2. FDA/CFSAN’s Science-based Approach to the Safety of Foods Derived from Modern Biotechnology Thomas A. Cebula, Ph.D. Director, Office of Applied Research and Safety Assessment Center for Food Safety and Applied Nutrition

3. The Process Requests notification when industry plans to market a product derived by bioengineered plants Encourages that industry consult with us and provide necessary documentation to ensure ‘reasonable certainty of no harm’  Opportunity to discuss plans for future cultivars

4. The Process Specific tests are not specified Intent: To focus on the characteristics of the food product

5. Scientific Evaluation u Food Safety u Strengths/Limitations

6. Approach is multidisciplinary  Agronomic and quality characteristics  Characteristics of new substances  Chemical and nutritional analysis  Genetic analysis A bioengineered variety is evaluated relative to its traditional counterpart Scientific Evaluation u Food Safety

7. Identity and source of introduced genetic materials Genetic stability Intended changes to the composition of the food Scientific Evaluation u Food Safety

8. Scientific Evaluation u Food Safety  Allergenicity  Toxins  Nutrient Levels  Antibiotic Resistance

9. Food Safety Assessment Description of rDNA plant Description of the host plant & use as food Description of the donor organism(s) Description of the genetic modification Characterization of the genetic modification

10. Safety Assessment, cont’d Expressed substances (non-nucleic acid) Compositional analyses (key components) Evaluation of metabolites Food processing Nutritional modification Other considerations (e.g. marker genes)

11. Description of the Genetic Modification The transformation process/host plant –Specific method (Agrobacterium-mediated) –Source, identity, function of DNA –Intermediate hosts The DNA to be introduced All genetic components (genes, markers, regulatory sequences, etc.) Size, identity; location/orientation; function

12. Characterization of the Genetic Modification/DNA Insertion Number of sites & organization; copy number & sequence data of insert & surrounding region, sufficient to identify expressed substances, or analysis of transcripts or expression products that may be present in food. Open reading frames & insertions with contiguous plant DNA (fusion proteins)

13. Characterization of the Genetic Modification/ Expressed Substances Gene products, including un-translated RNA Function & phenotype Level & site of expression; level of metabolites in food Amount of target gene product, if function is to alter endogenous mRNA or protein

14. Genetic Modification Additional Information Arrangement of genetic material Whether modifications to protein sequence affect post-translation/function Intended effect & heritable stability Expression in appropriate tissues & any evidence that host plant is affected Identity & expression of any fusion protein

15. As only one or a few genes are being incorporated into the plants, there is a limited number of manipulations. As we move forward, traditional breeding will likely be used to transfer a desired rDNA modification into desired plant varieties. u Strengths/Limitations  Scientific Scientific Evaluation

16. Evaluating Bioengineered Plants What tests are necessary? Are there tests that should be required?

17. What tests are necessary? Are there tests that should be required? RR vs rr: 62 of 636 protein spots on a 2-D gel are qualitatively different. R-locus affects sugar content, lipid content, storage protein composition, and shape and size of starch granules. Evaluating Bioengineered Plants

20. What tests are necessary? Are there tests that should be required? Afila (af) mutants which replace leaflets with tendrils, and the tendril-less (tl) mutant which replaces tendrils with leaflets. Both tl/tl and af/af lines have the identical 686 protein profiles. --Gottlieb & de Vienne, Genetics, 119:705-710 (1988) Evaluating Bioengineered Plants

21. Pleiotropy is virtually universal, i.e., essentially all gene substitutions have multiple phenotypic consequences when the phenotype is examined in sufficient detail.

22. Can Pattern Recognition Work?