Open Letter to Scientific Steering Committee on Farmscale Field Trials

We are writing to express our concern that the UK farmscale field trials of Aventis Chardon LL GM maize and other GM crops should not continue. Any new technology must be tested, but there are important scientific issues that must be addressed before GM crops can be released into the environment even in the context of testing. To conduct field trials before this has been done is both premature and hazardous; it is like carrying out clinical trials of a drug before the laboratory tests are complete. We present here some of the evidence which leads us to this conclusion.

1. Both the legality and safety of Chardon LL maize and other GM crops have been strongly
contested by scientists and others during the Chardon LL hearing held in the UK last year. The hearing was adjourned subsequent to a press release issued by UK Ministry of Agriculture Fisheries and Food (MAFF), October 30, 2000, admitting that Chardon LL has not passed the test for Distinctness, Uniformity and Stability required for commercial approval. We have pointed out that none of the GM crops could have passed this test on account of well-known problems of transgenic instability (1).

2. The possibility of cross-pollination with non-GM and organic crops as well as wild relatives is now generally acknowledged. In Canada, volunteer oil seed rape tolerant to three different herbicides has arisen in just two years after the three independent herbicide tolerant lines have been planted in adjacent fields (2). An interim report on UK field trials, similarly, confirmed that hybridisation between adjacent plots of different herbicide-tolerant GM oilseed rape varieties gave rise to hybrids tolerant to multiple herbicides. In addition, GM oilseed rape and their hybrids were found as volunteers in subsequent wheat and barley crops, and had to be controlled by standard herbicides (3). Contamination of non-GM and organic oilseed rape is bound to occur, just as, in the case of Chardon LL, cross-pollination with organic and non-GM sweet corn is inevitable. Maize pollen, generally carried by wind, can be transported over great distances depending on weather conditions. Pollen is also collected and eaten by bees and other insect pollinators. Bees are known to travel up to 10km or more in foraging for food (4). Maize flowers late in the season when few other plants are in flower, and so bees and other pollinators may have little choice but to visit maize plants to gather pollen. This puts at risk organic and non-GM crops, pollinators including bees, the honey produced, farm workers and the general public.

3. A MAFF sponsored study found pollen, transgenic DNA and protein in honey (5), indicating that local honey could readily be contaminated. This has been confirmed by other studies since (6). None of the GM crops field tested, including Chardon LL, has been approved for human consumption. Contamination of the human food chain is a serious matter, as judged by the repercussions from the contamination caused by Aventis’ Starlink GM fodder maize, first discovered in the United States, and then worldwide. Apart from the health risks, the total contribution of bee keeping in the UK - for both honey production and pollination - is estimated at £12 billion (MAFF figures).

4. A German study (in press - (7)) found transgenic DNA in microorganisms in the gut of bee larvae that had been fed GM pollen. This indicates that transgenic DNA, which includes the antibiotic resistance gene, can move from GM pollen into bee colonies. Many GM crops have intact antibiotic resistance genes, which are either expressed in the plants themselves or can be expressed when transferred to bacteria. Even though the ampicillin resistance gene in Chardon LL has lost its promoter, the promoter can be regained by recombination, or, the ampicillin resistance gene may insert into a special mobile element, an ‘integron’, which would provide the gene with a promoter (8,9). We first drew attention to this possibility in a report published in 1998 (10) and again in our submission of evidence to the Chardon LL hearing (1).

5. Widespread tetracycline antibiotic resistance has been reported by beekeepers across Canada, USA and Argentina where most of the GM crops have been planted. Tetracycline and ampicillin have been used for the past forty years to control fowl brood, a common disease in bees. Although further investigations are required, it is possible that transgenic crops with antibiotic resistance genes, or else those using the antibiotic tetracycline as gene control trigger, such as certain male-sterile terminator crops (11), may be responsible for the sudden appearance of tetracycline resistance in bees.

6. The transfer of antibiotic resistance genes to bacteria and yeast in the gut of bee larvae is an example of horizontal gene transfer (12). MAFF-funded research scientists have warned of the transfer of antibiotic resistance genes to bacteria that inhabit the mouth, and respiratory tract of human beings (13, 14 ) and farm animals (15) via transgenic pollen, dust and animal feed. We have reviewed several recent reports on horizontal gene transfer and spelt out the implications (16).

7. The UK’s Advisory Committee for Releases to the Environment (ACRE) reviewed a key scientific paper (17) which monitored, for the first time, the transfer of GM constructs from transgenic plant debris to soil bacteria after field release. ACRE concluded that "no construct specific sequences were detected in bacteria isolated from these soils" and that the study "therefore provided no evidence for horizontal gene transfer in the environment" (18). We are astonished at ACRE’s selective interpretation of the evidence. The researchers have found evidence suggesting that GM construct has transferred to soil bacteria. What they failed to do was to isolate the specific strain of bacteria, which, as they point out, is not surprising, as less than 1% of soil bacteria can be isolated by current techniques. We invite ACRE to consider our review of the same paper (19).

8. There are essentially two other reasons, offered by ACRE (18) and others promoting GM crops, for dismissing horizontal gene transfer. The first is that horizontal gene transfer occurs only under ‘optimised’ conditions. One of the optimum conditions for horizontal gene transfer is sequence homology (similarity), which can increase horizontal gene transfer a thousand to a million-fold. By this criterion, GM constructs are indeed optimised for horizontal gene transfer: they are routinely constructed by combining sequences from widely diverse sources of bacteria, viruses, plasmids and transposons and hence possess homologies to all those agents found in the environment. The second justification is that horizontal gene transfer is a natural process. Indeed it is, but GM constructs are anything but natural. They are new combinations of genes that have never existed in billions of years of evolution. The horizontal transfer of GM constructs cannot, therefore, be considered a natural process. On account of the predominant bacterial and viral origins of the genetic material constituting GM constructs, they have the potential to generate new bacterial and viral pathogens by recombination (see ref. 12 for detailed arguments).

9. There are other features of the GM construct in many transgenic plants that are both hazardous in themselves and/or enhance horizontal gene transfer. The hazards specific to terminator crops, such as Aventis’ spring and winter male-sterile oil seed rape included in the field trials, have been spelt out in a recent report (11). In the case of Chardon LL, we highlighted the cauliflower mosaic virus (CaMV) 35S promoter, the ‘origin of replication’ of the pUC plasmid vector, and uncharacterized plasmid sequences (1).

10. The CaMV 35S promoter and ‘origin of replication’ are both ‘recombination hotspots (20-22). Recombination hotspots exacerbate the widespread problem of trangene instability, and increase the likelihood of horizontal gene transfer. In addition, the origin of replication is a signal for making more copies of the plasmid (or the virus) and the genes it carries. Thus, any GM construct with an origin of replication has the potential to be multiplied independently as a plasmid when transferred to bacteria, thus further increasing the opportunities for horizontal gene transfer and recombination.

11. We have drawn attention to other potential hazards of the CaMV 35S promoter when it is subject to horizontal transfer: recombination with other viral sequences to generate new viruses, and reactivation of dormant proviruses that are now found in all genomes (23). Our critics dismissed the hazards by stating that humans have eaten CaMV-infected cabbage without apparent harm. In reply, we pointed out that the 35S promoter, removed from the virus and joined to new genes, is not the same as the whole virus or the whole viral genome (24, 25). Although the virus is specific for cruciferae, the isolated promoter is promiscuous across the entire living world. It is active not only in all plants, algae, bacteria and yeast, but, as we discovered in literature more than 10 years old, also in animal and human cells (26). Our critics have yet to address the new arguments, nor the additional evidence of transgenic instability we have provided recently (27, 28).

12. There are risks associated with the use of broad-spectrum herbicides. Beneficial organisms such as earthworms and mycorrhizal fungi and other microorganisms involved in nutrient recycling in the soil are susceptible to glyphosate (the active ingredient in Roundup herbicide). Glyphosate is so generally toxic that it has been considered for use as an antimicrobial (29). It is also linked to non-Hodgkin lymphoma (30). Glufosinate is known to cause birth defects (31-33) and to damage nerve cells (34-35). It is notable that the herbicide has not been authorised for commercial use in the UK.

13. Before approval for environmental release of any GM crop, full account must be taken of all the relevant scientific evidence; where the existing evidence is not sufficient, more research should be commissioned before approval is granted. There is nothing to be gained by conducting field trials when there are still important outstanding issues that can be addressed in the laboratory and in glasshouse experiments. The field trials themselves carry unacceptable risks. Post-release health and environmental monitoring must also be carried out. Government scientists should be systematically monitoring the scientific literature. Governments should also provide a scientific ‘clearing house’ where new scientific information is made promptly available to all ministries and agencies and to the general public.

Dr. Mae-Wan Ho, Director
& Angela Ryan, Science Monitor
Institute of Science in Society
24 Old Gloucester St.
London WC1N 3AL

Prof. Brian Goodwin
Biology
Schumacher College, Totnes,
Devon TQ9 6EA

Prof. Joe Cummins
Plant Genetics
University of Western Ontario
London, Ontario,
Canada.

Prof. Peter Saunders
Biomathematics
King’s College
University of London WC2R 2LS

Encl: Eight reports/papers in word files

Contacts: Dr. Mae-Wan Ho m.w.ho@i-sis.org.uk

Prof. Brian Goodwin bcgood1401@aol.com

1. Chardon LL public hearing October 26 2000 on behalf of Burnham Group Witness brief of Mae-Wan Ho www.i-sis.org.uk (enclosed).
2. Hall L, Topinka K, Huffman J, Davis L, and Good A. (2000). Pollen flow between herbicide-resistant Brassica napus is the cause of multiple-resistant B. napus volunteers. Weed Science 48: 688-694.
3. The BRIGHT Project: Botanical and Rotational Implications of Genetically Modified Herbicide Tolerance: Progress Report, March 2000, sponsored by MAFF, SERAD, HGCA, BBRO, Aventis, Crop Care, Cyanamid, Monsanto
4. Capaldi E.A. et al (2000) Ontogeny of orientation flight in the honeybee revealed by harmonic radar, Nature, Vol 403, p 537-40.
   Quote from this paper:
   "…our findings suggest that bees take multiply orientation flights before becoming foragers in order to visit different, and larger, portions of the landscape around the hive. These flights provide them with repeated opportunities to view the hive and its surroundings from different positions, suggesting that bees learn the local landscape in a progressive fashion. Bees navigate using a combination of cues, including the position of the sun and the location of salient landscape features, but it is not known how or whether information about these cues, obtained during sequential flights, is integrated. It is an extraordinary feat for an animal the size of a honeybee to be able to find a small nest from distances as great as 10 km…."
5. Honey from GM plants: integrity of DNA, & entry of GM-derived proteins into the food chain via honey April 1995- Oct 1997. MAFF project no 2B 067 (FS 0203) Submitted by Laboratory of the Government Chemist, Middx. This study not only found significant amounts of transgenic DNA in honey, but also contamination by transgenic protein.
   "Based on the levels of transgenic protein revealed by this study, a consumer would therefore be ingesting approximately 30 pg- 5ng of transgenic protein in every pot (500g) of honey, although caution must be exercised due to sources of potential errors in the extraction procedures. The results presented in this study are in the same order of magnitude as estimates of transgenic protein from another study. Estimates of the amounts of pollen
   and total protein found in honey indicate such levels of transgenic protein may not be hazardous to the vast majority of the consumer population. However since allergenic reactions to non-transgenic honey have been reported it would be unwise to be complacent. Improved data on specific quantities of a range of food allergens are required to resolve this issue."
6. Widmer A., Cozzolino S;.,Pellegrino G., Soliva M. and Dafni A. (2000). Molecular analysis of orchid pollinaria and pollinaria-remains found on insects. Mol Ecol 9, 1911-4.
7. Barnett, A. (2000). GM genes 'jump species barrier' The Observer, May 28, 2000. (A prepublication report of the work by Dr Kaatz at the University of Jena.)
8. Stokes, H.W. and Hall, R.M. (1989). A novel family of potentially mobile DNA elements encoding site-specific gene-integrating functions: integrons. Mole. Microbiol 3, 1669-83.
9. Rowe-Magnos, D.A., Gueront, A.-M., Ploncard, P., Dychinco, B., Davies, J. and Mazel, D. (2001). The evolutionary history of chromosomal super-intefrons provides an ancestry for multiresistant integrons. PNAS 98, 652-7.
10. Ho, M.W., Traavik, T., Olsvik, R., Tappeser, B., Howard, V., von Weizsacker, C. and McGavin, G. (1998b). Gene Technology and Gene Ecology of Infectious Diseases. Microbial Ecology in Health and Disease 10, 33-59.
11. Ho, M.W., Cummins, J. and Bartlett, J. (2001). Killing fields near you – terminator crops at large. ISIS News 7/8 Feb. 2001 ISSN: 1474-1547 (print); ISSN-1474-1814 (on line) www.i-sis.org.uk (article enclosed).
12. Ho, M.W. (2000). Horizontal gene transfer – the hidden hazards of genetic engineering. ISIS and TWN Report. www.i-sis.org.uk (enclosed).
13. Letter from N. Tomlinson, Joint Food Safety and Standards Group, MAFF, to US FDA, 4 December, 1998.
14. Mercer, D.K., Scott, K.P., Bruce-Johnson, W.A. Glover, L.A. and Flint, H.J. (1999). Fate of free DNA and transformation of the oral bacterium Streptococcus gordonii DL1 by plasmid DNA in human saliva. Applied and Environmental Microbiology 65, 6-10.
15. Duggan PS, Chambers PA, Heritage J and Forbes JM. (2000). Survival of free DNA encoding antibiotic resistance from transgenic maize and the transformation activity of DNA in ovine saliva, ovine rumen fluid and silage effluent. FEMS Microbiology Letters 2000, 191, 71-7.
16. Ho, M.W. (2001). Horizontal gene transfer happens II. ISIS Report May 4, 2001 www.i-sis.org.uk (enclosed)
17. Gebbard, F. and Smalla, K. (1999). Monitoring field releases of genetically modified sugar beets for persistence of transgenic plant DNA and horizontal gene transfer. FEMS Microbiology Ecology 28, 261-72.
18. Advice for the Secretary of State, July 2000: Horizontal Gene Transfer: Genetically Modified Crops and Soil Bacteria, published 1 December 2000, Department of the Environment, Transport and the Regions.
19. Ho, M.W. (2000). Horizontal gene transfer happens: a practical exercise in applying the precautionary principle. ISIS News 5, July 2000, ISSN: 1474-1547 (print); ISSN-1474-1814 (on line) www.i-sis.org.uk (enclosed).
20. Kohli, A., Griffiths, S., Palacios, N., Twyman, R.M., Vain, P., Laurie, D.A. and Christou, P. (1999). Molecular characterization of transforming plasmid rearrangements in transgenic rice reveals a recombination hotspot in the CaMV 35S promoter and confirms the predominance of microhomology mediated recombination. Plant J. 17, 591-601.
21. Kumpatla, S.P. and Hall, T.C. (1999). Organizational complexity of a rice transgenic locus susceptible to methylation-based silencing. IUBMB Life 48, 459-67.
22. Christou P, Kohli A, Stofer E, et al. Transgenic plants: a tool for fundamental genomics research. John Innes Centre & Sainsbury Laboratory Annual Report 1999/2000, p.29.
23. Ho, M.W., Ryan, A., Cummins, J. (1999). The cauliflower mosaic viral promoter – a recipe for disaster? Microbial Ecology in Health and Disease 11, 194-197
24. Ho, M.W., Ryan, A. and Cummins, J. (2000). Hazards of transgenic plants with the cauliflower mosaic viral promoter. Microbial Ecology in Health and Disease 12, 6-11.
25. Cummins, J., Ho, M.W. and Ryan, A. (2000). Hazards of CaMV promoter. Nature Biotechnology 18, 363.
26. Ho, M.W., Ryan, A. and Cummins, J. (2000) CaMV 35S promoter fragmentation hotspot confirmed, and it is active in animals. Microbial Ecology in Health and Disease (in press) www.i-sis.org.uk (enclosed).
27. Ho, M.W. (2001). Questionable ‘stability’ at JIC, ISIS Report, 4 March www.i-sis.org.uk (enclosed).
28. Cummins, J. (2001). GM crops may all be unstable. ISIS Report 8 April www.i-sis.org.uk (enclosed).
29. Roberts, G., Roberts, C.W., Johnson, J.J., Kyle, D.E. et al (1998). Evidence for the shikimate pathway in apicomplexan parasites. Nature 393, 801-5.
30. Hardell, H. & Eriksson, M. (1999).   A case-control study of non-Hodgkin lymphoma and exposure to pesticides. Cancer85, 1355-1360.
31. Watanabe, T. (1996). Developmental effects of glufosinate ammonium on mouse embryos in culture. Teratogenesis, Carcinogenesis and Mutagenesis 19, 287-99.
32. Fujii, T. (1997). Transgenerational effects of maternal exposure to chemicals on the functional development to the brain in the offspring. Cancer Causes and Control. 8, 524-8.
33. Garcia,A., Benavides,F., Fletcher,T. and Orts,E. (1998). Paternal exposure to pesticides and congenital malformations. Scand J Work Environ Health 24, 473-80.
34. Watanabe, T and Sano, T. 1998. Neurological effects of glufosinate poisoning with a brief review. Human & Experimental Toxicology 17. 35-9.
35. Cox, C. (1996). Herbicide Factsheet. Glufosinate. J. Pesticide Reform 16, 15-9.

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