OECD EDINBURGH CONFERENCE
on the Scientific and Health Aspects of
Genetically Modified Foods

1. The Biosafety Protocol agreed in Montreal in January formalises international recognition of the risks associated with the environmental release of genetically modified organisms (created using recombinant DNA technology).

2. The Protocol recognises the deficiencies in scientific knowledge in this area and permits the application of precautionary measures by sovereign nations on the basis of the precautionary principle, even in the event of the absence of scientific evidence.

3. However, published scientific papers catalogued in the latest annual report of the John Innes Centre (JIC) UK clearly demonstrate that the existence of risk generating phenomena in genetically modified crops are common place. The JIC research demonstrates that these phenomena are in fact inherent in the very nature of GMOs by simple virtue of the nature of the technology which is being used to create them.

4. The JIC has confirmed that these phenomena are responsible for important disturbances in gene expression. They are set out in more detail in Appendix A.

These are phenomena which are common features of transgenic plants, but not of conventionally bred ones.

As a result the JIC acknowledges that in conventionally bred plants "phenotypic variation usually falls within a familiar" range, but with genetic modification "there is the potential to change plants fundamentally".

Evidence of these and other types of biosafety phenomena have already arisen not only in the laboratory but also in the field after approval for commercial release in the case of a number of crops, including cotton, soya, tomatoes and canola (oilseed rape). Whilst most of these effects to date have caused problems mainly for farmers (with millions of dollars already paid in compensation) they indicate the inability of the science to pick up problems during the pre-release testing period.

5. Additional work published by the JIC in 1999 shows that important recombination (the breaking and joining of DNA) events may not be confined to virus resistant transgenic plants, but may also involve the viral CaMV promoter used in most transgenic plants. (More information on the CaMV promoter is given in Appendix B.)

Dr Pusztai has suggested that the use of the CaMV promoter may have played a part in the toxic affects which he considers were demonstrated in his government funded trials on genetically modified potatoes.

6. A summary of general advice given by the JIC on biosafety risks is given in Appendix A.

The following is the conclusion to one of its more broad ranging papers: "An understanding of the causes of transgene stability and expression is important for various reasons [including]...for assessing their potential impacts on human health and the environment.........A knowledge of transgene stability, expression and inheritance is fundamental for the successful and safe use of transgenes in large scale agricultural production. Many factors influence the ways in which transgenes express, but a factor of crucial importance is the effect of DNA sequences that are homologous to areas of transgene constructs. For those concerned with the development of transgenic brassicas [ie oilseed rape etc] the take home message from this paper is ‘watch out for homology.’" [our emphasis; note the paper makes clear that such phenomena are similarly relevant to other types of transgenic crops.]

11. It is a myth that genetics are the principal constraint on the development of sustainable agricultural production adequate for current and future global needs. Attention now needs to be given to addressing the wider issues facing world agriculture where real opportunities exist for fundamental progress in developing systems of farming in accordance with natural law.

12. These are:

i) A complete cessation of all environmental releases of genetically modified organisms.

ii) The initiation of a global review of the needs of world agriculture and food production.

Available at: www.btinternet.com/~nlpwessex/Documents/gmocarto.htm

ŸPosition effects - arising from the insertion of "alien gene sequences into random locations"

ŸPromoter methylation - because "plants do not readily take up and incorporate ‘invading DNA’ into the genome"

ŸInter-loci interactions - including "co-suppression where a transgene can modify the action of an endogenous gene, and interaction between transgenes when one transgene construct can modify the action of another"

ŸGene silencing - where transgenes "can be unstable and become silenced" [ie switched off]

ŸSequence homology - where transgene constructs interact with one another, which "may inactivate the expression of another construct in the same plant"

ŸHeteroencapsidation - assisting "long distance viral movement around infected plants" and possibly enhancing "the movement of a superinfecting virus that did not normally move systemically". Heteroencapsidation can take place between "viruses of the same group, and between unrelated viruses."

ŸTransgenes can have very high levels of instability

ŸTransgenes "frequently show considerable variation" in expression

0. Trangenes "can interact with resident genes, and with other transgenes"

ŸTransgenes can "influence characteristics apparently unrelated to the function of the transgene"

Ÿ"Most transgenic constructs contain some genetic sequences from plant pathogens"

ŸTransgene expression can be significantly affected by environmental influences

ŸTransgenes subsequently transferred sexually [i.e. by conventional pollination] into different genetic background can "vary in expression, stability and pattern of inheritance"

0. "The precise cause of interaction between transgenes and the background genotype is not known."

Ÿ"Transgenes can show abnormal tissue specificity and expression can vary through plant development and inheritance..."

0. "Trangenes can display abnormal inheritance"

0. "Transgenes or parts of them can be lost"

ŸTransgene silencing may lead to activation of allergens and toxins which other elements of the modification process have been designed to suppress

Ÿ"It is common to observe substantial variation between transgene expression in independently transformed plants"

Ÿ "Where their is homology [sequence compatibility] between trangenes and resident genes there is likely to be some interaction." Homology may result in "no native or transgene expression."

0. Where multi-construct transgenic plants are reproduced sexually constructs may become separated by segregation in subsequent generations where "it is possible that a formerly silenced or poorly expressing construct may become more highly expressed in subsequent generations"

Ÿ"It is possible that a rare event may have insignificant consequences when transgenic crops are grown on a small experimental scale, but become more important when transgenic crops are grown over thousands of hectares."

Ÿ"The area of concern specific to viral transgenes is the potential risks on any interactions between the viral or virus-related sequences being expressed from the transgene and another virus superinfecting that plant"

Ÿ"There is considerable evidence for extensive recombination in RNA viruses.... It is generally considered that recombination plays an important role in the evolution of RNA viruses. Evidence is now forthcoming of recombination between superinfecting viral RNA and RNA expressed from a transgene through the aberrant homologous recombination mechanism. The finding of recognizable host RNA sequences within viral RNAs is suggestive of nonhomologous recombination." [i.e. this section refers to the unintended creation of new plant viruses in certain types of transgenic plants]

ŸSpecifically in relation to crops genetically modified for viral resistance, (although recombination events are not confined to them) -: "It is difficult to devise detailed protocols in the field for the detection of recombinants produced in the field..... For small scale-releases, it is relatively easy to design monitoring procedures.... This will be much more difficult, if not impossible, for large-scale releases, in which the approach should be to educate farmers and extension personnel to identify any unusual event that might be associated with transgenic plants. This will be the challenge of the future...."

Ÿ"Recent research in our laboratory with Brassica napus plants containing the 35S promoter from the mosaic virus (CaMV) has shown that upon infection with the CaMV the driven transgene is silenced (Al-Kaff et al unpublished). Intensive research at present is directed towards understanding this silencing mechanism and its significance. As the 35S promoter is widely used to regulate transgenics in brassicas, it is important that we strive to obtain a clear understanding of the mechanisms of this silencing and its significance. This is important for two reasons, for assessing the use of the 35S promoter in agriculture and also for assessing the significance of this effect for biosafety."[our emphasis; also note this promoter is used in most other transgenic plants as well, including those already released into the environment]

Ÿ"An understanding of the causes of transgene stability and expression is important for various reasons [including]...for assessing their potential impacts on human health and the environment.........A knowledge of transgene stability, expression and inheritance is fundamental for the successful and safe use of transgenes in large scale agricultural production. Many factors influence the ways in which transgenes express, but a factor of crucial importance is the effect of DNA sequences that are homologous to areas of transgene constructs. For those concerned with the development of transgenic brassicas [ie oilseed rape etc] the take home message from this paper is ‘watch out for homology.’" [our emphasis; note the paper makes clear that such phenomena are similarly relevant to other types of transgenic crops.]

Additional work carried out by the JIC published in 1999 shows that recombination (the breaking and joining of DNA) events relating to viral sequences may not be confined to virus resistant transgenic plants. In fact, recombination events may also arise, for example, with the CaMV 35S promoter taken from the Cauliflower Mosaic Virus, a pathogen of members of the mustard family such as oilseed rape. Such viral promoters are used to artificially ‘fire up’ transgenes.

This promoter is present in every cell of almost all existing transgenic crops which have been released into the environment. The latest JIC annual report states: "Trangene rearrangements often occur at regions rich in DNA secondary structure, such as the CaMV 35S promoter.... This allows recombination to occur."

The full implication of this finding, which is only now coming to public attention (long after the release of GM crops into the environment) is unknown. The importance of this phenomenon is reflected in the fact that the JIC itself has been carrying out further intensive research on the behaviour of transgene promoters. It is already clear that the use of this particular promoter is associated with ‘gene silencing’ phenomena.

However, research in other laboratories suggests that the CaMV promoter may be capable of interacting with existing environmental pathogens with the possibility that new plant, and even animal, viruses could be created. The complete CaMV virus itself (from which the promoter is taken) is related to Hepatitis B and HIV . Recent research at the JIC demonstrates that a component of HIV is interchangeable with an equivalent element of CaMV, although it is not known whether the same would also apply to elements of the promoter itself.

Dr Puzstai has suggested that the use of the CaMV viral promoter may have played a part in the toxic affects which he considers were demonstrated in his government funded trials on genetically modified potatoes.

This situation further coincides with the release of a recent survey in the UK (Daily Telegraph 14 February 2000) revealing that: "One in three scientists working for Government quangos or newly privatised laboratories says he has been asked to adjust his conclusions to suit his sponsor". Amongst these some scientists had been asked to do so to obtain further contracts and some claimed they had been asked to make changes to discourage publication.

The newspaper report also highlighted potentially compromised research emanating from industry and quoted the Editor of the British Medical Journal as saying: "These competing interests are very important. It has quite a profound influence on the conclusions and we deceive ourselves if we think science is wholly impartial."