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How safe does transgenic food need to be?
Laura DeFrancesco1
Journal name:
Nature Biotechnology
Volume:
31,
Pages:
794–802
Year published:
(2013)
DOI:
doi:10.1038/nbt.2686
Published online 10 September 2013 Corrected online 26 September 2013
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How safe does transgenic food need to be?
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Disputes over how to assess a foodstuff's safety continue to play into
public fears about transgenic crops.
IntroductionIntroduction• Change history• References•
Author information• Supplementary information
Alamy Stock Photo
Genetically modified sweet corn seed has been part of the American diet
since 1998 when Syngenta's insect-protected corn was approved. Monsanto
started selling transgenic sweet corn three years later.
Transgenic crops are the most highly regulated foods in the world. In recent
years, there have been calls in the United States to relax some of the
rules for their oversight. And yet controversies over the safety of
transgenic food products continue to rumble, particularly in Europe, Africa
and now further afield in the Far East. Despite the fact that numerous
national and international scientific panels have concluded that food
derived through transgenic approaches is as safe as food produced in other
ways and that food-borne pathogens pose a much greater threat to human
health1, scare stories continue to appear in the media and questions
continue to be asked about the adequacy of current regulatory systems to
determine the safety of our food, transgenic or otherwise.
Why, after transgenic products have been in the human food chain for more
than a decade without overt ill effects, do these doubts persist? And will
it ever be possible to gather sufficient evidence to ameliorate the concerns
of skeptics and the public at large that these products are as safe as any
other foodstuff?
Different strokes
Regulators in the United States and the European Union (EU; Brussels)
approach the issue of safeguarding the food supply in different ways. The US
Food and Drug Administration (FDA) has a voluntary process that leaves the
burden of ensuring the safety of new foods to the developers, under the
notion of 'substantial equivalence': “if a new food is found to be
substantially equivalent to an existing food, the food can be concluded to
be as safe as the conventional food” (slightly edited for readability from
ref. 2).
“There are no pre-market reviews of approvals required of foods. Instead,
manufacturers or distributors bear the burden of ensuring that any finished
food placed on the market meets the safety levels implicit in the definition
of adulterated foods. FDA is authorized to seek sanctions against foods
that do not adhere to these standards through seizure, injunction or
criminal prosecution,” writes Emily Marden of the University of British
Columbia's Faculty of Law in Vancouver3. This holds for all new foods,
whether transgenic or not.
Notwithstanding the absence of legal underpinnings, a de facto regulatory
process (called a consultation) exists at the FDA, whereby companies submit
information on new genetically modified foods destined for the market (
Supplementary Box 1).
In contrast, since the European Council adopted Directive 90/220/EEC on the
deliberate release into the environment of genetically modified organisms in
1990 (ref. 4), the EU has increasingly employed the precautionary principle
, which requires developers to prove the safety of any new food that has “
not hitherto been used for human consumption to a significant degree within
the community” before it can be placed on the market. This includes
transgenic products under the EU Directive 90/220/EEC covering plants and
the Regulation (EC) 258/97, which relates to novel foods and food
ingredients. “In Europe...you can't get a food on the market until it's met
safety criteria,” says Julian Kinderlerer, professor of law at the
University of Cape Town, South Africa. In the United States, “foods are
subject to generally-recognized-as-safe criteria,” he adds. “The FDA can't
stop something from going on the market; they have to go to court to get it
off.”
The assessment process
The United States has had a tripartite regulatory process for transgenic
crops since 1986 when the Coordinated Framework for Regulation of
Biotechnology was laid out (51 Fed. Reg. 23302, June 26, 1986)5. Depending
on the exact nature of the change made to the crop, the US Department of
Agriculture (USDA), the US Environmental Protection Agency (EPA) and/or the
FDA has regulatory authority. The USDA, and the Animal and Plant Health
Inspection Service within it, is responsible for regulating agricultural
plant pests and noxious weeds under, among others, the Plant Protection Act
and so looks at the environmental impact of transgenic crops; similarly the
EPA is responsible for oversight of transgenic crops that contain pesticides
within them under regulations for “plant-incorporated pesticides.” But it
is the FDA and its Center for Food Safety and Applied Nutrition that is
responsible for oversight of the safety of food derived from transgenic
crops destined for human consumption. Under the “adulterated food
provisions” of the Federal Food, Drug, and Cosmetic Act6, the FDA regulates
such food using the principle of history of safe use: a substance may be
considered to have a history of safe use as a food if it has been an ongoing
part of the diet for several generations in a large genetically diverse
human population.
Seed companies developing food ingredients submit a package of information
on a transgenic product that includes the source of the gene,
characterization of the insert and some compositional analysis of the new
food. Tests are targeted to measure specific molecules or entities—plant
toxins, anti-nutrients and allergens—to look for unintended up- or
downregulation of critical molecules that might have occurred during the
creation of the transgenic plant. Toxicology and allergenicity studies are
typically conducted on the isolated proteins or molecules to be newly
expressed in the plant, although often the material for testing is made by
recombinant techniques in bacteria (and the resultant protein may have small
differences in post-translational modifications from the version made in
the transgenic plant), and rarely in the context of the plant. This is
because of the difficulty of isolating the protein from a plant in
sufficient quantities for testing and due to the complexity of feeding
studies with whole foods. No animal or human feeding studies are mentioned
in FDA's guidance document7.
Since 2002, the EU has had a consultancy in place—the European Food Safety
Authority (EFSA)—that specifically provides advice on risk assessment of
foods, including transgenic crops. The process for evaluating transgenic
crops is based largely on guidances set out by the United Nations' Food and
Agriculture Organization (FAO; Rome), the Organization for Economic
Cooperation and Development (Paris), the World Health Organization (WHO;
Geneva) and the FAO/WHO Codex Alimentarius (reviewed in ref. 8). EFSA's
guidance documents are more detailed than those of the FDA, but much is
still left up to the developers of new foods as to the exact information
they provide. Both the FDA and EFSA require similar kinds of information on
the nature of the genetic insert and the plant. Whereas feeding studies are
at least mentioned in EFSA guidances, they are not required. However, the EU
recently issued a revised regulation requiring 90-day feeding studies; EFSA
has always argued that it should be done only when deemed nedessary, as has
been discussed elsewhere9.
Compositional analyses of 129 transgenic crops submitted to the FDA for
marketing authority from 1995 to 2012 have all failed to detect any
significant differences—or any believed to have biological relevance—
between the engineered plant and its nonengineered counterpart or reference
species according to an analysis of the literature conducted jointly by FDA
and Dow AgroScience scientists10. Included in the compositional analysis are
proximates (crude measures of protein, fat, ash and fiber), amino acids,
fatty acids, calcium and phosphate. Were significant differences from
natural variation of an isogenic to be detected, they would become the focus
of further investigation.
For all transgenic events commercialized so far, the concentration of the
newly introduced protein in the context of a whole plant (and the consumable
parts derived from it) has been so low that it has been considered not to
pose a risk. Thus, the position of industry and US and EU regulators is that
a combination of targeted compositional analysis plus an event's phenotypic
and agronomic behavior provides everything needed to establish the safety
of a transgenic crop.
Allergenicity
Another food safety concern arising from an alteration in food composition
is the possibility of increased allergenicity. Several kinds of studies
address this. One type compares sequences from the new food to those of
known plant allergens, whose sequences are available in various public
protein databases, including one dedicated to protein allergens http://www.allergenonline.com/. The generally accepted standard for flagging a protein as a potential allergen is homology greater than 35% over a stretch of 80 amino acids or a stretch of identical amino acids, between 6 and 8 depending on the guidance. These are conservative metrics, according to Richard Goodman, at the University of Nebraska's Food Allergy Research and Resource Program in Lincoln. “It would capture marginal sequences that are unlikely to pose a risk of cross-reactivity,” he says. Work from Goodman's laboratory and elsewhere has shown that the eight amino-acid match, in particular, is not predictive of allergenicity (ref. 11 and unpublished work from the Goodman laboratory). Goodman says that as a consequence this is being used less by food developers and regulatory agencies. In fact, EFSA has dropped the eight amino-acid matching entirely in its most recent guidance document12, and the EU is expected to adopt this guidance this year, Goodman says.
Once regions of homology are found, various in vitro tests of allergenicity
can be done (testing serum from allergic individuals, basophil release assay
), although such tests on their own are not definitive. How do regulatory
agencies deal with this uncertainty?
Tests such as these are rarely relied upon, according to Goodman, as
proteins with high identity matches would be dropped. Instead, regulators
rely on a “weight of evidence” approach, which means you look at the
information in aggregate and make some kind of determination as to the
likelihood of problems occurring.
A second approach to determining allergenicity of a protein is to measure
its stability in low pH conditions and/or in the presence of pepsin.
Considerable effort has been put in by FAO and WHO to standardize these
tests13, but the exact conditions are determined by the developer of the
plant, not the regulatory agency.
A frequently cited example from the 1990s generally comes up when discussing
the ability to detect whether a newly created food is allergenic. A
methionine-rich protein (2S albumin) from the Brazil nut was inserted into
soybean by scientists at the University of Nebraska and the agbiotech
company Pioneer Hybrid of Johnston, Iowa, to improve the nutritional balance
of soy for use as poultry feed (and reduce the need for costly feed
supplements). However, the engineered soy plant was found to cause skin
reactions in people allergic to Brazil nuts, which confirmed that an
allergen can be transferred from one plant to another. This finding not only
eliminated the plant from the product pipeline before any harm was done—a
testament to the ability of the available tests to detect introduced
allergens—but also enabled researchers to identify the source of the
allergy in Brazil nuts, which, before this, was unknown14.
In this case, a protein was taken from a plant known to be allergenic in
humans, for which human immune sera exist for testing purposes. Nowadays,
such transfers are less likely to be done, which makes testing for
allergenicity a challenge, according to Hugh Sampson, professor of
pediatrics, allergy and immunology at Mt. Sinai Hospital in New York, who in
2001 served as an advisor to the EPA on allergenicity studies of the Cry9c
protein, present in Starlink corn. “If you bring a novel protein in, where
we don't know if people are allergic, we can't really screen for what we don
't know,” he says.
Whereas the incidence of food allergies are on the rise (CDC reports the
incidence of food allergies in children under 18 rose from 3.4% to 5.1%
between 1997 and 2011), the cause of the rise, as well as whether it is
linked to new allergens or existing ones, is not clear. However, the
possibility of introducing a food allergen exists in all new foods (e.g.,
kiwi fruit, introduced into the American diet rather recently, turned out to
be allergenic), and is not limited to genetically modified foods.
Neither allergenicity or toxicity has been a problem, according to Alan
McHughen, cooperative extension specialist in biotechnology for sustainable
agriculture at the University of California, Riverside, who was a member of
a panel convened in 2004 by the National Research Council of the US National
Academy of Sciences to assess safety testing of transgenic foods. “We say
in [the resulting report] that we were unable to identify any actual
incidence of harm from the consumption of genetically engineered foods, and
during our public input session, we requested people to bring us evidence.
None of those were borne out”15. However, this group did find the potential
for unintended changes to be higher for genetically modified crops than
most other modification techniques (Fig. 1).
Figure 1: The NAS committee on the safety of genetically engineered food
expressed the likelihood of unintended changes as a continuum with gene
transfer more likely than all other modification techniques other than
mutagenesis.
Full size image (169 KB)
Figures/tables index
Points of contention
The above processes represent some of the current best practices used to
assess the safety of foods. However, there are those who feel oversight is
still too lax. For example, the Center for Food Safety (CFS; Washington, DC)
, whose position on GMOs is that they should not be released unless and
until they have been proven safe for human health and the environment, has
criticized the voluntary system used by US regulators, going so far as to
say companies currently “game” the system by testing a wide diversity of
reference varieties so that differences in composition due to a transgenic
trait are masked. When statistically significant differences are seen in
compositional analyses, even dramatic ones that fall outside the range of
reference varieties, often they are discounted as not being biologically
relevant, according to the center's science policy analyst Bill Freese.
For example, in a review of the documents submitted to the FDA by Monsanto
for its Vistive Gold soybean oil and the plant from which it is derived (
MON87705, a transgenic hybrid with high oleic and low linoleic acid levels),
Freese notes that through targeted compositional testing the company found
differences in 9 fatty acids (out of 17 that they could measure), that were
unintended, in comparison to the conventional control as well as a number of
commercial varieties. Whereas the changes observed pose no hazard, their
presence, Freese says, indicates a need for further study, as other
potentially hazardous changes, not captured by targeted analysis, might have
occurred. To this criticism, a Monsanto spokesperson replies, “CFS refers
to many significant differences yet seems to confuse statistical
significance with unintended effects or biological relevance. The lack of
meaningful differences in the composition of MON87705 seed and processed
fractions does not form the basis for further non-targeted studies.”
Another critique is that only a few targeted components of a food (amino
acids, fatty acids, fiber, mineral and moisture) are analyzed in current
assessments. With the availability of transcriptomics, proteomics and
metabolomics, broader, systematic analytical testing of a new product could
be carried out. Several independent groups that have looked at risk
assessment of transgenic foods have concluded that better analytical methods
are needed. These include an EFSA GMO Working Group on Animal Feeding
Studies empaneled in 2008 (ref. 16), and the 2004 NRC panel. So far, omics
technologies have not been integrated in the testing despite calls since
2001 to do so17.
In an EU-sponsored project called SafeFoods, researchers conducted a series
of studies over the past few years to try to answer the question of how best
to apply omics technologies to plants. They looked not just at transgenic
crops but crops grown under different growing conditions. Esther Kok, who
was a member of the team, says that transcriptomics was the most informative
, whereas the other types of omics data provided only partial information,
representing as little as 10% of the 'ome' being analyzed18.
For their part, food companies stand behind their analysis. Barbara Mazur,
Vice President, Research Strategy for DuPont Pioneer, Johnston, Iowa, says,
“Two decades of comprehensive study have demonstrated the safety of plant
biotechnology. Analytical science is always producing more sensitive and new
instrumentation, but it's not always appropriate to apply. There has to be
a risk/benefit approach.
As transgenic foods already undergo extensively more testing than
conventional food, the question becomes when is enough testing enough?
Certainly, the amount of testing should be commensurate with the nature and
magnitude of the risk associated with the new food. And according to Bruce
Chassy, of the University of Illinois' Department of Food Science and Human
Nutrition in Urbana-Champaign, “there's significant science behind [saying]
that if you look at different varieties of the same crop, the
transcriptomes are all different, metabolomes are all different, the
proteomes are all different. If you look at a [transgenic] plant from one of
those varieties, the proteome, transcriptome and metabolome are more like
the parent variety than are other varieties of the same crop.” Thus, one
might invest considerable time and money into such analyses, without getting
closer to answering whether a food is safe.
How long is long enough?
It is generally accepted among regulators and food developers that 90-day
feeding studies with rodents are sufficient to detect chronic, long-term
problems that might occur when humans are exposed to a new foodstuff. This
notion appears to have come from studies carried out in the 1990s by the US
National Toxicology Program in which it was asked whether toxicological
effects of some 40 substances can be identified in subchronic, short-term
feeding studies19. According to EFSA's own description of this work, 70% of
findings (i.e., events connoting toxicity) at two years were predicted by a
three-month subchronic study8.
Last September, Gilles-Eric Séralini and his colleagues published a report
of a study (Box 1), whose aim was to follow rats fed corn engineered for
resistance to the Roundup Ready herbicide glyphosate for much longer than 90
days—in this case, two years20. According to Séralini, such long-term
feeding experiments are needed because too few studies attempt to model long
-term chronic effects from eating transgenic crops. Although numerous
problems have since been identified in the experiment's design and with its
statistical rigor, problems that undercut the plausibility of Séralini's
results and conclusions, a larger question remains as to whether the
existing short-term animal feeding studies (90 days or less) are a
reasonable surrogate for assessing the potential long-term, chronic effects
of a new food, whether or not it's transgenic, on human beings. In December,
the EU called for a two-year carcinogenicity study. So far, the GRACE
project (GMO Risk Assessment and Communication of Evidence), a EU FP7-
supported program, has performed only 90-day feeding studies with a year-
long one in their plans.
Box 1: Publish and be damned
Full box
Even some of those who back continued use of 90-day feeding studies feel
that such studies are a compromise. Martijn Katan, emeritus professor of
nutrition at Amsterdam's VU University says, “Few toxicologists ever stop
to think whether such animal tests really predict the effect in humans,
because if we start to doubt this dogma, the whole system collapses.”
Indeed, in the peer-reviewed literature, opinions are conflicting as to the
necessity of longer-term feeding studies. For example, two recent reviews on
the safety of some transgenic crops came to different conclusions as to
what the available evidence shows. A meta-analysis of 24 feeding studies
done by an international team of toxicologists and biologists led by
geneticist Agnes Ricroch of the University of Paris concluded that the long-
term studies did not add any information to the safety assessment of
individual crops21.
In contrast, Jose L. Domingo, a toxicologist at the Universitat Rovira i
Virgili in Reus, Spain, who has been probing the literature on the safety of
transgenic crops since 2000, finds that the numbers of studies showing no
harm are now roughly equal to those showing harm based on a selection of 30
articles22.
Nature Biotechnology's own survey of the peer-reviewed literature of feeding
studies designed to assess the effects of GMOs on human health reveals that
, whereas there is a large number of feeding studies (over 100 in an
nonexhaustive literature search; see Supplementary Table 1), 65% of the
studies (70/108) are short-term feeding studies (90 days or less). For the
most part, the literature is inconsistent in terms of the kinds of tests
performed, the length of time covered and the test animal used (Table 1).
Moreover, in only a few cases have there been follow-up studies either by
the original authors or others, all of which makes it challenging or
impossible to draw firm conclusions from the existing body of literature.
Publications from the industry itself account for only 20% of the peer-
reviewed literature. Finally, the number of traits for which any feeding
studies, long or short term, exist in the literature is small compared with
the number of traits that have completed their consultation at the FDA (
Table 2). However, it is difficult to draw a line from that group of traits
or the genetic events that contain them to what is being grown and sold for
food in the marketplace.
Table 1: Feeding studies for assessing chronic effects of transgenic food by
length of feeding time or nature of analysis
Full table
Figures/tables index
Next table
Table 2: Transgenes under review and study
Full table
Previous table
Figures/tables index
Only a few groups have conducted in-depth analyses (Table 1), including a
team associated with the Teagasc Food Research Centre in Ireland (funded
under the EU 7th Framework), which found that a diet of Bt maize caused no
long-term deleterious effects on the digestive and immune systems of pigs; a
group of Italian researchers (supported by the Italian Ministry of Health),
who over the years have identified some deleterious effects of glyphosate-
resistant soybean on the morphology and histology of detoxifying organs in
rodents and a group in South Dakota (supported by the state's agriculture
extension program), who in the early 2000s, found no significant long-term
effects of transgenic crops on testicular development in mice.
Chassy questions whether long-term feeding studies are even necessary. “
These kinds of feeding studies are extremely weak, they have no power to
distinguish between groups, are fraught with differences that are not
biologically significant between groups from simple variation and
probability. They are hypothesis-less fishing trips.” On the other hand,
the Union of Concerned Scientists' Doug Gurian-Sherman says a test that is
90 days or shorter is a poor surrogate. “I don't see how you can make
strong conclusions about long-term effects based on relatively short-term
tests with relatively small numbers of animals. They are both weaknesses.”
VU University's Katan also sees problems with the current system. “Ninety-
day rat trials are more or less dogma for the lack of anything else. Of
course, you have to do something. You can't just sit there and tell the
industry, well we're not certain so just go ahead and do your thing and
spread it around and if it causes cancer, we'll find out.” But he believes
better animal models and conducting a power analysis—a statistical
procedure that determines the number of required subjects needed to show a
difference at a predetermined level of significance and size of effect—
before launching a feeding study, would improve outcomes. “You have to be
very much aware of what is being tested for, what are the variabilities in
the outcome, how much of an effect do I want to pick up and how many animals
do I need to pick that up with reasonable confidence. I see very little of
that in animal experiments,” he says.
Lynn Goldman, epidemiologist and dean at the School of Public Health at The
George Washington University in Washington, DC, and a member of the National
Academy of Sciences panel convened in 2004 to assess the risk of GM foods15
, says that 90-day feeding studies remain a useful tool, but they have their
drawbacks. “What they'll tell you is whether there's a toxin so I wouldn't
say don't do them. What they don't tell you is whether there's a toxin that
works very slowly. If it's a toxin that kills you that's one thing, but
what if it causes neurological damage, something that is more like Parkinson
's?”
Reality checks
Critics and proponents of genetically modified organisms (GMOs) alike agree
that genetically modified foods have failed to produce any untoward health
effects, and that the risk to human health from foods contaminated with
pathogens is far greater than from GMOs. The US Centers for Disease Control
(CDC; Atlanta) reports that in 2012, there were 128,000 cases of food-borne
illnesses leading to hospitalizations, with 3,000 deaths http://www.cdc.gov/foodborneburden/index.html. Contrast that with none reported for transgenic foods in their decade-long history in the food supply. However, there has been no concerted effort to find out whether transgenic food has long-term effects on animal health, partly because of a lack of funding and partly because there is no consensus on how to carry out such studies.Of the over 100 peer-reviewed feeding studies done to assess such risks (Supplementary Table 1), the majority are short-term studies on a small number of traits, which would not reveal any chronic effects from long-term consumption of transgenic foods. And, absent food labeling or otherwise tracking transgenic foods, the impact of transgenic foods on those consuming it cannot be known.
This may explain in part why, after transgenic products have been in the
human food chain for more than a decade without overt ill effects, doubts
persist.
Whereas some argue that genetic engineering is different from conventional
breeding technologies and thus requires special oversight, others argue the
opposite, pointing out that humans have been genetically modifying plants
and animals for millennia. To be sure, there is no evidence that
transgenesis itself alters crop characteristics in a way that presents a
threat to human health. One could equally argue that the system of food
safety oversight should be the same for all new breeds of crops, regardless
of the method of production—the approach taken by US regulators since
transgenic crops first entered the US food supply. Yet, public uneasiness
about transgenic products, fueled by sensational food stories in the media,
misinformation from ideological opponents of transgenic crops and
maneuvering on the part of politicians, continues to maintain pressure on
regulators to scrutinize transgenic food products more carefully than
traditionally bred products and even those generated by alternative breeding
methods, such as chemical or irradiation mutagenesis.
Against this background, the system of food safety oversight is an imperfect
one, our understanding of all the factors that affect food safety remains
incomplete and the bounds of scientific knowledge and technology continue to
expand. This often conflicts with the expectations of a public that seeks
definitive and absolute answers to questions of food safety—a public that
does not understand why, a decade or more after transgenic products entered
the food supply, papers are still being published that question their safety.
Most of the transgenic food that we currently eat (Roundup Ready soy, for
example) is embedded in a variety of processed foods (at very low
concentrations). And measuring the effects of a complex foodstuff, in which
a transgenic ingredient may be one of many components, in the milieu of a
typical diet, is extremely challenging. Such effects are likely to be
vanishingly small and obscured by numerous confounding variables.
And Chassy suggests that these are paradoxical concerns. “A key problem
with the toxic new metabolite scenario is that while there are hundreds of
potentially toxic molecules found in crop plants, virtually none of them is
ever present at a concentration that would do harm—which is a good thing
for those of us that like salads! If a new metabolite were to appear, odds
are that it would not be present at a concentration sufficient to cause harm
,” he reasons. “If it were,” Chassy points out, “it would be easily
detectable.”
Much of the thinking currently views 90-day feeding studies as a reasonable
surrogate for assessing the long-term effects of ingestion of new food (
transgenic or otherwise). Indeed, our survey of the published literature
reveals that very few feeding studies longer than 90 days have ever been
carried out. Thus, there is scant evidence, one way or the other, about the
long-term effects of transgenic foods, or any other foods, on animal health.
Not only are these long-term feeding studies difficult to execute, but also
those who are best placed to fund them (i.e., seed companies) have no
motivation to spend the time, money and effort involved in doing them. Given
the lack of evidence for harm, the onus is on others (who regard this as a
key lacuna in our knowledge of food safety) to find funding for such studies
. But where should this funding come from? Opponents of transgenic
technology often summarily dismiss as biased and untrustworthy food safety
studies carried out by industry. If such a viewpoint is valid, then studies
funded by the organic lobby or opponents of transgenic technology showing a
negative effect may also be perceived to be biased and untrustworthy. If
independent government bodies will not step up, crowdsourcing has been
suggested as a way of raising funds for long-term feeding studies (Box 1).
Clearly, the amount of testing carried out on a new food should be in
proportion to the nature and magnitude of the risk associated with it.
According to Marion Nestle, professor of nutrition, food studies and public
health at NYU, there are two ways of looking at the problem of real risk
versus perceived risk. From the standpoint of the risk of illness,
hospitalization and death, the reality is that transgenic food is a very low
risk (by far the most serious problem is food poisoning through microbial
contamination).
But perception about food safety depends on how risk is communicated and
whether the food is familiar or foreign, natural or technical. “You have
this dichotomy where the biggest problem of food safety is bacterial or
viral illness. But because [cases of food poisoning] are familiar not
technical, understood, not imposed, somewhat voluntary, people don't get
upset about them.” In contrast, she says, “people get very upset about
food biotechnology because it's foreign, unfamiliar, technological and
imposed, even though there is very little evidence for harm.”
Beyond these issues, decreasing trust in institutions as a whole is likely
to erode the public's confidence in a food safety regulatory process that is
less than transparent. In a similar way to increasing calls for the release
of data used to support applications of drug products and greater post-
marketing oversight of drugs, it is possible that calls for post-marketing
studies of transgenic foods may also become an issue as society becomes more
open. It does not help that Monsanto leads the agribusiness sector in
lobbying spending, according to OpenSecrets.com.
Putting aside the question of who would pay for these studies, George
Washington University's Goldman offers several possible scenarios, from
labeling food to putting a barcode into the food itself that identifies what
exact variant is in the food. Alternatively, products could be followed
through the supply chain, she suggests. “People can tell you where they get
their food, and what brands they eat. There are a lot of different ways [of
tracking food],” she says. NYU's Nestle remains skeptical about post-
marketing studies, however. They “are very, very difficult to do,” she
says. “Unless there's something really wrong, you're not going to be able
to attribute it to a particular food.” Certainly, whether one runs an
epidemiological study or randomized, controlled clinical trial, it will be a
daunting challenge to find suitable population cohorts in which people have
consumed a food containing a transgenic component(s) and another equally
matched control group has not.
Thus, the circularity of the debate on the safety of transgenic food, the
length of time over which the same issues have been contested, addressed and
revisited, and the limited ability of the scientific community to counter
misinformation surrounding transgenic food suggest that these products will
continue to court controversy. As Gurian-Sherman puts it, the problem is a
societal one. “Clearly how much risk and how much uncertainty is accepted
is a social decision, a public decision. It is not a scientific decision.”
Laura DeFrancesco1
Journal name:
Nature Biotechnology
Volume:
31,
Pages:
794–802
Year published:
(2013)
DOI:
doi:10.1038/nbt.2686
Published online 10 September 2013 Corrected online 26 September 2013
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How safe does transgenic food need to be?
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Citation
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Disputes over how to assess a foodstuff's safety continue to play into
public fears about transgenic crops.
IntroductionIntroduction• Change history• References•
Author information• Supplementary information
Alamy Stock Photo
Genetically modified sweet corn seed has been part of the American diet
since 1998 when Syngenta's insect-protected corn was approved. Monsanto
started selling transgenic sweet corn three years later.
Transgenic crops are the most highly regulated foods in the world. In recent
years, there have been calls in the United States to relax some of the
rules for their oversight. And yet controversies over the safety of
transgenic food products continue to rumble, particularly in Europe, Africa
and now further afield in the Far East. Despite the fact that numerous
national and international scientific panels have concluded that food
derived through transgenic approaches is as safe as food produced in other
ways and that food-borne pathogens pose a much greater threat to human
health1, scare stories continue to appear in the media and questions
continue to be asked about the adequacy of current regulatory systems to
determine the safety of our food, transgenic or otherwise.
Why, after transgenic products have been in the human food chain for more
than a decade without overt ill effects, do these doubts persist? And will
it ever be possible to gather sufficient evidence to ameliorate the concerns
of skeptics and the public at large that these products are as safe as any
other foodstuff?
Different strokes
Regulators in the United States and the European Union (EU; Brussels)
approach the issue of safeguarding the food supply in different ways. The US
Food and Drug Administration (FDA) has a voluntary process that leaves the
burden of ensuring the safety of new foods to the developers, under the
notion of 'substantial equivalence': “if a new food is found to be
substantially equivalent to an existing food, the food can be concluded to
be as safe as the conventional food” (slightly edited for readability from
ref. 2).
“There are no pre-market reviews of approvals required of foods. Instead,
manufacturers or distributors bear the burden of ensuring that any finished
food placed on the market meets the safety levels implicit in the definition
of adulterated foods. FDA is authorized to seek sanctions against foods
that do not adhere to these standards through seizure, injunction or
criminal prosecution,” writes Emily Marden of the University of British
Columbia's Faculty of Law in Vancouver3. This holds for all new foods,
whether transgenic or not.
Notwithstanding the absence of legal underpinnings, a de facto regulatory
process (called a consultation) exists at the FDA, whereby companies submit
information on new genetically modified foods destined for the market (
Supplementary Box 1).
In contrast, since the European Council adopted Directive 90/220/EEC on the
deliberate release into the environment of genetically modified organisms in
1990 (ref. 4), the EU has increasingly employed the precautionary principle
, which requires developers to prove the safety of any new food that has “
not hitherto been used for human consumption to a significant degree within
the community” before it can be placed on the market. This includes
transgenic products under the EU Directive 90/220/EEC covering plants and
the Regulation (EC) 258/97, which relates to novel foods and food
ingredients. “In Europe...you can't get a food on the market until it's met
safety criteria,” says Julian Kinderlerer, professor of law at the
University of Cape Town, South Africa. In the United States, “foods are
subject to generally-recognized-as-safe criteria,” he adds. “The FDA can't
stop something from going on the market; they have to go to court to get it
off.”
The assessment process
The United States has had a tripartite regulatory process for transgenic
crops since 1986 when the Coordinated Framework for Regulation of
Biotechnology was laid out (51 Fed. Reg. 23302, June 26, 1986)5. Depending
on the exact nature of the change made to the crop, the US Department of
Agriculture (USDA), the US Environmental Protection Agency (EPA) and/or the
FDA has regulatory authority. The USDA, and the Animal and Plant Health
Inspection Service within it, is responsible for regulating agricultural
plant pests and noxious weeds under, among others, the Plant Protection Act
and so looks at the environmental impact of transgenic crops; similarly the
EPA is responsible for oversight of transgenic crops that contain pesticides
within them under regulations for “plant-incorporated pesticides.” But it
is the FDA and its Center for Food Safety and Applied Nutrition that is
responsible for oversight of the safety of food derived from transgenic
crops destined for human consumption. Under the “adulterated food
provisions” of the Federal Food, Drug, and Cosmetic Act6, the FDA regulates
such food using the principle of history of safe use: a substance may be
considered to have a history of safe use as a food if it has been an ongoing
part of the diet for several generations in a large genetically diverse
human population.
Seed companies developing food ingredients submit a package of information
on a transgenic product that includes the source of the gene,
characterization of the insert and some compositional analysis of the new
food. Tests are targeted to measure specific molecules or entities—plant
toxins, anti-nutrients and allergens—to look for unintended up- or
downregulation of critical molecules that might have occurred during the
creation of the transgenic plant. Toxicology and allergenicity studies are
typically conducted on the isolated proteins or molecules to be newly
expressed in the plant, although often the material for testing is made by
recombinant techniques in bacteria (and the resultant protein may have small
differences in post-translational modifications from the version made in
the transgenic plant), and rarely in the context of the plant. This is
because of the difficulty of isolating the protein from a plant in
sufficient quantities for testing and due to the complexity of feeding
studies with whole foods. No animal or human feeding studies are mentioned
in FDA's guidance document7.
Since 2002, the EU has had a consultancy in place—the European Food Safety
Authority (EFSA)—that specifically provides advice on risk assessment of
foods, including transgenic crops. The process for evaluating transgenic
crops is based largely on guidances set out by the United Nations' Food and
Agriculture Organization (FAO; Rome), the Organization for Economic
Cooperation and Development (Paris), the World Health Organization (WHO;
Geneva) and the FAO/WHO Codex Alimentarius (reviewed in ref. 8). EFSA's
guidance documents are more detailed than those of the FDA, but much is
still left up to the developers of new foods as to the exact information
they provide. Both the FDA and EFSA require similar kinds of information on
the nature of the genetic insert and the plant. Whereas feeding studies are
at least mentioned in EFSA guidances, they are not required. However, the EU
recently issued a revised regulation requiring 90-day feeding studies; EFSA
has always argued that it should be done only when deemed nedessary, as has
been discussed elsewhere9.
Compositional analyses of 129 transgenic crops submitted to the FDA for
marketing authority from 1995 to 2012 have all failed to detect any
significant differences—or any believed to have biological relevance—
between the engineered plant and its nonengineered counterpart or reference
species according to an analysis of the literature conducted jointly by FDA
and Dow AgroScience scientists10. Included in the compositional analysis are
proximates (crude measures of protein, fat, ash and fiber), amino acids,
fatty acids, calcium and phosphate. Were significant differences from
natural variation of an isogenic to be detected, they would become the focus
of further investigation.
For all transgenic events commercialized so far, the concentration of the
newly introduced protein in the context of a whole plant (and the consumable
parts derived from it) has been so low that it has been considered not to
pose a risk. Thus, the position of industry and US and EU regulators is that
a combination of targeted compositional analysis plus an event's phenotypic
and agronomic behavior provides everything needed to establish the safety
of a transgenic crop.
Allergenicity
Another food safety concern arising from an alteration in food composition
is the possibility of increased allergenicity. Several kinds of studies
address this. One type compares sequences from the new food to those of
known plant allergens, whose sequences are available in various public
protein databases, including one dedicated to protein allergens http://www.allergenonline.com/. The generally accepted standard for flagging a protein as a potential allergen is homology greater than 35% over a stretch of 80 amino acids or a stretch of identical amino acids, between 6 and 8 depending on the guidance. These are conservative metrics, according to Richard Goodman, at the University of Nebraska's Food Allergy Research and Resource Program in Lincoln. “It would capture marginal sequences that are unlikely to pose a risk of cross-reactivity,” he says. Work from Goodman's laboratory and elsewhere has shown that the eight amino-acid match, in particular, is not predictive of allergenicity (ref. 11 and unpublished work from the Goodman laboratory). Goodman says that as a consequence this is being used less by food developers and regulatory agencies. In fact, EFSA has dropped the eight amino-acid matching entirely in its most recent guidance document12, and the EU is expected to adopt this guidance this year, Goodman says.
Once regions of homology are found, various in vitro tests of allergenicity
can be done (testing serum from allergic individuals, basophil release assay
), although such tests on their own are not definitive. How do regulatory
agencies deal with this uncertainty?
Tests such as these are rarely relied upon, according to Goodman, as
proteins with high identity matches would be dropped. Instead, regulators
rely on a “weight of evidence” approach, which means you look at the
information in aggregate and make some kind of determination as to the
likelihood of problems occurring.
A second approach to determining allergenicity of a protein is to measure
its stability in low pH conditions and/or in the presence of pepsin.
Considerable effort has been put in by FAO and WHO to standardize these
tests13, but the exact conditions are determined by the developer of the
plant, not the regulatory agency.
A frequently cited example from the 1990s generally comes up when discussing
the ability to detect whether a newly created food is allergenic. A
methionine-rich protein (2S albumin) from the Brazil nut was inserted into
soybean by scientists at the University of Nebraska and the agbiotech
company Pioneer Hybrid of Johnston, Iowa, to improve the nutritional balance
of soy for use as poultry feed (and reduce the need for costly feed
supplements). However, the engineered soy plant was found to cause skin
reactions in people allergic to Brazil nuts, which confirmed that an
allergen can be transferred from one plant to another. This finding not only
eliminated the plant from the product pipeline before any harm was done—a
testament to the ability of the available tests to detect introduced
allergens—but also enabled researchers to identify the source of the
allergy in Brazil nuts, which, before this, was unknown14.
In this case, a protein was taken from a plant known to be allergenic in
humans, for which human immune sera exist for testing purposes. Nowadays,
such transfers are less likely to be done, which makes testing for
allergenicity a challenge, according to Hugh Sampson, professor of
pediatrics, allergy and immunology at Mt. Sinai Hospital in New York, who in
2001 served as an advisor to the EPA on allergenicity studies of the Cry9c
protein, present in Starlink corn. “If you bring a novel protein in, where
we don't know if people are allergic, we can't really screen for what we don
't know,” he says.
Whereas the incidence of food allergies are on the rise (CDC reports the
incidence of food allergies in children under 18 rose from 3.4% to 5.1%
between 1997 and 2011), the cause of the rise, as well as whether it is
linked to new allergens or existing ones, is not clear. However, the
possibility of introducing a food allergen exists in all new foods (e.g.,
kiwi fruit, introduced into the American diet rather recently, turned out to
be allergenic), and is not limited to genetically modified foods.
Neither allergenicity or toxicity has been a problem, according to Alan
McHughen, cooperative extension specialist in biotechnology for sustainable
agriculture at the University of California, Riverside, who was a member of
a panel convened in 2004 by the National Research Council of the US National
Academy of Sciences to assess safety testing of transgenic foods. “We say
in [the resulting report] that we were unable to identify any actual
incidence of harm from the consumption of genetically engineered foods, and
during our public input session, we requested people to bring us evidence.
None of those were borne out”15. However, this group did find the potential
for unintended changes to be higher for genetically modified crops than
most other modification techniques (Fig. 1).
Figure 1: The NAS committee on the safety of genetically engineered food
expressed the likelihood of unintended changes as a continuum with gene
transfer more likely than all other modification techniques other than
mutagenesis.
Full size image (169 KB)
Figures/tables index
Points of contention
The above processes represent some of the current best practices used to
assess the safety of foods. However, there are those who feel oversight is
still too lax. For example, the Center for Food Safety (CFS; Washington, DC)
, whose position on GMOs is that they should not be released unless and
until they have been proven safe for human health and the environment, has
criticized the voluntary system used by US regulators, going so far as to
say companies currently “game” the system by testing a wide diversity of
reference varieties so that differences in composition due to a transgenic
trait are masked. When statistically significant differences are seen in
compositional analyses, even dramatic ones that fall outside the range of
reference varieties, often they are discounted as not being biologically
relevant, according to the center's science policy analyst Bill Freese.
For example, in a review of the documents submitted to the FDA by Monsanto
for its Vistive Gold soybean oil and the plant from which it is derived (
MON87705, a transgenic hybrid with high oleic and low linoleic acid levels),
Freese notes that through targeted compositional testing the company found
differences in 9 fatty acids (out of 17 that they could measure), that were
unintended, in comparison to the conventional control as well as a number of
commercial varieties. Whereas the changes observed pose no hazard, their
presence, Freese says, indicates a need for further study, as other
potentially hazardous changes, not captured by targeted analysis, might have
occurred. To this criticism, a Monsanto spokesperson replies, “CFS refers
to many significant differences yet seems to confuse statistical
significance with unintended effects or biological relevance. The lack of
meaningful differences in the composition of MON87705 seed and processed
fractions does not form the basis for further non-targeted studies.”
Another critique is that only a few targeted components of a food (amino
acids, fatty acids, fiber, mineral and moisture) are analyzed in current
assessments. With the availability of transcriptomics, proteomics and
metabolomics, broader, systematic analytical testing of a new product could
be carried out. Several independent groups that have looked at risk
assessment of transgenic foods have concluded that better analytical methods
are needed. These include an EFSA GMO Working Group on Animal Feeding
Studies empaneled in 2008 (ref. 16), and the 2004 NRC panel. So far, omics
technologies have not been integrated in the testing despite calls since
2001 to do so17.
In an EU-sponsored project called SafeFoods, researchers conducted a series
of studies over the past few years to try to answer the question of how best
to apply omics technologies to plants. They looked not just at transgenic
crops but crops grown under different growing conditions. Esther Kok, who
was a member of the team, says that transcriptomics was the most informative
, whereas the other types of omics data provided only partial information,
representing as little as 10% of the 'ome' being analyzed18.
For their part, food companies stand behind their analysis. Barbara Mazur,
Vice President, Research Strategy for DuPont Pioneer, Johnston, Iowa, says,
“Two decades of comprehensive study have demonstrated the safety of plant
biotechnology. Analytical science is always producing more sensitive and new
instrumentation, but it's not always appropriate to apply. There has to be
a risk/benefit approach.
As transgenic foods already undergo extensively more testing than
conventional food, the question becomes when is enough testing enough?
Certainly, the amount of testing should be commensurate with the nature and
magnitude of the risk associated with the new food. And according to Bruce
Chassy, of the University of Illinois' Department of Food Science and Human
Nutrition in Urbana-Champaign, “there's significant science behind [saying]
that if you look at different varieties of the same crop, the
transcriptomes are all different, metabolomes are all different, the
proteomes are all different. If you look at a [transgenic] plant from one of
those varieties, the proteome, transcriptome and metabolome are more like
the parent variety than are other varieties of the same crop.” Thus, one
might invest considerable time and money into such analyses, without getting
closer to answering whether a food is safe.
How long is long enough?
It is generally accepted among regulators and food developers that 90-day
feeding studies with rodents are sufficient to detect chronic, long-term
problems that might occur when humans are exposed to a new foodstuff. This
notion appears to have come from studies carried out in the 1990s by the US
National Toxicology Program in which it was asked whether toxicological
effects of some 40 substances can be identified in subchronic, short-term
feeding studies19. According to EFSA's own description of this work, 70% of
findings (i.e., events connoting toxicity) at two years were predicted by a
three-month subchronic study8.
Last September, Gilles-Eric Séralini and his colleagues published a report
of a study (Box 1), whose aim was to follow rats fed corn engineered for
resistance to the Roundup Ready herbicide glyphosate for much longer than 90
days—in this case, two years20. According to Séralini, such long-term
feeding experiments are needed because too few studies attempt to model long
-term chronic effects from eating transgenic crops. Although numerous
problems have since been identified in the experiment's design and with its
statistical rigor, problems that undercut the plausibility of Séralini's
results and conclusions, a larger question remains as to whether the
existing short-term animal feeding studies (90 days or less) are a
reasonable surrogate for assessing the potential long-term, chronic effects
of a new food, whether or not it's transgenic, on human beings. In December,
the EU called for a two-year carcinogenicity study. So far, the GRACE
project (GMO Risk Assessment and Communication of Evidence), a EU FP7-
supported program, has performed only 90-day feeding studies with a year-
long one in their plans.
Box 1: Publish and be damned
Full box
Even some of those who back continued use of 90-day feeding studies feel
that such studies are a compromise. Martijn Katan, emeritus professor of
nutrition at Amsterdam's VU University says, “Few toxicologists ever stop
to think whether such animal tests really predict the effect in humans,
because if we start to doubt this dogma, the whole system collapses.”
Indeed, in the peer-reviewed literature, opinions are conflicting as to the
necessity of longer-term feeding studies. For example, two recent reviews on
the safety of some transgenic crops came to different conclusions as to
what the available evidence shows. A meta-analysis of 24 feeding studies
done by an international team of toxicologists and biologists led by
geneticist Agnes Ricroch of the University of Paris concluded that the long-
term studies did not add any information to the safety assessment of
individual crops21.
In contrast, Jose L. Domingo, a toxicologist at the Universitat Rovira i
Virgili in Reus, Spain, who has been probing the literature on the safety of
transgenic crops since 2000, finds that the numbers of studies showing no
harm are now roughly equal to those showing harm based on a selection of 30
articles22.
Nature Biotechnology's own survey of the peer-reviewed literature of feeding
studies designed to assess the effects of GMOs on human health reveals that
, whereas there is a large number of feeding studies (over 100 in an
nonexhaustive literature search; see Supplementary Table 1), 65% of the
studies (70/108) are short-term feeding studies (90 days or less). For the
most part, the literature is inconsistent in terms of the kinds of tests
performed, the length of time covered and the test animal used (Table 1).
Moreover, in only a few cases have there been follow-up studies either by
the original authors or others, all of which makes it challenging or
impossible to draw firm conclusions from the existing body of literature.
Publications from the industry itself account for only 20% of the peer-
reviewed literature. Finally, the number of traits for which any feeding
studies, long or short term, exist in the literature is small compared with
the number of traits that have completed their consultation at the FDA (
Table 2). However, it is difficult to draw a line from that group of traits
or the genetic events that contain them to what is being grown and sold for
food in the marketplace.
Table 1: Feeding studies for assessing chronic effects of transgenic food by
length of feeding time or nature of analysis
Full table
Figures/tables index
Next table
Table 2: Transgenes under review and study
Full table
Previous table
Figures/tables index
Only a few groups have conducted in-depth analyses (Table 1), including a
team associated with the Teagasc Food Research Centre in Ireland (funded
under the EU 7th Framework), which found that a diet of Bt maize caused no
long-term deleterious effects on the digestive and immune systems of pigs; a
group of Italian researchers (supported by the Italian Ministry of Health),
who over the years have identified some deleterious effects of glyphosate-
resistant soybean on the morphology and histology of detoxifying organs in
rodents and a group in South Dakota (supported by the state's agriculture
extension program), who in the early 2000s, found no significant long-term
effects of transgenic crops on testicular development in mice.
Chassy questions whether long-term feeding studies are even necessary. “
These kinds of feeding studies are extremely weak, they have no power to
distinguish between groups, are fraught with differences that are not
biologically significant between groups from simple variation and
probability. They are hypothesis-less fishing trips.” On the other hand,
the Union of Concerned Scientists' Doug Gurian-Sherman says a test that is
90 days or shorter is a poor surrogate. “I don't see how you can make
strong conclusions about long-term effects based on relatively short-term
tests with relatively small numbers of animals. They are both weaknesses.”
VU University's Katan also sees problems with the current system. “Ninety-
day rat trials are more or less dogma for the lack of anything else. Of
course, you have to do something. You can't just sit there and tell the
industry, well we're not certain so just go ahead and do your thing and
spread it around and if it causes cancer, we'll find out.” But he believes
better animal models and conducting a power analysis—a statistical
procedure that determines the number of required subjects needed to show a
difference at a predetermined level of significance and size of effect—
before launching a feeding study, would improve outcomes. “You have to be
very much aware of what is being tested for, what are the variabilities in
the outcome, how much of an effect do I want to pick up and how many animals
do I need to pick that up with reasonable confidence. I see very little of
that in animal experiments,” he says.
Lynn Goldman, epidemiologist and dean at the School of Public Health at The
George Washington University in Washington, DC, and a member of the National
Academy of Sciences panel convened in 2004 to assess the risk of GM foods15
, says that 90-day feeding studies remain a useful tool, but they have their
drawbacks. “What they'll tell you is whether there's a toxin so I wouldn't
say don't do them. What they don't tell you is whether there's a toxin that
works very slowly. If it's a toxin that kills you that's one thing, but
what if it causes neurological damage, something that is more like Parkinson
's?”
Reality checks
Critics and proponents of genetically modified organisms (GMOs) alike agree
that genetically modified foods have failed to produce any untoward health
effects, and that the risk to human health from foods contaminated with
pathogens is far greater than from GMOs. The US Centers for Disease Control
(CDC; Atlanta) reports that in 2012, there were 128,000 cases of food-borne
illnesses leading to hospitalizations, with 3,000 deaths http://www.cdc.gov/foodborneburden/index.html. Contrast that with none reported for transgenic foods in their decade-long history in the food supply. However, there has been no concerted effort to find out whether transgenic food has long-term effects on animal health, partly because of a lack of funding and partly because there is no consensus on how to carry out such studies.Of the over 100 peer-reviewed feeding studies done to assess such risks (Supplementary Table 1), the majority are short-term studies on a small number of traits, which would not reveal any chronic effects from long-term consumption of transgenic foods. And, absent food labeling or otherwise tracking transgenic foods, the impact of transgenic foods on those consuming it cannot be known.
This may explain in part why, after transgenic products have been in the
human food chain for more than a decade without overt ill effects, doubts
persist.
Whereas some argue that genetic engineering is different from conventional
breeding technologies and thus requires special oversight, others argue the
opposite, pointing out that humans have been genetically modifying plants
and animals for millennia. To be sure, there is no evidence that
transgenesis itself alters crop characteristics in a way that presents a
threat to human health. One could equally argue that the system of food
safety oversight should be the same for all new breeds of crops, regardless
of the method of production—the approach taken by US regulators since
transgenic crops first entered the US food supply. Yet, public uneasiness
about transgenic products, fueled by sensational food stories in the media,
misinformation from ideological opponents of transgenic crops and
maneuvering on the part of politicians, continues to maintain pressure on
regulators to scrutinize transgenic food products more carefully than
traditionally bred products and even those generated by alternative breeding
methods, such as chemical or irradiation mutagenesis.
Against this background, the system of food safety oversight is an imperfect
one, our understanding of all the factors that affect food safety remains
incomplete and the bounds of scientific knowledge and technology continue to
expand. This often conflicts with the expectations of a public that seeks
definitive and absolute answers to questions of food safety—a public that
does not understand why, a decade or more after transgenic products entered
the food supply, papers are still being published that question their safety.
Most of the transgenic food that we currently eat (Roundup Ready soy, for
example) is embedded in a variety of processed foods (at very low
concentrations). And measuring the effects of a complex foodstuff, in which
a transgenic ingredient may be one of many components, in the milieu of a
typical diet, is extremely challenging. Such effects are likely to be
vanishingly small and obscured by numerous confounding variables.
And Chassy suggests that these are paradoxical concerns. “A key problem
with the toxic new metabolite scenario is that while there are hundreds of
potentially toxic molecules found in crop plants, virtually none of them is
ever present at a concentration that would do harm—which is a good thing
for those of us that like salads! If a new metabolite were to appear, odds
are that it would not be present at a concentration sufficient to cause harm
,” he reasons. “If it were,” Chassy points out, “it would be easily
detectable.”
Much of the thinking currently views 90-day feeding studies as a reasonable
surrogate for assessing the long-term effects of ingestion of new food (
transgenic or otherwise). Indeed, our survey of the published literature
reveals that very few feeding studies longer than 90 days have ever been
carried out. Thus, there is scant evidence, one way or the other, about the
long-term effects of transgenic foods, or any other foods, on animal health.
Not only are these long-term feeding studies difficult to execute, but also
those who are best placed to fund them (i.e., seed companies) have no
motivation to spend the time, money and effort involved in doing them. Given
the lack of evidence for harm, the onus is on others (who regard this as a
key lacuna in our knowledge of food safety) to find funding for such studies
. But where should this funding come from? Opponents of transgenic
technology often summarily dismiss as biased and untrustworthy food safety
studies carried out by industry. If such a viewpoint is valid, then studies
funded by the organic lobby or opponents of transgenic technology showing a
negative effect may also be perceived to be biased and untrustworthy. If
independent government bodies will not step up, crowdsourcing has been
suggested as a way of raising funds for long-term feeding studies (Box 1).
Clearly, the amount of testing carried out on a new food should be in
proportion to the nature and magnitude of the risk associated with it.
According to Marion Nestle, professor of nutrition, food studies and public
health at NYU, there are two ways of looking at the problem of real risk
versus perceived risk. From the standpoint of the risk of illness,
hospitalization and death, the reality is that transgenic food is a very low
risk (by far the most serious problem is food poisoning through microbial
contamination).
But perception about food safety depends on how risk is communicated and
whether the food is familiar or foreign, natural or technical. “You have
this dichotomy where the biggest problem of food safety is bacterial or
viral illness. But because [cases of food poisoning] are familiar not
technical, understood, not imposed, somewhat voluntary, people don't get
upset about them.” In contrast, she says, “people get very upset about
food biotechnology because it's foreign, unfamiliar, technological and
imposed, even though there is very little evidence for harm.”
Beyond these issues, decreasing trust in institutions as a whole is likely
to erode the public's confidence in a food safety regulatory process that is
less than transparent. In a similar way to increasing calls for the release
of data used to support applications of drug products and greater post-
marketing oversight of drugs, it is possible that calls for post-marketing
studies of transgenic foods may also become an issue as society becomes more
open. It does not help that Monsanto leads the agribusiness sector in
lobbying spending, according to OpenSecrets.com.
Putting aside the question of who would pay for these studies, George
Washington University's Goldman offers several possible scenarios, from
labeling food to putting a barcode into the food itself that identifies what
exact variant is in the food. Alternatively, products could be followed
through the supply chain, she suggests. “People can tell you where they get
their food, and what brands they eat. There are a lot of different ways [of
tracking food],” she says. NYU's Nestle remains skeptical about post-
marketing studies, however. They “are very, very difficult to do,” she
says. “Unless there's something really wrong, you're not going to be able
to attribute it to a particular food.” Certainly, whether one runs an
epidemiological study or randomized, controlled clinical trial, it will be a
daunting challenge to find suitable population cohorts in which people have
consumed a food containing a transgenic component(s) and another equally
matched control group has not.
Thus, the circularity of the debate on the safety of transgenic food, the
length of time over which the same issues have been contested, addressed and
revisited, and the limited ability of the scientific community to counter
misinformation surrounding transgenic food suggest that these products will
continue to court controversy. As Gurian-Sherman puts it, the problem is a
societal one. “Clearly how much risk and how much uncertainty is accepted
is a social decision, a public decision. It is not a scientific decision.”