Amy P. Patterson, M.D. Acting Associate Director for Science Policy National Institutes of Health

1. Federal Oversight of Synthetic Biology ResearchPresident’s Commission for the Study of Bioethical Issues  9 July 2010 Amy P. Patterson, M.D. Acting Associate Director for Science Policy National Institutes of Health

2. Evolution of biotechnology and public policy: milestones • Federal oversight framework for biotechnology: applicability to synthetic biology • Challenges of oversight and foresight • Avenues of inquiry by the Commission: some thoughts Today’s Presentation

3. Emergent power of genetic technology…initial policy development Asilomar, 1975 NIH Guidelines,1976 DNA Sequencing technology 1st genetically engineered molecule 1977-78: rDNA techniques 1st used to produce recombinant human proteins in E. coli 1st recombinant organism In 1953, Watson and Crick unravel the structure of DNA 1950 1960 1970

4. 1996-97 Select Agent Rules ELSI Program established at NIH/DOE Coordinated Framework, 1986 1981: Development of 1st DNA synthesizers 1st automated DNA sequencing Gene Chip 1995 1984-85: PCR—polymerase chain reaction—technology becomes available Larry Wayne Harris and the threat of bioterrorism 1980 1990 Accelerated technological advances & applications…

5. NSABB Reports on Synthetic Genomics, Oversight Framework, Synthetic Biology, 2006-2010 Underway: USG dual use research policy + rDNA guidelines revision Syn Bio 1.0 @ MIT NSABB establishment 2004 2003 9/11 2007-2009 Genomic transplantation, assembly of whole bacterial genome, interspecies genomic transfer Amerithrax Human Genome Project, 2003 In vitro synthesis of polio virus, 2002 Artemisin, 2006 BioBricksTM 2000 2010 Synthetic biology comes into its own…in the shadow of 9/11 and Amerithrax

6. A continuum of incremental steps forward in science, coupled with a process of regulatory/oversight evolution From the 1970s to now, from recombinant DNA technologies to de novo gene synthesis

7. Oversight: Principles and Attributes • Reflects a fundamental premise: Whilebiotechnology offers many major benefits to society, the potential risks must be assessed and addressed • Is predicated on risk/benefit assessments and titrated according to risk • Categories of research presenting higher levels of risk or uncertainty are subject to higher degrees of oversight • Evolves to reflect advances in science and technology and advances in our understanding of potential risks and benefits • Develops through an ongoing process of open public dialogue

8. Major Categories of Risk Posed by Biotechnology Research Biosafety Biosecurity • Accidental exposure to a pathogen or toxin could adversely affect: • Laboratory workers • General public • Plants and animals • Environment • Deliberate misuse of technology to cause harm to: • Humans • Plants and animals • Environment

9. Major Categories of Risk Posed by Biotechnology Research Safety of Research Subjects Societal Norms • Clinical administration of biotechnology products could adversely affect: • Individual research subjects • Controversial uses and consequences of technology, e.g.: • Germline interventions • Enhancements • Genetically modified organisms

10. Oversight of Biotechnology Research *NOTE: The NIH Guidelines are currently being revised to more explicitly address synthetic nucleic acids.

11. Oversight of Biotechnology Research

12. Oversight of Biotechnology Research

13. Oversight of Biotechnology Research

14. Oversight of Biotechnology Research

15. Oversight of Biotechnology Research

16. Culture of Responsibility • Responsible and ethical conduct of synthetic biology, like all biotechnology research, rests upon the behavior of individual scientists • Federal oversight can guide the development of a culture of responsibility and accountability that must be fostered at the local level

17. Risk Assessment in a Context of Increasing Uncertainty About Biologic Properties Data underpinning risk/threat assessment ? Known agents Novel or uncharacterized agents

19. Expansion of DIY Synthetic Biology (2010) Democratization

20. Globalization and Commercialization

21. Open Access Environment:Boon for Scientific Progress, Challenge to Oversight • Increasingly available and affordable • Commercialized • Privatized • Democratized • Globalized

22. An Evolving Oversight Framework: Recent Developments • Revision of The NIH Guidelines for Research Involving Recombinant DNA Molecules to address Synthetic Nucleic Acid Molecules • US government draft Screening Framework Guidance for Providers of Synthetic Double-Stranded DNA • Available at http://frwebgate1.access.gpo.gov/cgi- • Development of US government policy on local and federal oversight of dual use research (which would encompass certain synthetic biology experiments) • USG tasked the NSABB to advise on strategies for outreach to all practitioners of syn bio, enhancing culture of responsibility, international engagement

23. An Evolving Oversight Framework: Recent Developments (continued) • National Academies study on Scientific Milestones for the Development of a Gene-Sequence-Based Classification System for Oversight of Select Agents • Periodic revision of Biosafety in Microbiological and Biomedical Laboratories • Fifth Edition available at: http://www.cdc.gov/biosafety/publications/BMBL_5th_Edition.pdf • Periodic revision of the Select Agent Rules • Additional information available at http://www.selectagents.gov/ • July 2, 2010 Executive Order on Optimizing the Security of Biological Select Agents and Toxins in the U.S.

25. The price of scientific freedom is eternal vigilance and responsibility. • “The price of freedom is eternal vigilance.” • Thomas Jefferson