GM WATCH COMMENT: We asked Dr Arpad Pusztai what he made of the following study of GM potatoes by Louise Shepherd and Howard Davies of the Scottish Crop Research Institute.

To understand the points Dr Pusztai makes it's necessary to remind ourselves of the details of the ground-breaking research Dr Pusztai conducted, while at the Rowett Research Institute in Scotland, into the safety of GM potatoes. This research, it may be remembered, found that when rats were fed on a diet of GM potatoes, they showed stunted growth, reduced immune function and damage to internal organs.

The study's findings, when disclosed on TV, made headlines around the world, and the Rowett's director, under enormous pressure and in the face of attacks on Dr Pusztai's integrity, had Pusztai's laboratory sealed off, his notebooks seized and his research team disbanded.

Dr Pusztai's - then preliminary - materials on his research were turned over to an audit committee while Dr Pusztai himself was indefinitely suspended and placed under a gagging order. The audit committee concluded Dr Pusztai's data did not support the findings he had claimed.

However, other scientists who reviewed the same material concluded that Dr Pusztai had been dealt with both harshly and unfairly by the Rowett and its Director. For instance, Professor S. Pierzynowski, from the Department of Animal Physiology, at Lund University, Sweden, concluded that "there is enough strong evidence that the work of the audit group was not objective and [was] per se dangerous, not only for Dr. Pusztai, but generally for free and objective science."

Similarly, Dr. Kenneth Lough, a former principal scientific officer at the Rowett Institute, said, "In my view the evidence presented in the audit report must be considered as unsafe and is without justification for use against the scientific reputation of Dr. Pusztai."

Dr Pusztai's research later passed a stringent peer review process and was published in The Lancet.

However, from the time the news first broke of Dr Pusztai's findings, claims were repeatedly made by GM supporting scientists that there was a simple explanation for the intestinal damage found in the GM-potato-fed rats that had nothing to do with GM. They argued that Dr Pusztai's findings could be far better explained by higher levels of glycoalkaloids in the GM potatoes.

These claims have continued to be made despite the fact that there is no data linking glycoalkaloids with this type of gut abnormality. In any case, the GM potatoes used in Dr Pusztai's research actually contained less glycoalkaloids than the non-GM ones.

Here are Dr Pusztai's comments on the Shepherd and Davies study.
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DR ARPAD PUSZTAI:

Thank you for sending this piece of news about GM spuds. No, I have not seen this before because I only look at proper scientific papers and this is not one. However, for your interest I can tell you a number of interesting things about this piece of what I regard, at best, as propaganda material.

Davies was one of the members of my "Audit Committee".

Davies just confirmed (without actually referring to the peer reviewed publication of Nick Birch who originally published this) that genetic modification did not increase but rather reduced the toxic solanine alkaloid content of potatoes. This is the final acknowledgement by the GM lobby that the toxicity of our GM potatoes could not have been due to the much trumpeted, but falsely claimed, increase in solanine glycoalkaloids.

Potato merchants such as Davies still could not grasp the scientific concept of what is a true comparison between GM and non-GM. The only scientifically valid comparison is that made between the GM- and the isogenic lines grown and harvested under identical conditions and not a sort of general comparison between potatoes, GM or otherwise. But how could a committed GM potato breeder ever come to appreciate the finer points of science?

All the best
Arpad
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SEARCHING FOR UNINTENDED COMPOSITIONAL CHANGES IN GE POTATOES
Louise VT Shepherd & Howard V Davies
http://www.isb.vt.edu/news/2006/news06.nov.htm#nov0603

GE risk assessment in the European Union

Prior to market approval in Europe, genetically engineered (GE) crops and products undergo a rigorous risk safety assessment based on a comparative approach. That approach assesses differences between the GEO and its derived products and their non-GE counterparts, the counterparts having a history of safe use.1,2 The risk assessment focuses on a range of parameters, which are described in the European Food Safety Authority (EFSA) guidance document.2 Compositional analysis is one of these parameters and the OECD (Organization for Economic Co-operation and Development) is providing guidance on which compounds should be targeted for analysis on a crop by crop basis. The analysis takes into account the crop-specific profile of compounds with nutritional or anti-nutritional characteristics. Significant intentional or unintentional changes in such compounds are likely to drive the need for more detailed risk assessment.3,4 If a trait or traits are introduced with the intention of modifying composition significantly, and where the degree of equivalence cannot be considered substantial, then the safety assessment of characteristics other than those derived from the introduced trait(s) becomes of greater importance. Whilst the potential for using modern transcriptomic, proteomic, and metabolomic approaches to assess the potential for detecting unintended effects is under evaluation (e.g., the EU "SAFEFOODS" project [http://www.safefoods.nl]), the targeted analysis of key nutrients and anti-nutrients remains the cornerstone of the compositional evaluations.1

GE potato as a case study for compositional analysis

Potatoes are the world’s fourth most important food crop and have long been used as a model crop for studies on gene function using Agrobacterium-mediated transformations. The cultivated potato has complex genetics (it is tetraploid), and genetic engineering approaches that add value to existing varieties with a strong pedigree in other characteristics remain attractive scientifically. The Scottish Crop Research Institute (http://www.scri.sari.ac.uk) has a history of producing a range of GE potatoes for experimental purposes; this has afforded opportunities to develop projects on the use of metabolomics to assess the potential for unintended effects.

We feel it is important, however, to use existing OECD guidelines to establish the baseline against which data on metabolomics can be compared. In its 2002 "Consensus Document on Compositional Considerations for New Varieties of Potatoes: Key Food and Feed Nutrients, Anti-nutrients and Toxicants," the OECD5 considers that if the analyses of specific compositional parameters listed in their document indicate that a novel variety falls within the ranges found in the literature (apart from intentional modifications resulting from transgenic approaches) then the variety can be considered equivalent with respect to its overall composition. In our experiment, metabolite analysis included soluble carbohydrates, glycoalkaloids, vitamin C, total nitrogen, and fatty acids. Trypsin inhibitor activity was also assayed. These are the major compounds recommended by the OECD in its 2002 consensus document.

Range of GE potatoes included

Using (primarily) the potato variety Desirée, the study included transgenic modifications to a range of metabolic and development processes, including primary carbohydrate metabolism, polyamine biosynthesis, and glycoprotein processing. The lines included some with extreme phenotypes, e.g., those with a modified glycoprotein processing protein (Fig. 1 [see ref. 6]), which produces stunted plants with poor tuber yield and modified leaf anatomy. Other lines overexpressed a gene that encodes S-adenosylmethionine decarboxylase (modified polyamine metabolism) and showed significant increases in tuber number (Fig. 2 [see ref. 7]), whilst yet another group of transgenics contained starch with amylose levels reduced by 90% (unpublished). All experiments included appropriate controls consisting of a) wild type non-GE tubers, b) non-GE tubers produced from plants regenerated through tissue culture (including a callus phase), and c) GE tubers derived from transformation with an ‘empty vector’, i.e., no specific target gene included (with the exception of the kanamycin resistance gene as a selectable marker).

What unintended effects were observed?

In general the targeted compositional analysis revealed no consistent differences between GE lines and respective controls. No construct specifically induced unintended effects. Statistically significant differences between wild type controls and specific GE lines did occur but appeared to be random and not associated with any specific genetic construct. Indeed such significant differences were also found between wild types and both non-GE, tissue culture derived, and GE tubers derived from transformation with the empty vector. More specifically, the study revealed a consistent and significant increase in vitamin C and a decrease in glycoalkaloids across many of the GE lines examined, but also in the "control" GE empty vector lines and in non-GE lines developed through tissue culture. Somaclonal variation may therefore underpin many of the compositional changes and may provide a mechanism by which "unintended" changes in plant composition might occur independently of the process of transformation and gene insertion itself. More extensive studies on the impact of tissue culture on compositional variation are ongoing at the SCRI.

Given the range of phenotypes used in this study, it is perhaps surprising that chemical composition is not affected more significantly. This indicates that visible, morphological phenotype is not necessarily a good guide to likely compositional changes. Similarly, compositional changes may not give rise to an agronomic phenotype. This is why a holistic and case-by-case analysis of specific GE lines is required to generate any opinion on potential risk.

In our study the values for specific potato components that we analyzed (and suggested by the OECD) fall well within published ranges for potato. It is therefore unlikely that any of the changes observed would raise issues with regard to food safety or nutritional value. However, several of these GE lines would not be considered substantially equivalent to the parent due to phenotypic perturbations.

References

1. OECD (1993) Safety evaluation of foods derived by modern biotechnology: concept and principles. (http://www.oecd.org/LongAbstract/0,2546,en_2649_34385_1946122_119666_1_1_1,00.html)

2. EFSA [European Food Safety Authority] (2004) Guidance document of the GMO Panel for the risk assessment of genetically modified plants and derived food and feed. (http://www.efsa.eu.int/science/gmo/gmo_guidance/660_en.html).

3. Kuiper HA and Kleter GA (2003) The scientific basis for risk assessment and regulation of genetically modified foods. Trends Food Sci and Tech 14, 277-293

4. Howlett J et al. (2003) The safety assessment of novel foods and concepts to determine their safety in use. Int J Food Sci Nutr 54 (Supplement), S1-S32

5. OECD (2002) Consensus Document on Compositional Considerations for New Varieties of Potatoes: Key Food and Feed Nutrients, Anti-Nutrients and Toxicants. http://www.oecd.org/document/9/0,2340,en_2649_34385_1812041_1_1_1_1,00.html

6. Taylor MA et al. (2000) A potato alpha-glucosidase gene encodes a glycoprotein-processing alpha-glucosidase II-like activity. Demonstration of enzyme activity and effects of down-regulation in transgenic plants. Plant J 24, 305-316

7. Pedros AR et al. (1999) Manipulation of S-adenosylmethionine decarboxylase activity in potato tubers. Planta 209, 153-160

8. Cellini F et al. (2004) Unintended effects and their detection in genetically modified crops. Food Chem Toxicol 42, 1089-1125

Dr Louise VT Shepherd
Post-doctoral Researcher
Quality, Health & Nutrition Programme
Scottish Crop Research Institute
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Prof Howard V Davies
Director of Science Co-ordination
Scottish Crop Research Institute
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