The Code Breaker, page 27
He got his PhD in physics but then decided that the future was in biology. Deem allowed him to go to conferences around the country and provided an introduction to the Stanford bioengineer Stephen Quake, who invited Jiankui to become a postdoc in his lab. Colleagues there remember him as funny and energetic, with a Texas-size passion for entrepreneurship.
Quake had founded a company to commercialize a gene-sequencing technology that he had developed, but it began sliding into bankruptcy. Believing that he could make the process commercially successful in China, Jiankui decided to start a company there. Quake was enthusiastic. “This has a chance to bring the phoenix back from the ashes,” he exulted to one of his partners.4
* * *
China was eager to nurture biotech entrepreneurs. In 2011, it launched an innovative new university, the South University of Science and Technology, in Shenzhen, a booming city of 20 million people bordering on Hong Kong. Responding to a job opening posted on the university’s website, Jiankui ended up getting hired there as a biology professor and announced on his blog that he was forming the “He Jiankui and Michael Deem Joint Laboratory.”5
Chinese officials had designated genetic engineering as critical to the country’s economic future and its competition with the U.S., and to that end they launched a variety of initiatives to encourage entrepreneurs and lure back researchers who studied overseas. Jiankui benefited from two of them: the Thousand Talents Recruitment Program and the Shenzhen government’s Peacock Initiative.
When he formed his new company to build gene-sequencing machines based on Quake’s technology in July 2012, Shenzhen’s Peacock Initiative provided an initial round of $156,000 in funding. “Shenzhen’s generosity in encouraging startups, especially venture capitalists, which is comparable to Silicon Valley, attracted me,” Jiankui later told the Beijing Review. “I am not a professor in the traditional sense. I prefer to be a research-type entrepreneur.”
Over the next six years, Jiankui’s company would receive about $5.7 million in funding from government sources. By 2017, its gene sequencer was on the market and the company, of which Jiankui had a one-third stake, was valued at $313 million. “The development of the device is a major technical breakthrough and will significantly improve cost-effectiveness, speed and quality of gene sequencing,” Jiankui said.6 In a scientific article describing the use of the machine for sequencing genomes, he claimed that the results “show comparable performance to the Illumina,” referring to the American company that dominates the market for DNA sequencers.7
With his smooth personality and thirst for fame, Jiankui became a minor scientific celebrity in China, where the state-run media was eagerly looking for innovators to tout as role models. The broadcast network CTV ran a series in late 2017 featuring the country’s young science entrepreneurs. As inspiring patriotic music played, Jiankui was shown talking about his company’s gene sequencer, which the narrator said works better and faster than American versions. “Somebody said we shocked the world with our machine,” a smiling Jiankui declared to the camera. “Yes, they’re right! I did that—He Jiankui! That’s me who did that!”8
* * *
Jiankui initially used his gene-sequencing technology to diagnose genetic conditions in early-stage human embryos. But in early 2018, he began to discuss the possibility of not only reading human genomes but also editing them. “For billions of years, life progressed according to Darwin’s theory of evolution: random mutation in DNA, selection and reproduction,” he wrote on his website. “Today, genome sequencing and genome editing provide powerful new tools to control evolution.” His goal, he said, was to sequence a human genome for $100, then move on to fixing any problems. “Once the genetic sequence is known, we can use CRISPR-Cas9 to insert, edit or delete the associated gene for a particular trait. By correcting the disease genes, we humans can better live in the fast changing environment.”
He did, however, say that he was against using gene editing for some forms of enhancement. “I support gene editing for the treatment and prevention of disease,” Jiankui wrote in a post on the social media site WeChat, “but not for enhancement or improving I.Q., which is not beneficial to society.”9
Networker
He Jiankui’s website and social media comments, which were in Chinese, did not garner much attention in the West. But as a promiscuous networker and conference hopper, he was beginning to develop a circle of acquaintances in the American scientific community.
In August 2016, he attended the annual CRISPR conference held at Cold Spring Harbor Laboratory. “The just-concluded Cold Spring Harbor Gene Editing Conference is the top event in this field,” he bragged on his blog. “Feng Zhang and Jennifer Doudna and other leading figures attended the event!” Accompanying the post was a selfie Jiankui took with Doudna seated in the auditorium under the oil portrait of James Watson.10
A few months later, in January 2017, Jiankui sent Doudna an email. As he had done with other top CRISPR researchers, he asked to meet with her when he next came to the United States. “I am working on the technology to improve the efficacy and safety of genome editing human embryos in China,” he wrote. The email arrived when Doudna was helping to organize a small workshop on “the challenge and opportunity of gene editing.” It had been two years since her Napa Valley conference, and the Templeton Foundation, which supports the study of big ethical questions, had provided funding for a series of discussions on CRISPR. Doudna invited twenty scientists and ethicists to a kickoff workshop in Berkeley, but few were from overseas. “We would be delighted to have your participation,” she wrote back to Jiankui, who, not surprisingly, was equally delighted to accept.11
The meeting opened with a public lecture by George Church in which he spoke of the possible benefits of germline editing, including ones that would augment human capacities. Church showed a slide listing simple gene variations that offer beneficial effects. Among them was a variant of the CCR5 gene that would make a person less receptive to the HIV virus that causes AIDS.12
On his blog, Jiankui wrote about the off-the-record meeting: “A lot of sharp issues caused fierce debates there, and the smell of gunpowder filled the air.” Particularly interesting was his interpretation of the report from the international summit on gene editing, which had just come out. He called it a “yellow light for human genetic editing.” In other words, instead of reading the report as a call to not proceed with heritable human embryo editing for the time being, he interpreted it as a signal that he could proceed cautiously.13
Jiankui’s turn to present came on the second day of the meeting. His talk, titled “Safety of Human Gene Embryo Editing,” was unimpressive. There was only one interesting part: his description of his work editing the CCR5 gene, the one that Church had mentioned in his lecture as a potential candidate for future germline editing. Jiankui described how he had edited the gene, which produces a protein that can serve as a receptor for the HIV virus, in mice, monkeys, and non-viable human embryos discarded from fertility clinics.
Other Chinese researchers had already prompted international ethics discussions by using CRISPR to edit CCR5 genes in non-viable human embryos, so nobody at the conference took much notice. “His talk made no impression on me,” Doudna says. “I found him very eager to meet people and be accepted, but he hadn’t published anything important, and he didn’t seem to be doing any important science.” When Jiankui asked Doudna if he could come to her lab as a visiting fellow, she was surprised at his audacity. “I deflected his request,” she says. “I had absolutely no interest.” What struck Doudna and others at the meeting was that Jiankui did not seem interested in the moral issues involved with making inheritable gene edits to embryos.14
Continuing to network and conference-hop, Jiankui returned to Cold Spring Harbor in July 2017 for its annual CRISPR conference. Wearing a striped shirt and with his dark hair youthfully mussed, he gave pretty much the same talk that he had given in Berkeley earlier that year, again eliciting yawns and shrugs. He ended on a cautionary note, with a slide showing a New York Times story on Jesse Gelsinger, the young man who died after receiving gene therapy treatments. “A single case of failure may kill the entire field,” he concluded. There were three perfunctory questions. No one thought that his experiments had produced any scientific breakthroughs.15
Editing babies
In this July 2017 talk at Cold Spring Harbor, Jiankui described editing the CCR5 gene in discarded, non-viable human embryos. What he did not say was that he had already made plans to edit the gene in viable human embryos with the intent of giving birth to genetically altered babies—in other words, making inheritable germline edits. Four months earlier, he had submitted a medical ethics application to Shenzhen’s Harmonicare Women and Children’s Hospital. “We plan to use CRISPR-Cas9 to edit the embryo,” he wrote. “The edited embryos will be transferred to women and pregnancy will follow.” His goal was to allow couples who suffered from AIDS to have babies who would be protected from the HIV virus, as would all of their descendants.
Because there were simpler ways to prevent AIDS infection, such as sperm-washing and screening for healthy embryos before implantation, the procedure was not medically necessary. Nor would it correct a clear genetic disorder; the CCR5 gene is common and probably has multiple purposes, including helping to protect against West Nile virus. So Jiankui’s plan did not meet the guidelines that had been agreed to at multiple international meetings.
But it did offer Jiankui the possibility, or at least he thought so, of achieving a major historical breakthrough and enhancing the glory of Chinese science. “This is going to be a great science and medicine achievement,” he wrote in his application, comparing it to “the IVF technology which was awarded the Nobel Prize in 2010.” The hospital ethics committee gave its consent unanimously.16
There are approximately 1.25 million HIV-positive people in China, a number that is still growing rapidly, and ostracism of victims is widespread. Working with a Beijing-based AIDS advocacy group, Jiankui sought to recruit twenty volunteer couples in which the husband was HIV positive and the wife was HIV negative. More than two hundred couples showed interest.
Two of the selected couples came to Jiankui’s lab in Shenzhen one Saturday in June 2017 and, in a meeting that was videotaped, were informed about the proposed clinical trial and asked if they wished to participate. He walked them through the consent form. “As the volunteer, your partner is diagnosed to have AIDS or has been infected with HIV,” it said. “This research project will likely help you produce HIV-resistant infants.” The two couples agreed to participate, as did five more recruited at other sessions. They produced thirty-one embryos, sixteen of which Jiankui was able to edit. Eleven were implanted into the volunteers unsuccessfully, but by the late spring of 2018 he was able to implant twin embryos into one mother and one embryo into another.17
Jiankui’s process involved taking sperm from the father, washing the cells to rid them of the HIV virus, and then injecting the sperm into the mother’s eggs. This was probably enough to ensure that the resulting fertilized eggs were free of HIV. But his goal was to guarantee that the children would never later be infected. So he injected the fertilized eggs with CRISPR-Cas9 that targeted the CCR5 gene. They were allowed to grow for five or so days in a Petri dish until they were an early-stage embryo more than two hundred cells large, and then their DNA was sequenced to see if the edits had worked.18
His American confidants
During his visits to the U.S. in 2017, Jiankui began hinting at his plans to a few of the American researchers he met, many of whom later expressed regret that they did not try harder to stop him or blow the whistle. Most notably, he confided in William Hurlbut, a neurobiologist and bioethicist at Stanford, who had co-organized the January 2017 Berkeley gathering with Doudna. They had, Hurlbut later told the journal Stat, “several long conversations, like four or five hours long, about science and ethics.” Hurlbut realized that Jiankui was intent on making embryo edits leading to live births. “I tried to give him a sense of the practical and moral implications,” he says, but Jiankui insisted that only “a fringe group” opposed making germline edits. If such edits could be used to avoid a dread disease, Jiankui asked, why would people be against it? Hurlbut viewed Jiankui as “a well-meaning person who wants his efforts to count for good” but who was spurred by a scientific culture “that puts a premium on provocative research, celebrity, national scientific competitiveness, and firsts.”19
Jiankui also confided his plans to Matthew Porteus, an accomplished and respected stem-cell researcher at Stanford Medical School. “I was stunned and my jaw dropped,” Porteus recalls. It turned from a polite conversation about scientific data into a half-hour lecture by Porteus about all the reasons he thought Jiankui’s idea was terrible.20
“There’s no medical need,” Porteus said. “It violates all the guidelines. You’re jeopardizing the entire field of genetic engineering.” He demanded to know if Jiankui had run it by his senior people.
No, Jiankui said.
“You need to talk to these people, the officials in China, before you proceed any further,” Porteus warned with rising anger.
At that point Jiankui became very quiet, his face flushed, and then he walked out of the office. “I don’t think he was expecting such a negative reaction,” Porteus says.
In hindsight, Porteus blames himself for not doing more. “I fear some people think I made an ass out of myself,” he says. “I wish that, while he was in my office, I had insisted that we jointly send emails to various senior people in China.” But it’s unlikely that Jiankui would have permitted Porteus to tell other people. “He thought that if he told people ahead of time, they would try to stop him,” Porteus says, “but once he succeeded in producing the first CRISPR babies everyone would recognize it as a great achievement.”21
Jiankui also confided in Stephen Quake, the Stanford gene-sequencing entrepreneur who had supervised his postdoctoral work and helped him launch the Shenzhen-based company that used Quake’s technology. As early as 2016, Jiankui told Quake that he wanted to be the first person to create gene-edited babies. Quake told him it was “a terrible idea,” but when Jiankui persisted, Quake suggested that he do it with the proper approvals. “I will take your suggestion that we will get a local ethic approval before we move on to the first genetic edited human baby,” Jiankui told Quake in an email, which was later reported by New York Times health writer Pam Belluck. “Please keep it in confidential.”
“Good News!” Jiankui wrote Quake in April 2018. “The embryo with CCR5 gene edited was transplanted to the women 10 days ago, and today the pregnancy is confirmed!”
“Wow, that’s quite an achievement!” Quake replied. “Hopefully she will carry to term.”
After an investigation, Stanford cleared Quake, as well as Hurlbut and Porteus, of any wrongdoing. “The review found that the Stanford researchers expressed serious concerns to Dr. He about his work,” the university declared. “When Dr. He did not heed their recommendations and proceeded, Stanford researchers urged him to follow proper scientific practices.”22
* * *
The most involved and tainted of Jiankui’s American enablers was Michael Deem, his PhD advisor at Rice. In a scene that was captured on videotape, Deem can be seen sitting at the table during the first of Jiankui’s sessions where prospective parents were advised about giving their consent to the gene editing of their embryos. “When this couple gave their informed consent,” Jiankui later said publicly, “it was observed by this United States professor.” Deem spoke to the volunteers through a translator, a member of the Chinese team told Stat.
In an interview with the Associated Press, Deem admitted being in China during the meeting. “I met the parents,” he said. “I was there for the informed consent of the parents.” Deem also defended Jiankui’s actions. But he then hired two Houston lawyers who issued a statement claiming that Deem was not involved in the informed-consent process, even though a scene from the video shows him sitting there. The lawyers also claimed, “Michael does not do human research and he did not do human research on this project.” That seemed to be contradicted when it was revealed that Deem was a coauthor of the paper Jiankui wrote on his human gene–editing experiments. Rice said that it would launch an investigation, but after two years had not issued a finding. By the end of 2020, Deem’s faculty page had been removed from the Rice website, but the university continued to refuse to offer any explanation.23
Jiankui’s PR campaign
As the Chinese pregnancies progressed in mid-2018, Jiankui knew that his announcement would be earth-shaking news, and he wanted to capitalize on it. The goal of his experiment, after all, was not merely to protect two kids from AIDS. The prospect of achieving fame was also a motivation. So he hired Ryan Ferrell, a respected American public relations executive he had worked with on another project, who found Jiankui’s plans to be so exciting that he left his agency and relocated temporarily to Shenzhen.24
Ferrell planned a multimedia announcement campaign. It included having Jiankui write an article on the ethics of gene editing for a journal, cooperate with the Associated Press on an exclusive story on the making of the CRISPR babies, and tape five videos that would be released on his website and YouTube. In addition, he would write a scientific piece, coauthored with Rice’s Michael Deem, that he would try to publish in a prestigious journal such as Nature.
