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Will gene-edited and other GM crops fail sustainable food systems?

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Abstract

Abstract: The role of GM crops in supporting sustainable food systems is an ongoing controversy. Underlying this controversy, I will argue, are radically different definitions of agricultural sustainability. One is a narrow definition, based on amelioration of current unsustainable practices, such as the use of synthetic pesticides in agriculture. The other is a broad definition, based on the long-term promotion of human and ecosystem health. In order to assess the sustainability impacts of GM crops, this review first provides (i) a brief summary of the sustainability impacts of herbicide tolerant and Bt pesticidal GM crops and (ii) an overview of GM plant breeding, with a focus on the problem of unintended traits (UTs) in commercial GM crops. These UTs, I argue, are a major yet underappreciated contributor to their lack of sustainability. The review asks next whether new and complex GM traits such as biofortification, or the subset of new GM techniques (nGMs) called gene editing, can benefit sustainable agriculture. Golden Rice provides a case study of unintended traits in GM crops carrying complex traits. Given the failings of Golden Rice, caused in part by UTs, a key question is whether gene editing techniques are more precise and their outcomes more predictable. To address this, the review summarizes the known unintended effects of gene editing and their potential for introducing UTs. I conclude that, despite the promise of new traits and techniques, GM crops, including gene-edited crops, are unlikely to meet either the narrow agronomic, or the broader social and environmental, requirements of sustainable agriculture. The review ends with a discussion of how plant breeders can best support and promote sustainable agriculture, and thus help create sustainable food systems.
Rethinking Food and Agriculture. https://doi.org/10.1016/B978-0-12-816410-5.00013-X
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13
Will gene-edited and other
GM crops fail sustainable food
systems?
Allison K Wilson
The Bioscience Resource Project, Ithaca, NY, United States
13.1 Introduction
Conventional agriculturea is a major driver of climate change (Foley etal., 2005).
Its intensive use of natural resources, synthetic fertilizers, and pesticides further de-
grades air, soil, and water quality and causes large-scale biodiversity loss (Foley etal.,
2005; Horrigan, Lawrence, & Walker, 2002; Kremen & Merenlender, 2018; Pretty
etal., 2000; Sánchez-Bayo & Wyckhuys, 2019; Tilman, 1998). Such assessments have
driven wide agreement that conventional agriculture must become more sustainable. A
transition to sustainable agriculture is also an essential component of sustainable food
systems. However, there are very different views on how to improve the sustainability
of agriculture while meeting food security goals (Godfray & Garnett, 2014; Holt-
Giménez & Altieri, 2013; Kremen & Merenlender, 2018; McMichael & Schneider,
2011; Mercer, Perales, & Wainwright, 2012; Perfecto & Vandermeer, 2010; Zaidi
etal., 2019).
The sustainability impact of biotech crops remains a key area of controversy. For
good or ill, this impact is likely substantial. According to the most commonly cited
source, in 2017 genetically modified (GM) crops were planted on 189.8 million ha
in 24 countries (ISAAA, 2017b). The majority of GM crops grown commercially are
either herbicide tolerant (HT crops) or they produce GM pesticides originating from
the bacterium Bacillus thuringiensis, an insect pathogen (Bt crops). The main HT and/
or Bt commodity crops grown globally are soybean (94.1 million ha), maize (59.7
million ha), cotton (24.1 million ha), and canola (10.2 million ha) (ISAAA, 2017).
The narrow view of sustainability sees the role of agriculture as providing food
security. It further equates food security with high yields (Latham, this volume). To
obtain its yields, conventional agriculture combines large-scale monoculture crop-
ping systems with the extensive use of off-farm inputs (e.g., hybrid seeds, agro-
chemicals, water, and fuel). Labor is replaced with mechanization. Soil fertility and
pests are managed with synthetic fertilizers, insecticides, fungicides, and herbicides.
a Conventional (also called industrial) agriculture includes input-heavy large-scale monoculture commodity
cropping systems and confined animal feeding operations.
b ISAAA (International Service for the Acquisition of Agri-biotech Applications) is funded by both govern-
ment organizations and the biotech industry to promote the uptake of agricultural biotechnology products,
including GM crops.
248 Rethinking Food and Agriculture
Hybrid seeds must be purchased each year. Consequently, increased sustainability is
framed as increased monocrop yield/acre and/or a concomitant decrease in the use off-
farm inputs. Biotechnology, specifically the use of GM crops (also called genetically
engineered or bioengineered, e.g., transgenic, cisgenic, RNAi, or gene-edited crops), is
often seen as necessary to achieve these sustainability goals (Ammann, 2005; Dibden,
Gibbs, & Cocklin, 2013; Godfray & Garnett, 2014; Pretty, 2001). In this paradigm it is
argued that, by increasing yields, GM crops can also benefit smallholder farming and
sustainable agricultural systems (Holt-Giménez & Altieri, 2013; Mercer etal., 2012;
Shelton, Hossain, Paranjape, & Azad, 2018).
The broad view of sustainability, in contrast, sees agriculture as intrinsically mul-
tifunctional, having diverse and interconnected environmental and social impacts
(McIntyre etal., 2009). To be sustainable therefore agriculture must (1) provide food
security and healthy diets and (2) support rural livelihoods and culture, while also
reducing poverty and inequality and (3) increase biodiversity and environmental
health, placing a strong emphasis on lessening climate change (Horrigan etal., 2002;
Kremen & Merenlender, 2018; McMichael & Schneider, 2011). Within this paradigm,
technologies and practices that support low-input small-scale agriculture, food and
seed sovereignty, and local food systems are considered essential (Adhikari, 2014;
Holt-Giménez & Altieri, 2013; Kremen & Merenlender, 2018; McIntyre etal., 2009).
However, there are many different possible sustainable farming systems. These can
include organic, agroecological, agroforestry, and traditional systems. What they have
in common is the use of biodiversity to achieve multiple agricultural, environmen-
tal, and societal goals (Altieri, 1999; Thrupp, 2000; Wickson, Binimelis, & Herrero,
2016). For example, both soil health and pests are managed by increasing on-farm
biodiversity via practices that include multispecies crop rotation, cover cropping,
and intercropping, as well as push/pull, SRIc and no-till techniques, and the incor-
poration of livestock and trees (Anderson, 2015; Hailu, Niassy, Zeyaur, Ochatum, &
Subramanian, 2018; Kremen & Miles, 2012; Midega, Pittchar, Pickett, Hailu, & Khan,
2018; Pretty, 2001; Thakur, Uphoff, & Stoop, 2016; Zhang, Postma, York, & Lynch,
2014). Such techniques can drastically reduce the need for off-farm inputs, with the
goal of eliminating them entirely (Nicholls, Altieri, & Vazquez, 2016). Within this
broad agroecological paradigm of sustainability, GM crops are often seen as incom-
patible (Adhikari, 2014; Altieri, 2005; Barker, 2014; Fischer, 2016; Garibaldi etal.,
2017; Kesavan & Swaminathan, 2018; Kremen & Miles, 2012; McIntyre etal., 2009;
Pengue, 2005; Schütte etal., 2017; Wickson etal., 2016).
The availability of a wide diversity of crops and cultivars is an integral component
of sustainable agriculture. Historically, farmer seed saving and selection created an
enormous diversity of crop varieties with widely varying properties and adaptations
(Villa, Maxted, Scholten, & Ford-Lloyd, 2005). The intention of plant breeding is
to contribute to this diversity by producing crops with beneficial new trait combina-
tions or characteristics. Conventional plant breeding achieves this via genetic crossing
of sexually compatible plants, and the selection of offspring with the desired traits.
c SRI stands for system of rice intensification, a set of practices that can reduce the use of water, seeds, and
other inputs, while increasing soil biodiversity and improving yields.
Will gene-edited and other GM crops fail sustainable food systems? 249
Occasionally, conventional plant breeders use intentional mutagenesis, somaclonal
mutation, or wide crosses to introduce novel traits (Wilson, Latham, & Steinbrecher,
2004). GM crop developers, in contrast, use a combination of lab-based techniques
(e.g., recombinant DNA [rDNA] technology, tissue culture, and plant transformation
[e.g., Agrobacterium infection or particle bombardment]) to introduce specific rDNA
sequences, specifying novel traits, into crop plants (Barampuram & Zhang, 2011). GM
techniques expand the range of traits available by conferring the ability to combine,
alter, and transfer DNA from any organism (e.g., viruses, bacteria, fungi, mammals,
nonfood plants) into a crop’s genome (Wickson etal., 2016). A suite of new GM tech-
niques (nGMs), including a variety of “gene editing” systems, has been developed for
use in plants (Eckerstorfer, Heissenberger, Reichenbecher, Steinbrecher, & Waßmann,
2019). In contrast to standard GM techniques, gene editing techniques can target DNA
integration and/or other modifications to specific regions of the genome (Fichtner,
Castellanos, & Ülker, 2014). The claimed benefits of GM and nGM technologies are
their ability (1) to transfer or alter specific sequences of DNA and (2) to introduce
novel DNA modifications and traits that cannot be introduced via conventional plant
breeding.
13.2 Impacts of HT and
Bt
crops
In theory, HTd crops and Bte crops were intended to promote sustainable agriculture
by (1) reducing overall pesticide use and (2) substituting safer pesticides (e.g., plant-
produced Bt toxins or glyphosate herbicides) for more harmful ones (Ammann, 2005;
Andow, 2010; Koch etal., 2015). HT crops have also been claimed to improve sustain-
ability by facilitating the uptake of no-till agriculture.
In practice, however, the widespread use of Bt and HT crops has led to the problem-
atic development of pest resistance, “superweeds,” and secondary pests (Benbrook,
2018; Bonny, 2016; Carrière etal., 2016; García etal., 2019; Gould, Brown, & Kuzma,
2018; Kilman, 2010; Kranthi, 2016; Mortensen, Egan, Maxwell, Ryan, & Smith,
2012; Stone & Flachs, 2018; Tabashnik & Carrière, 2017). In response to these prob-
lems, farmers increased both insecticide and herbicide use. Some also increased tillage
and other mechanical methods of weed control (Bonny, 2016; Green, 2014). The seed
industry response has been to add multiple Bt pesticide and/or HT traits (stacked and
d HT GM crops have one or more transgene(s) that specify a protein that either resists or detoxifies a specific
herbicide. For example, the herbicide glyphosate targets an essential plant enzyme, 5-enolpyruvoylshi-
kimate-3-phosphate synthase (epsps), to cause lethality. Roundup Ready (RR) glyphosate-tolerant GM
crops have a transgene that specifies a glyphosate tolerant version of the epsps enzyme.
e Bt crops have one or more recombinant cry transgenes (e.g., cry1Ab, cry3A) inserted into their genome,
each transgene specifying a different GM Bt toxin (Latham, Love, & Hilbeck, 2017). Plant-produced
Bt toxins are derived from the natural toxins produced by the insect gut pathogen Bacillus thuringiensis
(Sanchis, 2011). Different classes of Bt toxins are considered lethal to different orders of insects, and are
used to target different plant pests (Carrière, Fabrick, & Tabashnik, 2016). For example, B. thuringiensis
Cry1 toxins are thought to specifically target Lepidoptera (e.g., corn borers and cotton bollworms), while
Cry3 toxins are believed to specifically target Coleoptera (e.g., corn rootworm, Colorado potato beetle).
250 Rethinking Food and Agriculture
pyramided traitsf) to each variety, and to develop new plant-produced pesticides (e.g.,
VIP protein toxins and RNAi-based insecticides) (Bøhn & Lövei, 2017; Carrière etal.,
2016; Chakroun, Banyuls, Bel, Escriche, & Ferré, 2016; Gould etal., 2018).
In addition, the introduction of Bt and HT crops and their attendant pesticides has
encouraged a variety of changes to farmer practice that themselves have had highly
detrimental environmental impacts. First, the adoption of Bt and HT crops has un-
dermined the use of integrated pest management (Gray, 2010) and sustainable tech-
niques. They do so by substituting GM crop-produced and chemical pesticides for
pesticide-free control measures that include tillage, short season crops, cover crops,
crop rotation, and biological controls (Brainard, Haramoto, Williams, & Mirsky,
2013; Gutierrez, Ponti, Herren, Baumgärtner, & Kenmore, 2015; Kesavan &
Malarvannan, 2010; LaCanne & Lundgren, 2018; Lang, Oehen, Ross, Bieri, &
Steinbrich, 2015; Schütte etal., 2017; Stone & Flachs, 2018; Tooker, 2015). Second,
growing Bt crops (a decision made before actual insect pressures are known) ex-
poses the landscape, and consumers, to pesticide whether or not the targeted pest is
a threat, and whether or not Bt toxins provide effective protection. Wide uptake of
Bt crops is thus prophylactic pesticide use (Douglas & Tooker, 2015; Gray, 2010;
Stone & Flachs, 2018; Tooker, 2015). Finally, HT crops have decreased biodiver-
sity by encouraging simplified crop rotations and/or farming systems. They have
also permitted unrestricted spraying of broad-spectrum herbicides throughout the
growing season, further exacerbating biodiversity losses (Schreiner, 2009; Schütte
etal., 2017). As another consequence, HT soybeans on the US market have a high
level of glyphosate contamination (Bøhn etal., 2014).
Thus Bt and HT traits have exacerbated and expanded the pesticide treadmill (Altieri,
2000; Binimelis, Pengue, & Monterroso, 2009; Douglas & Tooker, 2015; Mortensen
etal., 2012; Pengue, 2005; Stone & Flachs, 2018). The resulting “technology-
facilitated pesticide treadmill” is described by Douglas and Tooker (2015):
Neonicotinoid seed treatments may also have “tagged along” with other technologies
that were attractive to farmers. They are usually one component of larger packages,
that, for instance in maize, can include germplasm (i.e., crop variety), up to eight
transgenes, and up to six or more different seed treatments (fungicides, nematicides,
and insecticides).
These well-documented outcomes indicate the adoption of HT and Bt crops is lead-
ing to dramatic increases in pesticide use over time, including the use of pesticides
known to be extremely toxic such as neonicotinoids, glufosinate, 2,4-d, and dicamba
(Douglas & Tooker, 2015; Mortensen etal., 2012; Schütte etal., 2017; Tooker, 2015).
Increased herbicide use with HT crops has been repeatedly demonstrated in the sci-
entific literature (Schütte etal., 2017). However, some authors claim that Bt crops
can reduce pesticide use (e.g., Klümper & Qaim, 2014; Naranjo, 2009). Short-term
f Stacked resistance traits are defined as multiple transgenes specifying tolerance to more than one herbi-
cide (e.g., glyphosate, dicamba, and 2,4-d) and/or to more than one target pest (e.g., corn root worm and
corn borer). Pyramided traits have more than one transgene targeting the same pest (e.g., Cry1Ab + Vip3A
to target Lepidoptera).
Will gene-edited and other GM crops fail sustainable food systems? 251
studies (e.g., before resistance develops), or failure to quantify the amount of plant-
produced Bt toxin(s) and/or seed coat insecticides, can account for these discrepan-
cies (Benbrook, 2012; Douglas, 2016). When applied pesticides, GM crop-produced
insecticides (e.g., Benbrook, 2012; Clark, Phillips, & Coats, 2005; Nguyen & Jehle,
2007; Saxena, Stewart, Altosaar, Shu, & Stotzky, 2004; U.S. Environmental Protection
Agency, 2010; van der Hoeven, 2014), and seed coat pesticides are taken fully into ac-
count, both Bt and HT crops increase pesticide use in farming systems (e.g., Benbrook,
2012; Bøhn & Lövei, 2017; Bonny, 2016; Capellesso, Cazella, Schmitt Filho, Farley, &
Martins, 2016; Douglas & Tooker, 2015; Heinemann, Massaro, Coray, Agapito-
Tenfen, & Wen, 2014; Kranthi, 2016; Perry, Ciliberto, Hennessy, & Moschini, 2016;
Yang, Iles, Yan, & Jolliffe, 2005).
13.2.1 Toxicity of GM crop-associated pesticides
Developers and US regulators of GM crops claim that Bt toxins and glyphosate
are low-toxicity pesticides (Koch etal., 2015; Williams, Kroes, & Munro, 2000).
However, for Bt crops, there is an ever-growing body of evidence showing Bt toxins
and Bt plants have harmful off-target effects, including toward mammals, beneficial
insects, and aquatic invertebrates (Andreassen etal., 2015; Hilbeck & Schmidt, 2006;
Latham etal., 2017; Paula etal., 2014; Venter & Bøhn, 2016). Many researchers have
pointed out the need for further biosafety research, in particular in planta studies and
research on the sublethal and long-term effects of exposure to Bt crops (e.g., Andow,
2010; Arpaia etal., 2017; Hilbeck & Otto, 2015; Latham etal., 2017; Sanchis, 2011;
Wolfenbarger, Naranjo, Lundgren, Bitzer, & Watrud, 2008). Similar concerns apply to
glyphosate-based herbicides. For example, glyphosate and/or its formulations affect
the composition of soil and gut microbiota and have negative effects on earthworms,
beneficial insects, and aquatic organisms (Schütte etal., 2017; Sharma, Jha, & Reddy,
2018). They are also linked to cancer and chronic kidney disease in humans (e.g.,
Jayasumana, Gunatilake, & Senanayake, 2014; McHenry, 2018; Myers etal., 2016).
Due to the large body of evidence documenting their harmful off-target impacts, cou-
pled with significant research gaps, there is no scientific consensus that Bt toxins and
glyphosate-based herbicides are low-toxicity pesticides (Ardekani & Shirzad, 2019;
Hilbeck etal., 2015; Krimsky, 2015).
13.3 Unintended traits in GM crops
Regardless of the intended trait, GM technology is frequently acclaimed for its preci-
sion. In particular, the ability to introduce novel traits without the problem of “yield
drag,” a problem that can complicate conventional plant breeding (Gepts, 2002). Yet,
despite these claims, reports of unexpected and harmful unintended traits (UTs) in GM
crops periodically surface in the media. For example, in 2012 various news outlets,
including the Wall Street Journal, reported that the stalks of GM corn and soy were
much tougher than those of conventional crops (Tita, 2012). The tougher GM stalks
puncture tractor tires. This unexpected trait has both economic and environmental
252 Rethinking Food and Agriculture
costs, as farmers are forced to buy new and expensive reinforced tractor tires and/
or replace tires more frequently. Like most such reports, the “tough stubble” trait has
not been fully followed up or acknowledged in the scientific literature. Yet, it raises
a host of important and neglected questions: (1) How precise and predictable is GM
technology? (2) Do developers and regulators prevent GM crops with harmful UTs
from reaching the market? (3) Are UTs an underappreciated barrier to sustainability?
A UT, sometimes called an unintended effect, is defined here as any significant dif-
ference, other than the intended GM trait, between a GM crop compared to a non-GM
isogenic line. UTs thus include, for example, statistically significant differences in
characters such as seed germination, weed suppression, pest resistance, drought toler-
ance, height, yield, and flowering time. UTs further include compositional differences
in nutrients, toxins, and other biochemicals. Such UTs are often revealed by transcrip-
tomic, proteomic, and metabolomic profiling studies (Cellini etal., 2004). Several
reviewers have collected examples of a wide variety of UTs recorded in the scientific
literature (Cellini etal., 2004; Haslberger, 2003; Kuiper, Kok, & Engel, 2003; Nature
Institute, 2019; Ricroch, Bergé, & Kuntz, 2011). Nevertheless, the number of docu-
mented examples is much greater than those already collected, precluding a compre-
hensive review.
13.3.1 Precision and predictability
If GM technology was precise and predictable, biotechnologists would only need to
create one GM plant, and this would be identical to the parent plant except for the
intended new trait. However, biotechnologists instead produce many hundreds or even
thousands of initial transformants.g For example, to identify a Roundup Ready (RR)
wheat event for commercialization, Hu etal. (2003) used either Agrobacterium or
the gene gun to introduce rDNA into over 98,000 plant tissue fragments. At the same
time they tested a number of different transgenes, since it was not clear which would
be the most effective in wheat. From their initial populations they selected over 1300
glyphosate-tolerant plants for further development, discarding the rest. Subsequent
rounds of selection assessed Roundup resistance and basic agronomic performance.
After four generations of such selection, six suitable events remained. Finally, after
3 years of “large-scale field trials,” one event was selected for commercialization and
submitted to the US Department of Agriculture (USDA) for approval. The petition for
deregulation of this event was subsequently withdrawn.
Research on large populations of initial transformants, created for the develop-
ment of Bt rice (Shu etal., 2002), Bt, or blight-resistant potato (Davidson etal., 2004;
Felcher, Douches, Kirk, Hammerschmidt, & Li, 2003), virus-resistant tobacco (Xu,
Collins, Hunt, & Nielsen, 1999), and virus-resistant barley (Bregitzer, Halbert, &
Lemaux, 1998), suggest similar problems for other GM crops and traits. Defects in ba-
sic agronomic traits such as yield, height, stem, and leaf morphology are frequent in re-
generated GM plants, and many initial transformants exhibit multiple UTs. Even when
only a few (from 2 to 22) traits are assessed, the proportion of initial transformants
g A transformant is a cell or an organism, such as a plant, into which foreign DNA has been introduced.
Will gene-edited and other GM crops fail sustainable food systems? 253
with UTs usually ranges between 20% and almost 100% (e.g., Bregitzer etal., 1998;
Dale & McPartlan, 1992; Davidson etal., 2004; Felcher etal., 2003; Hoekema,
Huisman, Molendijk, van den Elzen, & Cornelissen, 1989; Kumar, Rakow, &
Downey, 1998; Shu etal., 2002; Vickers, Grof, Bonnett, Jackson, & Morgan, 2005).
Later in GM crop development, diverse UTs are still frequently identified, even
after multiple rounds of selection. To take rice as a sample crop, decreased yield,
seed size, or vigor have all been reported for different Bt rice lines (e.g., Bashir etal.,
2004; Chen, Snow, Wang, & Lu, 2006; Jiang etal., 2018; Shu etal., 2002; Tu etal.,
2000; Wang etal., 2012; Wei-xiang, Qing-fu, Hang, Xue-jun, & Wen-ming, 2004;
Wu, Shu, Wang, Cui, & Xia, 2002), as have alterations to grain and straw quality (e.g.,
Bashir etal., 2004; Li etal., 2008; Wei-xiang etal., 2004; Wu etal., 2002). As well,
height, yield, and developmental UTs have been documented for glufosinate-tolerant
rice lines (Oard etal., 1996).
Additional examples of UTs are collected in Tables 13.1 and 13.2 of this review.
These, combined with examples collected by other reviewers, confirm that UTs are
not limited to any particular GM technique, trait, or plant species (Cellini etal., 2004;
Haslberger, 2003; Kuiper etal., 2003; Nature Institute, 2019; Ricroch etal., 2011).
13.3.2 UTs in commercial GM crops
Commercial GM crops are considered “the best of the best” that GM plant breed-
ing can offer. They undergo years of selection and development prior to “rigorous
compositional, nutritional, and safety evaluations” and, in some cases, environmental
risk assessments (Larkin & Harrigan, 2007). Finally, most GM crops currently grown
have undergone some form of regulatory process before their commercial release or
import was permitted (Davison, 2010; Pelletier, 2005). Nevertheless, Table13.1 pro-
vides examples of some of the many UTs that have been identified in commercial
GM crops. These UTs are documented in peer-reviewed papers and/or the petition
submitted to USDA/APHIS (U.S. Department of Agriculture/Animal and Plant Health
Inspection Service) to deregulate a particular crop or event in the United States. The
examples given in Table13.1 have been selected because they have implications for
sustainability.
Important conclusions can be drawn from Table13.1. First, it is not difficult to find
examples of commercial crops with UTs. In fact, many commercial GM crops have
multiple UTs. UTs documented for Mon810 maize, for example, include numerous
compositional differences (including increased lignin and the presence of an allergen),
increased moisture content, and negative impacts on beneficial soil organisms. Second,
UTs have different origins. Some, such as the increased lignin levels associated with
cry1Ab Bt maize, are likely pleiotropic effects of the transgene (i.e., the trait itself),
as they are seen with many independent cry1Ab events. Others, such as the loss of
resistance to root knot nematode in Bt Paymaster cotton, are event specific and likely
due to mutational damage at or near the transgene insertion site (Colyer etal., 2000).
Third, many UTs commonly documented in commercial GM crops have had un-
equivocal negative impacts on sustainability. For example, high moisture content,
as documented for MON810 and Bt11 maize, requires added energy during drying
GM crop
Transgene event
(transgene namea,b) Intended trait Unintended traits compared to non-GM parent or isogenic line (references)
Bt maize Event Mon810
(cry1Ab)
Lepidopteran
insect resistant
(pesticidal)
Increased lignin in stem (Flores, Saxena, & Stotzky, 2005; Poerschmann, Gathmann, Augustin,
Langer, & Górecki, 2005; Saxena & Stotzky, 2001)
Altered sugar content, osmolytes, branched amino acids, and proteins (including truncated pro-
teins and the presence of an allergen) in kernels (Barros etal., 2010; Manetti etal., 2006; Zolla,
Rinalducci, Antonioli, & Righetti, 2008)
Decreased protozoan and nematode numbers, and drier rhizosphere soils (Griffiths etal., 2005;
Höss etal., 2008)
Increased aphid susceptibility (Faria, Wäckers, Pritchard, Barrett, & Turlings, 2007) and thrip
numbers (Bourguet etal., 2002)
Delay in seed and plant maturation (La Paz, Pla, Centeno, Vicient, & Puigdomènech, 2014)
Higher moisture content in whole plant and grain at harvest (Ma & Subedi, 2005)
Delayed decomposition of Mon810 maize plant residues (Flores etal., 2005; Stotzky, 2004)
Bt maize Event Bt11
(cry1Ab)
Lepidopteran
insect resistant
(pesticidal)
Increased lignin in stem (Flores etal., 2005; Saxena & Stotzky, 2001)
Increased aphid susceptibility (Faria etal., 2007)
Higher moisture content in the whole plant and grain at harvest (Ma & Subedi, 2005)
Detrimental impacts on corn root colonization by beneficial mycorrhizal fungi (Castaldini etal.,
2005)
Bt maize Event 176 (cry1Ab) Lepidopteran
insect resistant
(pesticidal)
Increased lignin in stem (Poerschmann etal., 2005; Saxena & Stotzky, 2001)
Increased aphid susceptibility (Faria etal., 2007)
Detrimental impacts on corn root colonization by beneficial mycorrhizal fungi (Castaldini etal.,
2005)
Table13.1 Examples of unintended traits in commercial HT, Bt, or virus-resistant GM crops.
Roundup
Ready maize
Event NK603 (cp4
epsps)
Resistant to
glyphosate
herbicide
Decreased Υ-tocopherol and inositol; increases in potentially toxic polyamines, e.g., N-acetyl-
cadaverine (2.9-fold), N-acetylputrescine (1.8-fold), putrescine (2.7-fold), and cadaverine (28-
fold) in kernel (Barros etal., 2010; Mesnage etal., 2016)
Evidence of kidney and liver toxicity (Fagan, Traavik, & Bøhn, 2015)
Unintended proteomic and plant defense-related phytohormone differences in leaves (Benevenuto
etal., 2017)
Statistically significant differences for ear height and days to 50% silking (USDA/APHIS petition
00-011-01p)
Average maize yield for epsps glyphosate-tolerant GM maize varieties (such as NK603) de-
creased by 5.98 bushels per acre compared to conventional varieties (Shi, Chavas, & Lauer, 2013)
Roundup
Ready (RR1)
soybean
Event 40–3-2 (cp4
epsps)
Resistant to
glyphosate
herbicide
Yield decrease of 7%–11% (Gordon, 2007; Nelson, Renner, & Hammerschmidt, 2002; Elmore
etal., 2001; Benbrook, 1999; USDA/APHIS Petition P93–258-01)
Note: grown extensively in major soy producing countries such as the United States, Brazil, and
Argentina (e.g., over 93% of the US soybean crop is RR HT soy) (Oliveira & Hecht, 2016)
Genuity
Roundup
Ready
2 Yield
(RR2Y)
soybean
Event MON-
89788-1 (cp4 epsps)
Resistant to
glyphosate
herbicide
5% decrease in height (USDA/APHIS Petition 06-SB-167U; Horak etal., 2015)
RR1 and RR2Y have similar yields (Mason, Walters, Galusha, Wilson, & Kmail, 2017)
Virus-
resistant
squash
Event CZW-3
(three transgenes
specifying coat
proteins from
CMV, ZYMV, and
WMV2)
Resistant to
three viruses
affecting
cucurbits
Beta-carotene decreased to 1.5%, iron decreased to 87%, and fat to 50%, of control levels
(Table V, USDA/APHIS Petition no. 95-352-01p)
Vitamin A levels increased twofold and sodium increased fourfold, compared to control lines
(Table V, USDA/APHIS Petition no. 95-352-01p)
Other unintended traits include differences in floral traits and altered bee visits compared to an
isogenic line (Prendeville & Pilson, 2009)
Bt potato
Atlantic
NewLeaf
Atlantic NewLeaf
Clone 6 (cry3A)
Coleopteran
insect resistant
(pesticidal)
Loss of resistance to golden nematode, a key trait present in its non-GM parent plant
(Brodie, 2003; Brodie & Mai, 1989)
Continued
Table13.1 Continued
Bt cotton
Paymaster
Event 15560BG
(cry1Ac)
Lepidopteran
insect resistant
(pesticidal)
Loss of resistance to root knot nematode (Colyer, Kirkpatrick, Caldwell, & Vernon, 2000)
Bollgard
Bt cotton,
INGARD
Event: N/A
(cry1Ac)
Lepidopteran
insect resistant
(pesticidal)
Several varieties showed increased susceptibility to Fusarium fungal disease (Kochman etal.,
2000)
Chinese Bt
cotton
Event: N/A
(cry1Ac)
Lepidopteran
insect resistant
(pesticidal)
Two varieties had decreased resistance to Fusarium oxysporum fungal disease compared to
controls (Li etal., 2009)
Altered composition of root exudates (Li etal., 2009)
Bt cotton Event GK97 (N/A) Lepidopteran
insect resistant
(pesticidal)
Quantitative and qualitative differences in volatiles (Yan etal., 2004)
Roundup
Ready
oilseed rape
Brassica napus cv.
Quest
Event: N/A (cp4
epsps)
Resistant to
glyphosate
herbicide
Altered diversity of root-endophytic bacteria (Siciliano & Germida, 1999; Siciliano, Theoret,
De Freitas, Hucl, & Germida, 1998)
HT winter
rape
Events: N/A
Two cultivars:
Falcon pat (pat) and
cultivar ArtusLL
(N/A)
Resistant to
glufosinate
herbicide
Altered flowering in both cultivars (Pierre etal., 2003)
The UTs listed have implications for sustainability, for example, via decreased yields or potential impacts on ecological interactions.
Bt, Bacillus thuringiensis; CMV, cucumber mosaic cucumovirus; epsps, 5-enolpyruvoylshikimate-3-phosphate synthase; GM, genetically modified; HT, herbicide tolerant; WMV, watermelon mosaic
potyvirus 2; ZYMV, zucchini yellow mosaic potyvirus.
a “N/A” indicates no information was provided in the reference.
b Many transgenic events also include additional marker genes, which are usually recombinant antibiotic or herbicide resistance genes. Associated marker genes are not noted in most references and have not
been included in this table.
GM crop
Transgene event
(transgene namea,b) Intended trait Unintended traits compared to non-GM parent or isogenic line (references)
Will gene-edited and other GM crops fail sustainable food systems? 257
(Ma & Subedi, 2005). UTs such as a loss of pest resistance or decreased yield
potential undermine sustainability, particularly when farmers use more external
inputs (e.g., fuel, pesticides, fertilizer, water) to maintain yields. Table13.1 in-
cludes the large yield decreases documented for RR soybeans (7%–11% decrease),
glyphosate HT maize (5.98 bushels/acre decrease), and corn root worm-protected
Bt maize (12.22 bushels/acre decrease) (Gordon, 2007; Shi etal., 2013). Loss of
pest or pathogen resistance documented in Table13.1, includes increased aphid
and/or thrip numbers on Bt maize varieties, loss of nematode resistance in Atlantic
NewLeaf Bt potato and Paymaster Bt cotton, and decreased resistance to Fusarium
fungal disease observed with various Bt cotton varieties (Bourguet etal., 2002;
Brodie, 2003; Colyer etal., 2000; Faria etal., 2007; Li etal., 2009). Table13.1
thus illustrates that commercial GM commodity crops, many grown on millions of
acres worldwide, frequently have detrimental UTs, in addition to the "tough stalks"
of HT and Bt crops, UTs that contribute to their large and negative environmental
impacts.
Crop Intended trait
Unintended traits compared to non-GM parent
or isogenic line
Potato Increased tuber
dormancy
Lower tuber yield and/or fewer tubers per plant
(Marmiroli etal., 2000)
Potato Reduced browning Unintended alterations to glycoalkaloid and
sesquiterpene levels (Matthews, Jones, Gans,
Coates, & Smith, 2005)
Potato High amylose Large unintended increase in phosphorus; altered
sucrose levels, yield, and growth (Hofvander,
Andersson, Larsson, & Larsson, 2004)
Cotton Increased salt
tolerance
Decreased seed yield under normal growth
conditions (Zhang etal., 2009)
Buckwheat Increased salt
tolerance
Unintended agronomic and compositional changes
when grown under greenhouse conditions (Chen,
Zhang, & Xu, 2008)
Rice and
barley
Increased salt
tolerance
Numerous unexpected metabolic changes in both
rice and barley (Jacobs, Lunde, Bacic, Tester, &
Roessner, 2007)
Tomato Increased
provitamin A levels
Reduced lycopene (Römer etal., 2000)
Tomato Novel flavonoids Decreased seed set, color changes, parthenocarpy,
and enzymatic differences (Schijlen etal., 2006)
Maize Increased lysine
content
Agronomic and metabolic UTs (Bicar etal., 2008)
Rice Increased
tryptophan levels
Agronomic and metabolic UTs (Wakasa etal., 2006)
Table13.2 Examples of unintended traits (UTs) identified in crops having “complex”
genetically modified traits intended to improve their agronomic performance, resistance to
abiotic stress, or nutritional value.
258 Rethinking Food and Agriculture
Nevertheless, many biotechnologists tend to dismiss UTs as unimportant, even
when they are identified in commercial varieties (e.g., Fox, Morrison-Saunders, &
Katscherian, 2006; Larkin & Harrigan, 2007; Ricroch etal., 2011; Shepherd, McNicol,
Razzo, Taylor, & Davies, 2006; Sidhu etal., 2000). This was the case with the yield
loss UT documented for RR soybean. In their regulatory petition to the USDA, the
developers of RR soybean claimed they would improve yields through further breed-
ing, yet they were never able to do so (USDA/APHIS, Petition P93–258-01, 2020).
Likewise, large and statistically significant compositional UTs in CZW3 squash were
also dismissed, rather than interpreted as a red flag indicating a need for further risk
assessment, or for rejection of that particular event or crop (USDA/APHIS Petition
95–352-01p). Yet, small and large compositional UTs, such as quantitative or quali-
tative alterations to metabolites, nutrients, or potential toxins, can negatively impact
ecological interactions (Arpaia etal., 2017; Li etal., 2009; Mesnage etal., 2016;
Venter & Bøhn, 2016) and/or food or feed safety (Haslberger, 2003; Pelletier, 2005;
Schubert, 2008), traits essential to sustainability. Statistically significant differences
seen under one environment or in one field trial, but not others, are also routinely
dismissed. However, transgenes may be prone to large transgene × environment inter-
actions (Zeller, Kalinina, Brunner, Keller, & Schmid, 2010). Therefore UTs seen only
under specific conditions should also be considered as a starting point for more risk
assessment, as they could indicate a defect in environmental response or other signifi-
cant problems (Agapito-Tenfen, Guerra, Wikmark, & Nodari, 2013).
It is important to emphasize the examples in Table13.1 are not exhaustive of UTs that
have been documented in commercial GM crops. A number of factors further combine
to make it likely that the publicly available data seriously underestimate the number
of commercial lines with UTs and the number of UTs in each commercial line. Many
important sustainability traits, such as increased outcrossing, seed dormancy or seed-
bank persistence, might never be assessed, despite their potential for negative impacts
(e.g., Altieri, 2005; Bergelson, Purrington, & Wichmann, 1998; Linder, 1998; Linder &
Schmitt, 1995). Other limitations for commercial GM crops include the lack of stan-
dardization for compositional studies, a lack of -omic analyses, the use of inadequate or
inappropriate test conditions for many lab and field trials (e.g., inappropriate organisms
or life stage tested for toxicity, inadequate distances between field plots) and a lack of
studies on the long-term and sublethal effects of GM crops and products (Arpaia etal.,
2017; Booij, 2014; Hilbeck, Meier, & Trtikova, 2012; Pelletier, 2005; Schubert, 2008).
In addition, the proprietary nature of GM crops acts to restrict independent research
(Waltz, 2009). Universities and funders also do not encourage research that could
find harm from GM crops, and findings of harm are often heavily contested or even
suppressed (Fagan etal., 2015; Peekhaus, 2010; Waltz, 2009). Consequently, most
commercialized GM crops have undergone little or no independent testing or risk as-
sessment that could identify UTs (Diels, Cunha, Manaia, Sabugosa-Madeira, & Silva,
2011; Séralini, Mesnage, Defarge, & de Vendômois, 2014).
In summary, UTs are frequent, if not ubiquitous, in all crops developed using stan-
dard GM techniques, including commercial GM varieties. These UTs frequently have
a negative impact on sustainability, making GM crops an inappropriate choice for
sustainable agriculture and food systems (Kesavan & Swaminathan, 2018).
Will gene-edited and other GM crops fail sustainable food systems? 259
13.3.3 Standard GM techniques contribute to UTs
UTs can arise from unintended effects of the transgene (or accompanying selectable
marker genes). However, the techniques used to produce a GM crop can also give rise
to UTs (Wilson, Latham, & Steinbrecher, 2006).
Transgenes are introduced into a plant cell, usually via infection with Agrobacterium,
or else a “gene gun” is used to bombard plant cells with DNA-coated particles. The
transgene subsequently integrates into damaged regions of the plant genome, via the
plant’s natural DNA repair mechanisms. The genomic location of transgene integration
is therefore uncontrolled, and differs for each independent integration event. Modified
plant cells are then regenerated back into whole plants via tissue culture. Regenerated
plants with one or more transgenic events are selected (often with the aid of a cotrans-
ferred marker gene that specifies antibiotic or herbicide resistance) for further analysis.
Transgene insertion thus inevitably disrupts the endogenous plant genome.
Furthermore, Agrobacterium infection, particle bombardment, and tissue culture have
all been shown to be highly mutagenic. Together they can produce many thousands
of mutations. These mutations can be at, or linked to, the site of transgene integration,
and also spread throughout the genome (Wilson etal., 2006). Such mutations include
base pair changes, large and small DNA insertions and deletions, large-scale genome
rearrangements, as well as unintended integration of bacterial chromosomal DNA, vec-
tor DNA, multiple transgenes, and transgene fragments. Thus, the mutagenicity of GM
techniques contributes to the frequency and variety of UTs documented in GM crops
(Wilson etal., 2006). In some cases UTs can be removed via genetic recombination (out-
crossing or backcrossing). However, UTs genetically linked to the transgene insertion
site will be difficult if not impossible to separate from the desired trait. UTs are an even
greater problem for commercial crops that are propagated clonally or are otherwise dif-
ficult or impossible to cross. These include potato, banana, cassava, and most tree crops.
13.4 New GM traits and techniques
The UTs described in previous sections were identified in GM plants engineered for
a very limited number of traits: pest resistance, virus resistance, and/or herbicide tol-
erance. These are simple traits, specified by single transgenes whose novel products
were not intended to alter normal plant functions, structures, or biochemical pathways.
For complex traits with the potential to benefit sustainable agriculture, such as
increased tolerance to drought, salt, heat, or flood, intentionally altered levels of spe-
cific nutrients, or increased yield, UTs are likely to be an even greater obstacle (e.g.,
Flowers & Yeo, 1995; Kollist etal., 2019). Table13.2 lists some of the many docu-
mented examples of GM crops with such complex traits that also exhibit UTs.
13.4.1 Complex GM traits have a history of failure
Despite receiving frequent and positive media attention, most attempts to develop
commercial GM crops with complex GM traits have failed. At best they have lagged
260 Rethinking Food and Agriculture
far behind conventional plant breeding in producing viable products (e.g., Barker,
2014; Gilbert, 2016; McFadden, Smith, Wechsler, & Wallander, 2019; Stone & Glover,
2011, 2017).
It is only recently that an extremely limited number of GM crops with complex
traits have become commercially available (e.g., McFadden etal., 2019; Waltz, 2015).
However, despite the high risk of UTs, these new GM crops have undergone even less
independent research, risk assessment, and regulatory scrutiny than previous commer-
cialized GM crops (Camacho, Van Deynze, Chi-Ham, & Bennett, 2014; Waltz, 2016,
2018). In fact, for “drought-tolerant” soybean HB4, the developers themselves admit
they do not understand the mechanism of action behind their trait (Waltz, 2015).
13.4.2 Golden Rice case study
Golden Rice is a widely cited example of a nutritionally enhanced GM crop (Bollinedi
etal., 2014). Unusually, a significant amount of research on Golden Rice has been
published in the scientific literature. Golden Rice is thus useful as a case study of a
GM trait that could theoretically benefit sustainable agriculture.
Golden Rice varieties contain two transgenes specifying enzymes in the β-carotene
biosynthesis pathway (Bollinedi etal., 2014; Ye et a l. , 2 00 0 ). In theory, the targeted pro-
duction of these enzymes in the rice endosperm will increase grain levels of β-carotene
(provitamin A) (Dubock, 2014).
Since the first Golden Rice paper was published in 2000, public and private sec-
tor researchers have produced many iterations of Golden Rice, each one intended
to further increase the levels of β-carotene in the rice grain (Bollinedi etal., 2014).
Syngenta donated six of its GR2 events for public sector use (Bollinedi etal., 2014).
The International Rice Research Institute (IRRI) has used these in breeding efforts
targeted to countries deemed to have populations with high levels of vitamin A defi-
ciency (Bollinedi etal., 2014; IRRI, 2019; Stone & Glover, 2017). Two Golden Rice
events, GR2-R1 and GR2E, have been the subjects of the most research and develop-
ment (e.g., Bollinedi etal., 2017, 2019; Paine etal., 2005; Schaub etal., 2017).
13.4.2.1 The GR2-R1 event causes agronomic defects, including
dramatic yield loss
For many years, the GR2-R1 event was the focus of Golden Rice breeding efforts
(Bollinedi etal., 2017; Stone & Glover, 2017). GR2-R1 lines, however, gave consis-
tently low yields (Dubock, 2014; Stone & Glover, 2017). In addition, Indian research-
ers documented other UTs in GR2-R1, including dwarfism, bushy stature, pale green
leaves, root defects, late flowering, and low fertility (Bollinedi etal., 2017).
At least two underlying defects contribute to the UTs observed in GR2-R1 rice. The
first pertains to the introduced DNA itself. In GR2-R1 plants the enzymes specified by
the transgenes are active in other tissues apart from the grain (Bollinedi etal., 2017).
This indicates the failure of the GR2 transgene regulatory sequences to function as
intended, at least in GR2-R1 (Paine etal., 2005). The second defect was discovered
when the Indian researchers sequenced the site of GR2-R1 integration. In GR2-R1,
Will gene-edited and other GM crops fail sustainable food systems? 261
the integrated transgene disrupts a native gene, called OsAux1, that specifies an auxin
transport protein (Bollinedi etal., 2017). Auxins are plant hormones with vital func-
tions in growth and behavior.
Both the regulatory and the insertion-site defects are predicted to impact several
additional plant hormones, all with important roles in plant growth and development.
These include abscisic acid, gibberellin, and cytokinin. Indeed, the researchers found
levels of these three hormones were altered in leaves, stems, and flowering parts of
GR2-R1 rice, as compared to non-GM isogenic lines (Bollinedi etal., 2017). In light
of its many UTs and inherent molecular defects, efforts to further develop GR2-R1
were abandoned.
13.4.2.2 GR2E: Low levels of β-carotene in grain
As GR2-R1’s defects became clear, a second event, GR2E, was incorporated into
IRRI’s Golden Rice breeding program (Dubock, 2014). However, the effectiveness of
the Golden Rice trait to produce provitamin A varies widely between events (Bollinedi
etal., 2019; Paine etal., 2005). Of Syngenta’s six GR2 events, GR2E has the lowest
β-carotene levels (Bollinedi etal., 2014; Paine etal., 2005).
While other, sometimes higher, measurements exist in the scientific and regula-
tory literature (Bollinedi etal., 2019; FSANZ, 2017; Paine etal., 2005; Schaub etal.,
2017), the data submitted to regulators worldwide gave the β-carotene level of GR2E
rice as only 3.5 μg/g when milled and 0.5–2.35 μg/g when unmilled (FDA, 2018a,
2018b).
13.4.2.3 Golden Rice: β-carotene degrades rapidly in storage
Two different research groups have reported that β-carotene levels in GR2E rice grains
decrease rapidly in storage (Bollinedi etal., 2019; Schaub etal., 2017). After 3 weeks
of storage, Golden Rice GR2E retained only 60% of its original levels. After 10 weeks,
only 13% remained (Schaub etal., 2017). The second paper reported similar results,
this time for both GR2E and GR2-R1 (Bollinedi etal., 2019). For GR2-R1, rapid deg-
radation was shown to occur in several different genetic backgrounds. Cooking was
shown to further decrease β-carotene levels (Bollinedi etal., 2019). Together, these
results suggest that rapid degradation of β-carotene during normal storage and cooking
conditions is a general problem of Golden Rice varieties.
13.4.2.4 Golden Rice: Commercialization despite missing benefit
and risk assessment?
Agronomic and biosafety UTs in Golden Rice are likely to arise from two aspects of
the trait. First, UTs can arise from unintended alterations to the many biosynthetic
pathways that intersect with the β-carotene biosynthesis pathway, as demonstrated
in GR2-R1. These intersecting pathways produce a wide variety of compounds in
addition to plant hormones, including volatiles, other carotenoids, and unknown
signaling molecules (DellaPenna & Pogson, 2006). Such UTs in the grain might
impact nutrition, toxicity, seed dormancy, germination, and fertility, for example.
262 Rethinking Food and Agriculture
Second, the rapid breakdown of β-carotene in the grain raises questions about the
level and biosafety of the breakdown products (Schaub etal., 2017).
However, despite the high probability of UTs, there is currently a complete ab-
sence of -omic data or other applicable research for GR2E. Furthermore, key human
efficacy and safety studies are still lacking for targeted populations (Schubert, 2008;
Stone & Glover, 2017; Then & Bauer-Panskus, 2018). Yet, regulators in Australia,
the United States, and Canada have accepted developer’s biosafety claims for GR2E
(IRRI, 2019).
The data on Golden Rice thus conflict with proponents’ claims that critics and
overregulation are responsible for the ongoing failure of Golden Rice (Dubock, 2014;
Lee & Krimsky, 2016; Stone & Glover, 2017). Instead, the available data suggest
the commercialization of Golden Rice has been consistently hindered by technical
difficulties inherent to GM plant breeding. Furthermore, the current leading candi-
date, GR2E, is unlikely to make a useful contribution to the stated humanitarian goal
of helping to alleviate vitamin A deficiency in target populations. This is due in part
to the low initial levels, and subsequent rapid degradation, of β-carotene in GR2E
grains. Its commercialization would, however, introduce unnecessary agronomic and
biosafety risks into the food system. Vacuum packaging of Golden Rice, which has
been suggested to slow β-carotene degradation, would further undermine food system
sustainability (Bollinedi etal., 2019).
13.4.2.5 Golden Rice: Illuminating the failures of GM plant
breeding
The development of Golden Rice, a complex GM trait, exemplifies many of the in-
herent technical challenges faced by all GM plant breeders. These include (1) the
imprecision and mutagenic nature of the techniques used to introduce GM traits, (2)
inadequate scientific understanding of the biological processes underlying the rela-
tionships between transgenes and genome structure and function, and (3) the limited
scientific understanding of the relationships between genes and traits, and how these
are impacted by developmental and/or environmental factors.
These technical difficulties combine to make GM plant breeding prone to UTs
and, ultimately, failure. The history of Golden Rice development suggests that the
production of safe and robust crop varieties that successfully express complex GM
traits, those most likely to be useful for sustainable agriculture, is likely to be even
more problematic.
Golden Rice further highlights the overall institutional failure of regulators to
implement adequate risk assessment and regulation for GM crops. As many re-
searchers have already noted, more stringent regulation is needed (1) to ensure GM
traits and crops fulfill their stated purpose and also (2) to safeguard the food sys-
tem and the environment (Fox etal., 2006; Freese & Schubert, 2004; Heinemann,
Agapito-Tenfen, & Carman, 2013; Heinemann, Kurenbach, & Quist, 2011; Hilbeck
etal., 2015; Hilbeck & Otto, 2015; Latham etal., 2017; Mandel, 2003; Modonesi &
Gusmeroli, 2018; Pelletier, 2005, 2006; Schubert, 2008; Venter & Bøhn, 2016;
Wilson etal., 2006).
Will gene-edited and other GM crops fail sustainable food systems? 263
13.4.3 Are new GM techniques more precise?
Biotechnologists now claim that a new generation of genome modification techniques
(nGMs) is essential to sustainably increase food production (Stone, 2017; Zaidi etal.,
2019). These nGMs include cisgenesis/intragenesish and RNAi.i For the specific risks
arising from intragenic, cisgenic, and RNAi-based traits, the reader is referred to other
reviews (Casacuberta etal., 2015; Eckerstorfer etal., 2019; Gelinsky & Hilbeck, 2018;
Heinemann etal., 2013; Lundgren & Duan, 2013; Senthil-Kumar & Mysore, 2011).
The most recently developed nGMs for plants, and by far the most discussed,
include techniques that are referred to as “gene editing” (Agapito-Tenfen, Okoli,
Bernstein, Wikmark, & Myhr, 2018; Casacuberta etal., 2015; Eckerstorfer etal.,
2019; Hou, Atlihan, & Lu, 2014; Lusser & Davies, 2013). Gene editing is a disparate
family of techniques that include oligonucleotide-directed mutagenesis (ODM),j and/
or the use of site-directed nucleases such as meganucleases, TALENs,k ZFN,l and
CRISPR/Cas9m Of these, CRISPR/Cas9 is the most widely used (Fichtner etal., 2014;
Lusser & Davies, 2013; Sauer etal., 2016). The claimed benefit of gene editing is that
genome modifications can be precisely targeted to specific genomic locations.
A very wide variety of genome modifications can be intentionally introduced via
gene editing (Ahmad, Rahman, Mukhtar, Zafar, & Zhang, 2019; Eckerstorfer etal.,
2019; Fichtner etal., 2014; Lusser & Davies, 2013; Puchta, 2017). These extend from
single base-pair changes to large-scale insertions or deletions of DNA. Insertions
could include transgenes, cisgenes, RNAi-based traits, regulatory sequences, or mul-
tiple transgenes. CRISPR/Cas9 can further be used to create multiple changes at the
same time, in a single gene or at multiple sites in the genome. Called multiplexing, this
technique can be used, for example, to mutate or knock out several different members
of a gene family (Fichtner etal., 2014).
A key question for sustainability is whether gene editing, which is claimed to be far
more precise than standard GM, can introduce beneficial traits without the introduc-
tion of UTs. While the publicly available data for edited crop plants is still extremely
h Cisgenic/intragenic traits utilize only DNA derived from the host plant or a cross-compatible plant. In this
they differ from standard transgenic traits that routinely utilize DNA from distantly related organisms.
i RNAi-based traits specify double-stranded RNA molecules that trigger RNA interference (RNAi) path-
ways. This disrupts the cellular processes that connect specific genes with the production of specific
proteins (Heinemann etal., 2013). The target of the RNAi is specified by the nucleotide sequence of the
RNAi molecule.
j ODM is a generic term for a wide range of different methodologies that use synthetic oligonucleotides to
introduce a specific mutation at a particular site in the plant genome (ACRE, 2011). The oligonucleotides
used for ODM are homologous to the targeted endogenous plant sequences except for the site of the in-
tended mutation.
k TALENs stands for transcription activator-like effector nucleases. TALENs are engineered nucleases that
cut DNA at specific target sequences.
l ZFN stands for zinc finger nuclease. ZFNs are engineered DNA-binding proteins that cut DNA at specific
target sequences.
m CRISPR stands for clustered regularly interspaced short palindromic repeats. In the CRISPR/Cas system,
the engineered CRISPR RNA acts as a “guide” RNA that combines with a protein, for example, the Cas9
nuclease, and targets it to a specific DNA sequence.
264 Rethinking Food and Agriculture
limited, there are reasons to expect that plant gene editing methods are also prone to
introducing UTs.
First, virtually all gene editing protocols utilize standard GM techniques, i.e., tissue
culture and either Agrobacterium infection or the gene gun (Ahmad etal., 2019; Ding,
Li, Chen, & Xie, 2016; Eckerstorfer etal., 2019). These techniques serve to intro-
duce the gene editing reagents, which can include DNA, RNA, protein, or oligonucle-
otides, into plant cells. For example, Agrobacterium infection can be used to introduce
DNA that specifies the CRISPR RNA guide sequence and the Cas9 nuclease, either
transiently or via DNA integration. However, as discussed previously, tissue culture,
Agrobacterium infection, and the gene gun are highly mutagenic, able to introduce
thousands of mutations throughout the genome (Wilson etal., 2006). Proposed alter-
native methods, such as direct uptake of DNA-free reagents into protoplasts, may be
less mutagenic and thus less likely to introduce UTs. However, this assumption re-
mains to be tested experimentally. Furthermore, such methods are currently not avail-
able for most crop species (Ding etal., 2016).
Second, new evidence from both animals and plants indicates that gene editing
itself can result in unintended mutations at or near the target site. These include the
insertion of vector, bacterial, and other superfluous DNA, and the unintended intro-
duction of large DNA deletions and rearrangements (Biswas etal., 2020; Kosicki,
Tomberg, & Bradley, 2018; Li etal., 2015; Norris etal., 2019; Ono etal., 2015).
Third, new research from animals suggests that even precise and intended edits
can cause frequent on-target mRNA misregulation (Sharpe & Cooper, 2017; Tuladhar
etal., 2019). These include “exon skipping” and unintentionally altered RNA splicing.
Both can produce new protein coding sequences with the potential to result in UTs.
Fourth, it has been shown in both plants and animals that gene editing reagents can
make cuts at unintended sites in the genome. These cuts can result in off-target edits
and potentially UTs (Ahmad etal., 2019; Biswas etal., 2020; Fichtner etal., 2014;
Jin etal., 2019).
Fifth, gene editing is being applied to situations where researchers have little prior
research to guide them. Thus some researchers suggest gene editing can be used for
“fast tracking development of underutilized species or perhaps wild species into widely
adapted options to help improve global food security” (Van Eck, 2018). Additionally,
it is being adapted to target regions of the genome that, during conventional breeding,
are usually protected from genomic change (Kawall, 2019). The results of multiplex-
ing would also be difficult if not impossible to introduce via conventional plant breed-
ing (Kawall, 2019). Such novel uses of gene editing will likely increase the already
high likelihood of introducing UTs.
These observations support the conclusion that plant gene editing outcomes are im-
precise and unpredictable, and that, depending on the combination of techniques used,
gene editing can be highly mutagenic. However, because gene editing is a new field
of research, particularly for plants, there are still many knowledge gaps (Ahmad etal.,
2019; Schindele, Wolter, & Puchta, 2018). Lacking are whole genome sequences for
gene-edited crop plants and nonedited comparators. Also lacking are systematic anal-
yses of UTs in gene-edited crops. The knowledge gaps are especially large with regard
to the unintended effects of different types of gene editing techniques and different
Will gene-edited and other GM crops fail sustainable food systems? 265
types of edits, particularly in crops being developed for commercial use. That UTs in
gene-edited organisms will be frequent, however, is suggested by a recent news report.
This described gene-edited animals with UTs that ranged from spotted fleece to big
tongues, extra vertebrae, sickness, and death (Rana & Craymer, 2018). Nevertheless,
most plant gene editing papers have not systematically tested for UTs. However, one
group found that CRISPR-Cas9-generated promoter variants of the maize ARGOS8
gene, intended to improve maize grain yield under drought stress, exhibited UTs, in-
cluding statistically significant differences in plant height, ear height, and grain mois-
ture (Shi etal., 2017).
Therefore while biotechnologists frequently claim, “CRISPR in agriculture should
be best considered as simply a ‘new breeding method’ that can produce identical re-
sults to conventional methods in a much more predictable, faster and even cheaper
manner” (Gao, 2018), it is clear that CRISPR and other gene editing techniques are
more similar to GM than conventional plant breeding due to the use of plant transfor-
mation techniques to introduce DNA or other reagents, the use of tissue culture, and
the potential for exogenous DNA insertion (Eckerstorfer etal., 2019; Kawall, 2019).
Like standard GM, the number and type of UTs introduced using gene editing will
depend, in part, on the new trait being introduced and, in part, on the unintended ef-
fects wrought on the genome by the techniques themselves. All benefits, hazards, and
risks must therefore be assessed experimentally on a case-by-case basis for each inde-
pendently derived nGM trait and crop (Biswas etal., 2020; Eckerstorfer etal., 2019;
Gelinsky & Hilbeck, 2018; Hilbeck etal., 2015). This should include whole genome
sequencing comparisons with an isogenic line and -omic analyses.
13.5 Sustainable agriculture and plant breeding
As discussed, the introduction of GM crops has not made conventional agriculture
more sustainable. However, the failures of GM plant breeding, and of GM agriculture
more broadly, provide insight into the changes necessary for a transition to sustainable
systems.
An important insight comes from the experience of farmers who have turned to
regenerative agriculture. These farmers replace GM crops and their high-input man-
agement systems with some combination of sustainable practices that increase biodi-
versity, decrease topsoil loss, and increase natural soil fertility (e.g., complex cover
crops, intercropping, multiyear multicrop rotations, GM-free no-till agriculture, the
reintroduction of livestock). Research suggests regenerative farming leads to increased
financial and environmental sustainability (LaCanne & Lundgren, 2018). Financial
benefits occur primarily through the lower cost of conventional seeds, and because
improved soils and decreased pest pressures reduce the need for costly and polluting
inputs, including synthetic pesticides and fertilizers. In other words, the introduction
of new traits or cultivars is only one of the many components necessary to improve
sustainability. Conversely, to support sustainable agriculture, plant breeders must de-
velop traits specifically tailored to, and selected within, low-input sustainable systems
(Murphy, Campbell, Lyon, & Jones, 2007; van Bueren etal., 2011).
266 Rethinking Food and Agriculture
To date, however, the vast majority of conventional crop varieties used within or-
ganic and other sustainable systems have been bred for and selected within conven-
tional systems (Murphy etal., 2007; van Bueren etal., 2011). But varieties that give
high yields or perform best in conventional systems do not always do best in organic
systems (Murphy etal., 2007; van Bueren etal., 2011). This is because pests and
pathogens of primary concern for resistance breeding differ between the two systems.
Weeds also are differentially problematic, since herbicides are not used in organic sys-
tems (van Bueren etal., 2011). Additionally, non-GM cultivars developed for conven-
tional systems can have extremely negative trade-offs for sustainability. For example,
semidwarf cereal varieties, introduced to prevent lodging, have a variety of UTs, such
as decreased mineral nutrition and protein content; decreased root size and depth;
decreased disease resistance and nutrient use efficiency; and poorer weed suppression
(Marles, 2017; van Bueren etal., 2011). These defects can be masked in high-input
systems. Thus crops and traits bred specifically for sustainable systems could greatly
benefit both the yields and the performance of sustainable systems.
13.5.1 Traits for sustainable systems
Researchers have identified a number of characters and traits that are likely to be of
general importance when breeding cultivars for organic agriculture and other sustain-
able systems (van Bueren etal., 2011). These include increased nutrient-use efficiency
(vigorous root systems or root exudates that promote beneficial symbiosis with soil
microbiota) or uptake (increase in fine roots); resistance to fungal and bacterial dis-
ease; insect resistance (e.g., changes in life history, gross morphology, physical char-
acteristics, or metabolism to promote resistance; Carmona, Lajeunesse, & Johnson,
2011); improved ability to compete against weeds; improved tolerance to abiotic
stressors; and quality improvements, including improved nutritional value. Modern
conventional crop varieties, and, in particular, landraces or farmers varieties and their
wild relatives, all provide valuable sources of variation when breeding for sustainable
systems (Deb, 2014; Dwivedi etal., 2016; van Bueren etal., 2011).
The usefulness and impact of a particular trait will depend on the specific cropping
system and the crop species (van Bueren etal., 2011). For example, within no-till
systems, weeds are potential problems, as are deep planting depths and soil moisture
(Joshi, Chand, Arun, Singh, & Ortiz, 2007). Consequently, useful traits for herbicide-
free no-till systems include those leading to faster seed emergence (or other traits
that increase competitiveness against weeds); faster (or in some cases slower) residue
decomposition; the ability to germinate when deep seeded; and resistance to mechan-
ical weeding (Joshi etal., 2007; van Bueren etal., 2011). Other traits with potential
benefits include resistance to pests and pathogens that survive on crop residues and
resistance to phytotoxic organic acids released by some residues (Joshi etal., 2007).
The priorities for cultivars intended for use in polyculture systems (e.g., the ancient
“three sisters” maize/bean/squash system of the Americas, cereal and legume sys-
tems in Africa or Asia, or covercrop polycultures) differ from those of no-till. Useful
traits tend to promote complementarity rather than competition between the crops.
For example, researchers found maize, squash, and beans grown in a polyculture have
Will gene-edited and other GM crops fail sustainable food systems? 267
a niche complementarity-dependent yield advantage (as compared to being grown
in monoculture), likely arising from differences in root nutrient foraging strategies
(Zhang etal., 2014). Therefore traits that promote root or shoot plasticity could be
explored for polyculture crops (Zhang etal., 2014). On the other hand, allelopathic
traits, as suggested for no-till systems to promote weed suppression (van Bueren etal.,
2011), might negatively impact polyculture symbioses.
Natural ecosystems can suggest further traits. For example, prairies have inspired
efforts to breed perennial grains (e.g., wheat) and sunflowers (Piper, 1993). A recent re-
view suggests perennial grains, which require well-developed root systems, have lower
input requirements, and can support multifunctional sustainable systems. For example,
they can protect and improve soil on sloped land, when intercropped with annuals or
perennials, and/or in grazing systems or long-term rotations (Ryan etal., 2018).
13.5.2 Sustainable breeding: Considerations and strategies
For plant breeders to support the kinds of food and seed sovereignty goals embodied
by agroecological farming systems, they need to be responsive to farmer and commu-
nity needs. This in turn requires breeding strategies that are flexible and easily adapted
to differences in environment, scale, sustainable practice, and markets. Flexibility and
adaptability are essential given the large variety of low-input and sustainable systems
possible and the widely varying needs of local food systems. To these can be added the
growing uncertainty generated by climate change.
Participatory plant breeding strategies, where breeders collaborate with farmers
(and sometimes others, including consumers and traditional farmer-focused breeding
companies) are a promising method to achieve these multiple outcomes (Ceccarelli &
Grando, 2019; Cleveland, Daniela, & Smith, 2000; Mercer etal., 2012; Murphy,
Lammer, Lyon, Carter, & Jones, 2005; van Bueren etal., 2011). Involving farmers at
the start of the breeding program broadens understanding and should better ensure va-
rieties provide farmer-preferred traits. Holding variety trials in farmers’ fields, as well
as in test plots, and involving farmers in the selection process are other components of
participatory plant breeding. In addition to providing well-adapted local varieties, par-
ticipatory plant breeding has multiple other benefits. These include decreasing costs
while educating and empowering all parties. It also facilitates uptake of new varieties
(Najeeb etal., 2018).
Participatory plant breeding can also facilitate the optimization and use of suitable
variety mixtures. Mixtures are a promising strategy to increase resilience, especially
for self-pollinating or clonal crops. Different varieties planted in a single field can
improve yield stability under variable biotic or abiotic stress conditions, or allow for
continued adaptation to changing conditions (Cleveland etal., 2000; Murphy etal.,
2005; Phillips & Wolfe, 2005). For example, East African farmers grow mixtures of
many varieties of common bean that are resistant to different diseases at different sites.
Some Andean farmers maintain a large variety of different potato cultivars via harvest-
ing and planting bulk mixtures (Cleveland etal., 2000). Evolutionary plant breeding is
another strategy that can provide genetically diverse and resilient crops for sustainable
agriculture (Döring, Knapp, Kovacs, Murphy, & Wolfe, 2011; Murphy etal., 2005;
268 Rethinking Food and Agriculture
Phillips & Wolfe, 2005; Raggi etal., 2017). In this case breeders produce heteroge-
neous composite cross populations with high inherent genetic diversity, for exam-
ple to biotic or abiotic stressors (Jackson, Kahler, Webster, & Allard, 1978). These
populations are successively selected under low-input conditions in natural cropping
systems, often within participatory plant breeding programs. Over time, breeder and/
or farmer selection can produce heterogeneous populations or pure lines well-adapted
to variable low-input cropping systems.
A final important consideration running through all of plant breeding is one of
control, and thus power. Conventional and GM plant breeding currently encourage or
require the yearly purchase of seeds by farmers. GM crops also have patent restrictions
on research, seed saving, and use for breeding. Their development requires specialized
knowledge, equipment, and reagents. These factors keep control in the hands of seed
companies and large institutions. To support food and seed sovereignty, in addition to
using participatory methods, sustainable plant breeders must prioritize varieties that
facilitate farmer seed saving and adaptation. These should be unpatented and free from
other restrictions, particularly on seed sharing, breeding, or research.
13.6 Conclusions: Obstacles and opportunities
While in theory it might someday be possible to create a GM crop that meets the
broad requirements of sustainable agriculture, in practice this seems highly unlikely
to ever happen (Kesavan & Swaminathan, 2018; Wickson etal., 2016). Nevertheless,
despite their numerous technical, ecological, and social failings (e.g., Benbrook, 2018;
Fischer, 2016; Wickson etal., 2016), GM crops are commercially successful, domi-
nating the market for specific commodity crops in a number of countries. This suc-
cess has been attributed to various factors. Farmer surveys suggest HT crops can save
time and provide more spraying flexibility, and Bt crops are considered “insurance”
to reduce risk. Research also suggests farmers often have limited seed options, and
they often are locked into technological treadmills, in part due to a loss of knowledge
about alternatives, or a belief that a technology is inevitable (Pechlaner, 2010; Stone &
Flachs, 2018).
Ultimately, however, the commercial successes of GM crops are due to politics,
rather than technical factors. Science and technology are not neutral (O'Brien, 1993).
GM crops support conventional agriculture, which in turn supports a vast corporate
agro-industrial complex (Lima, 2015). For economic and ideological reasons, the US
government, nongovernmental organizations, universities, and academics work with
agribusiness to promote the uptake of GM crops and technologies, tailoring public
research, government regulation, and subsidies to promote their rapid acceptance
and expansion, while suppressing unwelcome findings and locking out alternatives
(Binimelis etal., 2009; Cáceres, 2015; Capellesso etal., 2016; Foscolo & Zimmerman,
2013; Harsh, 2014; Peekhaus, 2010; Pelletier, 2005, 2006; Robinson, Holland,
Leloup, & Muilerman, 2013; Schnurr, 2013; Schnurr & Gore, 2015; Schreiner, 2009;
Vanloqueren & Baret, 2009; Waltz, 2009). The mainstream media further support
Will gene-edited and other GM crops fail sustainable food systems? 269
these efforts by consistently portraying GM crops and technology as promising and
technically successful (Barker, 2014; Stone, 2017).
In spite of these systemic biases, there are signs of change. Some commodity crop
farmers in the United States have abandoned GM crops and substituted more sustain-
able regenerative practices (LaCanne & Lundgren, 2018). Some GM plant breeders
have switched from GM to conventional and participatory plant breeding (Ceccarelli &
Grando, 2019; Gilbert, 2016). Meanwhile, the acreage of land under organic pro-
duction has increased (Paull, 2017). Numerous researchers from different disciplines
have called for both agricultural practices and plant breeding to become more socially
and ecologically sustainable and reject GM crops (Kesavan & Swaminathan, 2018;
Kremen & Miles, 2012; McIntyre etal., 2009; van Bueren, Struik, van Eekeren, &
Nuijten, 2018). These are all hopeful signs that the scientific and political momen-
tum is building to end the transgenic treadmill and transition to the agroecological
and regenerative practices needed to underpin a sustainable food system, one that can
support healthy people on a healthy planet (Anderson & Rivera Ferre, 2020;
Valenzuela, 2016).
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... The benefits of GM crops in general and Bt crops in particular are broadly recognized resulting in its adoption in nearly 200 million ha worldwide (Brookes & Barfoot, 2020a; International Service for the Acquisition of Agribiotech Applications (ISAAA), 2020). Nonetheless, the subject is not devoid of controversies (Pellegrino et al., 2018;Wilson, 2021), which are also reflected in news cycles since 1996 (Morse, 2016), although generally perceived by academia as a relatively low-risk technology (Brookes & Barfoot, 2020b;Klümper & Qaim, 2014;Koch et al., 2015). ...
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