Monkeying With Motherhood

Last week, scientists at the Oregon Health and Science University reported [2] 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 [3], which occur in an estimated one in 200 births and include some of the most heartbreaking diseases we know, such as Leigh syndrome [4], 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 [5] 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.

Offspring of such an arrangement, like the Oregon monkeys, don’t really have “two mothers,” despite flashy headlines. The baby monkeys have one mother, the one who donated the nucleus—with an infinitesimal though crucial bit of mitochondrial DNA from the egg donor thrown in. But in the Washington Post, Lori Andrews, a lawyer and bioethicist from Chicago, wondered [6] whether, if the technique were ever used in humans, the third genetic parent would be justified in seeking visitation rights to the offspring. Really? Visitation rights to your 37 genes, in a baby whose other 23,000 genes came from two other people? The ethical objections may turn out to be more hyperbolic than real.

Instead, the real threat to this research is the dearth of human eggs on which to experiment. The next logical step in this work would be to move from monkeys to humans, to see if this version of nuclear transfer is safe for our species, too. But here we run into a new set of concerns, about creating human embryos specifically for research purposes, and a federal policy that has restricted the use of federal funds for this purpose since the 1970s. Scientists are limited, too, in procuring eggs, since every state but New York [7] (as of last June) prohibits them from paying women who want to donate their eggs to science.

It’s hard to picture women handing over their eggs to scientists for free, since egg donation is a tedious and somewhat risky process. And how many women can be truly altruistic when there are couples out there willing to pay big bucks for egg donors for ordinary IVF? Instead of relying on altruism, the editors of Nature argue, “more states should take New York's lead, and allow researchers to pay for egg donation. The potential for coercion, although real, is manageable. And the technique's move to the clinic would certainly be faster, and arguably more ethical, if donors were paid.”

If scientists do find the eggs to pursue it, it’s possible that this new technology of nuclear transfer, with the worthy goal of preventing mitochondrial disease, could also bring us closer to being able to do things about which there’s less consensus. Nuclear transfer is the first and most difficult step in cloning, and so if we perfect it, that could come next. Creating a baby with three genetic parents might be ethically acceptable if it means preventing mitochondrial disease; creating a clone with just one genetic parent, for whatever purpose, might be going too far. But it would be precipitous to stop promising research today simply because it could lead to scary scenarios tomorrow. The most reasonable response is to help scientists find the eggs they need, watch what they do, and keep talking about it.

Photograph of egg in mantle by Medioimages/Photodisc/Getty Images.