Responsible Use of Human Gene-Editing Technologies.

Responsible Use of Human Gene-Editing Technologies Victor J. Dzau 1 and Ralph J. Cicerone 2 President, National Academy of Medicine; 2 President, National Academy of Sciences. Over the last 40 years, a remarkable series of technological developments have greatly advanced scientists’ ability to manipulate genetic material. Current techniques for genome editing allow for more highly specific and efficient modification of DNA than previous editing tools. 1 Researchers can investigate gene function in various organisms, such as plants, insects, mice, zebrafish, and even human cell lines in vitro. In theory, the technol- ogy is capable of introducing or correcting single point mutations, 2 regulating transcription, 3 or even epigenetic modifications, 4 and therefore holds great promise for medicine. One powerful and efficient tool for genome engi- neering uses the clustered regularly interspaced short palindromic repeat (CRISPR) nuclease Cas9 to cut sequences specified by guide RNA molecules. This technique is in widespread use in research and has already engineered the genomes of more than a dozen species. In April, a Chinese research team 5 reported editing the genomes of human embryos using the CRISPR/Cas9 system. However, there are significant scientific and technical questions about the efficacy and risks of these technologies. The Chinese research team reported that the embryos were ‘‘mosaic,’’ meaning that only some cells had the desired changes, and there were a large number of ‘‘off-target effects’’ or mutations in nontargeted genes that were likely to be harmful if the embryos had been viable. Their work also raised significant concerns on the social and ethical aspects of human gene editing, especially on human embryos. Gene-editing technologies hold great promise for advancing science and improving human health. For instance, the genomes of plants and animals could be modified to boost agriculture and food production, and the technology potentially could be used to edit somatic cells to cure genetic diseases such as sickle cell disease. 6 However, these tech- nologies also raise a number of ethical and social considerations. Of particular concern is the poten- tial to make permanent modifications to human DNA in the nuclei of cells in eggs, sperm, or human embryos that are then passed down to succeeding generations. This is known as human germline editing. As a result, the National Academy of Sciences and the National Academy of Medicine are laun- ching a major initiative to guide decision making about research involving human gene editing. 7 We have appointed a multidisciplinary advisory group that will help steer our initiative. This fall, we will host an international summit to assemble researchers and other experts to explore the sci- entific, ethical, and policy issues associated with human gene-editing research. In addition, the academies will convene a multidisciplinary, inter- national committee to undertake an in-depth study to examine the scientific underpinnings; clinical implications; and ethical, legal, and social aspects of the use of current and developing human ge- nome editing technologies in biomedical research and medicine. The study will take a global per- spective, and committee members will represent a wide range of expertise from diverse disciplines such as bioethics. The academies have a history of providing lead- ership on emerging and controversial technologies. In 1975, the National Academy of Sciences convened the Asilomar conference, a landmark turning point for recombinant DNA research that resulted in guidelines for recombinant DNA research. 8 Our Correspondence: Victor J. Dzau, National Academy of Medicine, 500 5 th Street, NW, Washington, DC 20001. E-mail: vdzau@nas.edu; Ralph J. Cicerone, National Academy of Sciences, 500 5 th Street, NW, Washington, DC 20001. E-mail: naspresident@nas.edu HUMAN GENE THERAPY, VOLUME 26 NUMBER 7 a 2015 by Mary Ann Liebert, Inc. DOI: 10.1089/hum.2015.29004.vjd j