In 2010, a Rice University graduate student named He Jiankui published a paper describing the nitty-gritty details of a then-arcane bacterial immune system called CRISPR. It was well before scientists unlocked the knowledge that CRISPR could be used to manipulate DNA with a precision and ease that other genome editors lacked.
Now, just eight years later, and after returning to his native China, He has burst onto the global stage in the most spectacular way — an entrance he seems to have meticulously choreographed even as he ignored guidelines established by global scientific panels. Using YouTube rather than an academic journal, He claimed that with the aid of CRISPR, he had helped create the world’s first babies — twin girls born a few weeks ago — whose genomes had been edited as embryos. The announcement dropped like a surprise Beyonce album.
The claim, which has not been verified by outside researchers, was heralded by a few as a scientific milestone, an unprecedented step toward preventing all sorts of diseases. But others viewed it as quite the opposite: the reckless breaking of a scientific taboo for personal gain. After all, many far more experienced and respected researchers had the technical know-how to attempt what He did, but they honored the widely accepted ethical barriers. Such research is also illegal in the United States.
He Jiankui (pronounced HEH JEE’-an-qway), who was previously not known to many Western CRISPR experts, immediately found himself at the center of a firestorm of criticism over the lack of transparency in his research, the choice of gene that was edited, and his pursuit of this research at all.
“I am trying to understand what may have motivated the work he describes,” said a scientist who helped organize a major Hong Kong summit on human genome editing that starts Tuesday and who asked not to be named. “As far as I can tell, it was a combination of hubris, naivete, and perhaps a genuine desire to help people in need. He does not seem to have anticipated the profound public backlash against his work and the way it was conducted and publicized.”
He clearly knew the attention that his announcement would get. He reportedly worked with an American public relations specialist; gave advance interviews to the Associated Press, which has a global reach; timed the big reveal to the start of the summit; and posted a series of YouTube videos in English celebrating the achievement.
But he also caught the world off guard, keeping his activities hidden from the broader scientific community. Information about his clinical trial, for example, was posted on an online Chinese registry only this month. Experts envisioned the first edited baby to be born after rigorous discussions about regulations and ethics and with strict safeguards in place — all done in a manner that wouldn’t alarm the public.
Even He’s own university, from which he has been on leave since February, distanced itself from the research, saying that it knew nothing about the work and that it was “conducted outside of the campus” and “seriously violated academic ethics and codes of conduct.”
Beyond the condemnation, leading genome editing experts were simply left puzzled by the researcher behind the announcement. He doesn’t have an extensive history of publishing papers about genome editing or embryology or the gene he disabled in the embryos, CCR5, to try to confer resistance to HIV infection. Much of the social media scuttlebutt came back to this question: What was this guy doing editing embryos?
Perhaps He should have been more well-known. In a talk last year at Cold Spring Harbor Laboratory, He discussed editing the genomes of mouse, monkey, and human embryos (editing human embryos in the lab, that is — not for transferring into wombs and starting pregnancies).
That talk earned He a speaking spot at this week’s summit in Hong Kong; his panel is scheduled for Wednesday morning Hong Kong time. In a sign of how just how much He’s CRISPR’d embryos project caught the global scientific community by surprise, however, his speaking slot is not a plenary session, typically reserved for the biggest newsmakers of a conference.
He also co-authored a paper published this week in the CRISPR Journal proposing five “ethical principles” to guide the use of genome editing in the clinic. The second author on the paper: Ryan Ferrell, the American public relations professional who worked with He on the rollout of the CRISPR’d embryos project.
Among the elements He called for: open dialogue.
But He doesn’t seem to have followed his own recommendations.
In April 2016, He wrote to CRISPR pioneer Feng Zhang of the Broad Institute, identifying himself as CEO of his DNA sequencing company Direct Genomics and requesting a tour of Zhang’s lab in Cambridge, Mass. He did not visit then, but he did briefly drop by to visit Zhang’s lab this past August, Zhang told STAT on the sidelines of the genome editing summit.
What did He want to talk about? Methods to reduce off-target effects — cuts CRISPR can make in unintended places — in editing of mouse and human embryos, Zhang recalled.
“It was clear to me that he was having the same challenges as other researchers around lack of efficiency and lack of precision,” Zhang said. “I told him that the technology is neither efficient nor precise enough for real-world application in embryos, including in human IVF applications.”
For Zhang, that conversation has taken on a new tone in light of this week’s news. “Of course, now we know that by August, he must have been quite far along in his work in humans, at least according to his most recent claims,” Zhang said. “He certainly never mentioned this work when I saw him.”
From China to the U.S. and back
He’s career trajectory highlights a few salient facts: His scientific background is wide-ranging, but lacking in deep expertise in CRISPR and embryology. Public records indicate that he is just 34 years old, an age when many top researchers are just opening up their first labs.
He, who appears to have been born and raised in China, earned his undergraduate degree in physics from the University of Science and Technology of China in 2006. He then moved to Texas to earn his Ph.D., in biophysics, at Rice University in Houston; his adviser there, the bioengineering professor Michael Deem, would later collaborate with him on the CRISPR’d embryos project.
After graduating in 2010, He spent about a year doing his postdoc in the lab of Stanford bioengineer Stephen Quake. It was there that He learned about single-molecule sequencing ― a then-revolutionary method of sequencing single DNA molecules without first having to copy them using polymerase chain reaction, according to a 2015 story in the publication Bio-IT World.
He moved back to China around 2012. It’s not clear why he decided to return home, but a few factors may have come into play. He wanted to spin off companies from his academic research back in China, according to Bio-IT World. And financial incentives may have contributed to his decision: He moved back to China as part of the Thousand Talents program, an initiative in which the Chinese government has offered incentives to try to bring back its best and brightest scientists and entrepreneurs who did their training in the U.S.
He opened a lab at the Southern University of Science and Technology of China in Shenzhen. (His current leave from that role is scheduled to last until 2021.). He also started several companies, including Direct Genomics.
He appears to have retained some of the relationships he forged during his training in the U.S. — most notably with Deem, his Rice adviser.
Deem said that the research fit with the work they did on vaccines during He’s time in Houston. In addition to their 2010 study on CRISPR, Deem and He collaborated on studies about the speed of evolution of genes and ways to detect emerging and dangerous strains of influenza.
They were also both listed as authors on a study published last year that described using single-molecule sequencing to unravel the genome of a virus. Other authors on the 2017 paper worked at Direct Genomics.
On Monday, Rice said it had opened an investigation into Deem’s role in the CRISPR’d embryos project, saying the research “violates scientific conduct guidelines and is inconsistent with ethical norms of the scientific community and Rice University.” Deem could not be reached for comment.
Moving fast while preaching caution
In the YouTube videos that He used to unveil his stunning claims to the world, he sits in a nondescript lab with instruments in the background; he wears a light button-up shirt, with no tie and no lab coat. Speaking slowly and in English, He struck a remarkably emotional tone.
He described his work as light years away from creating “designer babies,” which he condemned. He also implored his audience to look beyond the criticism that his work would likely spark, voicing confidence that his project will be viewed favorably by history.
“Please remember that while there may be vocal critics, there are many silent families who have seen a child suffer from genetic disease and should not have to suffer that pain again,” He told the camera in one of the videos. “They may not be the director of an ethics center quoted by the New York Times, but they are no less authorities on what’s right and wrong — because it’s their life on the line.”
Crucially, though, He is not claiming to have tackled genetic disease with his CRISPR’d embryo project. Instead, he claims to have taken on HIV, a disease for which relatively simple ways already exist to keep HIV-positive parents from infecting their children.
And big questions remain about whether He’s project will actually help the family whose babies were purportedly gene-edited. Independent scientists who reviewed some of the documentation said there’s not yet enough evidence to tell whether the editing worked as intended or was safe. They’ve also raised concerns about the implications of He’s admission that one of the gene-edited twins had both copies of CCR5 altered, while the other had only one copy altered.
At the end of another one of He’s YouTube videos, he provides an email address for his lab — and another ([email protected]) for viewers who want to write to the two gene-edited newborns, who He says are named Lulu and Nana.
While He was slammed for doing too much too fast, he has previously emphasized moving patiently and deliberately when discussing edited embryos.
In his 2017 talk, He raised the 1999 death of Jesse Gelsinger in an early gene therapy trial, which set that field back by more than a decade.
Researchers who might be tempted to use a CRISPR’d embryo to start a pregnancy should remember that case, He suggested.
“I want to remind everyone that we should do this kind of slow and with a bit of caution,” He said, “because a single case of failure may kill the entire field.”
Sharon Begley contributed reporting from Hong Kong.