But before we condemn all future efforts to perform germline editing, let’s remember one important safety issue. A typical somatic gene-editing procedure in an adult might involve fixing the DNA of 100 million cells or more. “Each one of them is a different CRISPR event, any one of which could hit a tumor suppressor gene,” cautions George Church, who co-founded a company to do clinical genome editing. The consequences of that event as a cell amplifies could be serious. “But when you put it in an embryo, it is a single event, so the a priori probability of hitting a tumor suppressor exon is a billion times lower. How is that more risky?”13
Another egregious aspect of the CRISPR babies’ saga was the suspect manner in which JK obtained informed consent from the volunteer couples and the intense secrecy in which he conducted the experiments. “This was not a case of science outpacing ethical guidance or the law,” said Oxford University ethicist Dominic Wilkinson. “There were guidelines in place that warned against research of this sort. This appears to be a researcher who had no interest in attending to ethical guidelines relating to scientific research.”14 “The whole angle about germline editing per se is a red herring,” tweeted Leonid Kruglyak, chair of human genetics at UCLA. “It’s the blatant disregard of all the rules and conventions we have in place for how one should approach *any* proposed intervention.”
“Unborn children obviously cannot consent to an embryo-altering procedure,” said New York University bioethicist Art Caplan,15 although fetuses aren’t able to consent to anything much, including conception. Contravening accepted ethical standards, JK personally led the informed consent discussion. “The simple fact that he was directly involved in trying to get consent from the patients is a huge problem. You should never do that,” said Lovell-Badge. It is common for an independent third party to explain the risks to the patient or volunteer.
But the notion that JK somehow pressured hapless Chinese couples to take part in his quest for glory is diminished by the haunting words of one of the couples that participated in the trial. They framed their participation against the pervasive backdrop of HIV stigma and discrimination in Chinese society. In a letter shared with Benjamin Hurlbut, they wrote:
We were never misled. It was a form of compromise. The object of the compromise was society, and one could even say with the whole world. As an AIDS sufferer and family member, we firmly and deeply know that it is possible to use a preventative drug to have a healthy child… That drug can cure disease, but it cannot cure prejudice…
For everyone who is listening, please hear this. At a certain level our participation in the experiment was indeed forced, but we were not coerced by any person in particular. We were coerced by society.16
JK conducted his work in great secrecy. Indeed, it is remarkable that rumors did not leak out until Thanksgiving weekend 2018. Greely unequivocally condemned JK’s secret experiment that “against a near universal scientific consensus, privileged his own ethical conclusions without giving anyone else a vote, or even a voice.”17 And yet, while JK shielded his true ambitions from the scientific community, we now know he confided in his “circle of trust.” This included a trio of Stanford faculty—Quake, Porteus, and Hurlbut—as well as Hurlbut’s son Benjamin, DeWitt, Deem, Mello, and consultant Steve Lombardi.
Quake initially shrugged off media inquiries in the wake of the JK scandal, but as news of an official Stanford University inquiry spread, he finally broke his silence sharing communications and emails with the New York Times dating back to August 2016. Quake viewed JK as bright and ambitious—not uncommon among Stanford postdocs—but someone who might cut corners if needed. Quake insisted that he would have been “very aggressive about telling people” about JK’s intentions if he had any hints of misconduct. As Quake learned more about the pregnancy, he confided in two prominent scientists, but neither suggested he “notify the mythical science police.” Quake trusted that JK had the necessary ethical approvals and conceded he could have done more.18 The next day—Quake’s fiftieth birthday—Stanford officially cleared its three faculty members of any wrongdoing.19
Porteus wished he had done more in hindsight. The idea of breaking a confidence troubles him but if a patient plans to hurt themselves or others, a physician has an obligation to overrule the doctor-patient confidentiality and disclose. “Perhaps this fits that scenario where it’s such an egregious overstepping of bounds that it’s worth violating the unwritten culture,” he reflected.20
DeWitt habitually ignored media requests, so I was pleasantly surprised he agreed to talk to me. He doesn’t want his own career to be remembered for his interactions with JK. “It wasn’t just me telling him ‘no.’ He ignored everyone,” DeWitt said.21 “It was an evil and narcissistic quest to make this happen one way or another.… He should’ve been treated more like a criminal. He did things that were completely and utterly unacceptable and deeply unethical.” Now in Los Angeles, DeWitt is helping to treat sickle-cell patients using genome editing. In retrospect he wishes he had done more to report JK. “But it’s not exactly clear who I talk to?” Who indeed? The Dean? The director of the World Health Organization or the NIH? Antonio Regalado? Nobody knew what to do or where to turn.
It took a freedom of information request filed by the Associated Press to uncover Mello’s involvement with JK,22 although JK’s WeChat timeline left a clear trail. The Nobel laureate hastily resigned from JK’s company Direct Genomics after the CRISPR babies’ revelation. “Whistleblowing is never easy but we need a system where this does not happen again,” said Joyce Harper of University College London.23
Michael Deem has kept a vanishingly low profile since the JK scandal while Rice University conducts a confidential investigation. Deem’s lawyers, who specialize in white-collar crime, have sought to distance their client from any direct involvement in the gene-editing trial, despite Deem’s own admission (and visual evidence) that he participated in the informed consent process. Incredibly, eighteen months after the twins’ birth, my inquiries to Rice University are returned with an unobliging, unwavering note: “The investigation is ongoing.”
JK’s decision to implant genetically edited embryos was in flagrant defiance of every pronouncement and report on the ethics of germline editing. For almost four years, scientists and ethicists had grappled with the implications of CRISPR technology that were hurtling researchers toward the unthinkable. The warning signs were there before CRISPR burst on the scene. For example, in a 2009 story in the New York Times on the first gene therapy trial using genome editing, Porteus said: “In principle, there is no reason why a similar strategy could not be used to modify the human germ line,” quickly adding that he didn’t think society was ready for such a proposal.24
In January 2015, Doudna hosted a small retreat in Napa, California, where some fifteen invited experts, all Americans, discussed the potential misuses of CRISPR, including the prospect of engineering permanent, heritable fixes into human embryos. The guests included Asilomar veterans and Nobel laureates David Baltimore and Paul Berg, bioethicist Alta Charo, Carroll, Greely, Daley, and Church. Doudna’s concerns were amplified by her newfound celebrity status, which brought her to the attention of desperate parents. Amidst the emails pleading for help to find a cure for their child’s rare genetic disease were letters expressing unconditional love for the genetically disadvantaged. Doudna lost sleep worrying whether CRISPR could do more harm than good. “When I’m ninety,” she told Michael Specter, “will I look back and be glad about what we have accomplished with this technology? Or will I wish I’d never discovered how it works?”25 Or as Specter put it, “Not since J. Robert Oppenheimer realized that the atomic bomb he built to protect the world might actually destroy it have the scientists responsible for a discovery been so leery of using it.”26