Recently, using the DNA of three people, a baby was born. This was made possible using in vitro fertilization (IVF) technique called mitochondrial replacement therapy (MRT).
This raises the question what regulations, if any, should exist around MRT.
A baby was born recently in the United Kingdom from the DNA of three people using an in vitro fertilization (IVF) technique called mitochondrial replacement therapy (MRT). MRT swaps out the mother’s mitochondrial DNA, which may contain mutations for mitochondrial disease, with mitochondrial DNA from a healthy egg donor to prevent a child from being born with mitochondrial disease, a disorder in which the mitochondria can’t efficiently turn sugar and oxygen into energy, thereby inhibiting cell function.
These diseases can affect one part of the body or every organ system, including the brain, kidneys, muscles, heart, eyes, and ears. There’s no cure, and many babies with mitochondrial disease are born with life-threatening issues, like heart or liver failure, and die within a year of being born or in early childhood.
Only a handful of babies around the world have been born via MRT, and the research, though underway in some regions, is limited due to restrictions against MRT in many countries. The short and long-term risks are poorly understood and it’s unclear how well MRT prevents mitochondrial disease and whether babies could develop problems down the road or if future generations may inherit the diseases.
That said, the baby born via MRT recently, a first for the UK, is considered a scientific feat demonstrating the promise of using MRT to prevent mitochondrial disease. “The first child born through this process was reported in 2016. The more recent report of children being successfully born through this process in the UK has affirmed the utility of this procedure,” says Shaun C. Williams, an OB/GYN and a partner in reproductive endocrinology at Illume Fertility.
What we know about MRT’s ability to prevent disease
While the bulk of our DNA comes from both the mother and father, mitochondria is inherited exclusively from the mother, explains Paula Amato, MD, a professor of obstetrics and gynecology at Oregon Health & Science University’s School of Medicine who researches MRT.
With MRT, the baby gets all its nuclear DNA from its mother and father, so its overall genetic variability (i.e., the baby’s traits) won’t be impacted — and, thanks to the mitochondrial donation from another person’s healthy egg, it would be free of mitochondrial disease.
“Mitochondrial replacement therapy can be a successful way to prevent certain disorders, which in the past could only be treated with the use of an egg donor,” says Williams.
While MRT is most well-known for its use in preventing mitochondrial disease, it’s also being explored as a treatment for infertility. Though the research is mixed, some evidence suggests MRT could help rejuvenate eggs and boost pregnancy rates in women of advanced maternal age, according to Amato.
“It’s not been proven at this point, it’s just a hypothesis—but it hasn’t stopped several groups across the world from actually marketing it and using this technology for that purpose without really any evidence that it actually works,” she said.
Trials conducted in vitro have found that healthy embryos can be created via MRT. Animal models, in mice and monkeys, have discovered that MRT can successfully prevent inherited mitochondrial disease in newborns (and those effects can last for generations). A recent study that investigated MRT for infertility found that, in humans, embryos created with MRT can successfully implant, develop to term, and produce healthy newborns. However, in a portion of babies, about 15%, the mitochondrial may revert to the original and potentially cause disease. While this isn’t an issue for infertility, it could be a serious issue in people utilizing MRT to prevent the transmission of diseases.
Diane Tober, PhD, an associate professor at the University of Alabama and affiliate faculty at UCSF Institute for Health and Aging who specializes in reproductive technologies and bioethics, says there are benefits to MRT, but we don’t know what the immediate and longitudinal health effects might be on the children conceived this way along with their future generations.
“This is germ-line editing, so we don’t yet know the ramifications of that,” she said.
The future of MRT depends on the research and regulations
MRT is currently restricted in many countries, including the United States. Even in the UK, where MRT’s been legal since 2015, the Human Fertilisation and Embryology Authority (HFEA), the UK fertility regulator, must approve the procedure case-by-case.
In the US, scientists can test the technology in a laboratory setting and in animals—but they can’t implant MRT embryos in a person. There’s also no federal funding. The National Institutes of Health (NIH) does not support the creation or destruction of human embryos, which MRT technically falls under, says Dr. Amato. Even with private funding, US scientists would need approval from the Food and Drug Administration (FDA), but the organization does not support trials testing genetic modification of a human embryo.
That leaves the future of MRT largely in the hands of international scientists—particularly in the UK, Greece, and Australia. US scientists, including Amato and her team, may wind up testing the procedure abroad.
“Even though the technology was developed here, and we think we’re at a point where we’d like to move forward with clinical trials to see if it’s actually safe and effective, we’re unable to do that in the US,” Amato said.
If other countries show success with MRT, as the UK has potentially just done, MRT may eventually take off.
“The use of this therapy in the United States will likely not be available until data from other centers and clinics outside the US demonstrate significant safety parameters,” says Williams.
Tober hopes the global community will proceed with caution and enact reasonable, sensible regulations—so scientists can conduct the necessary research to better understand the risks and benefits—before MRT becomes widely used.
“As a global community, we should be having these conversations that take into account global ethics—and what can we agree upon, what we can't agree upon, and how we can proceed in a manner that is in the best interests of not only children born of these procedures but also future generations,” she said.
The future of MRT is hazy, but one thing remains clear: reproductive technologies are rapidly advancing. Any success, including the birth of this baby by MRT, motivates the scientific community to fight restrictions and explore new techniques that can transform IVF.
“MRT is one, gene editing for human embryos; and also to prevent genetic disease transmission, which is also very controversial and currently not allowed in the US,” says. Amato, “The latest technology we’re working on is in vitro gametogenesis, which is trying to create eggs from skin cells.”
The science is underway. And if any of these technologies become widespread, it will very well revolutionize IVF in the US and around the globe.