It is to Doudna’s credit that rather than shirk her responsibility or focus on research, she set about starting the conversation. In their recap of the Napa meeting,27 Baltimore, Doudna, and colleagues warned against any attempts to initiate human germline experiments to allow more debate among many stakeholders, including the public, and more research on the safety of CRISPR gene editing. But at least one meeting attendee wondered, “There may come a time when, ethically, we can’t not do this.”28
In seeking a sensible middle ground, a “prudent path” as they put it, Baltimore and Doudna inevitably drew flak from both flanks. Robert Pollack, a Columbia University geneticist, argued their recommendations were inadequate, opening the door to eugenics. “The best in the world will not remove the pain from those born into a world of germline modification but who had not been given a costly investment in their gametes,” Pollack said. Only a complete ban on germline modification would prevent such a powerful force for individualized medicine from becoming “the beginning of the end of the simplest notion of each of us being ‘endowed by our Creator with certain inalienable rights.’ ”29 But Stanford’s Henry Miller dismissed such abstract concerns as insensitive to the suffering of patients in need. Germline gene therapy should be used sparingly, he said, but “we don’t need a moratorium. We do need to push the frontiers of medicine to rid families of monstrous genetic diseases.”30
One of the recommendations from Doudna’s retreat was the need to widen the debate. A major conference on the ethics of genome editing took place at the National Academy of Sciences, overlooking the National Mall in Washington, DC, that December. It was a rare joint appearance (excluding prize ceremonies) by the three biggest names in CRISPR circles—Doudna, Charpentier, and Zhang. “We are close to altering human heredity,” said Baltimore. “The overriding question is when, if ever, we will want to use gene editing to change human inheritance.”31 Baltimore quoted Huxley’s Brave New World, in which he imagined “a society built on the selection of people to fill particular roles in society with environmental manipulation to control the social mobility and behavior of the population.” Huxley “couldn’t have conceived of gene editing,” Baltimore continued, but we should still heed his warnings as we assess “this new and powerful means to control the nature of the human population.”32
For three days, scientists, physicians, ethicists, and philosophers debated the dangers and potential applications of human germline editing. Although in the minority, some spoke out strongly in favor of germline editing, at least in principle. Manchester University philosopher John Harris quipped, “If sex had been invented, it would never have been permitted or licensed… it’s far too dangerous!” But the most electrifying moment came not on stage but from the audience. Sarah Gray rose up and spoke tearfully about the birth of her son with anencephaly, who suffered seizures for a week before his death. “If you have the skills and the knowledge to eliminate these diseases, then freakin’ do it!” she pleaded.
Summit organizers argued long into the night before issuing a closing statement agreeing on two main principles: first, issues of safety and efficacy must be resolved before contemplating germline editing. Second, there should be a broad societal consensus about each application. Germline editing mistakes can’t be corrected with a product recall notice. The ensuing New York Times story by Nicholas Wade opted for the M word, the headline reading: “Scientists seek moratorium on edits to human genome.” But summit organizers had deliberately refrained from issuing a direct call for a total ban on germline editing research. Rather, they felt it would be “irresponsible to proceed” with embryo editing until there was a broad societal agreement on the safety, value and wisdom of the technology. The M word debate would resurface a few years later.
The DC conference triggered a lengthy succession of ethics reports from scientific societies and ethical groups in Europe, Asia, and North America. More than sixty organizations issued reports and policy statements, some running two hundred pages or more. But the net result was more confusion than clarity.33 More than half of these reports concluded that no clinical germline editing should be performed, concerned about safety, medical necessity, and informed consent. Among them was a short statement from President Obama’s chief scientist, John Holdren, who declared “The Administration believes that altering the human germline for clinical purposes is a line that should not be crossed at this time.”34
Amid the noise, two reports—one American, one British—stood out for their provenance and thoroughness. On Valentine’s Day, February 2017, the National Academies of Science, Engineering and Medicine (NASEM) released a detailed report on human genome editing.35 The bill creating the National Academy of Sciences was signed into law by President Lincoln in 1863, at the height of the Civil War. The blue-ribbon committee, cochaired by Rick Hynes, a British expat molecular biologist at MIT, and the bioethicist Alta Charo, worked for more than a year to draft the report.
Surprisingly, the NASEM report left ajar the slim possibility of future clinical germline editing applications to correct genetic diseases—although not for enhancement. Trials could occur for “the most compelling circumstances,” subject to comprehensive oversight that would protect patients “and their descendants,” with safeguards against “inappropriate expansion” to less compelling uses. The committee offered a top ten list of criteria to support any future use of clinical germline editing, including: no reasonable alternatives to preventing a serious disease; genes should be edited to known DNA variants associated with ordinary health; and appropriate monitoring of patients and privacy protections.
Despite the preconditions, the report struck a much different tone than the DC summit fifteen months earlier. Far from saying germline editing was irresponsible and needed broad societal consensus, the NASEM committee concluded there was nothing inherently wrong with using germline editing to treat disease or disability. In a wood-paneled room at NAS, Hynes justified the change in stance. “In the past, there has been a line drawn by many that says one should refrain editing heritable features. That was mostly because there was no way of considering how to do that at all… so nobody was arguing that it should be done.”36 This was a brand new day.
It was a significant course correction from “impermissible as long as risks have not been determined” to “permissible if risks are accurately determined.”37 The report even left open the possibility of genetic enhancement, but only after public discussion. “Caution is needed, but being cautious does not mean prohibition,” said Charo.