DNA Testing's Double Bind

BLOOD MATTERS

From Inherited Illness to Designer Babies, How the World and I Found Ourselves in the Future of the Gene

By Masha Gessen

Harcourt. 321 pp. $25

Masha Gessen faced a searing personal dilemma. At 37, this journalist and mother of two young children learned that she had inherited a genetic mutation that greatly increases its possessor's risk of breast and ovarian cancer. Many doctors advise such women to have their breasts and ovaries preventatively removed -- as Gessen puts it, "cutting off their breasts to spite their genes." To force herself to decide what to do, and to gain a measure of psychological distance, Gessen contracted with Slate magazine to write a series of articles on her decision-making process, promising that she would reveal her choice in the last one. That desperate research lies at the heart of this book, and the author's unusual emotional investment in the topic renders her exploration of the world of genetic testing far more nuanced and insightful than a mere scientific primer.

As an Ashkenazi Jew, Gessen is fascinated by why certain mutations -- not only cancer-related ones like hers but others that can produce lethal brain disorders in childhood -- are unusually common in that population, which numbered more than 10 million before the Holocaust and stands at around 8 million today. A 2006 study suggests a likely reason: It offers evidence that all modern Ashkenazim are descended from four women who lived roughly 1,500 years ago. When just a few individuals are the recent "founders" of a population, certain genetic characteristics can rapidly become widespread among their descendants -- especially if some of the founders possessed and passed on health, fertility or other qualities that enabled them and their descendants to have many children.

Another theory to explain the persistence of some potentially harmful mutations in the gene pool is "selective advantage," the idea that possessing the mutation might somehow benefit the carrier. Except for those genes located on the X and Y chromosomes, each of us inherits two copies of every gene -- one from each parent. Some harmful mutations are dominant, which means that having even one mutated copy is enough to produce disease. Others are recessive, meaning that only those who inherit a mutated gene from each parent will develop the disease. Gessen cites intriguing evidence that certain recessive mutations common among Ashkenazi Jews may actually benefit a person who inherits only one, by enhancing intellectual ability. Ashkenazi Jews have the highest average IQ of any ethnic group that has been tested -- 108 to 115, compared with an average of 100 for the general population.

Like any science reporter, Gessen is a compulsive information seeker, but she discovers that too much foreknowledge is a painful burden. Counselors tell her that her chances of developing ovarian cancer are around 50 percent; the likelihood of breast cancer is as high as 85 percent. She embarks on a regimen of seemingly endless screening tests -- "I would always be ill until proven healthy" -- while considering preventive surgery.

The more she learns about the trade-offs involved, the more paralyzed she feels. For instance, women who have had their ovaries removed as part of a hysterectomy suffer increased rates of heart disease and hip fractures. Gessen interviews women who report depression, severe fatigue, memory loss and the disappearance of libido following such operations. "The payoff, it seemed, was . . . increasing the chances that I would die of something other than cancer -- whenever that happened," she acidly notes.

Yet gene-testing forces some unlucky recipients to confront news even worse than Gessen's. In the most moving chapter of her book, she visits people whose families suffer from Huntington's disease, caused by a dominant mutation that produces inexorable brain damage and dementia starting in midlife. Children of Huntington's victims have a 50 percent chance of developing it. It was the first disease for which a predictive genetic test was devised, and researchers confidently expected half to two-thirds of those at risk to seek testing. But in the absence of an intervention to prevent or delay the illness, it has turned out that few people from Huntington's families want to know their fate -- and who can blame them?

In the United States, genetics research has proceeded under the assumption that individuals will benefit from profiles of their personal vulnerabilities -- whether to cancer, heart disease or mental disorders. Certainly, a detailed understanding of how genetic changes affect the body's function will enable scientists to develop new treatments and to predict how individuals will respond. But it's far from clear that the psychological and ethical impact of full genetic disclosure is uniformly positive. National policies on genetic screening, counseling and prenatal diagnosis differ starkly. For example, in Israel, genetic testing of embryos created through in vitro fertilization is encouraged to try to ensure that those implanted in the uterus of an infertile woman will be healthy. Yet such testing is banned in Austria, Germany, Italy and Switzerland, presumably because of the history of Nazi abuses committed with the purported intent of improving the gene pool. As Gessen points out, most people who support a woman's right to have an abortion nevertheless oppose the use of genetic testing to discover the sex of a fetus followed by selective abortion of females -- a practice that has become common in a number of Asian countries.

Genetic testing has become big science and big business, and Gessen predicts that in her daughter's generation, people will use such information to "reshape their bodies -- and their fates." After reading her book, I feel like shouting, "Wait, Pandora -- slow down!"