Letter To California Food & Agriculture Dept

Letter to the California Department of Food and Agriculture

Secretary of Food and Agriculture A.G. Kawamura California Department of Food and Agriculture Division of Plant Health and Pest Prevention Services 1220 N Street, Room A-316 Sacramento, California 95814 attn:Stephen Brown, Special Assistant Email: sbrown@cdfa.ca.gov

April 3, 2004 Governor Arnold Schwarzenegger Governor's Office State Capitol Building Sacramento, CA 95814 Phone: 916-445-2841 Fax: 916-445-4633 governor@governor.ca.gov

Re: Biopharmaceutical rice in California

Dear Secretary Kawamura:

Greg Massa, an organic rice producer from California reported, "Well, they did it. The California Rice Commission let down their growers, ignored public comment, and approved Ventria Biosciences' protocol for the introduction of genetically modified, pharmaceutical rice to California." And, "The worst part is that they approved this protocol with a special "emergency" petition, so that the California Secretary of Agriculture has only 10 days to decide on the issue, rather than the standard 4 months. This was to allow Ventria to plant the rice this year. This "emergency" may completely eliminate the public's ability to comment on the decision."

There is a very disturbing side to the above development. Normally, commercial production is preceded by USDA/APHIS approving a petition to deregulate the crop in question. There does not appear to be any recorded decision to deregulate the crop published at this time, and a retroactive deregulation would not normally be considered legal. Along with the USDA/APHIS's deregulation, FDA must provide review and support for the commercial production and marketing, but no FDA action has been made public up to now. Finally, human lysozyme has been patented as a plant incorporated protectant, and thus the rice should have been evaluated by EPA as well as FDA and USDA/APHIS. None of these evaluations, which normally take years, have been made available to the public as normally required. Therefore, the rush to authorize spring planting this year seems to say that US federal law will be ignored, or else that federal bureaucrats have promised a quick, perfunctory evaluation, which is illegal, to say the least.

Biopharmaceutical rice modified with human genes for the proteins lactoferrin and lysozyme is presented as if the product were as safe as mother's milk. But the modified rice does not contain the native human genes and proteins. Instead, it contains synthetic copies of the native genes that are modified for high level production in plants. This involves changes in codons and amino acids as well as in the sugar molecules added to the final protein. The products are essentially untested for potential allergenicity and toxicity to humans, livestock and wild life. At any rate, prudence dictates that food crops modified with pharmaceutical products should be grown only in isolated and controlled greenhouses.

We are enclosing a special report on the hazards of the transgenic rice and other pharm crops for your attention.

In conclusion, once released, the modified rice cannot be recalled, and its polluting effects may persist for generations to come.

Yours sincerely,

Prof. Joe Cummins Dr. Mae-Wan Ho Institute of Science in Society http://www.i-sis.org.uk/ And Independent Science Panel http://www.indsp.org/

December 17 2003 Prof. Joe Cummins e-mail: jcummins@uwo.ca

Pharm Crops Near You?

In 2002, Greenpeace disclosed the location of a site in Northern California where rice plants modified with the human genes lactoferrin and lysozyme were being tested [1]. Lactoferrin acts against bacterial pathogens by preventing them from taking up iron needed for their growth, while lysozyme breaks down the cell wall material of the bacterial pathogens. The biopharmaceutical rice-crop was being tested by a California biotechnology company, Applied Phytologics [1,2].

The Greenpeace disclosure created an avalanche of concern from the public and from both conventional and organic rice farmers fearing that contamination of their crops would lead to economic disaster.

Washington State University field-tested barley altered with human genes for lactoferrin, lysozyme, antitrypsin and antithrombin [3] without any comment from the public even though this posed an obvious threat to both conventional and organic beer production and animal feed, not to mention the hazards to health.

Maize modified with human lactoferrin was field-tested by Biochem SA company and by Meristem Therapeutics company in France [4], again with no comment from the public even though such tests threaten both conventional and organic maize production in Europe.

Most of the field-testing of genetically modified (GM) biopharmaceutical crops appears to have been carried out in the United States (US), France and Canada. US completed 315 such tests between 1991 and 2002, including GM maize, rice, soya and Tobacco Mosaic Virus .The majority of tests were done in Nebraska, Hawaii, Wisconsin and Puerto Rico [5]. Canada completed 53 field tests of pharm crops between 1995 and 2003 [6] while France completed 24 such field tests between 1995 and 1998 [4]. In the US and Canada, field trials of pharm crops are veiled in secrecy under the "confidential business information (CBI)" designation, which hides the details of the gene-constructs as well as the exact locations of the field tests. Thus, people living near the field trials have no means of relating any illness or discomfort experienced from exposure to polluted plant debris or pollen, or to contaminated ground or surface water escaping from the test sites.

The GM rice pharm-crop, like other crops that produce pharmaceuticals in seed, has a gene construct that includes the human genes for the biopharmaceutical protein driven by a seed-specific promoter, and the protein is expressed with a fusion polypeptide (the signal peptide) that causes the fusion protein to accumulate in a cell compartment such as a vacuole or seed endosperm [7]. Human lactoferrin produced in plants has been described in a US patent granted in 2003 [8]. Human lysozyme incorporated in plants was patented in 1994 as a biopesticide to protect plants against fungal and animal pests [9], and its localization to the endosperm of transgenic rice has been reported more recently[10,11].

Expression of human milk proteins in plants was discussed by nutrition experts who said such products should be tested in rats and then in human volunteers [12]; but they have totally ignored the problem of inadvertent exposure to the products by consuming crops contaminated by the product resulting from the inevitable, "accidental"spread of pollen or seed. Chickens were fed GM rice with human lysozyme and lactoferrin, and the rice was reported to have antibiotic-like properties [13].

Lactoferrin participates in the regulation of immune functions and controls pathogens by binding iron required for bacterial growth. Lactoferrin has been implicated in asthma with fatal consequences [14]. Lactoferrin variants have been associated with localized juvenile periodontitis [15]. It has been suggested that milk lactoferrin possesses allergenic sites [6]. Lactoferrin is a protein modified by glycosylation, a modification that contributes to enzyme activity and to allergenicity of the protein. Human lactoferrin was found to be glycosylated differently from the human transgene protein produced in tobacco [17]. The different patterns of glycosylation observed in human and the tobacco transgene product should not be considered insignificant until full studies of allergenicity of the transgenic protein are completed.

Chicken egg lysozyme is a well- known potent food allergen [18] while human lysozyme is clearly not allergenic. Like lactoferrin, lysozyyme is a glycosylated enzyme and variants of human lysozyme have been characterized [19]. The glycosylation patterns of the transgenic enzyme produced in plants appear to have been neglected even though that pattern will influence allergenicity of the product. Clearly, both transgenic lactoferrin and transgenic lysozyme are potentially hazardous to human health, and such concerns should be made clear to those exposed at or near the field-test sites.

Transgenic rice crops may spread pollen or seed to adjacent fields thus contaminating those crops. Rice is known to be somewhat self fertilizing, but clearly capable of spreading both pollen and seeds to nearby fields. Studies on gene flow between commercial rice and weedy red rice [20, 21] suggest that transgenes may spread to non-transgenic rice. Once established, the transgenes may be difficult if not impossible to eliminate. Organic and conventional rice producers have a legitimate concern over the secrecy surrounding the field testing of the transgenic rice.

Transgenic glufosinate resistant rice (Liberty Link) was de-regulated in the US during 1999, the Animal Plant Food Inspection Service (APHIS) of US Department of Agriculture (USDA) thought that the transgenic rice would not pollinate weedy red rice, and even if it did, the weed could be eliminated using herbicides other than glufosinate [22]. I have outlined the concerns over the threat of transgenic rice to organic and conventional producers and the probable instability of transgenic rice due to somaclonal variability some years ago [23].

Recently, recombinant biopharmaceutical production in transgenic crops has been actively promoted, in spite of incidents of contamination of food production uncovered during field tests of such crops [24,25]. Production of the biopharmaceutical crops in confined greenhouses was deemed un-economic even though such production provides the barest essentials for isolating the pharm crops from contaminating our food crops as well as the atmosphere and groundwater.

Transgenic crops producing human milk proteins are promoted because "mother's" milk is presumed safe for all, but the transgenic "mother's milk" proteins are far from identical to the real thing. Furthermore, the transgenic milk-protein crops will soon be followed by anticoagulants, human growth hormone, antibodies and a range of other biopharmaceutical products all potentially significantly different from the original products. The biopharmaceutical dam may soon burst leaving the human population with an array of hidden non-prescribed medications in their food, plus a host of side-effects to boot.

References Greenpeace Press Release "Crop producing human proteins found growing in open field test" 2001 http://www.greenpeaceusa.org/media/press_releases/01_09_06text.htm

Wilson K. Crop producing human protein found growing in open field test. Synthesis/Regeneration 2002 http://www.greens.org/s-r/28/28-26.html

APHIS field test permits for bio-pharm crops. Washington State University, 2001 Barley http://www.colostate.edu/programs/lifesciences/TransgenicCrops/pharmpermit s. html

France, "Total number of summary notifications circulated" 2003 http://biotech.jrc.it/deliberate/FR.asp

Freese,B. "Manufacturing drugs and chemical crops :biopharming poses new threats to consumers, farmers, food companies and the environment" Friends of the Earth Genetically Engineered Food Alert 2002, pp1-98.

Canadian Food Inspection Agency, "confined field trials Canada pharmaceutical " 2003 http://www.inspection.gc.ca/english/plaveg/bio/triesse.shtml

Lemaux P, Cho M and Buchanan B. "Production of protein in plant seeds" 2003 US Patent 6,642,437 pp 1-48.

Legrand D, Salmon D, Spik G, Gruber V, Bournat P and Bertrand M. Recombinant lactoferrin, methods of production from plants and use. 2003 US Patent 6,569,831 pp 1-39.

Hain R. and Stenzel K. Use of lysozyme gene structure in plants to increase resistance. 1994 US Patent 5,349,122 pp 1-24.

Yang D, Guo F, Haung N and Watkins S. Expression and localization of human lysozyme in the endosperm of transgenic rice. Planta 2003, 216, 597-603.

Huang J, Nandi S, Wu L, Yalda1D, Bartley G, Rodriguez R., Lonnerda B and Huang N. Expression of natural antimicrobial human lysozyme in rice grains. Transgenic Research 2002 11, 229"39.

Lonnerdal B. Expression of human milk protein in plants. Journal of the American College of Nutrition 2002,, 18s-221s

Humphrey B, Huang N and Klasing K. Rice expressing lactoferrin and lysozyme has antibiotic like properties when fed to chicks. J. Nutr. 2002, 132, 1214-18.

Tsokos M. and Paulsen E. Expression of pulmonary lactoferrin in sudden onset and slow onset asthma with fatal outcome. Virchows Arch. 2002, 441, 494-99.

Velliyagounder K, Kaplan J, Furgang D, Legarda D, Diamond G, Parkin R. and Fine D. One of two human lactoferrin variants exhibits increased antibacterial and transcriptional activation activities and is associated with localized juvenile periodontitis. Infect Immun. 2003, 71, 6141-7.

Sharma S, Kumar P, Betzel C. and Singh T. Structure and function of proteins involved in milk allergies. J Chromatogr B Biomed Sci Appl. 2001, 756, 183-7.

Samyn-Petit B, Wajda Dubos J, Chirat F, Coddeville B, Demaizieres G, Farrer S, Slomianny M, Theisen M and Delannoy P. Comparative analysis of the site-specific N-glycosylation of human lactoferrin produced in maize and tobacco plants" 2003 European Journal of Biochemistry 2003, 270, 3235-42.

Yoshinori Y and Zhang J. Comparative studies on antigenicity and allergenicity of native and denatured egg white proteins. J. Agric. Food Chem. 2002, 50 , 2679-83.

Melcher R, Hillebrand A, Bahr U, Schroder B, Karas M and Hasilik A. Glycosylation-site-selective synthesis of N-acetyl-lactosamine repeats in bis-glycosylated human lysozyme. Biochem. J. 2000, 348, 507-15.

Newswise "Gene flow patterns may give clues to managing promiscuous plants" 2002 pp1-2 http://www.newswise.com/p/articles/view/?id=GENEFLOW.UAR

Song Z, Lu B, Zhu Y and Chen J. Pollen competition between cultivated and wild rice species. New Phyologist 2002, 153, 289-96.

APHIS "determination of non-regulated status for glufosinate tolerant rice" 1999 pp1-25 http://www.aphis.usda.gov/brs/aphisdocs/98_32901p.pdf

Cummins J. Liberty Link rice: Herbicide tolerant rice for the masses. 2001 pp1-4 http://www.amberwaves.org/web_articles/joecummins.html

Ma J, Drake P and Christou P. The production of recombinant pharmaceutical proteins in plants. Nature Reviews of Genetics 2003, 4, 794-806.

Peterson R. and Arntzen C. On risk and plant based biopharmaceutical. Trends in Biotechnology 2004, in press doi:10.1016/j.tibtech.2003.11.007

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