Friday, December 05, 2008

The Human Health Effects of B. t. and Starlink

I gathered this information a few years ago, but yesterday's questions have prompted me to post this all for public consumption, as it were:
From 2001 until 2004, a US subsidiary of the Swiss firm Syngenta allowed American farmers to plant 15,000 hectares of corn, or maize, that had been modified with an unapproved version of the B. t. gene (see Nature 434, 423; 2005).

Small batches of the unapproved seed were also exported to Europe. After Nature revealed this mistake, Syngenta claimed that there was no significant difference between the approved genetically modified corn, called Bt11, and the corn that had been inadvertently released, called Bt10. Only later did the company admit that Bt10 differs from Bt11 in that it contains an additional gene that confers resistance to the antibiotic ampicillin (see Nature 434, 548; 2005), a difference that most experts agree is of some significance. Even Monsanto says: “Rats fed B. t. corn developed kidney inflammation, altered blood cell counts and organ lesions. These and other changes suggested possible allergies, infections, toxins, anemia or blood pressure problems.”

StarLink corn was a product of the Aventis Corporation. It contained Cry9c, a B. t. protein that is heat stable and can not be excluded as an allergen. [Cry9c (MW of 68 kDa) shows some characteristics of known food allergens and relative resistance to gastric proteolytic degradation and to heat and acid treatment. It is probably a glycoprotein. It induces a positive IgE response in the Brown Norway rat and is a high IgE responder on intraperitoneal and oral sensitization (in contrast to the related Cry1Ab5 protein). It may be found intact in the bloodstream after oral feeding in a rat model.] It was approved by the EPA as a pesticide when produced for sale as an animal feed. In September 2000, it contaminated the human food supply.

Upon dry milling, the Cry9c content is reduced by 40 percent. Additional processing, such as alkaline cooking, decreases the protein content to 0.1 to 0.2 percent of the original Cry9c protein (FIFRA SAP, 2000b). This suggests a further reduction in allergenic potency; however, protein denaturation by heat or partial proteolysis may uncover new allergenic epitopes [An epitope is the part of a foreign organism or its proteins that is being recognized by the immune system and targeted by antibodies, cytotoxic T cells or both] (FIFRA SAP, 2000; Hefle, 1996 in Kuiper et al. 2001).
There was no way to easily determine if consumption of this genetically engineered protein was resulting in allergic reactions in humans. Fifty-one people reported signs and symptoms that varied from gastrointestinal illness to anaphylactic shock. These reports were entered into the FDA’s adverse events reporting system (Bucchini & Goldman 2002).

The Centers for Disease Control and Prevention developed a case definition that included: a suspected anaphylactic reaction that occurred within 1 hr of product consumption, dizziness, weakness or loss of consciousness; any of the following dermatological or oropharyngeal symptoms that occurred within 12 hr of product consumption, hives, rash, pruritus, oropharyngeal tingling or swelling; any of the following gastrointestinal symptoms that occurred within 12 hr of product consumption, vomiting, diarrhea, abdominal cramping (only experienced by one individual). These symptoms were not explained by any preexisting medical conditions.

Twenty-eight of the 51 reports were consistent with the case definition (Bernstein et al. 2005). A serological test for antibodies specific to acute hypersensitivity was considered to be the safest way to evaluate whether any of these people were indeed sensitive to the genetically modified protein in StarLink. The FDA developed an Enzyme-Linked Immunosorbent Assay (ELISA) test that found no IgE [Immunoglobulin E (IgE) is the least abundant antibody subclass, i.e., isotype, capable of triggering the most powerful immune reactions. Proteins that bind IgE from people with allergies are likely to be allergens.] antibody reactivity to Cry9c in any of the serum samples. The U.S. EPA SAP reviewed these data in 2001 and concluded that the technical approach for the detection of Cry9c protein and antigen-specific [For those of us not practicing the black art, an antigen is a foreign substance, e.g., a toxin, which induces an immune response in the body, esp. the production of antibodies.] IgEs is limited and cannot resolve the issue of the presence or absence of Cry9c-specific IgE in the serum of individuals reporting adverse reactions after eating corn (Bucchini & Goldman 2002).

Raybourne et al. (2003) came to the conclusion that, “while the results do not support the likely occurrence of allergic reactions to Cry9c, such reactions cannot be ruled out, nor can the possibility that sera might react with unique glycosylated epitopes of Cry9c that might be expressed in the corn plant/seed.”

The FDA’s IgE-specific ELISA did not include the StarLink-derived Cry9c protein, but the recombinant Cry9c expressed in E. coli as an antigen. It is possible that epitopes present on Cry9c in maize may not be present in the non-glycosylated E. coli-derived protein. A specific goat serum against Cry9c was included in the ELISA, as there was no human serum available that contained the IgE antibody to Cry9c. The result is that the possibility of lack of specificity for human anti-Cry9c IgE cannot be entirely dismissed (CDC 2001b and CDC 2001c in Kuiper et al. 2001).

Literature Cited:
Bucchini, L., Goldman., L. 2002. Starlink corn: a risk analysis. Environmental Health Perspectives 110(1): 5-13
Kuiper, H., G. Kleter, H. Noteborn and E. Kok. 2001. Assessment of the food safety issues related to genetically modified foods. The Plant Journal 27(6): 503-528

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