genome editing, drawing comparisons where appropriate to other national systems of oversight. With this grounding in principles and regulation, Chapters 3-6 delve into human genomeediting technology and the scientific issues, regulatory context, and ethical implications of four specific applications. Laboratory research conducted in somatic cells and non-heritable laboratory research in human germ cells, gametes, or early-stage embryos is covered in Chapter 3. Chapter 4 examines the uses of genome editing for somatic interventions focused on therapy, including fetal therapy. Chapter 5 addresses the use of genome-editing technology in germline cells for potential research and clinical therapeutic applications in human patients. Chapter 6 considers the potential use of human genome editing to enhance human functions rather than to treat or prevent disease or disability. The subsequent chapter (Chapter 7) turns from analysis of these categories of application to the role of public input in determining how genome-editing technology should be governed in the future, both in the United States and in other countries. The chapter considers public engagement for different categories of genome-editing applications and explores strengths and limitations of potential models for undertaking such public engagement. Finally, Chapter 8 returns to the set of overarching principles and the responsibilities that flow from them in the context of human genome editing. The chapter pulls together the report’s conclusions and recommendations in light of these fundamental concepts. Copyright © National Academy of Sciences. All rights reserved. Human Genome Editing: Science, Ethics, and Governance PREPUBLICATION COPY—SUBJECT TO FURTHER EDITORIAL REVISION 21 2 Oversight of Human Genome Editing and Overarching Principles for Governance12 Oversight of human genome editing fits within the overarching framework of oversight of gene therapy. That framework is embedded within the larger context of international conventions and norms for protection of human rights and, more specifically, for research involving human subjects and clinical care. From these international instruments, one can derive principles for governance of genome editing that have general application within the United States and across the globe, and are reflected in the specific statutory and regulatory rules that are adopted by various nations. This chapter begins by describing the overarching principles for human genome editing adopted by the committee for this study, which are informed by those international instruments and national rules, and which in turn inform the conclusions and recommendations presented in this report. It then provides an in-depth look at U.S. governance of gene transfer research and therapy, and a brief review of alternate approaches used in other countries (some of which are explored in greater depth in Appendix B). Conclusions regarding the adequacy of U.S. oversight systems to deal with the specific technical and ethical issues raised by genome editing appear in Chapters 3 through 6. PRINCIPLES FOR GOVERNANCE OF HUMAN GENOME EDITING Louis Pasteur once said: “La science n’a pas de patrie, parce que le savoir est le patrimoine de l’humanité” (Science has no homeland, because knowledge is the heritage of humanity). But while science is global, it proceeds within a variety of political systems and cultural norms. It is important to identify principles that can transcend these differences and divisions, while accommodating cultural diversity. This is no easy task. Achieving consensus around overarching ethical principles to undergird specific recommendations for action can be difficult, whether because no one theory of ethics has been accepted by philosophers and theologians or because no one algorithm for deriving principles from those theories has been found. Utilitarians may agree on the need to evaluate overall beneficial consequences, but may disagree on whether to evaluate the consequences of a rule or of a specific act. Deontologists not only will struggle to derive a defensible list of fundamental rules of behavior, but also will be confronted with specific cases in 12Portions of this chapter were adapted and updated from Institute of Medicine (IOM, 2014) and the National Academies of Sciences, Engineering, and Medicine (NASEM, 2016e). Copyright © National Academy of Sciences. All rights reserved. Human Genome Editing: Science, Ethics, and Governance 22 HUMAN GENOME EDITING PREPUBLICATION COPY—SUBJECT TO FURTHER EDITORIAL REVISION which adherence leads to results that are intuitively unacceptable or even destructive. Other theories suffer from similar complications. Bioethics, as a form of applied ethics, has suffered from all these complexities. It has also been dogged by long-standing debates about whether the best approach is high theory, from which all principles and specific actions flow, or anti-theory, in which deductive reasoning from specific cases leads to generalizable principles. And when bioethics is incorporated into public policy making, as opposed to individual clinical ethics analyses, it is necessary to incorporate a wider range of concerns about multicultural civil society, theories of democracy, and just distribution of burdens and benefits.13 Regardless of