In all cultures throughout history, people have been interested in the hereditability of traits. For thousands of years, they have practiced selective breeding of domesticated animals and plants, and selected a mate hoping to have beautiful, healthy children. All of this preceded the discovery of DNA as the molecular basis of heredity in the mid-twentieth century.
The modern era of genetic medicine has led to the identification of disease-causing mutations in human genes, leading to diagnostic and predictive genetic testing. Diagnostic genetic testing has joined neuroimaging and clinical electrophysiology as a standard tool in the neurologist's workup. Predictive genetic testing, however, differs substantially from other physician-patient encounters, because the patient is not being seen for routine screening of common diseases, or for diagnosis of symptoms already present. Rather, a healthy patient is being seen because of a strong family history of a disease, and may choose to undergo genetic testing to predict developing that specific disease some time in the future, possibly decades later.
Neurologists are most likely to be familiar with the concept of presymptomatic genetic testing for people at risk for Huntington disease. At the beginning of Blood Matters: From Inherited Illness to Designer Babies, How the World and I Found Ourselves in the Future of the Gene, journalist Masha Gessen's mother dies of breast cancer at the age of forty-nine. Another of her maternal female relatives died of ovarian cancer at age fifty-two. The BRCA1 gene, which caused their familial cancers, was discovered in 1994. This opened the possibility of presymptomatic testing in other family members, including Gessen herself.
DNA, THE TIE THAT BINDS
Eleven years after her mother's death, then thirty-seven-year-old Gessen is the mother of two young children. She chooses presymptomatic genetic testing, and learns that she inherited her mother's BRCA1 mutation. She writes, “I had my fortune told by a genetic counselor at a high-tech medical center in Boston.”
DNA is truly the tie that binds her to what she terms her mother's fatal flaw. Gessen writes: “The information we gain from genetic testing has a way of filling us with awe and a sense of having touched the forbidden: knowledge of the invisible and intangible and, more important, knowledge of the future.”
This would be a difficult and life-changing moment for anyone, but what makes Gessen's story unusual is how she deals with the news. Instead of discussing the options with her doctors and her family and making a private, personal decision about prophylactic oophorectomy or mastectomy, she decides to write a series of articles about making her decision for the online magazine Slate. In the process, she uses her journalism skills to understand as she writes “how people can make decisions in the age of medical genetics.”
Gessen jumps wholeheartedly into her research, learning that her lifetime risk of developing breast cancer is 85 percent and 50 percent for ovarian cancer. Prophylactic surgery to remove healthy organs will reduce the risk by 90- to 95-percent. Interested in more than stark survival statistics, she attempts to determine what the quality of her life would be after surgical menopause, and finds the effects would include loss of libido, and an increased risk of osteoporosis, heart disease, and cognitive difficulties. She discusses the consequences of her newfound genetic knowledge about herself: the anxiety provoked by repeated breast ultrasounds, MRIs, exams, and biopsies. She becomes what she terms a “previvor” someone who “would always be ill until proven healthy, and then I would have to prove it all over again in another month or two.”
To make the decision about prophylactic surgery, she interviews not only a professor of gynecologic oncology at Brigham and Women's Hospital, but also a nurse-scientist, a Harvard psychologist who studies happiness, and an economics professor about how people make decisions to maximize outcome. Eventually, Gessen makes her decision about surgery, and writes vividly about the immediate aftermath, but she left me wanting to know more about the followup: how did she felt about her decision a year or two afterwards?
Eventually, Gessen makes her decision about surgery. I will not reveal the answer here, but suffice it to say that her decision goes against conventional medical advice.
A JOURNEY AROUND THE WORLD
As compelling a story as her personal journey into the world of genetic testing and genetic counseling is, there is much more to Blood Matters. Gessen, a former war correspondent, travels to the frontlines of genetic medicine from Florida to Chicago, Siberia, Vienna and beyond for additional stories. For example, she takes us to Green Bay, WI, to meet Dr. Henry Lynch, a founding father in hereditary cancer syndromes, to small towns in Ontario to meet families with Huntington disease, to Lancaster County, PA, to meet Dr. Holmes Morton and the Old Order Amish and Mennonite families he treats for metabolic diseases such as maple syrup urine disease or glutaric aciduria type I, diseases most neurologists know about but rarely encounter. By history and culture, these families are genetically isolated, and therefore have an increased frequency of rare recessive genetic diseases. How Dr. Holmes Morton came to Pennsylvania and set up a clinic and research facility is one of the most interesting chapters in the book.
Gessen travels to New York, to learn about Dor Yeshorim, a genetic-disease prevention program, developed by a rabbi for Orthodox and Hasidic Jewish youths prior to marriage. The program developed policies and procedures counter to the mainstream of genetic counseling, which advocates full disclosure of results, and non-directiveness by the genetic counselor. In other words, in a mainstream genetics clinic, the genetic counselor provides information on genetic test results, and the range of possible choices as to what to do with the information in a neutral, non-judgmental fashion, and helps the patient make the best decision for himself based upon his personal, religious, and cultural values.
In the Dor Yeshorim program, the approach is paternalistic. The actual results are not disclosed to the individuals; instead, a young couple calls a telephone number with their identification numbers, and are only told they are a good match, or that they are genetically incompatible, meaning that if they married, they would be at risk for having children with one of the genetic diseases for which they had carrier testing. This approach would not work in a diverse population of patients accustomed to controlling their own medical information, but within that close-knit community, this program is widely accepted and has been effective in reducing the incidence of devastating, fatal childhood genetic diseases that include Tay-Sachs, Canavan disease, and Bloom syndrome.
DNA has penetrated the popular consciousness, with forensic DNA testing a staple of television crime shows, and frequent articles in newspapers and magazines on gene discovery, genetic testing, and gene therapy. Usually, however, the picture is incomplete: the public hears about gene therapy for severe combined immune deficiency “bubble boy” disease, but not about the leukemia caused by the gene transfer. The media reports the birth of the first cloned mammal, Dolly the sheep, but not the many failed attempts at nuclear transfer.
Gessen writes with grace and clarity about such diverse topics as predictive genetic testing, preimplantation genetic diagnosis, ethnic identity, molecular anthropology, and behavioral genetics. To be sure, some small errors will trouble those with medical training in genetics: the amino acid “leucine” is incorrectly written as “lucene.” Gessen's depiction of her own family pedigree is confusing: at one point in chapter 2, she concludes she inherited the BRCA1 mutation from her great-grandfather; later in the chapter, she writes it was inherited from her great-grandmother. The description of sex chromosome abnormalities in the final chapter contains inaccuracies. I suggest skipping the glossary of key terms entirely. Mostly, however, Gessen does a remarkable job of capturing the nuances and the inherent complexity of her topics.
One half of our 35,000 genes are expressed in the nervous system, and mutations in these genes cause all categories of neurological diseases. For neurologists, this book will bring up topics of increasing interest and relevance from the realm of genetics: counseling patients about genetic test results, implications of the results for other family members, rapidly changing applications of genetic technology to interlocking medical specialities, and how genetics is changing prevention and treatment of diseases.