year, a number of articles and commentaries appearing in scientific journals and the popular press called attention to scientific and ethical challenges that would be posed by CRISPR/Cas9 and similar genetic tools (Bosley et al., 2015; Editing Humanity, 2015; Lanphier et al., 2015; Maxmen, 2015; Specter, 2015). Professional bodies, international organizations, and national academies of sciences and medicine further raised the profile of genome editing by issuing statements on its appropriate uses, particularly in reference to the potential for creating heritable genetic modifications. Among others, they included the U.K. Academy of Medical Sciences and a number of collaborative partners; the European Group on Ethics in Science and New Technologies, an advisory body to the president of the European Commission; the Council of Europe; and the International Society for Stem Cell Research (AMS et al., 2015; Council of Europe, 2015; EGE, 2016; Friedmann et al., 2015; Hinxton Group, 2015; ISSCR, 2015). The United Nations Educational, Scientific and Cultural Organization (UNESCO) (2015) issued updated guidance to Copyright © National Academy of Sciences. All rights reserved. Human Genome Editing: Science, Ethics, and Governance 16 HUMAN GENOME EDITING PREPUBLICATION COPY—SUBJECT TO FURTHER EDITORIAL REVISION reflect genome-editing advances. Others launched activities to examine the implications of genome editing in greater detail, including the Académie Nationale de Médecine (France) (ANM, 2016); Institut Nationale de la Santé et de la Récherche Médicale (France) (INSERM; Hirsch et al., 2017); Berlin-Brandenburg Academy of Sciences and Humanities (BBAW, 2015); National Academy of Sciences Leopoldina in partnership with the Deutsche Akademie der Technikwissenshaften (National Academy of Science and Engineering: “acatech”); Union of German Academies of Sciences and Humanities, and German Research Foundation (Leopoldina 2015); Federation of European Academies of Medicine; UK Academy of Medical Sciences (FEAM and UKAMS, 2016); Royal Netherlands Academy of Arts and Sciences (KNAW, 2016); Nuffield Council on Bioethics (Nuffield Council, 2016b), and others (see Box 1-3). BOX 1-3 Excerpts from Selected Calls Around the World for Continued Study and Public Discussion China, the U.K. and the U.S. This is an important moment in human history and we have a responsibility to provide all sections of society with an informed basis for making decisions about this technology, especially for uses that would affect generations to come. (NASEM, 2016d) France “Our recommendations include setting up a European committee of experts from different disciplines to assess the scope, efficacy and safety of CRISPR–Cas9, and reviewing the ban on all genetic modifications to the germline” (Hirsch et al, 2017). “[We recommend the] establishment of multidisciplinary discussions on the questions posed by the techniques for the germline and embryonic genome editing...considered as part of a wider debate on all the medical technologies...with potential effects on the genome of unborn children and, possibly, that of subsequent generations” (ANM, 2016). Germany “It is important to have an objective debate that informs all stakeholders in a clear and transparent manner about the status of research and development into the techniques, and to ensure that any decisions taken are based on sound scientific evidence” (Leopoldina, 2015) The Netherlands “Public debate would give patients, care providers and society an opportunity to discuss controversial issues, to assess the risks, advantages and conditions of potential germline applications based on growing scientific insight, and to develop good practices and further regulation” (KNAW, 2016). UK “Active early engagement with a wide range of global stakeholders will therefore be needed, which should include, but not be limited to, biomedical and social scientists, ethicists, healthcare professionals, research funders, regulators, affected patients and their families, and the wider public” (AMS et al., 2015). Copyright © National Academy of Sciences. All rights reserved. Human Genome Editing: Science, Ethics, and Governance INTRODUCTION 17 PREPUBLICATION COPY—SUBJECT TO FURTHER EDITORIAL REVISION The Technologies New or improved tools facilitate scientific progress by making it possible to investigate new kinds of questions and to generate new solutions. In the area of health and medicine, scientists and clinicians have long sought to apply the techniques of molecular biology to understand basic biology—including embryonic development, physiology, and the immune and nervous systems—and to treat or prevent disease. Much progress has been made in elucidating the role of genetics in diseases, ranging from sickle-cell anemia, muscular dystrophy, and cystic fibrosis, to such conditions as deafness, short stature, and blindness. The development of many such diseases and conditions has a genetic component. Some result from straightforward single-gene changes, but most involve a complex interplay of genetic, environmental, and other factors that remain only imperfectly understood. Furthermore, genetic sequences themselves paint only part of the biological picture. Regulation of how and when genes