MOSCOW — Russian health officials are playing down international concerns that a Moscow researcher plans to create gene-edited babies any time soon, saying for the first time that the experiment would be “premature.”

Denis Rebrikov, the scientist who has said he wants to use the genome-editing technology CRISPR to alter embryos, has sparked widespread alarm among scientists who fear that he could become the second researcher to conduct such work, following the birth of gene-edited twins in China last year.

But in a statement issued last week to Russian wire services, the health ministry here said it fully supports the World Health Organization position against making changes to the human germline — the genome of eggs, sperm, and embryos — that would be inherited by future generations “until its implications have been properly considered.” The ministry said it views any clinical use of genome-editing technologies on human embryos “premature.”

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The ministry’s stance puts at least a temporary hurdle in front of Rebrikov, who would need the agency’s approval to proceed with his experiment to repair a mutated gene that causes deafness. It’s particularly significant given the lack of independence of hospital ethics committees that review medical experiments, and in the absence of definitive public statements on the ethics of the proposed research by scientific bodies, which have been suddenly thrust into the global spotlight by one man’s ambition.

Separately, Vladimir Chekhonin, the Russian Academy of Sciences’ vice president for medical sciences, told STAT that until proof of safety for genome editing is shown in experiments with human embryos, “there should be no clinical activity whatsoever.” He said the academy has not yet discussed Rebrikov’s project because there was no request for it to do so.

But Chekhonin, who said he knows Rebrikov well, said the scientist would not go against regulators in this matter: “I am confident he has the common sense not to break the law. I have no reason not to be confident in him.”

Elena Grebenshchikova, a bioethicist from the academy’s Institute of Scientific Information for Social Sciences, told STAT that the health ministry’s statement is important because “there is simply no entity in the scientific community that could come out with a consolidated opinion on this issue.” She noted that the academy used to have its own bioethics committee, but it went defunct in 2017 after the death of a prominent philosopher and bioethicist behind the effort.

“This is definitely affecting the public discussion, as people get their information mostly from journalists, who often exaggerate the words of experts,” said Grebenshchikova, who also works at Pirogov Medical University, where Rebrikov is vice rector.

Russian media first reported on Rebrikov’s work just weeks before Chinese scientist He Jiankui told the world last November about the births of Lulu and Nana, the gene-edited twins designed to be resistant to HIV. Rebrikov’s team at the time had successfully created embryos with a mutation in the same CCR5 gene, but had not implanted them — yet, as he later told the press.

After an eventual international media frenzy in the summer sparked by a Nature story, Rebrikov, 43, decided to switch from CCR5 to GJB2, a gene that, when mutated, causes a form of congenital deafness. In August, he told N+1, a Russian science news website, that he even had a couple lined up for the experiment, but the woman later stated they had decided to drop out.

Olga Andreeva, a legal scholar from the Tomsk State University who studies genomic research regulation, reviewed the Oct. 6 health ministry statement for STAT. She said its conclusion that clinical applications of embryo editing are “unacceptable” relies partly on the fact that the government’s guidance on IVF procedures in Russia has a strictly defined list of steps that does not include any genetic engineering manipulations.

“This, however, does not mean there is a ban on these manipulations,” Andreeva wrote in an email. “I think any such ban should be explicit, direct and enshrined in a law and not in a ministry document.” The ministry, she added, admits “the undisputable fact that we need complex regulation for human genome editing.”

Genome editing of human embryos for research purposes falls into a gray area that the health and science ministries are working together to address, according to the statement. In the absence of a law, it “is neither allowed nor banned in Russia, as there are no conditions and limits set on this method in the legal framework,” Andreeva said.

Scientists are hoping to have input into the review of Rebrikov’s project. Last year, five months before news of He Jiankui’s experiment broke, the Russian Foundation for Basic Research awarded the equivalent of about $1.8 million in grants to 41 projects exploring various aspects of genomic research regulation, from gene editing to organ bioprinting and genetic forensics.

Svetlana Borinskaya of the Vavilov Institute of General Genetics, who is part of one of these projects, said that a preliminary analysis of legal frameworks for genomic research in over 50 countries has led her team to conclude that even in the developed world, these frameworks tend to be patchy and inconsistent, just like in Russia. Borinskaya’s group has proposed to gather all 41 teams at a national conference in 2020 intended to identify remaining gaps in knowledge and a common further direction for research.

An ethics gap

Even though individual researchers are quite active in debating the ethics and oversight of boundary-pushing genomics like Rebrikov’s experiment, the Russian Academy of Sciences has yet to make an official statement on the matter. The academy, which has been struggling to find a new public role after a 2013 reform that greatly diminished its administrative powers, is having a general assembly this November to elect new members, and it could decide to use the gathering of all its members to discuss Rebrikov’s work.

In post-Soviet Russia, bioethics has yet to claim a prominent place in the research community. Vasily Vlassov, vice president of the Russian Society for Evidence Based Medicine and a professor at the Higher School of Economics, told STAT that ethics committees in hospitals are still “underdeveloped” and lack independence from management. “Ethics committees in research organizations mostly lead a miserable existence because no one wants to invest in them. Their control is mostly a formality,” Vlassov added.

Ivan Gordeev, who chairs the Pirogov Medical University ethics committee, told STAT that the committee has not reviewed Rebrikov’s work. Even though Rebrikov is a vice rector there, it is not required to do so because his research on genome editing is conducted at the Kulakov National Medical Research Center of Obstetrics, Gynecology and Perinatology. However, an upcoming international conference at the university at the end of October will discuss ethical questions around clinical studies, and Gordeev, who co-organizes the conference, thinks it’s a “good idea” to bring up the issue of human germline genome editing there.

The Ministry of Health ethics committee, established in 2015, is led by Sergey Kutsev, director of the Research Center for Medical Genetics and the government’s chief geneticist. He has openly called for a moratorium on Rebrikov’s project, even before it has been formally taken up for discussion by his committee, which oversees experimentation on humans.

Kutsev declined to comment for this story, citing work commitments. In earlier interviews with Russian media, he said Rebrikov’s planned intervention was medically unnecessary and dangerous and called on physicians to refrain from participating in these experiments.

Bioethicists with the Russian Academy of Sciences said there’s no particular “Russian way,” no distinctly Russian understanding of ethics, that would make Rebrikov’s experiments acceptable here though they veer outside global scientific norms. “If there is any ‘Russian way’ in solving ethical issues after all, it is unlikely to impact the problem of human genome editing. In this regard, Russia is likely to follow an international consensus and will not endorse ethically murky experiments,” said Olga Popova of the academy’s Institute of Philosophy.

When asked about a scenario where she personally would approve of Rebrikov’s experiment, Grebenshchikova listed reliability and safety as the main criteria. “In any case, once reliability and safety are convincingly shown, it can only be used for therapeutic purposes and not human enhancement. The latter, even at a purely experimental stage, leads to a slippery slope of people not willing to comply with norms and bans,” the researcher said.

Hugging bears and editing embryos

Amid the debate, the people at the center of it are extremely adamant they are not going rogue. Pirogov Medical University rector Sergey Lukyanov told STAT that Rebrikov’s work is strictly experimental with “absolutely no intentions” to move to clinical applications before official approval. “He is not going to do it without global public consensus on the acceptability of this too,” he added.

In the June 2019 interview with Nature, Rebrikov was famously quoted as saying, “I think I’m crazy enough to do it.” This remark prompted the journal to call in an editorial for the government to intervene and regulate such work, and a flurry of reports on “the next CRISPR babies” ensued, leading many to believe that these births were a matter of months, if not days, away.

Svetlana Borinskaya, who says she has known Rebrikov for many years and has co-authored research with him, thinks the true meaning of the molecular biologist’s words might have been lost in translation. “When he says ‘I’m crazy enough to do it,’ he means, ‘I’m crazy enough to jump through all the maddening hoops of legal approval for this in Russia and do it.’ He is a completely sane person, a fantastic and experienced lecturer — yet he just told the journalists what he thought, failing to account for the risk of being misunderstood,” she told STAT.

“I also feel there might be just a bit of stereotypes here. Oh, those Russian scientists hug bears and edit embryos — together with the bears, presumably,” Borinskaya quipped.

Yet in a July interview with Chrdk.ru, a Russian science news website, Rebrikov was also quoted as saying that if the health ministry gives the green light, he is “ready to implant the embryo tomorrow,” with seemingly little regard for international consensus on the issue.

Rebrikov himself told STAT he would not be giving any more interviews for the foreseeable future as he was not prepared to talk “theoretically” anymore and was tired of poor interpretations of his intentions. He would not say whether he still planned to submit an application to the health ministry this month for approval of the experiment, which he previously said he would.

“I have to get some data published in a reputable journal first. I don’t want to talk with nothing to show,” he said.

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