About six months ago, following a controversial fertility procedure in Mexico that’s banned in the United States, a Jordanian couple gave birth to a healthy baby boy who’s been dubbed the world’s first “three-parent baby.” The baby was conceived using his mother’s egg, his father’s sperm and the mitochondria (parts of a cell) from an anonymous donor’s egg. (The donor was used to edit out the mother’s genetic disease, which lives in her mitochondria.)
Unlike with egg donation, where an embryo is made using a donor egg, in this procedure, materials from the donor’s egg are transferred to the mother’s egg.
“The child will still have only two parents, similar to any normal IVF cycle that uses a donor egg,” says Dr. John Zhang, medical director of the New Hope Fertility Center in New York, who traveled to Mexico to perform the procedure. “The difference is that the child will be genetically similar to the mother, not the donor.”
Scientists say the term “three parent” is a misnomer for what the doctors at New Hope Fertility clinic actually did — a successful mitochondrial transfer. Admittedly, that’s not as catchy.
Nevertheless, critics argue that not only are there possibly unknown health and safety risks for the baby, but that the procedure itself may open a door to potential Gattaca-style gene editing in the future.
“Mitochondrial manipulations [are] another level of a fertility doctor flouting regulations and invading a public policy process,” says Marcy Darnovsky, executive director of the Center for Genetics and Society. “I think that’s a really dangerous precedent to set — for a patient’s safety, for trust in science, for trust in medicine.”
Mitochondria, often referred to as the “powerhouses of the cell,” are structures within a cell (but outside the nucleus) that produce energy through cellular respiration. Genetic information—like that determining eye color, hair color and perhaps even certain personality traits—is contained inside the nucleus.
In the case of the “three parent baby,” the baby’s mother carried the genetic material to trigger Leigh syndrome in her children. The syndrome causes progressive loss of mental and physical abilities and typically results in death within two to three years, usually due to respiratory failure. The mother had previously given birth to two children. One survived less than one year and the other lived to be 6. Both died due to Leigh syndrome.
In order to help her have a healthy baby that was her genetic child, doctors procured mitochondrial DNA from a donor.
“This is the first success in allowing someone to donate an egg without also donating the genetic information in the egg,” says Dr. Richard Paulson, president of the American Society for Reproductive Medicine.
“You can think of it as donating the ‘egg white’ without donating the ‘egg yolk,’” he says. “This means that women can be recipients of the part of the egg that helps them become pregnant and avoid some diseases, like in this case, but still be able to pass their own genes to the child, like curly hair.”
Zhang performed the “three-parent baby” procedure in Mexico because the FDA has banned it in the U.S., something that Zhang says, is frustrating.
“This technology could mean the end of maternally transmitted mitochondrial disease,” says Zhang. “It also lays the foundation for a number of other technologies including prolonging a woman’s naturally occurring fertility.
“Our research has spanned 20 years,” Zhang says, “[and] our technique has been proven to be successful.”
But critics say that the technique hasn’t been adequately proven, and that fertility doctors are jumping the gun with a technique that might not be ready — or safe. They’re concerned that the risks and the ethical concerns may outweigh the benefits, and believe that more research is needed.
While no public policy has been set in this country, Darnovsky says, “the procedure was used in an unauthorized way by Dr. Zhang in Mexico, and suddenly it’s being used in the Ukraine and maybe in China to treat infertility.”
She notes that while the procedure doesn’t involve any actual gene editing in the nucleus, there are still genetic risks, and that manipulating the mitochondrial DNA can still affect the genome.
Darnovsky argues that any germline modification (that is, forms of genetic engineering that involve changing genes in eggs, sperms or early embryos), also raises ethical questions. Where do we draw the line when it comes to these new technologies, and what we are manipulating where genes are concerned?
“Yes, there are risks. Are they worthwhile because we’re going to prevent the birth of children with diseases that can be devastating and life-threatening?” That, she says, may not yet be known.
“There are risks of a mismatch between the mitochondrial DNA and the nuclear DNA. There’s a constant conversation between the genes in the mitochondria and the genes in the nucleus and that’s especially critical during embryonic development,” she says. “Unfortunately, we don’t know what the risks would be from that.”
Art Caplan, founding head of the division of bioethics at New York University’s Langone Medical Center, says the benefits outweigh the risks.
“Fears of reproductive technology and eugenics are hanging this technology up in my view in a way that’s morally wrong,” Caplan says. “I’m of the camp that says we ought to be doing this, not banning it. And I think holding parents who’ve had a kid with mitochondrial disease hostage and saying, ‘Well, you can’t do this even though you’d had a baby die or who was very, very sick because of this problem’ — seems to be cruel.”
Caplan describes the mitochondria as battery units.
“They’ve got nothing to do with 99.9 percent of the DNA that makes us who we are. They’re just batteries. People, calm down!” Caplan says. “You’ll never be able to design anything using this technique if you wanted to engineer super babies or better babies.”
But Darnovsky says that because of the interactions between mitochondrial DNA and nuclear DNA, the battery analogy is misleading. “Also there’s concern about even small amounts of carry-over of the mutated mitochondrial DNA,” she says. That is, there might still be a risk of mitochondrial disease for the baby.
Caplan points out that there are many more common procedures that are already allowed in the U.S. — like sex selection — that alter a child’s genetic outcome much more than this one does. And that even practices that aren’t considered experimental, like egg freezing, still are.
“We’re not really sure how well that works yet,” he says.
“Things that we do with genetic diagnosis, looking at which embryos we’re going to use, you don’t want one that’s got hemophilia, you don’t want one that has some kind of hereditary disorder — that’s designing your descendants,” Caplan says. “It may be eliminating diseases, but you’re definitely doing much more than a mitochondrial transplant.”
Caplan understands people who may have fears around genetic manipulation and how easy it might be to make the leap from that to eugenics, especially in the current political climate.
“They worry about what happened in [Nazi] Germany, they worry about what it would mean in the U.S. given the racist and misogynist values that have been revealed in the election, I get all that,” he says. “I still would say this has nothing to do with that.”
Personally, he draws the ethical line at gene editing.
“When you’re finally able to do gene editing and change the genetics in an embryo and say, ‘I’m going to try and produce a trait that’s different or better or something I want’ — then that’s the place you have to draw the line and say, ‘No, you can’t do that,’” Caplan says.
But that’s not mitochondrial transfer.
Fertility treatments can run in the tens of thousands to hundreds of thousands of dollars and the technology comes at a price. Most couples would realistically not have the resources for even the diagnosis of mitochondrial disease, much less a procedure like this one to conceive a healthy child.
Zhang says that a lift on the FDA ban would be the first step in opening the door so that more people, including those with less money to spare, could access the technology.
(Though conventional IVF isn’t banned, it’s been around for decades and still costs more than a new car.)
The procedure was approved last year in the United Kingdom, though it has not yet been performed. There are reports that scientists in Ukraine have successfully done the procedure on two women who are pregnant and both due to give birth in 2017.
Meanwhile, Zhang says the procedure he did has been a success — the baby is over six months old now, and the family is doing great.
“We are hoping to help more families in the future,” Zhang says. And, looking for a term more accurate than “three parent baby” and sexier than “mitochondrial replacement therapy,” the newest industry term, Zhang now calls the procedure “HER IVF” — Human Egg Reconstitution In Vitro Fertilization.
“Today, everything is ‘I,’” Zhang says. “iPhone, iPad, iWatch. This is a technique for HER.”