1. How safe are transgenic crops? Regulatory systems Pat Byrne CSU Department of Soil & Crop Sciences

2. Regulatory process for transgenic crops in the U.S. Institutional Biosafety Committee Animal and Plant Health Inspection Service (APHIS) of USDA Food and Drug Administration (FDA) Environmental Protection Agency (EPA) International agreements

3. Institutional Biosafety Committee (IBC) Most research institutions have an IBC, which monitors potentially hazardous biological research and ensures compliance with NIH safety procedures. At CSU, for example, researchers must receive IBC approval if planning to work with recombinant DNA or other potentially dangerous agents.

4. Institutional Biosafety Committee (IBC) Depending on the nature of the work, a Biosafety Level is assigned. For transgenic plants, the level would be BL1-P to BL4-P. CSU's plant biotechnology greenhouse is a BL2-P facility: restricted access, concrete floor, screens to restrict small insects, autoclave for all plant waste.

5. Animal and Plant Health Inspection Service (APHIS) To transport or field-test transgenic plants, there are two procedures available: 1. Notification (for most common crops). A set of criteria for the introduced gene must be met:  stable integration  non-pathogenic to animals or humans  unlikely to be toxic to non-target organisms  low risk of creating new plant viruses

6. 2. If a transgenic plant does not meet the criteria for "Notification", the developer must formally apply for a permit to transport or grow the plant in the environment. Field testing requires procedures to minimize spread of the transgene and keep it out of the food supply. State or federal inspectors may monitor.

7. To commercialize a transgenic plant, the developer petitions APHIS for “non-regulated” status. This requires extensive data on the introduced gene construct, effects on plant biology, and effects on the ecosystem, including spread of the gene to other crops or wild relatives. “Non-regulated” status

8. Food and Drug Administration FDA staff consult with crop developers to ensure that appropriate testing is conducted by the developer. FDA review may be required for transgenic food crops if they involve known toxicants altered nutrient levels new substances allergenicity antibiotic resistance markers

9. The FDA consultation process for Roundup Ready soybeans included data on Molecular characterization of the transgene In vitro and in vivo allergenicity tests Compositional analysis of whole beans and soy-derived products Safety tests on rats, chickens, catfish, dairy cattle, and bobwhite quail

10. Environmental Protection Agency Regulates the use of plants that produce pesticidal substances. Sets tolerance limits for pesticides in food, or establishes an exemption from tolerance. Establishes tolerances for herbicide residues on herbicide-tolerant crops. May require a “resistance management plan” to slow development of resistance in the target pest.

11. Regulatory quiz Which federal agencies have jurisdiction over: Viral resistance in a food crop? Herbicide tolerance in a food crop? Herbicide tolerance in an ornamental crop? Modified oil content in a food crop? Modified flower color in an ornamental crop?

12. Resistance management EPA has mandated resistance management strategies for Bt releases, based largely on planting refuges of a non-Bt variety alongside the Bt fields. Resistant insects that survive in the Bt field will mate with susceptible insects from the refuge. Their offspring will be susceptible and will die if they attack Bt crops.

13. BT corn Non- BT corn R S S S S S Resistant (R) and susceptible (S) European corn borer adults

14. Potential problems with the refuge strategy The frequency of Bt-resistant alleles in insect populations may be greater than assumed in models. Bt-resistance may be dominant or semi-dominant rather than recessive. Resistant insects may mature earlier or later than insects in refuge areas. Only 71% of farmers followed rules in 2000.

15. Pink bollworm resistance did not increase in Bt cotton From 1997 to 1999 over half the cotton acreage in Arizona has been planted to Bt varieties. Bt-resistant alleles in pink bollworm were not rare in 1997 (0.13 - 0.16). But contrary to expectations, the frequency of resistant alleles did not increase over the 2-year period. Source: Tabashnik et al., 2000. Proc Natl. Acad. Sci. USA

16. In Jan. 2001, FDA  Proposed a requirement that it be informed at least 120 days before GM products are marketed.  Announced voluntary guidelines for labeling foods with and without GM ingredients. USDA panel is conducting a 2-year review of transgenic crop regulation. National Academy of Sciences suggested changes in an April 2000 report. The approval process for transgenic crops in the US may be modified

17. No evidence that transgenic foods are unsafe. Better methods of identifying potential allergens should be developed. Long-term studies should be initiated for effects of GM crops on heath and the environment. USDA, EPA, and FDA should more closely coordinate their regulatory activities, and make the process more open to the public. NAS report (April, 2000) “Genetically Modified Pest-Protected Plants: Science and Regulation”

18. If a bioengineered food has a significantly different nutritional property, its label must reflect the difference. If a new food includes an allergen that consumers would not expect to be present, the presence of that allergen must be disclosed on the label. Labeling of genetically engineered food: current FDA policy

19. What constitutes a GE food product:  Which technologies included as GE?  1% of any ingredient?  Products of livestock fed transgenic feed? Logistical difficulties of separating GE and non-GE food Testing not always informative At what cost to consumers? One study estimates 10% increase in food prices. Labeling of genetically engineered food

20. Proposed FDA policy for voluntary labeling This product contains cornmeal that was produced using biotechnology. Genetically engineered This product contains high oleic acid soybean oil from soybeans developed using biotechnology to decrease the amount of saturated fat. OK Underlined part is mandatory. Rest is voluntary.

21. Proposed FDA policy for voluntary labeling GMO free No Not genetically modified We do not use ingredients produced using biotechnology. OK This oil is made from soybeans that were not genetically engineered. OK This cantaloupe was not genetically engineered. May be misleading

22. International agreements Codex Alimentarius (FAO / WHO): voluntary standards for food safety testing of GM crops. International Biosafety Protocol: Goal is to protect biodiversity while regulating trade of GMO’s. Accepts “precautionary principle”, that a country can reject GM products if there is a lack of scientific certainty about the risks. Provides aid to developing countries to develop GM regulatory frameworks.

23. World Trade Organization: Can impose sanctions if a member country blocks import of a product for non-science based reasons. The WTO position on transgenic foods has not been determined. International agreements

24. Evaluating the use of transgenic crops Consider crops on a case-by-case basis, taking into account Nature of the introduced gene. Plant parts and growth stage in which the gene product is present. Presence of related wild species in the vicinity.

25. Evaluating the use of transgenic crops Consider also the environmental effects of alternatives to transgenic varieties: Would more harmful chemicals be applied? Would conservation tillage decrease? What are the probability and effects of gene escape from a non-transgenic variety?