A Russian biologist has thrust himself to the forefront one of the world’s most urgent medical-science debates by declaring his intention to use CRISPR gene-editing techniques to modify the genomes of human embryos and implant them in women.
Denis Rebrikov, a DNA-technology specialist who heads a genome-editing lab at a Moscow fertility clinic, vowed this month to seek Russian authorities’ approval to disable a gene, known as CCR5, in carefully selected embryos of would-be mothers who are HIV-positive or who suffer from specific genetic disorders.
The aim would be to block the transmission of the condition and at least boost resistance in the lab-altered newborns, beginning as soon as this year.
“I don’t like to use the term genetically modified,” Rebrikov told RFE/RL, in English, on June 27. “It’s just a correction of a mutation we have in [some] babies.”
The plan has raised an international outcry over the fate of such “CRISPR babies” and the ethical and technological implications, amplifying fears that arose when Chinese scientist He Jiankui made a shock announcement last year that he’d modified the genomes of recently born twin girls.
Scientists and ethicists have grappled for decades with the practical and moral obstacles to genetic engineering in plants and animals. Genome editing in human embryos that are then transferred into a woman is seen as a thick red line for many.
Rebrikov said he welcomed the controversy since the influential scientific journal Nature quoted him two weeks ago vowing to go forward as soon as he had suitable volunteers and local approval. “My position is that I don’t want to do it silently,” he told RFE/RL. “I want to do it publicly, with publicity so that we can talk about it.”
‘Crazy,’ Slippery Slope,’ ‘Designer Babies’
The debate over lab-directed gene mutations intensified when biologist He told the world in November he had edited the same CCR5 gene in “Lulu” and “Nana,” twin month-old girls who he said appeared to be healthy.
The revelation embarrassed Chinese authorities, who quickly suspended He’s activities, and added to the chorus of calls for a global moratorium on such work.
The 43-year-old Rebrikov works at the Kulakov National Medical Research Center for Obstetrics, Gynecology, and Perinatology as well as the Pirogov Russian National Research Medical University. Unlike the controversial Chinese scientist, Rebrikov said, “I didn’t show any babies — just work.”
The World Health Organization (WHO) has formed an expert advisory committee to develop “global standards for governance and oversight of human-genome editing,” but its conclusions appear to be at least a year off.
A number of the WHO committee’s members have already condemned Rebrikov’s eagerness to proceed, using terms like “irresponsible” and “cowboy.”
But WHO committee co-chairwoman and former U.S. Food and Drug Administration (FDA) director Margaret Hamburg acknowledged to the medical news site STAT that they don’t have “the teeth to do some of what may ultimately need to be done” in the face of such pioneering efforts.
Rebrikov must still find suitable cases and volunteer subjects from among a small subset of HIV-infected women or parents who share the mutation for a condition like deafness or dwarfism, and then convince at least three Russian regulatory bodies to green-light the plan.
“Russia now, I think, is a good country to do this type of experiment,” Rebrikov told ScienceInsider recently. “It’s not very free in politics, but it’s very free in science.”
Rebrikov expanded on that notion to RFE/RL, saying it was a reference to Russia’s regulatory environment. “In Russia, we have a very good system of idea centers,” he said. “The point is not the technology. It’s mostly all the same technology everywhere. It’s a regulatory point, and I think that the specificity of Russia is that we can make a decision to use some technology or clinical methods…on the level of a ministry or a local body.”
Nature published an editorial that acknowledged Rebrikov’s “skills, tools, and position” and praised his willingness to publicly discuss plans for his gene-altering work. But it urged the scientific community to “act now on CRISPR babies” and insisted “Rebrikov must listen to the concerns and the critics, and not move forward until the dangers are assessed.”
Almost overnight, the high-profile effort at a breakthrough by Rebrikov and his team has boosted Russia’s profile in genetic sciences and gene editing — a field that was revolutionized with the emergence in 2015 of the so-called CRISPR technique that employs molecular “scissors” to find and replace functional bits of DNA.
CRISPR’s appeal is that it helps modify genes — in theory, to remove unwanted characteristics for more desirable ones — without introducing outside DNA, for instance from a bacterial carrier agent.
But experts warn there could be unforeseen effects on “CRISPR babies” because of changes to the gene in question (“on-target” mutation) or a CRISPR mistake that alters the wrong snippet of a genome (“off-target” mutation).
Some of those consequences might only appear later in life, they say, and could include susceptibility to other diseases, shortened life spans, or other tragic outcomes.
They stress the tradeoff between the risk of error and the benefits of gene-editing to combat conditions that might be rare and otherwise mitigable.
Rebrikov said his lab had a system — “I think unique” — that allowed careful checking for “off-target” effects of a genome editor.
A bigger obstacle, he acknowledged, was ensuring that all the cells in a blastocyst that will develop into the embryo are free of problems, rather than just the five-to-seven cells that can be inspected in the lab.
Beyond scientific and ethical challenges, Rebnikov’s plans could invite objections on religious grounds. “The attempts of human beings to put themselves in the place of God by changing and ‘improving’ His creation at their will may bring to humanity new burdens and suffering,” the Russian Orthodox Church stated in a chapter on bioethics in its Basis Of The Social Concept.
The leadership of the Russian Orthodox Church wields considerable influence and boasts 90 million or so adherents.
“I think it’s a good situation that we’re talking about it, because the population should be ready for a [new] technology, and now they’re not ready,” Rebrikov told RFE/RL. “To make society ready, we should be talking about it — a lot. We need to discuss it over and over, until a majority [of] society says, ‘OK, the research is safe and researchers will do everything correctly,’ and society will accept it.”
He and his colleagues first hinted at his intentions in a research paper in the Biomedical Journal of Pirogov RNRMU in October. In it, they said preclinical work suggested that a CRISPR-Cas9 modification should “protect the fetus from HIV infection in utero and at childbirth” and provide “a potential lifelong immunity to HIV.”
“Importantly, the edited genome will be passed on to subsequent generations,” the paper predicted.
HIV/AIDS remains a growing epidemic in Russia, with nearly 1 million infections by official estimates but more than twice that number according to some.
Rebrikov has said his target group would be women who are resistant to antiretroviral (ARV) treatments to purge their blood of the HIV virus that can lead to AIDS but who nevertheless want to have children.
He conceded that statistics suggest the number of such women is only around 30 in all of Russia, out of a population of around 145 million people.
But because HIV is not always transferred “vertically” from a parent, Rebrikov would prefer to target cases where both parents suffer from a genetic disorder that is more likely to be passed. “I don’t like the HIV case because we couldn’t say 100 percent that the baby would be infected,” he told RFE/RL.
In plants and animals, genetic modification has been used for decades under evolving regulatory climates to boost crop resistance to disease or pestilence, to bring meatier cattle or fish to the table sooner, or to simplify the delivery of vaccines, among other things.
But scientists have warned about the threat genetically modified organisms pose to biodiversity, the mixing of modified stocks with wild animals, and more unforeseen problems.
And the public has been wary of the effects on consumers, the food chain, and the environment.