How to make a ‘three-parent’ baby

Zhang baby
Zhang baby

Fertility doctor John Zhang holds a baby boy (whose face has been blurred for privacy). The boy is the world’s first child created by spindle transfer — a technique to replace faulty mitochondria. Such children have been dubbed “three-parent” babies.

A baby born in April 2016 may have opened the door to a new world of reproductive medicine. This boy became one of the first intentional “three-parent” babies. The vast majority of this boy’s DNA came from his mother and his father. A small bit of extra DNA came from an unrelated woman. This child got some of his genetic inheritance from each of these adults.

Because of that bonus DNA from the unrelated woman, some people say babies like this boy have three parents.

Scientists didn’t go to all of the effort to mix the DNA from these three people as an experiment. In fact, they did it to overcome a problem in the boy’s mother. That woman had a problem with her mitochondria (MY-toh-KON-dree-uh). These are important little structures — or organelles — present in her cells.

Many cells, including those that make up humans, contain special components that function like little organs. That gives rise to their name, organelles, which actually means little organs. Organelles perform special tasks for their parent cells. And one of the more notable of these organelles is the mitochondrion. Its main job is to help power its cell. To do this, the mitochondria harvest energy contained in the bonds linking atoms in the cell’s fuel (such as glucose). Mitochondria then use that energy to create another molecule, known as ATP (for adenosine triphosphate). That ATP actually serves as the energy source for cells.

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animal cell diagram
Mitochondria, one of several types of organelles found within the cytoplasm of a cell, contain a small amount of DNA. A mutation in that DNA can cause disease.

But some of the mitochondria in the boy’s mother have a mutation. That genetic alteration causes Leigh syndrome, a fatal disorder. Most of her mitochondria work properly. That’s why the mom does not have the killer disease. But she can pass on DNA from the faulty mitochondria to her children. And this can put them at risk of Leigh syndrome. Two of her children had already died from the disease. She also had suffered four miscarriages.

It was in hopes of giving this couple a healthy baby that doctors worked to find healthy mitochondria to substitute for her unhealthy ones. Normally, a woman passes on her mitochondria to her offspring through her egg (dad’s sperm don’t contribute any). These organelles also contain a small amount of DNA — just 37 genes. (Most of the roughly 20,000 protein-producing genes needed to make a human are stored in a compartment called the nucleus.) Mutations in some mitochondrial genes most often pose a risk to organs that need lots of energy, such as the brain and muscles. There is no cure or effective treatment for many of these mitochondrial diseases.

The technique used to create the baby boy is new and controversial. His birth, though, caps nearly three decades of work to to produce healthy human eggs by manipulating the organelle. The new baby appears to have been saved from a deadly genetic disease. Still, there are ethical and safety concerns about his three-parent heritage.

And a three-parent baby girl born in January raises even more concerns — in part, just because she is a girl.

Producing healthy babies

Researchers first began swapping mitochondria between egg cells to treat infertility problems almost 20 years ago. Jacques Cohen was one of those researchers.

He’s a scientist who studies human embryos. In the late 1990s, he and colleagues at Saint Barnabas Medical Center in Livingston, N.J., were looking for a way to help women who were unable to have children by in vitro fertilization. Also known as IVF, this process involves taking egg cells from a woman and sperm cells from a man, then incubating them in a dish. Some of those eggs and sperm will combine to form embryos — the first stages of creating a new individual.

human embryo
With in vitro fertilization, or IVF, an embryo that developed in a laboratory dish is transferred into a woman’s womb where it may develop into a baby.

Doctors then transfer some of those embryos into the woman’s womb. With luck, one or more will develop into a baby. But some couples’ embryos never developed normally. No one knows why. Cohen’s group thought a dose of cytoplasm — the jellylike “guts” of a cell — from a donor egg might give the implanted embryos a better shot at success.

“Cytoplasm is the most complicated fluid in the universe,” says Cohen. It contains mitochondria, other organelles, proteins and other molecules that do the work of the cell. The mother’s egg normally supplies all the goodies an embryo needs to live for the first few steps of development. But Cohen thought that some of his patient’s eggs might need extra help.

So he extracted 10 to 15 percent of the cytoplasm from an egg donated by another woman. He injected this along with a single sperm cell into a recipient egg. From 1996 to 2001, he performed the procedure 37 times. And this technique proved quite successful. It produced 17 babies for 13 couples!

Cohen later tested eight of the children born this way. Two carried some mitochondria that had come from the donor. That was in addition to some that came from the child’s actual mother. Some…