THIRD WORLD NETWORK BIOSAFETY INFORMATION SERVICE



Dear friends and colleagues

Re: Debate on safety of Monsanto’s GM maize continues

The publication of the paper in the journal Food and Chemical Toxicology ‘Long term toxicity of a Roundup herbicide and a Roundup-tolerant GM maize’ by Seralini et al. (2012) has generated intense debate on the safety or otherwise of Monsanto’s GM maize NK603.

We reproduce below several commentaries that respond to the criticisms of the Seralini study:

1. Summary and Main Issues from ‘Questionable Biosafety of GMOs, Double Standards and, Once Again, a "Shooting-the-Messenger" Style Debate’ by the European Network of Scientists for Social and Environmental Responsibility (ENSSER). The full commentary is available at <http://www.ensser.org/democratising-science-decision-making/ensser-comments-on-seralini-study/>

2. ‘Seralini and Science: an Open Letter’. Originally authored by 9 scientists, it is now endorsed by over 120 scientists and academics from around the world.

3. ISIS report ‘Excess Cancers and Deaths with GM Feed: the Stats Stand Up’.

Russia and Kazakhstan have since halted imports of NK603 maize and more recently, the Kenyan Cabinet has issued a directive to stop the import of GM foods into the country due to inadequate research done on GMOs and scientific evidence provided to prove the safety of the food.

Given the debate around the issue where there is considerable scientific uncertainty, the precautionary principle should apply. In addition, the call to require more rigorous, long-term follow-up studies on GM food and feed should be seriously heeded.

With best wishes,

Third World Network

131 Jalan Macalister

10400 Penang

Malaysia

Email: twnet@po.jaring.my

Website: www.biosafety-info.net and www.twn.my

Item 1

Questionable Biosafety of GMOs, Double Standards and, Once Again, a "Shooting-the-Messenger" Style Debate^[1]

European Network of Scientists for Social and Environmental Responsibility (ENSSER)

Summary and Main Issues

The European Network of Scientists for Social and Environmental Responsibility (ENSSER) welcomes the study "Long term toxicity of a Roundup herbicide and a Roundup-tolerant genetically modified maize" of a group of research scientists of the French Committee for Research and Independent Information on Genetic Engineering (CRIIGEN), an institutional member of ENSSER. Séralini et al. (2012) report on a two-year, full life-cycle study with rats testing Monsanto’s NK603 glyphosate-tolerant GM maize (single trait glyphosate tolerance) and its Roundup co-technology in the journal Food and Chemical Toxicology.

The group of researchers led by Prof. Séralini has published previous toxicology studies on Roundup and its active ingredient glyphosate (Gasnier et al. 2009; Benachour et al. 2007; Benachour & Séralini 2009). The scientists also evaluated industry data submitted in support of the company’s dossiers seeking approval for food/feed import. When re-analysing the developer’s raw data, they found signs for toxicological effects on rat liver and kidneys after 90 days of feeding with GM maize, including the GM maize NK603 tested in this new study (de Vendômois et al. 2009; Séralini et al. 2007; Séralini et al. 2011).

Repeated calls that regulators should require more rigorous, long-term follow-up studies by the developers have consistently been ignored or rejected. Until 2011, the European Food Safety Authority (EFSA) rejected mandatory 90-day feeding studies as a requirement for applications for GM food and feed (European Food Safety Authority 2011). The few studies that were carried out by developers were voluntary and applied protocols of their choosing.

Main issues

1. CRIIGEN’s research^[2] was crucial in finally eliciting a policy response by the European competent authority, the European Commission’s Directorate-General SANCO (Health and Consumer Safety) in 2012. In its draft Implementing Regulation on applications for authorisation of genetically modified food and feed (European Commission 2012), the European Commission stated: "toxicological studies with the whole genetically modified food and feed shall be carried out." If adopted, applicants "shall include a 90-day feeding study with whole food and feed in rodents for the assessment of food and feed containing, consisting of or produced from genetically modified plants […].."
   

2. After a comparative analysis of both published industry data and the data of CRIIGEN, ENSSER concludes that many arguments which attempt to invalidate the Séralini et al. study cannot hold up to closer scrutiny. Raised criticisms are to a large extent either wrong or apply double standards. The weak point of the pilot study by Séralini et al. is the number of animals used, which does not allow a statistical analysis of the raw data regarding one parameter measured out of over 30 – mortality. This has been acknowledged by the authors and needs to be considered/remediated in follow-up studies.
   

3. The controversy and vitriolic attacks evoked by the study reveal one underlying aspect: The lack of appropriate and agreed methodologies for long-term studies to scientifically assess the effects of life-time consumption of GM foods.
   

4. The development of such methodology and tests, which have been demanded by concerned scientists ever since GM food was announced to be introduced into international markets, has systematically been blocked by lobby groups of industry and associated scientists. International bodies such as the Codex Alimentarius and national governments – including most EU governments and their authorities – accepted instead the concept of substantial equivalence and the concept of familiarity to evade any scientific mandatory testing of GM food for human health safety. These concepts enable authorities to easily and declare significant differences found between GMOs and their unmodified parents as ‘biologically irrelevant’ in an assumption-based approach without agreed methodology and thresholds.
   

5. The acceptance of these industry-led, constructed models providing the conceptual justification for evading testing of food-related risks associated with the introduction of this new technology and neglecting the clearly formulated demands of European citizens led to the crisis of trust in science and regulations that now come to light with full force.
   

6. Due to the proven close links between industry and EU risk assessors and the documented disproportional influence on regulations by developers and owners of the technology, it is predictable and expected that these authorities, including EFSA, will not be able to substantially revise their original assessment of GM maize NK603 (and any other application) as their credibility is at stake. These on-going conflicts of interests within EFSA have led to the European Parliament (2012) refusing the discharge of the EFSA 2010 budget as long as there is no fundamental change in policy, leadership and guidance.

Item 2

Seralini and Science: an Open Letter

http://independentsciencenews.org/health/seralini-and-science-nk603-rat-study-roundup/

A new paper by the French group of Gilles-Eric Seralini describes harmful effects on rats fed diets containing genetically modified maize (variety NK603), with and without the herbicide Roundup, as well as Roundup alone. This peer-reviewed study (Seralini et al., 2012), has been criticized by some scientists whose views have been widely reported in the popular press (Carmen, 2012; Mestel, 2012; Revkin, 2012; Worstall, 2012).  Seralini et al. (2012) extends the work of other studies demonstrating toxicity and/or endocrine-based impacts of Roundup (Gaivão et al., 2012; Kelly et al., 2010; Paganelli et al., 2010; Romano et al., 2012), as reviewed by Antoniou et al. (2010).

The Seralini publication, and resultant media attention, raise the profile of fundamental challenges faced by science in a world increasingly dominated by corporate influence. These challenges are important for all of science but are rarely discussed in scientific venues.

1) History of Attacks on Risk-finding Studies. Seralini and colleagues are just the latest in a series of researchers whose findings have triggered orchestrated campaigns of harassment. Examples from just the last few years include Ignacio Chapela, a then untenured Assistant Professor at Berkeley, whose paper on GM contamination of maize in Mexico (Quist and Chapela, 2001) sparked an intensive internet-based campaign to discredit him. This campaign was reportedly masterminded by the Bivings Group, a public relations firm specializing in viral marketing – and frequently hired by Monsanto (Delborne, 2008).

The distinguished career of biochemist Arpad Pusztai, came to an effective end when he attempted to report his contradictory findings on GM potatoes (Ewen and Pusztai, 1999a). Everything from a gag order, forced retirement, seizure of data, and harassment by the British Royal Society were used to forestall his continued research (Ewen and Pusztai, 1999b; Laidlaw, 2003). Even threats of physical violence have been used, most recently against Andres Carrasco, Professor of Molecular Embryology at the University of Buenos Aires, whose research (Paganelli et al. 2010) identified health risks from glyphosate, the active ingredient in Roundup (Amnesty International, 2010).

It was no surprise therefore, that when in 2009, 26 corn entomologists took the unprecedented step of writing directly to the US EPA to complain about industry control of access to GM crops for research, the letter was sent anonymously (Pollack, 2009).

2) The Role of the Science Media. An important but often unnoticed aspect of this intimidation is that it frequently occurs in concert with the science media (Ermakova, 2007; Heinemann and Traavik, 2007; Latham and Wilson, 2007). Reporting of the Seralini paper in arguably the most prestigious segments of the science media: Science, the New York Times, New Scientist, and the Washington Post uniformly failed to “balance” criticism of the research, with even minimal coverage of support for the Seralini paper (Carmen, 2012;  Enserink, 2012; MacKenzie, 2012; Pollack, 2012).

Nevertheless, less well-resourced media outlets, such as the UK Daily Mail appeared to have no trouble finding a positive scientific opinion on the same study (Poulter, 2012).

3) Misleading Media Reporting. A key pattern with risk-finding studies is that the criticisms voiced in the media are often red herrings, misleading, or untruthful. Thus, the use of common methodologies was portrayed as indicative of shoddy science when used by Seralini et al. (2012) but not when used by industry (see refs above and Science Media Centre, 2012). The use of red herring arguments appears intended to sow doubt and confusion among non-experts.  For example, Tom Sanders of Kings College, London was quoted as saying: “This strain of rat is very prone to mammary tumors particularly when food intake is not restricted” (Hirschler and Kelland, 2012). He failed to point out, or was unaware, that most industry feeding studies have used Sprague-Dawley rats (e.g. Hammond et al., 1996, 2004, 2006; MacKenzie et al., 2007). In these and other industry studies (e.g. Malley et al. 2007), feed intake was unrestricted. Sanders’ comments are important because they were widely quoted and because they were part of an orchestrated response to the Seralini study by the Science Media Centre of the British Royal Institution. The Science Media Centre has a long history of quelling GMO controversies and its funders include numerous companies that produce GMOs and pesticides.

4) Regulator Culpability. In our view a large part of the ultimate fault for this controversy lies with regulators. Regulators, such as EFSA (the European Food Safety Authority) in Europe and the EPA (Environmental Protection Agency) and FDA (Food and Drug Administration) in the US, have enshrined protocols with little or no potential to detect adverse consequences of GMOs (Schubert, 2002; Freese and Schubert, 2004; Pelletier, 2005).

GMOs are required to undergo few experiments, few endpoints are examined, and tests are solely conducted by the applicant or their agents.  Moreover, current regulatory protocols are simplistic and assumptions-based (RSC, 2001), which by design, will miss most gene expression changes – apart from the target trait –  induced by the process of transgene insertion (Heinemann et al., 2011; Schubert, 2002).

Puzstai (2001) and others have consequently argued that well-conducted feeding trials are one of the best ways of detecting such unpredictable changes. Yet feeding trials are not mandatory for regulatory approval, and the scientific credibility of those which have been published to date has been challenged (Domingo, 2007; Pusztai et al., 2003; Spiroux de Vendômois et al., 2009). For example, Snell et al. (2012), who assessed the quality of 12 long term (>96 days) and 12 multigenerational studies, concluded:  “The studies reviewed here are often linked to an inadequate experimental design that has detrimental effects on statistical analysis…the major insufficiencies not only include lack of use of near isogenic lines but also statistical power underestimation [and], absence of repetitions…”.

Apparently, the same issues of experimental design and analysis raised about this (Seralini) risk-finding study were not of concern to critics when the studies did not identify risk, resulting in ill-informed decision-makers. In the end, it is a major problem for science and society when current regulatory protocols approve GMO crops based on little to no useful data upon which to assess safety.

5) Science and Politics.  Governments have become habituated to using science as a political football. For example, in a study conducted by the Royal Society of Canada at the request of the Canadian government, numerous weaknesses of GM regulation in Canada were identified (RSC, 2001). The failure of the Canadian government to meaningfully respond to the many recommended changes was detailed by Andree (2006). Similarly, the expert recommendations of the international IAASTD report, produced by 400 researchers over 6 years, that GMOs are unsuited to the task of advancing global agriculture have been resolutely ignored by policymakers. Thus, while proclaiming evidence-based decision-making, governments frequently use science solely when it suits them.

6) Conclusion:  When those with a vested interest attempt to sow unreasonable doubt around inconvenient results, or when governments exploit political opportunities by picking and choosing from scientific evidence, they jeopardize public confidence in scientific methods and institutions, and also put their own citizenry at risk. Safety testing, science-based regulation, and the scientific process itself, depend crucially on widespread trust in a body of scientists devoted to the public interest and professional integrity. If instead, the starting point of a scientific product assessment is an approval process rigged in favour of the applicant, backed up by systematic suppression of independent scientists working in the public interest, then there can never be an honest, rational or scientific debate.

The Authors: Susan Bardocz (4, Arato Street, Budapest, 1121 Hungary); Ann Clark (University of Guelph, ret.); Stanley Ewen (Consultant Histopathologist, Grampian University Hospital); Michael Hansen (Consumers Union); Jack Heinemann (University of Canterbury); Jonathan Latham (The Bioscience Resource Project); Arpad Pusztai (4, Arato Street, Budapest, 1121 Hungary); David Schubert (The Salk Institute); Allison Wilson (The Bioscience Resource Project)

Item 3

Excess Cancers and Deaths with GM Feed: the Stats Stand Up

Prof. Peter Saunders

ISIS Report, October 16 2012

http://www.i-sis.org.uk/Excess_cancers_and_deaths_from_GM_feed_stats_stand_up.php

In September 2012, the research team led by Gilles-Eric Seralini at the University of Caen published the findings of their feeding trial on rats to test for toxicity of Monsanto’s genetically modified (GM) maize NK603 and/or Roundup herbicide in the online edition of Food and Chemical Toxicology [1].

Seralini and his colleagues had previously found evidence for toxicity of GM feed in data from Monsanto’s own experiments, which they had obtained through a Freedom of Information demand [2]. Monsanto challenged their conclusions and, to no one’s great surprise the European Food Standards Agency (EFSA) supported Monsanto [3]. So the team decided to run their own experiment, using an unusually large number of animals and over a period of about two years, roughly the life expectancy of the rats, rather than the usual 90 days required in toxicity trials including Monsanto’s.

What Seralini and his colleagues found was that NK603 and Roundup are not only both toxic as expected, but also carcinogenic, which was unexpected. The proportion of treated rats that died during the experiments was much greater than the controls; moreover, in almost all groups a higher proportion developed tumours, and the tumours appeared earlier.

As soon as the paper appeared, the GM lobby swung into action. In particular, the Science Media Centre (SMC), a London-based organisation partly funded by industry, quickly obtained quotes from a number of pro-GM scientists and distributed them to the media [4]. According to a report in Times Higher Education [5], the SMC succeeded in influencing the coverage of the story in the UK press and largely kept it off the television news.

Seralini has rebutted the pro-GM critics point by point on the CRIIGEN website [6].  The statistician Paul Deheuvels, a professor at the Universite Pierre et Marie Curie in Paris and a member of the French Academie des sciences, has now drawn attention to another serious error in the criticisms [7]: the complaint that Seralini used only 10 rats per group when the OECD guidelines [8] recommend 50 for investigations on carcinogenesis. Because the experiments did not follow the accepted protocol, their results, they argue, can be safely ignored.

In the first place, this was not a wilful disregard of the guidelines. The experiment was designed to test for toxicity, and for that the recommended group size is 10.

But Deheuvels pointed out that the fact Seralini and his colleagues had used smaller groups than recommended makes the results if anything more convincing, not less. That is because using a smaller number of rats actually made it less likely to observe any effect. The fact that an effect was observed despite the small number of animals made the result all the more serious.

To see why, we have to look carefully at how common statistical tests are carried out. We begin with a null hypothesis, which as the name suggests is essentially the hypothesis that nothing unusual has happened. Here it is the hypothesis that rats fed on GMOs and/or herbicide are no more likely to develop cancer than the controls. Clearly, we would like to reject the null hypothesis if it is false and accept it if it is true. But statistics is about taking decisions in the face of uncertainty – if there were no uncertainty there would be no need to use statistics – and so however careful we are, we may come to the wrong conclusion.

There are two ways in which we can go wrong. On the one hand, we can make a "Type 1 error" in rejecting the null hypothesis when it is correct. Here that would mean reporting that GMO and/or herbicide are carcinogenic when they are not. Or, we can make a "Type 2 error" in accepting the null hypothesis when it is false. Here that would mean reporting that GMO and/or herbicide are not carcinogenic when in fact they are.

Naturally we would like to design experiments to make either of those probabilities as small as possible, but there is a problem. The two types of error are linked. We can reduce the probability of making a Type 1 error by requiring stronger evidence before we reject the null hypothesis. But if we do that we necessarily require less evidence to accept it, but that increases the probability of making a Type 2 error. We have to find a balance, and usually what we do is insist that the probability of a Type 1 error must be very small, conventionally 0.05. That’s the origin of the "significant at 5 percent" level.

A probability of 0.05 is very small, so what we are saying is that we will only accept that the effect is real if we can be convinced "beyond reasonable doubt"; and most of the time that makes sense. If you’re thinking of installing a new manufacturing process or a new way of running your farm, you want to be very confident that it really is better before you make a major investment.

It is not so obviously sensible when safety is concerned. If there is scientific evidence that a product is hazardous, then it is hardly surprising if the manufacturer would not want to withdraw it unless the evidence is very strong indeed. The rest of us, however, might take a different view. Are we really willing to accept NK603 maize, or Roundup herbicide, unless and until they have been shown beyond reasonable doubt to be carcinogenic?

The standard statistical test does seem to be the wrong way around, but that’s partly because so far we have only been considering the Type 1 error, the false positive. But as Deheuvels reminds us, there is also the Type 2 error, the false negative. If NK603 and/or the herbicide are actually carcinogenic, what is the probability that we will fail to observe that?

The way to reduce the probability of a Type 2 error is to use larger groups. Because we would expect carcinogenicity to be slower to appear and harder to detect than toxicity, the group size for experiments on carcinogenicity should be larger than for toxicity, and this is precisely what the OECD Guidelines require.

If the experiment had not detected carcinogenicity, that might have been because the groups were too small. As the experiment did detect it, that the groups were small is not an issue. The scientists who were asked to supply sound bites for the Science Media Centre were quick to object that Seralini and his group had used the protocol for testing toxicity rather than the one for carcinogenesis. Had they taken a moment to ask themselves why the two protocols are different, they would have realised that in using the toxicity protocol (and remember, that was because it was what the experiment was designed to test) Seralini and his group made it less likely that they would detect carcinogenesis. To criticise a result because the experiment was conducted in a way that was more conservative than required is totally unjustifiable.

References

1.Seralini G-E, Mesnage R, Gress S, Defarge N, Malatesta M, Hennequin D and  de Vendômois JS (2012),  Long term toxicity of a Roundup herbicide and a Roundup-tolerant genetically modified maize. Food and Chemical Toxicity. http://dx.doi.org/10.1016/j.fct.2012.08.005

2.Seralini G-E, Cellier D and de Vendômois JS (2007).        New analysis of a rat feeding study with a genetically modified maize reveals signs of hepatorenal toxicity. Archives of Environmental Contamination and Toxicity 52, 596-602.

3.EFSA review of statistical analyses conducted for the assessment of the MON863 90-day rate feeding study, 2007, http://www.efsa.europa.eu/en/efsajournal/doc/19r.pdf

4.Science Media Centre press release: Expert Reaction to GM maize causing tumours in rats. 19 September 2012, http://www.sciencemediacentre.org/pages/press_releases/12-09-19_gm_maize_rats_tumours.htm

5."Shock troops check ‘poor’ GM study", Paul Jump, Times Higher Education, 4 October 2012.

6.Criigen Research Team FAQs, accessed 12 October 2012, http://www.criigen.org/SiteEn/index.php?option=com_content&task=view&id=368&Itemid=1

7.De Heuvels P. Étude de Seralini sur les OGM : pourquoi sa méthodologie est statistiquement bonne. Le nouvel observateur Le Plus, 2012, accessed 12 October 2012, http://leplus.nouvelobs.com/contribution/646458-etude-de-seralini-sur-les-ogm-pourquoi-sa-methodologie-est-statistiquement-bonne.html?utm_source=outbrain&utm_medium=widget&utm_campaign=obclick&obref=obinsource

8.OECD Guidelines for the Testing of Chemicals 451: Carcinogenicity Studies, 2009.

http://www.oecd-ilibrary.org/docserver/download/fulltext/9745101e.pdf?expires=1350053297&id=id&accname=freeContent&checksum=BB6C78E3268AD83DB887899FF18E8147