Book Review

Exploding the Gene Myth

N Engl J Med 1993; 329:1662-1663November 25, 1993

Article

Exploding the Gene Myth
By Ruth Hubbard and Elijah Wald. 206 pp., illustrated. Boston, Beacon Press, 1993. $24. ISBN: 0-8070-0418-9

This book is a sobering antidote to the intoxicating enthusiasm for genetic solutions to human diseases. The authors place disease in a social context, pointing out that with rare exceptions its occurrence and severity are influenced by socioeconomic status and environment and that, again with rare exceptions, reductions in the prevalence of disease have had more to do with improved living standards than with individual medical treatments. Some of the rare exceptions have been single-gene (mendelian) diseases that appear regardless of class or environment, although their course is influenced by these factors and by access to medical care. Now that scientists have the tools to identify virtually all genes, can we expect to find genes for many more diseases? To the extent that we do, will that improve the outcome for those afflicted with these diseases? The authors' answer to both questions is no.

Hubbard (the book is written in the first person singular) overlooks the fact that the genes for many more rare mendelian diseases remain to be identified. The combined prevalence of these diseases is between 0.1 and 1 percent, so collectively they are not rare. Efficient techniques of simultaneously detecting the genotypes for several hundred such diseases could soon be developed. How such multiplex technological capability should be applied, particularly when the diseases vary in symptoms and severity and few of them are treatable, is a question that urgently needs to be addressed.

Most people with common diseases do not have family histories consistent with mendelian inheritance. This means that although genes may play a part, other factors contribute to the occurrence and severity of disease, as Hubbard emphasizes. Consequently, finding a genetic factor will have low predictive value; not all the people with that factor, and not even most of them, will ever have the disease, whereas some of those without it will.

A small proportion of patients with colon cancer, breast cancer, or Alzheimer's disease do have family histories consistent with mendelian inheritance. Presymptomatic tests in such families could detect those with the genotypes conferring susceptibility. But we do not know how frequently, and by what age, people with those genotypes actually contract the disease. With few treatments available and gene therapy a remote possibility at best, what is to be gained by testing such families? Monitoring for the onset of clinical disease and making changes in lifestyle to reduce other risk factors are interventions whose value (in single-gene diseases) remains to be proved. Nevertheless, family members whose risk is lowered by a negative test result would not need monitoring and might have reduced anxiety. (Studies in families with Huntington's disease suggest, however, that those with negative results may feel profound guilt, since their siblings may not be so lucky.) Hubbard is skeptical about whether people who learn by genetic testing that they possess a susceptibility-conferring genotype will take action to lower their risk. Isolating a gene for lung cancer and then developing a test for it would not help people to quit smoking, she says.

The myth of a decisive role for genes in common diseases is perpetuated by the academic-industrial complex, Hubbard says. If “every health problem . . . is encoded in our genes . . . then every member of Congress will want scientists to find out everything they can about the human genome. . . . The benefits to medical research are clear, even if the benefits to us `patients' are questionable.” And once the genes are identified, “the best candidates for mass marketing are predictive tests that could be conducted on large numbers of healthy people . . . [helping to support a] new industry in the style to which it would like to be accustomed.” The authors document the growing alliance of academe with industry, expressing concern that it could taint university-based research. Surprisingly, they do not consider how government regulation -- such as that by the Food and Drug Administration, which has the authority to regulate the use of diagnostic devices -- could protect consumers from exaggerated claims and poor quality.

The authors, a professor of biology emerita from Harvard and a writer, succeed in presenting “clearly enough so that people without special training can understand” the principles of genetics, the identification of genes, the forensic uses of genetics, and gene therapy. I have touched on only a few of the provocative but clearly cogent points they make. This book is good reading for anyone who wants to learn more about the science underlying the quest for human genes and the political, social, and ethical implications.

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