Editing Humanity: The CRISPR Revolution and the New Era of Genome Editing

CHAPTER 18 CROSSING THE GERMLINE

The CRISPR babies scandal triggered a torrent of outrage and op-eds castigating JK. “Sooner or later it was bound to happen,” physician and author Eric Topol wrote in the New York Times hours after JK’s last public appearance in Hong Kong. “The potential risks to the babies grossly outweighed any benefits to them, and to science,” judged Hank Greely, a Stanford law professor.

But it was science writer Ed Yong who best framed the sheer scope and magnitude of JK’s transgressions. Writing in the Atlantic, Yong compiled a list of the major medical and ethical criticisms leveled at JK’s work and the community’s potential culpability. Under normal “rogue scientist” circumstances, a Top Ten list should have sufficed to capture the violations. Without much difficulty, Yong came up with no fewer than fifteen “damning details” of the JK affair. I can’t improve on that, so here’s the full list:¹

He didn’t address an unmet medical need.

The actual editing wasn’t executed well.

It’s not clear what those new mutations will do.

There were problems with informed consent.

He operated under a cloak of secrecy…

… but organized a slick PR campaign.

A few people knew about He’s intentions but failed to stop him.

He acted in contravention of global consensus.

He acted in contravention of his own stated ethical views.

He sought ethical advice and ignored it.

There is no way to tell whether He’s work did any good.

He has doubled down.

Scientific academies have prevaricated.

A leading geneticist (George Church) came to He’s defense.

This could easily happen again.

As the saying goes, there’s a lot to unpack there. We had reached a turning point in human history. The fictional and hypothetical warnings over decades about the perils and immorality of human genetic engineering were suddenly manifest in the form of twin babies. By excavating the germline of a pair of human embryos, JK had crossed a red line of medical practice and ethics. Had he put his ideas up for public debate or previewed them before the scientific community, he would have been shot down before he could even pick up a pipette.

Let’s take the first three items on Yong’s list. Just as David Liu had asked JK directly in Hong Kong, what was the unmet medical need for this couple? Why did JK pick HIV and CCR5? Why was genome editing even necessary given that JK’s team performed sperm washing prior to IVF to remove any risk of HIV? JK could not give Liu a straight answer, so instead he painted the scourge of HIV in broader terms. “I truly believe that not just for this case but for millions of HIV children, they need this protection because a vaccine is not available. I have personally experienced ‘AIDS village’ where 30 percent people were infected. They had to give their children to relatives.” JK said that he was proud of his work; the twins’ father had been depressed but had pledged to work hard and take care of his new family.

AIDS has claimed an estimated 35 million lives. There are an estimated 37 million people worldwide infected with HIV, including more than 800,000 in China. The advent of a cocktail of antiretroviral drugs is one of the great recent medical success stories. These drugs can suppress the titer of HIV to undetectable levels and effectively abolish the risk of HIV transmission through sex. An advertisement from antiviral drugmaker Gilead, spotted in a Broadway theater playbill, said: “Dear HIV, We didn’t give up. XOXO, Science.”

Earlier discussions about which disorders might prove candidates for heritable gene surgery seldom considered HIV, which was stuck in the “definitely maybe” category. Inactivating CCR5 to enhance protection against HIV isn’t in the same category as correcting a disease-causing mutation. But JK had identified two major reasons for his choice: safety and “real world medical value.”² He cited two decades of research on CCR5 and related clinical trials.³ He also considered his gene surgery as relatively simple, seeking to disrupt the CCR5 gene to scuttle the HIV receptor rather than trying to perform precision DNA surgery, swapping one letter in a gene for another, as would be needed if attempting to treat patients with muscular dystrophy or sickle-cell disease.

Worldwide about 100 million people carry the CCR5 Δ32 mutation, with the highest concentration among northern Europeans. All evidence suggests the deletion is safe. If JK had edited the CCR5 gene to mimic the naturally occurring Δ32 mutation, the scientific community’s concerns might have been muted. But the mutations JK engineered in Lulu and Nana did not produce the Δ32 deletion, raising serious questions about the impact of these man-made genetic alterations, never before seen in humans or tested in an animal model. JK targeted a spot in the CCR5 gene where he could land the Cas9 nuclease, like pointing a cursor on a particular word. But he couldn’t accurately control the extent of the edit itself. “These two lives are now an experiment, a matter of scientific curiosity, which is an outrageous way to relate to human lives,” said Ben Hurlbut.⁴

Sean Ryder, an RNA biologist at the University of Massachusetts Medical School, vented his fury on Twitter during the summit and subsequently in The CRISPR Journal. “Doudna warned us this might happen,” Ryder wrote. “I had trusted that my fellow scientists would ensure that human trials involving embryonic genome editing would be done transparently, ethically, and with strong moral purpose.”⁵ But no.

In Nana, both copies of CCR5 harbor so-called frameshift mutations: one copy carries a small deletion of 4 bases (-4), whereas the other copy actually has an insertion of a single base (+1); both mutations disrupt the natural phase of the genetic code.^I It is possible, even likely, that these mutations would abrogate the function of CCR5 similar to the Δ32 mutation. But we don’t know for certain. These mutations are “never-before-seen variants of unknown significance,” said Ryder. “They might inactivate CCR5 activity and block HIV uptake, but they might also incur new risks.”

The situation in Lulu was even less clear-cut: one copy of the gene appeared to be untouched, while the other carried a fifteen-base deletion. The resulting loss of five amino acids in the middle of an otherwise intact protein might abolish the function of CCR5 but this has never been tested. Moreover, in both twins, the edits appeared to be mosaic, meaning that not every cell in the twins carried the gene edits. Mosaicism is a natural phenomenon in biology—think heterochromia, a condition that results in different colored eyes. But no doctor, certainly not JK, could say with conviction that he had first done no harm.

There were also serious questions about off-target effects, despite JK’s denials, including some evidence that such an effect had occurred in Lulu, and others could be uncovered if more rigorous whole genome sequencing were performed. Ryder closed his CRISPR Journal commentary with an impassioned plea:

It is my fervent hope that Lulu and Nana will lead long healthy lives. It is certainly possible, even plausible, that they will remain healthy based upon what is known about CCR5. However, there are enough uncertainties about the function of the mutations to raise clear scientific objections to the work, in addition to the moral and medical objections. I pray that Lulu and Nana are never exposed to HIV. I hope we never have a chance to find out if the experiment ‘worked.’ To me, the best outcome is that the babies are unaffected by the procedures of the He lab. Worse outcomes are possible.⁶

Even the assumption that deactivating CCR5 neatly thwarts HIV with no other health consequences started to crumble. The Δ32 mutation arose in northern Europe but as Lovell-Badge pointed out “there are almost no people with the Δ32 mutation living in China. Therefore, it is necessary to ask why?”⁷ Although it is likely that the deletion hasn’t had time to spread through Asia, another possibility is that the CCR5 mutation might have some other impact on health. We know Δ32 increases the risk of West Nile and possibly influenza. And some have even questioned the dogma that inactivating CCR5 protects against HIV. Apparently there are rare strains of HIV, including one called X4, that bypass CCR5 by using a different portal into the cell.⁸

Months after the twins’ birth, more disturbing scenarios hit the news. “China’s CRISPR twins might have had their brains inadvertently enhanced,” screeched a trademark Regalado headline.⁹ Alcino Silva, a UCLA neurobiologist, said the CCR5 mutations might damage cognitive function in the twins—based on his work in mice. His team’s latest data suggested that individuals lacking CCR5 recover more quickly from strokes, while carriers of a single inactive CCR5 gene perform better in school.¹⁰ Meanwhile, a pair of Berkeley researchers mining the UK Biobank—a charity- and government-funded database of genomic and medical information on more than 500,000 Brits—reported that individuals with two copies of the Δ32 mutation were 20 percent more likely to die before age seventy-six than people with one normal copy of CCR5.¹¹ Media reports pounced on the supposed threat to the CRISPR babies’ life expectancy (ignoring that the twins’ edits were not the Δ32 deletion). But some excellent sleuthing by Sean Harrison, an epidemiologist at the University of Bristol in the UK, highlighted a systematic error in the study, leading eventually to its retraction.¹²

The CCR5 story spotlights a critical issue: how can we be certain that editing any gene will not have some unforeseen, knock-on, collateral damage? Our 10 trillion cells are sacks containing vast interconnected networks of protein-protein, RNA, and other biomolecular interactions laden with intracellular hubs and vesicles, membranes and molecular machines. When I studied biochemistry in college, we naïvely thought the key metabolic pathways of a cell could be displayed neatly on a wall poster. Today, we know that each of the more than 20,000 proteins in a cell interacts with dozens if not hundreds of other proteins. Predicting what happens next when editing any one of these important cogs and spokes may be possible one day with advances in artificial intelligence, but not today.

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

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.

One year later, the UK’s Nuffield Council on Bioethics concluded that germline editing might be “morally permissible” if it respected the well-being of the edited individual and did not exacerbate discrimination. “So long as heritable genome editing interventions are consistent with the welfare of the future person and with social justice and solidarity, they do not contravene any categorical moral prohibition,”³⁸ the report said. Being British, the report politely suggested that talks on an international governance framework should happen “sooner rather than later.” The editor of the Lancet, Richard Horton, welcomed the findings. “Given the current state of the world, where national solipsism is on the rise and scientific developments can sometimes take place unchecked, there is no time to waste: the recommendations should be put into practice immediately.”³⁹

For all of their prestige, authority, and credentials, ultimately the NASEM and Nuffield declarations came down to the results of small groups of experts with a strong Western bias trying to reach a consensus. As Sarah Chan, a bioethicist at the University of Edinburgh, put it, there is no shortage of edicts in genome editing. The National Academy listed seven principles, the Nuffield report two more. There were five dozen more reports stacked high in her office. “We don’t need more ‘principles’!” Chan said.⁴⁰ But for JK, the refusal to issue a blanket prohibition of germline editing from either of these two prestigious bodies was tantamount to lifting a velvet rope. Or as Ed Yong put it, “it’s as if he took the absence of a red light as a green one.”

In October 2018, JK submitted an essay on his own ethical guidelines—built around the five bullet points he had shown Regalado and Kiani—to The CRISPR Journal. I communicated with Ryan Ferrell in advance and invited submission, thinking the essay might offer an interesting ethical perspective on genome editing from within China, although I’d never heard of JK, the group leader. The authors didn’t say anything about conducting clinical research or implanting human embryos, nor did they disclose any conflicts of interest. The absurdity of that became clear the moment the CRISPR babies story broke. Specter called JK’s ethical guidelines “admirable… if only He had spent more time reading them over, he might have skipped this stunt.”⁴¹ In retrospect, the commentary appeared to be a sly effort to lay the ethical groundwork for the blockbuster report on the CRISPR babies’ birth. A few weeks later, the journal’s chief editor, Rodolphe Barrangou, ordered a retraction.⁴²

Where do we go from He? Or here? Two new highly credentialed commissions were launched in the aftermath of the JK fiasco. The World Health Organization (WHO) established an expert advisory committee tasked with “Developing global standards for governance and oversight of human genome editing.” The geographically diverse eighteen-member group kicked off in March 2019 in Geneva, Switzerland, under the leadership of Edwin Cameron, a South African supreme court justice, and former FDA commissioner, Margaret Hamburg. That first meeting stopped short of calling for a moratorium, but the committee did propose a global registry of germline editing research.

Another blue-ribbon committee was co-organized by NASEM and the Royal Society, chaired by Dame Kay Davies (no relation) and the Rockefeller University president Rick Lifton.⁴³ Both efforts received rare bipartisan support on Capitol Hill. Senator Dianne Feinstein tabled a resolution condemning JK’s actions and supporting the work of the commissions. “It’s vital that the United States lead the way in creating ethical standards for gene-editing research,” said Senator Marco Rubio, who cosigned the bill.⁴⁴

These reports will be important but unlikely to be the final word. We debate the pros and cons of human embryo editing without having any real comprehension of the research under discussion. In August 2018, I attended a conference at Cold Spring Harbor. (One of the sponsors creatively offered vials of mosquito repellant to help the throngs of scientists survive the outdoors.) During a debate on editing of human embryos, Dieter Egli, a Swiss developmental biologist at Columbia University who works with human IVF embryos,⁴⁵ asked for a show of hands: “Who has any direct experience of working with human embryos?” Not a single arm went up. It was a stark reminder of how little we know about the earliest moments of life, even as we debate how we should proceed.

Amid the chorus of condemnation pointed at JK, one or two figures struck a different note. “It seems like a bullying situation to me,” commented George Church.⁴⁶ “The most serious thing I’ve heard is that [JK] didn’t do the paperwork right.” Church concluded the saga could go in one of two directions: a medical tragedy on a par with the death of Jesse Gelsinger or a landmark advance in medical technology similar to the birth of Louise Brown. “As long as these are healthy, normal kids, it’s going to be fine for the family and for the field,” he said.

Samira Kiani, who had met JK, agreed that a piling on JK was “not going to be useful in the long term.” She said, “We’re not eliminating future trials [by vilifying JK], we’re just pushing them underground. Similar scientists will not come forward.”⁴⁷ Kiani’s concerns made sense but her fears were misplaced. In Russia, as we’ll see, a bear was stirring. And in the Middle East, an early sign of genuine interest in replicating JK’s endeavors. One week after his revelation, on December 5, 2018, JK received an email from a fertility and gynecology clinic in Dubai. The email, shared publicly by William Hurlbut at the World Science Festival, read:

Dear He Jiankui,

Congratulations on your recent achievement of the first gene editing baby delivered by your application!… Our embryologist is interested in partaking in a course regarding CRISPR gene editing for Embryology Lab Application. Does your facility offer this type of course?…

Hurlbut advised JK not to reply.

I. The genetic code is read out in triplets, so if a DNA sequence is mutated by the insertion or deletion of 1 or 2 bases (any number that is not divisible by 3), it will fall out of phase, changing the corresponding amino-acid sequence. If a mutation is a small deletion or insertion of 3 bases (or any multiple of 3), then the results could still be devastating, but the sequence beyond the mutation will still be intact. A good example is the most common mutation in the cystic fibrosis gene, called ΔF508, the deletion of three bases that encode the amino acid phenylalanine.