The Reignited Debate Over Gene-Edited Human Embryos: Moral Duty or Reckless Risk?
The global biomedical community was stunned in 2018 when Chinese researcher He Jiankui announced he had created the world’s first gene-edited infants, in an unregulated experiment widely decried as unethical, hasty, and deeply irresponsible. He was later sentenced to prison for the work, but the momentum to develop safe, clinical germline gene editing for reproductive use has not faded. Now 30-year-old biotech founder Cathy Tie is making the case that moving this technology forward is not just time-sensitive, but a moral imperative.
Tie launched her new startup Origin Genomics in March this year, with an explicit long-term goal of rolling out gene-edited embryo services for IVF clinics. In a newly published commentary in the Trends in Genetics journal, she calls for expanded public research funding and streamlined regulatory pathways to move therapeutic embryo editing out of the lab and into eventual clinical practice. But major unresolved questions hang over the entire field: what level of definitive evidence will regulators and researchers require to confirm edited embryos are safe enough to implant for a human pregnancy, and what unquantifiable, permanent risks might hang over any children born from this process?
“There are well-documented cautionary tales of early human trials where no obvious red flags popped up, and people still died,” notes Hank Greely, Stanford law professor and director of the university’s Center for Law and the Biosciences.
Germline gene editing works by modifying the DNA of reproductive cells, including early-stage embryos, meaning any tweaks made to the genome can be passed down to future generations. In theory, this offers a permanent, one-time fix for devastating heritable genetic mutations, but unintended stray DNA changes — referred to as off-target effects — could also introduce new, heritable health risks no one can predict. These extraordinarily high stakes are the core reason nearly 70 countries around the world have formally banned gene editing of human embryos intended for implantation and pregnancy.
For people at risk of passing on serious genetic diseases to their children, IVF paired with preimplantation genetic screening is already the standard of care, allowing clinicians to identify and select only disease-free embryos to transfer to the uterus. Critics of germline editing argue this existing tool eliminates nearly all real clinical demand for editing, with Greely noting it would only ever serve “a fraction of a fraction of a fraction” of families.
But the standard IVF process has major limitations: it is notoriously inefficient, and generating viable, chromosomally normal embryos can be an enormous, draining hurdle even for couples with no inherited disease risk. Ian Watts, a 36-year-old engineer based in Long Beach, California, and his partner Cheyenne Ziegler, went through three full rounds of IVF trying to conceive children free of the genetic variant that causes Watts’ Charcot-Marie-Tooth disease, a degenerative neurological condition that erodes fine motor skills and mobility. Even without extra genetic screening for the disease variant, most IVF cycles see large numbers of eggs fail to fertilize, or stall in development, or carry unviable chromosomal abnormalities. Adding screening for the disease variant culls even more potentially usable embryos. After three rounds, the couple only had 8 chromosomally normal embryos total, and just 3 of those did not carry the CMT genetic variant. That pool is far too small to give them the three or four children they hope to have one day.
“Right now the only real choices are to not have kids at all, or go through endless, brutal rounds of IVF,” Watts says. For families like his, safe embryo editing could expand their options dramatically. It could also serve the extremely rare subset of couples where every single embryo they could conceive would inherit a disease-causing mutation — for example, partners who both carry two copies of a harmful dominant genetic variant.
“We’re here to actually treat these diseases, not just discard affected embryos and call it a job well done,” says Tie, a former Thiel Fellow who has previously joked about branding herself as “biotech Barbie.”
CRISPR first made the possibility of gene-edited babies a tangible research goal more than a decade ago, and newer iterations of gene editing such as base editing and prime editing deliver far higher precision than early CRISPR systems. In June of this year, researchers at Columbia University published findings showing they had edited early human embryos using base editing with extremely high accuracy. Tie cites this study in her commentary, arguing that precision genome editing for embryos is now fully within technological reach. She writes that if medical interventions can safely and effectively prevent serious disease, access to those treatments should be counted as part of patient reproductive autonomy.
“Medicine’s core obligation is not just to avoid causing harm, but to prevent avoidable suffering when safe, effective interventions are available,” her commentary reads. Tie explicitly clarifies she does not support using embryo editing for non-therapeutic trait enhancement, such as modifying embryos to raise a child’s intelligence. Public opinion also appears to lean in favor of the option: a large European public opinion survey released in July found more respondents supported than opposed therapeutic human embryo editing.
Tie notes that New York City-based Origin Genomics is currently working to optimize base and prime editing tools on human embryos donated for research by IVF patients, though the team is only running tests on human embryonic stem cell lines for now. She expects the company to publish substantial safety and efficiency data for their editing platform in the coming months. Tie’s first embryo editing startup, Manhattan Genomics, abruptly shut down earlier this year after operating for just a few months.
Even with the promising Columbia data, major gaps remain. The Columbia research team never attempted to correct actual disease-causing mutations in their edited embryos, and some of the editing tools they tested produced inconsistent, unintended genomic changes. The team published a paper earlier this month concluding these unplanned, undesirable outcomes mean the technology is still not remotely ready for clinical use. This variability also means one editing tool that proves safe for one specific genetic mutation offers no guarantee an editor tailored for a different mutation will be safe too. “Every single unique disease mutation would effectively require its own custom-built medicine,” explains Dieter Egli, lead researcher of the Columbia study. This extra layer of technical complexity will make the process of developing clinical embryo editing treatments extraordinarily slow and prohibitively expensive for widespread access.
Tie has repeatedly stated she does not believe embryo editing is ready for use in human patients right now, but argues it is close enough that the U.S. needs to immediately dismantle existing legal and funding barriers holding back its development. Currently, U.S. federal funding for human embryo research is heavily restricted by longstanding legal provisions, and the U.S. Food and Drug Administration is formally barred from even reviewing clinical trial applications for procedures that create heritable changes to the human genome.
Most leading researchers in the space agree therapeutic embryo editing will one day be used in clinics, but they disagree sharply on when that point will come, and what safety milestones will be required to get there. Paula Amato, professor of obstetrics and gynecology at Oregon Health & Science University and advisor to gene editing firm Preventive, argues any path to clinical use requires extensive lab testing of edited embryos, followed by multi-generational trials in non-human primates to track for hidden unplanned changes that do not show up for years. Origin Genomics currently has no ongoing work with animal models, and no immediate plans to launch preclinical non-human primate trials.
Even with a perfect editing tool that passes every preclinical test, there is no way to guarantee an implanted edited embryo has zero unplanned genetic changes. Edited embryos are usually biopsied for genetic testing before transfer, but biopsies only sample a tiny handful of cells from the embryo, and those cells do not always represent the full genome of every other cell in the embryo, a condition called mosaicism. Undetected off-target effects could emerge years later, after a gene-edited child has grown to adulthood and even had children of their own.
“You can never be 100% sure you have caught every risk,” says Shoukhrat Mitalipov, director of OHSU’s Center for Embryonic Cell and Gene Therapy, who previously advised Manhattan Genomics. “You can think it’s safe, but at the end of the day you’re transferring a black box you can never fully map out.” Amato adds that any patients considering the procedure would need extensive, detailed counseling on these unknown long-term risks before making a choice.
For Watts and Ziegler, the risk of testing a novel, carefully vetted technology is well worth it to give their affected embryos a chance at a disease-free life. Ziegler is currently 20 weeks pregnant with one of their non-carrier screened embryos, but the couple has kept all their remaining embryos that carry the CMT genetic variant, in the hope that one day they will be able to safely correct the mutation.
“If the choice is to throw those embryos away, or give a thoroughly tested new technology a chance, I will always lean toward giving the new technology the benefit of the doubt,” Ziegler says.
