Expert Comments – GM maize and rats
In 2012, a study was published in Food and Chemical Toxicology by Séralini et al. titled “Long term toxicity of a Roundup herbicide and a Roundup-tolerant genetically modified maize.” The paper’s design, methodology and use of statistical tools attracted a great deal of criticism from the scientific community and the paper was eventually retracted by the journal.
The same group are now republishing the study in a different, open access journal, and launching their results to the media in Paris on Tuesday.The republished study: long-term toxicity of a Roundup herbicide and a Roundup-tolerant genetically modified maize’ by Gilles-Eric Séralini et al. will be published in Environmental Sciences Europe at 5:00 am Eastern Time on Tuesday 24th June 2014, which is also when the embargo will lift.
Here are some comments collected by the Science Media Centre of Canada: these comments are condensed from longer versions. If you’d like the complete comments from any one of these experts or if you need more help finding experts who can comment on this topic, give us a call at 514-887-8279 or 613-301-1187.
Additional comments from our colleagues at the Science Media Centre UK are included below.
Cami Ryan, Professional Affiliate with the Department of Bioresource Policy, Business and Economics, College of Agriculture and Bioresources, University of Saskatchewan and an independent research consultant.
First, and most importantly, this is the same poorly designed scientific study that has been widely discredited by health and food safety agencies all over the world when it was published in 2012 (and subsequently retracted in 2013 ) by Food and Chemical Toxicology. Sample sizes and controls are still a problem (there are well-articulated OECD guidelines on this: and there are several holes in terms of interpretation of data (see this, lots of links to other ‘takes’ on this).
If Seralini’s goal here was the pursuit of good, quality science, he would have accepted the original retraction, paid mind to the broader criticisms that he received from subject-matter scientific experts and organizations and executed a new study (using an appropriate methodology) before attempting to publish again. Quality science is published in quality journals. If Seralini was really onto something here, it most certainly would have been taken up by more reputable academic journals such as Nature or Science.
Disclosure statement from Cami Ryan
My current work is funded through various entities including not-for-profit grower groups and organizations as well as Genome Canada’s Genome Prairie/GELS program. No conflict.
__
Alan McHughen, Plant Biotechnologist and Geneticist at College of Natural and Agricultural Sciences, UC Riverside, USA. He is a public sector educator, scientist and consumer advocate. He helped develop US and Canadian regulations governing the safety of genetically engineered crops and foods. He served on US National Academy of Sciences panels investigating the environmental effects of transgenic plants, a second investigating the safety of genetically engineered foods and helped review a third looking at sustainability and economic impacts of biotechnology on US agriculture.
The number of rats used was too small to detect a meaningful difference in treatments. In this ‘new’ study, the number of rats remains the same, too small to yield meaningful results. To illustrate for those not familiar, it’s as if Seralini tossed a coin two times, and the coin came up ‘heads’ both times. With this result, Seralini is trying to convince us that he has a magic coin that only comes up ‘heads’.
The strain of rats used (Sprague-Dawley) was inappropriate for this type of two-year long study, as these rats have a natural predisposition to form tumors, regardless of the treatment. Seralini has not and can not justify this fatal error in experimental design
Seralini now asserts that he follows all European ethical guidelines for animal care. But he still shows rats with massive tumors, and the European ethical standards requires rats be euthanized when tumors reach 4mm diameter. Clearly the rats in the photos have tumors larger than 4mm, about the size of a small pea.
There’s no dose response. In toxicity or carcinogenicity studies, increasing the dose of an actual toxin or carcinogen leads to greater effect. But Seralini’s data do not show such dose effects, and Seralini still does not properly explain why.
In short, the ‘new’ paper will have the same impact as the original, retracted paper, because the original data were useless, and there is no new data. The methodology was faulty then, and, as there is no new methodology, it remains faulty now.
Disclosure statement for Alan McHughen:
I am happy to advise that I am a public sector academic scientist serving the public interest, and as such, my research program is funded entirely from public sources; I do not accept private funds. As a result, I have no research connection to either Mr Seralini (or his coauthors), or CRIIGEN, or Monsanto.
___
Robert Wager, Technician and faculty member in the Biology Department at Vancouver Island University. M.Sc in Biochemistry and Molecular biology (UBC 1993). His website has dozens of articles for the general public and he wrote several peer reviewed articles. He has given public talks (>30) on GMO’s and have been involved in GMO research with an emphasis on public education for 14 years.
There are two main issues with the data I think need explanation by Seralini. First, the basic rule of toxicology is the dose makes the poison. Everything can be toxic if the dose is high enough. Therefore all proper toxicology studies show dose response curves (the higher the dose, the greater the effect). None of the data in the Seralini paper show dose response curves.
The second point and probably more important point is the use of inappropriate strain of rats. Sprague-Dawley is a strain of rat that spontaneously generates tumors. For this reason they are extensively used in cancer research. One of the main criticisms of the original 2012 paper was the omission of the control rat data and photos. The re-release again does not show the control rats.
It is very clear that review of the science literature show the conclusions of Seralini et al. are not supported by the vast majority of publications in this area.
Disclosure statement for Robert Wager
“I have no financial connection with any biotech company. I have never received any personal pay from any biotech company, nor does my institute receive/administer and grants from biotech companies. I have serious difference of opinion on GMO’s with Seralini et al. but have no connection to him or his institute. I am an academic who hates the impact pseudo-science is having on public policy and that is my only motivation.”
__
Marcel Kuntz, biologist, director of research at Centre National de la Recherche Scientifique (CNRS, France) and professor at University of Grenoble-Alpes, author of two books about GMO: Les OGM, l’environnement et la santé (Ellipses, 2006) et OGM, la question politique (Presses Universitaires de Grenoble, 2014).
The authors reach essentially the same conclusions that were already refuted and they don’t take into account the fundamental criticisms addressed to them.
Looking specifically at the tumors: The breed of rats used is subject to spontaneous tumor development. To identify a statistically reliable increase in tumors in a group of rats requires a large number of individuals. This re-publication is still deficient on this point.
These tumors were the most spectacular element of the media operation conducted by the authors. It should be noted that they showed photographs of three rats: a rat who used the GMO NK603, another who drank Roundup and a third absorbed both. Unlike the most basic scientific approach, no control rats (which didn’t eat GMO or drink herbicide) were shown. These control rats are still not shown in the re-publication.
Disclosure statement for Marcel Kuntz
My only income comes from my employers mentioned above (and marginally the copyright of my books). I have no current contract with a private company, or as an individual, nor to my laboratory. My current scientific work is basic research, unrelated to the marketing of a variety of plant (GM or not). I don’t hold any patents, nor collect, nor received income as an inventor of a patent held by others. I do not identify any change in this situation in the foreseeable future.
____
The comments below were collected by our colleagues at the Science Media Centre UK
___
Science Media Centre Round-up VERSION 3
EMBARGOED UNTIL 10:00 UK TIME on Tuesday 24 June 2014
NEW COMMENT: Tom Sanders, Professor of Nutrition & Dietetics, King’s College London, said:
“Republishing data that was faulty in the first place in study design and analysis does not provide redemption. Furthermore, it is now possible to publish almost anything in Open Access journals!.
“Seralini did not follow conventional methods for assessing animal toxicity and made most of the measurements at the end of life. When a very large number measurements are made statistically significant differences will occur play of chance.
“The figures of an animal with a large tumour serve no scientific purpose. There are numerous omissions of probabilities which could lead the less critical reader to infer differences that are not statistically significant.
Prof David Spiegelhalter, Winton Professor of the Public Understanding of Risk, University of Cambridge, said:
“The article still does not appear to have had proper statistical refereeing, and the methods and reporting are obscure. The claimed effects show no dose-response, and so the conclusions rest entirely on a comparison with ten control rats of each sex. This is inadequate.”
“The study needs replicating by a truly independent laboratory using appropriate sample sizes. I agree with the authors that this whole area would benefit from greater transparency of data and improved experimental and statistical methods”
Professor Joe N. Perry,Visiting Professor of Biometry, University of Greenwich, said:
“This paper appears to be based on the same data as Seralini’s previous 2012 paper, with no real new information and only minor rephrasing and a few new references. Therefore, I doubt whether my conclusions would differ from those of the vast majority of independent members of the scientific community, who concluded in 2012 that there was insufficient evidence to justify the claims of CRIIGEN and Giles-Eric Seralini. However, I do welcome Seralini’s promise to publish his raw data and my hope is that all organisations involved in GM risk assessment will, wherever possible in the future, publish in full their raw data in the spirit of full transparency and openness.”
Declared interests
None declared
____
When originally published in Food & Chemical Toxicology the SMC UK sent the below Before the Headlines analysis, which has been amended to reflect changes in the republished study:
“Before The Headlines” analyses are structured in a simple format, with clear summaries of what the paper in question claims, and a concise assessment of the strengths and limitations.
Before The Headlines is a service provided to the SMC by volunteer statisticians: members of the Royal Statistical Society (RSS) and Statisticians in the Pharmaceutical Industry (PSI). For more information on Before the Headlines visit this site:
http://www.sciencemediacentre.org/working-with-us/for-journalists/headlines-for-journalists/volunteers/
Before The Headlines
| COMMENTARY |
| Title, Date of Publication & Journal |
| ‘Republished study: long-term toxicity of a Roundup herbicide and a Roundup-tolerant genetically modified maize’ by Gilles-Eric Séralini et al, published by SpringerOpen, 24 June 2014.
[Originally publication: ‘Long term toxicity of a Roundup herbicide and a Roundup-tolerant genetically modified maize’, Food and Chemical Toxicology,19 September 2012] |
| Claim supported by evidence? |
| The conclusions of the new study are written in different language to that of the original publication. Nonetheless the clear language regarding rats fed on a diet containing NK603 Roundup tolerant GM maize dying earlier and having more tumours than rats fed on a standard diet is not supported by statistical significance.
(Note: biochemical analysis has not been reviewed by a Before the Headlines statistician)
[Original publication: The paper does not prove the claim that rats fed on a diet containing NK603 Roundup tolerant GM maize died earlier than rats fed on a standard diet.] |
| Summary |
| Looking at the graphs of mortality for females (Fig 6), death might appear to be earlier with a GM diet than a standard diet; however this has not been proven statistically. Mortality is broadly similar for males with a GM diet and a standard diet. Similar comments apply to pathological findings.
It is evident that some treated groups have lower death rates / tumour rates than the comparable controls. This is not reported in the abstract.
There is no consistent dose-trend – if there were an effect, we would expect to see increases (e.g. in deaths) from 0 to 11 to 22 to 33. In contrast – in males, 33 (and C) have the lowest numbers of deaths.
[Same as original publication] |
| Strengths/Limitations |
| “In females, all treatment groups showed a two- to threefold increase in mortality, and deaths were earlier. This difference was also evident in three male groups fed with GM maize” * – this statement has not been subjected to standard methods of statistical analysis for survival time. The phrase “two- to threefold increase in mortality” is based on exceptionally small numbers.
The authors suggest a threshold – this rarely occurs in practice. We would expect greatest mortality/ toxicity at the highest dose in a well-designed study. With small numbers as in this study we would expect to see a general trend of mortality increasing with dose.
It seems likely that the numbers in each group are too small for standard methods of statistical analysis to find significant effects on mortality or pathological findings.
There are virtually no p-values presented. The group sizes are small. This should be interpreted with extreme caution.
It is notable that the figures do not present deaths in the control group in a similar manner (no step graph for controls). This makes it more difficult to compare the other groups with the controls.
There are many treated groups, and a number of parameters. There is obvious potential for selected reporting, selection of methods etc. In such small groups, with so many parameters this is a big issue. This issue is amplified in the abstract and further in the press release. Strong statements are issued without sufficient backing / explanation.
Deaths are compared to the control mean (for males and females). Due to the distribution of deaths (most deaths occur in old age), this is almost bound to exclude the large majority of deaths in the control groups. The 2 or 3 deaths in the control group is determined by their methods, but is inappropriately presented as a true observation.
*[In the original publication this quote was worded differently “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.” Otherwise same as original publication.] |
* ‘Republished study: long-term toxicity of a Roundup herbicide and a Roundup-tolerant genetically modified maize’ by Gilles-Eric Séralini et al. will be published by SpringerOpen at 10:00 UK time on Tuesday 24th June 2014, which is also when the embargo will lift.
** ‘Long term toxicity of a Roundup herbicide and a Roundup-tolerant
genetically modified maize’ by Seralini et al., published in Food and Chemical Toxicology on Wednesday 19th September 2012.
-30-
GM rats and maize | Expert Comments
Expert Comments – GM maize and rats
In 2012, a study was published in Food and Chemical Toxicology by Séralini et al. titled “Long term toxicity of a Roundup herbicide and a Roundup-tolerant genetically modified maize.” The paper’s design, methodology and use of statistical tools attracted a great deal of criticism from the scientific community and the paper was eventually retracted by the journal.
The same group are now republishing the study in a different, open access journal, and launching their results to the media in Paris on Tuesday.The republished study: long-term toxicity of a Roundup herbicide and a Roundup-tolerant genetically modified maize’ by Gilles-Eric Séralini et al. will be published in Environmental Sciences Europe at 5:00 am Eastern Time on Tuesday 24th June 2014, which is also when the embargo will lift.
Here are some comments collected by the Science Media Centre of Canada: these comments are condensed from longer versions. If you’d like the complete comments from any one of these experts or if you need more help finding experts who can comment on this topic, give us a call at 514-887-8279 or 613-301-1187.
Additional comments from our colleagues at the Science Media Centre UK are included below.
Cami Ryan, Professional Affiliate with the Department of Bioresource Policy, Business and Economics, College of Agriculture and Bioresources, University of Saskatchewan and an independent research consultant.
First, and most importantly, this is the same poorly designed scientific study that has been widely discredited by health and food safety agencies all over the world when it was published in 2012 (and subsequently retracted in 2013 ) by Food and Chemical Toxicology. Sample sizes and controls are still a problem (there are well-articulated OECD guidelines on this: and there are several holes in terms of interpretation of data (see this, lots of links to other ‘takes’ on this).
If Seralini’s goal here was the pursuit of good, quality science, he would have accepted the original retraction, paid mind to the broader criticisms that he received from subject-matter scientific experts and organizations and executed a new study (using an appropriate methodology) before attempting to publish again. Quality science is published in quality journals. If Seralini was really onto something here, it most certainly would have been taken up by more reputable academic journals such as Nature or Science.
Disclosure statement from Cami Ryan
My current work is funded through various entities including not-for-profit grower groups and organizations as well as Genome Canada’s Genome Prairie/GELS program. No conflict.
__
Alan McHughen, Plant Biotechnologist and Geneticist at College of Natural and Agricultural Sciences, UC Riverside, USA. He is a public sector educator, scientist and consumer advocate. He helped develop US and Canadian regulations governing the safety of genetically engineered crops and foods. He served on US National Academy of Sciences panels investigating the environmental effects of transgenic plants, a second investigating the safety of genetically engineered foods and helped review a third looking at sustainability and economic impacts of biotechnology on US agriculture.
The number of rats used was too small to detect a meaningful difference in treatments. In this ‘new’ study, the number of rats remains the same, too small to yield meaningful results. To illustrate for those not familiar, it’s as if Seralini tossed a coin two times, and the coin came up ‘heads’ both times. With this result, Seralini is trying to convince us that he has a magic coin that only comes up ‘heads’.
The strain of rats used (Sprague-Dawley) was inappropriate for this type of two-year long study, as these rats have a natural predisposition to form tumors, regardless of the treatment. Seralini has not and can not justify this fatal error in experimental design
Seralini now asserts that he follows all European ethical guidelines for animal care. But he still shows rats with massive tumors, and the European ethical standards requires rats be euthanized when tumors reach 4mm diameter. Clearly the rats in the photos have tumors larger than 4mm, about the size of a small pea.
There’s no dose response. In toxicity or carcinogenicity studies, increasing the dose of an actual toxin or carcinogen leads to greater effect. But Seralini’s data do not show such dose effects, and Seralini still does not properly explain why.
In short, the ‘new’ paper will have the same impact as the original, retracted paper, because the original data were useless, and there is no new data. The methodology was faulty then, and, as there is no new methodology, it remains faulty now.
Disclosure statement for Alan McHughen:
I am happy to advise that I am a public sector academic scientist serving the public interest, and as such, my research program is funded entirely from public sources; I do not accept private funds. As a result, I have no research connection to either Mr Seralini (or his coauthors), or CRIIGEN, or Monsanto.
___
Robert Wager, Technician and faculty member in the Biology Department at Vancouver Island University. M.Sc in Biochemistry and Molecular biology (UBC 1993). His website has dozens of articles for the general public and he wrote several peer reviewed articles. He has given public talks (>30) on GMO’s and have been involved in GMO research with an emphasis on public education for 14 years.
There are two main issues with the data I think need explanation by Seralini. First, the basic rule of toxicology is the dose makes the poison. Everything can be toxic if the dose is high enough. Therefore all proper toxicology studies show dose response curves (the higher the dose, the greater the effect). None of the data in the Seralini paper show dose response curves.
The second point and probably more important point is the use of inappropriate strain of rats. Sprague-Dawley is a strain of rat that spontaneously generates tumors. For this reason they are extensively used in cancer research. One of the main criticisms of the original 2012 paper was the omission of the control rat data and photos. The re-release again does not show the control rats.
It is very clear that review of the science literature show the conclusions of Seralini et al. are not supported by the vast majority of publications in this area.
Disclosure statement for Robert Wager
“I have no financial connection with any biotech company. I have never received any personal pay from any biotech company, nor does my institute receive/administer and grants from biotech companies. I have serious difference of opinion on GMO’s with Seralini et al. but have no connection to him or his institute. I am an academic who hates the impact pseudo-science is having on public policy and that is my only motivation.”
__
Marcel Kuntz, biologist, director of research at Centre National de la Recherche Scientifique (CNRS, France) and professor at University of Grenoble-Alpes, author of two books about GMO: Les OGM, l’environnement et la santé (Ellipses, 2006) et OGM, la question politique (Presses Universitaires de Grenoble, 2014).
The authors reach essentially the same conclusions that were already refuted and they don’t take into account the fundamental criticisms addressed to them.
Looking specifically at the tumors: The breed of rats used is subject to spontaneous tumor development. To identify a statistically reliable increase in tumors in a group of rats requires a large number of individuals. This re-publication is still deficient on this point.
These tumors were the most spectacular element of the media operation conducted by the authors. It should be noted that they showed photographs of three rats: a rat who used the GMO NK603, another who drank Roundup and a third absorbed both. Unlike the most basic scientific approach, no control rats (which didn’t eat GMO or drink herbicide) were shown. These control rats are still not shown in the re-publication.
Disclosure statement for Marcel Kuntz
My only income comes from my employers mentioned above (and marginally the copyright of my books). I have no current contract with a private company, or as an individual, nor to my laboratory. My current scientific work is basic research, unrelated to the marketing of a variety of plant (GM or not). I don’t hold any patents, nor collect, nor received income as an inventor of a patent held by others. I do not identify any change in this situation in the foreseeable future.
____
The comments below were collected by our colleagues at the Science Media Centre UK
___
Science Media Centre Round-up VERSION 3
EMBARGOED UNTIL 10:00 UK TIME on Tuesday 24 June 2014
NEW COMMENT: Tom Sanders, Professor of Nutrition & Dietetics, King’s College London, said:
“Republishing data that was faulty in the first place in study design and analysis does not provide redemption. Furthermore, it is now possible to publish almost anything in Open Access journals!.
“Seralini did not follow conventional methods for assessing animal toxicity and made most of the measurements at the end of life. When a very large number measurements are made statistically significant differences will occur play of chance.
“The figures of an animal with a large tumour serve no scientific purpose. There are numerous omissions of probabilities which could lead the less critical reader to infer differences that are not statistically significant.
Prof David Spiegelhalter, Winton Professor of the Public Understanding of Risk, University of Cambridge, said:
“The article still does not appear to have had proper statistical refereeing, and the methods and reporting are obscure. The claimed effects show no dose-response, and so the conclusions rest entirely on a comparison with ten control rats of each sex. This is inadequate.”
“The study needs replicating by a truly independent laboratory using appropriate sample sizes. I agree with the authors that this whole area would benefit from greater transparency of data and improved experimental and statistical methods”
Professor Joe N. Perry,Visiting Professor of Biometry, University of Greenwich, said:
“This paper appears to be based on the same data as Seralini’s previous 2012 paper, with no real new information and only minor rephrasing and a few new references. Therefore, I doubt whether my conclusions would differ from those of the vast majority of independent members of the scientific community, who concluded in 2012 that there was insufficient evidence to justify the claims of CRIIGEN and Giles-Eric Seralini. However, I do welcome Seralini’s promise to publish his raw data and my hope is that all organisations involved in GM risk assessment will, wherever possible in the future, publish in full their raw data in the spirit of full transparency and openness.”
Declared interests
None declared
____
When originally published in Food & Chemical Toxicology the SMC UK sent the below Before the Headlines analysis, which has been amended to reflect changes in the republished study:
“Before The Headlines” analyses are structured in a simple format, with clear summaries of what the paper in question claims, and a concise assessment of the strengths and limitations.
Before The Headlines is a service provided to the SMC by volunteer statisticians: members of the Royal Statistical Society (RSS) and Statisticians in the Pharmaceutical Industry (PSI). For more information on Before the Headlines visit this site:
http://www.sciencemediacentre.org/working-with-us/for-journalists/headlines-for-journalists/volunteers/
Before The Headlines
[Originally publication: ‘Long term toxicity of a Roundup herbicide and a Roundup-tolerant genetically modified maize’, Food and Chemical Toxicology,19 September 2012]
(Note: biochemical analysis has not been reviewed by a Before the Headlines statistician)
[Original publication: The paper does not prove the claim that rats fed on a diet containing NK603 Roundup tolerant GM maize died earlier than rats fed on a standard diet.]
It is evident that some treated groups have lower death rates / tumour rates than the comparable controls. This is not reported in the abstract.
There is no consistent dose-trend – if there were an effect, we would expect to see increases (e.g. in deaths) from 0 to 11 to 22 to 33. In contrast – in males, 33 (and C) have the lowest numbers of deaths.
[Same as original publication]
The authors suggest a threshold – this rarely occurs in practice. We would expect greatest mortality/ toxicity at the highest dose in a well-designed study. With small numbers as in this study we would expect to see a general trend of mortality increasing with dose.
It seems likely that the numbers in each group are too small for standard methods of statistical analysis to find significant effects on mortality or pathological findings.
There are virtually no p-values presented. The group sizes are small. This should be interpreted with extreme caution.
It is notable that the figures do not present deaths in the control group in a similar manner (no step graph for controls). This makes it more difficult to compare the other groups with the controls.
There are many treated groups, and a number of parameters. There is obvious potential for selected reporting, selection of methods etc. In such small groups, with so many parameters this is a big issue. This issue is amplified in the abstract and further in the press release. Strong statements are issued without sufficient backing / explanation.
Deaths are compared to the control mean (for males and females). Due to the distribution of deaths (most deaths occur in old age), this is almost bound to exclude the large majority of deaths in the control groups. The 2 or 3 deaths in the control group is determined by their methods, but is inappropriately presented as a true observation.
*[In the original publication this quote was worded differently “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.” Otherwise same as original publication.]
* ‘Republished study: long-term toxicity of a Roundup herbicide and a Roundup-tolerant genetically modified maize’ by Gilles-Eric Séralini et al. will be published by SpringerOpen at 10:00 UK time on Tuesday 24th June 2014, which is also when the embargo will lift.
** ‘Long term toxicity of a Roundup herbicide and a Roundup-tolerant
genetically modified maize’ by Seralini et al., published in Food and Chemical Toxicology on Wednesday 19th September 2012.
-30-
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