The DNA Dilemma
Grappling With Bad News From Genetic Testing
By LAURA LANDRO
April 5, 2008; Page W8
Pretty Is What Changes
By Jessica Queller
Spiegel & Grau, 247 pages, $24.95
By Masha Gessen
Harcourt, 321 pages, $25
Genetic testing is ushering in a new era in human health, raising the possibility of preventing disease and identifying people who are most likely to benefit from new drugs. But prying into the secrets of DNA has also opened up a Pandora's Box of medical and ethical dilemmas for both doctors and patients: As we learn more about our risks of developing a wide range of cancers and diseases, how and when should we use that information in making life-altering decisions?
That is the question tackled in two books, both of them written by women in their 30s who are of Ashkenazi Jewish descent and who learn that they carry the BRCA breast- and ovarian-cancer gene mutation that is common to their ethnic heritage. When Jessica Queller, a television writer, and Masha Gessen, a journalist, are confronted with the prospect of imminent prophylactic mastectomies and the future removal of their ovaries, they find themselves weighing the elevated cancer risk against their unrealized personal goals and their fear of disfiguring surgery. The women also have to contend with the often conflicting advice they receive from genetic counselors, scientists, physicians and fellow patients.
By far the most engaging read is Ms. Queller's "Pretty Is What Changes," the title taken from lyrics in Stephen Sondheim's "Sunday in the Park With George." A single woman and an up-and-coming writer for "The Gilmore Girls" and "Felicity," Ms. Queller was living a life that could have been fodder for a West Coast version of "Sex and the City": advancing in her career, looking for love in all the wrong places, and navigating intense relationships with friends and family. Looming especially large in the mix is her mother, a dynamic, successful fashion designer whose self-absorption Ms. Queller finds trying even as she adores the woman. When her mother survives breast cancer only to be diagnosed with advanced-stage ovarian cancer at age 62, Ms. Queller is prompted to investigate her own genetic make-up and discovers a ticking time bomb that wasn't in her original script.
After nursing her mother through an agonizing decline -- it is hard to read the unflinching account of the last days without emotion -- Ms. Queller sees a genetic counselor and takes the test for the BRCA mutation. When the results come back positive, she must face up to the terrifying odds: an 85% to 90% chance of developing breast cancer before she turns 50 and a 44% chance of ovarian cancer by age 70. Although she is aware of research showing that breast-cancer risk varies widely among women who are carriers of the BRCA1 and BRCA2 mutations, and that other unknown genes influence the hazard as well, Ms. Queller concludes that her risk is still dauntingly high -- and she does not want to gamble with the disease.
Devastated, Ms. Queller sees her dreams of a husband and family fading before her. She wants to preserve her breasts and her ability to have children and fears that no one will want her otherwise. But she feels that the time is growing short when she might be able to fall in love and have a baby before undergoing surgery. She ponders the possibility of settling for a spouse who is merely acceptable, but she worries about her longstanding pickiness -- in her 20s, a gay male friend assured her that she was just admirably discerning, but now her friend says: "He's got shoes? Marry him." Ms. Queller is encouraged when tentative sparks fly during a date with a promising prospect, but she is crushed when he later confesses that he doesn't want to get involved with someone in the middle of a health crisis.
As Ms. Queller contemplates having a child by using her own egg and donor sperm, she reflects on the fresh moral and ethical dilemmas that technology will present in the age of genomics. While today she can select an embryo that doesn't carry the BRCA gene mutation, in the future it may be possible to engineer embryos without DNA flaws such as hers -- and to screen unborn children for signs of genetic disease. But how will such information be used, she wonders, and what percentage of risk is the "cut-off point"? As Ms. Queller observes, these are uncharted waters.
Wrestling with a multitude of concerns, Ms. Queller does her research, quizzes doctors, juggles blind dates and reconnects with old loves. She doesn't find her soul mate, but she is comforted by a powerful support network: her father, her sister and a close circle of friends. She also takes inspiration from others who face cancer diagnoses, including Anna, a woman of extraordinary fortitude whose example goads Ms. Queller to stop feeling herself a victim. When they met for the first time, at a New York City coffee shop, the author writes: "Anna apologized for being late -- she told me she'd just ridden her bike across the park from her radiation appointment. I was awestruck." Three months later, Anna's cancer metastasizes and soon claims her life.
In the end, Ms. Queller has a double mastectomy, confident that it will banish the breast-cancer threat, but she decides to put off having her ovaries removed until she turns 40 -- giving herself a few more child-bearing years. And her life is now informed by the knowledge that "my mother and Anna lived fervently until their lives were cut short," Ms. Queller writes. "We are living in an age in which scientific advances give us new opportunities to live. Seize them."
As Masha Gessen relates in "Blood Matters," she was still nursing her daughter when a genetic test -- following the death of the author's mother from breast cancer -- revealed that she carried the BRCA mutation. In addition to plunging Ms. Gessen into personal dilemmas about how to proceed, the news spurred her to undertake a reportorial mission. "Blood Matters" delves into the history of genetic testing, from horrifying Nazi experiments with eugenics to the discovery of the predictive test for Huntington's disease. Ms. Gessen also describes modern efforts to identify mutations in the narrow gene pools of Ashkenazi Jews and the Amish and Mennonite religious sects. She does a good job of explaining some of the more complex details of genetic science, especially as they relate to decisions about treatment; she even asks an economics professor to work up an Excel spreadsheet to help her calculate the relative value of undergoing preventive surgeries.
But "Blood Matters" goes off on too many tangents, veering from studies of cancer families in Wisconsin to ruminations on the genetic screening of newborns and then on to a discussion of the theory of "genetic drift," which posits that the smaller the population, the more likely things are to go awry. Ms. Gessen is fascinated by efforts to intervene in genetic destiny, such as Dor Yeshorim, a Jewish premarital screening program for genes that cause 10 recessive diseases, including cystic fibrosis. A man and a woman participating in Dor Yeshorim can find out anonymously whether they carry a mutation for the same disorder; the aim is to prevent a union that would produce children with life-threatening or extremely debilitating inherited diseases.
Unlike Ms. Queller, Ms. Gessen is reserved with her personal story. In addition to a young daughter, she has an adopted son. But Ms. Gessen spends little time on the emotional or physical aspects of her ordeal. We learn, briefly, that she had a troubled relationship with her own mother and that her longtime partner was a woman with a history of substance abuse. The woman's behavior, Ms. Gessen fears, may have had as much influence on her son's growing interest in alcoholic beverages as the genes from his HIV-positive biological mother, who is assumed to have had a history of drug use. Once Ms. Gessen knows about her errant gene, she becomes a "previvor," someone who doesn't yet have cancer but most likely will -- and though she wants to stave off a decision about surgery until her daughter has stopped nursing, she feels that if she doesn't act, she will become a "professional patient" who will always be ill until proven healthy -- not a way she wants to live. Like Ms. Queller, she undergoes a double mastectomy but delays the removal of her ovaries.
Though her description of the breast surgery and the recovery is intensely personal -- she goes from feeling "pervasive regret" in the days after the procedure to, within weeks, a sense of "awe of my own body, which had somehow leaped over the violence I had done to it and was back to serving me so soon" -- Ms. Gessen quickly turns from this scene to more general matters. The last third of the book is devoted to "The Future."
While "the study of genetic heritage combines science that is staggeringly precise with what are at best decent estimates and respectable probabilities," Ms. Gessen notes, it will be hard for consumers to resist the latest pitchmen: companies offering genetic testing to the general population. "In the era of the genome, we all want a printout of who we really are."
Ms. Landro, an assistant managing editor at The Wall Street Journal and its Informed Patient columnist, is the author of "Survivor: Taking Control of Your Fight Against Cancer" (1998).
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