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ISIS’ Final Reply to ACRE: Let the People Decide

 

The evidence is laid bare, let the people judge for themselves, say Dr. Mae-Wan Ho and Prof. Joe Cummins.

Science advisors are anti-precautionary


In a long-running battle with UK’s scientific advisory committees on GM, we at ISIS have repeatedly challenged their persistent refusal, either to acknowledge scientific evidence suggesting genetic modification is not safe, or to address areas of uncertainty with appropriate independent scientific investigations.

The Advisory Committee on Releases to the Environment (ACRE) has published its latest denial on its website last week [1]. The “ISIS’ Comments” referred to were made months earlier and posted on the GM Science Review website. We have since submitted another critique [2], directed at the GM Science Review First Report [3], a document remarkably similar in substance to ACRE’s present (and past) responses: the same bland reassurances by assertion, the same selective and misleading interpretation of the scientific evidence.

The most striking aspect of the ACRE reply to ISIS is ACRE’s underlying assumption that nothing about T25 (Chardon LL) maize should be considered unsafe unless proven so, by a standard set to be as permissive as possible for GM crops. The burden of proof is blatantly anti-precautionary.

It would be tedious to address ACRE’s latest response in detail, which has, in any case, been overtaken by our critique [2] of the GM Science Review Report.

Rather, we want to summarize, for the benefit of the public, the major areas of disagreement between scientists like ourselves and those who advise our government. Details are contained in the just published Independent Science Panel (ISP) Report, The Case for a GM-Free Sustainable World [4]. Yet further details are contained in Living with the Fluid Genome [5].

 

Some main points of contention that remain unanswered


There are both a priori and empirical evidence suggesting that GM is inherently unsafe and unpredictable, which remain to be refuted.

1. GM is distinct from conventional breeding methods, including mutations induced by X-rays or chemicals. It is unreliable, uncontrollable, unpredictable and unstable; and introduces new risks (see below).
Ironically, the paper [6] cited by ACRE in support of transgenic stability is actually one reviewed and exposed by ISIS two years ago, which showed overwhelming instability, even on the most generous interpretation of a poor dataset [7]. That paper is one example among many of the way scientific evidence is misinterpreted and misreported by GM proponents: the claim of transgenic stability made in the abstract is contrary to the evidence reported in the rest of the paper.

Transgenic instability obviously compromises agronomic performance of the GM crop, it is also an important safety issue. Apart from uncontrollable and unexpected changes in the safety profile of the GM crop, there is the possibility of transgenic DNA spreading directly to other organisms in a process called horizontal gene transfer.

More seriously, ACRE appears to hold that ‘event specific’ molecular characterisation of transgenic lines is not necessary as evidence of stability. (This is to ascertain that the transgenic DNA integrated into the genome stays in the same form and in the same location in the plant’s genome.) It states (p.7): “ACRE maintain that monitoring for stable expression of transgenes rather than any inherent instability (which can occur in natural DNA also) is sufficient and suitable. Event specific characterisation of successive generations would offer no further information regarding the safety of T25…” ACRE should be reminded that such characterisation is indeed required by the European Directive for Deliberate Release.

2. GM DNA is definitely not the same as non-GM or natural DNA.
ACRE still maintains that transgenic DNA is no different from other DNA. This is at best an untested, unjustified hypothesis. GM greatly increases the scope of horizontal gene transfer and recombination, which pose the most insidious dangers. The genetic material of any and every species on earth can be recombined and transferred in the laboratory. There is no evolutionary precedent for this situation. New genes and new combinations are being introduced into our environment and food chain that have never existed.

The hypothesis of the equivalence of GM and non GM DNA has been contradicted, prima facie, by the one single experiment ever done in the world to test it [8]. One main difference may indeed be that GM DNA is known to be structurally unstable from the beginning of genetic engineering, and is hence more likely to spread than non GM DNA, possibly by horizontal gene transfer.

3. Many GM DNAs possess ‘recombination hotspots’ making them extra-unstable, and hence extra-prone to horizontal gene transfer and recombination, with all the attendant risks.
The CaMV 35S promoter is just one example of GM DNA with a recombination hotspot. We need not repeat our concerns as these are widely known, and people will draw their own conclusion. ACRE still does not mention that the promoter is active in animal and human
cells. ACRE claims our 1999 paper [9] was not subject to peer review, citing a commentary in Nature Biotechnology, which was so obviously defamatory and possibly libellous that the journal had to give us a right to reply.

4. Direct evidence of hazards inherent to the technology is swept aside and misrepresented.
Topping the list of the direct evidence of hazard inherent to the technology is the study of Pusztai and co-workers [10, 11], who found dramatic ‘growth-factor like’ effects in the stomach and intestine lining of young rats fed GM potato for just 10 days, which were not present either in rats fed non-GM potatoes or in rats fed non-GM potatoes spiked with the transgene product. These results have been dismissed in the absence of any attempt made to repeat the experiments.

5. Positive evidence of horizontal gene transfer denied and dismissed as “very low frequency”.
It is remarkable that there has been only one single field monitoring experiment after millions of hectares of GM crops have been planted, and just one human feeding trial involving 19 individuals fed a single meal containing GM soya flour. Despite that, positive evidence of horizontal transfer of GM DNA to bacteria in the soil and in the human gut has been found. More remarkable still, our Government’s science advisors persist in denying and dismissing this evidence.

ACRE says whether the transgene persists, after horizontal gene transfer depends on ‘selection pressure’. We have exposed this to be false [12]. Experiments dating back to the early 1990s have already found that antibiotic resistance genes persist in bacteria that have acquired them long, long after the antibiotic was withdrawn [13,14].

ACRE has further misrepresented Ho’s citation of Hohlweg & Doerfler [15]. Ho said it was the latest of a series of papers [e.g., 16, 17] dating back to the early 1990s which have shown that transgenic DNA can pass through the gut and the placenta into the blood stream and end up in cells, including those of the fetus and newborn. Hohlweg & Doerfler [15] did not show transgenic DNA transfer to germline, but there was copious transfer to somatic cells. Foreign DNA inserting into genomes of cells can lead to “insertion mutagenesis” and “insertion carcinogenesis”. Ho’s citation of cancer arising from gene therapy experiments here is surely not “out of context”.

ACRE, in dismissing concerns about GM DNA transferring to gut bacteria, state, “Microbes in samples from ileal digesta were cultured and despite exhaustive attempts, no bacteria harbouring the transgene were isolated”. This is a misrepresentation, as the researchers, while reporting that they were unable to isolate these particular bacteria, confirmed that there were bacteria with the GM DNA present in the gut. Also, ACRE states, “In people with intact tracts, they found that although transgene DNA from GM soya survived passage through the human small bowel, it was completely degraded in the colon and was not detected in faeces”. But the researchers did not investigate if the GM DNA had entered the bloodstream and cells of various tissues and organs, and we know that this can happen [16, 17].

ACRE dismisses the possibility, suggested by the UK government’s own commissioned research that Agrobacterium in the vector system used in making transgenic plants, and found to remain in transgenic plants, may be a vehicle for gene escape by horizontal gene transfer. ACRE makes the misleading comparison between natural Agrobacterium found in the soil, which have no ready access to mammalian cells, and the Agrobacterium in the transgenic plants, which might easily be eaten by animals and human beings. Equating genetically manipulated with natural Agrobacterium is also spurious, and once again, depends on the unfounded, unjustified assumption that GM DNA is the same as non-GM DNA.

ACRE says there is no evidence transgenic DNA can transfer to bacteria. Here are two of the relevant publications cited, albeit incompletely, by the GM Science Review First Report. Duggens and coworkers [18] found that the entire coding sequence of the Cry1A(b) transgene could still be detected in sheep rumen fluid 5 hours after feeding GM maize grains, and fragments more than 200bp long were detected 24 hours later. Plasmid containing the transgene and kanamycin resistance marker gene could still transfer the entire transgene as well as kanamycin resistance to E. coli after being kept for 5 minutes in the sheep’s mouth. The authors remarked, “DNA released from feed material within the mouth has potential to transform naturally competent oral bacteria.” Similarly, Mercer and coworkers [19] showed that both plasmid and chromosomal DNA fragments were incompletely degraded after incubation in the human mouth, and can still transform Streptococcus gordonii, which normally lives in the mouth.

A host of other problems also dismissed by ACRE
Other problems and hazards to health and the environment in growing GM crops, such as toxicity and allergenicity of the transgene products, toxicity of herbicides used with herbicide tolerant GM crops, herbicide tolerant weeds and transgene contamination of non-GM and organic crops, are dealt with in the ISP Report [4]. Needless to say, those are also ignored by ACRE.

Some definitive experiments that remain to be done
Like ACRE, we see no point in going over the same disagreements or recycling the same arguments. At a public meeting last November, Ho has submitted to the Advisory Committee for Novel Foods and Processes (ACNFP) – ACRE’s sister committee – a list of experiments that should be done to address areas of uncertainty, and these are reproduced below, in a slightly improved form [4], in the (vain) hope that ACRE will advise our government to commission such research, and thereafter, to convey the results without distortion and misrepresentation.

Some definitive experiments that could inform on the safety of GM food and crops

1. Feeding experiments similar to those carried out by Pusztai’s team, using well-characterized transgenic soya and/or maize meal feed, with appropriate, unbiased monitoring for transgenic DNA in the faeces, blood and blood cells, and post-mortem histological examinations that include tracking transfer of transgenic DNA into the genome of cells. As an added control, non-transgenic DNA from the same GM feed sample should also be monitored. In addition, the possible role of the CaMV 35 S promoter in producing the ‘growth-factor-like’ effects in young rats should be investigated.

2. Feeding trials on human volunteers using well-characterized transgenic soya and/or maize meal feed, with appropriate, unbiased monitoring for transgenic DNA and horizontal gene transfer in the mouth and in the faeces, blood and blood cells. As an added control, non-transgenic DNA from the same GM feed sample should also be monitored.

3. Investigation on the stability of transgenic plants in successive generations of growth, especially those containing the CaMV 35S promoter, using appropriate quantitative molecular techniques.

4. Full event specific molecular characterisation of all transgenic lines to establish uniformity and genetic stability of the transgenic DNA insert(s), and comparison with the original data supplied by the biotech company to gain approval for field trials or for commercial release.

5. Tests on all transgenic plants created by the Agrobacterium T-DNA vector system for the persistence of the bacteria and the vectors. The soil in which the transgenic plants have been grown should be monitored for gene escape to soil bacteria. The potential for horizontal gene transfer to the next crop via the germinating seed and root system should be carefully monitored.

 

Sources

1. “Response to ISIS Comments on ACRE’s Advice Concerning T25 Maize”. http://www.defra.gov.uk/environment/acre/advice/pdf/acre_advice34.pdf

2. See “GM Science Review Deeply Flawed”, Science in Society 2003, 19, www.i-sis.org.uk

3. GM Science Review First Report, July 2003 <www.gmsciencedebate.org.uk/report/default.htm>

4. Ho MW, Lim LC, et al. The Case for a GM-Free Sustainable World, Independent Science Panel Report, ISIS and TWN, London & Penang, 2003.

5. Ho MW. Living with the Fluid Genome, ISIS and TWN, London & Penang, 2003.

6. Gahakwa D, Maqbool SB, Fu X, Sudhakar D, Christou P and Kohli A. Transgenic rice as a system to study the stability of transgene expression: multiple heterologous transgenes show similar behaviour in diverse genetic backgrounds. Theor Appl Genet 2000: 101: 388-99.

7. Ho MW. Questionable stability at JIC, ISIS News 9/10, July 2001, ISSN: 1474-1547 (print), ISSN: 1474-1814 (online) www.i-sis.org.uk reviewing ref. 6.

8. Bergelson J, Purrington CB, Wichmann G. Promiscuity in transgenic plants. Nature 1998, 395, 25.

9. Ho MW, Ryan A and Cummins J. Cauliflower mosaic viral promoter – a recipe for Disaster? Microbial Ecology in Health and Disease 1999 11, 194-7.

10. Ewen S and Pusztai A. Effect of diets containing genetically modified potatoes expressing Galanthus nivalis lectin on rat small intestine. The Lancet 1999, 354, 1353-4; also http://plab.ku.dk/tcbh/PusztaiPusztai.htm for Pusztai’s full rebuttal to his critics.

11. Pusztai A, Bardocz S and Ewen SWB. Genetically modified foods: Potential human health effects. In Food Safety: Contaminants and Toxins, (J P F D’Mello ed.), Scottish Agricultural College, Edinburgh, CAB International, 2003.

12. Ho MW. Genetic Engineering Dream or Nightmare? TWN, Gateway, Gill & Macmillan, Continuum, Penang, Bath, Dublin, New York, 1998, 1999, Chapter on The Immortal Microbe and the Promiscuous Genes.

13. Tschape H. The spread of plasmids as a function of bacterial adaptability. FEMS Microbiology Ecology 1992, 15, 23-32.

14. Schrag SJ & Perrot V. Reducing antibiotic resistance. Nature 1996, 381, 120-1.

15. Hohlweg U. and Döerfler W. On the fate of plant or other foreign genes upon the uptake in food or after intramuscular injection in mice. Mol Genet Genomics 2001, 265, 225-33.

16. Schubbert R, Rentz D, Schmitz B and Döerfler W. Foreign (M13) DNA ingested by mice reaches peripheral leukocytes, spleen and liver via the intestinal wall mucosa and can be covalently linked to mouse DNA. Proc. Nat. Acad. Sci. USA 1997, 94, 961-6.

17. Döerfler W, and Schubbert R. Uptake of foreign DNA from the environment: the gastrointestinal tract and the placenta as portalsof entry. Wien Klin. Wochenschr. 1998, 110, 40-4.

18. Duggan PS, Chambers POA, Heritage J & Forbes JM. Fate of genetically modified maize DNA in the oral cavity and rumen of sheep. British J. Nutrition 2003, 89, 159-66.

19. Mercer DK, Scott KP, Melville CM, Glover LA & Flint HJ. Transformation of an oral bacterium via chromosomal integration of free DNA in the presence of human saliva. FEMS Microbiology Letters 2001, 200, 163-7.



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