On March 10-11, 2016, the National Academies of Sciences, Engineering, and Medicine held a public symposium on potential U.S. government policies for the oversight of gain-of- function (GOF) research. This was the Academies' second meeting held at the request of the U.S. government to provide a mechanism to engage the life sciences community and the broader public and solicit feedback on optimal approaches to ensure effective federal oversight of GOF research as part of a broader U.S. government deliberative process. The first symposium, held in December 2014, examined the underlying scientific and technical questions surrounding the potential risks and benefits of GOF research involving pathogens with pandemic potential. The second symposium focused on discussion of the draft recommendations regarding GOF research of a Working Group of the National Science Advisory Board for Biosecurity. This report summarizes the key issues and ideas identified during the second symposium. Table of Contents Front Matter 1 Introduction 2 The Draft National Science Advisory Board for Biosecurity Policy Framework, the Risk and Benefit Assessment, and Insights for the Policy Process 3 Issues for U.S. Policy 4 International Policy 5 Summing Up Bibliography Appendix A: Board and Committee Members of Collaborating Units Appendix B: Committee Biographies Appendix C: Symposium Agenda Appendix D: Speaker and Panelist Biographies Appendix E: List of Attendees

On October 17, 2014, spurred by incidents at U.S. government laboratories that raised serious biosafety concerns, the United States government launched a one-year deliberative process to address the continuing controversy surrounding so-called "gain-of-function" (GOF) research on respiratory pathogens with pandemic potential. The gain of function controversy began in late 2011 with the question of whether to publish the results of two experiments involving H5N1 avian influenza and continued to focus on certain research with highly pathogenic avian influenza over the next three years. The heart of the U.S. process is an evaluation of the potential risks and benefits of certain types of GOF experiments with influenza, SARS, and MERS viruses that would inform the development and adoption of a new U.S. Government policy governing the funding and conduct of GOF research. Potential Risks and Benefits of Gain-of-Function Research is the summary of a two-day public symposia on GOF research. Convened in December 2014 by the Institute of Medicine and the National Research Council, the main focus of this event was to discuss principles important for, and key considerations in, the design of risk and benefit assessments of GOF research. Participants examined the underlying scientific and technical questions that are the source of current discussion and debate over GOF research involving pathogens with pandemic potential. This report is a record of the presentations and discussion of the meeting. Table of Contents Front Matter 1 Introduction 2 Assessing Risks and Benefits 3 Gain-of-Function Research: Background and Alternatives 4 Potential Benefits of Gain-of-Function Research 5 Potential Risks: Biosafety and Biosecurity 6 Policy Implications References Appendix A: Key Issues for Risk/Benefit Assessment for Gain-of-Function Research Appendix B: Committee Biographies Appendix C: Agenda Appendix D: Speaker Biographies Appendix E: List of Attendees Appendix F: Acronym List