THE BEST KEPT SECRET OF GM CROPS

[Guest guest]

The Best Kept Secret of GM Crops

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Witness Statement to ACRE

For ACRE open hearing on the criticisms of T25 GM maize risk assessment

The hearing will take place from 10.00am to 2.00pm on Wednesday, 20

February, in Room 7A, B and C, Ashdown House, Department for Environment,

Food and Rural Affairs, 123 Street, London SW1E 6DE.

Dr. Mae-Wan Ho

Institute of Science in Society, PO Box 32097, London NW1 0XR, UK

I am speaking against the market approval of T25 because there is no

evidence that it is a genetically stable, uniform line, the single most

important criterion for approval. For unless it is genetically stable, you

might as well forget about environmental or health risk assessment. And

genetic instability is also a serious safety issue. The public hearing on

T25 was suspended over a year ago when it was found not to have passed the

required EC test for Distinctiveness, Uniformity and Stability (the DUS

test), as I pointed out when giving evidence to the hearing [1].

The new EC Directive on deliberate release requires strict molecular

evidence of genetic stability, which is also necessary for establishing the

identity of the transgenic line and to ensure traceability. The best-kept

secret of GM crops is that they are not stable.

There is a large literature on gene silencing, in which the transgenes

remain in the genome, but are not expressed. More serious, from the safety

point of view, is structural instability, the tendency for the transgenic

DNA to come loose, to rearrange or become lost in part or in whole in

successive generations [2,3]. This could change the transgenic line in

unpredictable ways in terms of health and environmental risks. And it will

increase the chance of transgenic DNA being taken up by unrelated species to

make new combinations with their genetic material. That's referred to as

horizontal gene transfer and recombination. Transgenic DNA can spread to

every species that interact with the transgenic plant, in the soil, in the

air, in the mouth and gut and the respiratory tracts of animals including

human beings.

New viruses and bacteria that cause diseases could be generated, and

antibiotic resistance marker genes could spread to the pathogens. Transgenic

DNA may also get into human cells and insert into the human genome; and a

large body of evidence from so-called gene therapy experiments have amply

demonstrated this does occur [4]. The constructs used in gene therapy are

very similar to those used in transgenic plants, and one main side-effect of

transgenic DNA inserting into human genome during gene therapy is cancer.

Despite that, our regulators have not required biotech companies to provide

molecular evidence of stability. ACRE's latest guidelines for industry put

out for public consultation asks industry to provide molecular evidence of

genetic stability over one generation only [5], which is derisory. We need

data for at least five successive generations [6]. No such data have come

forward from the companies. On the contrary, companies have been allowed to

hide under 'commercial confidentiality'.

I am putting to you twelve reasons why trangenic DNA is different from

natural DNA, and is more likely to spread by horizontal gene transfer and

recombination, both by design and otherwise. I hope you will refute these

point by point.

(The details are in two ISIS reprint collections on transgenic instability

and horizontal gene transfer that I am presenting to ACRE, for free.)

All artificial constructs tend to be unstable, so much so that this is a

topic in a standard text-book on genetic engineering [7]. Transgenic DNA is

more likely to break and join up again, ie, to recombine.

Transgenic DNA typically contains DNA from widely different sources, mainly

bacteria and viruses and other genetic parasites that cause diseases and

spread antibiotic resistance, and hence, has the potential to recombine

homologously with all those agents, ie, due to similarities in DNA

base-sequence. Homology enhances horizontal gene transfer 10 million to 100

million-fold [8].

Transgenic DNA is designed to cross species barriers and to invade genomes.

They are flanked by recombination sequences, such as the left and right

borders of T-DNA or the terminal repeats of viral vectors, which enable them

to jump into genomes. By the same token, they could jump out again. Enzymes

catalysing jumping in also catalyse jumping out.

Certain 'receptive hotspots' have now been identified in both the plant [9]

and the human genome [10]. These may also be 'recombination hotspots', prone

to breaking and rejoining. That would mean inserted transgenes are more

likely to be lost, to recombine, or to invade other genomes.

There are mechanisms in the cell that actively seek out, inactivate or

eliminate foreign DNA from the genome [11].

Cell and embryo culture methods are well-known to induce unpredictable,

uncontrollable (somaclonal) variations that persist in the plants generated.

There is now evidence that the transformation process for making transgenic

plants induces further genetic instability [12-14] leading to chromosomal

rearrangements, genome scrambling, in other words.

Monsanto's Roundup Ready soya, commercially grown for years, was finally

analysed by molecular methods. Not only is the gene order of the insert

found to be scrambled, the plant genome at the site of insertion is also

scrambled, and there is a 534 bp fragment of unknown origin in there as well

[15]. All very different from the original data provided by Monsanto.

Recombination hotspots within the transgenic DNA, such as that associated

with the ubiquitous cauliflower mosaic virus (CaMV) 35S promoter, could

enhance horizontal gene transfer and recombination. We highlighted that in

1999 [16-18], and demanded that all transgenic crops with the promoter

should be immediately withdrawn for safety reasons. Two years later, the

researchers who discovered the promoter's recombination hotspot also

recommended that it should no longer be used [19], not because of safety,

but because its instability compromises agronomic performance.

Recently, landraces of corn growing in remote regions of Mexico were found

contaminated with transgenic corn DNA by probing with the CaMV 35S promoter

[20]. Molecular analysis showed that the sequences next to the promoter are

very diverse, as consistent with horizontal gene transfer and recombination

[21].

CaMV 35S promoter is active in species across the entire living world,

including frog eggs and human cells [18], as we uncovered in the literature

more than ten years old that had apparently escaped the notice of plant

geneticists who attacked us. CaMV 35S promoter, if transferred to human or

animal cells, could activate cancer-associated genes as well as dormant

viruses that are in all genomes. Another side effect of gene-therapy is the

generation of active viruses in cell lines used to package the gene-therapy

vectors [4]. Our critics are still dismissing the risks of CaMV 35S

promoter, but are avoiding doing any experiments. It is a case of don't

look, don't see [5].

Transgenic DNA from GM plants was found to transfer to soil bacteria. The

possibility of transfer to bacteria in the mouth and gut of animals was

suggested in laboratory investigations funded by the UK government. There is

also evidence suggesting that transgenic DNA from crop plants has

transferred to soil bacteria in the field [22]. But ACRE has ignored that by

a selective interpretation of the scientific evidence that seems to me

contrary to both the precautionary principle and good science [23].

In summary, there is no reason to believe T25 is stable. Furthermore, it has

especially hazardous sequences, including the CaMV 35S promoter and an

ampicillin resistance gene that, though inactive, can easily be transferred

into integrons that will provide it with a promoter to make it functional

[1]. T25 has uncharacterised sequences that might be involved in causing

diseases. Finally, it has an origin of replication, which enables the

transgenic DNA to be replicated as a plasmid if transferred into bacteria,

thereby greatly increasing horizontal gene transfer on to other species. The

origin of replication is also a recombination hotspot, and there have been

strong recommendations from a recent joint FAO/WHO Expert Consultation on

Foods Derived from Biotechnology that transgenic lines containing this

sequence should not be approved on safety grounds [24].

1. Ho MW. Chardon LL Public Hearing Ocober 26 2000 on behalf of Burnham

Group, also in transcript.

2. See Ho MW. Genetic Engineering Dream or Nightmare? Gateway, Gill &

Macmillan, Bath and Dublin, 1998, 1999, Chapter on Perils amid Promises of

Genetically Engineered Foods.

3. ISIS Reprints on Transgenic Instability, 1999-2001, ISIS Publications,

London.

4. Ho MW, A, Cummins J and Traavik T. Slipping Through the Regulatory

Net: 'Naked' and 'Free' Nucleic Acids, Third World Network Biotechnology

Series, Third World Network, Penang 2001.

5. See Watering down EC Directive on Deliberate Release ISIS Report,

February 2002.

6. Ho MW and Steinbrecher RA. Fatal flaws in food safety assessment:

critique of the joint FAO/WHO Biotechnology and Food Safety Report.

Environmental & Nutritional Interactions 1998, 2, 51-84.

7. ISIS Reprints on Horizontal Gene Transfer, 1999-2001, ISIS Publications,

London.

8. Principles of gene manipulation, by Old and Primrose, Blackwell Science,

5th ed, 1994.

9. DeVries J, Meier P and Wackernagel W. The natural transformation of the

soil bacteria Pseudomonas stutzeri and Acinetobacter sp. by transgenic plant

DNA strictly depends on homologous sequences in the recipient cells. FEMS

Microbiology Letters 2001, 195, 211-5.

10. Kumar S and Fladung M. 2000. Transgene repeats in aspen: molecular

characterisation suggests simultaneous integration of independent T-DNAs

into receptive hotspots in the host genome. Mol Gen. Gent 2000, 264, 20-8.

11. DG, Rutledge EA and DW. Chromosomal effects of

adeno-associated virus vector integration. Nature genetics 2002, 30, 147-8.

12. Kumpatla, S.P., Chandrasekharan, M.B., Iyer, L.M., Li, G. and Hall, T.C.

(1998). Genome intruder scanning and modulation systems and transgene

silencing. Trends in Plant Sciences 3, 96-104.

13. Horvath H, Jensen L,Wong O, Kohl E, Ullrich S, Cochran J, Kannangara C,

and von Wettstein D. Stability of transgene expression, field performance

and recombination breeding of transformed barley lines, Theor Appl Genet.

2001,1-11.

14. Svitashev S, Ananiev E, Pawlowski WP, and Somers DA. 2000. Association

of transgene integration sites with chromosome rearrangements in hexaploid

oat. Theoretical and Applied Genetics 2000, 100,: 872-80.

15. Tax FE and Vernon DM. T-DNA-associated duplication/transloations in

Arabidopsis. Implications for mutant nanalysis and functional genomics.

Plant Physiology 2001, 126, 1527-38.

16. Windels P, Taverniers I, Depicker A, Van Bockstaele E and De Loose M

(2001). Characterisation of the Roundup Ready soybean insert. Eur Food Res

Technol DOI 10.1007/ s002170100336, © Springer-Verlag; see also " Scrambled

genome of Roundup Ready soya " by Mae-Wan Ho, ISIS Reprints on Transgenic

Instability, 1999-2001, ISIS Publications, London.

17. Ho MW, A and Cummins J. Cauliflower mosaic viral promoter - a

recipe for Disaster? Microbial Ecology in Health and Disease 1999: 11:

194-197.

18. Ho MW, A and Cummins J. Hazards of transgenic plants with the

cauliflower mosaic viral promoter. Microbial Ecology in Health and Disease

2000: 12: 6-11.

19. Ho MW, A and Cummins J. CaMV35S promoter fragmentation hotspot

confirmed and it is active in animals. Microbial Ecology in Health and

Disease 2000: 12: 189.

20. Christou P, Kohli A, Stoger E, Twyman RM, Agrawal P, Gu X. Xiong J,

Wegel E, Keen D, Tuck H, M, Abranches R and Shaw P. Transgenic

plants: a tool for fundamental genomics research. Innes Centre &

Sainsbury Laboratory Annual Report 1999/2000, p. 29. See " Top research

centre admits GM failure " ISIS Reprints on Transgenic Instability,

1999-2001, ISIS Publications, London.

21. Quist D and Chapela IH. Transgenic DNA introgressed into traditional

maize landraces in Oaxaca, Mexico. Nature 2001, 414, 541-3, 2001.

22. " Transgenic pollution by horizontal gene transfer? " by Mae-Wan Ho, in

ISIS Reprints on Horizontal Gene Transfer, 1999-2001, ISIS Publications,

London.

23. " Horizontal gene transfer happens. A practical exercise in applying the

precautionary principle " by Mae Wan Ho in ISIS Reprints on Horizontal Gene

Transfer, 1999-2001, ISIS Publications, London.

24. Joint FAO/WHO Expert Consultation on Foods Derived from Biotechnology,

WHO Headquarter, Geneva, September 24-28, 2001.

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