New Breeding Technologies: Comparing Old and New Ways to Genetically Change Organisms

1. New Breeding Technologies:Comparing Old and New Ways to Genetically Change Organisms Adrianne Massey, PhD Managing Director, Science and Regulatory Affairs amassey@bio.org

2. History of Crop Genetic Modification • Understanding the historical development of crop genetic modification is essential for: • understanding relative risks • designing appropriate regulations (hopefully)

3. Genetic modification of food is not new • Humans have intentionally changed the genetic makeup of all • Crops we grow • Livestock we raise • Microorganisms we use in food processing • “GMO” = all food, except wild fish/game and • wild fruit (e.g., berries)

4. History of Crop Genetic Modification • Crop domestication = Crop genetic modification. Began 10,000 years ago. • Selected seeds from certain plants to be planted for the next year’s crop. • Genetic modification through artificial selection. • [artificial (human) selection vs. natural selection]

5. Teosinte – wild ancestor of maize Modern Maize

6. Historical Development of Maize Wild, weed relative Evolution by Artificial SelectionEarly humans changed teosinte into maize by “selecting for” certain traits (genes) and “selecting against” other traits (genes)

7. Historical Development of Maize Of the 59,000genes in maize, early humans focused on selecting for traits encoded by only 1700 genes. What do those other 57,300 genes do? Who knows?????

8. History of Crop Genetic Modification Stage 1. Artificial Selection – work with existing variation Stage 2: Selective Breeding Began when we learned how plants reproduce (1660’s) Controlled which plants reproduced - Shaped the variation in the population. Then selected certain seeds for next year’s crop. male female

9. Selective Breeding Within Same Species Same Species Shared gene pool Can exchange genes naturally through sexual reproduction At first……

10. Next Step: Selective breeding between different species Same species Same genus Different species “Wide Crosses” that would not occur naturally

11. Selective Breeding Across Species Some varieties of all major crops came from breeding different species with each other. Corn Tomato Rice Oat Canola Wheat Soy Potato BarleyBeets Squash Cotton First fertile, between-species cross in 1700’s “Not natural”

12. Different genus Different species Same species Next Step: Selective Breeding between different genera Same genus Different species Different genus Different species

13. Selective Breeding Across Genera Bread wheat has beencrossed with at least eleven different species insix different genera. 1890’s - first fertile between-genus cross

14. A Set of Lab Techniques Made “Wide Crosses” Possible • Bridge species • Chromosome doubling (chemical colchicine) • Embryo rescue • Treat with hormones, immunosuppressants • Protoplast fusion • Anther culture • Diploid tissue culture

15. “Natural” Plant Breeding (long before genetic engineering)

16. Genetic Modification through Mutagenesis • What if the existing genetic variation in accessible gene pools is limited? • Plant breeders create new genes in crop plants with mutagens, such as X-rays. • This form of genetic modification is mutagenesis breeding.

17. Genetic Modification through Mutagenesis • Since the 1930s, plant breeders have used mutagenesis to create new genes in more than 2700 crop varieties that were introduced to the food supply.

18. Genetic Engineering • The next step in the continuum of genetic modification techniques. • Most like selective breeding because it uses existing genetic variation. • “ Recombinant DNA technology ” - rDNA • Genetic engineering Transgenic crops

19. Each dot - thousands of genes Except single gene - disease resistance. Thousands of genes with Unknown functions

20. One gene Known function Inserted into familiar crop variety. new variety

21. “Genetically Modified” Crops Genetic modification technological continuum • Selective Breeding -within same species (8000 BC) - between different species* (1700s) - between different genera* (1890s) • Mutagenesis Breeding* (1930s) • Genetic Engineering* (1983) • * - “unnatural”

22. History of Genetic Modification Continuum of technological change characterized by • Improved precision and predictability • Increased dependence on scientific understanding

23. Modification Precision Continuum Selective Breeding thousands of genes unknown function Mutagenesis totally random unknown number of genes unknown function Genetic Engineering 1-2 genes known function

24. New Plant Breeding Technologies • The trend continues ……….. • Increased dependence on scientific understanding • Improved precision and predictability

25. New Plant Breeding Technologies • Examples: • Zinc finger nucleases - ZFN (3 types) • Oligonucleotide directed mutagenesis (ODM) • Induced DNA methylation

26. New Plant Breeding Technologies (NBTs) Past: Random insertion of new gene cisgene (same species) or transgene Now: Targeted gene insertion (ZNF -3)

27. New Plant Breeding Technologies • Zinc finger nucleases – ZFN-1 and ZFN-2 • Oligonucleotide directed mutagenesis (ODM) • These technologies allow very precise editing of plant’s existing genetic material (genome) • Single gene deletion • Single nucleotide changes • New genes are not added to crop

28. New Plant Breeding Technologies • Induced DNA methylation • No change in genome/gene • Change in gene expression

29. Regulation of NBTs What does this mean for regulation? • Increased scientific understanding • Improved precision and predictability

30. Genetic Improvement of Crops Breeding ? Thousands of genes unknown function or GE? Single gene ofknown function

31. Costs of Regulatory Compliance $ 0 Breeding GE $15-36 million

32. History of Crop Genetic Modification • Understanding the historical development of crop genetic modification is essential for: • understanding relative risks • Seems irrelevant for • designing appropriate regulations • As we learn more about the molecular biology of plants, the regulatory system becomes increasingly burdensome.

33. 1980’s Scientific Consensus on Risks • Risk GE crops = Risks GM crops • Product vs Process Risk Assessment • - National Academy of Sciences • - OECD Expert Panel • - Ecological Society America • - American Society Microbiology • - American Medical Association • - Office Technology Assessment (US Congress) • - Environmental Defense Fund • - Audubon Society

34. Risk and Regulation Science-Based Risk Assessment • Regulatory policy is shaped by: • Science-based risk • Public perception of risk “Public” Perception of Risk

35. Sample of Scientific Community Support American Council on Science and Health American Dietetic Association American Institute of Biological Science American Medical Assoc. Council on Scientific Affairs American Phytopathological Society American Society of Agronomy American Society for Cell Biology American Society for Horticulture science American Society for Microbiology American Society of Plant Biologists American Society of Plant Physiologists Brazilian Academy of Sciences Chinese Academy of Sciences Council for AgriScience and Technology Crop Science Society of America Entomological Society of America • Federation of Animal Scientific Societies • Food and Agriculture Organization Genetics Society of America Indian National Science Academy Institute of Food Science and Technology Institute of Food Technologists International Academy of Sciences International Society of African Scientists Mexican Academy of Sciences National Academy of Science & Technology of the Philippines National Academy of Sciences of USA New Zealand Royal Commission Society of Nematologists Society In Vitro Biology Pontifical Academy of Sciences The Royal Society of London Third World Academy of Sciences Weed Society of America New Plant Breeding Technologies

36. Number of pages/year in the U.S. Code of Federal Regulations Executive Orders Callingfor Regulatory Reform Regulation: A Primer by Dudley and Brito

37. USA Health and Environment Regulations Economic Regulations Regulation: A Primer by Dudley and Brito