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DEPARTMENT: Biohazards by Paige Comstock Cunningham

Family Trees & Family Threes

On the Creation Three-Parent Embryos

by Paige Comstock Cunningham

Recently I came across a study that traced the ancestry of one-half of Ashkenazi Jews to four women who lived in Europe before the twelfth century. These maternal founders established a population now estimated to be about 8,000,000 strong.1 The key to tracing this family tree was the use of mitochondrial DNA (mtDNA). Located outside the nucleus of the egg, mtDNA is passed on directly from mother to child, without being recombined with DNA from the father's sperm.

This genetic connection with our mothers, stretching back hundred of generations, is one basis for using DNA to search for ancestors. (Y-chromosome testing traces back from son to father.) The results can be stunning. One woman wrote:

Because I was abandon [sic] at birth I went into this hoping only to find a clue to my nationality. Instead I not only found out that my ancestors were Hungarian Jews, but I found two distant cousins. First relatives I've ever known other than my children.2

In other contexts, however, mtDNA is viewed not as a benefit, but as a liability that burdens progeny. That's because mtDNA may contain genes for serious diseases, such as multiple sclerosis. About one in 4,000 children develop some kind of mitochondrial disease by the age of 10.

A team of researchers in Oregon tested a novel way to bypass this problem. They created several dozen human embryos with three genetic parents, two female and one male.3 They removed the nucleus from an egg containing diseased mtDNA, inserted it into another woman's egg (with the nucleus removed), and then fertilized the egg to produce an embryo without diseased mtDNA. If this process is perfected (many embryos in the study did not survive, and all were eventually destroyed), carriers of mitochondrial diseases could use it to avoid passing illnesses on to their offspring.

But the process would also cause unalterable changes in a child's genetic inheritance, which would be passed down for generations. It crosses the line between somatic gene therapy, which affects only the patient, and germline therapies, which affect both the child and his descendants. Germline engineering is risky for the embryo, and manipulating DNA also increases the risk of mutations that could be harmful or lethal.
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And while creating three-parent embryos to prevent debilitating diseases sounds beneficent, it could open the ethical door to genetic tinkering of all sorts. Once we approve genetic manipulation to eliminate serious diseases, what would bar parents from selecting a prospective child's eye color, height, weight, IQ, or physical prowess? The line between "curing" and "improving" would become increasingly difficult to draw.

But perhaps most significantly, the three-parent embryo would have two genetic mothers: the mitochondrial DNA connecting him to one "mother," and the nuclear DNA linking him to another.

And this brings us back to the family tree. Let's assume that a Greek woman with diseased mtDNA uses a donated egg from a German woman to engender a baby girl with disease-free mtDNA. Just whose daughter will this child—let's call her Leto—be? Physically, she is likely to resemble the contributors of her nuclear DNA, that is, the sperm donor (her biological father) and the Greek woman. Yet she also carries mtDNA from the German egg donor. So if Leto were to trace her maternal family tree using the mtDNA method, she would conclude that her maternal ancestors were not from Greece but from Germany.

Thus, even if producing a three-parent embryo were not ethically suspect in itself, the question would still remain: Which is a child's "real" family tree? 

1. Behar, Doron M., et al., "The matrilineal ancestry of Ashkenazi Jewry: Portrait of a recent founder event," The American Journal of Human Genetics 78, no. 3 (2006), 487–497.
2. Family Tree DNA:
3. Nick Collins, "'Three parent embryos created from human eggs," The Telegraph (Oct. 24, 2012):

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