1. Brian Ellis Biotechnology Laboratory - UBC May 02, 2001

2. Health Canada is mandated to ensure that the Canadian public is not put at risk from food or health care products HC must assess all novel foods

3. From other geographic regions From new manufacturing processes Origins of Novel Foods From plant breeding

4. History of safe human consumption? Contains known toxicants? Assessment of Novel Foods Nutritional value altered?

5. Plant Breeding Development and evaluation of new genotypes 1. Create variation 2. Select 3. Repeat….

6. 1. creates new allelic combinations within a species genome 2. samples mutational / recombinational changes Classical Plant Breeding

7. Progeny Evaluation SEXUAL CROSSES Existing varieties Distantly related species Induced mutants Closely-related species Landraces Selections

8. products of plant breeding are generally regarded as safe “barley is barley is barley” long history highly selected

9. How do GMO genotypes fit within this model? derived from known (GRAS) germplasm very few new genetic elements added to parental variety

10. Do a comprehensive (and slow and expensive) food safety assessment ? The conundrum….

11. …or assume that the genetic background is benign, The conundrum…. assess traits directly related to the transgene, and establish “ substantial equivalence ”

12. comparison of the GMO product with the conventional Substantial Equivalence assesses differences between them focuses on the transgene and on hallmarks of conventional genotype

13. Strengths Substantial Equivalence Focuses on most likely impacts Uses established methodologies

14. Weaknesses Substantial Equivalence Assumes linear responses to genetic change Uses targeted rather than global analytical methodologies

15. Differential gene expression in the Arabidopsis hypocotyl wildtype ein 4 mutant S. Regan, Carleton U.

16. Cellular systems are highly integrated at all levels PLEIOTROPY Plant metabolism is extraordinarily plastic - adapted to creation of new metabolites

17. Fiehn et al, Nature Biotechnology (2000) Metabolic shifts induced by single-gene changes in Arabidopsis thaliana dgd-1 sdd-1

18. Assume that pleiotropic effects will occur in GMO organisms Strengthening Substantial Equivalence Develop and adopt global profiling methodologies Focus safety assessment on revealed differences