AI-designed editors tested on cells with disease mutations
Origin Genomics CEO Cathy Tie led NPR reporters into a New York City laboratory on an exclusive tour, the exact location of which she asked the network to keep secret for security reasons. Wearing a white lab coat bearing her name and the company logo, she opened a gray metal cryogenic tank filled with liquid nitrogen, releasing wisps of white fog as she pulled out a long metal rod cradling frosted glass tubes.
“So as you can see there’s four tubes in here,” Tie said. “Each tube can contain up to 10 embryos.”
The embryos inside were donated by couples whose families have been plagued for generations by life-threatening genetic disorders. Origin’s scientists extract stem cells from them to test experimental gene editors — molecular tools the company says might one day safely correct inherited defects before a child is born.
Tie wants to convince the world that the benefits of her company’s gene-editing technology outweigh its risks. Editing genes in human embryos that would be passed down for generations has long been taboo because of ethical and safety concerns, and in the United States, using gene-edited embryos to create babies is against federal law.
“Hundreds of millions of people around the world have these diseases: Huntington’s, cystic fibrosis, hereditary cancers, Tay-Sachs,” Tie said. “What we are proposing is something completely revolutionary: apply this amazing precision genome editing to embryos that have a mutation before they are born. That allows the next generation to not be born with these diseases. It changes the entire paradigm of medicine as we know it.”
She says it may be time to reconsider.
In a separate room, Tie showed NPR researchers testing gene editors designed with the help of artificial intelligence on other cells carrying disease-causing mutations — including induced pluripotent stem cells made from adult skin or blood cells, fibroblasts, and cells carrying a mutation for breast cancer that Origin is trying to repair. She lifted a clear plastic tray from an incubator and placed it under a microscope, where fluorescent-green cells appeared on a monitor.
“What you see here is the gene editor actually going into the cells,” Tie said, explaining that cells glowing a lighter green indicated the editor had successfully entered.
“What this means is now we have a really great platform to introduce our proprietary gene editors into those cells to then correct the mutation,” Tie said. “You’re looking at the very first step.”
The work is still at an early stage. At least one other U.S. startup — Preventive, based in San Francisco — is pursuing similar research, NPR reported. Silicon Valley venture capitalists, East Coast entrepreneurs and others have already emerged to try to push the field forward.
The emergence of these companies comes against a history in which Chinese scientist He Jiankui was imprisoned for three years after he announced in 2018 that he had used CRISPR gene editing to create the first genetically modified babies. At the time, scientists warned the technology was too new to know if it was safe for the babies or future generations; any inadvertent dangerous mutations could be passed down for generations.
Most scientists think it remains premature to try to use genetically modified human embryos to produce babies — and it may never be safe, NPR reported. Newer, more precise gene-editing techniques such as prime editing and base editing have since improved the technology’s accuracy, and some scientists and bioethicists argue the advances raise the possibility that embryo editing might one day be ethical to use in narrow circumstances to prevent devastating genetic diseases.
“It’s giving people false hope,” said Robin Lovell-Badge, a biologist at the Francis Crick Institute in London. “And I am concerned that they are rushing ahead too fast and making some mistake, which would then set back the field — and the hope that people may have these techniques may eventually help them will be lost.”
Even if embryo editing could be proven safe, some researchers and advocates fear allowing it could open the door to designer babies and a future of genetically enhanced people. Other companies are already screening embryos for traits like IQ and height in addition to disease risk, NPR reported.
“I’m very concerned about where this could be headed,” said Katie Hasson, who runs the Center for Genetics and Society, a watchdog group. “Some of the Silicon Valley investors behind these firms are very open about their vision for the future. It’s a vision of mass-produced, genetically engineered humans that’s horrifying.”
Fyodor Urnov, who studies gene editing at the University of California, Berkeley, said he believes the private-sector researchers are not being transparent about their goals. “I just don’t think they’re being honest with us about why they’re really doing this,” Urnov said. “They’re really in the business of embryo — and thus ultimately baby — improvement.”
Tie rejected the characterization, stressing she has no interest in anything except helping people have healthy children. Some also worry that commercial pressure could drive unregulated clinics to spring up overseas to offer embryo editing where regulations are looser.
“I’m very concerned about genome-editing tourism,” said R. Alta Charo, professor emerita of law and bioethics at the University of Wisconsin-Madison, who is now consulting for government agencies and private companies. “This is my fear for what comes next.”
Tie’s work draws additional scrutiny because she was personally involved with He Jiankui after the Chinese scientist was released from prison. Tie said He is not involved in Origin in any way. She said she is moving slowly and methodically, with independent oversight and transparency to make sure embryo editing would be safe.
“This is a very powerful technology. Safety must come first,” Tie said. “I think that if you have a technology that can be proven to be safe, and it can help hundreds of millions of people that suffer from these diseases, it is unethical to not pursue this research. My hope is that humanity can capture the upside of this technology.”
She said she hopes Origin will eventually produce enough data to convince Congress to lift the long-standing ban that prevents the Food and Drug Administration from even considering experiments involving gene-edited human embryos, as well as persuade regulators in other countries.
“Clinicians, regulators, bioethicists, regulators, patient advocates — all of us must come together to make sure this technology is used in the right way,” Tie said.
To illustrate what is at stake, Tie asked NPR to meet one of the families she is working with. A reporter and photographer traveled to a penthouse in midtown Manhattan to meet Nicole and Asaf Ezra.
Nicole, 38, originally from the United Kingdom, and Asaf, 37, from Israel, said they would love to have three children. “I’ve always wanted physically my blood and flesh children. I want to have my biological children,” Nicole said. “I want it to be a little me or him running around and be like, ‘Yep, that’s my kid.’”
But the couple has struggled for years because Nicole comes from a family affected for generations by familial adenomatous polyposis, a rare genetic condition in which a mutation causes precancerous growths called polyps to form in the digestive system. The polyps can become cancerous if they are not removed.
“When I found out we had it, I was petrified,” Nicole said. “It was a slam in the face. It was very hard.”
Nicole had most of her large intestine removed at age 13. She regularly undergoes procedures to spot and remove polyps and lives in fear she will get colorectal cancer, like her grandfather, her mother, and many other relatives. “It’s horrible,” she said.
She has gone through rounds of in vitro fertilization to try to produce embryos without the mutation. The couple did finally get one healthy embryo, but lost that pregnancy to a miscarriage. The couple is still trying.
But Asaf also heard about Origin Genomics.
“We just don’t want to pass on cancer to our kids,” Asaf said. “Who would want that, right?”
Nicole, a therapist, and Ezra, who works at a venture capital firm, invested in Origin and donated three of their affected embryos for the company’s research.
“The amount of women this would help would be amazing,” Nicole said, choking back tears. “I know I’m crying now because I’m thinking about it. But it’s really tears of joy for people with the chance that they’ll get. It would do so much good for the world, and there’s so many women who won’t get the trauma that I’ve had.”
The couple noted that when IVF was first developed it raised similar fears. “Society just needs to regulate this technology to make sure it’s used for the right reasons,” they said.
“We shouldn’t give up technology for fear of creating other things,” Asaf said. “I don’t think that’s the moral high ground here.”