Science in Society Archive

Important Books & Reports

Banishing Glyphosate

Banishing Glyphosate - Dr. Eva Sirinathsinghji, Dr. Mae-Wan Ho and others

Glyphosate/Roundup, falsely claimed by Monsanto to be safe and harmless, has become the world’s most widely and pervasively used herbicide; it has brought rising tides of birth defects, cancers, fatal kidney disease, sterility, and dozens of other illnesses - more

Ban GMOs Now

Ban GMOs Now - Dr. Mae-Wan Ho and Dr. Eva Sirinathsinghji

Health & environmental hazards especially in the light of the new genetics - more

Living Rainbow H2O

Living Rainbow H2O - Dr. Mae-Wan Ho

A unique synthesis of the latest findings in the quantum physics and chemistry of water that tells you why water is the “means, medium, and message of life” - more

The Rainbow and the Worm - the Physics of Organisms

The Rainbow and the Worm - the Physics of Organisms - Dr. Mae-Wan Ho

“Probably the Most Important Book for the Coming Scientific Revolution” - more

Pharm Crop Products In US Market

Prof. Joe Cummins discovers that dangerous GM pharmaceutical crops have been produced and marketed in the United States for at least two years, unbeknownst to the public, via a gaping loophole in the regulatory process.

There has been a great deal of public opposition recently to the testing of rice genetically modified to produce the human proteins lysozyme and lactoferrin in the United States [1]. So far, those tests have been stalled (see SiS 22).

But, Sigma-Aldrich, a US chemical company, has been marketing the biopharmaceutical products trypsin, avidin and beta-glucuronidase (GUS) processed from transgenic maize, for at least two years [2]. Meanwhile, Prodigene Corporation and Sigma-Aldrich are marketing aprotinin (AproliZean) from maize [3] and from a transgenic tobacco [4].

Trypsin is a digestive enzyme used extensively in research, to treat disease and in food processing. The product TrypZean is marketed as an animal free product, and is produced jointly by Sigma-Aldrich and Prodigene (the company fined for contaminating food crops with biopharmaceuticals in the United States last year [5]).

The development of genetically modified (GM) food crops generally follows a certain pattern in the United States: First, controlled field tests are undertaken for a number of seasons. Then, the proponent applies for deregulation of the GM crop following reviews by the Animal Plant Health Service (APHIS) of the Department of Agriculture (USDA), the Food and Drug Administration (FDA) and by the Environmental Protection Agency (EPA) if the GM crop includes a plant incorporated bio-pesticide. Upon completion of the process, the GM crop is deemed to be deregulated and can be grown without monitoring.

However, none of the biopharmaceutical-producing GM crops appears to have gone through the usual regulatory process. Instead they appeared to have progressed from field-testing to marketing without the benefit of final regulatory approval, with apparently full cooperation of the FDA and USDA (the agriculture department has proprietary interest in some of the biopharmaceuticals). The biopharmaceuticals have proceeded to the market via the backdoor, thanks to a loophole in the regulation of field tests.

According to the Pew Initiative on Food and Biotechnology, "current APHIS regulations do allow the commercialization of a GE [genetically engineered] crop without a prior affirmative approval by the agency and without public notice. Developers are not required to file a petition for non-regulated status before they produce a plant commercially. It is possible for developers to grow plants at a commercial scale under notification or field trial permits, even if the plants might pose some identifiable environmental or human health risk" [6].

Crop production facilities are permitted as "field tests", but locations of such facilities are designated "confidential business information" and are not disclosed to people living nearby, even though the genes and products of such sites can easily contaminate crops, ground water and surface water. There seems to be no direct way to find out where the production facilities are, except via producers and government regulators.

The US government seems committed to going ahead with a procedure that bypasses public input and scrutiny, and which if, when disclosed, will threaten the marketability of US food exports. In contrast, the Canadian Food Inspection Service maintains that "plant products of test sites cannot be marketed" [7], even though numerous plant biopharmaceutical products have been tested.

The regulation of plant-derived biopharmaceuticals was reviewed by the FDA in 2000 [8], and by the Pew Initiative in 2004 [6]. Only the Pew report came to grips with the practice of marketing virtually untested products commercialized without public input.

A review of the Prodigene products was published in 2002 [9]. As indicated earlier, test plot permits for crops producing biopharmaceutical proteins are usually designated confidential business information so that the nature of the products is hidden from the public as well as the location of the test sites. APHIS does, however, record the crop and the state in which the modified crop is tested. Between 2003 and 2004, Prodigene had test plots in Nebraska, Texas, Iowa and Missouri [10].

Production of the commercial biopharmaceuticals was, for the most part, achieved using maize, even though it is a food crop of fundamental importance and should not have been used to produce biopharmaceuticals, especially when the products are by no means benign for humans and animals exposed to them.

Trypsin is an enzyme produced in the pancreas to digest proteins. It is extensively used in laboratory applications, in wound treatment and to treat diabetes. It is also used in food processing and often put into infant formulations to aid in digestion. The plant-produced product is desirable because it is free of prions and animal viruses [11].

According to the safety data sheets provided by trypsin manufacturers, the product is capable of causing allergy - it is a skin, eye and respiratory irritant and may be a mutagen [12, 13].

Avidin is a protein found in birds' eggs. It functions to bind the vitamin biotin, which is required for many insect pests. The pests are inactivated by the absence of the necessary vitamin. Transgenic maize modified for avidin production is resistant to storage insect pests [14, 15].

A case study done by the Friends of the Earth provided substantial evidence that the protein avidin caused dangerous biotin deficiency in humans and animals, leading to immune deficiency and growth retardation [16]. Even marginal biotin deficiency is teratogenic in mice [17] and implicated in human birth defects [18].

Aprotinin is a protease inhibitor normally prepared from bovine pancreas and lung. Recombinant aprotinin produced in plants is currently marketed as indicated above. Bill Freese of Friends of the Earth reviewed the product and the problem of allergy and pancreatic disease from ingestion of the biopharmaceutical [19].

Aprotinin is further listed as a reproductive hazard [20]. There is serious danger to those exposed to aprotinin after having had a previous exposure. For example, a two-year old child suffered severe anaphylactic shock after a test dose of aprotinin [21]. Fatal anaphylaxis followed aprotinin exposure in a local application of fibrin glue [22]. A similar application led to an immediate skin reaction following re-exposure to fibrin sealant [23].

Secret field testing of plant-based recombinant aprotinin could result in severe or fatal anaphylaxis, either in a brief exposure in the maize field of someone previously treated during surgery, or exposure of someone exposed to the maize field followed by treatment during surgery.

The final commercial recombinant protein in maize is beta-glucuronidiase (GUS). The gene is used in a wide range of experimental situations but does not appear to have therapeutic importance. It has been observed that formula milk for infants had a low content of GUS while mother's milk had elevated GUS.

Elevated GUS has been implicated in bilirubinaemia (jaundice) of breast-fed infants [24] and breast-fed infants of diabetic mothers [25]. GUS is used extensively as a marker, believed to have little effect on the phenotype of the test organism. However, GUS was found to enhance the feeding activity of the peach aphid [26], suggesting that the marker may not be entirely without effect on the phenotype of organisms.

In conclusion, the secretive production of dangerous pharmaceuticals in food crops is a truly disturbing development. The sale of such products without transparent public approval is adding insult on injury, reinforcing the public perception that the regulatory authorities are putting corporate profit far above public safety.

Article first published 26/05/04



References

  1. Cummins J. Pharm crop stalled for now. Science in Society 2004, 22, 28-29,
  2. Horn M, Woodward S and Howard J. Plant molecular farming: systems and products. Plant Cell Reports 2004 in press, DOI: 10.1007/s00299-004-0767-1
  3. Prodigene. "Aprolizean recombinant aprotinin from maize", 2004, http://www.prodigene.com/pdf/AproliZean(tm)%20Backgrounder.pdf
  4. Yahoo Finance. "LSBC and Sigma-Aldrich announce an agreement to manufacture and distribute plant-produced recombinant aprotinin", 2004, http://biz.yahoo.com/bw/040308/85333_1.html
  5. USDA News Release. "USDA announces actions regarding plant protection act violations involving Prodigene, Inc.", 2002, http://www.usda.gov/news/releases/2002/12/0498.htm
  6. Pew Initiative on Food and Biotechnology. "Issues in the regulation of genetically engineered plants and animals", 2004. pp1-174.
  7. Perron F. personal communication, CFIA, 2004.
  8. Graham S. "Plant derived biologics meeting", 2000, pp1-145, http://www.fda.gov/cber/minutes/plnt1040500.pdf
  9. Hood E. From green plants to industrial enzymes. Enzyme and Microbial Technology 2002, 30, 279-83.
  10. APHIS. "Prodigene permit activity" 2004, http://www.aphis.usda.gov/cgi-bin/parse-company.pl, pp1-2.
  11. Prodigene. "TrypZean recombinant trypsin from maize", 2004, pp1-3, http://www.prodigene.com/pdf/TrypZean(tm)%20Backgrounder.pdf
  12. Safety data "Safety (MSDS) data for trypsin from bovine pancreas", 2003, pp1-2, http://physchem.ox.ac.uk/MSDS/TR/trypsin.html
  13. Specialty Media. "MSDS EDTA, MSDS and trypsin MSDS", 2004, pp1, http://www.specialitymedia.com/05Resources/MSDS%20SM-2002-C.htm4/
  14. McGraw L. Avidin an egg-citing insecticide protein in corn. Agricultural Research 2000, http://www.ars.usda.gov/is/AR/archive/aug00/egg0800.htm
  15. Kramer K, Morgan T, Throne J, Dowell F, Bailey M and Howard J. Transgenic avidin maize is resistant to storage insect pests. Nature Biotech 2000, 18, 670-5.
  16. Freese B. Biopharming: case study of avidin corn, 2002, Friends of the Earth http://www.foe.org/biopharm/csavidin.pdf
  17. Mock D, Mock N, Stewart C, LaBorde J and Hansen D. Marginal biotin deficiency is teratogenic in ICR mice. J Nutr. 2003, 133, 2519-25.
  18. Zemleni J and Mock D. Marginal biotin is teratogenic (in human). Proc Soc Exp Biol Med 2000, 223, 14-21.
  19. Freese B. Biopharming: case study of corn producing aprotinin. 2002, Friends of the Earth, pp1-5, http://www.foe.org/biopharm/csaprotinin.pdf
  20. Research Safety "Appendix B: Reproductive Hazard", 2002, pp1-22, http://www.northwestern.edu/research-safety/pdf
  21. Ryckwaert Y, Barthlet Y, Bonnet-Boyer M, Rochette A, Capdevila X and d'Athis F. Anaphylactic shock after a test dose of aprotinin in pediatric orthopedic surgery. Ann Fr Anesth Reanim 1999, 18, 904-8.
  22. Oswald A, Joly L, Gury C, Disdet M, Leduc V and Kanny G. Fatal intraoperative anaphylaxis related to aprotinin after local application of fibrin glue. Anasthesiology 2003, 99, 762-3.
  23. Beierlein W, Scheule A, Antoniadis G, Braun C and Schlosser R. An immediate allergic skin reaction to aprotinin after exposure to fibrin sealant. Transfusion 2000, 40, 302-5.
  24. Gourley G and Arend R. Beta-Glucuronidase and hyperbilirubinaemia in breast fed and formula fed babies. Lancet 1986, 22, 644-6.
  25. Sirota L, Ferrera M, Lerer N and Dulitzky F. Betagucuronidase and hyerbiirubinaemia in breast fed infants of diabetic mothers. Arch Dis Child 1992, 67, 120-1.
  26. Cherqui A, Alla S, Saguez J, Doury G, Sangwan-Norreel B. and Giordanengo P. Probiotic effects of beta-glucuronidase on the peach-potato aphid Myzus persicae (Aphididae). J Insect Physiol 2003, 49,1199-209.

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