Can Genetically Engineered Food Crops Be Used to Make Pharmaceuticals? Could They Contaminate the Food Supply?

In the early 1990s, efforts were made to evaluate the effectiveness of plants and foods to deliver pharmaceuticals, particularly vaccines. These efforts involved using tobacco to express a bacterial surface protein to prevent dental caries and to express the hepatitis B surface antigen (1, 2). Since then, maize, potato, rice, soybean, and tomato have been used to produce vaccines for both humans and animals (3). These include subunit vaccines against pneumonic and bubonic plague, shown to be immunogenic in mice (4); a potato-based vaccine for hepatitis B that raises an immunological response in humans (5); a GE pollen vaccine that reduces symptoms in allergy sufferers (6); and an edible rice based vaccine targeted to allergic diseases such as asthma, seasonal allergies, and atopic dermatitis (7) (see “What Is in the Crop Biotechnology Pipeline?”).

Plant vaccines have the advantage of being readily consumed with limited or no processing and of obviating the need for cold storage, clear advantages in developing countries. However, with this ease of delivery comes the possibility that such products could enter the food supply if food crops are engineered. Under U.S. regulations, GE plants containing pharmaceutical or industrial products are not permitted to enter the food supply. The FDA prohibits “adulterated” foods in the supply chain, including foods from GE crops that might contain potentially harmful proteins (8). APHIS, which regulates the movement and field testing of GE plants (see “Do Genetically Engineered Foods Have Changes in Nutritional Content?”), requires special steps to prevent plants that produce drugs or industrial enzymes from contaminating food crops: i ) labeling, packaging, and segregating regulated plant materials; ii ) reproductive isolation to prevent GE pollen from fertilizing conventional plants; iii ) postharvest monitoring to remove volunteer plants; and (iv) proper disposal of the transgenic material.

In 2005 these rules were tightened to include the following: i ) exclude field growth without a permit; ii ) include crop inspections seven times/year, twice after harvest; iii ) increase field isolation distances; and iv) use dedicated farm equipment (9). This tightening resulted from early violations of fieldtesting permits. For example, in two cases regulators found volunteer engineered corn plants producing a pharmaceutical protein (10) that had tassled in a soybean field.

Cases like these demonstrate that “pharming” in food plants can result in mixing with food. The Grocery Manufacturers of America urged the USDA to restrict plant-made pharmaceutical production to nonfood crops (11). The National Corn Growers Association countered by proposing safeguards such as i ) using plants that are male-sterile or that produce non-GE pollen, ii ) dedicated production systems that isolate pharma crops, iii ) third-party verification, and iv) grower training programs (12). In September 2002, the FDA released a guidance document that recommends multiple strategies to prevent pharma crops from contaminating human or animal feed (13). This document suggests that those who are growing drug-producing plants that cross pollinate, such as corn and canola, strengthen containment procedures by growing plants in geographical regions where little or none of that crop is grown for food. Following this strategy, Ventria, a company that developed self-pollinating rice engineered to produce human lysostaphin and lysozyme to shorten the duration of childhood diarrhea, relocated their fields from their home ricegrowing state, California, to Kansas, where commercial rice is not grown (14).

References:

1. Curtiss RI III, Cardineau CA. 1990. Genetically modified plants for use as oral immunogens. World Patent Appl. WO 90/02484

2. Mason HS, Lam DM, Arntzen CJ. 1992. Expression of hepatitis B surface antigen in transgenic plants. Proc. Natl. Acad. Sci. USA 89:11745–49

3. Pascual DW. 2007. Vaccines are for dinner. Proc. Natl. Acad. Sci. USA 104:10757–58

4. Alvarez ML, Pinyerd HL, Crisantes JD, Rigano MM, Pinkhasov J, et al. 2006. Plantmade subunit vaccine against pneumonic and bubonic plague is orally immunogenic in mice. Vaccine 24:2477–90

5. Thanavala Y, Mahoney M, Pal S, Scott A, Richter L, et al. 2005. Immunogenicity in humans of an edible vaccine for hepatitis B. Proc. Natl. Acad. Sci. USA 102:3378–82

6. Niederberger V, Horak F, Vrtala S, Spitzauer S, Krauth M-T, et al. 2004. Vaccination with genetically engineered allergens prevents progression of allergic disease. Proc. Natl. Acad. Sci. USA 101:14677–82

7. Takagi H, Hiro T, Yang L, Tada Y, Yuki Y, et al. 2006. A rice-based edible vaccine expressing multiple T cell epitopes induces oral tolerance for inhibition of Th2-mediated IgE responses. Proc. Natl. Acad. Sci. USA 102:17525–30

8. Food Drug Adm. (FDA). 2004. Federal Food, Drug, and Cosmetic Act: Chapter IV—Food. http://www.fda.gov/opacom/laws/fdcact/fdcact4.htm. Last accessed 2011-12-9. PDF

9. Animal Plant Health Insp. Serv., USDA. 2005. Introductions of plants genetically engineered to produce industrial compounds. Docket No. 03–038–2. Fed. Regist. 70:85

10. Animal Plant Health Insp. Serv., USDA. 2002. USDA Investigates Biotech Company for Possible Permit Violations. http://www.aphis.usda.gov/lpa/news/2002/11/prodigene.html. Last accessed 2011-12-9. PDF

11. Grocery Manuf. Am. 2002. GMA urges the use of non-food crops for biotech drugs: ProdiGene's errors raise serious concerns, say GMA. http://www.plantpharma.org/2002/11/gma-urges-the-use-of-non-food-crops-for-biotech-drugs-prodigenes-errors-raise-concerns-gma-says/.  Last accessed 2011-11-28. PDF

12. Natl. Corn Growers Assoc. 2002. NCGA commends APHIS on quick action concerning biotech compliance infractions. http://www.ncga.com/news/notd/2002/november/112702.htm

13. U.S. Department of Health and Human Services (HHS), Food and Drug Administration (FDA), Center for Drug Evaluation and Research (CDER), Center for Biologics Evaluation and Research (CBER). August 2011. Guidance for Industry E16 Biomarkers Related to Drug or Biotechnology Product Development: Context, Structure, and Format of Qualification Submissions http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM267449.pdf. Last accessed 2011-11-26. PDF

14. Fox JL. 2006. Turning plants into factories. Nat. Biotechnol. 24:1191–93

Updated 2/16/12