The National Academy of Sciences arranged summits and reports in an attempt to set some boundaries. In 2017 the academy concluded that using Crispr for human genetic enhancement was a hard no. But they stopped short of a full moratorium. What about gene editing to address serious, incurable diseases? Well, that could maybe one day be fine, provided it was proven safe and effective. But that 2017 report didn’t spell out exactly how one might prove those things…Still, the revelation that someone had gotten as far as he [He Jiankui] had sent scientists and policymakers scrambling to lay down some firmer ground rules. China formed a national ethics committee tasked with enforcing the country’s new clinical research guidelines. The World Health Organization assembled a panel to establish global regulatory standards for governments to follow. (Its first order of business was to urge all nations to put a hold on any experiments that would lead to the births of more gene-edited humans until the implications of such work could be more fully examined.) And another National Academies commission was formed. This one was international—with 18 members from 10 nations—and was assigned a less sprawling task: to set clear, explicit, scientific standards for heritable gene editing in humans.
On Thursday, after more than a year of work, the commission finally released its 225-page report—the most comprehensive and highly technical such document to date. It describes in great detail the types and quality of evidence that scientists must provide to show they’ve correctly edited an embryo, before they can attempt to try it out in humans. It is, in essence, a road map for how to safely and responsibly get to clinical trials. But importantly, say the report’s authors, it’s not an endorsement.
“No attempt to establish a pregnancy with a human embryo that has undergone genome editing should proceed unless and until it has been clearly established that it is possible to efficiently and reliably make precise genomic changes without undesired changes in human embryos”, the report states. “These criteria have not yet been met and further research and review would be necessary to meet them.”
…For that reason, the authors of the report lay out exactly how many and what kind of off-target effects might be acceptable. They put that threshold at no more than the average rate of new mutations an embryo spontaneously acquires. DNA replication isn’t perfect, and most people are born with a few dozen mutations that don’t exist in either of their biological parents’ genomes. Gene editing shouldn’t introduce any more genetic variations than occur naturally, the authors concluded, and the types of changes should be carefully studied in the lab to make sure they don’t lead to adverse outcomes.
The trouble is, though, that right now there aren’t any good methods for assessing off-target effects in embryos. Doing so requires collecting large amounts of DNA, which can only be done by sacrificing a number of cells from the embryo for genetic sequencing. In addition to being unreliable, these methods harm the viability of the embryo, making it less likely to result in a pregnancy. It could take years for better methods of evaluation to be developed, says commission member Haoyi Wang, a reproductive biologist at the Institute of Zoology and Institute for Stem Cell and Regeneration at the Chinese Academy of Sciences. “From the genome editing to the genome sequencing of a single embryo, there are still many gaps to be filled”, Wang told reporters at a press briefing Thursday.
The commission was more narrowly focused on addressing these sorts of scientific gaps, while other authorities, like the WHO, will look more broadly at how societies might decide to accept human germline editing and how governments will regulate the technology. Developing ethical frameworks can’t just be about autonomy, privacy, and justice, says commission member Bartha Maria Knoppers, who directs the Centre for Genomics and Policy and serves as the Canada Research Chair in Law and Medicine at McGill University in Montreal. “For me, scientific quality and safety are primordial ethical considerations; they’re not peripheral”, she says. “I think this report reflects the emphasis on getting those aspects right.”