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

The BioWatch program, funded and overseen by the Department of Homeland Security (DHS), has three main elements-sampling, analysis, and response-each coordinated by different agencies. The Environmental Protection Agency maintains the sampling component, the sensors that collect airborne particles. The Centers for Disease Control and Prevention coordinates analysis and laboratory testing of the samples, though testing is actually carried out in state and local public health laboratories. Local jurisdictions are responsible for the public health response to positive findings. The Federal Bureau of Investigation is designated as the lead agency for the law enforcement response if a bioterrorism event is detected. In 2003 DHS deployed the first generation of BioWatch air samplers. The current version of this technology, referred to as Generation 2.0, requires daily manual collection and testing of air filters from each monitor. DHS has also considered newer automated technologies (Generation 2.5 and Generation 3.0) which have the potential to produce results more quickly, at a lower cost, and for a greater number of threat agents. Technologies to Enable Autonomous Detection for BioWatch is the summary of a workshop hosted jointly by the Institute of Medicine and the National Research Council in June 2013 to explore alternative cost-effective systems that would meet the requirements for a BioWatch Generation 3.0 autonomous detection system, or autonomous detector, for aerosolized agents . The workshop discussions and presentations focused on examination of the use of four classes of technologies-nucleic acid signatures, protein signatures, genomic sequencing, and mass spectrometry-that could reach Technology Readiness Level (TRL) 6-plus in which the technology has been validated and is ready to be tested in a relevant environment over three different tiers of temporal timeframes: those technologies that could be TRL 6-plus ready as part of an integrated system by 2016, those that are likely to be ready in the period 2016 to 2020, and those are not likely to be ready until after 2020. Technologies to Enable Autonomous Detection for BioWatch discusses the history of the BioWatch program, the role of public health officials and laboratorians in the interpretation of BioWatch data and the information that is needed from a system for effective decision making, and the current state of the art of four families of technology for the BioWatch program. This report explores how the technologies discussed might be strategically combined or deployed to optimize their contributions to an effective environmental detection capability. Table of Contents Front Matter 1 Introduction 2 Overview of the BioWatch Program 3 Public Health's Perspective on the Role of BioWatch in the Decision-Making Process 4 Potential Technologies for the BioWatch Program 5 Final Thoughts Appendix A: References Appendix B: Biographical Sketches of Workshop Participants Appendix C: Workshop Agenda Appendix D: Registered Attendees Appendix E: Technology Readiness Levels in the Department of Defense Appendix F: White Paper 1: The BioWatch Program: What Information Is Needed to Inform Decision Making? Appendix G: White Paper 2: Nucleic-Acid Signatures at Three Levels of Readiness for BioWatch Appendix H: White Paper 3: State of the Art for Autonomous Detection Systems Using Immunoassays and Protein Signatures Appendix I: White Paper 4: State of the Art for Autonomous Detection Systems Using Genomic Sequencing Appendix J: White Paper 5: State of the Art for Autonomous Detection Systems Using Mass Spectrometry