Rice with human genes: pharming in California

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 acts against the cell wall material of the bacterial pathogens. The biopharmaceutical rice crop was being tested by a California biotechnology company, Applied Phytologics.(1,2). In spite of the intense public scrutiny efforts are being made to continue the open field testing of the rice plants modified with two human genes. The Greenpeace disclosure created an avalanche of concern from the public and from both conventional and organic rice farmers who feared 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) but that field test release was not acknowledged by the public even though it posed a threat to both conventional and organic production of beer and animal feed. Maize modified with human lactoferrin was field tested by Biochem SA company and by Meristem Therapeutics company in France (4). The French field tests do not appear to have been acknowledged by the public even though such tests threatened both conventional and organic maize production on the continent.

Most of the field testing of genetically modified (GM) biopharmaceutical crops appears to have been done in the United States (US), France and Canada. US completed 315 such tests between 1991 and 2002, the main modified organisms included maize, rice soy and Tobacco Mosaic Virus .The majority of tests were done in Nebraska, Hawaii, Wisconsin and Puerto Rico (5). Canada completed 53 field tests of biopharmaceutical crops between 1995 and 2003 (6) while France completed 24 field tests on GM biopharmaceutical crops 1995 and 1998 (4). The US and Canadian field trials of GM biopharmaceuticals are clouded by the use of confidential business information (CBI) designations which hide the details of the gene construction and the exact locations of the field tests. Those neighboring 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 site to the GM biopharmaceuticals being tested, certainly an unjust situation.

Returning to the rice GM biopharmaceutical genetic construct, like other biopharmaceuticals produced in seed , the construct includes the human genes for the primary 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 (8). Human lysozyme produced in plants has been patented as a biopestide to protect plants against fungal and animal pests (9). Human lysozyme produced in rice has been localized to the endosperm of transgenic rice (10,11).

Expression of human milk proteins in plants has been discussed by nutrition authorities who have maintained that such products should be tested using feeding experiments in rats then human volunteers(12). The problem of inadvertent exposure to the products by consuming crops contaminated by the products by accidental spread of pollen or seeds was not discussed. Chicks were fed rice bearing human lysozyme and lactoferrin and the rice was found to have antibiotic like properties (13).

Lactoferrin is a protein that participates in regulation of immune functions and contols pathogens by binding iron required for bacterial growth. Lactoferrin has been in asthma with fatal outcomes (14). Lactoferrin variants has been associated with localized juvenile periodontitis (15). It has been suggested that milk lactoferrin possesses allergenic sites (16). Lactoferrin is a protein modified by glycosylation, a modificatoion 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 pattern 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 studied (19). The glycosylation patterns of the transgenic enzyme produced in plants seems 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 to the field test sites or those living nearby.

Transgenic rice crops may spread pollen or seeds 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. Gene flow has been studied between commercial rice and weedy red rice (20,21). These studies suggest that transgenes may spread to non-transgenic rice. Once established the transgenes may be difficult to impossible to eliminate. Organic and conventional rice producers have a legitimate concern over secretive field testing of transgenic rice.

Transgenic glufosinate resistant rice (Liberty Link) was de-regulated in the US during 1999, the Animal Plant Food Inspection Service (APHIS) of USDA guessed that the transgenic rice would not pollinate weedy red rice but even if it did the weed could be eliminated using herbicides other than glufosinate (22). Concern over the threat of transgenic rice to organic and conventional producers was outlined and the probable instability of transgenic rice do to soma clonal variability was discussed (23).

Recently, recombinant biopharmaceutical production in transgenic crops has been actively promoted , in spite of incidents of contamination of food production observed during field test releases of the transgenic biopharmaceutical crops (24,25). Production of the biopharmaceutical crops in confined greenhouses was deemed un-economic even though such production provides the barest essentials for protecting the food crops from genetic pollution. The unacceptable practice deeming secretive field tests to be confidential business information must be stopped. Both testing and production of transgenic crops producing biopharmaceuticals should be restricted to confined greenhouses that provide isolation from the atmosphere and groundwater. Transgenic crops bearing human milk proteins are promoted because “mother’s” milk is presumed safe for all, but the crop transgenic “mother’s milk” is far from identical to the real thing. Furthermore , the transgenic milk 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 medications in their food.

 

References are available on request , please state the name of the paper