CRISPR Scandal Drags in Another US Researcher, Stanford's Quake

illustration of CRISPR

When a big scandal occurs and the fallout is investigated, two of the big questions asked are: “Who knew about it?” and “When did they know?” This is almost exactly what is occurring in the wake of the scandal surrounding the creating of a set of Chinese babies who were prenatally treated with CRISPR gene editing.

He Jiankui, a researcher with the Southern University of Science and Technology of China, used CRISPR to alter the embryos of seven couples to make them resistant to HIV. In November 2018, He Jiankui made his announcement at the Second International Summit on Human Genome Editing held at the University of Hong Kong. The details of the research were met with widespread condemnation and criticism by researchers globally.

He Jiankui has been investigated by the Chinese government and accused of ethics violations. In the U.S., He was assisted by Michael Deem, a professor at Rice University in Houston, used CRISPR gene editing during in vitro fertilization (IVF) procedures. Additional investigations by Rice University and the National Institute of Health were initiated in the U.S. into the role of Deem.

For his part, in December, Deem’s attorney stated, “Michael does not do human research and he did not do human research on this project.”

In a statement issued by his attorneys later, they said, “Michael Deem has done theoretical work on CRISPR in bacteria in the past, and he wrote a review article on the physics of CRISPR-Cas. But Dr. Deem has not designed, carried out, or executed studies or experiments related to CRISPR-Cas9 gene editing—something very different.”

The attorneys also say that Deem was not present at the consent process of the parents who gave birth to twins.

A call for a moratorium was written by 18 leading researchers and bioethicists from seven countries, including Feng Zhang and Emmanuelle Charpentier, who in separate labs, are noted as the competing inventors of CRISPR.

But as investigations have continued, numerous scientists in the U.S. and worldwide have divulged earlier communications with He, many of which sent warning lights flashing for the scientists, although few if any did anything—nor is it clear what they should or could have done.

The most recent is Stephen Quake, a Stanford University bioengineer and inventor, who recently shared several years’ worth of email communications between himself and He with The New York Times. Quake is also the co-president of the Chan Zuckerberg Biohub, an independent research center set up by Priscilla Chan and her husband, Facebook chief executive officer Mark Zuckerberg, to coordinate activities between scientists at UCSF, UC Berkeley and Stanford.

Stanford has launched an investigation into Quake’s interaction with He. It was initiated when the president of He’s Chinese university wrote a letter 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,” the letter claimed. The Chinese administration further alleged that Quake “violated the internationally recognized academic ethics and codes of conduct, and must be condemned.”

Quake denies this, telling The New York Times that He had been a postdoctoral student in his laboratory eight years ago and that their interactions have been misinterpreted. “I had nothing to do with this and I wasn’t involved,” Quake told The Times. “I hold myself to high ethical standards.”

And, in fact, the bulk of the emails The New York Times quote seem to indicate that when He told Quake of his experiments, Quake not only encouraged He to run his experiments past his university’s and hospital’s ethics committees, but was concerned enough to bring them to the attention of an unnamed leading CRISPR expert.

The New York Times writes, “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.”

Quake’s communications with the unidentified CRISPR expert also suggest that neither researcher was surprised by He’s actions, and both were concerned. Quake found many of He’s statements worrisome. He tells The New York Times, “The little corner-cutting thing came up again: ‘Well, there were actually two hospitals involved and you know, we had approval from one and we did work at both hospitals.’ And I said, ‘Well you better make sure you have that straightened out.’”

Apparently Quake also tried to convince He not to publicly release the information at the Hong Kong meeting, but to instead work on the peer-review publications and discussions with people in the field. He Jiankui apparently emailed Quake, saying, “I do not want to wait for 6 months or longer to announce the results, otherwise, people will say ‘a Chinese scientist secretly hide the baby for 6 months.’”

Quake had responded, “It is prudent to let the peer review process follow its course.”

But He, as everyone now knows, headed to Hong Kong and made his presentation, along with a YouTube video, then quickly left the country after widespread criticism and condemnation.

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Although Quake is currently under scrutiny, it’s been clear for some time that He was in communication with a number of prominent researchers prior to his announcement.

For example, prior to his announcement at the meeting, He Jiankui had requested a private meeting with Jennifer Doudna, the University of California, Berkeley researcher who is most often identified as being the discoverer of CRISPR (along with Emmanuelle Charpentier, and in a competing patent claim, MIT-Harvard Broad Institute scientist Feng Zhang).

Doudna met He in the lobby of the hotel where the summit was being held. “His demeanor was an odd combination of hubris and naivete,” Doudna told STAT. “He was very confident in his work, and totally not understanding what an explosion he had caused.”

Doudna and three of the organizers of the summit arranged a dinner with He at the hotel and focused dozens of very technical questions on the researcher. He lasted an hour under the scrutiny, STAT reports, before he threw some cash on the table “and stormed off. Fearful of his safety, he left the Meridien and checked into another hotel.”

Numerous researchers are now looking back at earlier meetings with He and seeing all the seeds of the recent scandal. Sheila Jasanoff, with Harvard University, told STAT, He “clearly did not have deep misgivings about plugging ahead with gene editing, and I sensed no exposure to the sorts of ethical debates our guys are routinely involved in.”

And computational biologist Max Haeussler of UC Santa Cruz, who shared a double room with He at a conference, remembered He discussing the dangers of editing human embryos. “I found this remark already strange back then,” Haeussler told STAT. “Everyone in the room knew that it’s out of the question to edit human embryos. Why mention that it’s dangerous?”

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