When the Chinese scientist He Jiankui announced in 2018 that he had created the first gene-edited babies, the experiment was widely condemned as reckless and premature. It ended with He in prison.
But that hasn’t stopped the push for gene-edited human embryos, with biotech entrepreneur Cathy Tie arguing that doing so isn’t just urgent—it’s a “moral imperative.”
Tie is the 30-year-old founder of Origin Genomics, a company that launched in March with plans to bring gene-edited embryos to IVF clinics. In a new commentary published in the journal Trends in Genetics, she argues for public funding and new regulatory pathways to advance gene-edited babies and eventually move into clinical use.
But questions remain about what evidence researchers will need to determine whether gene-edited embryos are safe enough to attempt a human pregnancy—and what risks might remain for the resulting children.
“There are cautionary tales of first human trials where there was really no flashing red light, and people died,” says Hank Greely, a law professor and director of the Center for Law and the Biosciences at Stanford University.
So-called germ-line gene editing involves modifying cells involved in human reproduction, like embryos. Any changes made could be passed on to future generations. That could mean, for example, correcting a devastating genetic mutation for good. But accidental DNA edits elsewhere, known as “off-target effects,” could introduce new health risks that could also be passed down. Those high stakes are part of why dozens of countries have banned gene-editing of human embryos intended for pregnancy.
People at risk of passing a genetic disease on to their children can use IVF combined with genetic screening to identify disease-free embryos before transfer to the womb. Critics of embryo editing argue that screening tools make the need for it very small. Gene-editing embryos, Greely says, would be helping “a fraction of a fraction of a fraction.”
The drawback of the current approach is that IVF is inefficient; viable embryos can be hard to come by, even for people without an inherited disease risk. Ian Watts and Cheyenne Ziegler, for example, underwent three rounds of IVF in their attempt to have children that do not carry the genetic variant responsible for Watts’ Charcot-Marie-Tooth disease, a degenerative neurological disorder that impacts fine motor skills and mobility. With any IVF cycle, eggs regularly don’t fertilize, and those that do often stall in development or have chromosomal abnormalities. Adding additional screening for disease means that some viable embryos also don’t make the cut.
In Watts and Ziegler’s case, three rounds of IVF have produced eight chromosomally normal embryos, but only three without Watts’ variant. Those three embryos are likely not enough to give the couple the three or four children they hope to have one day.
“The choices currently available are either not having children or doing lots of IVF,” says Watts, a 36-year-old engineer in Long Beach, California. Gene editing could give people like him more chances at a future family. It could also help couples in the extremely rare situation where every embryo would inherit a disease-causing mutation, such as partners who each have two copies of a harmful variant.
“We’re here to treat these diseases, not just exclude embryos and call it a day,” says Tie, a former Thiel fellow who’s alluded to herself as “biotech Barbie.”
The invention of CRISPR raised the possibility of gene-edited babies more than a decade ago, and newer forms of gene editing offer increasing precision. In June, researchers at Columbia University revealed that they had edited early-stage human embryos using a technique called base editing with incredible accuracy. Tie cites this work in her commentary, arguing that precision editing is now well within reach.
If medicine can safely and effectively prevent a disease, she writes, deciding whether to use that treatment should be part of a patient’s reproductive choice. “The obligation of medicine is not only to avoid causing harm but also to prevent avoidable suffering when effective interventions exist,” she writes. Tie says, though, the technology shouldn’t to enhance traits such as intelligence.
And people seem to want the choice: A European survey released in July found that more people supported than opposed human embryo editing.
Tie says that New York City–based Origin is currently working on “optimizing” base- and prime-editing tools on human embryos that IVF patients have donated for research. (The company is currently only testing it in human embryonic stem cell lines.) She expects the company to have significant data in the coming months showing that its embryo-editing tools are safe and efficient. Tie’s first human embryo-editing company, Manhattan Genomics, abruptly shuttered this year after operating for only a few months.
But while the Columbia work demonstrated that precise genetic changes to human embryos are possible, the researchers didn’t correct disease-causing mutations. Some of the editing tools they developed also resulted in unwanted and inconsistent genomic changes, leading them to conclude in a paper published this month that “undesirable consequences” meant the technology was not ready for clinical use.
Variability also means that one editor working doesn’t establish that another will be safe.
“Each and every mutation will therefore be a new medicine,” says Dieter Egli, who led the Columbia work. On top of the added technical challenges, that could make embryo-editing especially time-consuming and expensive to develop.
Tie is clear that she does not think embryo editing is ready for human patients, but she argues it’s close enough that it’s time to address the legal and funding barriers that stand in the way of developing it for use in US clinics. Federal funding for human embryo research is currently legally restricted, and the Food and Drug Administration is barred from considering clinical trials involving embryos with heritable genetic modifications.
Many scientists working on embryo editing believe it will one day come to clinics. Where they differ is when and what it will take to establish it as safe enough.
Doing so, says Paula Amato, a professor of ob-gyn at Oregon Health & Science University who also advises gene-editing company Preventive, will require rigorous assessment of embryos in the lab before moving to trials in nonhuman primates. Those studies should also follow several generations to make sure there are no unexpected changes. Origin, though, is not currently working with animal models, nor does it have immediate plans to do so.
But even with an editing tool that appears to perform perfectly in studies, it will be impossible to ensure that any embryo implanted in a human is free of unintended genetic changes. Before transfer, edited embryos would likely undergo genetic testing. Embryo biopsies sample only a few cells, though, which may not reflect whether different cells carry different genetic changes.
Undetected off-target effects could manifest years later, after a gene-edited baby has grown up and had children of their own.
“You can never be sure that you did your homework,” says Shoukhrat Mitalipov, director of the Center for Embryonic Cell and Gene Therapy at OHSU. “You think that it’s safe, but you’re transferring a kind of black box.” (Mitalipov advised Manhattan Genomics.)
Patients, Amato says, will have to be counseled on these risks.
Watts and Ziegler say that the risks of a novel technology would be worth it for the chance of giving one of their affected embryos a disease-free life. Ziegler is currently 20 weeks pregnant with one of their unaffected embryos, but they have continued to hold on to the ones with Watts’ variant in hopes that correcting them will be an option one day.
“If the choices are to discard or to give a new technology a chance, I would lean toward giving new technology a chance,” Ziegler says.
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