By Katherine Drabiak
Recently, media outlets around the world have been reporting on children born from pronuclear genome transfer (sometimes called “3-parent IVF,” “mitochondrial donation” or “mitochondrial replacement therapy”) at Newcastle Fertility Center in the United Kingdom. Twenty-two women underwent the procedure, which resulted in eight children, who now range in age from six months to over two years old. Some have called it an “important milestone” and a “pioneering” technique to spare children from fatal disease.
New England Journal of Medicine published two articles describing the process, and the follow-up exams of the children. This is not the first time mitochondrial replacement therapy (MRT) has been used to create children. In 2016, a U.S. physician traveled to Mexico to create an infant using MRT; and clinics in Greece, Ukraine and Cypress advertise MRT as a “treatment” for infertility.
MRT is not a curative therapy, or simply a new type of IVF. MRT is an experimental procedure that creates an embryo using the DNA from three people. Here, researchers fertilized both the mother’s egg and a donor egg with the father’s sperm to create zygotes. Then, they removed the nuclear DNA out of the donor zygote, and replaced it with the nuclear DNA from the mother’s zygote. The aim is to transfer the nuclear DNA into a zygote with healthy mitochondria, but some of the mother’s mitochondria with faulty mutations is inevitably also transferred in this procedure, resulting in a new mixture of mitochondria.
Mitochondria are organelles found in almost every cell in the human body and serve a number of functions like energy production, controlling metabolic processes, and programming cell growth and death. Mitochondria also interact and communicate with our nuclear DNA, which impacts how cells function and grow throughout our lifetime.
Mitochondrial disease can be caused by mutations in nuclear DNA or mutations in mitochondrial DNA, which are passed down through our mothers. Mitochondrial disease is rare, occurring in about 1 in 10,000 people. Mitochondrial disease can be devastating, resulting in organ failure, seizures, or developmental delays. There is no cure for mitochondrial disease. However, the majority of mitochondrial disease occurs from mutations in nuclear DNA. MRT does not address mutations in nuclear DNA, but only the very rare cases when the mother’s mitochondria contains faulty mutations.
MRT appeals to what many of us want from science: it promises parents the chance to have a healthy, genetically related baby. Despite optimistic headlines announcing that the children are healthy, this assessment is based on narrow and incomplete data. Parents affected by mitochondrial disease, and the public, should understand several critical points.
Despite using the word “treatment” and “therapy,” MRT is a research experiment to manipulate embryos and create children – it is not a clinically proven treatment. The UK was the first country to amend its law to allow MRT, and it can only be conducted as part of a clinical research trial. In this case, researchers were focused on the narrow question whether the experiment had the intended results of producing viable embryos and stopping transmission of faulty mitochondria to the children. In five children, the researchers reported that it worked as intended so far. In three children, MRT reduced – but did not stop – the transmission of faulty mitochondria. Despite claims that the children are healthy, this report only gives us a tiny glimpse into the children’s health right now, because it is based on limited medical testing.
Levels of faulty mitochondria can differ throughout the body. Researchers only tested a small blood or urine sample from each child, but this does not offer any insight about mitochondria in other tissues or organs that researchers did not test. This means that the children may have high levels of faulty mitochondria in other areas of their body that went undetected by the scope of testing. Mitochondria are also unpredictable and unstable. The amount of faulty mitochondria can increase over time, which is called reversion. Even if the children appear healthy today, their mitochondria may revert and the children could develop mitochondrial disease in the future. Observing how the children grow and develop is an ongoing experiment, but this clinical trial is only designed to monitor the pregnancies and children for five years.
The risks are not only that MRT did not work as intended to eliminate the faulty mitochondria in some of the children. Using MRT introduces additional risks. Some scientists suggest MRT could induce other types of disease and health complications, partly attributed to the mismatch between mitochondrial DNA and nuclear DNA. Some research suggests MRT could cause diseases like developmental disorders, expedited aging, increase the risk of cancer, or premature death.
Finally, MRT is legally and ethically controversial based on these significant risks and because it creates an embryo by combining the genetic material from three people. This genetic manipulation affects every cell of the resulting person, and it is irreversible. This new combination of DNA will be passed on to future generations. Dozens of countries prohibit procedures on embryos that will result in changes to the human genome based on human rights principles that prohibit treating the genetic material of future people as an object to manipulate and experiment upon.
We can hope that the children are – and continue to remain healthy – but hope is not evidence of safety or efficacy.
Author: Katherine Drabiak, JD
Affiliation: Professor of health law, public health law, and medical ethics in the College of Public Health at the University of South Florida.
Conflicts of Interest: None to declare