He Jiankui, a young Chinese scientist known to his American colleagues as JK, dreamed of remaking humanity by exploiting the emergent technology of gene editing. He had academic polish, and an aptitude for securing institutional support. As a student, he had left China for the United States, where he did graduate work in physics at Rice and a postdoc in a bioengineering lab at Stanford. At the age of twenty-eight, he was recruited into a prestigious Chinese government program for foreign-educated talent, and was offered a founding position in the biology department of the Southern University of Science and Technology.
SUSTech was a newly created research institute in Shenzhen, a city in the midst of a biotech boom. JK, who arrived in 2012, likened Shenzhen’s startup culture to that of Silicon Valley—bold creativity was encouraged, and there was plenty of capital on hand. With colleagues from his lab, he often held brainstorming sessions at a café near campus, delineating his plans. In the first ten years, he would tackle a variety of genetic diseases; in the ten years after that, he’d extend the human life span to a hundred and twenty years. In a PowerPoint that he presented at the café, he wrote, “As a result of promoting genome editing, humanity is smarter, stronger, and healthier. Humanity enters an age of controlling destiny.”
JK’s agenda was spectacularly ambitious, and the pace he projected was aggressive—lifetimes of work in mere decades. To start, he would focus on what he believed was an achievable task: eradicating a disease governed by a single gene. He selected AIDS, an illness regarded in China as both pernicious and shameful but one for which there might be an elegant fix. H.I.V. enters human cells by way of a receptor created by a gene called CCR5. JK planned to use the gene-editing tool CRISPR to disrupt CCR5 in human embryos, which would, in theory, render the babies impervious to infection.
The experiment required volunteers, and, through a chat group associated with an H.I.V./AIDS charity, he began recruiting couples: H.I.V.-positive men married to uninfected women. Chinese law denies in-vitro fertilization and adoption to H.I.V.-positive people, and natural conception carries a risk of transmission. For couples with an infected partner, JK’s program was a chance at parenthood. It promised confidentiality, which was critical for a marginalized community; an H.I.V. diagnosis in China can cost a person his job. The treatments would take place discreetly, at facilities where only key employees were aware of the experiment.
JK’s “vaccine,” as he described it, was intended to break a cycle of stigma, encoding protection that would be passed down through generations. Not only would the babies be immune to H.I.V.; their children would be, too. One volunteer wrote that, when he got a letter accepting him into the program, “I smiled and I shed a great many tears. The country loved us after all and hadn’t given up on us.”
Editing human embryos for reproduction is taboo in the world of genetic engineering; the possibility is too great that a scientist will accidentally introduce mutations that harm the subject and affect future generations. JK knew that he would need to manage his experiment’s unveiling carefully. But in November, 2018, Antonio Regalado, an investigative journalist at MIT Technology Review, discovered data that JK’s lab had uploaded to a Chinese registry for clinical trials. Believing that the data might indicate the existence of an edited human fetus, Regalado sent it to Fyodor Urnov, an expert on gene editing, for verification. “I did not want to open that file,” Urnov told me. “I’m, like, ‘Please, please, please, no. Nobody’s that crazy.’ ” He shuddered, remembering the moment that his fear was confirmed. “I’m, like, Life will never be the same again.”
A few days later, as scientists from around the world prepared for a gene-editing conference in Hong Kong, JK released a series of YouTube videos, announcing the birth of a set of twins, edited as embryos with CRISPR. A slim, nervous-seeming man in a pale-blue shirt, he looked earnestly into the camera and said, “Two beautiful little Chinese girls named Lulu and Nana came crying into the world, as healthy as any other babies.” He went on to explain how, when each was only a single cell, he had used CRISPR to delete CCR5. “I understand my work will be controversial,” he said. “But I believe families need this technology, and I’m willing to take the criticism for them.”
China’s state-run media celebrated the news, but the scientific community reacted with dismay. A group of Chinese researchers condemned the study as madness. David Baltimore, a Nobel Prize-winning biologist who chaired the Hong Kong event, called it “irresponsible,” saying, “I think there has been a failure of self-regulation by the scientific community.” At the conference, JK had been scheduled to present preclinical data, involving mice, monkeys, and nonviable human embryos. Instead, the organizers insisted that he speak about the edited children.
After a few awkward moments, JK walked across the stage and stood before a lectern. “First, I must apologize that these results leaked unexpectedly,” he said, his forehead glazed with perspiration. He thanked his university, but maintained that it knew nothing of his endeavors. In a tense exchange that followed, he fielded questions from colleagues. Were there any unintended consequences of the edits? How many embryos had been modified? How many implanted? How many born? There were three edited babies, he acknowledged: along with Lulu and Nana, another was on the way.
As JK took questions, he looked like a schoolboy startled to be reprimanded when he’d been expecting praise. Alta Charo, a professor of law and bioethics who met him in Hong Kong, was struck by his combination of grandiosity and naïveté. “He seemed to truly believe in what he was doing,” she told me. “I figured he has to be deluding himself—not just others but himself—to be able to have such a sincere belief in something that logically made no sense.”
Video From The New Yorker
Swift Justice: A Taliban Courtroom in Session
To view this video please enable JavaScript, and consider upgrading to a web browser that supports HTML5 video
The Chinese government swiftly withdrew its enthusiasm for JK’s research, and, soon after he returned to the mainland, his lab was locked and he was placed under house arrest. In 2019, he was sentenced to three years in prison for “illegal medical practices,” and fined nearly half a million dollars. Two of his collaborators were given lesser sentences and fined. Among scientists, there was a pervasive sense of embarrassment. JK had misused a powerful technology and gambled with the health of children—experimental subjects he himself had created—without, in the scientists’ view, a compelling medical reason to compensate for the risk. Urnov told me, “He has taken a jar of tar, poured it over the field of CRISPR, and left an indelible stain. We will never wash that stain off. I am prepared to say that he’s not a fellow-scientist. He’s persona non grata.”
JK was released from prison in the spring of 2022, and quickly resumed his efforts at gene editing. When I spoke to him by Zoom this past January, he was in Shenzhen, with his wife and two young daughters, celebrating a spring festival. The family, he said, was moving to Beijing, where he was opening a new laboratory. He was posting regularly on Twitter, interspersing job listings for lab positions with blue-sky images of him teeing off on the golf course.
JK is thirty-nine, and wore a blue oxford shirt and a tweed blazer. He said that his new lab would be a nonprofit providing affordable gene therapy for rare conditions, and that he would focus first on Duchenne muscular dystrophy, a fatal disease that causes irreversible muscle damage, primarily in boys. This time, his patients would be not embryos but young children desperate for a cure. I asked if it was an attempt to redeem himself in the scientific community. “I don’t know if I’d use the word ‘redeem,’ ” he said. “I want to do it to help people today.”
Copy link to cartoon
Link copied
Shop
Open Gallery
He refused to discuss his embryo-editing experiment in any detail. Rocking back and forth as he spoke, he periodically broke out in uncomfortable laughter. “Hmm! I don’t know,” he said, smiling, when he was dodging a question. I asked if Lulu, Nana, and the third baby, Amy, knew that they had been edited. He looked at the ceiling and smiled. “I’m not going to answer this,” he finally replied. But he did want to dispel a rumor that had been circulating online. “The twins were not killed or sterilized,” he said. “They are living happily with their parents.”
As for the debacle that his experiment had caused, JK would admit to no greater error than bad timing. “I do acknowledge that I have done it too quickly,” he said. In one of his YouTube videos, he predicted that in twenty or thirty years gene-edited babies will no longer be controversial, or even remarkable. He likened himself to the pioneering founder of the field of I.V.F., Robert Edwards, whose career had followed a heroic arc. In 1978, when the first I.V.F. baby was born, Edwards was a figure of scandal and opprobrium. In 2010, he was awarded the Nobel Prize.
CRISPR, which may be the single most transformative biological technology of the twenty-first century, is a natural phenomenon, evolved over billions of years. It was first observed in the nineteen-eighties, when researchers noticed unexplained sequences of viral DNA in E. coli. Eventually, they realized that these sequences played a role in the bacteria’s immune system: they could find and destroy other pieces of viral DNA. Isolated and distributed in tiny vials to laboratories around the world, CRISPR would become the primary tool of genetic engineering. A couple of drops, introduced by pipette to a cell, could reliably cut the double strand of DNA, changing the function of its genes. Research that once consumed years of a scientist’s career could now be completed in a few weeks.
The CRISPR system is often likened to a pair of scissors. In 2012, Jennifer Doudna and Emmanuelle Charpentier found a hand to direct those scissors: a guide-RNA protein that could target specific genes. It was a monumental discovery, and in 2020 they won the Nobel Prize.
Doudna and Charpentier’s method was highly replicable and relatively inexpensive. You can buy a vial of CRISPR and a guide RNA on the Internet for a few hundred dollars. Gene-editing research has accelerated rapidly, along with efforts to commercialize the technology. Doudna, a professor at Berkeley, founded the Innovative Genomics Institute to study practical applications of CRISPR, and five companies to exploit the discoveries.
CRISPR promised to transform medicine, providing a way to cure a patient of genetic disease by editing the DNA of the affected tissues. That form of editing is known as “somatic”; the changes it introduces are limited to the individual patient. Editing an embryo, by contrast, changes the DNA of the embryo’s future eggs or sperm—its “germline”—causing modifications that will pass down to subsequent generations. As CRISPR became available, a broad consensus emerged among scientists that they should, at least for the time being, resist the temptation to make heritable changes to the human genome. CRISPR was too new and too poorly understood. “You never know what you will introduce,” Charpentier told me. “Is it the realization of a nightmare?”
The precarity recalled an earlier moment in bioscience: the advent of gene splicing, which allows DNA from disparate species to be combined. In 1975, amid fears of superpathogens and laboratory leaks, scientists gathered at a conference center at Asilomar State Beach, in California, to discuss the hazards and the potential. Their work resulted in guidelines adopted by the National Institutes of Health. According to Hank Greely, who directs the Center for Law and the Biosciences at Stanford, it also had a dampening effect on further regulation, by discouraging Congress from imposing more restrictive laws.
Like Charpentier, Doudna recognized the danger posed by the new technology. In 2014, she read a paper by a group in China that had used CRISPR to modify monkey embryos and then successfully implanted them in a mother, creating “mutant” offspring with altered DNA. Monkeys, the researchers noted, “have served as one of the most valuable models for modeling human diseases.” To Doudna, this was a clear indication that human germline editing was next. “It made me feel like I needed to really get out in public about it and speak about the importance of responsible use of the technology,” she said.
Several months later, Doudna convened a group of scientists and ethicists in Napa. The event deliberately evoked the debates of the nineteen-seventies; two of the participants, David Baltimore and Paul Berg, had helped organize Asilomar. At the time, rumors were circulating about another Chinese study, this one using CRISPR to edit human embryos. The researchers, who soon published their work, had designed the experiment carefully, balancing on the threshold of societal acceptance; they worked with nonviable embryos and did not transfer them into a uterus. “They were covering their butts,” Greely, the Stanford professor, said. “When they were criticized, they could say, ‘We didn’t implant, and it wouldn’t even have worked if we did.’ ”
After Napa, Doudna and her colleagues outlined what they called “a prudent path” for genetic engineering. While there might eventually be circumstances in which heritable editing was acceptable, they wrote, CRISPR wasn’t yet ready. One major concern is that the CRISPR scissors don’t behave predictably: like the brooms in “The Sorcerer’s Apprentice,” they sometimes cut the targeted gene and then keep on cutting, leading to “off target” mutations. Even the “on target” edits can have negative consequences; disabling a gene can solve one health problem while creating another. (For instance, there’s a gene that has spread widely by natural selection through Africa, India, and Latin America because it protects against malaria. But the same gene, if both parents carry it, can cause sickle-cell disease, an excruciatingly painful blood disorder.) A further complication is that, as embryonic cells divide and multiply, and the CRISPR scissors keep snipping, they often fail to edit every cell. The growing embryo becomes a “mosaic” of edited and unedited DNA.
Doudna and her cohort weren’t the only ones who were concerned. In a 2015 position paper bluntly titled “Don’t Edit the Human Germline,” another group of scientists argued that the controversy over editing human embryos would imperil the prospects of somatic editing, which could save the lives of millions of people who were already alive and suffering.
It would be easy, they added, for heritable editing to be used to create “non-therapeutic modifications.” Fyodor Urnov, who was among the authors, said, “I’ll give you three use-case scenarios right now which we should be very afraid about. Fear number one: the weaponization of the military. We know how to make a human being who runs on four hours of sleep—I can tell you what mutation to make. Two: We know what gene to edit to reduce pain sensation. If I were a rogue nation wishing to engineer a next generation of quasi-pain-free special-forces soldiers, I know exactly what to do. It’s all published. And three: physical strength. You don’t need a large lab operation. You just need the ill will.”
In the United States, editing human embryos for reproduction is forbidden, and virtually all human-embryo research is ineligible for federal grants. Some seventy other countries limit heritable genome editing; there are explicit prohibitions in Canada, Brazil, Israel, South Korea, Japan, and Australia. But there is nothing approaching an international edict against the practice. In many jurisdictions, there are either no laws or no mechanisms to enforce them, and “jurisdiction shopping” is a pervasive problem.
Even in some places that have banned heritable genome editing, the consensus in the scientific community may be unstable. In 2017, the U.S. National Academies of Sciences, Engineering, and Medicine issued a report stating, “Heritable genome-editing trials must be approached with caution, but caution does not mean they must be prohibited.” Among other recommendations, the report proposed that any future trials be limited to preventing serious diseases, targeting genes well understood to cause those diseases, and converting those genes to versions that already exist in the human population. As JK began to implement his plans, he convinced himself that CCR5 met these criteria.
He Jiankui was born at home in 1984, into a farming family in Hunan Province. An outstanding student with an acute memory, he attended the University of Science and Technology of China, which is known as China’s Caltech. He majored in physics, and won a scholarship to continue his studies abroad. At Rice, he earned a Ph.D. in three years. In 2010, he entered a postdoctoral program at Stanford.
At Stanford, JK worked under Stephen Quake, a professor of bioengineering and applied physics who was also an inventor and entrepreneur, known for creating a blood test that radically simplified the detection of Down syndrome in fetuses. Quake is an imposing, broad-shouldered man, a heli-skiing enthusiast who has founded at least ten companies with a total value once estimated at $1.5 billion. His approach is multidisciplinary, stretching from fluid dynamics to immunology. “I blunder into other people’s domains without much courtesy,” he has said. An investor in several of his enterprises told a reporter, “Steve is out to hunt death down and punch him in the face.”
For decades, Stanford has encouraged its researchers to innovate, and to commercialize their discoveries. “That’s the spirit of Stanford,” JK told me. “You have an invention in the lab, then you have the duty to transfer the lab invention to a product that is given to people.” Quake epitomized that ethos, and JK worked hard to emulate him. He told me that, early in his time at Stanford, he approached Quake for guidance: “I said, ‘Hey, Steve, you’re a good scientist, and a very successful businessman as well. And, yeah, I want to be that.’ ”
While JK was working at Quake’s lab, studying flu vaccines, Steve Jobs died. As students and other disciples flocked to Jobs’s house, JK was struck by the outpouring of emotion. For a researcher, the pinnacle of accomplishment might be a publication in Nature that a hundred people read. “Jobs made something that benefits everyone,” JK said. “Even a kid could use the iPhone.”
In 2012, JK left Stanford for the Southern University of Science and Technology, where he described himself not as “a professor in the traditional sense” but as “a research-type entrepreneur.” His ties to top American universities were valuable to SUSTech, which was determined to become a world-class institution. He founded a joint laboratory with Michael Deem, his Ph.D. adviser at Rice, and set about commercializing one of Quake’s inventions, a method for sequencing DNA from a single molecule. With funding from angel investors and the city government, he started Direct Genomics, which sought to build a desktop sequencer for use in hospitals.
JK was a skilled networker—people responded to his sincerity and drive—and he stacked his company’s advisory board with prominent scientists from China and the U.S., including Craig Mello, a Nobel-winning biologist. Ryan Ferrell, an American publicist who worked with him, told me, “I think JK was definitely trying to build his own career outside from the shadows of Stephen Quake’s name.”
Like many of his peers, JK was captivated by CRISPR. In a document that he created called “Change the World,” he referred to it as “God’s magic scissors.” In 2016, he attended a CRISPR conference, and introduced himself to Jennifer Doudna, asking her to take a selfie with him, which he posted on his blog. Gene editors typically devote years to the study of one or two genes, governing one or two diseases. JK didn’t have time for that. He wanted to develop a product with the broadest possible relevance: a “genetic vaccine” that could prevent cancer, diabetes, Parkinson’s, and Alzheimer’s.
If JK was looking for permission to tinker with the human genome, he could find it, by implication, all around. George Church, the eminent Harvard scientist who is trying to bring back the woolly mammoth by editing elephant DNA, frequently invoked CCR5 on a list of “large impact” genes—which also included those that could make muscles leaner, bones stronger, and bodies less sensitive to pain. In 2017, JK met James Watson, a co-discoverer of the structure of DNA, and asked if it was acceptable to modify genes in an embryo. Watson, whose later career has been marred by unrepentant racism, gave him a handwritten response, which JK hung in his lab: “Make people better.”
JK began to conduct studies in mice, monkeys, and humans, using CRISPR to delete CCR5 in embryos that would not be implanted. It was important, he knew, to reflect an understanding of the ethical concerns that some of his Western colleagues were raising about editing human embryos. Presenting at a conference in 2017, he said, “We should do this slow, and with caution, because a single case of failure may kill the entire field.”
Even as JK urged patience, though, he had already recruited volunteers for a first-in-human clinical trial. The study promised to pay for I.V.F., delivery costs, an extended hospital stay, and health insurance for the babies. (It would also cover abortion costs in the case of a serious genetic defect.) All told, each couple would receive some forty thousand dollars’ worth of medical services and stipends.
Copy link to cartoon
Link copied
Shop
Open Gallery
Although the study was presented as a benefit to its subjects, its designer did not disguise his commercial interest. Volunteers were warned to “strictly observe the secrets of the project team” and forbidden to “disclose any commercial secrets.” JK would have the exclusive right to publicize the experiment, and to exploit imagery of the babies, including in elevators and on billboards and cars. The risk, however, rested with the subjects. The contract insured that the embryos would be tested before implantation, but it exempted the researchers from responsibility for any unexpected mutations.
JK limited the candidates to educated volunteers, making him less vulnerable to claims of exploitation. When he had assembled eight couples, fertility treatments began. In early 2018, he implanted an edited embryo in one of the women, but it didn’t take. Then he tried with another couple, Grace and Mark, implanting two CRISPR-modified embryos. These would become Lulu and Nana.
He Jiankui was an eclectic, constant note-taker—documenting meetings, underlining books, screenshotting, memorializing. He shared this trove of material with employees, propping his MacBook Air on a table while they gathered around. Though he now claims to recall little of the material or its creation, I was able to gain access to some of the files, which reveal a young man imagining himself on a historical stage. “Mission: science and technology changes the world,” he wrote. “Vision: China’s Edison.” In notes from a meeting with a potential collaborator, he jotted down a Chinese proverb: “You’re standing there talking, but your back isn’t the sore one.” The saying dismisses hand-wringers and armchair critics who gripe while others do the hard work.
Throughout 2017 and 2018, JK contacted dozens of fellow-scientists, including a number of Nobel winners, to get technical advice and build consensus around his project. Michael Deem, his Ph.D. adviser at Rice, was closely involved. A video leaked to Science shows Deem sitting at a conference table during an informed-consent conversation with potential volunteers. (Deem, who left Rice after the scandal broke, has said through an attorney that he “did not meet the parents of the reported CCR5-edited children.”) A member of the Chinese Academy of Sciences was also in the room. When questioned about his role, he acknowledged that he was there, but claimed he didn’t follow what was happening, adding that he often goes to meetings and doesn’t pay attention.
As JK made progress, he provided Stephen Quake with updates. The Times reported that in the spring of 2018 he sent an exultant e-mail: “Good News! The women [sic] is pregnant, the genome editing success!” Quake wrote back, “Wow, that’s quite an achievement!” Six months later, JK e-mailed again, letting Quake know that the babies had been born, and requesting a meeting in San Francisco to discuss “how to announce the result, PR, and ethics.” According to notes that JK kept in a document titled “Stephen Quake advice,” Quake was encouraging, saying, “Congratulations! You made something big! Your life will be changed.” He wrote that Quake also cautioned him to document everything, lest he be suspected of scientific fraud. (Quake, who is now, in addition to his role at Stanford, the president of the Chan Zuckerberg Biohub Network, says that JK’s notes mischaracterize his involvement.)
Some scientists later said that they felt duped by their encounters with JK: he would ask questions and posit research hypotheticals without revealing that his clinical trial was already under way. Many apparently expressed serious reservations about his project’s safety, ethics, and legality. “I’m glad for you, but I’d rather not be kept in the loop on this,” Craig Mello wrote when JK informed him of Grace’s pregnancy. Pei Duanqing, a prominent Chinese stem-cell biologist, was furious when he found out about the twins. He told JK that the research was an embarrassment, and warned him that he would go to jail.
JK proved impervious to criticism. He tended to cherry-pick good news, and had a cringey habit of name-dropping to create the illusion of broad support from prominent colleagues. Presenting his work in Hong Kong, he thanked William Hurlbut, a neurobiology professor at Stanford, who in fact had tried to dissuade him from proceeding. (Hurlbut, along with Quake and another professor whom JK consulted, were investigated by Stanford and cleared of misconduct.)
JK understood that his work needed to be framed correctly—as a miracle, not a catastrophe. Otherwise, he wrote in a strategy document, it could easily be “swallowed up by public opinion.” In early 2018, he reached out to Ferrell, the publicist, who had a background in science and spoke some Mandarin, and persuaded him to join the project. “He’s an enthusiastic, infectious individual who had a history of making stuff happen,” Ferrell told me. “It’s pretty easy to be convinced by him.”
Ferrell was alarmed to discover how far along JK was. “When I heard that a woman was pregnant, I thought, Oh, Jesus—I don’t think she’s understood what she’s done. There’s no way that CRISPR is ready for this,” he said. Nonetheless, he agreed to steer JK through the critical next few months. “I thought I might have some influence with this guy,” he said. “That was a very naïve thought.”
Ferrell moved to Shenzhen, and got his first look at JK’s lab. Afterward, he texted his partner, “This is just totally fucked.” He told me, “There’s a whole bunch of issues in recordkeeping there that were just atrocious.” The preliminary animal studies that JK had conducted to test the safety of the procedure were undermined when someone in the lab deleted raw data. (JK says that the data were later recovered, and denies that there were problems with recordkeeping.) Meanwhile, Ferrell said, “the pregnancy was a ticking clock.” He recalls that he confronted JK, saying, “You can’t do any more human implantations. You need to take care of this woman and these two children with your full attention. And you should spend all of your time looking for what could have gone wrong.” Nevertheless, the experiment continued. A total of thirty-one embryos were created and treated with CRISPR; six women were implanted with edited embryos.
That August, JK travelled to the United States on behalf of his genome-sequencing company. Increasingly worried about his judgment, Ferrell thought to introduce him to John Zhang, a Chinese-born reproductive endocrinologist who has two I.V.F. clinics in New York. Zhang had been involved in a controversy two years earlier, for conducting a procedure in which he transferred mitochondrial DNA from one egg to another, which he then fertilized, creating a so-called three-parent baby. Mitochondrial transfer is banned in the United States, so Zhang implanted the new egg into his patient in Mexico, where, he said, “there are no rules.” The F.D.A. censured him amid a frenzy of publicity.
Ferrell thought that Zhang’s experience would serve as a cautionary tale. Instead, he said, “they met and instantly, unfortunately, became friends.” JK’s notes from the meeting suggest that Zhang took an unusually bullish stance on gene editing. “Zhang supports genome editing even for human enhancement purpose,” he wrote. “People do cosmetic surgery to become beautiful, why is it wrong to do it at birth, there is no difference.” As for the embryo-editing project, JK noted, “Zhang encouraged me to move on to clinical trial and ignore the ethics controversy.”
JK and Zhang agreed to collaborate on a for-profit center in Hainan, where a special economic zone supported investment and eased regulations. In a draft of a presentation that they used to pitch officials, they proposed creating “China’s Mayo Clinic,” a world center for gene editing and mitochondrial transfer, which would soon generate a hundred and forty million dollars a year. “Because of ethical and social disagreements, the development of these technologies has been held back,” the presentation states. In Hainan, though, “certain medical products and medical technologies can be imported and used before they are approved” by Chinese regulators. They proposed a meeting with President Xi Jinping, because “genome editing has to become a national strategic point”—what electronics was to Japan in the eighties, and the Internet was to the U.S. in the nineties. By 2020, they predicted, “Chinese genome-editing products will become fashionable around the world.” (Zhang did not respond to requests for comment, but he previously told Science that he had abandoned any plans of working with JK.)
At the time, a Chinese regulation forbade “genetic manipulation on gametes, zygotes, and embryos for the purpose of reproduction,” but enforcement was lax, and there were no criminal penalties attached. According to Eben Kirksey, a medical anthropologist who has written a book about the CRISPR babies, various government officials encouraged JK to pursue his experiments; perhaps, in the light of a scientific breakthrough, the rules would be flexible. One of his confidants, a high-ranking Communist Party official in Beijing, ran economic development for the Thousand Talents Plan, a recruitment and funding program that, in 2017, gave JK a cash grant. Ferrell told me the official “said that he would offer support as long as it wasn’t too controversial.” Locally, JK had an ally in Xie Bingwen, the deputy head of a district in Shenzhen. Ferrell said that Xie, who took JK to see a village where AIDS was rampant, “was a direct supporter, and influenced JK’s choice of CCR5.”
China is notorious for its surveillance programs, and yet, Ferrell told me, JK was notably indiscreet. He wasn’t trying to hide his project; he was trying to attract support. “JK was speaking with the military-hospital head in the lobby, with security guards listening,” he said. “He had his lab meetings in a café right near SUSTech, talking loudly out in the open.”
China, like many other countries, has a formal ethical-review process for research on human subjects, which draws on the Nuremberg Code, adopted after the atrocities of Nazi human experimentation. JK filed an application for approval with HarMoniCare Shenzhen Women’s and Children’s Hospital, a high-end clinic. His project, he wrote, would be the greatest medical achievement since the invention of I.V.F. He cited the 2017 report by the U.S. National Academies of Sciences, Engineering, and Medicine, saying that it had endorsed “experimental study on the gene editing of embryos as therapeutics for the treatment of serious diseases.” He left out the report’s many caveats, including a warning that the science was not yet safe for use in humans.
HarMoniCare granted the approval. But, Ferrell told me, the procedures—egg extraction, fertilization, CRISPR, and implantation—did not take place there. They were performed instead at a hospital in Guangzhou, where JK did not have approval but did have a relationship with a compliant doctor. (The hospital did not respond to a request for comment.) When Quake learned of this discrepancy, he urged JK to resolve it, saying that it was imperative to have approval from all the participating institutions. According to JK’s notes, Quake warned him, “Everything you do will be carefully viewed with a magnifying glass, and you must address the ethics.” JK wrote that Quake also provided some tactical advice for overcoming concerns: “Tell the director of the hospital that if the hospital agrees to the ethics, their hospital would instantly become well-known globally,” and that a “great medical accomplishment would be born there.” (Quake denies coaching JK in this way.)
According to Ferrell, the administrators of the Guangzhou hospital were informed of the procedures that had taken place there only after the twins were born, at which point they hurriedly signed a document recognizing HarMoniCare’s approval and “backdated the form to CYA.” During the investigation, HarMoniCare said that its ethics committee had never met to review the approval, suggesting that JK had forged the form. Ferrell argued that this was “deceptive”—that the real fraud was on the part of the hospital in Guangzhou. He said, “That’s a messier truth that points to a system affected by more than one ‘rogue scientist.’ ”
In the months before the twins’ birth, JK girded himself to justify his choices. The CCR5 gene was well studied—familiar to researchers, and even to some sectors of the general public. A decade earlier, the world had learned about CCR5 through the seemingly miraculous case of the Berlin Patient, an H.I.V.-positive man in Germany. The patient, who later revealed that his name was Timothy Ray Brown, was dying of leukemia, and needed a stem-cell transplant, so his doctor proposed finding a donor with a mutation that disabled CCR5. (This mutation occurs naturally in about one per cent of Northern Europeans.) Brown agreed, and, on the day of his transplant, he stopped taking antiretroviral medicine; when tests afterward found no detectable virus, he was declared the first person ever to be cured of H.I.V.
The success of the Berlin Patient, JK believed, provided some assurance that editing CCR5 could work in a human subject. But gene surgery is not required to prevent H.I.V. infection, and questions about JK’s true motivations have persisted. Studies have shown that CCR5-edited mice exhibit marked improvements in cognitive function and memory—a golden egg of eugenics. “He used the excuse that he was trying to confer H.I.V. resistance,” one prominent stem-cell scientist told me. “I suspect it was an attempt at enhancement.”
Along with the potential benefits, editing CCR5 may have significant drawbacks. The same gene that creates a receptor for H.I.V. also helps protect the body from West Nile virus and the flu. Without it, Lulu, Nana, and Amy could be more vulnerable to infection. There is also evidence that disrupting CCR5 affects bone growth. Had JK created superpeople? Or had he inadvertently condemned unconsenting not-yet-born victims to potentially serious health problems?
Similar anxieties accompanied the birth of Louise Brown, the first I.V.F. baby, in 1978. For years, controversy had been growing about the possibility of “test-tube babies,” along with dire warnings that they could be severely deformed. The interest in Brown was as intense as the skepticism about the process. A camera crew was present at her delivery, at a hospital in England. After she was born—healthy—an I.V.F. expert told the Washington Post that the science wasn’t yet settled, saying, “The normality of the offspring is still somewhat in question.” Test tubes stained with fake blood were sent to her parents’ home by groups opposing what they considered unnatural and immoral conception. Brown, who is now forty-five, was an involuntary celebrity before she was born, and is still pursued by news crews from as far away as Uzbekistan.
Three years after Brown’s birth, Elizabeth Carr became the first baby born by I.V.F. in the United States. Armed guards were posted in the hospital, and her parents received hate mail. “For anybody that had a problem with the way I was born, it always came down to: You’re tampering with nature,” Carr told me. “You’re playing God.”
As a child growing up in public, Carr said, she felt enormous pressure to prove her normalcy. Her birthdays, like Louise Brown’s, were celebrated with major media coverage. At checkups, in addition to monitoring the regular developmental indicators, doctors subjected Carr to psychological testing; she remembers having her brain waves measured. “I was part of many studies up until my late twenties,” she told me. “At that point, they finally kind of gave up. ‘We can’t find anything wrong with her.’ ”
Copy link to cartoon
Link copied
Shop
Open Gallery
Carr works at a genetic-testing company, which screens for mutations and abnormalities in embryos before they are implanted. (Pre-implantation genetic testing is increasingly common in I.V.F., and is often cited as a reasonable alternative to embryo editing.) I asked what she thought when she heard about Lulu and Nana’s births. “I remember thinking, Oh, I hope that the press doesn’t go after that,” she said. “These kids had no say, right? Regardless of how they got here, they’re here now.”
Because of the stigma associated with H.I.V. in China, JK and his team took pains to protect the subjects’ anonymity. Lulu, Nana, and Amy are pseudonyms; so are Mark and Grace. This shield became more crucial once controversy erupted. Mark and Grace were the object of death threats online; five days after the twins’ birth was revealed, Ferrell received a message from a worried member of the research team. “Mark and Grace is extremely pressure,” he wrote. “They are consider suicide with Lulu Nana. So please release no more news. No one disturb them. Let it calm down.”
In the five years since the experiment, very little information has come out about the twins, and almost none about Amy; all that is known is that she was born sometime in 2019. According to Ferrell, while JK was in prison his wife assumed responsibility for supporting the families, sending money for their medical care, until the government interceded. The volunteers, induced to participate by the stigma associated with H.I.V., now faced an even more threatening stigma for their children: they were the world’s first edited humans, and society might reject them as dangerous mutants.
From the moment the children’s existence was made public, scientists have clamored for information about their genetic health, amid dire warnings of likely abnormalities. Because JK’s data have never been published, experts have been left to pore over his short talk at the Hong Kong conference and an accompanying slide presentation, and to scrutinize his few statements. In one of his YouTube videos, he said that he had sequenced Lulu and Nana’s entire genome before implanting the embryos, and again after they were born. The results, he said, indicated that the procedure had worked safely, as intended. “No gene was changed except the one to prevent H.I.V. infection,” he said.
This was, at best, a gross oversimplification. In the Northern European variant of CCR5 deletion, thirty-two base pairs of DNA are missing from both the maternal and the paternal chromosomes. JK’s results didn’t match this standard. Instead, in one twin, he had created a novel mutation of thirteen base pairs—probably but not definitely enough to prevent an H.I.V. infection. The other twin had one mutated and one normal copy of the CCR5 gene, weakening the prospect of immunity.
Another serious concern is that both twins are likely genetically “mosaic,” made up of edited and unedited cells, which may mean that neither of them has any special resistance to H.I.V. at all. Kiran Musunuru, a prominent gene editor, argued that JK’s work was not a CRISPR breakthrough—it was “a graphic demonstration of attempted gene editing gone awry.”
The same scientists who condemned JK for conducting the experiment remain intensely curious about its results. Even if the research was abhorrent, the data were unprecedented and potentially significant. Why not learn from them? David Baltimore, who has suggested a registry for gene-edited children, told me, “It should be studied, and we do not know whether there is anybody studying these children. JK is silent on that, and the Chinese authorities are silent.”
Last year, two Chinese ethicists published a paper calling on the government to provide “special protection” for the children, including ongoing examination of their genomes, access to psychological treatment, and the establishment of a center to study diseases that may arise from the edits. “It is a fact that CRISPR-edited persons form a new group in human beings,” they wrote. “So is there any moral difference between this new group and the rest of human beings?”
In our conversations, JK reiterated that the edited children are “living happily with their parents,” and said that he and his research team are still available to the families. Although his informed-consent documents included a plan for eighteen years of medical support, genetic testing, and the release of data to the public, JK opposes the idea of a research institute devoted to the CRISPR babies. Their privacy is too important, especially now that the experiment that brought them into existence is viewed as monstrous. “I always put the happiness of the family first,” he said. “If they need any support on any health issues of the children, they will contact me.”
Ferrell believes that even routine medical treatment will be complicated for the families. “There’s always this risk that a new doctor is going to say, ‘Oh, my God, you’re those people.’ And their identities might be revealed locally. And so then what does that do? Does your child start getting lower levels of care because you simply don’t seek it? I think there’s an absolute critical need for these families to receive confidential medical care outside of China.”
This past March, several hundred of the world’s leading genetic scientists convened at the Francis Crick Institute, in London, for the Third International Summit on Human Genome Editing. Long planned as the final such conference to address the CRISPR revolution, it was the first time the group had gathered since the 2018 Hong Kong conference, and the meeting became a de-facto referendum on the legacy of JK’s work.
On a plaza in front of the institute’s swooping façade, a small group of protesters held up a banner that read “STOP DESIGNER BABIES.” Inside, an exhibit called “Cut + Paste” invited the public to share views on gene editing: “Would you erase disease? Would you enhance your body? Where would you draw the line?” Researchers presented the latest developments, particularly in somatic genome editing. One patient, Victoria Grey, delivered a moving account of her arduous and groundbreaking treatment. After having her bone-marrow cells edited with CRISPR, she was now functionally cured of sickle-cell disease.
Leading up to the London summit, JK had appeared at various academic meetings—part of an apparent comeback campaign. The summit participants began to dread the possibility that he would show up in London, too. “Crisis management started months ago,” Eben Kirksey, the medical anthropologist, told me at the conference. In a series of worried phone calls, the scientists had discussed how they might react to his presence: “Would we have security take him out? Would we welcome him in?” As it turned out, JK skipped the conference. Instead, he posted a short video on Twitter, congratulating his colleagues on a successful meeting and offering some “ethical principles” for genome editing, as if he were not the most reviled figure in the field.
In JK’s absence, his work was invoked as an aberration, a bug that had been fixed. There were discussions of laws, regulations, and problems of enforcement, including an entire session devoted to reforms that China has made since JK’s breach; in 2021, it amended its criminal code to ban the implantation of edited human embryos. Benjamin Hurlbut, a bioethicist at Arizona State University who is the son of Stanford’s William Hurlbut, has been deeply engaged with JK since before his arrest. He told me that his punishment and excommunication provided a false resolution, allowing other scientists to pursue their work without facing its implications. “It was a geopolitical P.R. move,” he said. “He has become a kind of scapegoat onto which you collect the pollution in the community.”
The summit made it clear that genetic engineering continues to move, albeit gingerly, toward the future that JK sought to hasten into existence. On the last morning, there was a panel during which British and American scientists were celebrated for their laboratory work editing human embryos—the same kind of work that, when it was done in China nearly a decade ago, caused Western scientists to mobilize and write editorials. When the question of ethics arose, the panelists mumbled uncomfortably and passed the mike. The situation struck a delegate from China, who asked not to be named, as absurd. Afterward, he called out to me, “See the double standard?”
For many in the field, the ethics of editing human embryos are contingent on the science. When the protocol is safe—when the problems of unintended mutations and mosaicism are solved in the lab—the urgency of exploiting the new technology to save lives seems likely to push any remaining reservations aside.
Shoukhrat Mitalipov, a researcher at Oregon Health & Science University, in Portland, runs one of two laboratories in the U.S. that edit human embryos; his lab is unique in being authorized to use donated human eggs, rather than relying solely on discards from I.V.F., which are typically of lower quality. Mitalipov, who was born in Kazakhstan, is a small, dark-haired man with a lilting accent. His office has a view of the Willamette River, and its walls are decorated with patents, cover stories from Nature and Cell, and front-page newspaper writeups of his work. For the past decade, he has been conducting preclinical studies on embryos, working to eliminate mosaicism. “We have very high-bar standards,” he told me. “If you have a hundred embryos, ninety-nine probably have to be purely repaired. There should be no side effects.” At that point, he believes, the technology will be ready to use to prevent disease in human beings. (His other interest is in mitochondrial transfer—“three-parent babies”—which he is pursuing in countries where it is permitted. Last year, he helped an I.V.F. clinic in Athens conduct the procedure on twenty-five infertile families, resulting in six births, and he is now planning a full clinical trial outside the United States.)
Mitalipov is an undaunted advocate for heritable editing in humans. A hundred million people suffer from rare genetic diseases, and he believes that somatic editing can do only so much to help them. “It’s not going to alleviate transmission to the next generation,” he said. “The diseases will keep recurring over and over. If you want to really get rid of the root, you have to go back to the germline.” The idea behind somatic editing, he said, is “Let them be born and then we will deal with them.” Heritable editing, by contrast, is meant to cure disease before it can manifest—and eventually to eradicate disease altogether. Among other arguments, he notes that gene editing is more efficient than later interventions. “It’s one cell versus the whole body,” he said.
Mitalipov studies genes that cause hypertrophic cardiomyopathy, a heart condition that afflicts one in five hundred people, and is the leading cause of sudden death in young athletes. In 2017, he published a paper focussed on one of those genes, showing that he had been able to use CRISPR to disrupt it without creating off-target edits, and with only limited instances of mosaicism.
The lab is divided into spaces designated for working on mouse embryos (where the equipment is federally funded) and for working on human embryos (where it is not). In the human-embryo room, I met Nuria Martí Gutierrez, the lab’s chief embryologist. She had three eggs to fertilize that day, two from the donor program and one an I.V.F. discard. Working under a microscope, she prepared a petri dish with three drops of oil. To the first, she added the CRISPR solution. In the next, she placed sperm, donated from the hospital’s cardiac department, that had a deleterious mutation at the MYH7 gene, a cause of hypertrophic cardiomyopathy. To the third drop, she added an oocyte—an egg.
Martí Gutierrez moved the dish over to a larger microscope, equipped with pipettes manipulated by joysticks. With a narrow, bevel-tipped pipette, she bopped a sperm on the tail, immobilizing it so that she could draw it into the pipette’s chamber. Then she washed the sperm in the CRISPR solution. “Now it’s all going inside the oocyte,” she said. Invisibly, the CRISPR, with its guide-RNA protein, found and cut MYH7. In minutes, she had made two edited human embryos. Within a few days, after the cells had divided several times, the lab would sequence the DNA of each cell, checking to see if the desired edit had occurred in each one, before disposing of them.
“Do you want to try it?” Mitalipov asked me, then added, chuckling, “Don’t tell anyone.”
Martí Gutierrez set me up with the discarded I.V.F. egg, which was less likely to fertilize properly, and therefore less precious to their research. With one joystick, I chased sperm around the petri dish: a sex-ed version of the tag games that I’m constantly deleting from my children’s phones. When I finally caught one, I dipped it in CRISPR. Switching to the other joystick, which maneuvered a larger pipette, I braced the egg. Then, using the pipette with the edited sperm in it, I pierced the egg’s membrane. “Keep going,” Martí Gutierrez said. “There is good.” I glanced at a monitor attached to the microscope. What I saw was as familiar as the image of Earth from space: the large bobbling egg, the restless sperm. Basic human life, and an outermost frontier.
Mitalipov thinks that there will be legitimate clinical studies of heritable editing within a decade. Already, two new techniques, base editing and prime editing, have been developed that improve the capabilities of CRISPR—not just cutting DNA to disable genes but chemically rewriting parts of the genetic code, a process that some liken to a find-and-replace function in a word processor. David Liu, of the Broad Institute of M.I.T. and Harvard, who invented these new techniques, told me, “If progress continues at this remarkable current pace, there will be a point at which people might legitimately ask, ‘Is it unethical to not treat?’ ”
Copy link to cartoon
Link copied
Shop
Open Gallery
Before leaving Portland, I visited Marlo and Joe Urbina. In 2008, they became the parents of twins, Max and Sofia. Unbeknownst to Marlo and Joe, they were both carriers for Batten disease, a rare degenerative disorder that destroys the central nervous system. The kids are now teen-agers. Max is healthy. Sofia has Batten, for which there is no known cure.
In their back yard, we sat at a picnic table beside a bountiful vegetable garden, and they told me about the course of Sofia’s illness. When she was a little girl, they hadn’t noticed anything different about her. She was an early reader, and looked after her brother. “She seemed a bit clumsy and inattentive,” Joe said. “But there was no big deal at first. It was just, you know, normal kids.” In kindergarten, though, Sofia started to lose vision, and was given a diagnosis; by second grade, she was functionally blind. “They tell you, ‘Go home, make memories, because it’s gonna get ugly,’ ” Marlo said.
As the disease progressed, Sofia began to change. “Her cognitive skills were dropping off, and her emotional swings were getting to be tremendous,” Joe said. She had problems with self-regulation, and her memory deteriorated. She became angry, ruminative, and rigid. “They call it juvenile dementia,” Marlo said. Kids with Batten rarely live into adulthood.
At fourteen, Sofia can no longer walk, and it’s hard to understand her when she talks; she has thrashing and screaming fits that can last for hours. Max, who has maintained a close relationship with his twin, has to go into his room and turn on a noise machine to get his homework done. Marlo said that Sofia understands her prognosis. “She’s aware and she’s, you know, heartbroken,” she said. “She will say, a lot lately, ‘My eye, my eye, my brain, my eye.’ She knows that it’s Batten, and that’s why she can’t see and that’s why she can’t stop screaming and that’s why she can’t walk. She’ll scream for forty-five minutes, and then she’ll say afterwards, ‘I’m sorry, my brain.’ You know, you just hug her and you just say, ‘It’s O.K., baby, it’s not your fault, it’s O.K.’ She’s scared.”
When the Urbinas first heard about CRISPR being used in somatic gene therapy, they were hopeful that Sofia might one day benefit. As that hope has faded, they have redirected their energy to the future. “Max is not affected, but Max is a carrier,” Marlo said. “And that means he can pass that disease on. This is a horrible disease. It’s like A.L.S. and Alzheimer’s had a baby. I want to see this disease gone.”
Gene editing, she believes, has the potential to eliminate Batten, along with hundreds of other devastating diseases. “I think most Americans would say that we do this kind of science so that we can cure these things,” Marlo said. “And to me the best cure is keeping the disease from happening in the first place.”
Marlo estimates that Sofia has two to three more years to live. She told me, “Last night, I’m holding her, and she’s shaking and she’s, like, ‘When, when, when?’ And I said, ‘You know, people’s bodies get tired, and it’s O.K. when they get tired. And if you’re feeling tired now, we’ll just rest. And when your body can’t do it anymore, it’s O.K.’ ”
Before I left, Marlo asked me if I wanted to meet Sofia. We went into her room. Sofia, a tall adolescent with a pale complexion, was lying in a hospital bed. A Scooby-Doo cartoon was on the television, and her grandmother sat nearby. Sofia was playing with some brightly colored squishy toys that resembled jellyfish. She suddenly seemed to worry that they might be real. Marlo reassured her, and mentioned that Sofia always loved the beach. “We have lots of seashells that we have collected and bought over the years,” Marlo said. “And, Sofia, we’re going to go visit the beaches soon again.” I told Sofia that it was time for me to go; I had to fly home on an airplane.
“I can’t,” she said.
At home later that night, I got a series of texts from Marlo, including videos of Sofia as one of her fits came on. Marlo held her, but she looked terrified. It sounded like she was saying, “Help.”
In 2015, when scientists began to wrestle in earnest with how to manage the terrific potential of CRISPR, the laboratory work was so rudimentary that the ethical questions could be deferred. Back then, David Baltimore told me, “we didn’t have to resolve the thorny issues, because the technology was simply not good enough to get a targeted result. Nobody would be stupid enough to use this at this point.”
Until He Jiankui, Baltimore believes, a kind of moral force field prevented scientists from taking the next logical step with their research. “That’s bound to weaken as the science gets better,” he said. “There will come a moment when all the big questions have been answered, and where a doctor is facing a patient.”
But who decides which conditions are worthy of treatment? Though most of the scientists I talked to supported tight restrictions on heritable gene editing, and all strongly opposed using the technology for enhancement, very few suggested outlawing it entirely. “There’s a presumption of a self-evident distinction between legitimate and illegitimate work,” Benjamin Hurlbut, the bioethicist, said. “They build on each other’s work, and it becomes part of this wheel that’s only going in one direction.”
In 2018, JK had been mindful to present his work as a treatment for serious disease, not as an exercise in eugenics. In the videos he released, he said, “Gene editing is and should remain a technology for healing. Enhancing I.Q. or selecting hair or eye color is not what a loving couple does.” But to Hurlbut the H.I.V.-prevention therapy represents a troubling precedent. JK was able to recruit volunteers because, in China, H.I.V. dooms its carriers to difficult lives. In other cultures, different urgencies could prevail: imagine an attempt to address the profound social inequality associated with race in the United States by editing away features that can drive discrimination. “If you move into the zone of fixing social problems with genetic changes, that’s throwing a door wide open that takes us to terrifying places,” Hurlbut said. “The mandarins of science have a remarkable inability to see that’s the doorway this first experiment passed through, and it is the most plausible doorway, and people will be inclined to avail themselves of it again.” In mid-August, he sent me a paper from a group at Stanford, documenting newly discovered genes governing the production of melanin, which determines skin pigmentation.
By refusing to accept the role of rogue scientist, JK presents a kind of rolling crisis for the scientific community—a dark mirror of its own ambitions. Expanding beyond his goal of devising a therapy for Duchenne muscular dystrophy, he said last November that he was hoping to cure as many as five genetic diseases in two to three years. Weeks before the Third International Summit on Human Genome Editing, in London, he made headlines when a “top talent” visa that he had obtained to enter Hong Kong was revoked. Chinese scientists took the opportunity to call on the government to stop his work. “[We] strongly condemn He Jiankui’s refusal to reflect on his crime,” they wrote. On Twitter, JK acted as if nothing had happened. A post a few days later read, “Summer intern hiring! Anyone who supports human genome editing is welcomed to apply.”
At the end of June, he posted a research proposal on the use of base editing to target a gene involved in Alzheimer’s. Noting that CRISPR tools “may have unwanted and potentially dangerous consequences if they are applied to human embryos,” he said that he planned to start in mice, before moving on to nonviable human embryos. JK was, it seemed, returning to the plan that he’d laid out years before. He had disrupted a single gene, CCR5, when he edited Lulu, Nana, and Amy. Now he was progressing to complex diseases in which many genes were implicated. In the Alzheimer’s proposal, he pointed to another beneficial side effect of the edit he contemplated. “The mutation,” he wrote, “may also help prolong the lifespan of its carriers.” The protective variant had been found in the brain of a person almost a hundred and five years old.
The last e-mail I got from JK, in which he told me that he wasn’t taking more interview requests at the moment, suggested how and where he would conduct the next phase of his research. His e-mail signature listed a new position, at Wuchang University of Technology, in Wuhan, where he is now the director of the Institute of Genetic Medicine. ♦
/w=3840,quality=90,fit=scale-down)
