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Do GM potatoes with lectins harm rat organs as
Pusztai claims?
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The Claim:
According to the study, diets containing genetically engineered potatoes expressing the lectin, Galanthus nivalis agglutinin (GNA), showed some detrimental effects on different parts of the rat gastrointestinal tract.
Comments by Prof. Klaus Ammann
The safety of food derived from GM crops is scientifically proven and in many cases it can be said that GM food is safer or at least as safe as food derived from crops from conventional breeding methods.
It is really interesting to know about the background and reasoning of R. Horton (Horton, 1999a, b), the editor in chief of Lancet, why he decided to publish the study of Ewen and Pusztai (Ewen & Pusztai, 1999a)
Hortons justification for the publication of the paper in a peer reviewed journal, including some critical remarks from readers:
“The trigger for much of this despondency was the public debate that followed Pusztai’s television revelations. The data on which this media furore was founded are published for independent assessment in this week’s issue of The Lancet, 18 months after their first public release. The Research Letter by Stanley Ewen and Pusztai was received by the journal towards the end of 1998. Since then, it has been peer reviewed by six specialist advisers—a nutritionist, a human pathologist, a veterinary pathologist, an agricultural geneticist, a plant molecular biologist, and a statistician —who had several requests for clarification about the design of the study, the laboratory methods used, and the statistical tests applied. Some advised rejection; others encouraged us to go ahead and publish.The authors revised their letter three times to try to meet our reviewers’ criticisms. The Royal Society’s own internal review of the Pusztai data had led to the damning verdict that the study “is flawed in many aspects of design, execution, and analysis and that no conclusions should be drawn from it”. So why publish the paper? The answer lies partly in a February, 1999, statement from the UK’s chief scientific adviser, Robert May.4 While criticising the researchers’ “sweeping conclusions about the unpredictability and safety of GM foods”, he pointed to the frustration that had dogged this entire debate:
“Pusztai’s work has never been submitted for peer review, much less published, and so the usual evaluation of confusing claim and counter-claim effectively cannot be made”. This problem was underlined by our reviewers, one of whom, while arguing that the data were “flawed”, also noted that, “I would like to see [this work] published in the public domain so that fellow scientists can judge for themselves . . . if the paper is not published, it will be claimed there is a conspiracy to suppress information”. Publication of Ewen and Pusztai’s findings is not, as some newspapers have reported,5 a “vindication” of Pusztai’s earlier claims. On the contrary, publication of a paper after substantial review and revision provides a report that deserves further scientific attention. Such wider appraisal begins in this week’s Lancet with the commentary by Harry Kuiper and colleagues.”
Starting from a text of one of the most important accounts on food safety from the National Academy of Sciences Committee on Environmental Impacts (2000) (National Academy of Sciences Committee on Environmental Impacts, 2000) we can summarize the situation as follows:
p. 68-69
The potential for transgenic pest-protected plants to pose a threat to human or animal health must be considered against the background of existing information. To date no such effects have been shown with commercialized transgenic crop plants. The work of Ewen and Pusztai 1999 (Ewen & Pusztai, 1999a) hints of some possible interaction between a lectin expressed in potato and alterations in the potato caused by the genetic engineering process. According to the study, diets containing genetically engineered potatoes expressing the lectin, Galanthus nivalis agglutinin (GNA), showed some effects on different parts of the rat gastrointestinal tract. Those effects fell into two categories, ones caused by the GNA transgene itself and others caused by pleiotropic effects of expressing the transgene.
However, analysis of the work of Ewen and Pusztai by the Royal Society 1999 http://www.royalsoc.ac.uk/st_pol54.htm and by Harry Kuiper et al. (Kuiper et al., 1999), Lachmann(Lachmann, 1999) and many others in an extensive controversy (Ewen & Pusztai, 1999b, c; Feldbaum, 1999a, b; Horton, 1999a, b; Malcom, 1999; Mowat, 1999) indicates that the study lacked scientific rigor.
Ewen and Pusztai’s replies were not very convincing (Ewen & Pusztai, 1999b). For example, data concerning the biochemical composition of the potatoes used in the study show that the nontransgenic variety differed significantly from the transgenic variety. These differences could be attributable to natural variations in potato lines and are not necessarily due to the genetic modification (Kuiper et al.1999).
Several later peer reviewed publications, based on extensive research and reviewing the existing literature on food safety have been published, only two named here: Konig et al, based on an important multiannual research programme of the EU, ENTRANSFOOD from 2004, (Konig et al., 2004) and a very extensive report on food safety by the National Academy of Science of the US from 2004: (National Research Council NAP, 2004), here the most interesting paragraphs on the comparison of traditional and biotech breeding and its safety consequences on pages 179 ff:
“All new crop varieties, animal breeds (see cloning subreport), and microbial strains carry modified deoxyribonucleic acid (DNA) that differs from parental strains. Methods to genetically modify plants, animals, and microbes are mechanistically diverse and include both natural and human-mediated activities. Health outcomes could be associated with the presence or absence of specific substances added or deleted using genetic modification techniques, including genetic engineering, and with unintended compositional changes.
The likelihood that an unintended compositional change will occur can be placed on a continuum that is based on the method of genetic modification used (see Figure 3-1 and comment http://www.botanischergarten.ch/Pusztai/NAS-Excerpt-Continuum-fig3-2004.pdf ).
The genetic modification method used, however, should not be the sole criterion for suspecting and subsequently evaluating possible health effects associated with unintended compositional changes.
All evidence evaluated to date indicates that unexpected and unintended com positional changes arise with all forms of genetic modification, including genetic engineering. Whether such compositional changes result in unintended health effects is dependent upon the nature of the substances altered and the biological consequences of the compounds. To date, no adverse health effects attributed to genetic engineering have been documented in the human population.”
A further extensive report taking care of many other potential risks of GMOs has been published by the Flanders Interuniversity Institute for Biotechnology (Custers et al., 2000). As a whole, there is a rich literature on food safety published, and it is generally accepted in the academic community of food safety researchers that food derived from GM crops is as safe as conventional food.
Some NGOs notoriously opposed to GMOs try from time to time to disqualify the science behind those many studies, but it takes usually a few weeks until the rebuttals are published, the latest case is the controversy on a Bt maize: A paper by Seralini et al. (Seralini et al., 2007) purporting to invalidate the Monsanto conclusions (incidentally based on old data) has just been dismissed by EFSA: “following a detailed statistical review and analysis by an EFSA Task Force, EFSA’s GMO Panel has concluded that this re-analysis of the data does not raise any new safety concerns”. As a matter of fact the Seralini study operates with an unprofessional and flawed approach in statistics. This topic will be extensively treated in a separate ASK-FORCE contribution.
( http://www.efsa.europa.eu/en/press_room/press_release/pr_efsa_maize_Mon863.html
A recent similar case has been purported in numerous websites by Irina Ermakova: Supposedly GM soybeans (heribicide tolerant) show detrimental effects in rat feeding experiments. Again this text is hotly debated before it has been published in a peer reviewed paper, this is why the editor in chief of Nature Biotechnology has interviewed Ermakova and confronted her with the opinions of experts, the result is clearcut negative for the interpretations of Ermakova: Marshall in Nature Biotechnology (Marshall, 2007). Again this case will be treated exensively in a separate ASK-FORCE contribution.
Many more comments on the experiments of Arpad Pusztai have been published, here a few important ones: Cellini et al. (Cellini et al., 2004) suggest that carbohydrate profiling and chemical fingerprinting in some incidences, together with appropriate extended controls, might at least limit animal feeding studies when testing for unintended effects. Another comprehensive review with numerous experts in the field of food safety has been published in 2004: (Chassy et al., 2004)
As chairman of international conferences on GM food Sir John Krebs published a balanced report on the Pusztai debate in Great Britain: (Krebs, 2000)
References
Cellini, F., Chesson, A., Colquhoun, I., Constable, A., Davies, H.V., Engel, K.H., Gatehouse, A.M.R., Karenlampi, S., Kok, E.J., Leguay, J.J., Lehesranta, S., Noteborn, H., Pedersen, J., & Smith, M. (2004)
Unintended Effects and Their Detection in Genetically Modified Crops. Food and Chemical Toxicology, 42, 7, pp 1089-1125
<Go to ISI>://000221924900004 AND http://www.botanischergarten.ch/Food/Cellini-Unintended-2004.pdf
Chassy, B., Hlywka, J.J., Kleter, G.A., Kok, E.J., Kuiper, H.A., McGloughlin, M., Munro, I.C., Phipps, R.H., & Reid, J.E. (2004)
Nutritional and Safety Assessments of Foods and Feeds Nutritionally Improved through Biotechnology: An Executive Summary. Comprehensive Reviews in Food Science and Food Safety, 3, 2, pp 38-104
<Go to ISI>://000224587300001 AND http://www.botanischergarten.ch/Food/Chassy-ILSI-Report-2004.pdf
Custers, R., Pedersen, J., Eriksen, F.D., Knudsen, I.B., K., A., Jacot, Y., Rufener Al Mazyad, P., Kinderlerer, J., Penninks, A., Klippels, L., Houben, G., & Gay, P. (2000)
The Safety of Genetically Engineered Crops. In Safety of Genetically Engineered Crops (ed R. Custers), pp. 159. Flanders Interuniversity Institute for Biotechnology, Zwijinarde, BE.J. Bury, VIB Vib Publication
http://www.vib.be and http://www.botanischergarten.ch/Geneflow/VIBreport.pdf
Feldbaum, C.B. (1999a)
Gm Food Debate. Lancet, 354, 9191, pp 1729-1729
<Go to ISI>://000083652800050
Feldbaum, C.B. (1999b)
Health Risks of Genetically Modified Foods. Lancet, 354, 9172, pp 70-70
<Go to ISI>://000081243200045
Konig, A., Cockburn, A., Crevel, R.W.R., Debruyne, E., Grafstroem, R., Hammerling, U., Kimber, I., Knudsen, I., Kuiper, H.A., Peijnenburg, A., Penninks, A.H., Poulsen, M., Schauzu, M., & Wal, J.M. (2004)
Assessment of the Safety of Foods Derived from Genetically Modified (Gm) Crops. Food and Chemical Toxicology, 42, 7, pp 1047-1088
http://www.sciencedirect.com/science/article/B6T6P-4C0TB0F-2/2/c05e63997072ff97fe1511166846e65f and http://www.botanischergarten.ch/Food/Konig-et-al.Food-Assessment-2004.pdf and F1000-evaluation http://www.facultyof1000.com/article/15123382/evaluation
Malcom, A.D.B. (1999)
Health Risks of Genetically Modified Foods. Lancet, 354, 9172, pp 69-70
<Go to ISI>://000081243200044
Klaus Ammann, Guest Professor
Delft University of Technology
Julianalaan 67, 2628 BC Delft, Netherlands
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