PREPUBLICATION COPY—SUBJECT TO FURTHER EDITORIAL REVISION Use of Genome Editing for “Enhancement” Although much of the current discussion around genome editing focuses on how these technologies can be used to treat or prevent disease and disability, some aspects of the public debate concern other purposes, such as the possibility of enhancing traits and capacities beyond levels considered typical of adequate health. In theory, genome editing for such enhancement purposes could involve both somatic and germline cells. Such uses of the technologies raise questions of fairness, social norms, personal autonomy, and the role of government. To begin, it is necessary to define what is meant by “enhancement.” Formulating this definition requires a careful examination of how various stakeholders conceptualize “normal.” For example, using genome editing to lower the cholesterol level of someone with abnormally high cholesterol might be considered prevention of heart disease, but using it to lower cholesterol that is in the desirable range is less easily characterized, and would either intervention differ from the current use of statins? Likewise, using genome editing to improve musculature for patients with muscular dystrophy would be considered a restorative treatment, whereas doing so for individuals with no known pathology and average capabilities just to make them stronger but still within the “normal” range might be considered enhancement. And using the technology to increase someone’s muscle strength to the extreme end of human capacity (or beyond) would almost certainly be considered enhancement. Regardless of the specific definition, there is some indication of public discomfort with using genome editing for what is deemed to be enhancement, whether for fear of exacerbating social inequities or of creating social pressure for people to use technologies they would not otherwise choose. Precisely because of the difficulty of evaluating the benefit of an enhancement to an individual given the large role of subjective factors, public discussion is needed to inform the regulatory risk/benefit analyses that underlie decisions to permit research or approve marketing. Public discussion also is needed to explore social impacts, both real and anticipated, as governance policy for such applications is developed. The committee recommends that genome editing for purposes other than treatment or prevention of disease and disability should not proceed at this time, and that it is essential for these public discussions to precede any decisions about whether or how to pursue clinical trials of such applications. Public Engagement Public engagement is always an important part of regulation and oversight for new technologies. As noted above, for somatic genome editing, it is essential that transparent and inclusive public policy debates precede any consideration of whether to authorize clinical trials for indications that go beyond treatment or prevention of disease or disability (e.g., for enhancement). With respect to heritable germline editing, broad participation and input by the public and ongoing reassessment of both health and societal benefits and risks are particularly critical conditions for approval of clinical trials. At present, a number of mechanisms for public communication and consultation are built into the U.S. regulatory system, including some designed specifically for gene therapy, whose purview would include human genome editing. In some cases, regulatory rules and guidance documents are issued only after extensive public comment and agency response. Discussion is fostered by the various state and federal bioethics commissions, which typically bring together technical experts and social scientists in meetings that are open to the public. And the National Institutes of Health’s Recombinant DNA Advisory Committee offers a venue for general public Copyright © National Academy of Sciences. All rights reserved. Human Genome Editing: Science, Ethics, and Governance 8 HUMAN GENOME EDITING PREPUBLICATION COPY—SUBJECT TO FURTHER EDITORIAL REVISION discussion of gene therapy, for review of specific protocols, and for transmission of advice to regulators. Other countries, such as France and the United Kingdom, have mechanisms that involve formal polling or hearings to ensure that diverse viewpoints are heard. PRINCIPLES TO GUIDE THE GOVERNANCE OF HUMAN GENOME EDITING One of the charges to the committee was to identify principles that many countries might be able to use to govern human genome editing. The principles identified by the committee are detailed in Box S-1. The committee recommends that any nation considering governance of human genome editing can incorporate these principles¾and the responsibilities that flow therefrom¾into its regulatory structures and processes. BOX S-1 Principles for the Governance of Human Genome Editing 1. Promoting well-being: The principle of promoting well-being supports providing benefit and preventing harm to those affected, often referred to in the bioethics literature as the principles of beneficence and nonmaleficence. Responsibilities that flow from adherence to this principle include (1) pursuing applications of human genome editing that promote the health and well-being of individuals, such as treating or