research involves interventions with human subjects. In the United States and most other countries with robust regulatory systems, proposed clinical applications must undergo a supervised research phase before becoming generally available to patients. Clinical applications of genome editing that target somatic cells affect only the patient, and are akin to existing efforts to use gene therapy for disease treatment and prevention; they do not affect offspring. By contrast, germline interventions would be aimed at altering a genome in a way that would affect not only the resulting child but potentially some of the child’s descendants as well. Copyright © National Academy of Sciences. All rights reserved. Human Genome Editing: Science, Ethics, and Governance SUMMARY 3 PREPUBLICATION COPY—SUBJECT TO FURTHER EDITORIAL REVISION A number of the ethical, legal, and social questions surrounding gene therapy and human reproductive medicine provide a backdrop for consideration of key issues related to genome editing. When conducted carefully and with proper oversight, gene therapy research has enjoyed support from many stakeholder groups. But because such technologies as CRISPR/Cas9 have made genome editing so efficient and precise, they have opened up possible applications that have until now been viewed as largely theoretical. Germline editing to prevent genetically inherited disease is one example. Potential applications of editing for “enhancement”—for changes that go beyond mere restoration or protection of health—are another. Because genome editing is only beginning to transition from basic research to clinical research applications, now is the time to evaluate the full range of its possible uses in humans and consider how to advance and govern these scientific developments. The speed at which the science is developing has generated considerable enthusiasm among scientists, industry, healthrelated advocacy organizations, and patient populations that perceive benefit from these advances. It is also raising concerns, such as those cited earlier, among policy makers and other interested parties to voice concerns about whether appropriate systems are in place to govern the technologies, and whether societal values will be reflected in how genome editing is eventually applied in practice. Public input and engagement are important elements of many scientific and medical advances. This is particularly true with respect to genome editing for potential applications that would be heritable—those involving germline cells—as well as those focused on goals other than disease treatment and prevention. Meaningful engagement with decision makers and stakeholders promotes transparency, confers legitimacy and improves policy making. There are many ways to engage the public in these debates, ranging from public information campaigns to formal calls for public comment and incorporation of public opinion into policy. APPLICATIONS OF HUMAN GENOME EDITING Genome editing is already being widely used for basic science research in laboratories; is in the early stages of development of clinical applications that involve somatic (i.e., nonreproductive) cells; and in the future might be usable for clinical applications involving reproductive cells, which would produce heritable changes. Basic Science Laboratory Research Basic laboratory research involving genome editing of human cells and tissues is critical to advancing biomedical science. Genome-editing research using somatic cells can advance understanding of molecular processes that control disease development and progression, potentially facilitating the ability to develop better interventions for affected people. Laboratory research involving genome editing of germline cells can help in understanding human development and fertility, thereby supporting advances in such areas as regenerative medicine and fertility treatment. The ethical issues associated with basic science research involving genome editing are the same as those that arise with any basic research involving human cells or tissues, and these issues are already addressed by extensive regulatory infrastructures. There are, of course, enduring debates about limitations of the current system, particularly with respect to how it addresses the use of gametes, embryos, and fetal tissue, but the regulations are considered Copyright © National Academy of Sciences. All rights reserved. Human Genome Editing: Science, Ethics, and Governance 4 HUMAN GENOME EDITING PREPUBLICATION COPY—SUBJECT TO FURTHER EDITORIAL REVISION adequate for oversight of basic science research, as evidenced by their longevity. Special considerations may come into play for research involving human gametes and embryos in jurisdictions where such research is permitted; in those cases, the current regulations governing such work will apply to genome-editing research as well. Overall, then, basic laboratory research in human genome editing is already manageable under existing ethical norms and regulatory frameworks at the local, state, and federal levels. Clinical Uses of Somatic Cell Editing for Treatment and Prevention of Disease and Disability An example of the application of genome editing to alter somatic (nonreproductive) cells for purposes of treating or preventing disease is a recently authorized