Science-Based Regulation of GE Crops Requires More Long-Term Rat Feeding Studies with NK603 Corn

Although May 2014 will mark the 20th anniversary of the U.S. FDA’s approval for and Calgene’s market launch of the world’s first commercially available genetically engineered (GE) whole food, the Flavr SavrTM tomato, it’s amazing how relevant that GE tomato remains in today’s ongoing debate over use of the powerful technology used to create it. Take the recent case of the long-term study by Séralini and colleagues of rats fed Monsanto’s NK603 GE corn, for example.

Just as Séralini’s “inconclusive” (preliminary?) results suggest that an unintended change might have occurred in NK603 corn, one particular variety of Flavr Savr tomato tested for unintended changes back in early 1992 initially appeared to have one as well: variety CR3-623 apparently caused lesions to form in the stomachs of rats while rats fed other Flavr Savr tomato varieties or control tomatoes did not.

It was Calgene’s response to those unexpected, unintended results that is relevant to today’s ongoing debate over GE foods.

Calgene immediately initiated additional experiments on the offending tomato variety. The subsequent studies replicated the original experiment, tested for a dosage effect (the hypothesis being that if the lesions were really related to variety CR3-623, then feeding rats twice the original amount of fruit should cause a corresponding increase in the number of stomach lesions formed), and carefully analyzed levels of toxins normally found in green tomatoes to determine whether elevated glycoalkaloid levels could have been responsible for the lesions. Basically, the scientists at Calgene responded to the unexpected results with more science in an effort to get to the bottom of the issue.

Similarly, a scientific response was launched after publication in 1999 of “Transgenic Pollen Harms Monarch Larvae” in the journal Nature. Stakeholders from the biotech industry, academia and various non-profit organizations gathered together and planned the scientific investigations to determine whether the lab results published in Nature could be relevant to monarch larvae in and around the hundreds of thousands of acres in the United States where GE corn plants engineered to express proteins like the one that harmed monarch larvae in the lab were already growing.

A scientific study, “Investigation of Human Health Effects Associated with Potential Exposure to Genetically Modified Corn,” was also conducted by the U.S. Centers for Disease Control and Prevention (CDC) in the wake of the discovery in 2000 of contamination of human food products in U.S. grocery stores with StarLinkTM corn, a GE corn variety which had been EPA-approved only for animal consumption.

And more science is also the proper response to the results obtained by Séralini and his colleagues.

Séralini’s manuscript and raw data were scrutinized by the Editor-in-Chief of Food and Chemical Toxicology who “unequivocally…found no evidence of fraud or intentional misrepresentation of the data.” The journal deemed Séralini’s results “not incorrect” but “inconclusive” because “the number of animals in each study group and the particular strain” of rat used posed “cause for concern;” the paper was subsequently retracted.

Regardless of whether retraction was warranted…the proper scientific response to this scientific controversy is clear: Séralini’s experiments should be repeated using a different strain of rat and more animals in each study group.

And since the FDA informed Monsanto, after the company completed a voluntary consultation with the agency prior to its marketing of NK603 corn, that “it is Monsanto’s continued responsibility to ensure that foods marketed by the firm are safe [and] wholesome…”, it appears that it is Monsanto’s responsibility to make sure that conclusive evidence related to safety and wholesomeness is available in this matter related to NK603 corn.

What kind of results have follow-up studies of GE crops produced over the last two decades?

The field studies of Bt-expressing corn pollen, comprising four papers in Proceedings of the National Academy of Sciences U.S.A., largely exonerated the GE corn varieties that were commercially available at the time of posing risks to monarch butterfly larvae out in the real world. According to the USDA’s interpretation of these results, “monarch caterpillars have to be exposed to pollen levels greater than 1,000 grains/cm2 to show toxic effects” and “corn pollen levels on milkweed leaves were found to average only about 170 pollen grains/cm2 in corn fields.” However, one GE corn variety, Bt176, “was found to have some negative effects on monarch caterpillars with pollen concentrations of only 10 grains/cm2.” On a web page last modified 10/26/2017, USDA indicated that Bt176 “likely will be phased out by 2003.”

The CDC study of StarLink corn’s potential to cause allergies in humans did not “provide any evidence that the reactions that the affected people experienced [in 2000] were associated with hypersensitivity to the [GE] protein” produced in the StarLink corn. The study concluded, however, that “difficulties of this investigation highlight the importance of evaluating the allergic potential of genetically modified foods before they become available for human consumption.” And enough concern remained that, at the recommendation of the FDA, more than 4 million tests for the presence of the infamous GE StarLink protein were performed on 4 billion bushels of yellow corn at grain mills throughout the U.S. between 2000 and 2007.

After repeating our rat-feeding study at Calgene, lesions were again identified in the stomachs of rats fed tomato variety CR3-623; but stomach lesions were found in rats fed non-GE tomatoes too (see Table 1 in the FDA Agency Summary Memorandum on the Flavr Savr tomato) and FDA deemed the Flavr Savr tomato, including variety CR3-623, “as safe as other commonly consumed tomatoes.” My recollection is that Calgene did not commercialize Flavr Savr tomato variety CR3-623, but the company certainly could have if it had wanted to.

Whether long-term studies of rats fed NK603 will conclusively reveal any unintended, unexpected consequences of the genetic engineering process on that GE corn variety remains to be seen. But follow-up experiments to address this controversy should definitely be undertaken.

Hopefully, the appropriate experiments are already underway. If not, perhaps the FDA should ensure that those experiments are carried out. After all, if the regulatory system for GE crops in the U.S. is truly “science-based” as is often stated, conducting more science in order to get to the bottom of the NK603 corn controversy should be an automatic response.

This entry was posted in Biotechnology and tagged , , , , , , , , , , , , , . Bookmark the permalink.

17 Responses to Science-Based Regulation of GE Crops Requires More Long-Term Rat Feeding Studies with NK603 Corn

  1. Linda says:

    Is there reliable information available to the public re the testing process for the GM purple tomato that’s being touted as a food that will fight cancer & increase lifespan?

    • Belinda says:

      According to a web site of a scientist at the John Innes Centre (last modified 15 November, 2013) involved in the project, juice from those GE purple tomatoes grown under glass in Canada “will be used for further health studies and to obtain regulatory approval for commercialization in N. America.” So, it sounds like voluntary consultation with the U.S. FDA is not yet underway (and I couldn’t find mention of the project on FDA’s “Submissions on Bioengineered New Plant Varieties-Inventories of New Protein Consultations” web site, a good source for reliable information on regulation of particular GE foods).
      If the foreign DNA added to the GE purple tomato still contains DNA from an organism on USDA’s “plant pest” list (as it did when described in a scientific paper published in 2008), then it will also have to be “de-regulated” by that agency before if can be grown freely/commercialized in the United States. I did not find mention of this GE tomato on USDA’s web site, another good source of general, reliable information about the regulatory status of GE crops in the U.S.

  2. Linda says:

    After thinking further about your points here, it occurs to me whether it’s important that the scientists who perform follow-up studies not have biases one way or another, including institutional biases created by biotech industry funding of research, & whether it’s even possible to eliminate biases in the US, since independent research funding has become so limited. Also, how do we even determine whether biases exist within a research team in the first place? Re these biases, I think back to the interview with Thierry Vrain, in which he talked about being a part of the dogma/paradigm within the GE industry, a dogma that relies on a “Patent & Get Rich” business model that has replaced the “Publish or Perish” model, & then retiring from that industry & gaining a different perspective only after retiring.

    • Belinda says:

      You raise a very important point, one that I plan to cover in more detail in a future post. For now I’ll just mention that 20 years ago when I was conducting experiments in an effort to demonstrate the safety of Flavr Savr tomatoes, the FDA much preferred that the results of those experiments be published in peer-reviewed scientific journals, the idea being that the blind, peer-review process could “control” for the kind of bias you’ve mentioned. (However, the agency did accept some unpublished data we submitted anyway.)
      The fact that the NK603 corn results, generated by scientists independent of the biotech industry, had gone through the peer-review process successfully at a journal well respected in terms of these types of animal-feeding studies but were still essentially attacked by multiple plant scientists, some of whom have affiliations, funding, or financial holdings that could be perceived as affecting their objectivity in relation to these results, is cause for concern about not only the possible bias of scientists (on both sides of the debate) but also the integrity of the scientific peer-review process itself.

  3. Mary Darragh says:

    Timely! Glad to see you’re posting again about GE plants.


  4. Linda says:

    I searched your site for bt cotton but came up empty-handed. Would love to read any comments you may have about this article. FYI – As a layperson/consumer who is trying to educate myself on the issue of ge technology & how it’s being applied to crop production, I find it next-to-impossible to find commentary on the internet that isn’t one-sided. How this issue is being discussed currently reminds me of how implementation of the ACA in California has been discussed in Sacramento, a discussion that consists of consumer activist organizations pitted against the health care industry that includes insurance, hospitals & other provider-facilities, & private practice businesses, & that resulted in an overly complex law (regulation/compliance) that nobody likes & that may not even solve the problems that existed in the first place. When there are 2 sides that attack one another instead of collaborating productively, nobody wins because an enemy has to be destroyed. Will this be the end result of the GMO discussion? I hope not. I’ll check in periodically for any comments about this motherjones article. Thanks.

    • Belinda says:

      I agree with you that most information out there related to genetic engineering is one-sided and that this polarization is not conducive to our deciding, as a society (species?), how best to utilize, or not, this new technology. This blog reflects my attempt to help rectify that situation.
      Part of the problem is that the devil is in the details. Take the Mother Jones article you cite, for example. First, its title implies defense of all GE crops when the article itself is really only about Bt crops. Bt crops are just one example of the use of this technology, one that I have very mixed feelings about.
      Bt pesticides are mentioned in Silent Spring as being relatively eco-friendly and, because Bt plants make these pesticides themselves, less pesticide needs to be sprayed on Bt crops in the field. Many other GE crops, however, are engineered to tolerate applications of other pesticides, like glyphosate (the active ingredient in Roundup) and 2,4-D, and therefore much, much more glyphosate, e.g., has been applied to many hundreds of thousands of acres of crops in the U.S. over the last 15 years than was applied prior to that time…an increase in pesticide usage that could be expected to have profound consequences (and does or does not depending on which side of the polar debate about GE crops the author of what you happen to be reading at the time is).
      Also, Sarah Zhang’s claim in the article that “none of” the accusations that Bt proteins cause harm to, for example, monarch butterflies “is true,” is false. If she had carefully read the paper she linked to as evidence of “scientific refutation” of the claim that Bt protein [in a Bt crop] could harm monarch butterflies she would have learned that of the dozen or so Bt crops that have been commercialized thus far, one, Bt176, in which the Bt toxin was expressed at especially high levels specifically in corn pollen, “could give cause for concern” and was being withdrawn from the market. (See also other links to Bt176 information in my blog post.) The lesson to be learned? Each new GE product must be evaluated individually for its risks/costs versus its benefits.
      Zhang’s post also neglected to mention StarLink corn, an example of a Bt crop that would probably NOT be considered “in defense of genetically modified crops” by nearly everyone due to the possible allergenicity of the particular Bt protein it makes. (Again, see my post for more information about StarLink corn.)
      I hope these examples illustrate why I have mixed feelings about Bt crops, how the devil really is in the details (and there are LOTS of details about GE crops), and why regulation of GE crops/foods in the U.S. should be required (not voluntary or only when the crop makes makes a pesticide or involves a plant pest as is currently the case in the U.S.). I agree with Zhang that “just as we do not blame a murder on, say, a knife,” we should not blame genetic engineering as a whole for individual ill-conceived or inadvertently ill-advised GE crops. I also agree that this technology could come in handy “when we use [it] properly.” But, in the first two decades since GE crops have been marketed there have been multiple examples of improper use of this powerful technology. It’s time to get more serious about using this technological “knife” more safely.

  5. Pingback: Hyper-propagandizing crop genetic engineering in The New Yorker? | Biotech Salon

  6. Pingback: The New Yorker Sells Out to Biotech | Natural Society

  7. Pingback: The Absurdity of Claiming that “All GMOs are Safe” | Biotech Salon

  8. Hi Belinda, I wonder if you had a chance to see this new study: “An integrated multi-omics analysis of the NK603 Roundup-tolerant GM maize reveals metabolism disturbances caused by the transformation process,” by Robin Mesnage, Sarah Z. Agapito-Tenfen, Vinicius Vilperte, George Renney, Malcolm Ward, Gilles-Eric Séralini, Rubens O. Nodari & Michael N. Antoniou, Scientific Reports, Vol. 6, Article number: 37855; December 2016 (14 pages) [an HTML format can also be found here: ]. And there is also a related summary article which is here: “GMO maize NK603 is not substantially equivalent to its non-GMO counterpart,” by Claire Robinson; GMWatch; December 19, 2016 … I remembered that you have raised the question why Séralini’s original study has never been replicated to either confirm or refute his findings. This is not a replication of that study, but it is about NK603, and I thought you might be interested in case you hadn’t heard about it yet.

    • I should have included this follow-up article as well, which summarizes criticisms of the study and responses to those criticisms from the authors: “Science Media Centre ‘experts’ misrepresent study findings, get facts wrong,” by GMWatch; December 21, 2016

    • Belinda says:

      Thanks and, yes, I have seen the latest paper by Mesnage et al. My initial reaction is that it’s especially relevant because one of the main recommendations made in the latest National Academies of Science report on GMOs (released in May 2016) was to use the various “omics” technologies to look for unintended changes that could have occurred as a result of the genetic engineering process; in fact, I recently participated in an NSF-funded workshop with the chairperson of the committee that put together that report, Fred Gould, and he stressed the importance of using such “omics” analyses to workshop participants. It would be interesting to learn what Dr. Gould thinks of this paper.
      FYI, Dr. Gould also said that Séralini’s original study should never have been retracted and that GMOs had been “oversold.”

      • I did not know that about Fred Gould. That’s very interesting; my impression of him has just changed! Soon after I posted my initial comment I saw that another related study had been published yesterday which you may also find interesting (in case you haven’t seen it yet!): “Multiomics reveal non-alcoholic fatty liver disease in rats following chronic exposure to an ultra-low dose of Roundup herbicide,” by Robin Mesnage, George Renney, Gilles-Eric Séralini, Malcolm Ward & Michael N. Antoniou, Scientific Reports Vol. 7, Article 39328; January 9, 2017. That study can be found here:
        By the way, the report released in May 2016 was the pre-publication version (407 pages). The final version of “Genetically Engineered Crops Experiences and Prospects” was released this past December – it’s a bit bigger at 607 pages. For anyone interested, the report can be downloaded for free at their link:

  9. Pingback: Scientific Uncertainty and Professional Ethics as Related to GMOs | Biotech Salon

  10. Pingback: Una de las creadoras del primer transgénico comercializado habla sobre la incertidumbre científica en torno a la ingeniería genética | Observatorio OMG – Associació Salut i Agroecologia (ASiA)

Leave a Reply

Fill in your details below or click an icon to log in: Logo

You are commenting using your account. Log Out /  Change )

Facebook photo

You are commenting using your Facebook account. Log Out /  Change )

Connecting to %s