Book Review

The Troubled Dream of Genetic Medicine: Ethnicity and Innovation in Tay–Sachs, Cystic Fibrosis, and Sickle Cell Disease

N Engl J Med 2006; 355:1401-1402September 28, 2006

Article

The Troubled Dream of Genetic Medicine: Ethnicity and Innovation in Tay–Sachs, Cystic Fibrosis, and Sickle Cell Disease
By Keith Wailoo and Stephen Pemberton. 249 pp. Baltimore, Johns Hopkins University Press, 2006. $60.00 (cloth); $21.95 (paper). ISBN: 0-8018-8325-3 (cloth); 0-8018-8326-1 (paper).

The associations of Tay–Sachs disease with ethnicity and of cystic fibrosis and sickle cell disease with race have been mined before, as the extensive references in this book testify. The authors are particularly interested in the role of ethnicity and race in the treatment of these conditions, as well as their “prevention,” by which they mean avoiding the birth of affected fetuses by abortion or avoiding their conception altogether.

Because of the blood–brain barrier, enzyme replacement is not an option in the treatment of Tay–Sachs disease; the alternatives are carrier testing and the abortion of affected fetuses. Ultra-Orthodox groups of Jews, who reject abortion, choose instead to screen their adolescent members for the disease and to proscribe mating between carriers. One motive the authors impute to this program, called Dor Yesharim, is “ethnic group preservation by means of prevention.” Jews have been and may still be at risk of extinction, but undetected Tay–Sachs disease will not lead to it.

Color-Enhanced Scanning Electron Micrograph of Sickled and Other Red Cells.

The fact that cystic fibrosis is primarily a disease of whites has been played up when that association attracted funds for research and management; it has been played down when the association was not beneficial to fund-raising. Cystic fibrosis has attracted more funds than sickle cell disease, although the respective incidences of these diseases in the U.S. population are similar. One result of the successful fund-raising efforts for cystic fibrosis has been much more comprehensive care of patients, which has contributed substantially to their remarkable improvement in longevity. The authors report that what is needed in the treatment of “the complex malady” that is sickle cell disease is also a “comprehensive system” that can provide patients with better access to a range of therapies. Quoting a 1995 study by Faletta and colleagues, they state, “Children with sickle cell anemia who are receiving comprehensive care have a low risk of having pneumococcal bacteremia or meningitis regardless of whether or not they continue to receive prophylactic penicillin.” Unfortunately, few of them receive such care.

By the time the “promise” — a word that is overused in the book — of gene therapy arose in the late 1980s, improvements in survival, which had been negligible for people with sickle cell disease, had begun to flag for patients with cystic fibrosis. Because of past successes, the families of patients with cystic fibrosis (and older patients themselves) easily fell prey to a “troubling modern hybrid: the researcher/entrepreneur.” By 1998, after several gene-therapy trials for cystic fibrosis proved fruitless, the researcher/entrepreneur whose company had raised $20 million primarily for gene-therapy research for cystic fibrosis stated that his company was now “concentrating on gene therapy for cardiovascular disease.” The entire gene-therapy enterprise came to a screeching halt in 1999 with the death of Jesse Gelsinger in a gene-therapy experiment for another disease.

The intrusion of the commercial sector into clinical research, largely through dubious agreements between academia and industry, is a problem of greater magnitude in genetic research on diseases other than those linked to race and ethnicity. Admittedly, race and ethnicity are important in the three diseases discussed in this book, but not in many other diseases. A notable exception is thalassemia, which has led to controversial public policies in Sardinia and Cyprus and possibly elsewhere. The authors do not dwell on it.

I was surprised that there was little mention in the book of newborn screening for either cystic fibrosis or sickle cell disease. Nor do the authors mention that screening for Tay–Sachs disease has been incorporated into routine obstetrical care. The only other fault in the book is some repetition, a relatively minor problem.

Neil A. Holtzman, M.D., M.P.H.
Johns Hopkins Medical Institutions, Baltimore, MD 21205
nholtzma@jhsph.edu