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.

Contents

• THE NATIONAL ACADEMIES
• COMMITTEE ON GAIN-OF-FUNCTION RESEARCH WITH H5N1/H7N9 AVIAN INFLUENZA: A SYMPOSIUM
• BOARD ON LIFE SCIENCES
• COMMITTEE ON SCIENCE, TECHNOLOGY, AND LAW
• BOARD ON HEALTH SCIENCES POLICY
• Acknowledgments
• 1. Introduction
• 2. Assessing Risks and Benefits
  • DEFINING “RISK” AND “BENEFIT”
  • ASSESSING RISKS AND (EXPECTED) BENEFITS
  • HUMAN BEHAVIOR AS A SOURCE OF VULNERABILITY AND RESILIENCE
  • PUBLIC ENGAGEMENT
  • SUMMARY OF RISK AND BENEFIT OVERVIEW
• 3. Gain-of-Function Research: Background and Alternatives
  • TYPES OF GAIN-OF-FUNCTION (GOF) RESEARCH
  • APPLICATIONS OF GOF RESEARCH
  • GOF RESEARCH AS DEFINED BY THE U.S. GOVERNMENT
  • ALTERNATIVES TO GOF RESEARCH
• 4. Potential Benefits of Gain-of-Function Research
  • SURVEILLANCE, DETECTION, AND PREDICTION
  • TREATMENT AND RESPONSE
• 5. Potential Risks: Biosafety and Biosecurity
  • KEY CONSIDERATIONS IN RISK ASSESSMENT
  • BIOSAFETY
  • BIOSECURITY
  • SPECIFIC TOPICS FOR CONSIDERATION
• 6. Policy Implications
  • CLOSING REMARKS
• References
• APPENDIXES
  • 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

Rapporteurs: Frances Sharples, Jo Husbands, Anne-Marie Mazza, Audrey Thevenon, and India Hook-Barnard.

This study was supported by Contract No. 10002374 between the National Academy of Sciences and the National Institutes of Health, by the John D. and Catherine T. MacArthur Foundation, the Alfred P. Sloan Foundation, the Wellcome Trust, and by internal support from the National Academies. Any opinions, findings, conclusions, or recommendations expressed in this publication are those of the author(s) and do not necessarily reflect the views of the organizations or agencies that provided support for the project.

NOTICE: The project that is the subject of this report was approved by the Governing Board of the National Research Council, whose members are drawn from the councils of the National Academy of Sciences, the National Academy of Engineering, and the Institute of Medicine. The members of the committee responsible for the report were chosen for their special competences and with regard for appropriate balance.