By tucking two crucial sentences inside a federal spending bill last year, the U.S. Congress effectively banned the human testing of gene-editing techniques that could produce genetically modified babies. But the provision, which is up for renewal this year, has also flustered proponents of a promising technique that could help mothers avoid passing certain devastating genetic disorders to their children.
The language in the bill is a clear reference to the use of techniques like CRISPR to modify the human germline (see “Engineering the Perfect Baby”). Most scientists agree that testing germline editing in humans is irresponsible at this point. But regulators have decided that the description also fits mitochondrial replacement therapy, which entails removing the nucleus from a human egg and transplanting it into one from a different person to prevent the transmission of debilitating or even deadly mitochondrial disorders to children.
Mitochondria are the components of the cell responsible for producing energy. They also have their own DNA, separate from the DNA in the nucleus. Babies always inherit their mother’s mitochondrial genome. Mutations in the mitochondrial genome, in the nuclear genome, or both can lead to a wide range of mitochondrial disorders, many with severe and even debilitating symptoms. Between 1,000 and 4,000 children are born with mitochondrial diseases every year, and there are no licensed therapies or cures for these diseases.
Shoukhrat Mitalipov, director of Oregon Health and Science University’s Center for Embryonic Cell and Gene Therapy, was working with the U.S. Food and Drug Administration to develop plans for human testing of mitochondrial replacement therapies before the federal spending bill passed last December. Mitalipov and his colleagues have shown in monkeys that a replacement mitochondrial genome from another mother can be effectively and safely passed to offspring along with the nuclear DNA from the actual mother. They have also demonstrated the “three parent” approach during in vitro fertilization of human embryos, though they did not implant them.
But that’s as far as the research will go in the U.S., at least for now. Mitalipov says policymakers should draw a clearer distinction between genetic enhancements and genetic corrections.
“This is not about designer babies and selecting traits,” says Philip Yeske, science and alliance officer for the United Mitochondrial Disease Foundation. A narrow population—women of childbearing age who have mitochondrial disorders and who want to have children—stands to benefit. “We don’t feel it’s a slippery slope at all,” says Yeske.
He says these patients may have to consider going to the United Kingdom, where the government has opened the door to clinical testing.
Congress’s ban on clinical testing of mitochondrial replacement therapy is also at odds with report published in February by the National Academies of Science, Engineering, and Medicine. The expert panel behind the study, which the FDA itself commissioned, called clinical testing of mitochondrial replacement therapy “ethically permissible” if done under two crucial conditions: testing should only occur in male embryos, to ensure that the modification is only passed to one generation, and it should be limited to women at risk of passing on a mitochondrial disease that could lead to a child’s early death or “substantial impairment.”
R. Alta Charo, professor of law and bioethics at the University of Wisconsin Law School, co-chairs the National Academies study group looking at human gene editing, and was also part of the study focused on mitochondrial replacement therapy. She says the use of the term “heritable” in the bill’s language that refers to the genetic modification being banned could prove important to the fate of mitochondrial replacement therapy.
If the FDA were to move forward with clinical testing involving male embryos only, the mitochondrial replacement “would not be heritable because it would stop with that first generation,” she says. That could provide an avenue for the agency to work around Congress’s restriction.