1. Gene Editing Technologies: Importance and Implications for Farmers Drew L. Kershen Earl Sneed Centennial Prof. Emeritus United Soybean Board February 10, 2015

2. Wayne Parrott, Ph.D., Professor, Plant Breeding and Genomics, Crop & Soil Sciences, University of Georgia, is coauthor of this PowerPoint. Date of Completion January 20, 2015

3. Policy Issue Plant Breeding Techniques NAS (1987): “Several conclusions can be drawn from this review of the relationship between traditional genetic manipulation techniques and the R-DNA techniques developed during the last 15 years, and of the experience gained from the application of each: – There is no evidence that unique hazards exist either in the use of R-DNA techniques or in the movement of genes between unrelated organisms. – The risks associated with the introduction of R-DNA engineered organisms are the same in kind as those associated with the introduction of unmodified organisms and organisms modified by other methods. – Assessment of the risks of introducing R-DNA engineered organisms into the environment should be based on the nature of the organism and the environment into which it is introduced, not on the method by which it was produced.”

4. Policy Issue Plant Breeding Techniques White House OSTP 1992: “Exercise of oversight in the scope of discretion afforded by statute should be based on the risk posed by the introduction and should not turn on the fact that an organism has been modified by a particular process or technique. … [O]versight will be exercised only where the risk posed by the introduction is unreasonable, that is, when the value of the reduction in risk obtained by additional oversight is greater than the cost thereby imposed.”

5. Policy Issue Plant Breeding Techniques ACRE [UK] (2013): Executive Summary – “Our understanding of genomes does not support a process-based approach to regulation. The continuing adoption of this approach has led to, and will increasingly lead to, problems. This includes problems of consistency, i.e. regulating organisms produced by some techniques and not others irrespective or their capacity to cause environmental harm.” – “Our conclusion, that the EU’s regulatory approach is not fit for purpose for organisms generated by new technologies, also applies to transgenic organisms produced by ‘traditional’ GM technology. … the potential for inconsistency is inherent because they may be phenotypically identical to organisms that are not regulated.”

6. Policy Issue Plant Breeding Techniques Canadian Regulators (2015) Conclusion: – “It was hypothesized that if insertional effects are found to be similar to other genetic changes that occur in plants, they should present a similar level of risk. We have illustrated here that the insertional effects associated with genetic engineering are similar to the genetic changes that occur in conventionally bred plants. Based on this similarity, insertional effects should present a similar level of risk as genetic changes associated with conventional breeding. …” – Schnell et al. in references.

7. Regulatory Paradigms Paradigm One – Risk, not Hazard; Product (Trait), not Process – Presumption that regulation often not needed and should focus on novel, unreasonable risks – Science and scientific development trusted and encouraged Paradigm Two – Presumption favoring regulation and risk aversion – Precautionary Principle – Social and Political Consideration should be considered more important than science and scientific development – Politics, not Science

8. Importance and Impacts Paradigm Two will kill directed genetic modification technologies, including synthetic biology, before they have a chance to get started – Society (including farmers) deprived of new scientific discoveries – Farmers deprived of new technologies Imperative that U.S. regulatory systems move to Paradigm One – Presumption against regulation – Attitude of confidence in science and scientists – Avoidance of burdensome, discriminatory regulations – Consumer Perception Proper scientific education Consumer benefits – one example in High-Oleic soybeans and oils Positive labels versus stigmatizing, derogatory labels Access to products rather than threatened boycotts

9. Importance and Impacts Imperative that EU, New Zealand, others, and Cartagena Protocol move to Paradigm One – Failure to do so means: – Burdensome, discriminatory, unpredictable regulatory system – Trade wars – e.g. asynchronous approvals; U.S. lawsuits; WTO complaints – Veto of science and innovation – e.g. China, EU Reluctance to bring to market approved crops/traits Where are the markets in the near-future; short term gain versus long- term gain and vision – Human Misery Golden Rice and its travails – hidden hunger Diseases – plants and animals for vaccines National Security – for our grandchildren

10. Alphabetical List Sources Advisory Committee on Releases to the Environment (ACRE), Report 2: Why a modern understanding of genomes demonstrates the need for a new regulatory system for GMOs. (Sept. 2013) Akst, J., Designer Livestock, The Scientist Magazine Blog (June 1, 2014) at http://www.the- scientist.com/?articles.view/articleNo/40081/title/Designer-Livestock/http://www.the- scientist.com/?articles.view/articleNo/40081/title/Designer-Livestock/ Bar-Yam, S. et al., The Regulation of Synthetic Biology: A Guide to United States and European Union Regulations, Rules and Guidelines (SynBERC and iGEM ver. 9.1 January 10, 2012) Biotechnology and Biological Sciences Research Council (UK), New Techniques for Genetic Crop Improvement (Sept. 2014) Carter, S. et al., Synthetic Biology and the U.S. Biotechnology Regulatory System: Challenges and Options (J. Craig Venter Institute, May 2014) EFSA Panel on GMOs: Scientific opinion addressing the safety assessment of plants developed using ZFNs-3 and other SDN with similar functions, EFSA Journal 2012, 10:2943- 2974 Eriksson, D. et al., (August 2014) The slippery slope of cisgenesis, Nat. Biotech. 32:727 (correspondence) – Shouten, H., (07 August 2014) Reply to Eriksson et al., Online publication doi:10.1038/nbt.2981 European Commission, Directorate-General Environment, Working Group on the Establishment of a List of Techniques Falling under the Scope of Directive 2001/18/EC (unpublished, available as a Web-leaked document, August 2013)

11. Alphabetical List Sources European Commission-ERASynBio, Next steps for European synthetic biology: a strategic vision from ERASynBio (April 2014) European Commission-Scientific Committees, Preliminary Opinion on Synthetic Biology I: Definition (4 June 2014) Friends of the Earth et al., The Principles for the Oversight of Synthetic Biology (Oct. 17, 2013) Herring, R. On Risk and Regulation: Bt Crops in India, GM Crops & Food x:xx (manuscript accepted for publication) (in possession of co-authors) Leyser, O., (June 2014) Moving Beyond the GM Debate, PLOS-Biology Open Access e1001887 at www.plosbiology.orgwww.plosbiology.org Lusser, M. et al., (2011) New Plant Breeding Techniques: State-of-the-art and prospects for commercial development (JRC Scientific and Technical Reports) Lusser, M. & Davies, H.V., (2013) Comparative regulatory approaches for groups of new plant breeding techniques, New Biotechnol., 30(5):437-446 McGuiness Institute, An Overview of Genetic Modification in New Zealand 1973-2013: The first forty years (August 2013) Minikel, E. (2013) TALENs and ZFNs, www.cureffi.orgwww.cureffi.org Nagamangala, C., et al., (2014) Looking forward to genetically edited fruit crops, Trends in Biotech. (in press) (available on the Web) National Academy of Science (USA), Introduction of Recombinant DNA-Engineered Organisms into the Environment: Key Issues (1987)

12. Alphabetical List Sources NZ-EPA, Determination of whether or not an organism is a new organism under section 28 of the Hazardous Substances and New Organisms (HSNO) Act 1996, http://www.epa.govt.nz (19 April 2013)http://www.epa.govt.nz OECD, Emerging Policy Issues in Synthetic Biology (2014) Pennisi, E. (2013) The CRISPR Craze, Science 341:833-836 Podevin, N. et. al, (2013) Site-directed nucleases: a paradigm shift in predictable, knowledge-based plant breeding, Trends in Biotechnology, 31:375-383. Pollock C. & Hails, R., (February 2014) The case for reforming the EU regulatory system for GMOs, Trends in Biotech. 32(2):63-64 Presidential Commission for the Study of Bioethical Issues, New Directions: The Ethics of Synthetic Biology and Emerging Technologies (December 2010) Oye, K. et al., (8 Aug. 2014) Regulating Gene Drives, Science 345:626-628 Regalado, A., On the Horns of the GMO Dilemma (2 September 2014) MIT Tech. Rev. Online edition Schnell et. al., (Jan. 2015) A comparative analysis of insertional effects in genetically engineered plants: considerations of pre-market assessment, Transgenic Res. 24:1-17

13. Alphabetical List Sources Smyth, S. et al., (March 2014) Investment, regulation, and uncertainty: Managing new plant breeding technologies, GM Crops & Food 5(1):44-57 Sustainability Council of New Zealand Trust against The Environmental Protection Authority, CIV 2013-485-877, 2014 NZHC 1067 [High Court, Wellington] Synthetic Biology Project et al., Creating a Research Agenda for the Ecological Implications of Synthetic Biology (7 May 2014) ter Meulen, V., Time to settle the synthetic controversy, (08 May 2014) Nature 509:135 – IAP Statement on Realising Global Potential in Synthetic Biology: Scientific Opportunities and Good Governance (7 May 2014) US-APHIS, Regulated Letters of Inquiry at http://www.aphis.usda.gov (viewed September 4, 2014)http://www.aphis.usda.gov US-EPA, Meeting Minutes FIFRA Scientific Advisory Panel on “RNAi Technology as a Pesticide: Problem Formulation for Human Health and Ecological Risk Assessment” (Jan. 28, 2014), http://www.epa.gov/sciploy/sap ; plus especiallyhttp://www.epa.gov/sciploy/sap – Written comments to the SAP meeting by James Carrington, President, Donald Danforth Plant Science Center; Craig Mello, Nobel Prize winner, Univ. of Massachusetts Medical School; Weed Science Society of America

14. Alphabetical List Sources US-FDA, Regulation of Genetically Engineered Animals Containing Heritable Recomibinant DNA Constructs – Final Guidance for Industry (rev. May 17, 2011) at http://www.fda.gov/AnimalVeterinary/DevelopmentApprovalProcess/ http://www.fda.gov/AnimalVeterinary/DevelopmentApprovalProcess/ – US-FDA, Fact Sheet on Genetically Engineered Animals (updated May 5, 2014) – US-FDA, General Q&A Genetically Engineered Animals (viewed September 4, 2014) Voytas, D. & Gao, C., (June 204) Precision Genome Engineering and Agriculture: Opportunities and Regulatory Challenges, PLOS-Biology OpenAccess e1001877 at www.plosbiology.orgwww.plosbiology.org World Health Organization, Guidance Framework for Testing of Genetically Modified Mosquitoes – Confidential Draft (unpublished, available as a Web-leaked document, 2013) Xue, K., Synthetic Biology’s New Menagerie, (Sept-Oct 2014), Harvard Magazine pp. 42-49

15. Thank you Drew L. Kershen 300 W. Timberdell Road Norman, OK 73019-5081 dkershen@ou.edu (405) 325-4784