Three-parent IVF is here, and there’s nothing to fear

In 1871, a German ophthalmologist named Theodor Leber discovered a curious illness, with otherwise healthy men suddenly losing their central vision. Some lost it all at once. Others lost it in one eye and then the other.

It took researchers more than a century to understand what was causing it: mutations in so-called mitochondrial genes found in the liquid part of mothers’ eggs. And only now have doctors come up with an experimental treatment to prevent it, a therapy known as three-parent IVF.

It’s a dazzling scientific achievement that starts with standard in vitro fertilization, in which two parents’ egg and sperm are combined in the lab — but then mitochondrial genes from a third parent are added to the mix. In doing so, it raises ethical questions of a kind we’ve never seen before. It would create children with three genetically distinct parents. And it would affect not only the person treated but all of that person’s offspring as well.

The response has been confused. Professional medical organizations cannot agree on whether or how this treatment should be used. The U.S. Food and Drug Administration held a meeting on the treatment in February but explicitly deferred consideration of the ethical issues to focus on scientific and technical matters.

Press coverage, too, has raised the specter of a new era in which we could select our children’s characteristics as easily as choosing options on a new car. This “could open the door to creating ‘designer babies,’ whose eye color, intelligence and other characteristics are selected by parents,” The Washington Post reported. The New York Times cited critics who called it “an ethical minefield.”

But is the chilling prospect of made-to-order children enough to deny treatment to people who need it? To answer that, we need to know more about what happens inside a fertilized egg, what can go wrong and how it might be fixed.

The disease Leber discovered — now called Leber’s hereditary optic neuropathy, or LHON — is the result of an unusual kind of genetic mutation. When a sperm fertilizes an egg, most of the action occurs in the nucleus of the egg, akin to the yolk of a bird’s egg. That’s where nearly all of an egg’s genes reside, ready to become part of a woman’s offspring.

After a sperm enters the egg, its genes combine with the genes in the egg’s nucleus, and the stage is set for the growth of an embryo, then a fetus and — if all goes well — the birth of a child.

But human eggs have another set of genes outside the nucleus, in what you might call the white of the human egg, the liquid around the nucleus. These genes are in structures called mitochondria, tiny furnaces that provide power for the cell. Mothers pass these genes on to their children. (A sperm cell, in contrast, is mainly a nucleus with a tail. It doesn’t have many mitochondria, and they are not passed on to the next generation.)

LHON is the consequence of mutations in a mother’s mitochondrial genes. That explains why, as doctors have observed, only mothers can transmit it to their children. Such mutations can also lead to heart and other muscle damage, seizures and delayed motor development in children.

The proposed treatment enables doctors to prevent the effects of such mutations. If a woman is found to have mutations in her mitochondrial genes, doctors can remove the nucleus of her egg and insert it into a donor egg with healthy mitochondria from which the nucleus has been removed. It’s a kind of mitochondrial transplant.

That egg now has nuclear genes from the mother and mitochondrial genes from another woman. When it is fertilized, the resulting egg has three parents: the mother, the father and the woman who donated the healthy mitochondria — three-parent IVF.

The child that grows from that egg will have all three sets of genes, and females will pass the genes to their children, and so on indefinitely.

This has widely — and wrongly — been described in the media as a way to produce “designer” babies — tall, handsome and with a predilection for the violin, if that’s your preference.

It’s a reasonable fear but, at least in the case of three-parent IVF, misplaced. It came up more properly last year when the biotech company 23andMe was granted a patent for a technique that would let parents select desired characteristics from their genes. But in the resulting media fury, the company said it had no plans to offer such a service to its customers.

But such selection is not a concern with respect to treatment of mitochondrial diseases. The mitochondrial genes being added to the mix have nothing to do with any of the characteristics we might want to select for our offspring. Those are all found in the nuclear genes — the sperm and the yolk of the egg.

If we are not careful, however, unfounded fears concerning “designer” babies could deny this proposed treatment to families who need it. Three-parent IVF promises to prevent some rare but serious illnesses, and we should not let misinformation stand in the way of its use.

Medical societies’ hesitation also stands in the way of such treatments. The American Congress of Obstetricians and Gynecologists and the American Society for Reproductive Medicine cannot even agree on whether it should be proper to use genetic testing to select the sex of a child. That puts them a long way from considering such issues as mitochondrial gene transplants.

This is not to say that there are not serious concerns, particularly with regard to modifying genes in a way that could have unknown effects on future generations. While it’s not clear exactly what those effects could be, it’s possible they wouldn’t appear until they had spread through multiple generations — a frightening prospect. In addition, the treatment would likely be very expensive, available only to the wealthy.

We should proceed — but cautiously. We will learn something about human biology and head off some rare but potentially devastating diseases.

While we cannot ask Leber his opinion, he might well have taken a more pragmatic view, as doctors often do. “If you have something that will prevent blindness in my patients,” we can imagine him saying, “I want it now.”

Families with these mutations might say the same thing.