The code breaker, p.28
The Code Breaker, page 28
The ethics story, which Jiankui and Ferrell titled “Draft Ethical Principles for Therapeutic Assisted Reproductive Technologies,” was intended for a new publication called the CRISPR Journal, edited by the CRISPR pioneer Rodolphe Barrangou and the science journalist Kevin Davies. In his draft, Jiankui listed five principles that should be followed when deciding whether to edit human embryos:
Mercy for families in need: For a few families, early gene surgery may be the only viable way to heal a heritable disease and save a child from a lifetime of suffering.…
Only for serious disease, never vanity: Gene surgery is a serious medical procedure that should never be used for aesthetics, enhancement, or sex selection.…
Respect a child’s autonomy: A life is more than our physical body.…
Genes do not define you: Our DNA does not predetermine our purpose or what we could achieve. We flourish from our own hard work, nutrition, and support from society and our loved ones.…
Everyone deserves freedom from genetic disease: Wealth should not determine health.25
Instead of following guidelines such as those established by the National Academy of Sciences, Jiankui had crafted a framework that, at least by his thinking, would justify his use of CRISPR to take out the receptor gene for HIV. He was following moral principles that had been propounded, sometimes quite convincingly, by some prominent Western philosophers. For example, Duke professor Allen Buchanan was the staff philosopher for President Reagan’s Commission on Medical Ethics, was on the Advisory Council for the National Human Genome Research Institute under President Clinton, and is a fellow of the prestigious Hastings Center. Seven years before Jiankui decided to edit the CCR5 gene in human embryos, Buchanan had supported the concept in his influential book Better Than Human:
Suppose we learn that some desirable gene or set of genes already exists, but only in a small number of humans. This is precisely the situation for genes that confer resistance to certain strains of HIV-AIDS. If we rely on the “wisdom of nature” or “let nature take its course,” this beneficial genotype may or may not spread through the human population.… Suppose it were possible to ensure that such beneficial genes spread much more quickly by intentional genetic modification. This could occur by injecting genes into the testicles or, more radically, by inserting them into a large number of human embryos, utilizing in vitro fertilization. We would get the benefits… without the carnage.26
Buchanan was not alone. At the time of Jiankui’s clinical trial, many serious ethical thinkers, and not just gung-ho scientific researchers, had publicly argued, using the CCR5 gene as a specific example, that gene editing to cure or prevent diseases could be permissible and even desirable.
* * *
Ferrell gave an Associated Press team—Marilynn Marchione, Christina Larson, and Emily Wang—exclusive access to Jiankui. They were even allowed to videotape a non-viable human embryo being injected with CRISPR in Jiankui’s lab.
With Ferrell’s guidance, Jiankui also prepared videos that featured him in his lab speaking directly to the camera. In the first one, he outlined his five ethical principles. “If we can protect a little girl or boy from certain disease, if we can help more loving couples start families, gene surgery is a wholesome development,” he said. He also made a distinction between curing disease and making enhancements. “Gene surgery should only be used for treating serious disease. We should not use it for increasing I.Q., improving sports performance or changing skin color. That’s not love.”27
In the second video, he explained why he felt it was “inhuman for parents not to protect their children if nature gives us the tools to do so.” The third video explained why he had chosen HIV as his first target. The fourth, which was in Chinese and delivered by one of his postdoctoral students, explained the scientific details of how the CRISPR edits were made.28 They held off making the fifth video until they could announce the live births of the two babies.
Birth
The public relations campaign and release of the YouTube videos was planned for January, when the babies were due to be born. But one evening in early November 2018, Jiankui got a call saying that the mother had gone into labor prematurely. He dashed to the Shenzhen airport to fly to the city where the mother lived, taking some of the students in his lab. She ended up giving birth, after a caesarean section, to two apparently healthy girls, who were named Nana and Lulu.
The births happened so early that Jiankui had not yet submitted the official description of his clinical trial to Chinese authorities. On November 8, after the twins were born, it was finally submitted. It was written in Chinese, and for two weeks it went unnoticed in the West.29
He also finished the academic article he had been working on. Titled “Birth of Twins after Genome Editing for HIV Resistance,” it was submitted to the prestigious journal Nature. It was never published, but the manuscript, a copy of which was given to me by one of the American researchers he sent it to, offers details about his science and glimpses into his mindset.30 “Genome editing at the embryonic stage has potential to permanently cure disease and confer resistance to pathogenic infections,” he wrote. “Here, we report the first birth from human gene editing: twin girls who had undergone CCR5 gene editing as embryos were born normal and healthy in November 2018.” In the article, Jiankui defended the ethical value of what he had done. “We anticipate that human embryo genome editing will bring new hope to millions of families seeking healthy babies free from inherited or acquired life-threatening diseases.”
Buried in Jiankui’s unpublished paper were some disturbing pieces of information. In Lulu, only one of the two relevant chromosomes had been properly modified. “We confirmed Nana’s CCR5 gene was edited successfully with frameshift mutations on both alleles and Lulu’s was heterozygous,” he admitted. In other words, Lulu had different gene versions on her two chromosomes, which meant that her system would still produce some of the CCR5 protein.
In addition, there was evidence that some unwanted off-target edits had been made and also that both embryos had been mosaics, meaning there had been enough cell division before the CRISPR editing was done that some of the resulting cells in the babies were unedited. Despite all of this, Jiankui later said, the parents chose to have both embryos implanted. Kiran Musunuru of the University of Pennsylvania later commented, “The first attempt to hack the code of life and, ostensibly, improve the health of human babies had in fact been a hack job.”31
The news breaks
In the first few days after the babies were born, Jiankui and his publicist, Ferrell, tried to keep it under wraps until January, when they hoped that Nature would publish their scholarly paper. But the news was too explosive to hold. Just before Jiankui was scheduled to arrive at the Second International Summit on Human Genome Editing, to be held in Hong Kong, news of his CRISPR babies leaked.
Antonio Regalado, a reporter at the MIT Technology Review, combined a knowledge of science with the news instincts of a scoop-magnet journalist. He was in China in October, and he happened to be invited to a meeting with Jiankui and Ferrell just as they were making plans for the announcement. Although Jiankui did not reveal his secret, he did discuss the CCR5 gene, and Regalado was a good enough reporter to suspect that something was afoot. By searching on the internet, he discovered the application Jiankui had submitted to the Chinese Clinical Trial Registry. “Exclusive: Chinese Scientists Are Creating CRISPR Babies” was the headline on his story, which went online November 25.32
With Regalado’s story online, Marchione and her colleagues unleashed a well-balanced story brimming with details. Their lead sentence captured the drama of the moment: “A Chinese researcher claims that he helped make the world’s first genetically edited babies—twin girls born this month whose DNA he said he altered with a powerful new tool capable of rewriting the very blueprint of life.”33
All of the high-minded discussions that ethicists had been having about germline gene editing were suddenly preempted by an ambitious young Chinese scientist who wanted to make history. As with the birth of the first test-tube baby, Louise Brown, and the cloning of Dolly the sheep, the world had entered a new era.
That evening, Jiankui released the videos he had previously made along with a final one in which he made his momentous announcement on YouTube. Speaking calmly but proudly to the camera, he declared:
Two beautiful little Chinese girls named Lulu and Nana came crying into the world as healthy as any other babies a few weeks ago. The girls are home now with their mom, Grace, and their dad, Mark. Grace started her pregnancy by regular IVF with one difference. Right after we sent her husband’s sperm into her egg, we also sent in a little bit of protein and instructions for it to do gene surgery. When Lulu and Nana were just a single cell, this surgery removed the doorway through which HIV enters to infect people.… When Mark saw his daughters, the first thing he said was that he never thought he could be a father. Now he has found a reason to live, a reason to walk, a purpose. You see, Mark has HIV.… As a father of two girls, I can’t think of a gift more beautiful and wholesome for the society than giving another couple a chance to start a loving family.34
I. His name, 賀建奎, is transliterated as He Jiankui and pronounced HUH JEE’-an-kway. His family or “last” name is He. Because it is confusing to refer to him as He, I refer to him by his given name, Jiankui.
He Jiankui coming onstage
With Robin Lovell-Badge and Matthew Porteus
CHAPTER 38 The Hong Kong Summit
On November 23, two days before He Jiankui’s news broke, Doudna received an email from him. The subject line was dramatic: “Babies Born.”
She was puzzled, then shocked, and then alarmed. “At first I thought it was fake, or maybe he was crazy,” she says. “The idea that you would use ‘Babies Born’ as a subject line for something like this didn’t seem real.”1
He had included the draft of the manuscript he had submitted to Nature. When Doudna opened the attachment, she knew the situation was all too real. “It was a Friday, the day after Thanksgiving,” she recalls. “I was over in our condo in San Francisco with family members and longtime friends when this email came in like a bolt out of the blue.”
Doudna realized that the news would become even more dramatic because of its timing. In three days, five hundred scientists and policymakers were due to converge in Hong Kong for the Second International Summit on Human Genome Editing, the successor to the December 2015 summit in Washington. Doudna was one of the core organizers, along with David Baltimore, and He Jiankui was scheduled to be a speaker.
Doudna and the other organizers had not originally put Jiankui on the list of invited speakers. But they had changed their minds a few weeks earlier when they heard rumors that he had dreams or delusions of editing human embryos. Some on the planning committee felt that involving him in the summit might help dissuade him from crossing the germline.2
Upon getting Jiankui’s shocking “Babies Born” email, Doudna tracked down Baltimore’s cell phone number and reached him as he was leaving to fly to Hong Kong. They agreed that she would change her flight and arrive a day earlier than planned so that they could gather with some of the other organizers and decide what to do.
When she landed at dawn on the morning of Monday, November 26, and turned her phone back on, Doudna saw that Jiankui had been desperately trying to reach her by email. “The nanosecond I landed at the airport, I had just a ton of emails from Jiankui,” Doudna told Jon Cohen of Science. He was driving to Hong Kong from Shenzhen, and he wanted to meet as soon as possible. “I have to talk to you right now,” he emailed. “Things have really gotten out of control.”3
She did not reply because she wanted to meet first with Baltimore and the other organizers. Soon after she checked into Le Méridien Cyberport hotel, where the conferees were staying, a bellman knocked at her door with a message from Jiankui, saying to call him right away.
She agreed to meet with Jiankui in the hotel lobby, but first she hastily convened some of the organizers in a fourth-floor conference room. Baltimore was already there, sitting with George Daley of Harvard Medical School, Robin Lovell-Badge of London’s Francis Crick Institute, Victor Dzau of the U.S. National Academy of Medicine, and bioethicist Alta Charo from the University of Wisconsin. None of them had seen the scientific paper that Jiankui had submitted to Nature, so Doudna showed them the copy he had emailed to her. “Our group all scrambled to decide whether Jiankui should be allowed to remain on the conference program,” Dzau recalls.
They quickly decided that he should. In fact, they decided it was important not to let him withdraw. They would give him a solo spot on the program and ask him to address the science and methods he used to make the CRISPR babies.
After fifteen minutes, Doudna went down to the lobby to meet Jiankui. She took with her Robin Lovell-Badge, who would be chairing Jiankui’s session. The three of them sat on a couch, and Doudna and Lovell-Badge told Jiankui that they wanted his presentation to explain exactly how and why he had proceeded with his experiment.
Jiankui flummoxed them by insisting that he wanted to stick with his original slide presentation and not discuss the CRISPR babies. Lovell-Badge, whose usual hue is an English pale, turned almost white as he listened. Doudna politely pointed out that Jiankui was being ludicrous. He had triggered the most explosive scientific controversy in years, and there was no way he could avoid discussing it. That seemed to surprise Jiankui. “I think that he was oddly naïve as well as glory-seeking,” she recalls. “He had intentionally caused an explosion and yet wanted to act like it hadn’t happened.” They convinced him to have an early dinner with some members of the organizing committee to discuss the issue.4
On her way out of the lobby, shaking her head in amazement, Doudna ran into Duanqing Pei, the American-educated stem-cell biologist from China who heads the Guangzhou Institute of Biomedicine and Health. “Have you heard?” Doudna asked him. When she told him the details, he had trouble believing it. Pei and Doudna had become friendly after many conferences, including the 2015 first international summit in Washington, and he had repeatedly told his American colleagues that there were regulations in China against germline editing in humans. “I assured people that, in our system, everything is carefully controlled and licensed, so this type of thing couldn’t occur,” Pei later told me. He agreed to come to the dinner with Jiankui that evening.5
Showdown over dinner
The dinner, a Cantonese buffet in the hotel’s fourth-floor restaurant, was tense. When Jiankui arrived, he was defensive, even a bit defiant, about what he had done. He pulled out his laptop to show his data and the DNA sequencing he had performed on the embryos. “We were increasingly horrified,” Lovell-Badge recalled. They peppered him with questions: Had there been oversight on his consent process? Why did he believe germline embryo editing was medically necessary? Had he read the guidelines that the international academies of medicine had adopted? “I feel I complied with all those criteria,” Jiankui answered. His university and hospital knew all about what he was doing and had approved, he insisted, “and now that they’re seeing the negative reaction, they’re denying it and hanging me out to dry.” When Doudna walked through the reasons why germline editing was not “medically necessary” to prevent HIV infection, Jiankui got very emotional. “Jennifer, you don’t understand China,” he said. “There’s an incredible stigma about being HIV positive, and I wanted to give these people a chance at a normal life and help them have kids when they otherwise might not have.”6
The dinner became increasingly fraught. After an hour, Jiankui shifted from being plaintive to being angry. He stood up abruptly and tossed some bills on the table. He had been receiving death threats, he said, and now he was going to move to an undisclosed hotel where the press couldn’t find him. Doudna chased after him. “I think it’s very important that you appear on Wednesday and present your work,” she said. “Will you come?” He paused and then agreed to, but he wanted security. He was afraid. Lovell-Badge promised to have Hong Kong University provide police protection.
* * *
One reason Jiankui was defiant was that he had thought he would be hailed as a Chinese hero, perhaps even a global one. Indeed, the first Chinese news reports did so. The People’s Daily, a government organ, ran a story that morning with the headline “The World’s First Gene-Edited Babies Genetically Resistant to AIDS Were Born in China,” and it called Jiankui’s work “a milestone accomplishment China has achieved in the area of gene-editing technologies.” But the tide quickly turned as scientists, even in China, began to criticize his actions. Later that evening, the People’s Daily deleted the story from its website.7
After Jiankui left the hotel restaurant, the organizers stayed at the table discussing how to handle the situation. Pei looked at his smartphone and reported that a group of Chinese scientists had put out a statement condemning Jiankui. Pei began translating it for the others at the table. “Direct human experimentation can only be described as crazy,” they declared. “This is a huge blow to the global reputation and development of Chinese science, especially in the field of biomedical research.” Doudna asked Pei whether the statement had come from the Chinese Academy of Sciences. No, Pei replied, but a group of more than a hundred prestigious Chinese scientists had signed it, which meant that the statement had official blessing.8
Doudna and her dinner partners realized that they, as the conference organizers, should put out a statement as well. But they did not want to make it too strong for fear that it would provoke Jiankui to cancel his talk. Truth be told, Doudna admitted, their motives were not merely scientific. The global buzz was huge, eyes were on Hong Kong, and it would be quite a letdown if Jiankui drove back to Shenzhen and they all missed the chance to be part of a historic moment. “We put out a very short statement that was quite bland and got criticism for that,” she says, “but we wanted to ensure that he would show up.”
