Truth: Few long-term studies have been carried out, but some show unexpected toxic effects
Myth at a glance
Some GMO proponents and scientists say that many long-term animal feeding studies have concluded GM foods are safe. But this claim is not accurate. Few long-term and in-depth studies have been carried out and several studies that have been carried out have found toxic effects.
A review by Snell and colleagues purporting to present long-term studies showing long-term safety is misleading, with double standards being used to dismiss findings of harm while findings of safety are accepted at face value.
Some GMO proponents and scientists say that many long-term animal feeding studies have concluded GM foods are safe. But this claim is not accurate. Few long-term and in-depth studies have been carried out and several studies that have been carried out have found toxic effects. An analysis of one genuinely long-term study and a review purporting to examine long-term studies on GMOs follows.
The Séralini study
This study, covered in detail in Myth 3.2 above, found that a Monsanto GM Roundup-tolerant maize and tiny amounts of the Roundup herbicide it was engineered to be grown with caused severe organ damage and hormonal disruption in rats fed over a long-term period of two years. Unexpected additional findings were increased rates of large palpable tumours and premature death in some treatment groups.1
The study was retracted by the journal that published it for reasons that cannot be scientifically or ethically justified (see Myth 3.2).
The extreme shortage of long-term studies on GM foods was emphasized by two of France’s national regulatory agencies, the HCB (High Council for Biotechnology) and ANSES (the French national food safety agency), in their critiques2,3 of the Séralini 2012 study.1 ANSES noted that it had conducted a search for long-term animal feeding studies on GMOs and their associated pesticides that were comparable with Séralini’s study – and found only two.3,4 One, by Manuela Malatesta’s group in Italy, found health problems in mice fed GM soybeans (see Myth 3.1).5 The other is only available in Japanese and cannot be evaluated by the international scientific community.6
The Snell review
A review by Snell and colleagues (2011) purports to examine the health impacts of GM foods as revealed by long-term and multi-generational studies. The Snell review concludes that the GM foods examined are safe.7 However, this cannot be justified from the data presented in the review.
Some of the studies examined by Snell and colleagues are not even toxicological studies that look at health effects. Instead they are so-called animal production studies that look at aspects of interest to food producers, such as feed conversion (the amount of weight the animal puts on relative to the amount of food it eats)8 or milk production in cows.9
Several of the studies examined are not long-term studies, in that they do not follow the animal over anything approaching its natural lifespan. For example, Snell and colleagues categorized a 25-month feeding study with GM Bt maize in dairy cows by Steinke and colleagues9 as a long-term study. But although most dairy cows are sent to slaughter at four to five years old because their productivity and commercial usefulness decreases after that age, a cow’s natural lifespan is 17–20 years. A 25-month study in dairy cows is equivalent to around eight years in human terms. So from a toxicological point of view, Steinke’s study is not long-term and could at most be described as medium-term (subchronic).
Similarly, Snell and colleagues categorized a seven-month study in salmon10 as long-term. But a farmed salmon lives for between 18 months and three years before being killed and eaten and a wild salmon can live for seven to eight years. Snell and colleagues also categorized as long-term some studies in chickens lasting 3511 and 42 days,8 even though a chicken’s natural lifespan is around seven years, depending on breed and other factors. So again, these are not long-term studies.
Moreover, in Steinke’s study, nine cows from the treatment group and nine from the control group – half of the 18 animals in each group – fell ill or proved infertile, for reasons that were not investigated or explained. In a scientifically unjustifiable move, these cows were simply removed from the study and replaced with other cows. No analysis is presented to show whether the problems that the cows suffered had anything to do with either of the two diets tested.9
It is never acceptable to replace animals in a feeding experiment. For this reason alone, this study9 is irrelevant to an assessment of health effects from GM feed and Snell and colleagues should not have included it in their analysis.
Many of the studies reviewed are on animals that have a very different digestive system and metabolism to humans and are so are not considered relevant to assessing human health effects. These include studies on broiler chickens, cows, sheep, and fish.
Some of the studies reviewed did in fact find toxic effects in the GM-fed animals, but these were dismissed by Snell and colleagues. For example, findings of damage to liver and kidneys and alterations in blood biochemistry in rats fed GM Bt maize over three generations12 are dismissed, as are the findings of Manuela Malatesta’s team, of abnormalities in the liver, pancreatic, and testicular cells of mice fed on GM soy,13,14,15,5 in both cases on the basis that the researchers used a non-isogenic soy variety as the non-GM comparator. This was unavoidable, given the refusal of GM seed companies to release their patented seeds to independent researchers.16
An objective assessment of Malatesta’s findings would have concluded that while the results do not show that GM soy was more toxic than the non-GM isogenic variety (because the isogenic variety was not used), they do show that GM herbicide-tolerant soy was more toxic than the wild-type soybean tested, either because of the herbicide used, or the effect of the genetic engineering process, or the different environmental conditions in which the two soy types were grown, or a combination of two or more of these factors.
In an extraordinary move, Snell and colleagues offered as the main counter to Malatesta’s experimental findings a poster presentation offering no new or existing data and with no references, presented at a Society of Toxicology conference17 by two employees of the chemical industry consultancy firm Exponent.18 Though at first glance the reference given by Snell and colleagues has the appearance of a peer-reviewed paper, it is not. An abstract of the presentation was also published by the Society of Toxicology in its collection of conference proceedings.19
Presentations given at conferences are not usually subjected to the scrutiny given to peer-reviewed publications. They certainly do not carry sufficient weight to counter original research findings from laboratory animal feeding experiments with GM foods, such as Malatesta’s. This is particularly true when they do not base their argument on hard data, as in the case of this opinion piece.
Snell and colleagues use double standards
Snell and colleagues dismiss studies findings of risk on the basis that the researchers did not use the non-GM isogenic comparator, while accepting findings of safety in studies with the same methodological weakness.
They also accept as proof of GMO safety some studies in which the number of animals is not stated,6 meaning that it is not possible to analyze the statistics to see if the findings are statistically significant (and therefore meaningful).
Other studies accepted by Snell and colleagues as proof of GMO safety include some with such small group sizes (for example, of six animals) that no conclusions can be drawn from them.11
It is educational to recall how critics of Séralini’s 2012 study1 claimed that his groups of ten animals per sex per group were too small to draw any conclusions.20 Though this allegation is incorrect according to the standards of the Organization for Economic Cooperation and Development for chronic toxicity studies, which requires that only ten animals per sex per group are analyzed for blood and urine chemistry,21 it is clear that studies using sample sizes of only six animals cannot be used to claim safety for GM foods.
As a result of these double standards, Snell and colleagues’ review is fatally biased and no conclusions can be drawn from it.
Russian long-term studies not followed up
Two long-term multigenerational studies conducted by Russian researchers found worrying results but were never followed up. On the contrary, at least one of the research studies was deliberately suppressed.
This was a multigenerational study in rats by the researcher Irina Ermakova. The study found decreased fertility in rats and decreased weight gain and increased mortality in pups, in groups fed GM Roundup-tolerant soy.22,23
Ermakova never had the chance to publish her findings in full in an international journal. Instead her work was subjected to a deceptive and highly irregular review process by the editor of the journal Nature Biotechnology. She was sent a dummy proof of what she thought was going to be her article, complete with her byline as author.24 However, the article as published was very different. It was an attack on her work by four pro-GM critics.
Contrary to the ethics of scientific publishing, the critics’ conflicts of interest with the GM crop industry went undisclosed by the journal.25 Also Ermakova was not shown their criticisms before the article was published, so she did not have a chance to defend herself in the same issue of the journal.26
Ermakova’s treatment at the hands of the editor of Nature Biotechnology and the four pro-GM scientists attracted condemnation from scientists27 and in the media.28,29,30
Harvey Marcovitch, director of the Committee on Publication Ethics (COPE), which sets ethical standards for academic journals, commented, “This is a type of publication which I have never encountered.” He said that while reading it he was struck by “some surprising things”. He was unwilling to speculate as to what exactly happened: “Either the editor was trying out a new form of experimentation, in which not everything went according to plan, or there was indeed a conspiracy or whatever one wants to call it.”28
Nevertheless, the journal editor kept his job and Ermakova was deprived of any chance of ever publishing her work in an international journal.
In a separate experiment that was only reported in the Russian media and not published in a peer-reviewed journal, Russian biologist Alexey V. Surov and his team fed three generations of hamsters different diets (one without soy, one with non-GM soy, one with GM soy, and the final one with higher amounts of GM soy). By the third generation, the pups from the fourth group suffered a high mortality rate and most of the adults lost the ability to reproduce.31
It is not possible to judge the quality of Ermakova’s or Surov’s studies because neither study has been published in full in an international journal. The studies should be repeated to confirm or refute the reported findings.
Few long-term and in-depth studies have been carried out on GM foods and several studies that have been carried out have found toxic effects. A review by Snell and colleagues purporting to present long-term studies showing long-term safety is misleading, with double standards being used to dismiss findings of harm while accepting at face value findings of safety. A Russian long-term study that produced concerning results was suppressed and has not been followed up.
There is no evidence that commercialized GM foods are safe to eat over the long term and conversely there is some evidence that they are not safe.
- Séralini GE, Clair E, Mesnage R, et al. [RETRACTED:] Long term toxicity of a Roundup herbicide and a Roundup-tolerant genetically modified maize. Food Chem Toxicol. 2012;50:4221–4231.
- Haut Conseil des Biotechnologies Comité Scientifique (France). Avis en réponse à la saisine du 24 septembre 2012 relative à l’article de Séralini et al (Food and Chemical Toxicology, 2012). 2012. Available at: http://bit.ly/ZODCdn.
- ANSES (French Agency for Food Environmental and Occupational Health & Safety). Opinion concerning an analysis of the study by Séralini et al. (2012) “Long term toxicity of a ROUNDUP herbicide and a ROUNDUP-tolerant genetically modified maize.” 2012. Available at: http://www.anses.fr/sites/default/files/files/BIOT2012sa0227EN.pdf.
- ANSES (French Agency for Food Environmental and Occupational Health & Safety). ANSES highlights the weaknesses of the study by Séralini et al., but recommends new research on the long-term effects of GMOs. 2012. Available at: http://www.anses.fr/en/content/anses-highlights-weaknesses-study-s%C3%A9ralini-et-al-recommends-new-research-long-term-effects.
- Malatesta M. A long-term study on female mice fed on a genetically modified soybean: effects on liver ageing. Histochem Cell Biol. 2008;130:967–977.
- Sakamoto Y, Tada Y, Fukumori N, et al. [A 104-week feeding study of genetically modified soybeans in F344 rats]. Shokuhin Eiseigaku Zasshi J Food Hyg Soc Jpn. 2008;49:272–82.
- Snell C, Aude B, Bergé J, et al. Assessment of the health impact of GM plant diets in long-term and multigenerational animal feeding trials: A literature review. Food Chem Toxicol. 2012;50:1134–48.
- Brake J, Faust MA, Stein J. Evaluation of transgenic event Bt11 hybrid corn in broiler chickens. Poult Sci. 2003;82:551–9.
- Steinke K, Guertler P, Paul V, et al. Effects of long-term feeding of genetically modified corn (event MON810) on the performance of lactating dairy cows. J Anim Physiol Anim Nutr Berl. 2010;94:e185–93. doi:10.1111/j.1439-0396.2010.01003.x.
- Sissener NH, Sanden M, Bakke AM, Krogdahl A, Hemre GI. A long term trial with Atlantic salmon (Salmo salar L.) fed genetically modified soy; focusing general health and performance before, during and after the parr–smolt transformation. Aquaculture. 2009;2009:108–117.
- Flachowsky G, Aulrich K, Böhme H, Halle I. Studies on feeds from genetically modified plants (GMP) – Contributions to nutritional and safety assessment. Anim Feed Sci Technol. 2007;133:2–30.
- Kilic A, Akay MT. A three generation study with genetically modified Bt corn in rats: Biochemical and histopathological investigation. Food Chem Toxicol. 2008;46:1164–70. doi:10.1016/j.fct.2007.11.016.
- Malatesta M, Biggiogera M, Manuali E, Rocchi MBL, Baldelli B, Gazzanelli G. Fine structural analyses of pancreatic acinar cell nuclei from mice fed on genetically modified soybean. Eur J Histochem. 2003;47:385–388.
- Malatesta M, Caporaloni C, Gavaudan S, et al. Ultrastructural morphometrical and immunocytochemical analyses of hepatocyte nuclei from mice fed on genetically modified soybean. Cell Struct Funct. 2002;27:173–80.
- Vecchio L, Cisterna B, Malatesta M, Martin TE, Biggiogera M. Ultrastructural analysis of testes from mice fed on genetically modified soybean. Eur J Histochem. 2004;48:448–54.
- Waltz E. Under wraps – Are the crop industry’s strong-arm tactics and close-fisted attitude to sharing seeds holding back independent research and undermining public acceptance of transgenic crops? Nat Biotechnol. 2009;27(10):880–882. doi:10.1038/nbt1009-880.
- Williams AL, DeSesso JM. Genetically-modified soybeans: A critical evaluation of studies addressing potential changes associated with ingestion; Abstract 1154, Poster Board 424, Safety Concerns of Food and Natural Products. 2010. Available at: http://www.exponent.com/files/Uploads/Documents/news%20and%20features/SOT%20Presentation%20Handout_draft.pdf.
- Williams AL, Watson RE, DeSesso JM. Developmental and reproductive outcomes in humans and animals after glyphosate exposure: A critical analysis. J Toxicol Environ Health Part B. 2012;15:39–96.
- Williams AL, DeSesso JM. Genetically-modified soybeans: A critical evaluation of studies addressing potential changes associated with ingestion; Abstract 1154. The Toxicologist. 2010;114:246.
- GMOSeralini.org. Criticism: Séralini used too few animals to draw any conclusions. 2013. Available at: http://gmoseralini.org/criticism-seralini-used-too-few-animals/.
- Organisation for Economic Cooperation and Development (OECD). OECD guideline no. 452 for the testing of chemicals: Chronic toxicity studies: Adopted 7 September 2009. 2009. Available at: http://bit.ly/LxJT1Z.
- Ermakova I. Genetically modified soy leads to the decrease of weight and high mortality of rat pups of the first generation. Preliminary studies. Ecosinform. 2006;1:4–9.
- Ermakova I. [Influence of soy with gene EPSPS CP4 on the physiological state and reproductive function of rats in the first two generations]. Contemp Probl Sci Educ. 2009;5:15–20.
- Nature Biotechnology. Supplementary materials 1: Email correspondence between Nature Biotechnology and Irina Ermakova; and Supplementary materials 2: Galley proof for Irina Ermakova. 2007. Available at: http://www.nature.com/nbt/journal/v25/n12/extref/nbt1207-1359-S1.pdf.
- Marshall A. GM soybeans and health safety – a controversy reexamined. Nat Biotechnol. 2007;25:981–987.
- Ermakova IV. GM soybeans – revisiting a controversial format. Nat Biotechnol. 2007;25:1351–1360.
- Ermakova I, John B, Ho MW, et al. Letters to the editor. Nat Biotechnol. 2007;25:1351–1360.
- Fischer R. The excommunication of a heretic. WOZ. http://www.gmwatch.org/latest-listing/46-2007/5861-the-excommunication-of-a-heretic. Published November 13, 2007.
- Latham J, Wilson A. What is Nature Biotechnology good for? Indep Sci News. 2007. Available at: http://independentsciencenews.org/health/nature-biotechnology/.
- John B. Journal editor admits involvement in Ermakova “set-up.” GM-Free Cymru. 2007. Available at: http://www.gmfreecymru.org/pivotal_papers/involvement_ermakova.htm.
- Domnitskaya M. Russia says genetically modified foods are harmful. Voice of Russia. http://english.ruvr.ru/2010/04/16/6524765.html. Published April 16, 2010.