GENOME: The Story of the Most Astonishing Scientific Adventure of Our Time -- The Attempt to Map All the Genes in the Human Body
By Jerry E. Bishop & Michael Waldholz
Simon and Schuster. 352 pp. $22.95
MAPPING OUR GENES
The Genome Project and The Future of Medicine
By Lois Wingerson
Dutton. 368 pp. $19.95
IT TOOK A century and a quarter after the Austrian monk Gregor Mendel discovered that the characteristics of pea plants were inherited for genetics to dominate biomedical research. But that time has arrived.
As the 20th century closes, genetics promises to revolutionize medical treatment. Physicians are close to being able to control the genes that underlie nearly every disease, from the nearly 4,000 inherited illnesses to cancer to heart disease to alcoholism and even mental illness.
Newspapers regularly report on newly identified genes that cause major disorders such as Duchenne's muscular dystrophy, cystic fibrosis, cancers of the colon and eye and an inherited form of heart disease. In mid-July, it was the gene for neurofibromatosis, once called Elephant Man's disease.
The increasingly successful assault on these genetic disorders led the federal government to launch an organized attempt to find every one of the estimated 50,000 to 100,000 genes in the human body -- the so-called human genome project.
A genome is the sum total of all genes found in a plant's or animal's cells. It is the original set of instructions to build an organism; knowing it is like having the ultimate owner's manual. That's why Congress and the administration decided to spent an estimated $3 billion over 15 years on the genome project.
These two new books, however, by a team of Wall Street Journal science writers and free-lance science writer Lois Wingerson, are not about the genome project, despite what the titles imply. They are just the first of what surely will be many books on cracking the genetics of human diseases.
In a sense, they are prologues, telling the history of the advances in the last decade or so that made scientists think it would be possible to map the location of the genes on the 23 long strands of DNA, the chemical essence of the gene, that are wrapped up in the chromosomes found in every cell in the body.
Both books describe a key meeting in April 1978 that helped launch the whole idea. During an argument at a retreat for geneticists at an Alta, Utah, ski lodge, David Botstein, then at the Massachusetts Institute of Technology, had a brainstorm about how genetic markers could be distributed throughout the genome.
The markers would act like street signs giving the locations of genes that were arranged between them like houses on a city block. With a marker, a researcher could find the address of virtually any gene, including those that cause disease.
Mark Skolnick, a geneticist at the University of Utah, said Botstein's insight was more like "a prolonged roll of thunder," instead of a flash. By the time the essential details were worked out on how to do it, a dozen key researchers around the country were involved.
Both books make clear that research advances occur because people become passionate, even obsessed, about finding a cure, or at least an explanation of why an illness has struck a family member. But, for most laboratory scientists, helping people who are ill is "not the fundamental drive," writes Wingerson, quoting David Housman of the Massachusetts Institute of Technology. Instead "they want to solve puzzles."
Housman used the new genetic techiques to find the "street sign" for Huntington's disease, a lethal mental disorder that strikes late in life and is perhaps best known for killing folk singer Woody Guthrie. The discovery of the Huntington's "street sign" became the basis for a test that could tell whether a person had inherited the Huntington's gene and would get the disease.
But Housman could never have made the advance without Nancy Wexler, now a psychologist and researcher at Columbia University, who became obsessed with Huntington's disease after it struck her mother. The inheritance pattern of the disease is such that Wexler and her sister have a 50-50 chance of developing it themselves.
Wexler's quest for an explanation to her family's disease, a story that is better told in the Bishop and Waldholz book, led her to several poor Venezuelan fishing villages, where German or Spanish sailors apparently introduced the gene that causes Huntington's disease in the 1800s. Because of the relative isolation of the villages, many families became inbred, giving rise to large numbers of Huntington's victims. Walker studied them, sending blood and cell samples back for analysis in the stainless steel labs of America's high-tech universities. There, Housman and others found the gene marker.
The result was one of the first gene tests for a major inherited disease. (Wexler has never made public whether she herself has taken the test or whether she carries the gene and will eventually become ill.)
Overall, Bishop and Waldholz give a fairly linear explanation of the major advances in genetics, describing the major ideas generated by the leading players, and provide a better history.
While Bishop and Waldholz talk mostly about the scientists and their ideas, Wingerson richly describes the lives and cultures of afflicted families and the roles they played in helping scientists reach new understandings. Reading about the families helps explain why the genome project is so compelling. Bishop and Waldholz pay more attention to the ethical difficulties society will face as these new genetic tests become available. Will people carrying a genetic defect become "biologically unemployable" or unable to get health or life insurance? Who will protect a person's privacy? The issues already are hotly debated in the professional journals and, to some extent, in the popular press, but solutions are not always obvious.
Those issues worry James D. Watson, the Nobel laureate who co-discovered the structure of DNA in the 1950s and now heads the NIH genome project, so much so that he appointed Wexler to head an ethics committee for the genome project.
Wingerson spends a little more time on the actual nuts and bolts of the genome project, but she does not develop the high political drama that emerged in the middle-1980s when the U.S. Department of Energy and the National Institutes of Health struggled for control of the project and the funding it would bring. Currently, the nation has two cooperating, but also competing, genome projects run by different federal agencies.
Although expectant parents already are going in for certain gene screens to ensure their children will be healthy, the benefits from the genome project will come sometime in the next century. For those who want to understand the implications of those technologies, these books are a good place to start.
Larry Thompson is the science editor of The Washington Post Health section.