Science in Society Archive

Comment on Assessment ReportC/GB/02/M3/03 (herbicide tolerant and insect resistant hybrid maize, NK603xMon810)

No credible evidence that NK603xMon810 is safe for animal and human health

The Assessment Report C/GB/02/M3/03 contains no credible evidence that NK603xMon810 is safe for animal and human health.

  • No independent molecular data were provided to ascertain that the transgene inserts are stable as claimed by the company
  • No independent molecular data were provided to ascertain that the transgene inserts remained stable in the seeds set that will be used for animal feed and human food
  • No toxicological studies were carried out
  • No tests for allergenicity were conducted
  • No feeding trials were done on cows or pigs
  • No data accompanied Monsanto's own feeding trial on chickens
  • Not a single reference was made to peer-reviewed scientific literature
Thus, there is no justification for the advice from ACRE (Advisory Committee for Releases to the Environment) that this hybrid GM maize "does not pose a risk to human health or the environment".

ACRE has ignored all evidence to the contrary

On the contrary, ACRE has totally ignored existing evidence suggesting that NK603xMon810 may not be safe. We consider first the parental lines, Mon810 and NK603.

1. Parental lines proven unstable and hence illegal under European legislation
The transgene insert in the parental line Mon810 has proven to be unstable, i.e., it has rearranged since characterized by the company [1-5]. Likewise, the transgene insert in the NK603 line was also found to have rearranged [6], which may be part of the reason why its application for import into Europe for food and processing has failed to gain the required majority vote in the Regulatory Committee on the release of GMOs into the environment on 18 February 2004.

According to the new European Directive for deliberate release 2001/18/EC, event specific characterization of the transgenic insert as proof of transgenic stability is required for approval. Such even-specific characterization is also necessary to satisfy EC Novel Foods Regulation 258/97 and regulations 1139/98/EG and 49/2000 for traceability and labeling. Thus, both parental lines should be considered illegal within current European legislation. This applies all the more so to the hybrid NK603xMon810 derived from the two parental lines.

2. NK603xMon810 needs to be characterized for stability
Independent re-characterization of the transgenic inserts in NK603xMon810 is required because of the strong possibility of non-homologous recombinations (genome scrambling) between the two non-allelic inserts in the parental lines which nevertheless possess sequence homologies, specifically, in the cauliflower mosaic virus (CaMV) 35S promoter with enhancer (e35S) and the hsp70 intron used to drive transgene expression in both events NK603 and Mon810.

3. Transgene instability is above all a safety issue
The stability of the transgene insert in a GMO is above all a safety issue. The fact that the transgenic lines have undergone genetic rearrangement since the company carried out safety tests automatically invalidates all those tests. As everyone knows, the characteristics of a transgenic line depend entirely on where in the genome and in what form the inserts have integrated; if an insert has rearranged or moved elsewhere, then the transgenic line, by definition, has lost its original identity and become a different line.

4. Mon810 insert associated with a mobile genetic element
The insert for Mon810 has been extensively characterized in the published literature. The host genome flanking the 5' (head) end of the insert shows homology to the long terminal repeats (LTR) of the maize alpha Zein gene cluster; but no homology to the maize genome was detected at the 3' site, indicating that there had been scrambling of the maize genome at the insertion site [1-3]. Long terminal repeats are found in mobile genetic elements and often contain strong promoters that respond to environmental signals. That not only makes secondary mobility of the insert (horizontal gene transfer) much more likely, but also lead to major disturbances in host gene expression.

Transgene inserts in general show a strong preference for mobile genetic elements. One study [1] found that the insert in Chardon LL T25, recently approved by the UK government for commercial growing, is located in a retrotransposon.

5. The CaMV 35S promoter remains a major safety concern
We have raised serious safety concerns over the CaMV 35S promoter, which is known to have a recombination hotspot and to be active in species across the living world, including human cells [7-9]. We note that both events NK603 and Mon810 have transgenes driven by this promoter, as have other GM maize lines that the UK government has recently approved: Bayer's Chardon LL T25, and Syngenta's Bt 176. The safety of this promoter has been set as one of a list of "self tasking activities" recorded in the minutes of the European Food Safety Authority 5th Plenary Meeting of the Scientific Panel on Genetically Modified Organisms held on 11 December 2003 [10]. The relevant paragraph is reproduced below:

"10. TERMS OF REFERENCE FOR SELF TASKING ACTIVITIES
The members of the GMO Panel are invited to provide written comments by the next plenary meeting on the following proposals for self tasking activities:
- Impact of GMOs on microbial biodiversity and function in the soil environment
- Post market monitoring of crops
- Assessment of allergenicity of genetically modified (GM) foods
- Post market surveillance of genetically modified (GM) foods
- Safety of use of viral promoters and specifically of the cauliflower mosaic virus (CaMV) promoter. "
The minutes of the subsequent meeting held in January 2004, recorded that this issue remains unresolved, and is "deferred to a later stage" [11].

6. Major incidents involving GM maize with Bt toxins
Finally, we draw your attention to two incidents involving GM maize containing Bt toxins (from soil bacterium Bacillus thuringiensis). Only one case is under investigation by scientists.

Syngenta's Bt176

Between 2001 and 2002, 12 dairy cows died on a farm in Woelfersheim in the state of Hesse in Germany after being fed Syngenta's Bt 176 maize; and other animals in the same herd had to be slaughtered on account of mysterious illnesses [12]. The Robert Koch Institute made little attempt to investigate the deaths and illnesses and the local district council in Giessen issued a statement in August 2003 stating that "the cause of incidents referred to could not be determined."

We pointed out [13] that Bt 176 suffers from the worst transgenic instability of all the transgenic lines examined recently by French and Belgian government scientists, who found that the company may also have misidentified or misreported the particular Cry1A protein present. Syngenta claims that the transgene in Bt176 is crylAb, but on analysis, the sequence of the transgene was 94% similar to a synthetic crylAc gene, and has only 65% homology with the native cry1Ab gene of Bacillus thuringiensis subsp kurstaki, from which it was supposed to have been derived.

This incident highlights the regulatory sham surrounding Bt crops [14, 15]. Bt toxins encompass a large superfamily of Cry proteins made by different strains of B. thuringiensis. The Bt transgenes incorporated into GM crops, however, are often synthesized in the laboratory, containing truncated (pre-activated) versions of the natural toxins (as in the case of Mon810) which means that they can harm non-target insects and other animals, or changes in amino acid sequences, or hybrid sequences of two or more Cry toxins, such that the toxicities to insect pests and other animals are totally unknown and untested. Yet, regulators have routinely accepted toxicity and allergenicity tests based on the natural toxins isolated from B. thuringiensis.

Mon810

Last year, scores of villagers in the south of the Philippines living near fields planted with Dekalb 818 YG - which turns out to be a hybrid between Mon810 and a locally adapted variety (Dekalb 818) - became ill when the maize started to flower. Dr. Terje Traavik, director of the Norwegian Institute of Gene Ecology, found antibodies reacting against the Bt toxin Cry1Ab, which is produced by Mon810, in the sera of 39 farmers who were affected. He reported this finding, along with other results of research in progress during a workshop preceding the Meeting of the Parties of the Cartagena Biosafety Protocol in Kuala Lumpur, Malaysia on 22 February 2004. He considered those results too important for public health to wait until the scientific reports appear in print after a lengthy "peer-review" process, and wanted to issue a timely warning to the delegates attending the official biosafety meeting

This provoked an immediate reaction from the pro-GM lobby, which has been running a campaign to discredit Traavik ever since. Traavik has reaffirmed his findings in answer to his critics [16]:

"We have used direct and inhibitory ELISAs (enzyme-linked immuno-sorbent assays) to demonstrate IgA, IgG and IgM antibodies specifically binding to Bt-toxin Cry1Ab in sera from Philippine farmers. A general interpretation would be that the farmers had been exposed, in an immunologically meaningful way, to Cry1Ab, or an antigen sharing epitopes with Cry1Ab, during the last 6-9 months before blood samples were taken. This might indicate coincidence in time between three observed events: the very first pollination season for Bt-transgenic maize, an outbreak of respiratory/intestinal disease among individuals living close to the Bt-maize field, and the production of serum antibodies. I strongly emphasized that the tests could not establish any cause-effect relationships between the 3 events, neither could the results preclude such relationships, and hence they might represent an early warning. As I said at the time, even if I had been able to present the detection of specific anti-Cry1Ab IgE antibodies, my conclusions would have been the same."

The companies have repeatedly denied that Bt toxins are allergenic, but there are reports in scientific literature that Cry1Ac is a strong immunogen [17-19], and hence a potential allergen. Cry1Ac shares many Cry1A epitopes with CrylAb. Furthermore, as Travvik points out, "Bacillus thuringiensis spraying has elicited specific Cry1A antibodies in farm workers, within the same classes we detected, as well as allergy-related IgE antibodies. These findings were published already in 1999.." [20].

Recently, researchers in Japan's National Institutes of Animal Health, Food Research, and Livestock and Grassland Science found that Cry1Ab protein in GM maize Bt11 survives digestion in the gut of pigs [21, 22]. Its digestibility was estimated to be 92% by comparison with indigestible chromic oxide. Researchers from the Center for Genetic Engineering and Biotechnology in Havana Cuba had earlier identified 6 proteins in the brush border that bind specifically to Cry1Ac [23, 24], a toxin in the same family as Cry1Ab.

Conclusion

In conclusion, we consider the approval of NK603xMon810 and other GM maize mentioned, T25 and Bt176, to be a serious abuse of science in face of scientific and other evidence indicating that these GM crops pose serious health risks.

Dr. Mae-Wan Ho
Prof. Joe Cummins
Institute of Science in Society
And Independent Science Panel

Article first published 09/04/04


References

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  2. Holck A, Va M, Didierjean L, Rudi K. 5'-Nuclease PCR for quantitative event-specific detection of the genetically modified Mon 810 MaisGard maize. Eur Food Res Technol 2002, 214, 449-53
  3. Hernandez M, Pla M, Esteve T, Prat S, Puigdomenech P and Ferrando A. A specific real-time quantitative PCR detection system for event MON810 in maize YieldGard based on the 3'-transgene integration sequence. Transgenic Research 2003, 12, 179-89.
  4. Ho MW. Transgenic lines proven unstable. I-SIS Report, 23 October 2003 ; also Science in Society 2003, 20, 35.
  5. Ho MW. Unstable transgenic lines illegal. I-SIS Report 3 December 2003 ; also Science in Society 2004, 21, 23.
  6. "Opinion of the Scientific Panel on Genetically Modified Organisms on a request from the Commission related to the safety of food and food ingredients derived from herbicide-tolerant genetically modified maize NK603, for which a request for placing on the market was submitted under Article 4 of the Novel Food Regulation (EC) No 258/97 by Monsanto (Question No EFSA-Q-2003-002) The EFSA Journal 2003, 9, 1-14.European Food Safety Authority www.efsa.eu.int/science/gmo/gmo_opinions/177_en.html
  7. 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.
  8. Ho MW, Ryan A and Cummins J. Hazards of transgenic plants with the cauliflower mosaic viral promoter. Microbial Ecology in Health and Disease 2000, 12, 6-11.
  9. Ho MW, Ryan A and Cummins J. CaMV35S promoter fragmentation hotspot confirmed and it is active in animals. Microbial Ecology in Health and Disease 2000, 12, 189.
  10. Minutes of the European Food Safety Authority 5th Plenary Meeting of the Scientific Panel on Genetically Modified Organisms held on 11 December 2003 http://www.efsa.eu.int/science/sci_commitee/sci_meetings/238_en.html
  11. Minutes of the European Food Safety Authority 6th Plenary Meeting of the Scientific Panel on Genetically Modified Organisms held 20 and 21 January 2004 (adopted 10 February 2004) http://www.efsa.eu.int/science/sci_commitee/sci_meetings/244_en.html
  12. Henning Strodthoff and Christoph Then. Is GM maize responsible for deaths of cows in Hesse? Greenpeace Report, Greenpeace e.V. 22745 Hamburg. 12/2003.
  13. Ho MW and Burcher S. Cows ate GM maize and died. Science in Society 2004, 21, 4-6.
  14. Cummins J. Regulatory sham on Bt crops. Science in Society 2004, 21, 30.
  15. Cummins J. Bt toxins in genetically modified crops: regulation by deceit. I-SIS Report 23 March 2004 www.i-sis.org.uk
  16. Traavik T. A response to criticism about our work on GE biosafety. 19 March 2004.The Cartagena protocol, the Precautionary principle, "sound science"and "early warnings" www.genok.org
  17. Moreno-Fierros L, Garcia N, Lopez-Revilla R, Vazquez-Padron RI. Intranasal, rectal and intraperitoneal immunization with protoxin Cry1Ac from Bacillus thuringiensis induces compartmentalized serum, intestinal, vaginal and pulmonary immune responses in Balb/c mice. Microbes and Infection 2000, 2,885-90.
  18. Vazquez RI, Moreno-Fierros L, Neri-Bazan L, de la Riva GA. Bacillus thuringiensis Cry1Ac protoxin is a potent systemic and mucosal adjuvant. Scand J. Immunol. 1999, 49, 578-84.
  19. Vazquez-Padron RI, Moreno-Fierros L, Neri-Bazan L et al. Characterization of mucosal and systemic immune response induced by Cry1Ac protein from Bacillus thuringiensis HD 73 in mice. Braz. J. Med. Biol. Res. 2000, 33, 147-55.
  20. Bernstein IL, Bernstein JA, Miller M, Tierzieva S. et al. Immune responses in farm workers after exposure to Bacillus thuringiensis pesticides. Environmental Health Perspectives 1999, 107, 575-82.
  21. Chowdhury EH, Kuribara H, Hin A, Sultana P, Mikami O, Shimada N. Guruge KS, Saito M and Nakajima Y. Detection of corn intrinsic and recombinant DNA fragments and CrylAb protein in the gastrointestinal contents of pigs fed genetically modified corn Bt11. J Anim Sci 2003, 81, 2546-51.
  22. Ho MW. Transgenic DNA & Bt toxin survives digestion. Science in Society 2004, 21, 11.
  23. Vázquez-Padrón RI, Gonzáles-Cabrera J, Garcia-Tovar C, Neri-Bazan L, Lopéz-Revilla R, Hernández M, Moreno-Fierro L and de la Riva GA. CrylAc protoxin from Bacillus thringiensis sp. kurstaki HD73 binds to surface proteins in the mouse small intestine. Biochem Biophys Res Commun 2000, 271, 54-8.
  24. Ho MW. Bt toxin binds to mouse intestine. Science in Society 2004, 21, 7.

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