Larry Kerr, Ph.D. Office of Science and Technology Policy Assistant Director for Homeland Security

1. United States Government Policy Efforts to Tackle the Dual Use Dilemma Franca R. Jones, Ph.D. National Security & International Affairs Office of Science and Technology Policy Larry Kerr, Ph.D. Office of Science and Technology Policy Assistant Director for Homeland Security Center for International and Security Studies at Maryland Biosecurity Workshop October 2, 2010

2. The Threat “Advances within the life sciences hold extraordinary potential for beneficial progress, but they also can empower those who would use biological agents for ill purpose.....the pace and progress of the life sciences require tailored approaches to mitigate the potential for misuse with minimal impacts upon beneficial use.” President Barack Obama National Strategy for Countering Biological Threats National Security Council, November 2009

3. Today’s Discussion • USG Policy Efforts on Dual Use Research: • Conduct and Review of Dual Use Research • Synthetic Biology • Biological Select Agents and Toxins

4. The “Dual Use” Dilemma • Life sciences research underpins: • Biomedical and public health advances • Improvements in agriculture • Safety and quality of food supply • Environmental quality • Strong national security and economy • However,good science can be put to bad uses

5. NSABB Recommendations: Oversight of Dual Use Research • June 2007 NSABB report 1, Proposed Framework for the Oversight of Dual Use Life Sciences Research: Strategies for Minimizing the Potential Misuse of Research Information • Not intended as comprehensive guidelines for oversight but rather to serve as a framework or springboard for the USG to develop a comprehensive and coordinated oversight policy 1Report can be accessed at http://oba.od.nih.gov/biosecurity/biosecurity_documents.html

6. USG Consideration of NSABB Report • NSABB recommendations considered through a trans-federal policy coordination process • Led by White House National Security Staff and Office of Science and Technology Policy

7. USG Working Group on Dual UseResearch Oversight: Charge • Briefings on extant models of oversight and other relevant issues • Analyze the NSABB recommendations • Identify and address any gaps and unresolved issues • Develop additional tools for facilitating oversight of dual use research • Develop a draft policy • Consultation with stakeholders, as appropriate • Federal agency review and comment • Publish in Federal Register for broad public comment • Revise as necessary and finalize policy

8. Screening Framework Guidance for Synthetic Double-Stranded DNA Providers

9. The Issue • Synthetic biology and the underlying technologies together can provide significant scientific, health, and economic benefits. • Nucleic acid synthesis technology is a potentially enabling technology for the de novo reconstruction of dangerous pathogens, either in part or in whole. • De novo synthesis of naturally-occurring pathogens • Access to sequences and organisms of concern. • Evasion of current regulatory and physical access controls (e.g., U.S. Select Agents, Australia Group, pathogen security processes and procedures). • De novo synthesis of novel biological agents • Pathogens with unique properties. • Development of any oversight mechanism must… • balance the need to minimize the risk of misuse with the need to ensure that science and innovation are encouraged; and • involve engagement of the synthetic nucleic acid industry, the scientific community, and other stakeholders.

10. NSABB Recommendation: Develop Screening Framework • December 2006 NSABB report, Addressing Biosecurity Concerns Related to the Synthesis of Select Agents, NSABB recommended the U.S. Government, in consultation with outside experts, develop a screening process to be used by providers of synthetic DNA.

11. Key Milestones for USG Efforts on Synthetic DNA and Security 2006 2007 2008 2009 NSABB report on synthetic genomics USG begins interagency policy development process Roundtable on screening framework USG screening framework approved Workshop on screening and synthesis capabilities USG draft guidance to double-stranded synthetic DNA industry released

12. Guidance Overview • Primary Goal: • Minimize the risk that unauthorized individuals or individuals with malicious intent will obtain “toxins and agents of concern” through the use of nucleic acid synthesis technologies • Simultaneously minimize any negative impacts on the conduct of research and business operations • The USG recommends that all orders for synthetic double-stranded DNA 200 base pairs or longer be subject to a screening framework that incorporates both sequence screening and customer screening. • If either customer screening or sequence screening raises any concerns, providers should perform follow-up screening. • If follow-up screening does not resolve issues, providers should contact designated entities within the USG for further information and assistance.

13. Process Summary and Next Steps • Draft Guidance was posted for public comment in the Federal Register on November 27, 2009 and was open for a period of 60 days • Received 22 (61 pages) individual comments from scientists, industry associations, scientific societies, and individual companies • A public meeting was hosted by the American Association for the Advancement of Science on January 11, 2010 to solicit additional feedback from scientists and others on the draft Guidance • Please see http://edocket.access.gpo.gov/2009/E9-28328.htm for a copy of the draft Guidance. • An interagency Sub-Working Group reviewed public comments and amended the draft Guidance accordingly. • The final Guidance will be publicly released at the conclusion of the process. • An interagency Sub-Working Group has been established to develop plans to monitor the implementation and evaluate the effectiveness of the Guidance

14. NIH Guidelines for Research Involving Recombinant DNA Molecules

15. NSABB on Synthetic Genomicsand Biosafety Some practitioners of synthetic genomics are: Educated in disciplines that do not routinely entail formal training in biosafety Uncertain about when to consult an Institutional Biosafety Committee Ensure that biosafety principles and practices are applicable to synthetic genomics and easily understood.

16. Synthetic Genomics NSABB recommended: Development and dissemination of harmonized guidance Development of standards & practices for sequence providers to include nucleic acid screening A review of current biosafety guidelines to ensure that they are adequate for synthetically derived DNA Continued consultation with experts to develop a predictive framework for determining pathogenicity Charge: Examine the potential biosecurity concerns raised by the synthesis of select agents, and synthetic biology in general, and recommend strategies for addressing these concerns

17. Consideration and Implementation of NSABB Recommendation NSABB recommendations considered through a trans-federal policy coordination process Led by White House National Security Staff and Office of Science and Technology Policy Recommendation on need for biosafety guidance accepted by USG NIH tasked with implementation NIH Recombinant DNA Advisory Committee consulted

18. Revisions to NIH Guidelinesare Underway Proposed expansion of the scope of NIH Guidelines to apply to research with synthetic nucleic acids as well as research with recombinant nucleic acid molecules Proposed exemption for certain research with non-replicating synthetic nucleic acids based on biosafety risks Expanding guidance on risk assessment and risk management to address unique aspects of synthetic biology, e.g. risk assessment of novel organisms

19. Current Status June 2010: NIH Recombinant DNA Advisory Committee (RAC) finalized its recommendations Final Federal Register notice developed and undergoing internal review

20. Additional Information For more information on revisions to the NIH Guidelines with respect to synthetic nucleic acids: http://oba.od.nih.gov/rdna_rac/rac_pub_con.html Email: OBA@OD.NIH.gov

21. Biological Select Agents and Toxins Definition: Biological agents and toxins with the potential to pose a severe threat to public health and safety, animal and plant health, or animal and plant products and whose possession, use, and transfer are regulated by the Department of Health and Human Services and the Department of Agriculture under the Select Agent Regulations.

22. USG Efforts in Security of Dangerous Pathogens CDC and USDA/APHIS final Select Agent Regulations published in 20051 January 9, 2009: Executive Order 13486 “Strengthening Laboratory Biosecurity in the United States” 1 Established a working group co-chaired by HHS and DoD with representatives from other federal agencies-report published in 20093 A policy process was initiated in Fall 2009 to review all inputs to include other reports from the NSABB, NAS, biosafety, WMD commission, published statements of .professional organizations July 2, 2010: Executive Order 13546 “Optimizing the Security of Biological Select Agents and Toxins in the United States” 4 – effort ongoing 1http://www.selectagents.gov/ 2http://www.fas.org/irp/offdocs/eo/eo-13486.htm 3http://orise.orau.gov/emi/scapa/files/biosecurity-report.pdf 4http://www.fas.org/irp/offdocs/eo/eo-13546.htm

23. EO 13546 Policy Statement “It is the policy of the United States that: (a) A robust and productive scientific enterprise that utilizes biological select agents and toxins (BSAT) is essential to national security; (b) BSAT shall be secured in a manner appropriate to their risk of misuse, theft, loss, and accidental release; and (c) Security measures shall be taken in a coordinated manner that balances their efficacy with the need to minimize the adverse impact on the legitimate use of BSAT. ”

24. EO 13546 Subgroups Federal Experts Security Advisory Panel (FESAP) – interagency panel Tieiring of BSAT Personnel Reliability Physical /Cyber Security Oversight and Inspections

26. Summary of Guidance Recommendations Customer Screening The U.S. Government recommends that, for every order, synthetic nucleic acid providers: Verify the customer’s identity. Screen customers against several lists of proscribed entities. Check for ‘red flags.’ In any case where customer screening raises a concern, providers should conduct follow-up screening.

27. Summary of Guidance Recommendations, Continued Sequence Screening The U.S. Government recommends that: Nucleic acid sequences be screened against GenBank using a ‘‘Best Match’’ approach to identify nucleic acids that are unique to Select Agents and Toxins. For foreign orders, nucleic acids be screened using a ‘‘Best Match’’ approach to identify nucleic acids that are unique to pathogens and toxins on the Commerce Control List and nucleic acids that are unique to Select Agents and Toxins. Sequence screening be performed for both DNA strands and the resultant polypeptides derived from translations using the three alternative reading frames on each DNA strand (or six-frame translation). Sequence alignment methods should permit the detection of hidden ‘‘sequences of concern’’ as small as 200 bps. In any case where sequence screening raises a concern, providers should conduct follow-up screening.

28. Summary of Guidance Recommendations, Continued Follow-up Screening When customer screening reveals any ‘red flags’ or sequence screening identifies a sequence of concern, the U.S. Government recommends that Providers ask for information regarding the customer’s proposed end-use of the order to assess their need and the scientific legitimacy of their work. Providers take additional steps to verify the customer’s identity and need. Domestic and Foreign Orders The U.S. Government reminds providers to check against various lists of restricted entities before filling every order; these lists vary for domestic and foreign customers. Contacting the U.S. Government In cases where follow-up screening cannot resolve concerns raised by customer screening or sequence screening, or when providers are otherwise unsure about whether to fill an order, the U.S. Government recommends that providers contact relevant agencies.

29. Summary of Guidance Recommendations, Continued Sequence Screening Software and Expertise The U.S. Government recommends that: Providers select a sequence screening software tool that utilizes both a global and local sequence alignment technique. Providers have the necessary expertise in-house to perform the sequence screenings, analyze the results, and conduct the appropriate follow-up research to evaluate the significance of dubious sequence matches. Records Retention The U.S. Government recommends that providers retain electronic copies of customer orders for at least eight years.