seeds encouraged a false economy and that farmers
although private sector altruism has limits. Gene- were better off buying the more expensive, privately
edited products that have reached the market are produced, seeds. He went on to explain how the
present in products such as seeds, food, animals benefits from private research were largely reaped
and microbes (e.g. making vat-based protein by farmers despite the private companies only
and cheese). The development of such products, capturing six percent of the benefits of their own
especially with respect to the regulatory process, research. They were happy nonetheless because
is often very costly. To be able to recover the costs, their internal rates of return were sufficiently
the private sector often secures investments by high. This example illustrates that competition
protecting their work with patents. Patents allow between the public and private sectors is not as
the owner of the patent exclusive rights for a straightforward as it might initially seem, and that
set period. This excludes others from using the private industry incentives can be compatible with
patent-protected product without the consent small-scale farmer needs and circumstances.

41
Roles of the private and public sectors and transformative partnerships

Intellectual property considerations significant barriers to smaller developers and

farmers represented by patents and ownership
A more general debate has emerged with surrounding CRISPR technologies and gene-edited
respect to assigning property rights to seeds. seeds (de Wit, 2020). Consequently, opponents
The International Union for the Protection of New to patenting of plants argue that farmers will
Varieties of Plants (UPOV) is an intergovernmental become more dependent on seed companies,
organization that supports the protection of plant which deprives farmers of the right to access
breeders’ rights. UPOV was established by the their proprietary seed and the ability to not only
International Convention for the Protection of New select them but also to produce, store, use,
Varieties of Plants (UPOV Convention: adopted on exchange and sell them. Yet, these seeds are
December 2, 1961). The UPOV convention does of great importance to farmers because they
not cover patents, which were introduced at a often represent the bedrock of smallholder seed
later stage. Specific activities are patented and if systems (Agriculture Food, 2017; Goray and
used for seeds, the seeds are also protected by Bessa, 2019). However, farmers retain the right
the patent. This has been questioned. Is breeding to continue using their ancestral seed stocks or
a new plant an innovation that did not exist before, buy seed from other sources. Those in favour of
and hence patentable? One of the landmark patent/variety protection of seeds argue that the
decisions was that of the Harvard mouse, the first lack of protection disincentivizes bringing better
patented mammal. The mouse was developed by seed varieties to market, thus leaving farmers
researchers at Harvard University with funding from at a disadvantage in comparison with farmers in
DuPont. Harvard gave the company exclusive rights countries where the situation is improved because
for commercializing any inventions resulting from Intellectual Property (IP) is protected. In the case of
the research. The patentability of the transgenic GMOs, some private sector seed companies have
mouse set the precedent for patentability of not pursued IP litigation in LMICs and a number of
transgenic plants and for private sector funding clearinghouse mechanisms have been developed
of public research via exclusive licensing of the to facilitate access to IP-protected technologies for
results, such as the Novartis deal of UC Berkeley. LMICs (Graff, Roland-Holst, and Zilberman, 2005).
This line of reasoning is not limited to patents. Also,
Some regions have more restrictive rules on the protection of plant breeders’ rights limits the
patents based on moral reasoning. Article 53(a) reuse of seeds. Nevertheless, certified seeds are
of the European Patent Convention states that often of higher quality and represent an economic
“inventions, the publication or exploitation of which incentive to purchase new seed. Hence, this is
would be contrary to ordre public or morality are a more general issue that is independent of the
excluded from patentability.” This has set some breeding technology applied.
limits on patents for seeds and crops (Gehrke,
2019). Public-private and transformative partnerships

If seeds are protected by patents, it can The links that have been established through
negatively impact farmers because they are not research funding and property rights between
permitted to save seeds, or only a limited amount. public and private sector organizations have
Consequently, they must buy new seeds each resulted in numerous transformative partnerships
year, especially if patented genetic use restriction (Alston, Pardey and Rao, 2022). Such partnerships
technology, which stops harvested seeds can contribute to transforming agrifood systems
germinating, is applied commercially (Kabir et al., towards improved sustainability (Alston, Pardey
2022; Ohlgart, 2002; Lombardo, 2014). Important and Rao, 2022; Trigo et al., 2021). In these
research is increasingly being done by large transformative partnerships, the private and public
multinational corporations, which control usage sectors work together and use their comparative
through patents, and lately trade secrets, which advantages to increase the efficiency of
are even more restrictive and could potentially limit transforming agrifood systems. Examples include
the use of advanced technologies in agriculture cyanaophycin-enriched transgenic tobacco plants
(UNCTAD, 2021; OECD, 2001). However, given (Huckauf et al., 2022), insect resistant Bt cowpea
the costs associated with regulatory procedures, in Africa (GAIN, 2022), a virus-resistant potato with
it is often only multinationals that can afford to an industrial tuber starch quality (Glais, Bellstedt
commercialize products. Furthermore, there remain and Lacomme, 2017), microalgae-based production

42
 Gene editing and agrifood systems

of industrially relevant mycosporine-like amino (Rausser, Simon and Ameden, 2000). For example,
acids and replacing trans-fatty acids in oil seeds Australia’s system of end-point royalties for wheat
(Zambelli, 2020). varieties, as a mechanism for implementing and
enforcing plant breeder’s rights, has led to the birth
Private sector investment in agricultural and food of public- private-sector partnerships because the
research and development (R&D) is growing seed companies that collect the royalties comprise
more rapidly and is proprietary, creating additional of a mix of private, producer and public-sector
costs on farms compared with public R&D. partners (Alston and Gray, 2000).
Additionally, the formation of CGIAR led to an
increased participation of the private sector in The role of public-private partnerships in
global agricultural and food R&D as a response to transforming agrifood systems through gene-
changes in the policy and practice of intellectual editing technologies may, however, be hampered
property or market structures throughout the food by the discrepancies in regulatory frameworks.
value chain, in addition to new innovations that For instance, some countries in Latin America and
have made research benefits more appropriable the United States of America view gene-edited
by private investors. More specifically, private organisms as being distinct from GMOs, while
sector spending on agricultural R&D increased others, including South Africa and the European
from 32 percent in 1980 to 50.4 percent in 2015 Union, view them as being like GMOs and therefore
(Alston, Pardey and Rao, 2022). However, much subject to the same stringent regulations governing
of the private sector spending on agricultural GMOs. This, in turn, limits development, release
R&D is concentrated in high income countries and adoption of gene-edited crop products in LMICs
(52.5 percent in 2015) and is less pronounced in (Falck-Zepeda et al., 2022; Mayet, 2022). Additionally,
the LMICs (private sector share of 12.3 percent many partnerships encounter financial constraints
in 2015). This can be attributed to the farming during implementation because of the insufficiency
systems that are unattractive for private sector of market assessment and feasibility studies, which
investment such as the small farms, low usage of leads to longer payback periods and lower returns to
purchased inputs and the limited post-farm food investments. Ultimately, this challenges survival of
logistics, food processing, and demand for food- many partnerships (FAO, 2016).
away-from-home (Alston, Pardey and Rao, 2022).
This has consequently limited the role of the private Identifying and managing conflicts of interest
sector in agricultural R&D for the LMICs. The in public-private partnerships
public sector often has a comparative advantage
in conducting unconstrained research, while the Public and private partnerships face diverse
private sector’s comparative advantage is in more problems that originate from differing incentive
directed research and delivering the product to systems. There is potential for conflict between
market. Examples of public-private partnership the public and the private sectors. More
include the collaboration in the international specifically, the public sector has a keen interest
research centres of CGIAR (Alston, Pardey and in development and adoption of technologies and
Rao, 2022). The overall expectation is that the maintains a very strong interest in controlling
partnerships generate more funding for addressing and ensuring the safety of new technologies.
societal challenges as, for example, detailed in The private sector, however, has interests mainly
the SDGs (Di Sibio, 2022). Other transformative centred on maximizing profits (Byiers et al., 2016).
partnerships have developed that support public The private sector often views safety regulations
communication on gene editing. However, public as generating additional costs. The incentives of
and private sector partnerships have limitations the private sector are to keep costs to a minimum,
because of differences in focus, especially when it but this has not necessarily always been the case.
comes to high-end technologies, high profit-margin The public sector advocates stringent ex ante
areas and crops, and the perceived mistrust, lack safety regulations while the private sector would
of transparency and non-adherence to agreement prefer to see less stringent safety regulations.
among partners (Trotsenko and Slukin, 2020). From an economic perspective, both viewpoints
Additionally, public-private-producer partnerships must be considered. If only public sector regulatory
are increasingly becoming very important in activities were operational, a stringent ex ante
areas of agricultural innovation that were once regulatory system could affect the incentives of
predominantly public- or private-sector domains the private sector to invest, which could result in

43
Roles of the private and public sectors and transformative partnerships

reduced benefits. If safety regulations were left to agreements may exclude others gaining access to
the private sector only, the safety measures might the technologies. To avoid exclusion of patent users
not be optimal from a social perspective. Public from LMICs, several patent owners made patents
sector regulators could face the problem of striking freely available (Wageningen University in 2021
the optimal balance between ex ante regulations and the BROAD Institute in 2017). These types of
and ex post liabilities (Lema, 2019; Shleifer, 2010). agreement are not without problems, especially
when they result in patent infringements. The
Regarding gene editing, it has been argued that the liability for possible damages can become a
ex post liabilities for society are close to zero and problem. Another question being raised is why
that the technology is substantially overregulated, public sector financed research results are patented
which reduces incentives for investment (e.g. and are not automatically freely available. The
Eriksson et al., 2018; Wesseler et al., 2022). advantage of patenting public sector research is
This is an important issue also for public-private to maintain control over a technology and avoid
partnerships. The distribution of the risk between privatization of the technology by the private sector
the public and the private sectors could result in (Scheinerman and Sherkow, 2021). Nevertheless,
costs being socialized and benefits privatized. Many legal issues concerning patent ownership are to
public sector organizations that have developed be expected, as illustrated by the struggle over
patented gene-editing technologies have entered CRISPR-Cas related patents. This could result in
into licensing agreements with private sector conflicts over property rights and licencing fees and
companies (Contreras and Sherkow, 2017). Such their distribution.

44
6 T he way forward
Agriculture is the cornerstone of human existence, and environmental consequences of the Green
but it is facing hitherto unmatched pressures. Revolution were positive – it was not a panacea.
Hunger, malnutrition and environmental erosion are
among the consequences of the pressures, and With advances made in genetics and molecular
are increasing in magnitude as the pressures build. biology, it was suggested that the next revolution
These issues represent a problem that science and in agriculture might be the gene revolution (Davies,
society must address if all people are to be able to 2003), building on where the Green Revolution left
have regular access to sufficient high-quality food off. While many of the tools furnished by research
to lead active, healthy lives. into molecular genetics assisted plant and animal
breeders in their work, the production of transgenic
The causes of the current problems are not new, organisms raised a series of questions about
but they have grown in intensity and importance the risks and benefits to human health and the
over recent years. Climate change is among the environment, in addition to fundamental concerns
most potent of the forces that currently affect over what is intrinsically beneficent and acceptable
agrifood systems; severe and often unpredictable and what is not. Much of the disapproval of
weather events taking a substantial toll. Excessive genetic engineering emanated from unintended
heat and drought, as well as heavy rainfall and consequences of the technology, its perceived
inundation, make it impossible for agriculture to imprecision. However, more than three decades of
function. Such extreme weather events lead to research into the risks associated with genetically
erosion of agricultural land and force demographic engineered crops indicates that they have been no
changes, large numbers of people having to leave riskier than conventionally bred crops (EASC, 2013;
their homes, many in already marginal areas of NASEM, 2016a).
production, because their sole means of livelihood
vanish. The climate effects are compounded by the Among the most recently developed technologies
spread of disease, the recent COVID-19 pandemic that can be applied in future efforts to improve
being a particularly calamitous example. Conflict plant and animal breeding is gene editing. This
is also frequently an aggravating factor that represents an advance over producing transgenics
stimulates migration, as well as being destructive because it is inherently more precise and more
in its own right. versatile, and not prone to some of the errors
associated with previous technologies, although in
The challenge for society, and scientists in this regard it is not problem-free. Another advantage
particular, is to develop solutions to the problems gene editing has over other technologies is that
that ease the burden on those most affected by the it is relatively rapid, which will be very important
problems. Interventions must be made that reduce given the speed of climate change. Development
the severity of the effects of climate change, and application of techniques such as CRISPR
conflict and displacement, among other forces, but has already generated an enormous amount of
which do not, inadvertently, inflict more damage. information on the genetic workings of an array
of plants, animals and microorganisms, and has
Past efforts to increase agricultural production and also made it possible to breed new germlines of
address issues of hunger, malnutrition and inequity many agriculturally important organisms. However,
have been many, but arguably the most impactful despite its success and the promise it has shown,
was the Green Revolution. This represented the gene editing has come up against many of the
application of knowledge of genetics to breeding barriers that previous technologies have faced.
more productive varieties of wheat and rice, in
the main. The benefits derived from sowing the Not only are the barriers ethical in nature, whether
high-yielding varieties were numerous in terms the benefits outweigh the risks, they also include
of reducing hunger, promoting human health and the need to fit the products of gene editing into
raising living standards. However, as with the functional regulatory frameworks. In addition, for
introduction of all new technologies, there were gene editing to make a substantial impression
unintended effects, and not all the socioeconomic on world hunger, it must be applied to the major

45
The way forward

crops, those on which most of humankind relies far superior (Bullock, Wilson and Neadeau, 2021).
for its nutrition. Wheat, rice and maize contribute There is a much higher probability of success in
nearly half of the world’s calories. However, this the discovery phase (25 versus 5 percent) and the
creates a dilemma because the most vulnerable lack of strict regulatory approval in many countries,
communities, in terms of pressures on agrifood combined with the relatively rapid development
systems, are those in marginal areas, often in of products, speeds up commercialization. Other
LMICs, where agriculture is already in jeopardy. benefits of gene editing over genetic modification
The problem will not solely be one of total food mean that potential market sizes for gene-edited
production, but one of improving resilience of crops are considerably smaller than for genetically
agrifood systems that might not represent prime modified crops (up to 96 percent), which makes it
investments. Moreover, applications of gene more attractive for development of crops and traits
editing to major crops, to enhance their resistance with lower area potentials and for niche features.
to various stresses, would have to be balanced Moreover, a decline in break-even areas means
against direct introduction of, for example, drought that some traits that would never be economically
resistant minor crops such as amaranth and fonio, attractive for genetic modification are attractive
or even reintroduction of traditional crops. For for gene editing. These include many traits for
example, in some areas of Africa, sorghum and allergenicities. Bullock, Wilson and Neadeau (2021)
pearl millet are making a reappearance because also suggested that for many traits, development
maize cultivation is increasingly difficult as rainfall and marketing would become more efficient
becomes unpredictable and often insufficient. and would stimulate closer relationships among
Under such conditions, when crop replacement is all those involved in gene editing, including
seen as the solution to a changing environment, developers, providers and growers.
gene editing is unlikely to be helpful regarding
the crop that needs to be replaced. However, Another major issue is that adaptive traits must
as conditions for agriculture deteriorate further, be targeted to have a significant impact, and it is
gene editing could contribute to ensuring that inevitable that some specific traits in particular
replacement crops, possibly old traditional species will be more easily manipulated than
crops, are better able to withstand the changing others. It also must be recognized that such
conditions by having the capacity to tolerate scientific interventions, as represented by
prevailing abiotic and biotic stresses. Moreover, gene editing, will not have any effect on world
as crops change, so do nutritional profiles, hunger, and evening up of other inequalities, in
and gene editing for changed and improved environments that are no longer able to support
micronutrient content could become an important food production. This applies to terrestrial and
consideration. This is particularly important given aquatic ecosystems, many of which, because of
that plant breeders have often prioritized yield over the effects of unmanageable abiotic and biotic
nutritional content, resulting in high-yielding cereals stresses, are irreparably damaged, at least in the
sometimes being micronutrient deficient (DeFries short term. In brief, there are many barriers to
et al., 2015). Because of this, calorie undernutrition progress in alleviating world hunger, not all of which
has declined more slowly than micronutrient are surmountable.
deficiency (Gödecke, Stein and Qaim, 2018).
If gene editing is to help reduce world hunger,
Whichever way gene-editing technologies are used, malnutrition and other inequities, it will be part
and their products deployed, there will inevitably of a consolidated effort that incorporates a range
be trade-offs in terms of who benefits, much as of other interventions. Gene editing will have
occurred for the Green Revolution. As Doudna to be a component in a partnership approach to
(2022) has said, “One risk that is often overlooked problem solving, involving representatives from the
is the real possibility that some of the advances we public and private sectors, and, most importantly,
make in genome editing will benefit a small fraction representatives from the communities where the
of society. With new technologies this is often interventions are to be made. In this way, many
the case at first, so we have to consciously work of the problems previously encountered with
from the start to make new cures and agricultural attempted introduction of new technologies might
tools that are accessible and affordable.” Recent be obviated. Coalitions formed among scientists,
research on the economics of gene editing versus representatives from commerce, politicians and
genetic modification indicates that gene editing is the public will ensure that all interested parties

46
 Gene editing and agrifood systems

have a voice. Moreover, to ensure that smallholder Coordination will be essential to ensure optimal
agriculture benefits from gene editing, small-scale impact of any interventions made in agrifood
producer circumstances must be better appreciated systems, requiring that communication channels
than is currently often the case. They rely heavily are well maintained and fully functional. It is in this
on the work done by, and the products from, area that FAO, among other organizations, can play
public institutions, including NARS. Small-scale a leading role by stimulating discussion, providing
producers are usually not foremost in the minds of information and hosting fora (Directorate-General
representatives of the private sector and so public for Research and Innovation of the European
sector services must be bolstered to make sure Commission et. al, 2022).
that they do not miss out. Naturally, this would also
mean that small-scale producer crops and livestock In summary, gene editing does not represent a
would be prioritized and researched by public stand-alone technology. It will be necessary to
sector bodies. ensure that it is incorporated into currently used
plant and animal breeding systems and that it is
Innovative agricultural research remains a priority, used in conjunction with improved husbandry
and identification of priority agrifood systems practices. Its products should be available to those
and crops will become necessary to ensure that that need them most, and account should be
efforts are optimally directed and that there is taken of the crops and animals that are important
minimal waste of resources. Because gene editing to small-scale producers living in vulnerable
is a sophisticated technology, requiring relatively environments. The use of gene editing should
well-equipped laboratories, it might be most not be confined to or dominated by multinational
effective to set up regional research facilities and corporations at the expense of those most in
programmes. The scale and speed of changes to need of gene-editing technologies and products.
the world’s weather patterns means that there is Only through sustained research on the technical
an urgency to address the most pressing problems aspects of gene editing, and the associated
in the most vulnerable areas, recognizing that benefits and risks, will its potential be fully realized.
some agrifood systems and environments are Previous radical changes to agrifood systems
beyond rehabilitation. Low income households in have not been without difficulties, but innovative
Africa and Asia are likely to be most affected by applications of science and technology have
climate change because they are most susceptible invariably led to positive outcomes. Gene editing
to changing prices and because large proportions may represent an additional step towards the
of their populations are heavily dependent on transformation of current agrifood systems that can
agriculture for their livelihoods (Wheeler and withstand better the pressures they are currently
von Braun, 2013). Levels of hunger in Africa are facing and will face, possibly to an even greater
much higher than in other regions (FAO, 2022). extent, in the future.

47
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Appendices
Appendix A

Gene editing sequence of a targeted protein, which would

in essence knock-out the protein and eliminate
Gene editing refers to using molecular tools to edit protein expression, or a genomic regulatory
the genome of a host cell at precise locations to region. SDN-2 utilizes a foreign donor DNA or RNA
make targeted changes. Gene editing can involve template to encode a precise edit around the DNA
foreign gene or genetic sequence incorporation, cut site. This donor template encodes homology
but foreign genes are not always incorporated with the endogenous genomic sequence and a
at the target site and they can be removed from desired edit, which gets incorporated into the cell’s
the final product. Some gene-edited products are own genome through DNA repair. However, the
analogous to those obtained by mutation breeding. generation of precise SDN-2 editing is inefficient
The advantage of gene editing is its precision over and would usually result in SDN-1 outcomes: DNA
other methods of genetic manipulation. insertions and deletions. SDN-3 also uses a foreign
donor DNA but relies on the insertion of this DNA
Principles of gene editing sequence into the cut site. Unlike SDN-2, which
typically confers small precise DNA changes, SDN-
Gene-editing approaches, such as mega nucleases, 3 can be a large DNA fragment insertion such as a
zinc finger nucleases (ZFNs), and TALENs, rely promoter and gene. Similarly to SDN-2, SDN-3 is
on intricate and specific protein-DNA interactions also inefficient and most outcomes are small DNA
to target protein effectors for desired DNA insertions or deletions. Newer precision genome
sequences. Although effective at targeting a editing technologies such as base editing and
specific site, it is difficult to rapidly and simply prime editing can enable precise genome edits
reprogramme targeting of protein domains to without the formation of a DNA double-strand DNA
new genomic sites of interest. The discovery and intermediate. This suggests the need for additional
engineering of clustered regularly interspaced short genome-edited categories in the future.
palindromic repeats (CRISPR) has simplified the
process (Doudna and Sternberg, 2017). Protein-based gene-editing systems

Gene editing relies upon two distinct processes. Mega nucleases, ZFNs and TALENs are biological
One, to be able to target any DNA sequence of tools that can be used for genome editing. Mega
interest in living cells, and two, to be able to edit the nucleases (also known as homing endonucleases)
DNA. The DNA of all eukaryotic systems is stored are large protein complexes that are programmed
securely in the nucleus. Therefore, to be able to to specifically recognize a particular DNA sequence
edit, a DNA-targeting protein module must be able (Kostriken et al., 1983; Jacquier and Dujon, 1985).
to enter the nucleus of a living cell, search through These proteins rely on a complex network of
the tightly packaged DNA and bind to a specific interactions between the protein and the targeted
targeting region. Subsequently, the genome editing DNA sequence.
machinery must perform a modification at that
targeted region of DNA. Endogenous cellular DNA Zinc finger proteins are small protein modules
replication and repair converts the change into a that can recognize a particular three DNA base
permanent editing event. sequence. A chain of zinc fingers can be fused
together to enable user-defined targeting of
Gene-editing technologies for use in agriculture the entire protein to a genomic DNA sequence.
have been categorized into three site-directed Researchers have fused these zinc finger proteins
nuclease methods, termed SDN-1, SDN-2, or SDN- with other proteins that can manipulate DNA.
3. The three methods share the common feature FokI is a bacterial restriction endonuclease found
of initiating genome editing through creation of a in nature that is composed of a DNA binding
DNA double-strand break (DSB) at a targeted site domain and a DNA cleaving domain. Researchers
in the genome of a living cell. SDN-1 relies on the have harnessed just the DNA cleavage domain
cell’s endogenous repair machinery to repair the and fused this with zinc-finger modules to permit
DSB non-specifically, which often results in the targeted cleavage of DNA. Such fusion complexes,
creation of DNA insertions or deletions around ZFNs, function in human, animal and plant cells
the cut site. These small DNA base additions or (Urnov et al., 2010).
subtractions can result in a frame-shift in the coding

64
Transcription activator-like (TAL) effectors are small DNA repair affecting outcomes
bacterial proteins found in plant pathogens that
bind to the DNA of plant host cells and engage Meganucleases, ZFNs, TALENs and Cas proteins
in infection events. Each individual TAL effector all result in the creation of a DNA DSB at a stretch
can bind to a particular DNA base (adenine, of DNA sequence in the genome of living cells
thymine, guanine, or cytosine). Similarly to ZFNs, that is specifically recognized and targeted for
researchers have fused FokI cleavage domains editing, either by a protein domain or a guide
to TALEs (transcription activator-like effectors) to RNA. The generation of a DSB marks a significant
generate TALE nucleases (TALENs), which are fully perturbation in a living cell’s growth condition.
protein-encoded programmable genome editing Therefore, on generating a DSB, the cell’s
technologies (Sander and Joung, 2014). endogenous DNA repair machinery will rapidly
recognize the break and seek to repair the break
CRISPR systems without error (West, 2003). If the break is not
repaired, the cell ultimately dies. The DNA repair
The discovery of clustered regularly interspaced machinery can result in an error in DNA repair,
short palindromic repeat (CRISPR) arrays which typically arises in the form of small DNA
originates from researchers seeking to uncover insertion or deletion (known as indels) at the cut
the function of this stretch of DNA array in the site (Deriano and Roth, 2013). This repair process
bacterial genome. CRISPR arrays encoded in a is known as non-homologous end joining (NHEJ)
bacterium’s own genome are transcribed to RNA or microhomology-mediated end joining (MMEJ).
and processed within the cell into individual short These random, small DNA indels surrounding a
stretches each of which is programmed to reflect target site may result in frame shifting the coding
a particular sequence. These short CRISPR RNAs sequence of a protein. This type of editing is known
then associate with Cas proteins, which program as a genetic knockout, in which the outcome of the
the Cas protein to recognize a DNA sequence genome editing event is the complete elimination
encoded by the RNA. The targeting sequence of a protein’s expression in a cell.
in the CRISPR RNA can be easily replaced and
programmed with a user-defined sequence and that Although powerful, gene editing to generate indels
this replacement completely alters and controls is limited to applications in which a user seeks
the genomic sequence a Cas protein targets (Jinek to knock out a protein. However, often there is a
et al., 2012; Gasiunas et al., 2012; Cong et al., desire to alter the coding sequence of a protein
2013). This is the first time in which the re-targeting rather than completely knock out its activity. In
of a protein complex can be easily dictated by such cases, there is a need to be able to generate
replacing a nucleic acid sequence, unlike previous precise genome editing events rather than rely on
approaches, which all required complex and spontaneous and random DNA repair. Homology
laborious protein engineering. It is also because directed repair (HDR) is another DNA repair process
of ease in programming that there is gene editing in which a cell’s endogenous DNA repair machinery
based on the CRISPR-Cas system. recruits a DNA donor template to use as a reference
for repairing a DNA cut (West, 2003). In this case,
Once the guide RNA is programmed to recognize a a user seeking to perform the desired genome edit
particular sequence of DNA, it enters the nucleus can encode the edit in a foreign donor template and
of a cell and can find the targeted sequence. co-deliver this template with a nuclease domain that
Upon recognition, the Cas protein unwinds the can perform a targeted cut on the DNA. Following
DNA double helix and base pairs its guide RNA the cell’s HDR repair machinery using this template
(gRNA) sequence with the complementary strand as a donor, the programmed edit on the donor can
of DNA while releasing the other strand of DNA be transferred into the cell’s own DNA sequence,
as a single-stranded DNA (ssDNA) R-loop region. thus resulting in a permanent editing alteration of
Following Cas binding, the protein complex uses the cell’s genome. Although programmable and
its nuclease domains to cut both strands of the precise, this type of editing event is rare and occurs
DNA, thus initiating the process of editing the DNA much less frequently than the NHEJ/MMEJ pathway
of a living cell. in which indels are produced surrounding the DNA
cut site (Deriano and Roth, 2013; Cong et al., 2013;
Shan et al., 2013; Voytas, 2013).

65
Appendix A

There is still a great need for gene-editing resulting in undesired editing outcomes such as
technologies that can efficiently change the indel mutations. Although CBEs and ABEs are
sequence of DNA in a programmable and extremely useful in creating CG-to-TA or AT-
predictable approach. The following two sections, to-GC base conversions respectively, there exist
namely base editing and prime editing, discuss many other types of genome edits, such as other
new technologies that address this limitation and base conversions and programmable insertions
can very precisely edit the DNA of living cells. and deletions, which require newer precision-
editing techniques. The next section, prime
Base editing editing, discusses a recently developed gene-
editing approach that addresses these remaining
Base editing relies on the target search and DNA limitations.
binding activity of Cas proteins. However, rather
than cutting both strands of the DNA, base editors Prime editing
are comprised of an additional DNA-modifying
protein element fused to the Cas protein. These Prime editing was developed recently to address
extra domains are deaminase proteins that can the unmet biotechnological need for realizing a
specifically perform a chemical transformation range of genome editing outcomes (Anzalone et al.,
known as a deamination reaction on single-stranded 2019). Prime editors fundamentally rely on a Cas
DNA. Because Cas proteins unwind the double helix protein to dictate a particular region of DNA in living
upon binding and expose a short single-strand DNA cells for editing. Prime editors are encoded with
segment, this area can serve as a substrate for the a foreign nucleic acid template. The prime editing
locally tethered deaminase protein, thus enabling a guide RNA (pegRNA) comprises an extension of
site-specific chemical modification of individual DNA the Cas protein guide RNA. On the pegRNA, a
bases on a single strand. primer binding site can be specifically encoded,
which is complementary to the released single-
The first class of base editors engineered are known stranded R-loop from the Cas protein nick, and a
as cytosine base editors (CBE) (Komor et al., 2016). template region encoding a particular desired DNA
CBEs utilize cytosine deaminases as key enzymes editing event.
in the editing protein. These enzymes can convert
cytosine bases specifically in single-stranded DNA In addition to the Cas protein, prime editors
into a uracil base. Following endogenous cellular comprise a reverse transcriptase protein domain,
repair, this uracil base intermediate is resolved into a which can use RNA as a template to extend DNA.
thymine base, ultimately resulting in a single Therefore, once the prime editor nicks one strand
CG-to-TA base edit. of DNA, it releases a single-stranded DNA primer
region, which is complementary to and can base
The second class of base editors are adenine base pair with the nearby pegRNA. This intermediate
editors (ABE) (Gaudelli et al., 2017). ABEs leverage is recognized by the fused reverse transcriptase,
the fact that a deamination chemical transformation thus initiating DNA polymerization directly on the
on adenine bases results in an intermediate, endogenous genome using the user-encoded
inosine, which is recognized by endogenous cellular RNA as a template. Following subsequent DNA
polymerases as guanine. However, unlike CBEs, replication and repair, the newly synthesized DNA
there is no naturally occurring deaminase enzyme sequence is permanently encoded into the living
that specifically recognizes adenine bases in single- cell’s genome. Since the type of genome edit
stranded DNA. Therefore, researchers established a desired can be directly encoded into the pegRNA,
directed protein evolution platform to evolve a new prime editing offers the ability to perform versatile
enzyme capable of performing this desired reaction edits with high efficiency and precision.
on DNA in living cells (Gaudelli et al., 2017; Richter
et al., 2020). Specificity

Both CBEs and ABEs can edit DNA precisely During the development and application of the
and efficiently. In contrast with Cas-mediated original ZFN and TALEN genome editing systems,
HDR editing of individual bases, these base scientists discovered that these editing tools
editors can edit desired base residues without sometimes have off-target effects, which refers to

66
events in which the editing system can sometimes studies note the possibility of altering specific
target genomic sites other than the targeted locus residues in the Cas protein to decrease the
in the genome of a cell (Kim et al., 2009; Mussolino propensity of Cas-dependent off-target editing (e.g.
et al., 2011). Off-target effects dictated by the Casini et al., 2018; Lee et al., 2018; Hu et al., 2018).
location and type of edit will affect the specificity, Furthermore, researchers have demonstrated a
which is critical for realizing the full potential of correlation between the mode of delivery vs. the
gene-editing systems in all applications. off-target potential of genome editing agents (e.g.
Liang et al., 2017; Zhang et al., 2018b; Rees et al.,
During the process of CRISPR-Cas editing, the 2017). The persistent expression of gene-editing
guide RNA forms a complex with a Cas protein, tools in living cells increases the proportion of off-
which activates the complex to scan through the target editing, which can be explained by the fact
genome to identify the targeted site of interest. that after the editing tool performs the desired edit,
If the Cas protein inadvertently binds to and edits any further expression can only result in undesired
other sites in the genome, not dictated by the editing outcomes (Rees et al., 2017). Therefore,
guide RNA sequence, these events are known as delivery approaches that limit the half-life of the
an off-target edit. editing protein in living cells can substantially
decrease off-target editing effects. These include
The off-target effects of gene-editing tools can efforts reliant on the transient expression of the
be largely divided into two categories based on editing reagent, especially when delivered as RNA
their fundamental mechanism. The first class is or protein complexes, because these get degraded
characterized as guide RNA-dependent off-target rapidly (Rees et al., 2017).
editing (Anzalone et al., 2020; Gao, 2021; Jeong,
Song and Bae, 2020). During the development and Researchers next evaluated whether Cas proteins
application of CRISPR-Cas systems for eukaryotic would randomly cut genomic DNA within the
genome editing, many studies found that Cas genome independently of the guiding role of
proteins can still bind to regions of DNA even when sgRNA, thereby causing random DNA breaks. The
there is a 1–2 base mismatch between the desired evaluation of off-target effects based on individual
target sequence and off-target binding. genome sequencing data in mice, cotton and rice
has successively found that the number of insertion
The second class is known as guide RNA- or deletion mutations in cells treated with CRISPR-
independent off-target editing, which encompasses Cas editing tools is not different when compared
changes in genomic locations other than the target with control groups treated without the Cas
location caused by overexpression of genome protein, therefore concluding that the CRISPR-Cas
editing agents, and that these locations do not system does not increase any genome-wide guide
resemble the desired on-target editing sequence RNA-independent off-target editing (Iyer et al.,
(Anzalone et al., 2020; Gao, 2021; Jeong, Song and 2018; Li et al., 2018; Tang et al., 2018; Willi et al.,
Bae, 2020). 2018). This demonstrates that Cas proteins only
edit at sites in which the guide RNA can bind to
During initial characterizations of CRISPR-Cas the double helix and that these editing tools do not
binding to a target site, experiments showed uncontrollably and spontaneously generate double-
that the extent of guide-dependent off-target strand breaks throughout the genome.
editing is related to the position and sequence
of mismatch sequences between the targeted Precision gene-editing tools such as base editors
sequence and off-target sequence. Extensive also face the need for thorough evaluation any
studies have developed approaches that are able guide-dependent and guide-independent off-target
to massively profile Cas protein-dependent off- editing. During the development of the cytosine
target editing based on the mismatch identities base editor, it was demonstrated that Cas protein
(Fu et al., 2013; Hsu et al., 2013; Pattanayak et al., off-target binding sites were also off-target sites for
2013). Furthermore, unbiased methods based on CBEs if a cytosine is positioned within the binding
isolating sites of Cas protein cleavage genome- region (Kim et al., 2017). However, initial evaluations
wide enable high-throughput profiling of a Cas of the adenine base editor found that ABEs are
protein’s editing precision. Through extensive much more precise and generate far less guide
protein engineering and evolution efforts, many

67
Appendix A

RNA-dependent off-target editing compared with from the base editing system, the off-target effects
Cas nuclease cleavage or CBEs (Liang et al., 2019). of the prime editing system can be divided into
two main categories, one of which is pegRNA-
Researchers began to evaluate guide-independent dependent off-target editing, which was low in
off-target editing of base editors using genome- cells possibly because of multiple distinct DNA
wide sequencing in mouse embryos and rice (Jin hybridization events required to enable active
et al., 2019). The initial studies all demonstrated prime editing outcomes (Anzalone et al., 2020).
that CBEs generated off-target editing events The three unique DNA hybridization events refer
sporadically throughout a cell’s genome, while to the principles governing prime editing require
ABEs were more specific and resulted in minimal the binding of the guide RNA sequence to the
guide-independent off-target editing. This effect targeted DNA strand, the binding of a primer
was further explained by the fact that the binding site to the nicked flap in the genomic DNA,
deaminase domain of base editors can react with and the complementation of newly edited DNA
single-stranded DNA regions in living cells, such with endogenous DNA sequences. Recently, a
as areas of active transcription or DNA replication. comprehensive evaluation of pegRNA-dependent
To decrease the propensity of off-target editing and pegRNA-independent off-target editing was
effects, variants of the deaminase domains were performed using rice as a model system (Jin
engineered to maintain high levels of precise et al., 2021). It was noted that prime editors are
on-target editing while minimizing any off-target extremely specific and precise in their editing
editing effects (Jin et al., 2020; Doman et al., 2020.; outcomes. Furthermore, there is no perturbation
Yu et al., 2020; Lee et al., 2020). on the cell’s endogenous state and there does
no significant perturbation to the cell’s overall
Prime editing systems were also thoroughly gene regulatory system (Jin et al., 2021). These
evaluated for their propensity to cause off-target properties suggest that prime editing is superior in
editing. Because the guide RNA used in the prime generating accurate, precise and safe gene-editing
editing system is a pegRNA, which is different events in living cells.

68
Appendix B.1a
Case study – Powdery mildew resistance

Powdery mildew is one of the most common durable resistance to powdery mildew disease.
plant pathogens worldwide. The yields of many Because bread wheat has a more complex genome
cereal crops, including barley, wheat and oats, than barley, the probability of generating powdery
are affected by powdery mildew infection. Some mildew resistance through natural variation and
horticultural crops are also susceptible to powdery mutation breeding is extremely low. Gene-editing
mildew, such as grapes, strawberries, cucumbers, technologies therefore represent the only realistic
tomatoes and peppers (Glawe, 2008). A recessive chance of rapidly obtaining powdery mildew
powdery mildew resistance gene (mlo, an allele of resistant bread wheat. Following this success,
the MLO locus) was first identified in barley over similar efforts were directed at tomatoes and
70 years ago and has been successfully used on grapes, with the rapid creation of new resistant
a commercial scale for decades, and continues to varieties (Nekrasov et al., 2017; Wan et al., 2020).
provide effective resistance (Büschges et al., 1997).
The resistance in barley was mutation induced. Although the initial bread wheat variety with three
Similar resistances have not been identified in knocked out copies of MLO exhibited durable
other cereal crops. However, the advent of genome powdery mildew resistance, the gene editing
editing technologies provides an opportunity resulted in some undesirable pleiotropic growth
for researchers to generate powdery mildew defects and the variety was low yielding. Recently
resistance directly in other species. however, researchers described an improved
gene-editing approach (Li et al., 2022). In total, four
Bread wheat has three distinct copies of the genetic perturbations mediated by CRISPR-Cas9
powdery mildew locus, which if knocked out using enabled rapid creation of new bread wheat varieties
gene-editing techniques can promote a similar exhibiting desired phenotypes. This work highlights
resistance effect as evident in barley. Initial studies the potential of gene editing to accelerate bread
in 2014 demonstrated that TALEN gene editing wheat breeding by directly performing targeted
was able to knock out all three copies of MLO edits in elite varieties without recourse to extensive
(Wang et al., 2014), conditioning broad-spectrum, and laborious crossing.

69
Appendix B.1b
Case study – PRRSV-resistant pigs

Porcine reproductive and respiratory syndrome on the surface of lung defence cells (macrophages)
(PRRS) is an endemic disease that severely affects critical for the PRRS virus to enter the lung cell and
domestic pigs. The disease triggers breathing cause an infection. Using the CRISPR-Cas9 system,
problems and deaths in young animals, increases the pig’s genome was modified at a single point,
susceptibility to secondary bacterial infection, stopping production of the section of the CD163
and can cause pregnant sows to lose their litters. protein required for PRRSV to cause an infection.
The causal agent is the porcine reproductive and The effectiveness was tested by placing gene-
respiratory syndrome virus (PRRSV). The syndrome edited pigs in pens with control pigs (animals that
was first identified in the United States of America still produced CD163) and challenging all animals
in 1987, and the virus was detected in Netherlands with a standardized dose of PRRSV. The control
in 1991 (OIE, 2021). pigs got the disease and showed clinical and tissue
level signs of the virus associated with acute PRRS
Unfortunately, vaccines have not successfully infection. None of the gene-edited/CD163 “knock-
stopped the spread of PRRSV, which is endemic out” pigs showed signs of illness, and tissue
in most pig-producing countries and causes sampling demonstrated that they were free of
considerable economic damage (The Roslin the virus. Even the foetus of knockout dams was
Institute, 2021). PRRSV shows complex interactions protected from PRRSV, showing that resistance is
with the immune system and a high mutation rate, heritable (Thompson and Benjamin, 2021).
making the development and implementation of
control strategies a significant challenge (Montaner- The research on gene-edited/CD163 pigs continues
Tarbes et al., 2019). The virus results in annual and could impact the fight against the virus. The
losses in excess of £1.3 billion to the European pig Roslin Institute also produced pigs resistant to
industry and over £500 million to the United States PRRSV. A recent study shows that their gene-
of America pig industry (The Roslin Institute, 2020). edited pigs are healthy under standard husbandry
The direct and indirect impacts of PRRS make it the conditions and maintain the biological function of
most economically significant pig disease in North the CD163 protein while being resistant to PRRSV
America, Europe and Asia (Whitworth et al., 2016). infection (Burkard et al., 2018). However, it will
Even 30 years after the PRRSV was first detected in likely take several more years before gene-edited/
the United States of America, there are no effective CD163 pigs can be used in commercial operations.
vaccines or drugs to address the problem. Numerous additional hurdles will have to be
overcome, and the technology must pass through
However, in 2016, animal science researchers appropriate regulatory channels in the United
at the University of Missouri and Kansas State States of America, China and other countries.
University made progress in the fight against The case of PRRSV-resistant pigs emphasizes the
PRRS using the CRISPR-Cas9 system. Pigs were potential of gene editing for achieving disease
produced that are resistant to infection by PRRSV. resistance in animals in cases where progress has
Pigs have the CD163 gene that encodes a protein been slow and costly.

70
Appendix B.1c
Case study – CRISPR-Cas9 and fish

Sea bream (madai) accounts for ten percent of gain. Gene-edited fish are about twice as heavy at
the total value of Japanese aquaculture and is the same growth stage as non-edited fish.
therefore very important. In 2021 a gene-edited sea
bream was approved for commercial use in Japan, In Japan, gene-edited products do not have to
representing the first gene-edited animal food. adhere to the same regulations as genetically
CRISPR-Cas9 was used to knock out the gene for modified products that contain foreign genes.
myostatin production (Pm-mstn), which normally
suppresses muscle growth. The resulting fish has CRISPR-Cas9 has also been used to gene edit
a proportionally larger edible part, 20–60 percent other fish species. Baloch et al. (2019) worked
more edible yield, and a 14 percent improved feed with sturgeon, a critically endangered fish species
utilization efficiency. Ohama et al. (2020) reported due to overfishing for caviar and interference in
a 16 percent increase in skeletal muscle in fish their natural habitats. With life spans exceeding
that had had the Pm-mstn gene knocked out. It 100 years and sexual maturity only being reached
was suggested that gene editing can speed up fish at 20–25 years, they are difficult to work with.
breeding considerably. However, the related sterlet reproduces quickly and
can function as a surrogate for sturgeons. All germ
A second gene-edited fish species was developed cells in developing embryos derive from primordial
in 2021 in Japan and approved for commercial germ cells. The dnd1 gene conditions formation
production. A tiger puffer (22-seiki fugu) had four and migration of primordial germ cells. Knocked-
leptin receptor genes knocked out with CRISPR. out embryos devoid of primordial germ cells were
Those genes control appetite and when removed successfully used as sterile hosts for surrogate
result in a fish with enhanced appetite and weight sturgeon production.

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