UKs ThreeParent Baby Trial Shows Success
Ten years after the UK first approved mitochondrial donation, the very first official results from the technique are now out. In two studies in The New England Journal of Medicine, eight babies have been born through the groundbreaking fertility technique and all are said to be healthy.
This landmark, spearheaded by researchers and doctors in Newcastle, has been described as a milestone. The method was designed to enable women who have defective mitochondrial DNA to prevent passing on serious genetic disorders, including Leigh syndrome, to their offspring.
These conditions are related to how cells generate energy and can result in severe disability or premature death during infancy.
But whereas the findings constitute an unambiguous scientific achievement, they raise serious issues; ethical, clinical, and procedural.
Mitochondrial donation is the process of mixing DNA from three people: the nuclear DNA of the biological parents of the child and healthy mitochondrial DNA from a donor. The procedure was licensed under the UK's Human Fertilisation and Embryology (Mitochondrial Donation) Regulations in 2015, after vociferous parliamentary debates.
Although there were safety and side effect concerns at the time, the delivery of eight healthy babies is a milestone that was greeted with open arms by patient advocacy groups and researchers alike. Nonetheless, there are questions regarding how the process was handled and explained.
One significant area of concern is the withholding of information. With the large-scale public investment and the UK's leadership in genomic and reproductive science, it has invited criticism with the lack of transparency.
'In a nation self-proclaimed to be at the forefront of the practice and regulation of reproductive and genomic medicine, there should be transparency as a fundamental ethic', the article contends. Offering outcomes and limitations in public view not only facilitates additional research, but also keeps patients and families up to date.
While 32 applications have been authorized since 2017, the year the Newcastle team was granted its licence—mitochondrial donation was performed in just 22 instances, yielding eight births. This is well short of the estimated 150 births each year originally forecast.
"Is this strong enough data to demonstrate the effectiveness of the technology and was it worth all the significant efforts and investments over nearly two decades of campaigning, argument and research?" the author queries.
Concerns also arise regarding numbers of eligible families, and why so many didn't proceed with the treatment, and whether hopes might have been unrealistically set up.
Safety is still a main issue. Higher concentrations of the mother's initial mitochondrial DNA were detected in two of the eight cases, and there is a risk that the defective genes may return.
This effect 'reversal' was also noted in a recent Greek study, when the procedure was applied to address infertility. As a result of this, the Newcastle team no longer positions the technology as one that prevents mitochondrial disease, but as one that diminishes the risk.
"But is reducing the risk sufficient to make the technique available to more patients?" the paper queries. "And what will the risk of reassertion do to the children born as a result and their parents, who could live with the ongoing uncertainty that the condition might appear later in life?
Others propose piloting the procedure on women with fertility problems (though not mitochondrial disease) to improve the monitoring of reassertion risks before more widespread application.
There are also gaps in knowing the patient experience, why just a few of the 32 approved cases proceeded, how many others requested it but were rejected, and how families reacted after failed attempts.
"How do they reconcile with not having the healthy biological child they had been promised?" the article wonders. It is important to grasp the emotional impact of a treatment with so much emotional import.
There is no doubt that the birth of these eight children represents a breakthrough of great strides. "The birth of eight healthy children is a real scientific breakthrough that families affected by mitochondrial diseases have waited decades to witness."
Nevertheless, the article demands prudence. "Breakthroughs come with responsibilities." If the UK is to maintain its leading position in reproductive medicine, it has to agree to share both its successes and its limitations.
"The families still waiting to have the procedure and those who may never receive it, deserve nothing less than complete honesty about what this treatment can and cannot deliver."
