treatment of human diseases? 5. Do current ethical and legal standards for human subjects research adequately address human gene editing, including germline editing? What are the ethical, legal, and social implications of the use of current and projected gene-editing technologies in humans? 6. What principles or frameworks might provide appropriate oversight for somatic and germline editing in humans? How might they help determine whether, and which applications of, gene editing in humans should or should not go forward? What safeguards should be in place to ensure proper conduct of gene-editing research and use of gene-editing techniques? 7. Provide examples of how these issues are being addressed in the international context. What are the prospects for harmonizing policies? What can be learned from the approaches being applied in different jurisdictions? drugs, devices and biologics. See FDA “Regulation of Intentionally at https://www.regulations.gov/document?D=FDA-2016-N-4389-0001 (accessed January 30, 2017). 9 The regulatory roles of the federal departments and agencies, and the overall framework for regulation of applications of biotechnology, are outlined in “Modernizing the Regulatory System for Biotechnology Products: Final Version of the 2017 Update to the Coordinated Framework for the Regulation of Biotechnology” (January 4, 2017) and “National Strategy for Modernizing 01/04/increasing-transparency-coordination-andpredictability-biotechnology-regulatory (accessed January 30, 2017). Copyright © National Academy of Sciences. All rights reserved. Human Genome Editing: Science, Ethics, and Governance INTRODUCTION 13 PREPUBLICATION COPY—SUBJECT TO FURTHER EDITORIAL REVISION The committee will address these questions and prepare a report that contains its findings and recommendations. The report will provide a framework based on fundamental, underlying principles that may be adapted and adopted by any nation that is considering the development of guidelines. The report will also include a focus on advice for the United States. STUDY CONTEXT The NAS and the NAM Human Gene-Editing Initiative In light of the promise of genome editing and the associated regulatory and ethical issues, the NAS and the NAM established an initiative to explore these issues in greater depth and facilitate U.S. and international dialogue on how to address them. The first activity of this Human GeneEditing Initiative was the convening of the International Summit on Human Gene Editing: A Global Discussion jointly with the Chinese Academy of Sciences and The Royal Society of the United Kingdom. This 3-day event addressed a number of scientific advances in the development of modern genome-editing tools, potential medical uses of these tools in human patients, and ethical and social issues their uses might pose. The organizing committee released a statement that summarized its conclusions from the meeting (NASEM, 2016d). Panel chair David Baltimore also noted “we hope that our discussion here will serve as a foundation for a meaningful and ongoing global dialogue” (NASEM, 2016d). All three nations embraced the statement’s call for continued research on gene editing, further deliberation with regard to heritable changes, and a continued public discourse on the topic.10 The summit provided important input to the present study, as did other studies by the NAS and the NAM on related topics (see Box 1-2). BOX 1-2 Related Studies of the NAS and the NAM Genome Editing in Nonhuman Organisms Because genome-editing methods such as the CRISPR/Cas9 system are simply tools, they can be applied in myriad ways to achieve genetic changes in cells in the laboratory, in microbes, in nonhuman organisms, or in human subjects. The present study, which focuses on the use of genome editing in humans, is part of a broader examination by the U.S. National Academies of the implications of genome editing across a number of applications that also includes projects addressing the following: · Genetically Engineered Crops: Experiences and Prospects—This report addresses safety, environmental, regulatory, and other aspects of food crops developed through the use of genetic engineering technology. Such crops can be produced using a number of methods, and new genome-editing tools are among them (NASEM, 10Statement by Ralph J. Cicerone, President, U.S. National Academy of Sciences; Victor J. Dzau, President, U.S. National Academy of Medicine; Chunli Bai, President, Chinese Academy of Sciences; Venki Ramakrishnan, President, The Royal Society; d January 24, 2017). Copyright © National Academy of Sciences. All rights reserved. Human Genome Editing: Science, Ethics, and Governance 14 HUMAN GENOME EDITING PREPUBLICATION COPY—SUBJECT TO FURTHER EDITORIAL REVISION 2016c). · Gene Drives on the Horizon: Advancing Science, Navigating Uncertainty, and Aligning Research with Public Values—This report focuses on a specific application enabled by CRISPR/Cas9 technology that allows genetic changes to spread in a population in the absence of selective advantage. This technology is not applicable to every species and is most