In late 2016, JK reached out to Mark DeWitt, a lesser known scientist at Doudna’s Innovative Genomics Institute (IGI), who had recently published a paper on genetically editing cells for sickle-cell disease.3 After meeting for lunch, DeWitt accepted JK’s surprise invitation to visit China to give a lecture at SUSTech, but not before reiterating that Berkeley had no interest in supporting experiments on human embryos. “I’m a little reluctant to speak about it again,” DeWitt told me by phone. “It’s important but it’s not what I want to be known for.”4
In January 2017, JK was honored to be invited to attend a small workshop at IGI organized by Doudna and Stanford bioethicist William Hurlbut on the topic of public education and engagement around human genome editing. JK was the youngest scientist at the meeting, and other than delivering a short talk presenting preliminary data on editing in human embryos, focusing on the safety of CRISPR technology, kept a low profile. On his blog, he posted a summary of his talk, which highlighted five safety issues, including off-target effects and mosaicism, that would require further study. He signed off his report by stating that the behavior of anyone performing germline editing would be “extremely irresponsible,” unless and until these important safety issues were resolved. He also noted something else of interest: the Valentine’s Day publication of the National Academy of Sciences report on germline editing, which (as we will see later) in JK’s view gave a “yellow light” for human germline editing.5
The meeting began with a bang: a public lecture by George Church, provocatively titled “Future, Human, Nature: Reading, Writing, Revolution.”6 Church spoke openly about germline therapy, speculating that mitochondrial germline therapy would move into treatments for infertility. Compared to our ancestors, “we are already augmented,” Church said, mostly through physics and chemistry rather than genetics. He noted humanity’s ability to see, to hear, to fly, to reach altitudes, to plumb the ocean’s depths, further than our ancestors could have dreamed. But geneticists would get their chance: near the end of his talk, Church displayed a list of “protective alleles”—variants in certain genes that offer beneficial traits with no known or serious downsides. Among those genes was CCR5. “Wow, that was wonderful,” said Doudna, Church’s host for the evening, probably echoing JK’s sentiments in the audience.
During the meeting, JK also met William Hurlbut and his son Ben, a science historian at Arizona State University. Looking back, Ben Hurlbut concluded that JK’s motivations were familiar and mundane,
driven by the high-octane milieu of contemporary biotechnology, both in the United States and in China. He internalized ideas that led him to believe that his experiment would elevate his status in the international scientific community, advance his country in the race for scientific and technological dominance, and drive scientific progress forward against the headwinds of ethical conservatism and public fear.7
Two years later, JK shared with Hurlbut that one particular statement at the IGI conference really affected him. “Many major breakthroughs are driven by one or a couple of scientists… cowboy science,” JK said. “You need a person to break the glass.”8
JK was following progress in the arena of CRISPR gene editing. China was racing ahead in offering CRISPR-based somatic therapies to dozens of cancer patients “unhampered by rules,” although it was unclear how successful these early efforts were.9
But JK was interested in going much further, to “break the glass”: engineering a permanent, heritable change to human DNA as a means to treat or prevent a disease not only in a patient but also in their children forevermore. In the three years following the groundbreaking human embryo experiments performed in Guangzhou in 2015,10 nine more human embryo editing studies were published. All but two came from research groups in China.11, 12, 13, 14, 15, 16, 17 In March 2017, a group at Guangzhou Medical School reported editing a pair of disease genes in human embryos. Although none of the studies had been designed to actually implant an edited embryo, there was a feeling that it was only a matter of time. When Nature Biotechnology asked leaders in the genomics field whether germline editing was inevitable, including Doudna, Dana Carroll, Hank Greely, Robin Lovell-Badge, and Craig Venter, they concurred it was.18
In contrast to the Chinese reports on gene editing in human embryos, two other studies—one in Europe, the other in the United States—were given top billing in Nature. One was led by Kathy Niakan at the Francis Crick Institute in central London, the $1 billion crown jewel of British molecular biology research. The institute was officially opened by the Queen in 2016, who unveiled a portrait of Crick that had been commissioned by Jim Watson. Niakan is a widely respected developmental biologist who studies the fundamental mechanisms by which embryos develop in the critical first few days and weeks after fertilization. Understanding how specific genes orchestrate cell growth and development could help identify risk factors for miscarriages and other complications of pregnancy, and improve the success rate of IVF.
In 2016, the UK HFEA granted Niakan limited permission to use CRISPR-Cas9 to engineer DNA alterations in human embryos.19 She used spare embryos created during IVF and donated for research, growing them for no more than fourteen days. “I promise you she has no intention of the embryos ever being put back into a woman for development,” insisted her colleague, Lovell-Badge. In September 2017, using CRISPR, Niakan’s team reported in Nature a key role for a gene called OCT4 in human embryonic development.20
A bigger splash came just a month earlier. ONE GIANT STEP FOR DESIGNER BABIES was the exclusive front-page headline in a British tabloid. The scoop, from science journalist Steve Connor, also ran in MIT Technology Review under a more sober title: “First human embryos edited in U.S.”21 Connor had heard the news several weeks before Nature was due to publish a report from a leading American IVF center. The journal editors were “incandescent that their thunder had been stolen,” which is music to any science reporter’s ears.I
The study’s lead author was Shoukhrat Mitalipov of the privately funded Oregon Health & Science University in Portland, so was not subject to the federal funding prohibition on human embryo research. Originally from Kazakhstan, Mitalipov trained in Moscow before emigrating to the United States in the mid-1990s. An expert in stem cell and embryo research, his group reported the first cloned monkeys and the first individualized stem cells (by genetically reprogramming a patient’s skin cells). His work in mitochondrial replacement therapy earned him recognition as one of Nature’s top ten personalities of 2013.
So why did Nature, despite the many Chinese human embryo precedents, elect to publish Mitalipov’s paper? It surely wasn’t just because the controversial field of human embryo editing had been carried out on American soil.22 Mitalipov’s work stood out for two reasons: first, the team’s results were technically impressive. Mitalipov’s group had created dozens of embryos by fertilizing donated eggs with sperm from a man with hypertrophic cardiomyopathy. (This disease can cause sudden, fatal heart attacks, notably in young athletes such as former Boston Celtics star Reggie Lewis.) The Oregon team used CRISPR to repair the faulty copy of the MYBPC3 gene, which had a four-base deletion. Of the fifty-eight treated embryos, forty-two were apparently repaired with two healthy copies of MYBPC3, without any serious off-target effects.