Séralini affair

The Séralini affair is a controversy over an experiment involving feeding genetically modified maize (called corn in North America) to rats. The study claimed that the diet was toxic to the animals. The experiment was conducted by a group led by French molecular biologist Gilles-Éric Séralini. The experiments involved feeding Monsanto's RoundUp-tolerant NK603 maize and the herbicide RoundUp to rats.

The group's conclusions and experimental design were heavily criticized, along with its publication strategy. The paper also received support from the scientific community. At the press conference announcing the publication of the paper, Seralini displayed photographs of rats with large tumors, and emphasized his cancer findings. The press conference received extensive coverage in the media; "within hours, the news had been blogged and tweeted more than 1.5 million times. Lurid photos of tumor-ridden rats appeared on websites and in newspapers around the world..." At the press conference, Séralini also announced that he was releasing a book and a documentary film on the research. Séralini required journalists to sign a confidentiality agreement before viewing the study in advance of the conference. The confidentiality agreement prohibited them from contacting other researchers in advance of the conference.

After the paper was published, scientists and regulatory agencies concluded that the conclusions of the paper to be invalid on the basis of the experimental design; each arm in the study had too few rats to obtain useful data in a lifetime study of Sprague-Dawley rats, which get cancer at a high rate over their lifetime. Other publicly funded long term studies uncovered no health issues.

In November 2013, Food and Chemical Toxicology (FCT), retracted Séralini's paper after the authors refused to withdraw it. The article was republished in June 2014 in the journal Environmental Sciences Europe, without further peer review. Reviewers instead checked that the content of the paper matched the previously peer-reviewed version.

Background

Gilles-Éric Séralini is a professor of molecular biology at the University of Caen in France. He is founder and president of the scientific advisory board of the Committee of Research and Independent Information on Genetic Engineering (CRIIGEN), which is publicly opposed to genetically modified food (GM food). Séralini founded CRIIGEN because he judged that studies on GM food safety were inadequate, and questioned their acceptance.

In 2004, Monsanto sought approval in Europe to introduce corn rootworm resistant (MON 863) Bt maize, which led to controversy over acceptance by regulatory bodies of industry-funded toxicity studies and over their study design. Séralini was on the committee that reviewed MON 863 for the French government. He was a major figure in those controversies and continues to be a critic of toxicity study design.

In 2004, the genetically modified organism (GMO) Panel of the European Food Safety Authority (EFSA) recommended the approval of MON 863. Its report and referenced changes in blood cell parameters and in kidney weights of tested rats. Greenpeace sued for release of the rat feeding studies that Monsanto had provided. Monsanto contested the suit in order to protect its trade secrets. In June 2005 a German court ordered the release of the original study. With the full study in hand, critics of GM foods, including Séralini and Jeffrey M. Smith, pointed to differences in kidney size and blood composition, suggesting that the observed differences, as well as the study designs, challenged the regulatory concept of substantial equivalence.

Previous Séralini papers

Prior to 2012, Séralini had published other peer-reviewed papers that concluded there are health risks to GM foods. However, some members of the scientific community and food safety authorities questioned whether Séralini's data were sufficient to support his conclusions.

In 2007, Séralini and two other authors from University of Caen and the University of Rouen published a Greenpeace-funded study of these data. The study concluded that MON 863 caused health problems in rats, including weight changes, triglyceride level increases in females, changes in urine composition in males, and reduced function or organ damage in the liver, kidney, adrenal glands, heart, and haematopoietic system. The study further recommended that safety experiments continue beyond than 90 days, as chronic organ problems are rarely evident in that amount of time. Greenpeace cited the study in a press release, in which it called for a MON 863 recall and a review of testing methods.

The paper prompted EFSA to reexamine the MON 863 safety data. It asked EU countries for any new data about the strain, new opinions on the original Monsanto study and a technical meeting with the authors of the 2007 CRIIGEN paper. EFSA concluded that all blood chemistry and organ weight values fell within the normal range for control animals and that the paper used incorrect statistical methods. These conclusions were reported by Markos Kyprianou (European Commissioner for Health and Consumer Policy) to the European Parliament on 9 July 2010. The French Commission du Génie Biomoléculaire (AFBV) also reached critical conclusions. Food Standards Australia New Zealand reviewed the 2007 Séralini study and concluded that "...all of the statistical differences between rats fed MON 863 corn and control rats are attributable to normal biological variation."

In 2009, the Séralini lab published another study (Séralini 2009), which re-analyzed toxicity data for NK 603 (glyphosate resistant), MON 810 and MON 863 strains. The data included three rat feeding studies published by Monsanto scientists on MON 810 (Bt corn). This study concluded that the three crops caused liver, kidney and heart damage in the rats.

EFSA reviewed Séralini 2009 and concluded that the authors' claims were not supported by the data in their paper, that many of the statistical criticisms of the 2007 paper also applied to the 2009 paper and that it included no new information that would change the EFSA's conclusions. The French High Council of Biotechnologies Scientific Committee (HCB) reviewed Séralini 2009 and concluded that it "..presents no admissible scientific element likely to ascribe any haematological, hepatic or renal toxicity to the three re-analysed GMOs." The HCB also questioned the authors' independence, noting that, in 2010, the Séralini web page still showed a 2008 Austrian anti-GM article that had been previously withdrawn by the authors as flawed. Food Standards Australia New Zealand concluded that the results from Séralini 2009 were due to chance alone.

In 2010, Séralini sued University of Paris VII Professor Marc Fellous, president of the French Association of Plant Biotechnology and the Association, for libel, claiming that they had unjustly criticized his scientific ability and his research because of its funder, Greenpeace. The judge ruled that because Fellous and other critics had financial ties to the agricultural biotechnology industry, their charge about the Greenpeace funding was defamatory, but refused to rule on the scientific matter. Fellous was fined 1000 euros. Séralini was awarded a symbolic 1 euro in damages and court costs.

A 2011 review by the Séralini lab, which used 19 published animal feeding studies, as well as data from several animal feeding studies submitted for regulatory approval, continued to find that GM food had liver and kidney effects that were sex and dose dependent, and advocated for longer and more elaborate toxicology tests for regulatory approval.

2012 study

On 19 September 2012, Séralini and his colleagues published a peer-reviewed paper titled "Long-term toxicity of a Roundup herbicide and a Roundup-tolerant genetically modified maize" in FCT. The research cost €3.2 million. It was funded by and run with CRIIGEN. It involved a two-year study of NK603 fed to rats.

The abstract stated, "The health effects of a Roundup-tolerant genetically modified maize (from 11% in the diet), cultivated with or without Roundup, and Roundup alone (from 0.1 ppb in water), were studied 2 years in rats. In females, all treated groups died 2–3 times more than controls, and more rapidly. This difference was visible in 3 male groups fed GMOs. All results were hormone and sex dependent, and the pathological profiles were comparable." The study used 200 Sprague-Dawley rats, 100 male and 100 female, and divided them into twenty groups with 10 rats each; ten experimental conditions were separately tested on male and female rats for two years.

Scientific evaluation

The study has been criticized by various regulatory authorities and scientists.

Many claimed that Séralini's conclusions were impossible to justify given the statistical power of the study. Sprague-Dawley rats have a lifespan of about two years and have a high risk of cancer over their lifespan (one study concluded that over eighty percent of males and over seventy percent of females developed cancer under normal conditions). The Séralini experiment covered the normal lifespan of these rats. The longer an experiment continues, the more rats get cancer naturally, that makes it harder to separate statistical "noise" from the hypothetical signal. For the study to achieve such separation (statistical power), each control and test group would have to include sufficiently many subjects. Organisation for Economic Co-operation and Development (OECD) guidelines recommend 20 rats for chemical-toxicity studies, and 50 rats for carcinogenicity studies. In addition, if the survival of the rats is less than 50% at 104 weeks (which is likely for Sprague-Dawley rats) the recommended number of rats is 65. The Séralini study had only ten per group.

Tom Sanders from King's College London noted a lack of data on amount of food given, and on growth rates. Further noting that rats are susceptible to mammary tumors when food intake is not restricted. Sanders said, "The statistical methods are unconventional ... and it would appear the authors have gone on a statistical fishing trip."

The Washington Post quoted Marion Nestle, Paulette Goddard professor in the Department of Nutrition, Food Studies and Public Health at New York University and food safety advocate: "'[I] can’t figure it out yet....It’s weirdly complicated and unclear on key issues: what the controls were fed, relative rates of tumors, why no dose relationship, what the mechanism might be. I can’t think of a biological reason why GMO corn should do this.....So even though I strongly support labeling, I’m skeptical of this study.'" Likewise, Dan Charles, writing for NPR, noted that in the study, rats that ate 33% GM food developed fewer tumors than did those who ate 11% GM food, suggesting the absence of a dose response. University of Calgary Professor Maurice Moloney publicly wondered why the paper contained so many pictures of treated rats with horrific tumors, but no pictures of control group rats.

Many national food safety and regulatory agencies condemned the paper. The German Federal Institute for Risk Assessment VP Reiner Wittkowski said in a statement, ""The study shows both shortcomings in study design and in the presentation of the collected data. This means that the conclusions drawn by the authors are not supported by the available data." A joint report by three Canadian regulatory agencies also "identified significant shortcomings in the study design, implementation and reporting." Similar conclusions were reached by the French HCB and the National Agency for Food Safety, the Vlaams Instituut voor Biotechnologie, the Technical University of Denmark, Food Standards Australia New Zealand, the Brazilian National Technical Commission on Biosafety, and EFSA. EFSA concluded:

The study as reported by Séralini et al. was found to be inadequately designed, analysed and reported...The study as described by Séralini et al. does not allow giving weight to their results and conclusions as published. Conclusions cannot be drawn on the difference in tumour incidence between treatment groups on the basis of the design, the analysis and the results as reported. Taking into consideration Member States’ assessments and the authors’ answer to critics, EFSA finds that the study as reported by Séralini et al. is of insufficient scientific quality for safety assessments.

The European Federation of Biotechnology industry association, which counts Monsanto and other biotech firms among its members, called for the paper to be retracted, calling its publication a "dangerous failure of the peer-review system." Six French national academies (of Agriculture, Medicine, Pharmacy, Science, Technology and Veterinarians) issued a joint statement – "an extremely rare event in French science" – condemning the study and the journal that published it. The joint statement dismissed the study as 'a scientific non-event'. FCT, an Elsevier imprint, has a peer review process, and at least three scientists reviewed the paper prior to publication. The journal published a statement in their November 2012 issue, that "the Editors have encouraged those people with concerns to write formally to the Editor-in-Chief, so that their views can be publicly aired."

In March 2013 FCT published a letter from Erio Barale-Thomas, Principal Scientist of Johnson & Johnson Pharmaceutical Research and Development and the President of the Conseil d’Administration of The Société Française de Pathologie Toxicologique (SFPT, French Society of Toxicologic Pathology). SFPT is "a non governmental/non profit organization formed by veterinarians, physicians, pharmacists and biologists specialized in veterinary and toxicologic pathology. Its aim is to promote knowledge in pathology, toxicology and laboratory animal sciences for safety studies of drugs, chemicals and food products, and the role of the pathologist in the study design and data interpretation." The letter criticized the Seralini study on several fronts, and concluded: "However, given this study presents serious deficiencies in the protocol, the procedures and the interpretation of the results, the SFPT cannot support any of the scientific claims drawn by the authors, and any relevance for human risk assessment. This letter presents the consensus scientific opinion of the Conseil d’Administration of the SFPT."

The Belgian Federal Minister of Public Health asked the Belgian Biosafety Advisory Council (BBAC) to evaluate the paper. The BBAC was asked to "inform the Minister whether this paper (i) contains new scientific information with regard to risks for human health of GM maize NK603 and (ii) whether this information triggers a revision of the current authorisation for commercialisation for food and feed use of this GM maize in the European Union (EU)." The BBAC committee, whose members are drawn from the Belgian biotech Professoriat, pointed out that "the long duration of this study is a positive aspect since most of the toxicity studies on GMOs are performed on shorter periods," and concluded that:

"Given the shortcomings identified by the experts regarding the experimental design, the statistical analysis, the interpretation of the results, the redaction of the article and the presentation of the results, the Biosafety Advisory Council concludes that this study does not contain new scientifically relevant elements that may lead to reconsider immediately the current authorisation for food and feed use of GM maize NK603. Considering the issues raised by the study (i.e. long term assessment), the Biosafety Advisory Council proposes EFSA urgently to study in depth the relevance of the actual guidelines and procedures. It can find inspiration in the GRACE project to find useful information and new concerted ideas."

Responses

Research community

Séralini and supporters defended the study design, the interpretation of the results, and manner and content of the publication. Scientists claim that the criticism originated from "an industry-driven media and lobbying campaign" and the attempted suppression of this study is a good example of how industry can undermine the scientific process to subvert results that are not sufficiently industry-friendly.

Support for the study came from the European Network of Scientists for Social and Environmental Responsibility (ENSSER), of which CRIIGEN is a member. An open letter in support of Seralini's article, signed by about 130 scientists, scholars, and activists, was published in Independent Science News, a project of the Bioscience Resource Project. A study funded by and conducted in consultation with ENSSER also concluded that EFSA applied double standards.

The German research group Testbiotech posted a report critical of the EFSA's reaction to the study as not applying the same standards to studies submitted by industry as it did to Séralini 's study.

A statement opposing the controversy, and especially the attacks on Seralini, was published in Le Monde, signed by 140 French scientists; the letter said: "We are deeply shocked by the image of our community that this controversy gives citizens. Many of the threats to our planet have been revealed by scientists isolated and confirmed by many studies coming from the scientific community. In this case, it would be more efficient to implement research on the health and environmental risks of GMOs and pesticides, improve toxicological protocols used for placing on the market and finance a variety of researchers in this domain...."

Public and government officials

At the time of the initial release, French Prime Minister Jean-Marc Ayrault said that, if the results are confirmed, the government would press for a Europe-wide ban on the maize and The European Commission instructed the EFSA in Parma, Italy, to assess the study. In late September 2012, Russia temporarily suspended importing GM corn as a result of the study and in November 2012, Kenya banned all GM crops.

Media

The press conference led to wide media coverage, which "energized opponents of GM food, especially in Europe". Le Nouvel Observateur covered the press conference in a story called, "Yes, GMOs are poisons!".

Jon Entine in Forbes stated, "Seralini's research is anomalous. Previous peer-reviewed rat feeding studies using the same products (NK603 and Roundup) have not found any negative food safety impacts. The Japanese Department of Environmental Health and Toxicology released a 52-week feeding study of GM soybeans in 2007, finding "no apparent adverse effect in rats." In 2012, a team of scientists at the University of Nottingham School of Biosciences released a review of 12 long-term studies (up to two years) and 12 multi-generational studies (up to 5 generations) of GM foods, concluding there is no evidence of health hazards." Andrew Revkin dubbed it another instance of "single-study syndrome", and contended that the study was in support of an "agenda".

Henry I. Miller, writing for Forbes, said of the study that "the investigators have refused to release all the data from the experiment, which constitutes scientific misconduct." Séralini responded by saying, "...that he won't make any data available to the EFSA and the BfR until the EFSA makes public all the data under-pinning its 2003 approval of NK603 maize for human consumption and animal feed."

The Guardian's Environmental Blog stated that the study linking GM maize to cancer "must be taken seriously by regulators" and that although it "attracted a torrent of abuse", "it cannot be swept under the carpet". They also noted CRIIGEN's funding of the research and reported Séralini's response: namely, that studies in support of GM food are usually funded by "corporates or by pro-biotech institutions". Proponents of California's GM labeling referendum, Proposition 37, hailed the study.

Publication strategy

Séralini held a press conference on the day the study was released in which he "promoted the cancer results as the study’s major finding" and which featured large images of rats with tumors. At the press conference he also announced the release of a book and film about the study. Selected journalists were given early access to the paper on the condition that they sign a confidentiality agreement that prevented them from discussing the paper with other scientists before the embargo expired. The agreement included a penalty for non-compliance: “A refund of the cost of the study of several million euros would be considered damages if the premature disclosure questioned the release of the study.” In contrast, embargo guidelines by journals such as Nature allow such disclosures.

This approach was widely criticized. The original Agence France-Presse story noted: "Breaking with a long tradition in scientific journalism, the authors allowed a selected group of reporters to have access to the paper, provided they signed confidentiality agreements that prevented them from consulting other experts about the research before publication."

A Nature editorial noted: "With such strong claims and the predictably large effect they will have on public opinion, researchers should take care how they present their findings to the public and the media. They should spell out their results clearly; emphasize the limitations and caveats; and make it clear that the data still need to be assessed, and replicated, by the scientific community. That didn't happen. The paper was promoted in a public-relations offensive, with a related book and film set for release this week. Furthermore, journalists wishing to report the research had to sign confidentiality agreements that prevented them from contacting other scientists for comment on the paper until after the embargo had expired. Some, to their credit, refused, or accepted and then revisited the story critically once their hands were no longer tied by these outrageous restrictions. The result was the exclusion of critical comment in many of the breaking stories — the ones that most people will remember."

NPR program On the Media discussed the issue on 28 September 2012, with science journalist Carl Zimmer, who criticized science journalists who participated, as well as criticizing the Séralini lab. Zimmer had earlier posted on his blog at Discover magazine, "This is a rancid, corrupt way to report about science." Cosmos Magazine's Elizabeth Finkel, wrote, "...a clause barring the gathering of independent opinions is extraordinary. What it meant was that Séralini’s story, when it broke, got to prance unfettered in the media limelight before second opinions could dull its shine. By the time the storm of criticism blew in, the media limelight had moved on." The ethics committee of the French National Centre for Scientific Research (CNRS) also criticized the public-relations offensive as "inappropriate for a high-quality and objective scientific debate, and reminded researchers working on controversial topics of the need to report results responsibly to the public."

Retraction and republication

In November 2013, Elsevier announced that FCT was retracting the paper, after the authors refused to withdraw it. The journal's editors concluded that, after an in-depth look at the study's raw data, no definitive conclusions could be reached regarding the role of either NK603 or glyphosate in overall mortality or tumor rates, given the high incidence of tumors in Sprague-Dawley rats and the small sample size. Normal variance could not be excluded as the cause of the results.

Séralini and his supporters strongly objected to the retraction, and Séralini himself threatened to sue FCT. In January 2014, an online petition calling for the Séralini study be reinstated was posted by a group of Séralini's supporters from the Bioscience Resource Project.

In June 2014, the original study was republished in the journal Environmental Sciences Europe. The editor said that the paper was republished without further scientific peer review, "because this had already been conducted by Food and Chemical Toxicology, and had concluded there had been no fraud nor misrepresentation". The republication renewed the controversy, but now with additional controversy over the behavior of the editors of both journals.