Why Monsanto's attempt to "disappear" tumours by using historical control data is invalid
An Earth Open Source briefing
26 September 2012
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Summary

Monsanto has invoked "historical norms" to dismiss findings of increased tumours and mortality rates in rats fed GM maize NK603, as well as in rats exposed to levels of Roundup claimed by regulators to be safe, in a 2-year study by Professor Gilles-Eric Seralini's research team in France.

Monsanto says that the increased mortality rates and tumour incidence "fall within historical norms for this strain of laboratory rats, which is known for a high incidence of tumours".

By "historical norms" and "within this historical range", Monsanto means historical control data data from various other studies that they find in the scientific literature or elsewhere. 

However, the use of historical control data is an unscientific strategy used by industry and some regulators to dismiss statistically significant findings of toxicity in treated (exposed) groups of laboratory animals in toxicological studies intended to evaluate safety of pesticides, chemicals, and GMOs.

The only scientifically valid control for such experiments is the concurrent control, not historical control data. This is because scientific experiments are designed to reduce variables to a minimum. The concurrent control group achieves this because it consists of animals treated identically to the experimental group, except that they are not exposed to the substance under study. Thus, the only variable is exposure to the substance(s) being tested in the case of Seralini's experiments, NK603 maize and Roundup.

With this experimental design, any differences seen in the treated animals are very likely to be due to the substance being tested, rather than due to irrelevant factors, as is the case with historical control data. 

Historical control data consists of a wide range of data gathered from diverse experiments performed under widely differing conditions. As a result, factors totally irrelevant to the study are responsible for the majority of differences in historical control data. Such factors may include environmental conditions, different diet for the animals, different pesticide residue exposures, different genetic background of the animals, even different years in which the experiments were performed, which is known to affect results for reasons that are poorly understood.

In contrast, using the concurrent controls reduces such variables to a minimum and enables researchers to reach evidence-based conclusions about the effects of the substance being tested. 

For these reasons, toxicological studies performed by independent (non-industry) scientists and published in the peer-reviewed literature hardly ever invoke historical control data. They certainly do not use it to dismiss statistically significant findings of harm in treated groups of animals. 

Those who do use historical control data in this way include industry-affiliated sources and some regulators. The practice was introduced into risk assessment by the Organisation for Economic Cooperation and Development. Even the OECD, however, advises caution in the use of such data and warns against it in evaluating findings of tumours (such as those seen in Seralini's study). Even by weak OECD standards, Seralini's findings are valid. 

Even if we were to follow Monsanto's recommendation and use historical control data in evaluating Seralini's findings, the historical control data cited by Monsanto is invalid because it relates to rats of a different origin (SD rats from Charles River Labs) than Seralini's rats (SD rats from Harlan). Seralini took historical data on the Harlan SD rat fully into account in his study and the results still show that the tumour increase and other effects were statistically significant. The tumour incidence in the test groups in his study was overall around three times higher than the normal rate observed in the Harlan SD rat strain he used, as reported in the literature.

Finally, the "tumour-prone rat" argument used by Monsanto and others to dismiss Seralini's findings of increased tumours is spurious. The key point about Seralini's tumour findings was that the controls got some tumours, but the treated groups got significantly more tumours, and these appeared sooner and were more aggressive than those of the control groups.

So what matters in this study is not whether the rat strain was or was not prone to develop tumours, but 
(a) the earlier and more rapid rate of tumour development in the treated groups of animals, compared with the concurrent control, and
(b) the larger number of tumours caused by the treatment, over and above the "spontaneous" background level. 

To illustrate the point by analogy: a small proportion of people who never smoke get lung cancer. If you smoke, your risk of getting lung cancer is about 12 times higher than if you don't smoke. The measurement is called a "relative risk". So even if there were an ethnic group of people with a higher rate of naturally occurring lung cancer, if people in that group smoke, their rate of lung cancer will still increase like that of everyone else.

This is a basic principle of science and it is worrying that attempts are being made by pro-GM lobbyists to override it in the interests of keeping the products of powerful multinational biotechnology companies on the market.

The responsibility now lies with Monsanto to pay for a full 2-year carcinogenicity study on its NK603 maize and the associated pesticide, Roundup. Such a study would, however, have to be carried out, not by industry or its contracted labs, but by independent scientists commissioned by an impartial publicly funded body consisting of a wide range of stakeholders representing the public interest. 

In the meantime, NK603 must be immediately withdrawn from the market and all GMOs must be subjected to long-term testing.