Science in Society Archive

GM Egg Plant Contains Bt Toxin Linked to Hundreds of Allergy Cases and Thousands of Sheep Deaths

It would be unthinkable and irresponsible to approve the genetically modified eggplant. Dr. Mae-Wan Ho and Prof. Joe Cummins find no published studies nor experimental details on safety tests in the application for field releases of the Bt brinjal and raise serious questions

Bt brinjal a test case for other GM food crops

The Indian subsidiary of US seeds corporation Monsanto, Maharashtra Hybrid Seed, has developed genetically modified (GM) brinjal resistant to fruit and shoot borer and is applying for large-scale test releases [1]. Brinjal, an eggplant, is widely consumed in India and recognized for its health promoting properties such as reducing serum levels of cholesterol. Field trials of other GM crops, including mustard and potatoes, will follow the brinjal test releases.

The GM brinjal contains the same Cry1Ac toxin from the soil bacterium Bacillus thuringiensis as the widely cultivated GM cotton that has been implicated recently in major health controversies in India. Hundreds of farm workers and cotton handlers developed allergic reactions [2] (More illnesses linked to Bt crops, SiS30) and thousands of sheep died from toxic reactions after grazing on the post-harvest GM cotton fields [3] (Mass deaths in sheep grazing on Bt cotton, SiS30).

These controversies on the health hazards of Bt crops corroborate findings dating back to the 1980s, which linked Bt bacteria and spores producing a mixture of Cry proteins to allergic reactions [4]. Cry1Ac itself has been identified as a potent systemic and mucosal immunogen [5] and adjuvant comparable to cholera toxin [6]. Thus, not only can the Bt toxin provoke immune reactions to itself, it can also sensitize a person to develop allergies to other components in the diet. At least 12 dairy cows died in Germany after feeding on GM maize containing a gene coding for a protein similar to Cry1Ac [7] (Cows ate GM maize and died SiS21).

Cry1Ac is not the only Bt transgenic protein linked to serious health problems. Dozens of villagers fell ill in the south of the Philippines when a Bt maize with Cry1Ab came into flower in 2003, and five have died since [8] (GM ban long overdue, dozens ill & five deaths in the Philippines, SiS 29). Illnesses and death associated with numerous other GM crops with different transgenes have been reported in many species. The most dramatic recent example is the severe stunting and premature deaths in the litter of female rats fed GM soya throughout their pregnancy [8], and the debilitating inflammation of the lungs in mice tested with a transgenic pea containing a normally harmless bean protein [9] (Transgenic pea that made mice ill, SiS 29).

A comprehensive public enquiry into the health hazards of GM crops is long overdue, as is a global ban while the enquiry is in place. It is unthinkable and irresponsible to release yet another GM crop with a transgenic protein that has already been implicated in so many illnesses and fatalities.

The Report accompanying the application for field release [1] provides such a superficial description of the GM brinjal and unpublished experiments on environmental and health impacts that it would never have passed muster in Europe; which is not to say that Europe’s regulatory system is adequate. We concentrate on health impact studies that, according to the company, show Bt brinjal is as safe as non Bt brinjal.

Toxicological studies raise worrying questions

Toxicological studies were all unpublished experiments conducted (except for one) at Intox Pvt Ltd., and amounted to bland assurances that none of the tests caused any toxicity.

However, some statements in the Report should be examined carefully. On p. 7, it states (emphasis added): “Acute oral administration of transgenic Bt brinjal expressing CrylAc protein to Sprague Dawley rats at the limiting dose of 5000mg/kg did not cause any toxicity.” What exactly is the limiting dose? Does it mean that beyond 5 000 mg/kg the Bt brinjal was in fact acutely toxic? After all, that is equivalent to a person weighing 50 kg eating a medium-size brinjal, which is not unusual.

The next paragraph reports the results of subchronic oral toxicity study, where it states that “the no-observed-adverse-effect (NOAEL) of transgenic Bt brinjal expressing Cry1Ac protein in Sprague Dawley rat, following oral administration for 90 days was found to be more than 1000 mg/kg body weight. This study demonstrates that Bt brinjal expressing Cry1Ac protein is non-toxic to the study animal by oral route.” 

The designation of “NOAEL” (no-observed-adverse-effect-level) is worrying as it has no scientific precedent. Does that mean doses higher than 1 000mg/kg body weight could be toxic? So, a person weighing 50 kg eating a quarter of a brinjal a day might be putting herself in danger?

The “allergenicity” studies, unpublished and conducted by another company, Rallis India Limited, contained even less details to support the statement of “no differences between the allergenicity or inflammatory characteristics of the 5 brinjal extracts tested including transgenic Bt brinjal and non transgenic brinjal.”

The same goes for the “primary skin irritation test”, and the “mucous membrane irritation test”, both conducted by Intox Pvt. Ltd.

Nutritional studies highly questionable

Another series of  “nutritional studies”, involved “compositional analysis”, which, the company claims, shows that Bt brinjal is “substantially equivalent” to “control brinjal” and thus “the food and feed derived from Bt brinjal will also be substantially equivalent to the food and feed derived from non-Bt counterpart.” Again, there are no experimental details given whatsoever.

Compositional studies have long been rejected by the European public as a demonstration of “substantial equivalence”, and “substantial equivalence” itself is widely seen as unscientific and unacceptable as a principle of risk assessment [10] (The Case for a GM-free Sustainable World).

Another series of unpublished feeding studies with Bt brinjal on fish, chickens cows, goats and rabbits are reportedly, carried out in a variety of companies and institutions, all demonstrating “no significant differences” between Bt and non-Bt brinjal.

In the only case (chickens) where the amount of Bt brinjal eaten is stated, it constituted 5 or 10 percent of the diets. That is equivalent to little more than a mouthful of Bt brinjal at each meal for a human being.

No molecular data

There are no molecular data in the Report to indicate where and in what form the transgenes have inserted into the brinjal genome, and whether the insert has remain stable, which would have been required under the European directive for deliberate release. It is now generally accepted that genetic modification is “event-specific”, the transformation causing a lot of collateral mutational damage to the genome including [10-12] as well as the tendency of the integrated insert to be unstable [10-11, 13-15] (The Case for A GM-Free Sustainable World; Living with the Fluid Genome; Transgenic lines proven unstable; Unstable transgenic lines illegal).

The only molecular information provided is that the Cry1Ac gene is driven by an “enhanced CaMV 35S promoter” (no further details), and two antibiotic resistance marker genes are present: the nptII gene coding for neomycin phosphotransferase II (NPTII) (kanamycin resistance) derived from the prokaryotic transposon Tn5; and the aad gene coding for aminoglycoside adenyl transferase (AAD) (spectinomycin and streptomycin resistance) isolated from bacterial transposon Tn7. The aad gene is under the control of a bacterial promoter and hence not expressed in Bt brinjal, though it would be fully active in bacteria.

Horizontal gene transfer not considered

There is strong likelihood that the two antibiotic resistance marker genes will spread to pathogenic bacteria in all environments by horizontal gene transfer [16-18] (FAQs on genetic engineering; Recent evidence confirms risks of horizontal gene transfer) and hence exacerbate resistance to antibiotics that are currently used in human and veterinary medicine. Horizontal gene transfer is not considered at all in the Report.

There is evidence that such resistance markers may spread to bacteria in the gut of animals including human beings [19]  (DNA in GM food and feed, SiS 23), as well as to bacteria in the soil and water [16] simply because DNA does not break down fast enough in all environments.

Conclusion

In conclusion, it would be courting disaster to release yet another GM crop with a transgenic protein that has already been implicated in so many illnesses and fatalities. The company’s dossier is highly unsatisfactory and incomplete, and raises some serious safety questions. It can give no comfort to farmers and cotton handlers who have suffered allergic reactions to Bt cotton, nor to farmers who have lost their sheep to Bt cotton.

Instead of approving more GM crops, regulatory authorities in India should start a comprehensive enquiry into the health impacts of Bt cotton and impose a ban on further releases of all GM crops.

Article first published 13/07/06


References

  1. Maharashtra Hybrid Seed, Company DEVELOPMENT OF FRUIT AND SHOOT BORER TOLERANT BRINJAL 2006 http://www.envfor.nic.in/divisions/csurv/geac/macho.pdf
  2. Ho MW. More illnesses linked to Bt crops. Science in Society 2006, 30, 8-10, https://www.i-sis.org.uk/isisnews.php
  3. Ho MW. Mass death in sheep grazing on Bt cotton. Science in Society 2006, 30, 12-13, https://www.i-sis.org.uk/isisnews.php
  4. Bernstein IL, Bernstein JA, Miller M, Tierzieva S, Bernstein DI, Lummus Z, Selgrad MJK, Doerfler DL, Seligy VL. Immune responses in farm workers after exposure to Bacillus thuringiensis pesticides. Environmental Health Perspectives 1999, 107 (7), http://www.ehponline.org/members/1999/107p575-582bernstein/bernstein-full.html
  5. Vázquez-Padrón R, Moreno-Fierros L, Neri-Bazan L, de la Riva G and López-Revilla R. Intragastric and intraperitoneal administration of Cry1Ac protoxin from Bacillus thuringiensis induces systemic and mucosal antibody responses in mice.  Life Sci. 1999, 64, 1897-912.
  6. Vazquez RI, Moreno-Fierros L, Neri-Bazan L, De La Riva GA and López-Revilla R. Bacillus thuringiensis Cry1Ac protoxin is a potent systemic and mucosal adjuvant. Scand J Immunol 1999, 578-84.
  7. Ho MW and Burcher S. Cows ate GM maize and died. Science in Society 2004, 21, 4-6, https://www.i-sis.org.uk/isisnews.php
  8. Ho MW. GM ban long overdue, dozens ill and five deaths in the Philippines. Science in Society 2006, 29, 28-29, https://www.i-sis.org.uk/isisnews.php
  9. Ho MW. Transgenic pea that made mice ill. Science in Society 2006, 29, 26-27, https://www.i-sis.org.uk/isisnews.php
  10. Ho MW, Lim LC et al. The Case for A GM-Free Sustainable World, Independent Science Panel Report, TWN and ISIS, Penang and London, 2003, republished as GM-Free, Vital Health Publishing, Ridgefield, CT, 2004, translated into Spanish, French, German, Portuguese, Chinese and Indonesian, https://www.i-sis.org.uk/onlinestore/books.php#232
  11. Ho MW. Living with the Fluid Genome, TWN, ISIS, Penang, London, 2003, https://www.i-sis.org.uk/onlinestore/books.php#232
  12. Latham JR, Wilson AK, Steinbrecher RA. The mutational consequences of plant transformtion. J Biomed Biotech 2006, Article ID 25476, pp. 1-7.
  13. Collonier C, Berthier G, Boyer F, Duplan M-N, Fernandez S, Kebdani N, Kobilinsky A, Romanuk M, Bertheau Y. Characterization of commercial GMO inserts: a source of useful material to study genome fluidity. Poster presented at ICPMB: International Congress for Plant Molecular Biology (n°VII), Barcelona, 23-28th June 2003. Poster courtesy of Pr. Gilles-Eric Seralini, Président du Conseil Scientifique du CRII-GEN, www.crii-gen.org
  14. Ho MW. Transgenic lines proven unstable. Science in Society 2003, 20, 35, https://www.i-sis.org.uk/isisnews.php
  15. Ho MW. Unstable transgenic lines illegal. Science in Society 2004, 21, 23, https://www.i-sis.org.uk/isisnews.php
  16. Ho MW. Recent evidence confirms risks of horizontal gene transfer. ISIS contribution to ACNFP/Food Standards Agency Open Meeting 13 November 2002, https://www.i-sis.org.uk/FSAopenmeeting.php
  17. de Vries J, Herzfeld T and Wackernagel W. Transfer of plastid DNA from tobacco to the soil bacterium Acinetobacter sp. by natural transformation. Molecular Microbiology 2004, 53, 323-34.
  18. Nielsen K, van Elsas J and Smalla K. Transformation of Acinetobacter sp. strain BD413(pFG4DeltanptII) with transgenic plant DNA in soil microcosms and effects of kanamycin on selection of transformants.  Appl Environ Microbiol. 2000, 66,1237-42.
  19. Ho MW. DNA in GM food and feed. Science in Society 2004, 23, 34-36, https://www.i-sis.org.uk/isisnews.php

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