Scientific advances in molecular biology over the past 50 years have produced remarkable progress in medicine. Some of these advances have also raised important ethical and societal issues – for example, about the use of recombinant DNA technologies or embryonic stem cells. The scientific community has consistently recognized its responsibility to identify and confront these issues. In these cases, engagement by a range of stakeholders has led to solutions that have made it possible to obtain major benefits for human health while appropriately addressing societal issues.
Fundamental research into the ways by which bacteria defend themselves against viruses has recently led to the development of powerful new techniques that make it possible to perform gene editing – that is, precisely altering genetic sequences – in living cells, including those of humans, at much higher accuracy and efficiency than ever before possible. These techniques are already in broad use in biomedical research. They may also enable wide-ranging clinical applications in medicine. At the same time, the prospect of human genome editing raises many important scientific, ethical, and societal questions.
After three days of thoughtful discussion of these issues, the members of the Organizing Committee for the International Summit on Human Gene Editing have reached the following conclusions:
1. Basic and Preclinical Research. Intensive basic and preclinical research is clearly needed and should proceed, subject to appropriate legal and ethical rules and oversight, on (i) technologies for editing genetic sequences in human cells, (ii) the potential benefits and risks of proposed clinical uses, and (iii) understanding the biology of human embryos and germline cells. If, in the process of research, early human embryos or germline cells undergo gene editing, the modified cells should not be used to establish a pregnancy.
2. Clinical Use1: Somatic. Many promising and valuable clinical applications of gene editing are directed at altering genetic sequences only in somatic cells – that is, cells whose genomes are not transmitted to the next generation. Examples that have been proposed include editing genes for sickle-cell anemia in blood cells or for improving the ability of immune cells to target cancer. There is a need to understand the risks, such as inaccurate editing, and the potential benefits of each proposed genetic modification. Because proposed clinical uses are intended to affect only the individual who receives them, they can be appropriately and rigorously evaluated within existing and evolving regulatory frameworks for gene therapy, and regulators can weigh risks and potential benefits in approving clinical trials and therapies.
3. Clinical Use: Germline. Gene editing might also be used, in principle, to make genetic alterations in gametes or embryos, which will be carried by all of the cells of a resulting child and will be passed on to subsequent generations as part of the human gene pool. Examples that have been proposed range from avoidance of severe inherited diseases to ‘enhancement’ of human capabilities. Such modifications of human genomes might include the introduction of naturally occurring variants or totally novel genetic changes thought to be beneficial.
Germline editing poses many important issues, including: (i) the risks of inaccurate editing (such as off-target mutations) and incomplete editing of the cells of early-stage embryos (mosaicism); (ii) the difficulty of predicting harmful effects that genetic changes may have under the wide range of circumstances experienced by the human population, including interactions with other genetic variants and with the environment; (iii) the obligation to consider implications for both the individual and the future generations who will carry the genetic alterations; (iv) the fact that, once introduced into the human population, genetic alterations would be difficult to remove and would not remain within any single community or country; (v) the possibility that permanent genetic ‘enhancements’ to subsets of the population could exacerbate social inequities or be used coercively; and (vi) the moral and ethical considerations in purposefully altering human evolution using this technology.
It would be irresponsible to proceed with any clinical use of germline editing unless and until (i) the relevant safety and efficacy issues have been resolved, based on appropriate understanding and balancing of risks, potential benefits, and alternatives, and (ii) there is broad societal consensus about the appropriateness of the proposed application. Moreover, any clinical use should proceed only under appropriate regulatory oversight. At present, these criteria have not been met for any proposed clinical use: the safety issues have not yet been adequately explored; the cases of most compelling benefit are limited; and many nations have legislative or regulatory bans on germline modification. However, as scientific knowledge advances and societal views evolve, the clinical use of germline editing should be revisited on a regular basis.
4. Need for an Ongoing Forum. While each nation ultimately has the authority to regulate activities under its jurisdiction, the human genome is shared among all nations. The international community should strive to establish norms concerning acceptable uses of human germline editing and to harmonize regulations, in order to discourage unacceptable activities while advancing human health and welfare.
We therefore call upon the national academies that co-hosted the summit – the U.S. National Academy of Sciences and U.S. National Academy of Medicine; the Royal Society; and the Chinese Academy of Sciences – to take the lead in creating an ongoing international forum to discuss potential clinical uses of gene editing; help inform decisions by national policymakers and others; formulate recommendations and guidelines; and promote coordination among nations.
The forum should be inclusive among nations and engage a wide range of perspectives and expertise – including from biomedical scientists, social scientists, ethicists, health care providers, patients and their families, people with disabilities, policymakers, regulators, research funders, faith leaders, public interest advocates, industry representatives, and members of the general public.
1 “Clinical use” includes both clinical research and therapy.