FDA hearings in Washington this week have raised an ethical quandary: If we have the scientific power to help a sick woman give birth to healthy children, should we do it? Even if it requires us to cross an ethical line in the sand drawn decades ago by hundreds of nations worldwide?
A reproductive biologist from the Oregon Health and Science University in Beaverton, Shoukhrat Mitalipov, has asked the federal government for permission to test an unprecedented gene replacement technique in people. If he succeeds, women with mitochondrial diseases will be able to have their own, biological children, without passing on their disease.
But some others worry that this research will open up an ethical Pandora's Box, legitimizing human genome manipulation. Plus, they say, the science is premature. This technique has only been tested in a handful of monkeys and it's way too early to try in people, they say.
At root is some pretty technical science in an area that's not yet well understood.
Mitochondrial disease is driven by mistakes in the 37 genes that drive the mitochondria — which, as you might remember from freshman biology, provide every cell with energy. Mitochondria is passed down from mother to child; the father’s mitochondria dies with him.
Mitalipov wants to get rid of the mother's flawed mitochondria and replace them with a healthy donor's. He would take the nucleus of an egg cell from the sick woman and implant it in an egg cell from a healthy donor, after the donor's nucleus has been removed. When the egg is fertilized, the 20,000 genes in the mother's nuclear genome will mix with the same number from the father's, plus 37 healthy genes from the mitochondria of the donor. The result, Mitalipov says, will be a normal child.
Not everyone agrees with that last point. Even if the child appears healthy, it’s possible that it will have genetic problems during development, later in life or that will only appear when that child has children.
One potential problem: some of the mother’s unhealthy mitochondria will survive the transfer and show up in the child, unnoticed perhaps for generations, before another descendent gets sick. Mitalipov says this is impossible, that his technique promises nearly 100 percent swap of mitochondria, but some scientists remain unconvinced.
Mixing mitochondria from two “mothers” can put mice at higher risk for diabetes, stroke and heart disease, according to research.
In an unauthorized “test” of what would happen if human mitochondria were mixed, fertility clinics in the late '90s and early 2000s experimented with a technique that led to at least a few dozen children with such a mix. Of 17 such pregnancies studied, two fetuses — never born — would have had a genetic disorder called Turner Syndrome.
One child went on to have autism, though it’s not clear whether that was related to the way he was conceived. Another one, interviewed last year (by me, for a story in The New York Times), appears totally healthy and normal. Read more about the child, Alana Saarinen, now 13, here.
Another cause for concern is something called genetic incompatibility: the donor mother's mitochondrial genes might not "match" with the nuclear genes because they did not evolve together.
Clearly, ethical and scientific questions remain.
In the earlier Times story, Nita Farahany, a professor of law, philosophy and genome sciences and policy at Duke University says the technique is, indeed, morally defensible:
The technique is “not only promising, but morally preferable to leaving a woman without a choice for having her own healthy genetic children.”
But in a Times opinion piece Monday, Marcy Darnovsky, executive director of the Center for Genetics and Society, calls this type of "mitochondrial manipulation" a "dangerous step." She writes:
...these procedures are deeply problematic in terms of their medical risks and societal implications. Will the child be born healthy, or will the cellular disruptions created by this eggs-as-Lego-pieces approach lead to problems later on? What about subsequent generations? And how far will we go in our efforts to engineer humans?
Karen Weintraub, a Cambridge-based Health/Science journalist, is a frequent contributor to CommonHealth. Follow her on Twitter @kweintraub.