LAUSR

the academic-discussion stage—we are completely in the real-world stage,” he says. Given the pace of development of CRISPR–Cas9 and other genome editing technologies, it’s a moot point whether the National Academies’ report, compiled by a group of US and international scientific, medical, legal and ethical experts, will have any impact in jurisdictions with little or no regulatory oversight. “It may be that the committee that authored the report felt a certain sense of inevitability,” says Urnov, who acted as a reviewer on the report. “That train has left the station, and the academies wished to set some standards before there is some rogue attempt at this that goes horribly wrong and achieves a lot more harm than good.” A small number of Western scientists, including Fredrik Lanner at the Karolinska Institute, in Stockholm, and Kathy Niakan at The Francis Crick Institute, in London, are using CRISPR–Cas9 to edit early human embryos. Each is studying the early events in embryonic development rather than researching the feasibility of producing genetically edited humans. “We want to see which genes are critical to establish normal early development and how pluripotent stem cells are established in the human embryo,” Lanner says. Scientists in China had previously published two studies that involved editing human embryos, each of which employed abnormal triploid embryos, which could never have fully developed (Protein Cell 6, 363–372, 2015; J. Assist. Reprod. Genet. 33, 581–588, 2016). The most recent study, conducted by Lichun Tang, at the National Center for Protein Sciences, in Beijing, and colleagues at the Third Affiliated Hospital of Guangzhou Medical University, in Guangzhou, used potentially viable diploid embryos generated from immature eggs discarded during in vitro fertilization (IVF) procedures. The research did not have any reproductive goals attached—the material used in the experiments was later destroyed. Nevertheless, it represents both a summary of the progress that has been achieved to date in human germline editing and a catalog of the obstacles that remain if the approach is ever to be considered an acceptable option for therapeutic use. The group created 20 zygotes by intracytoplasmic sperm injection of 20 wild-type oocytes with sperm obtained from heterozygous carriers of a mutation in either the hemoglobin subunit beta (HBB) gene, which causes beta-thalassemia, or in the gene encoding the enzyme glucose-6-phosphate dehydrogenase (G6PD), which causes favism, a metabolic condition that can give rise to hemolytic anemia. Four mutant-HBB and two mutant-G6PD heterozygotes resulted from the IVF step. Eighteen hours after intracytoplasmic sperm A report from two of the US National Academies released in February for the first time, adopts a cautiously permissive stance on editing the human germline, starting a process of normalizing what was once considered an absolute taboo in genetic research. The field had been edging closer to this position in recent years, following the emergence and rapid global adoption of the CRISPR–Cas9 genome editing system. Now, with the joint authorship of Human Genome Editing: Science, Ethics, and Governance by the National Academy of Sciences and the National Academy of Medicine, the nature of the discussion has quickly changed from a tentative exploration of the issues (Science 348, 36–38, 2015) to the considered view of two authoritative and influential bodies. The report’s publication was quickly followed by a genome editing study from China, the first to use potentially viable human embryos (Mol. Genet. Genomics doi: 10.1007/s00438017-1299-z, 2017). Scientists and clinicians have started contemplating what was once unthinkable—the introduction of changes to the human genome that can be passed on from generation to generation. The report stresses that human germline editing should be considered only for serious conditions where no reasonable alternatives are available and for which convincing evidence exists that mutations in a particular gene cause or contribute to the disorder in question. It states that trials of such therapies should be contemplated only in situations where the risk–benefit analysis is credible, and where broad oversight and follow-up across several generations are possible. The public should also have a role in assessing the wider societal risks and benefits, it argues. As for the use of germline editing technologies for genetic enhancement, the report explicitly rules this out. How these caveats are interpreted and implemented will, of course, vary in different sociopolitical and cultural contexts. The bottom line is that our species is on the brink of what will be, in all likelihood, an irrevocable change. “We’ve witnessed over the past 60 years— since the era of Franklin, Watson and Crick—a fairly dramatic speed of translation of basic research to practice,” says Fyodor Urnov, a pioneer of gene editing with zinc finger nucleases while at Sangamo Biosciences, of Richmond, California, and now associate director of the not-for-profit Altius Institute for Biomedical Sciences, in Seattle. “We are completely out of CRISPR–Cas9 gives scientists a way to edit faulty genes that cause devastating diseases out of the human germline. Te tr a Im ag es / A la m y St oc k P ho to NEWS