As powerful as the gene-editing technique Crispr is turning out to be—researchers are using it to make malaria-proof mosquitoes, disease-resistant tomatoes, live bacteria thumb drives, and all kinds of other crazy stuff—so far US scientists have had one bright line: no heritable modifications of human beings.
On Wednesday, the bright line got dimmer. MIT Technology Review reported that, for the first time in the US, a scientist had used Crispr on human embryos.
Behind this milestone is reproductive biologist Shoukhrat Mitalipov, the same guy who first cloned embryonic stem cells in humans. And came up with three-parent in-vitro fertilization. And moved his research on replacing defective mitochondria in human eggs to China when the NIH declined to fund his work. Throughout his career, Mitalipov has gleefully played the role of mad scientist, courting controversy all along the way.
Yesterday’s news was no different. Editing viable human embryos is, if not exactly a no-no, at least controversial. Mitalipov and his colleagues at Oregon Health and Science University fertilized dozens of donated human eggs with sperm known to carry inherited disease-related mutations, according to the Tech Review report. At the same time, they used Crispr to correct those mutations. The team allowed the embryos to develop for a few days, and according to the original and subsequent reports a battery of tests revealed that the resulting embryos took up the desired genetic changes in the majority of their cells with few errors. Mitalipov declined to comment, saying the results were pending publication next month in a prominent scientific journal.
Big if true, as the saying goes. Mitalipov’s group never intended to implant the eggs into a womb, but the embryos were “clinical quality” and probably could have survived implantation. That makes this only the second time scientists anywhere have edited viable embryos—if that’s indeed what Mitalipov did. Maybe this news is important enough to make it to the popular press without a peer-reviewed, published paper, but without one it’s impossible to be definitive on what Mitalipov actually did versus what he’s claiming to have done.
Let’s say it’s all real. Is it creepy? Maybe. But it’s also legal—at least in Oregon, where embryo research is kosher as long as it doesn’t involve federal funding. Officials at OHSU confirmed that the work took place there, and that it met the university’s Institutional Review Board criteria for safeguarding the rights and welfare of subjects involved in human research—presumably the donors of the eggs and sperm, in this case. No one on the outside knows which exact genetic tweaks the researchers actually made or how safe the procedure was. Tech Review was light on details.
That lack of transparency could turn into a real problem. “These are special cells and they should have special considerations given to them if you’re going to Crispr them,” says Paul Knoepfler, a stem cell researcher at UC Davis who wrote a book on designer babies called GMO Sapiens. Knoepfler worries that incautious work like this could lead to political backlash against Crispr more broadly, like what happened to stem cell research in the 2000s under George W. Bush. “We don’t have an unlimited amount of time to talk about these things and figure them out,” Knoepfler says. “This stuff is moving at warp speed and we need to get our act together on establishing guidelines that are much clearer about what is OK and what isn’t.”
Not that scientists haven’t tried. In February the National Academy of Sciences produced a report with its first real guidelines for Crispr research. It did not go so far as to place a moratorium on gene editing of the human germline—modifications that a person’s offspring could inherit—though it did suggest limitations. Scientists are only supposed to edit embryos to prevent a baby from inheriting a serious genetic disease, and only if the doctors meet specific safety and ethical criteria, and if the parents have no other options.
Those obstacles aren’t insurmountable, and a particularly slippery slope winds between them. At the Aspen Ideas Festival last month, UC Berkeley biologist Jennifer Doudna, one of the people who discovered Crispr, stressed the need for a unified policy on germline editing before scientists really start doing it. “Once that begins, I think it will be very hard to stop,” she said. “It’ll be very hard to say, ‘I’ll do this thing but not that thing.’ And at that point, who decides?”
In the US, it’ll probably be the federal government. Congress has already banned federal funding for the human testing of gene-editing techniques that could produce modified babies. That provision is tucked into an appropriations rider that has to be renewed each year, so it’s an annually moving target. Congress has also barred the US Food and Drug Administration from even considering clinical trials of embryo editing. But even if those laws did change, the FDA’s approval process for these kinds of technologies is among the strictest in the world. They would require years and years of animal studies before the first test embryo could conceivably be conceived.
“For this to be something other than just a reckless person doing something crazy, we’re looking at least a decade and maybe more of safety testing,” says Hank Greely, a law professor and bioethicist at Stanford. In countries with laxer laws, it could happen sooner—like, say, China, where scientists have reported three attempts at using Crispr to modify human embryos.
The first two studies used genetically defective embryos that could never come to term, but the most recent, published in March, used viable embryos. And while all three studies produced mixed results, Crispr was most successful at repairing faulty genes in the normal embryos. Experiments are also moving forward in Sweden and the UK that use Crispr to knock out different genes in viable embryos to study effects on development.
Still, don’t panic. “Modifying embryos that are never going to be implanted is not close to the boundary,” Greely says. “Doing it in embryos you might want to implant is real close to the boundary and shouldn’t be done without any discussion. But that’s not what Mitalipov did.” Maybe. All the institutions apparently involved with the research refused to comment citing an embargo, which would make sense if there were an embargo to break. There wasn’t, according to Antonio Regalado, who covers genetics for Tech Review but didn’t write this story. Consider it instead just a good new-fashioned leak.
If you think of viable-embryo Crispr research as a journey and not a destination, right now scientists all over the world are on the same path. But at some point the road will fork: Someone will implant an engineered embryo into a human womb. “The work coming out of China and Mitalipov’s lab has this implied assumption that someday it will wind up being used heritably in humans,” Knoepfler says. “And I think that requires a unique obligation for being more open about it.” Mitalipov’s research is not a good start.