SMC refuses to set the record straight or to offer the study authors right of reply

The UK Science Media Centre (SMC) predictably rushed out a collection of denigrating quotes from “experts” about the new study showing profound molecular differences between GM maize NK603 and its closest non-GM relative, including an increase in two potentially toxic compounds in the GM maize.

The problem is, the SMC's chosen “experts” apparently got the facts wrong. That is perhaps understandable, given the extreme hurry in which the SMC collected, published and circulated the quotes on the same morning that the paper was published by the journal. But it’s not excusable in a body that claims to provide accurate and evidence-based information to the public and policymakers.

Two of the authors of the original study, Dr Michael Antoniou and Dr Robin Mesnage, emailed their responses to the “expert” quotes to the SMC, pointing out that they contained factual inaccuracies and misrepresentations of the paper. They politely asked that the SMC publish the responses on the same web page as the spoiler quotes.

But Tom Sheldon of the SMC refused to do so. He responded, “I'm afraid we can't publish them” on the grounds that “We would end up being a discussion forum for scientists, and we’re not that.”

In other words, apparently uniquely among websites and publication outlets of all types, the SMC refuses to offer any right of reply to those whose work is misrepresented and libelled on its site. This confirms our long-held view that the SMC is an unaccountable body that sacrifices scientific accuracy in favour of defending and promoting GMOs and their associated pesticides, along with other risky and controversial industrial products.

That’s hardly surprising given that 70% of the SMC’s funding comes from industry.

For those members of the public and journalists who are interested in scientific accuracy and fairness, below are the scientists’ responses to the SMC-provided quotes. These responses have been widely circulated by email and are published here with permission of the authors.
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Dr Michael Antoniou and Dr Robin Mesnage respond to “Expert reaction to multiomics analysis of NK603 GM maize as published in Scientific Reports”* – quotes collected by the Science Media Centre

Dr Dan MacLean, Head of Bioinformatics at The Sainsbury Laboratory, said:

“A big issue with this analysis is that materials were collected under potentially quite different conditions. Different parts of the same farm, potentially different chemical makeups in the soil, different water contents, different elevations, exposures and temperatures. Under tight laboratory conditions the metabolome and proteome are very variable and the statistics presented here do not go anywhere near controlling for those factors.
 
“There are a huge amount of things that could be affecting the expression and levels of everything in those plants and no exploratory and controlling statistics are presented. The analysis just jumps straight into ‘everything is equal, let’s do tests’ and then uses underpowered ones. Much better statistical modelling of the variables is required to allow the workers to definitively ascribe any protein/metabolome changes to any of the experimental variables supposedly under test.
 
“This has the effect of making the decisions about what pathways are changing moot. No clear conclusions can be reached, and certainly not on the basis of p-values. Hence all downstream analyses could not be expected to show clearly any patterns because of considerable noise in the list of things that are changing.”

Dr Michael Antoniou and Dr Robin Mesnage respond:

Dan MacLean states that different growing conditions could account for the differences found between the GM and non-GM crops. However, this suggests that he has not read the paper in sufficient detail, since we state in the Materials and Methods section that all these factors were carefully controlled for, thus minimizing the possibility of their being significant contributors to the changes found in the GM crop. The soil type across all the growing areas was the same, as shown in the soil analysis in the supplementary online data (Additional File 1). The plots of land on which the different crops were grown were not sufficiently spaced to present significant differences in elevation, water content, exposures or temperature.

We also minimized the possibility that different growing seasons may be responsible for the differences. As mentioned in our article, “the fold changes observed in the comparisons of the NK603 maize sprayed with Roundup, the unsprayed NK603 maize and the isogenic control corn were highly correlated between the two cultivations performed during two different growing seasons”.

However, even though our experimental design takes into account the effect of the growing season, further experiments conducted under different environmental conditions would be needed to determine the full range of effects of the GM transformation process on this maize type.
 
Dan MacLean takes issue with the statistical analytical methods used. However, these methods have been used for decades to explore the significance of differences seen in biomedical research. It is widely known that errors can be made by using underpowered statistics when a study is measuring multiple variables and this is why we adjusted the p-values using the Benjamini-Hochberg multi-test method for a high number of comparisons.

The investigation we have undertaken using these established molecular profiling and statistical analytical methods solidly establishes the biological differences between the GM maize and its non-GM counterpart by looking at 1) the biochemical pathways affected in the plants, 2) the two maize cultivations, and 3) previously published studies. The results of these analyses were highly consistent and robust.

It is unclear which “experimental variables supposedly under test” Dan MacLean is referring to, because in fact only one experimental variable was under test – the effect of the GM process on this maize type.

Our experiment has established the biological differences between the GM and non-GM maize types tested, including elevated levels of two potentially toxic polyamines (putrescine and cadaverine) in the GM maize. However, the toxicological effects on the consumer are outside the scope of the study, as stated in the paper.

Dr Joe Perry, former Chair of the European Food Safety Authority GMO Panel, said:

“In contrast with compositional analysis, which is done for every application, and reported by EFSA, and which involves proper replicated field trials, this study appears to have been done with single, unreplicated plots.

“Therefore it is not possible to say with any certainty whether the differences reported are due to differences between the treatments or differences between the two fields (or two plots within the fields) used.
 
“In other words the basic tenets of experimental design seem not to have been followed. For that reason I could not yet describe this as a thorough piece of science.

 “Further details about the conduct of the experiment would be useful to confirm or otherwise this initial impression.”

Dr Michael Antoniou and Dr Robin Mesnage respond:

Joe Perry is incorrect in claiming that our study was done with single, unreplicated plots. In reality there were two cultivations of maize over two growing seasons, and the results were consistent over both, as presented.

The compositional analyses of GM crops performed by the GMO producer companies and submitted to regulators in support of market authorisation are extremely superficial, looking at major elements such as total proteins, carbohydrates and fats. They do not examine the types of proteins or metabolites that are present, yet these factors can determine whether a GM crop is substantially equivalent to the non-GM crop and safe to eat.

As we explained in response to Dan MacLean, differences between the fields in which the maize varieties were grown were controlled for and thus were not a significant factor in explaining the differences in the GM maize.


Prof Johnjoe McFadden, Professor of Molecular Genetics at the University of Surrey, said:
 
“The science is good as far as it goes. But the analysis only emphasises the inadequacy of the ‘substantial equivalence principle’. How equivalent does it need to be? If you perform this detailed level of analysis on any perturbation of any organism you will detect this level of change – organisms are extraordinary sensitive and, for example, similar changes are produced when treated with e.g. pesticide or herbicides or when attacked by pests.

 “I would expect that practically any perturbation to an organism will generate a response that can be detected by these powerful techniques – that is after all what life does.

“So all it shows is that GM, like pesticides, herbicides, drought, predation or even growing in a different field will produce a response by the organism. If GM was banned on these grounds then so would all herbicide pesticides and indeed anything that causes a change (which is everything).”

Dr Michael Antoniou and Dr Robin Mesnage respond:

Johnjoe McFadden seems to imply that our analysis is too detailed, but the methods employed are both cutting-edge and widely used in both research and diagnosis. If he is implying that differences in pesticide or herbicide use could be responsible for the changes in the GM maize, he is incorrect, since these factors were taken into account. Our analysis did indeed reveal an effect resulting from the application of Roundup herbicide on the GM Roundup-tolerant maize, but this factor did not make such a large difference as the GM process itself (see Figure 2 in our paper).

In addition, we conducted a detailed analysis of pesticide residues in the GM and non-GM maize (Additional File 2) and found there were none above levels of detection. There were no differences in pesticide or fertilizer use between the GM and non-GM maize, except that Roundup herbicide was applied to one cultivation of the GM maize, in accordance with how this type of maize is designed to be grown. Therefore the differences observed in the GM maize cannot be attributed to differences in pesticide use or presence.

However, even if the toxicological relevance of the differences remains unclear, what is clear is that the use of these molecular profiling tools allows a better understanding of the composition of GM plants and thus could improve the risk assessment of the non-target effects of genetic modification. In fact, genetic engineers cannot control or predict the effects of genetic engineering on plants and currently these are not measured at the molecular level.


* ‘An integrated multi-omics analysis of the NK603 Roundup-tolerant GM maize reveals metabolism disturbances caused by the transformation process’ by Robin Mesnage et al. published in Scientific Reports at 10am UK time on Monday 19 December.
http://www.nature.com/articles/srep37855