When Chinese scientist He Jiankui announced he had edited the genomes of two babies last November, he sparked an international outcry. Many feared he had opened the floodgates to human genetic engineering. It seems those fears were well-founded after a Russian researcher said he plans to do the same by year-end.
Denis Rebrikov is the head of a genome-editing laboratory at the Kulakov National Medical Research Center for Obstetrics, Russia’s largest fertility clinic. He told Nature he plans to use the gene-editing technology CRISPR on human embryos to disable the CCR5 gene, the same one He targeted, which is believed to confer immunity to HIV.
Russia’s regulations on genome editing are hazy, but Rebrikov says he plans to ask the relevant ministries for permission before moving ahead. His goal is to edit embryos for women with HIV so they don’t pass on the infection to their children, and he says he is already working with an HIV center to find women willing to take part in the experiments.
What’s controversial about both Rebrikov and He’s research is that unlike gene therapies that retroactively alter the genes of adults to treat inherited disease (currently making their way into clinics), their approach attempts to alter germline DNA. That refers to editing genes in sperm, eggs, or embryos, leading to changes that will be passed on to future generations.
The news of Rebrikov’s plans have been broadly decried by experts. The complaints are the same as those raised following He’s announcement, primarily that we still don’t understand the process of gene editing and the potential risks well enough to justify even supposedly medically-inspired uses of the technology.
For a start, CRISPR is still a fairly imprecise technology and can often lead to significant “off-target” effects where unintended changes are made to genes that weren’t the focus of the study. “On-target” effects, where the correct gene is edited but not as intended, are also a concern.
Even if the therapy only edits the correct gene in the correct way, it’s still hard to be sure exactly what the effect will be. Genetics isn’t as simple as one gene encoding for a single easily identifiable trait; hundreds of genes and developmental factors can interact to control something like your propensity for obesity. A recent study that suggested that the mutation to the CCR5 gene He introduced could shorten the life expectancy of the children highlights the potential unintended consequences.
That’s prompted scientists to call for a global moratorium on human germline DNA editing, and bodies like the World Health Organization and National Academies have launched panels to try to work out how to govern this emerging technology. But there are big question marks over how feasible it will be to come up with sensible rules for this emerging field—and whether it’s even really possible to police.
Working out whether germline edits have negative effects will take lifetimes or even generations, Katie Hasson, from the Center for Genetics and Society, writes in The Hill. And even if that’s eventually resolved, there’s no technical solution for the biggest problem with this technology: the inevitability of creating genetic haves and have nots based on whether parents are wealthy enough to buy their kids genetic upgrades.
“No matter how sophisticated genome editing techniques become or how many safety criteria they meet, these fundamental social risks cannot be mitigated in a lab,” she writes.
Unfortunately, it seems the genie is already out of the bottle. STAT reported that shortly after his announcement He received multiple inquiries from fertility clinics asking him to teach them how to carry out CRISPR editing of embryos.
While CRISPR editing in humans is undoubtedly incredibly complex, it’s not out of reach for a smart and well-resourced biologist. And it’s not hard to imagine that there are plenty of rich people and even organizations that would be happy to bankroll that kind of effort.
We still don’t really understand how genes contribute to most of our traits or what the consequences of meddling with them are, but there are enough unscrupulous people in the world willing to sell the dream anyway. It’s quite possible such projects are already underway, and that it’s only He and Rebrikov who have talked about them publicly.
Current regulation of the technology is highly variable between countries, so such efforts may not even be illegal. Rebrikov says Russian law doesn’t currently prohibit germline editing, though he expects rules to be updated. And despite his subsequent upbraiding, Chinese law didn’t actually set any penalties for what He did, though that looks likely to change soon. Even in the US, legal restrictions were nearly dropped earlier this month and the law still appears up for debate.
But even if an international moratorium or ban is agreed upon—probably a long shot given the fractured geopolitical environment—the technology and know-how required to do germline editing is generic enough that clandestine projects would be fairly easy to keep hidden.
Whether we like it or not, the Pandora’s box of human gene editing has been opened. The question now is, can we work out how to manage the impact?