science and served discriminatory political goals (Wailoo et al., 2012). Looking Beyond Safety and Efficacy Although the nature of the debate surrounding genome editing is not new, the tools available in the past for making genetic modifications in human cells were time-consuming, difficult, and expensive, and were unlikely to be used outside of specialized medical applications. Recent genome-editing technologies, particularly the CRISPR/Cas9 system, have greatly expanded the landscape of potential applications and potential users. Their rapid development and adoption also have shortened the timeline for discussion of what appropriate governance structures need to be identified or developed. As the safety and efficacy of these technologies continue to improve, the critical question will become not whether scientists and clinicians can use genome editing to make a certain change, but whether they should. There is already discussion of do-it-yourself Copyright © National Academy of Sciences. All rights reserved. Human Genome Editing: Science, Ethics, and Governance INTRODUCTION 19 PREPUBLICATION COPY—SUBJECT TO FURTHER EDITORIAL REVISION (DIY) editing and the use of genome editing tools by the biohacker and DIY biology communities, albeit in non-human organisms (Brown, 2016; Ledford, 2015). Thorny issues around acceptable uses of the technology in humans will depend on more than scientific considerations, and may increasingly involve weighing factors beyond individual-level risks and benefits (NRC, 1996). Layered on the scientific and ethical issues associated with human genome editing is the question of how to govern its application so as to facilitate its appropriate use and avoid its misuse. Determining the limits of the technologies’ uses and the regulatory mechanisms needed to enforce these limits will vary according to each nation’s cultural, political, and legal context. But whether and how best to move human genome editing forward has implications for transnational scientific cooperation that require ongoing public discussion and input into policy making. There is ample precedent for scientists and other stakeholders to engage in just such activities, and this report is intended to build on points raised by a number of international conventions and declarations, such as the Oviedo Convention (1997), the International Declaration on Human Genetic Data (2003), and the Universal Declaration on Bioethics and Human Rights (2005) (Andorno, 2005; UNESCO, 2004a, 2005). STUDY APPROACH To address its complex task (see Box 1-1), the committee included members with expertise in basic and clinical research, in the development of human genetic therapies, and in U.S. and international legal and regulatory frameworks. It included biologists, bioethicists, and social scientists, and incorporated perspectives from potentially affected patient and stakeholder communities. Because the ethical and social issues posed by human genome editing transcend national boundaries, the committee included not only U.S. members but also those who are citizens of or are currently working in Canada, China, Egypt, France, Germany, Israel, Italy, Spain, and the United Kingdom. Brief biographies of the committee members are found in Appendix D. This study was informed not only by the International Summit described earlier, which immediately preceded the committee’s first meeting, but also by review of the salient literature, additional meetings, and speakers who generously shared their knowledge with the committee. Further information on the process by which the committee conducted this study is provided in Appendix C. In evaluating the implications of new genome-editing tools, the committee also reviewed scientific progress, ethical debates, and regulatory structures related to the use in humans of medical developments such as assisted reproductive technologies, stem cell therapies, gene transfer, and mitochondrial replacement techniques. These developments interface with those of genome editing since editing of stem cells has potential clinical applications for treating or preventing disease, and reproductive technologies would have to be used in combination with genome editing for any heritable application of the latter technologies. As these other technologies have advanced, legal and regulatory frameworks and ethical norms of conduct have been developed to provide guidance on their appropriate human uses and oversight (Health Canada, 2016; HFEA, 2014; IOM, 2005; NASEM, 2016e; NRC and IOM, 2007, 2008; Nuffield Council, 2016a; Präg and Mills, 2015; Qiao and Feng, 2014). The reports cited here helped provide a basis for the committee’s assessment of the use of genome-editing tools in humans and are referenced in subsequent chapters where relevant. Copyright © National Academy of Sciences. All rights reserved. Human Genome Editing: Science, Ethics, and Governance 20 HUMAN GENOME EDITING PREPUBLICATION COPY—SUBJECT TO FURTHER EDITORIAL REVISION ORGANIZATION OF THE REPORT The report begins by reviewing international norms that are embodied in the set of overarching principles adopted by the committee for governance of human genome editing (Chapter 2). The chapter continues with an overview of the U.S. regulation of research and clinical application of