American scientist played more active role in ‘CRISPR babies’ project than previously known

BEIJING — An American scientist at Rice University was far more involved in the widely condemned “CRISPR babies” experiment than has previously been disclosed. Most notably, STAT has learned that Rice biophysicist Michael Deem was named as the senior author on a paper about the work that was submitted to Nature in late November.

Deem’s prominent authorship indicates that a respected American researcher played an instrumental role in the controversial project, which sparked a worldwide furor. His involvement could have encouraged volunteers to join the experiment and lent credibility to He Jiankui, the Chinese scientist who led the work.

Emails provided to STAT show that Deem was listed as the last author — which, in the life sciences, is typically reserved for the senior researcher who oversees a study. The paper, titled “Birth of twins after genome editing for HIV resistance,” has another nine contributors, including He as the first author, where the person who makes the most hands-on contribution is credited.

The now infamous Chinese scientist created a sensation when he announced the birth of twin girls, whose genes had been altered using CRISPR technology, before an international conference in Hong Kong last November. He received intense criticism for violating scientific and ethical norms against starting a pregnancy with genetically modified human embryos, and Nature quickly decided not to proceed with peer review of the paper.

He was fired by the Southern University of Science and Technology in Shenzhen last week after an official investigation found that his work seriously violated Chinese government rules, according to the Xinhua News Agency. The inquiry also concluded that He’s project team involved “overseas personnel.” It didn’t name Deem or detail his contributions, but he’s the only foreign scientist known to have been involved in He’s genome-editing research.

A Chinese scientist who worked on the project said Deem was more than a bystander: Deem collaborated with He on the experiment and participated as a member of the research team during meetings with several volunteers in 2017 as they were recruited and went through the informed-consent process — a crucial component of a clinical trial. Deem helped to obtain the volunteers’ consent, speaking with them through a translator, said the Chinese member of the team, who asked not to be identified because the person was not authorized to speak to a reporter.

“As a prominent scientist from an elite university in the U.S., Deem’s presence is likely to have a significant role in persuading potential candidates to jump on board,” said Jia Ping, a human rights lawyer who is founder and chief executive officer of the Beijing-based nongovernmental organization Health Governance Initiative. They would not have known that neither Deem nor He had any experience conducting clinical trials.

Researchers contacted by STAT say it’s important to get to the bottom of Deem’s role. “The nature of the incident would be quite different with or without his involvement,” said Jennifer Doudna, a genome-editing pioneer of the University of California, Berkeley.

Deem, a bioengineering and physics professor, was He’s Ph.D. adviser when He was a graduate student at Rice between 2007 and 2010. Deem told the Associated Press in its initial story on the project in November that “I met the parents. I was there for the informed consent of the parents” — referring to the twins’ parents — though why he was there was unclear. His remarks prompted Rice to launch an investigation into Deem’s involvement.

Then last month, Deem’s attorney issued a statement saying that, “Michael does not do human research and he did not do human research on this project.”

While Deem might not have physically done the lab work, such as handling the embryos, being listed as an author, especially the last author, of the CRISPR-babies paper is strong evidence for Deem’s participation in the research in a significant way, said Hank Greely, a lawyer and bioethicist at Stanford University.

An early draft of the paper listed He as the last author — Deem was the second-to-last author, according to excerpts provided to STAT. But for unknown reasons, the order of authors was changed in the version submitted to Nature in late November: It listed He as the first or lead author, and Deem the last.

Deem has declined to comment. But his lawyers issued a statement this week denying that he was “the lead, last, or corresponding author” on the paper submitted to Nature: “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.”

Deem’s lawyers, David Gerger and Matt Hennessy of Houston, disputed the claim that he was present when the parents of the gene-edited twins went through the consent process. “Dr. Deem was not in China, and he did not otherwise participate, when the parents of the reported CCR5-edited children provided informed consent,” they said, in a statement that seems to contradict what the AP reported. The AP told STAT that it accurately quoted Deem and that it “stands by its story.”

The lawyers did not respond to follow-up questions about whether they denied Deem’s involvement in the CRISPR babies project in any way.

Paul Knoepfler, a stem-cell biologist at the University of California, Davis, said Deem’s participation might have made He feel more confident about proceeding with the experiment. “I don’t think He Jiankui would have done the project if Deem had been strongly disapproving of it,” the UC biologist said. The fact that his lawyers didn’t categorically deny Deem’s involvement in the project is telling, suggesting that he did have some sort of a role, Knoepfler added: “My best guess is he was intellectually involved in the project in some important way.”

STAT has also found that Deem and He co-authored two preclinical papers that tested the CRISPR gene-editing technology in mouse, monkey, and human embryos — without establishing any pregnancy in humans. Both papers’ “Author Contributions” statements say that Deem designed the project and wrote and edited the manuscript. STAT was provided one of the papers and a scientist with a copy of the other manuscript read aloud its author-contributions statement over the phone.

One paper — submitted to Nature along with the CRISPR-babies paper in late November — modified the CCR5 gene, which encodes a protein that helps HIV enter and infect cells, the same gene He claimed he had altered in the twins to protect them against infection with the AIDS-causing virus. The other paper, which reported on the editing of the PCSK9 gene that encodes a protein that helps regulate the level of cholesterol in the bloodstream, was submitted to Science Translational Medicine. Both were rejected.

Both journals said they couldn’t comment on any possible submissions because they are confidential. But editors at both journals said they have a policy of automatically sending an email to every author of a submission. The email notifies the individual that they are listed as an author and includes the title of the paper. This gives researchers the opportunity to notify the journal if they were unaware of the paper, have not approved of the content/submission, or do not qualify as an author. This can be grounds for rejection, and the journal would not send it out for peer review under such circumstances.

Deem’s lawyers said “he did not authorize submission of manuscripts related to CCR5 or PCSK9 with any journal, and he was not the lead, last, or corresponding author on any such manuscript.” But in response to followup questions from STAT, they then acknowledged that Deem was listed as an author on all three gene-editing papers and said he had had instructed the journals to remove his name from all the manuscripts.

In addition to the submissions to Nature and Science Translational Medicine, Deem and He have eight published papers together, the latest in 2017. While none is related to gene editing, they show that the two have closely collaborated since He graduated from Rice.

To many researchers, a key question is whether Deem’s involvement in the CRISPR babies trial broke U.S. rules on human-subjects research, because he didn’t obtain approval from Rice University. Even if he didn’t use federal funds for the work, government regulations require researchers to seek approval from an ethics committee at their institution should they want to carry out clinical trials abroad.

At least two active federal grants — from the National Science Foundation and the Department of Energy — contributed to Deem’s recent work in his own lab. The NSF provided a five-year, $12-million grant, which will come to an end this August, for Rice’s Center for Theoretical Biological Physics that supports Deem’s research.

Neither Deem nor his lawyers would comment on whether he has broken federal regulations on human-subjects research or whether he used any of his federal grants on the CRISPR babies work.

NSF’s Office of Inspector General said it could not comment on the existence of an investigation, and DOE did not respond.

Rice has said in a statement that it was unaware of the CRISPR babies work, and that to its knowledge, none of the clinical work was performed in the U.S. The university began a full investigation in late November and wouldn’t offer further comments.

If Deem violated human-subjects protection regulations, said Dr. Kiran Musunuru, a genome-editing expert at the University of Pennsylvania, “it would be a career suicide.”

Any federal grants Deem has could be in jeopardy. “That could be a very powerful sanction,” said Greely. “It could put him out of business.”

Regardless of the outcome of Rice’s investigation, Deem may not remain at the university for much longer. Last June, he gave a talk at the City University of Hong Kong, apparently as part of a job interview for the deanship of the College of Engineering. He was offered the job a few months later, a professor at the university told STAT. Deem was supposed to assume the position in early January, but the university has appointed an acting dean instead, the professor added.

Deem’s possible involvement in the CRISPR babies experiment has led the Hong Kong university to review the contract, which is now “pending on the result of the investigation undergoing at the Rice University,” said the Hong Kong university’s press office. It would not say if it would terminate Deem’s contract if he is found to have been involved in the project. His lawyers would not comment on the matter.

“If Deem was an active participant in the research, then I don’t think it would be appropriate” for him to be a university dean, said Greely. “I’d not want to hire him, and I’d advise other universities not to hire him, because he has shown very bad judgment at the very least.”