Eight healthy babies have been born in Britain using an experimental reproductive technique that incorporates DNA from three people to help mothers avoid passing devastating rare diseases to their children, according to research published Wednesday in the New England Journal of Medicine.
The groundbreaking study, conducted by experts at Newcastle University and Monash University in Australia, represents a significant advancement in preventing mitochondrial diseases—conditions that can cause muscle weakness, seizures, developmental delays, major organ failure, and death in children.
Revolutionary Three-Person DNA Technique
The technique addresses mutations in mitochondrial DNA, which exists outside the cell nucleus in structures called mitochondria. Unlike nuclear DNA inherited from both parents that determines individual characteristics, mitochondrial DNA mutations can cause a range of severe diseases in offspring.
Researchers developed a method that uses healthy mitochondria from a donor egg to circumvent this problem. The process involves taking genetic material from the mother's egg or embryo and transferring it into a donor egg or embryo that contains healthy mitochondria but has had its key nuclear DNA removed.
"This marks an important milestone," said Dr. Zev Williams, who directs the Columbia University Fertility Center and was not involved in the work. "Expanding the range of reproductive options will empower more couples to pursue safe and healthy pregnancies."
Clinical Results and Safety Profile
The research team performed the technique on fertilized embryos from 22 patients, resulting in eight babies that appear to be free of mitochondrial diseases. One woman remains pregnant. The genetic material from the donated egg makes up less than 1% of the baby born after this technique.
One of the eight babies born showed slightly higher than expected levels of abnormal mitochondria, according to Robin Lovell-Badge, a stem cell and developmental genetics scientist at the Francis Crick Institute who was not involved in the research. However, he noted this level was still not considered high enough to cause disease, though it should be monitored as the baby develops.
"If you had a bone marrow transplant from a donor, you will have much more DNA from another person," Lovell-Badge explained, emphasizing that any resulting child would have no traits from the woman who donated the healthy mitochondria.
Regulatory Landscape and Clinical Application
The technique required a 2016 U.K. law change to approve its use and is also permitted in Australia, but remains prohibited in many other countries, including the United States. In the U.K., every couple seeking a baby born through donated mitochondria must be approved by the country's fertility regulator. As of this month, 35 patients have been authorized to undergo the technique.
Dr. Andy Greenfield, a reproductive health expert at the University of Oxford, called the work "a triumph of scientific innovation," noting that the method of exchanging mitochondria would only be used for a small number of women for whom other ways of avoiding passing on genetic diseases, like testing embryos at an early stage, was not effective.
U.S. Regulatory Restrictions
In the United States, pronuclear transfer is not permitted for clinical use, largely due to regulatory restrictions on techniques that result in heritable changes to the embryo. For about a decade, Congress has included provisions in annual funding bills banning the Food and Drug Administration from accepting applications for clinical research involving techniques "in which a human embryo is intentionally created or modified to include a heritable genetic modification."
"Whether that will change remains uncertain and will depend on evolving scientific, ethical, and policy discussions," Williams said in an email.
Patient Advocacy and Hope
The research offers hope for families affected by mitochondrial diseases. Liz Curtis, whose daughter Lily died of a mitochondrial disease in 2006, now works with other families affected by these conditions. She described the devastating experience of being told there was no treatment for her eight-month-old baby and that death was inevitable.
"The diagnosis turned our world upside down, and yet nobody could tell us very much about it, what it was or how it was going to affect Lily," Curtis said. She later founded the Lily Foundation in her daughter's name to raise awareness and support research into the disease, including the latest work done at Newcastle University.
"It's super exciting for families that don't have much hope in their lives," Curtis said.
Future Considerations
Critics have previously raised concerns about the long-term implications of such novel techniques, warning that it's impossible to know the impact these methods might have on future generations. However, advocates argue that in countries where the technique is allowed, it could provide a promising alternative for families facing these devastating genetic conditions.
