“In this case, the techniques are within the capacity of highly skilled experts and mitochondrial genetic disease can be devastating,” said John Carroll, a biomedical professor at Monash University in Australia, in an email. “When combined with rules that make it illegal to carry out these manipulations there is a perfect storm for drastic action, such as setting up the technique in a country where the rules don’t exist.”
In the United States, privately funded embryonic research is legal. But in 2016, Congress barred the Food and Drug Administration from evaluating mitochondrial transfer and any methods that alter human embryos, by removing support from the agency’s budget. Such congressional restrictions on embryonic science are supported by groups such as the Catholic Church, which rejects “the notion that human life is a commodity to be created for experimentation,” as an official of the U.S. Conference of Catholic Bishops said in 2003, when the House voted to ban cloning.
The sparse details surrounding the transfer, too, have left some advocates of mitochondrial donation with several questions.
There was too little information about the technique used in this case for Sean Murray, executive of the Australian Mitochondrial Disease Foundation, to speculate on what this boy’s birth means for mitochondrial transfers in the future. But he said by phone early Wednesday that the technique itself was a “real source of hope” among the mitochondrial-disease community.
Baby, as they say, makes three. But in this case, mitochondrial donation does not quite bump everyone up to four: Although the boy has been described as a baby with three parents, a more accurate descriptor would be a 2.001-parent baby, as The Washington Post’s Rachel Feltman reported Tuesday. The vast majority of the DNA — 99.9 percent of it — came from the mom and dad’s chromosomes. The parental DNA strands dictate familiar genetic traits, such as eye and hair color.
The other 0.1 percent of the child’s DNA originated with a third woman, who donated her mitochondria. A mitochondrion is more than just the powerhouse of the cell, as it also contains a genome with 37 genes. In the parlance of the Economist, such a donation makes her “mitomum.”
(You have inherited all of your mother’s mitochondrial DNA. That is, unless you are one of the few dozen people alive who could read this and were also conceived with donated mitochondria — thanks to a different process called cytoplasmic transfer. The Food and Drug Administration, worried about genetic abnormalities, banned cytoplasmic transfer in 2001. )
The birth mother’s mitochondria carry genes that can lead to Leigh syndrome, a disease that is often fatal by age 3. Although she is healthy, her two previous children died of the disease. During the procedure, the doctors replaced each of five donated eggs with a cell nucleus from the mother. Then the newly combined egg was fertilized with the father’s sperm.
Thanks to a successful nuclear swap, the boy has only about 2 percent of his mother’s mitochondrial DNA. The new technique, called “spindle nuclear transfer,” will be presented by Zhang and his colleagues at a conference in October.
Unlike in Britain, neither the United States nor the Australian government has approved mitochondrial donations. Zhang defended the choice to perform the technique in Mexico, which has “no rules” on mitochondrial donation, to New Scientist. “To save lives is the ethical thing to do,” he said.
Questions remain about what will happen next. Although “it would be way too early for us to suggest it sets a precedent,” Murray told The Post, the announcement “brings the conversation to the fore” regarding mitochondrial donation. The Australian Mitochondrial Disease Foundation is advocating for the Australian government to allow the procedure.
Hurdles in the United States, too, exist, with doctors hobbled by the congressional ban on genetically altered embryos. When information about this case becomes available, it could serve to inform U.S. practice moving forward. As Nita Farahany wrote at The Washington Post in 2014, the safety of such techniques in humans is unknown without experimental evidence: “We have accepted that risk in the past, when overwhelming scientific evidence gives us confidence to move ahead to small-scale clinical trials. But there is no way to know for sure without permitting some trials to proceed.”
Should the boy grow up to be healthy, it may encourage patients to travel abroad to receive the technique if it is not available in the United States. Medical tourism is already an increasingly popular option for Americans looking to save money by turning to foreign health care. IVF is no exception: Israel is a popular destination for Americans looking for cheaper, aggressive in vitro fertilization treatments.
Given the experimental nature of this mitochondrial donation, though, international availability of the technique remains unclear. As Murray put it: “We know very little about this circumstance.”
It is unusual — as Carroll put it, “quite rare” — for doctors as well as patients to travel abroad. “But it certainly happens when there is a strong medical need,” he said. “I also expect it won’t be long before this approach is leading to Mito-disease prevention in countries where laws have not been put in place.”
It is also unclear whether Zhang, or American doctors who would follow in his footsteps and perform mitochondrial donation abroad, will face professional repercussions. The American Medical Association suggests that physicians get permission at home before performing studies outside the United States. According to is code of ethics: “When U.S. investigators participate in international research they must obtain approval for such protocols from U.S. Institutional Review Boards.” Simply because the procedure was carried out abroad, though, does not preclude it from being ethical.
U.S. fertility experts are also hopeful that government agencies could be persuaded to reconsider their stance. Columbia University stem-cell researcher Dieter Egli told Science magazine that “the lesson here is that it’s very important that regulatory agencies like FDA move forward.” In February, the Institute of Medicine told the FDA that mitochondrial transfer should be approved in specific circumstances; one such circumstance is that the baby is a boy. Because males cannot pass their mitochondrial DNA to future generations, any complications that arise would not have long-term ramifications within human bloodlines.
Conservatively, about 1 in 5,000 people are born with a mitochondrial disease. A technique such as mitochondrial donation could benefit an estimated 778 women in the United States and 152 women in Britain annually, according to a 2015 New England Journal of Medicine report.
“This is about saving lives,” Murray said, “and offering hope to a community.”
Researchers at the New Hope Fertility Center were unable to respond to a request for comment from The Post; a representative for the New York clinic said that Zhang was busy with patients, telling Science that they “come first.”