Arpad Pusztai’s findings that GM potatoes were unexpectedly toxic are widely misunderstood and misreported – and still highly relevant

Back in the 1990s, Arpad Pusztai’s findings that GM insect-resistant potatoes were unexpectedly toxic shocked the world. Because of the misinformation that is still circulated by the pro-GMO lobby about this study, we are publishing the following summary of his findings, which was written and checked by scientists, with a few extra clarifications by GMWatch.
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A resume was prepared, as at 24 Oct 2008, to affirm a few facts about Dr Pusztai's background and, in respect of his research some 10 years ago, his sources of funding, sources of materials, crucial components of the experimental design and overall nature and aims of the project.
 
1. Dr Pusztai was awarded a collaborative research grant from the UK government (Scottish Office: Agriculture, Environment, and Fishery Department; grant number FF 818) succeeding against stiff competition. The design of the toxicological studies he conducted would have been extensively peer reviewed and suggested modifications from “experts” incorporated prior to the awarding of the grant. Therefore the experimental design was passed as highly rigorous.
 
2. Dr Pusztai's experience in conducting animal feeding studies to assess toxicological and other effects is contained in his published work that employs these techniques (e.g. see Pusztai, A., Ewen, S.W.B., Grant. G., Peumans, W.J., van Damme, E.J.M., Rubio, L., Bardocz, S., 1990. Relationship between survival and binding of plant lectins during small intestinal passage and their effectiveness as growth factors. Digestion 46 (Suppl. 2), 308-316; Pusztai, A., Grant, G., Duguid, T., Brown, D.S., Peumans, W.J., Van Damme, E.J.M., Bardocz, S., 1995. Inhibition of starch digestion by α-amylase inhibitor reduces the efficiency of utilization of dietary proteins and lipids and retards the growth of rats. J. Nutr. 125, 1554-1562; Pusztai, A., Grant, G., Bardocz, S., Alonso, R., Chrispeels, M.J., Schroeder, H.E., Tabe, L.M., Higgins, T.J.V., 1999. Expression of the insecticidal bean α-amylase inhibitor transgene has minimal detrimental effect on the nutritional value of peas fed to rats at 30% of the diet. J. Nutr. 129, 1597-1603). Therefore Dr Pusztai was impeccably qualified to undertake this research.
 
3. The aim of the award was to develop standard animal feeding trial testing methods for assessing possible unexpected toxicological effects arising from the GM plant transformation process. Dr Pusztai at the time could have been classed as an advocate of the use of GM in agriculture. He was just as surprised as anyone else of the potential adverse health effects that his studies revealed but being a truly objective scientist he reported his data as it stood for the wider scientific community and regulatory authorities to consider. His priorities were clearly with the respect to the heath implications of his studies and not the vested interests of industry or government.
 
4. The research grant held by Dr Pusztai was a collaboration between himself and a group at the University of Durham. The GM plant production expertise was provided by the University of Durham end of the collaboration. The University of Durham generated, cultivated and provided all the GNA GM potatoes used in the tests (Gatehouse AMR, Down RE, Powell KS, et al. Transgenic potato plants with enhanced resistance to the peach-potato aphid Myzus persicae. Ent Exp Appl 1996; 79: 295-307). GNA is a lectin (a type of protein) found in snowdrops, which Pusztai knew from previous experiments he had carried out was not toxic to mammals in its natural form. It is toxic to insects, which is why it was thought to be a good choice for genetically engineering insect-resistant crops.
               
5. The trials carried out by Dr Pusztai consisted of 4 feeding groups of rats. Each group was fed respectively the same amount of the isocaloric (having the same energy value) and iso-proteinic (having the same amount of protein) diets.
 
In experiment A (published as Ewen and Pusztai, 1999. Effect of diets containing genetically modified potatoes expressing Galanthus nivalis lectin on rat small intestine. Lancet 354:1353-4), the four diets were as follows:
(i) normal, non-GM parent line of potatoes
(ii) normal, non-GM parent line of potatoes spiked with GNA lectin
(iii) GNA GM potatoes
(iv) LA (lactalbumin) protein diet, for healthy growth, as an internal control.

The lymphocytes of rats fed with these diets were challenged with ConA lectin (Concanavalin A, a protein found in jack-beans) and PHA lectin (phytohemagglutinin, a protein found in legumes), but this part of the experiment did not form part of the publication in The Lancet.
 
In a separate experiment (experiment B), which the researchers carried out earlier and which was not published in a journal, the same amount of the following isoproteinic and isoproteinic diets were fed to rats:
(i) LA (lactalbumin protein) as an internal control
(ii) Lactalbumin spiked with ConA
(iii) Lactalbumin spiked with the same amount of GNA as was the ConA
(iv) non-GM potato spiked with GNA
(v) non-GM potato spiked with ConA

In all other respects the diets were equivalent. So if there was any inadequacy in the GNA GM potato feeding group diet, this would have been the same in all groups and therefore a constant. Some have commented that “feeding growing rodents raw potato would cause serious damage to their growth”. However, this is, in fact, a non-argument, since raw potatoes were fed to all experimental groups and would therefore have been expected to produce adverse effects even in the negative non-GM potato feeding group.

Comparing experiments A and B, the weight, sex, and age of all rats were the same, as was the amount of feed given to each animal and the length of the experiment. The two experiments showed the same growth curve, and internal organ weight and all other parameters were identical in the LA (internal control) groups. On this basis the two treatments (ConA and GNA) could be compared, but they were not part of the same experiments.
 
Only 2 groups from these two experiments showed adverse effects:

(ii) From experiment A, those fed the GNA GM potatoes – implying that the GM transformation process (tissue culture plus gene insertion procedure) had produced a line of potato with unexpected toxic effects.

(i) From experiment B, those fed the Con A spiked normal potatoes, which was as expected for a known toxin and therefore acted as a good positive control (in which a substance already known to be toxic is fed to a group of animals to test whether the experimental design is sensitive enough to detect the toxic effects). This result in combination with the lack of adverse effects with the non-GM and the non-GM + GNA feeding groups confirmed the soundness of the overall experimental design;

In neither experiment were GM ConA potatoes tested. The researchers had the GM ConA potatoes ready, but they were not allowed to carry out that experiment.
 
In conclusion, the experimental design by Dr Pusztai was appropriately internally controlled and therefore consistent. The studies used the best materials and knowledge made available to him by his collaborators. The results obtained are therefore highly significant and remain extant.

NOTE: An earlier version of this article could have been interpreted as implying that non-GM ConA lectin-spiked potatoes were fed as part of experiment A. We are happy to clarify that this is not the case and that experiment A did not use ConA in any form. Updated 15 Feb 2015.