Pictures of rats plagued with large tumours were published in the Daily Mail today, alongside the following headline: “Cancer row over GM foods as study says it did THIS to rats”. The accompanying article claimed that genetically modified (GM) foods “can cause organ damage and early death in humans”.

This controversial claim has met with fierce criticism from some members of the international scientific community, who raised concerns about how the trial was conducted.

This two-year animal research included 200 rats (100 of each sex) divided across 10 groups. Three groups each containing male and female rats were fed different concentrations of a GM maize crop. Another three groups were fed GM maize that had been treated with the herbicide “Roundup”. These six groups were then compared with one control group of rats fed untreated, non-GM maize.

The researchers also included another three groups of rats who were fed non-GM maize but were given varying concentrations of diluted Roundup in their drinking water.

Controversially, the control group only consisted of 20 rats (10 male and 10 female), which some scientists argue is a small number in a trial of this kind. Most researchers would have gone for a 50-50 split, which in this case would have meant 100 control group rats and 100 GM-fed rats.

Over the two-year study, the researchers found that rats given any GM feed died slightly earlier than the control rats, and were quicker to develop tumours. But the fact that the control group was so small means that this result could be due to chance.

Another criticism is that the choice of rat breed (virgin albino Sprague-Dawley rats) is known to have a high risk of developing tumours, which means that many of the rats in the GM group may have developed tumours anyway.

Therefore, the fact that this trial was conducted in such an unusual way makes it difficult to view its results as reliable.

Update – December 6 2012

The European Food Standards Agency has recently published (November 2012) a review of the study stating that the study ‘does not meet acceptable scientific standards and there is no need to re-examine previous safety evaluations of genetically modified maize NK603.’

They have called on the Food and Chemical Toxicology journal to retract the study.

See the Further Reading section for more information.

Where did the story come from?

The study was carried out by researchers from the University of Caen in France and the University of Verona in Italy. The authors reported no conflicts of interest. The researchers acknowledged support from the Association CERES, the “Charles Léopold Mayer pour le progrès de l’Homme” Foundation, the French Ministry of Research and the Committee for Research and Independent Information on Genetic Engineering. This last source of funding is a non-proft organisation with the stated aim of making “every effort towards the removal of the status of secrecy prevailing in genetic engineering experiments and concerning genetically modified crops (GMOs), both being likely to have an impact on the environment and/or on health”.

The study was published in the peer-reviewed scientific journal Food and Chemical Toxicology.

The authors of the study reported that they had no conflict of interests.

The majority of the reporting on this study was accurate in acknowledging that the study findings had met with considerable criticism. However, the Mail’s headline was needlessly alarming, but this is not surprising, given that the paper has been running a campaign against so-called “Frankenstein foods”.

What was the reception to the study?

The study has generated considerable controversy, both in France and worldwide.

For example, Anthony Trewavas, professor of cell biology at Edinburgh University, is reported to have opposed the findings and questioned the way the research had been conducted, arguing that the number of rats involved in the study was too small to draw any meaningful conclusions. He was quoted as follows: “To be frank, it looks like random variation to me in a rodent line likely to develop tumours anyway.”

However, Mustafa Djamgoz, professor of cancer biology at Imperial College London, said in support of the findings: “We are what we eat. There is evidence what we eat affects our genetic make-up and turns genes on and off. We are not scaremongering here. More research is warranted.”

What kind of research was this?

This was animal research designed to see what happened when rats were fed for two years on:

genetically modified (GM) maize that had been cultivated with the herbicide Roundup, or

GM maize that had been cultivated without the herbicide Roundup, or

Roundup alone, diluted in water

The researchers said that several previous studies fed rats for just 90 days, and these investigations have mostly involved either maize or soy that is genetically engineered to be tolerant to the herbicide Roundup (so that the herbicide would not actually kill the crop), or maize genetically engineered to produce an insecticide toxin itself. These shorter-term studies have demonstrated changes in rat kidney and liver function, suggesting toxic effects, which they speculated may be due to residues in the GM crops. The researchers also said that many other studies looking at the toxic effect of herbicides have only looked at the active ingredient – glyphosphate – when it is necessary to look at all the chemicals included in the total formulation.

Therefore, to try to address these gaps in knowledge, the researchers performed a detailed two-year rat-feeding study, looking at the effects of feeding rats GM maize, treated with or without Roundup, and also feeding other rats this herbicide diluted in water.

What did the research involve?

The researchers used a US maize crop that was genetically modified to be tolerant to Roundup. One field of this GM maize crop was treated with Roundup and one was not treated. They also used as a control its closest non-GM maize crop. The three corns were then harvested and dried rat feed was then made, with dry rat feed containing either:

11%, 22% or 33% GM maize, from the crop treated with Roundup

11%, 22% or 33% GM maize, from the crop not treated with Roundup

untreated, non-GM maize

An additional test substance they looked at was Roundup diluted in drinking water at three different dilutions, starting from 0.1 parts per billion in water. In addition to the treated water, the rats in these groups were fed the control untreated, non-GM maize.

The research involved a total of 200 rats: 20 rats in each test group with 10 of each sex. Two rats were housed in each cage.

In total there were nine active intervention groups and one control group consisting of only 20 rats (10 male and 10 female).

Each group was given the feed daily for two years. Blood, urine samples and weight were taken and the animals were examined twice a week. Their behaviour, eyesight and organs were also studied.

What were the basic results?

Males fed the control, untreated, non-GM feed survived on average for 624 days, while females survived on average for 701 days. In the control group, 30% of males (only three) and 20% of females (only two) died. This was compared with 50% of all males having any GM feed dying before the average lifespan, and 70% of females having GM feed. Therefore both males and females fed the GM diets died earlier, and mortality rates did not appear to be particularly affected by the concentration of GM maize in the diet. The researchers also noted that the first rats to die in the GM groups – both male and female – did so from tumours.

Female rats fed GM maize tended to develop large mammary tumours earlier than control animals, with tumours of the pituitary gland being the next most common. Males fed GM maize were more likely than control rats to have large, palpable tumours. They also observed that, compared with the control rats, kidney disease was more common in rats of both sexes fed GM, and liver disease was more common in males fed GM.

Females who drank the water containing Roundup were also observed to die earlier than controls, but there seemed to be less of an effect on male rats in this group.

How did the researchers interpret the results?

The researchers said that animal studies have previously observed that glyphosphate (the active chemical in herbicides) consumption in water above authorised limits can have an effect on kidney and liver function. They said that their results clearly demonstrate that lower levels of the complete herbicide formulation, at concentrations well below official safety limits, have an effect on kidney and liver function and the mammary glands. They said that the observations in their study may be an effect of both the herbicide Roundup and the genetically modified maize.

Conclusion

This study is reported to involve the highest number of rats regularly studied in a GM-diet study. The research also benefits from testing three different dietary concentrations of GM maize over a two-year period, along with GM maize treated with and without Roundup and Roundup alone diluted in water. All the rats in these groups were compared with rats fed only untreated, non-GM feed. The researchers also said that the Roundup concentration in water started at a dose below the range of levels permitted by regulatory authorities.

Animal research such as this is highly valuable for looking at the possible toxic effects. However, claims that GM food may have a similar toxic effect in humans cannot be justified using the results of this study, which was poorly conducted.

There are several significant limitations to the research, including the following:

Although the study did include a large number of rats overall, there were only 10 males and 10 females in each group. All comparisons were made with just one control group of 10 male rats and 10 females, and a larger group of control rats may not have given identical average lifespan and health data. Such a small control group makes it more likely that the results are due to chance.

Humans are biologically different from rats, and we may not have identical susceptibilities to disease and illness.

One expert argument was that the rats in this study were a breed already susceptible to tumours, especially if they are given unlimited access to food. This seems plausible as the rats are described to have been virgin albino Sprague-Dawley rats; however, their tumour susceptibility is not discussed in the paper.

The method of statistical analysis used to assess the results was described by the researchers as being a "robust method for modelling, analysing and interpreting complex chemical and biological data", but is complicated and fairly impenetrable, even to those with training in statistics.

The rats were fed a regular, concentrated diet of the test substance, and how this dose relates to any human intake is unclear.

This two-year period roughly equated to a rat’s lifetime. It is difficult to equate this directly to humans. Does it represent lifelong, daily consumption of GM foods treated with herbicides, and at what age adverse effects – if any – may be expected to be seen in humans?

The very unusual way in which the trial was conducted makes it hard to lend much weight to its conclusions. In any case, given the public hostility to GM foods in the UK, it is unlikely that supermarkets are going to start stocking GM foods on the shelf any time soon.

Research and debate into the safe levels of GM foods and herbicides in the diet is likely to continue.

Analysis by Bazian

Edited by NHS Website