What can Science Say on the Safety of GM Foods?
Arpad Pusztai
Private consultant, formerly with the Rowett Research Institute, Scotland
(Presentation made at the launch of the Independent Science Panel on 10 May 2003, London)
Arpad Pusztai stressed the need for a science-based protocol that assesses the safety or otherwise of GM foods. In particular, he described science that should have been done before GM crops and foods were commercialised. This was what they (Ewen and Pusztai) had attempted to do in the GM potato research, part of which was published in The Lancet in 1999. (‘Effects of diets containing genetically modified potatoes expressing Galanthus nivalis lectin on rat small intestine’, Lancet 1999, 354, 135-1354.)
He explained that the science behind the approval of GM foods so far relies on the concept of ‘substantial equivalence’. But substantial equivalence has never been defined or quantified scientifically, and has thus been rightly criticised. Substantial equivalence as a concept needs to be put on a more rational and scientific basis, and compositional comparison between GM and non-GM foods needs to be done in a better way than at present. Pusztai said that looking through the literature, most of the comparisons were done, in his opinion, neither biologically nor statistically in the right way. Hence ‘substantial equivalence’ is flawed, if it remains without improvement.
Pusztai emphasised that for meaningful comparisons between the effects of GM and non-GM crops and foods, the parent and transformed line must be grown under identical conditions, and must be treated and harvested the same way. This was exactly what was done in their GM potato study. A parent line and two GM lines (using the same vector construct) were grown at Rothamstead for 2 years, and then re-grown in fields under tents, under identical conditions.
Chemical compositional analysis was then done on the potatoes. There were significant differences observed between the parent and GM lines. Furthermore, although the two GM potato lines were produced at the same time, their protein contents were different (7.2% for one GM line, 5.6% for the other GM line). The amounts of several important nutritional components, such as lectin, were also substantially different.
The researchers thus drew the conclusion that it is very difficult to get two lines of GM potatoes or the parent line that have exactly the same composition. The lines were clearly not substantially equivalent, so further research investigated whether the differences that exist mattered and whether any differences were observed when tested with mammalian laboratory species (rats in this case).
Pusztai clarified that as GM food is unlikely to be highly poisonous, ‘toxicity’ is an unhelpful concept and would be difficult to assay at the low doses found in GM food. In contrast, nutritional studies, where diets based on GM crops are fed to young growing animals, should reveal their possible harmful effects on metabolism, organ development, immune and endocrine systems and gut flora. These together determine the safety of the GM crop and the development of the young into healthy adults.
Since GM food is food, he reiterated that it should be tested as food; hence nutritional studies such as theirs would provide insight. The protocol they used comprised established nutritional tests, which they have been conducting for 40 years. He pointed out the irony that much more is known about animal than human nutrition, and asked why couldn’t such protocols be applied to GM food.
Pusztai then described the procedure of nutritional testing, which needs to be rigorously standardised. Iso-proteinic and iso-energetic diets (having the same protein and energy levels) need to be formulated in which most of the dietary protein is preferably derived from the GM crop. The composition of the control diets should be the same as the GM diet but based on the parent line, with or without supplementation with the isolated gene product at the same level as it is expressed in the GM line. If the gene product is present, but not through genetic modification, the effect of GM itself can then be judged (nobody has investigated this apart from Ewen and Pusztai).
He further described how they used standard nutritional laboratory procedures for testing with rats, such as ensuring that the animals’ initial weights were similar. (In contrast, the tests by Aventis to support the safety of Chardon LL, a GM maize, used rats whose weights varied by a factor of two). The rats should be pair-fed, so that food intake is exactly the same, and there should be short and long term experiments, with collection of urine and faecal samples. If the rats are fed on two different diets, which have the same protein and energy levels, and if they don’t support the growth of the animals in the same way, then there is clearly a problem.
It is also essential to examine the animals’ organs. Young rats were used, so all their vital organs are developing. The animals were weighed daily and any abnormalities observed. The animals were then killed, dissected, their guts rinsed and the contents saved for further studies, sections were taken for histology, and wet and dry weights of organs recorded and analysed.
With few exceptions, Ewen and Pusztai were the only people who did such thorough and systematic work.
In their 110-day study, some rats were fed GM potatoes, engineered to express the snowdrop bulb lectin (GNA) gene. Other rats were fed potatoes from the parent line (non-GM) and still others were fed non-GM potatoes spiked with the gene product, GNA. These rats were fed cooked potatoes.
At the end of the study the rats were killed. The organs were weighed and significant differences for the kidney, liver and small intestine were found. These differences identify that there is something happening that should be further investigated.
He showed a slide of the rats’ small intestine, showing a clear difference between the rats fed GM potatoes and those fed non-GM potatoes. [The slide indicates the possibility that the small intestine of the GM potato-fed rats underwent hyperplastic growth (enlargement due to increased reproduction rate of its cells, often as an initial stage in the development of cancer).]
Furthermore, if there is an immune effect, the gut will send out lymphocytes (white blood cells that produce antibodies). They found that the number of lymphocytes in the jejunal mucosa had increased in rats fed GM potatoes, indicating that there was some adverse effect at the gut level.
They also took blood samples before, during and at the end of the experiments to conduct studies on immune responsiveness. They found that GM potatoes did seem to depress immune response. This is important, as the rats were young animals, so their immune systems were not fully developed yet. If GM foods are reducing the potential responsiveness of the immune system, then the long-term effects could be great.
Pusztai explained that if there are differences in any of these parameters between animals fed GM and non-GM parent line diets, this indicates that the genetic modification must have had an effect on the utilisation and nutritional value of the crop and that there is some problem with the GM crop/food in question. This is the starting point, even if we don’t know what causes the problem.
If the parent line diet spiked with the gene product also shows differences, then the use of this gene in the GM food/feed is not acceptable. If negative effects of the GM food are not observed with the parent line diet containing the gene product, it is likely that the harm is caused by the use of that particular transgenic construct or by an unwanted or unforeseen effect of the gene insertion in the genome. The latter was what they found in their research.
He reiterated that these are merely the first steps in a protocol for safety testing of GM foods, and must be further developed. The GM potato work with male rats also showed abnormalities in the development of their sexual organs; the effects on female rats and long-term reproduction thus need to be investigated further.
With such a safety protocol, if there is no indication of harm to the animals, the results have to be validated with human volunteers in clinical double-blind, placebo-controlled drug type testing, but keeping in mind that harm can be most acute in the young, elderly and sick, particularly those suffering from diseases.
Pusztai concluded by stressing that we ought to take the issue of GM food safety seriously. So far, in any study that has been conducted properly, and that is independent and without bias, there seems to be problem, which cannot be explained. This is the starting point, not the end point, and should be investigated further.
In the Question and Answer session, Pusztai was queried about a study conducted by Chinese researchers that supposedly repeated his work but found no effects. Pusztai pointed out that this research has not been published, and in science if it not published, then it does not exist.
He explained that his new review looks only at peer-reviewed papers, with the exception of the Flavr Savr tomato and Chardon LL studies, as the former was the first GM food developed, and the latter, the first GM seed intended to be placed on the UK’s National List. As his review shows, there is a conspicuous lack of data on GM food safety. (Pusztai A, Bardocz S and Ewen SWB. ‘Genetically Modified Foods: Potential Human Health Effects’, Chapter 16 in Food Safety: Contaminants and Toxicants. JPF D’Mello, ed. 2003. CABI Publishing. See the ISP website www.indsp.org for the link to the paper.)
Pusztai also stressed that while it might take many years before science can establish firmly the effects of GM foods, this should not be an excuse used by industry not to conduct thorough testing. Controversies would disappear if there is considerable weight of published experimental evidence, because then the appropriate conclusions can be drawn. The current controversy over GM foods rests in the fact that there are no major experiments or enough published data. Additionally, these have to be confirmed and done independently.
He questioned why there have not been any more studies to look seriously at the issues they raised. Their 110-day study found significant differences, and the long-term implications really need to be looked at, although are much more difficult to assess.