Monkeying With Motherhood

Photograph of a female Rhesus Macaque and her child in Red Fort Agra, Inda by Mieciu K2/Wikipedia.

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Last week, scientists at the Oregon Health and Science University reported in Nature that they had created four healthy monkeys using a difficult lab procedure—nuclear transfer, the same technique used in cloning. The nucleus (which contains virtually all of an organism’s DNA) is removed from a cell, and the nucleus from another cell is inserted in its place. What was special about the Oregon experiment is that instead of doing this in embryos, the scientists did it in unfertilized eggs. And because the eggs that receive the nucleus retain traces of their own DNA, they have some genetic material from two different females. The monkey babies born from the experiment thus have three genetic parents.

The scientists hope to use this method in humans some day, to prevent a class of devastating genetic disorders called mitochondrial diseases. If the research is to continue, though, vast numbers of donated human eggs will be needed. Currently, New York is the only state that lets scientists pay women up to $10,000 for their eggs. So where will research eggs come from?

And what of the ethics behind this futuristic experiment? It’s one thing, say bioethicists, to use reproductive technology to facilitate couplings ordinarily seen in nature—one male, one female—by giving things a little boost in the lab. It’s quite another to use it to produce embryos straight out of science fiction—either cloned embryos, which have just one genetic parent, or embryos like these monkeys, which have three.

The ethical questions prove relatively easy to answer. This new research could someday help prevent mitochondrial diseases, which occur in an estimated one in 200 births and include some of the most heartbreaking diseases we know, such as Leigh syndrome, a degenerative disorder that destroys the brain, spinal cord, and muscle beginning in infancy. These diseases are caused by defects in mitochondrial DNA, which represents just a smattering of the genetic material of a person’s full complement and is found outside the cell nucleus. Most of our genes are wrapped in a tight and tidy package inside the nucleus: the father’s genes (one-half of the full set) in the nucleus of the sperm, the mother’s (the other half) in the nucleus of the egg. When the sperm fertilizes the egg, the nuclei fuse, and the resulting embryo has almost all of the DNA we need—for humans, an estimated 23,000 genes.

But 37 other human genes are found outside the nucleus. They are in the cytoplasm of the egg, the part of the cell surrounding the nucleus, attached to structures called the mitochondria. This mitochondrial DNA is passed on to offspring, too, since the egg’s cytoplasm eventually develops into the embryo itself.

Here’s where the Oregon monkeys come in. Take a mother with a known defect in her mitochondrial DNA that could cause a devastating disease. Extract the DNA from the nucleus in her egg. Insert that DNA into the egg of a female donor whose mitochondrial DNA is known to be healthy, a donor egg from which the nuclear DNA has already been removed. What you have, then, is an egg with nuclear DNA from the first mother, and stray bits of mitochondrial DNA from the donor. And when you fertilize that egg with the father’s sperm, you create an embryo that has genetic material not from two parents but from three.