Séralini-Affäre

The Séralini affair began in September 2012, and involved the experiments conducted by Gilles-Eric Séralini; the results were widely criticised by parts of the scientific community. The experiments involved feeding Monsanto's Roundup-resistant NK103 maize (called corn in North America) and the herbicide Roundup to rats, over the rats' two-year lifespan. In the paper and in the press conference, Séralini claimed that the results showed that Roundup-resistant maize and Roundup are toxic.

The press conference was widely covered in the media, the paper was used in the debate over Proposition 37 in California (a referendum over labeling of GM (genetically modified) food that was voted on in November 2012), and it led to bans on importation of certain GMOs in Russia and Kenya. Séralini had required that journalists sign a confidentiality agreement in order to receive a copy of the paper prior to the press conference - an extremely rare requirement in scientific publishing. During the press conference Séralini also announced that he was releasing a book and a documentary film on the research. The release of the book and movie in conjunction with the scientific paper, and the requirement that journalists sign a confidentiality agreement, were also widely criticized and critically peer reviewed.

After the paper was published, the conclusions that Séralini drew from the experiments were widely criticized, as was the design of the experiments. The paper was also refuted by many food standards agencies. Other long term studies, which were publicly funded, have uncovered no health issues.

Background

Gilles-Eric Séralini is a professor of molecular biology at the University of Caen in France, and is founder and president of the scientific advisory board of the Committee of Research and Independent Information on Genetic Engineering (CRIIGEN), which is known for being opposed to genetically modified food. Séralini founded CRIIGEN because he judged that studies on the safety of GMOs are inadequate, and questioned their scientific evaluation.

In 2004, Monsanto sought approval in Europe to introduce a rootworm resistant (MON863) maize, which led to controversy over acceptance by regulatory bodies of industry-funded toxicity studies and over the design of those studies. Séralini, who was on the committee that reviewed MON863 for the French government, was a major figure in those controversies and continues to be a critic of toxicity study design.

In 2004, the GMO Panel of the European Food Safety Authority (EFSA) recommended the authorisation of MON863. Its report described the data that Monsanto provided, and referenced changes in some blood cell parameters and in kidney weights of rats that were tested. Because of concerns in general but specifically referencing these changes, Greenpeace sued for release of the rat feeding studies that Monsanto had provided. Monsanto fought against 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, pointed to differences in kidney size and blood composition found in this study, suggesting that the observed differences, as well as the design of the studies, raised questions about the regulatory concept of substantial equivalence.

Previous Séralini papers and reactions to them

Before 2012, Séralini had published other papers which stated that there were health risks to genetically modified foods. In each case, the scientific community and food safety authorities had concluded that Séralini's data were insufficient to support his conclusions.

In 2007, Séralini and two other authors from Caen University and the University of Rouen published a study of these data, funded by Greenpeace. The study concluded that MON 863 caused numerous 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.Vorlage:Primary source-inline The study concluded that evaluating MON 863 safety required experiments longer than 90 days, as chronic organ problems are rarely evident within such a short amount of time.Vorlage:Primary source-inline Greenpeace cited the study in a press release, in which it said that MON 863 should be completely recalled from the global market and called for a strict review of current testing methods.

The paper prompted the European Food Safety Authority (EFSA) to reexamine the MON 863 safety data. This included asking EU countries for any new data about the strain and new opinions on the original Monsanto toxicity study, and a technical meeting with the authors of the 2007 CRIIGEN paper. The EFSA concluded that all blood chemistry and organ weight values fell within the normal range of values 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 also 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, which re-analyzed the toxicity data for NK603 (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.Vorlage:Primary source-inline

The EFSA reviewed the 2009 Séralini paper and concluded that the authors' claims were not supported by the data in their paper, that many of their fundamental statistical criticisms of the 2007 paper also applied to the 2009 paper, and that there was no new information that would change the EFSA's conclusions that the three GM maize types were safe for human and animal health, and for the environment.

The French High Council of Biotechnologies Scientific Committee (HCB) also reviewed the Séralini 2009 study 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 which had been previously withdrawn by the authors themselves as flawed.

Food Standards Australia New Zealand concluded that the results from the 2009 Séralini study 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, on the grounds that they had unjustly criticized his scientific ability, and on the grounds that they had criticized the science as invalid because it was funded by Greenpeace. The judge ruled that because Séralini was able to show that Fellous and other critics had financial ties to the agricultural biotechnology industry, their charge about the Greenpeace funding was defamatory; the judge refused to rule on the scientific grounds. Fellous was fined 1000 euros and 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 and release

The paper published on 19 September 2012 by Séralini and his colleagues was titled "Long-term toxicity of a Roundup herbicide and a Roundup-tolerant genetically modified maize" and was published in the journal Food and Chemical Toxicology. The published research was funded and run with CRIIGEN, and comprised a two-year study of the effect of Monsanto's genetically modified maize NK603, which is resistant to the herbicide Roundup, on rats.

The abstract indicates: "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 tested on male rats and separately on female rats for two years.

Séralini held a press conference on the day the study was released that also included an announcement of the release of a book and film about the study; selected journalists were given access to the paper prior to the press conference, and each writer was required to 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.”

Scientific evaluation

The study has been widely criticised.

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 tendency to get cancer over their lifespan (one study found that over eighty percent of males and over seventy percent of females got cancer under normal conditions). The Séralini experiment lasted the normal lifespan of these rats, and the longer the experiment goes, the more statistical "noise" there is - the more rats get cancer naturally, regardless of what you do to them. So for the experiment to have adequate statistical power, all the groups - control groups and test groups - would have to include at least 65 rats per group in order to sort out any experimentally caused cancers from cancers that would occur anyway - but the Séralini study had only ten per group. OECD (Organisation for Economic Cooperation and Development) 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 given the Sprague-Dawley rats used in the study) the recommended number of rats is 65.

Kings College London Professor Tom Sanders wrote that since Sprague-Dawley rats are susceptible to mammary tumors when food intake is not restricted, data should have been provided about how much food the rats were fed (as well as the presence of fungus in the feed, another confounder). Sanders also wrote of this study, "The statistical methods are unconventional ... and it would appear the authors have gone on a statistical fishing trip." The Washington Post quoted Marion Nestle, the 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.'" University of Calgary Professor Maurice Moloney, among others, went on record wondering why there were so many pictures in the study, and in sympathetic news reports about it, of treated rats with horrific tumors, but no pictures of the rats in the control group.

Many national food safety and regulatory agencies reviewed the paper and condemned it. 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 the European Food Safety Authority (EFSA). The conclusions of the EFSA evaluation were:

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.

On 11 October 2012, the European Federation of Biotechnology lobby, which counts Monsanto and other GM firms among its members, called for the paper to be retracted, calling its publication a "dangerous failure of the peer-review system."

On October 19, 2012, six French national academies (of Agriculture, Medecine, 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'.

The Food and Chemical Toxicology journal, an Elsevier imprint, has a full peer review process, and at least three scientists were needed to endorse the Seralini article prior to publication. The journal in question 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, the same journal that published the Seralini study, 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."

As a result of the publication of the Séralini paper, 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)." Responding to the two point mandate, 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."

Support for the study came from ENSSER (European Network of Scientists for Social and Environmental Responsibility), of which CRRIGEN, the institute that Seralini founded and that funded the study, 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, both of which oppose GM crops.

The German research group Testbiotech, which opposes GMOs and which believes that regulators have been captured by the biotech industry, 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 Seralini's study.

A statement opposing the controversy, and especially the attacks on Seralini, was published in the newspaper Le Monde and was 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...."

Reaction by 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 independent European Food Safety Agency (EFSA) in Parma, Italy, to assess the study. In late September 2012, the government of Russia temporarily suspended importing genetically-modified corn as a result of the study and in November 2012, the government of Kenya banned all GM crops.

Reaction in the media

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

As Jon Entine put it at Forbes, "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, wrote 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.

Criticism of the way the study was publicized

The method by which the Séralini team publicized their 2012 paper 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." The confidentiality agreement contained a severe penalty for breaching the agreement: "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." An editorial at the prestigious scientific journal, Nature, 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." National Public Radio's program, On the Media, discussed the way the paper was released to the media on 28 September 2012, with Carl Zimmer, a science journalist, who was especially critical of science journalists who allowed themselves to be manipulated, 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."

Further reading

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