PALO ALTO, Calif. — “Success!” read the subject line of the email. The text, in imperfect English, began: “Good News! The women is pregnant, the genome editing success!”
The sender was He Jiankui, an ambitious, young Chinese scientist. The recipient was his former academic adviser, Stephen Quake, a star Stanford bioengineer and inventor.
“Wow, that’s quite an achievement!” Quake wrote back. “Hopefully she will carry to term …”
Months later, the world learned the outcome of that pregnancy: twins born from genetically engineered embryos, the first gene-altered babies. Reaction was fierce. Many scientists and ethicists condemned the experiment as unethical and unsafe, fearing that it could inspire rogue or frivolous attempts to create permanent genetic changes using unproved and unregulated methods.
A Chinese government investigation concluded in January that He had “seriously violated ethics, scientific research integrity and relevant state regulations.”
Questions about other American scientists’ knowledge of He’s plans and their failure to sound a loud alarm have been an issue since He revealed his work in November.
Quake is facing a Stanford investigation into his interaction with He. That inquiry began after the president of He’s Chinese university wrote to Stanford’s president alleging that Quake had helped He.
“Prof. Stephen Quake provided instructions to the preparation and implementation of the experiment, the publication of papers, the promotion and news release, and the strategies to react after the news release,” he alleged in letters obtained by The New York Times. Quake’s actions, he asserted, “violated the internationally recognized academic ethics and codes of conduct, and must be condemned.”
Quake denied the allegations in a lengthy interview, saying his interaction with He, who was a postdoctoral student in his lab eight years ago, had been misinterpreted.
“I had nothing to do with this, and I wasn’t involved,” Quake said. “I hold myself to high ethical standards.”
Quake showed The Times what he said were the last few years of his email communication with He. The correspondence provides a revealing window into the informal way researchers navigate a fast-moving, ethically controversial field.
When to report controversial ideas?
The emails show that He, 35, informed Quake, 49, of milestones, including that the woman became pregnant and gave birth. They show that Quake advised He to obtain ethical approval from Chinese institutions and submit the results for vetting by peer-reviewed journals, and that he agreed to He’s requests to discuss issues like when to present his research publicly.
None of the notes suggest Quake was involved in the work. They do contain expressions of polite encouragement like “good luck!” Though Quake said he urged He not to pursue the project during an August 2016 meeting, the emails, mostly sent in 2017 and 2018, don’t tell him to stop.
As global institutions like the World Health Organization work to create a system to keep cowboy scientists from charging into the Wild West of embryo editing, Quake’s interactions with He reflect issues that leading scientific institutions are grappling with.
When and where should scientists report controversial research ideas that colleagues share with them in confidence?
Have scientists acted inappropriately if they provide conventional research advice to someone conducting an unorthodox experiment?
“A lot of people wish that those who knew or suspected would have made more noise,” said R. Alta Charo, a bioethicist at the University of Wisconsin-Madison who co-led a 2017 national committee on human embryo editing.
But she said scientists were not necessarily complicit if instead of trying to stop rogue experimenters, they advised them to follow ethical and research standards in hopes that institutions would intervene.
Rice University has been investigating Michael Deem, He’s Ph.D. adviser, because of allegations that he was actively involved in the project; he had said publicly that he had been present during parts of it. Deem’s lawyers issued a statement strongly denying the allegations.
The correspondence Quake shared provides new details about He’s project, called germ line editing, including indications that the twin girls were quite premature and remained hospitalized for several weeks. They were born in October, contrary to previous reports.
Quake is an entrepreneur whose inventions include blood tests to detect Down syndrome in pregnancy and to avoid organ transplant rejection. He is co-president of an institute funded by Facebook founder Mark Zuckerberg and his wife, Dr. Priscilla Chan. He does not do gene editing and said he was surprised when He told him during a 2016 visit to Stanford that he wanted to be the first to create gene-edited babies.
“I said, ‘That’s a terrible idea. Why would you want to do that?’” Quake recalled. “He kind of pushed back, and it was clear that he wasn’t listening to me.”
Quake changed tack. “I said, ‘All right, if you’re not going to be convinced that I think this is a bad idea and you want to go down this path, then you need to do it properly and with proper respect for the people who are involved, and the field.’”
That meant obtaining ethical approval from the equivalent of U.S. institutional review boards (known as IRBs), Quake advised, as well as getting informed consent from the couples participating and only editing genes to address a serious medical need.
“I didn’t think it was something he would seriously do,” said Quake, adding that he assumed if He sought ethical approval and was rebuffed, “presumably he’d stop.”
Soon afterward, He emailed: “I will take your suggestion that we will get a local ethic approve before we move on to the first genetic edited human baby. Please keep it in confidential.”
In June 2017, He, nicknamed JK, emailed a document saying a hospital ethics committee had approved his proposal, in which he boasted that his plan could be compared to Nobel-winning research.
In He’s 2017 correspondence, he said he would be editing a gene called CCR5, altering a mutation that allows people to become infected with HIV. Many scientists have since argued it was medically unnecessary because babies of HIV-positive parents can be protected other ways. Quake said he believed there was not scientific consensus about that.
In early April 2018, He’s “Success!” email said “the embryo with CCR5 gene edited was transplanted to the women 10 days ago, and today the pregnancy is confirmed!”
Quake did not reply immediately. Instead, he forwarded the email to someone he described as a senior gene-editing expert “who I felt could give me advice.”
He redacted the name of the expert.
“FYI this is probably the first human germ line editing,” Quake wrote. “I strongly urged him to get IRB approval, and it is my understanding that he did. His goal is to help HIV-positive parents conceive. It’s a bit early for him to celebrate but if she carries to term it’s going to be big news I suspect.”
The expert replied: “I was only telling someone last week that my assumption was that this had already happened. It will definitely be news ...”
Quake considered that response “very blasé,” he said. “He’s not surprised at all. And he’s not saying, ‘Oh my God, you got to notify the mythical science police.’”