Last year, for example, researchers studying 19 members of a three-generation family were able to isolate the gene that carries one form of osteoarthritis, a crippling joint disease. With such information, doctors not only can diagnose a genetic illness, but they can also screen for the problem gene in those who are not ill. And any increase in the basic knowledge of the disease may one day lead to a cure or treatment.
But as Mulvihill's cancer study shows, families have medical importance for more than hereditary disease studies. Any disease that affects or stems from gene function--as cancers are suspected of doing--or any disease with suspected ties to environmental or lifestyle factors can be studied in a family lab.
For instance, in the early 1970s, researchers at the National Cancer Institute saw a frightening pattern of lung cancer among eastern-seaboard shipyard workers and their wives. Studying the lifestyle as well as the medical history of the couples, researchers were able to discover an environmental culprit. The workers, who built and repaired asbestos-encased boilers, and their wives, who shook out and washed their husbands' clothes, were inhaling asbestos fibers, which are carcinogenic.
"Certain families just give you incredible, incredible clues," says Nancy Wexler, president of the Santa Monica-based Hereditary Disease Foundation. "They give you a way of looking at everyone else in the population. Sometimes all it takes is some exceptional patient, or family, to crack an entire disease."
NANCY WEXLER talks with a light grace and an almost carefree style. She is 45 years old, a clinical psychologist and a faculty member at Columbia University medical school in New York City. But when she speaks about the research the Hereditary Disease Foundation supports, the shadows in her life begin to emerge.
Wexler (see sidebar, page 12) has a 50% chance of dying young and horribly--as her mother died and her uncles died--from Huntington's disease, a degenerative neurological disease programmed by a single inherited gene. Huntington's victims slowly lose all coordination and muscle control; their bodies move constantly, and their mental capacity withers. "Seeing a person with Huntington's," says Wexler, "is like watching a giant puppet show. Their limbs are jerked as if by an unseen puppeteer, and there is nothing the person can do about it."
There is no treatment and certainly no cure for a disease like Huntington's. Doctors know very little about it; and much of what they do know, they owe to family-based research. The progress made in understanding Huntington's, in fact, is a classic example of the genre.
The disease was described in 1872 by Dr. George Huntington, who first saw it when he was a young boy, traveling with his father and grandfather. "We suddenly came upon two women, mother and daughter, both tall, thin, almost cadaverous, both bowing, twisting, grimacing," he wrote.
By the time he became a doctor, he had observed three generations of "chorea" sufferers \o7 (chorea \f7 means "dance"). Huntington was the first to trace the hereditary pattern of the disease and to conclude that children born to someone with the disease had a one-in-two chance of becoming ill themselves.
Nancy Wexler first learned that she was at risk for the disease shortly after she graduated from college. It was 1968, and understanding of the disease had barely progressed beyond Huntington's initial study.
But in the 1970s, genetic research techniques transformed the study of Huntington's. The breakthrough was a sophisticated method of exploring DNA--deoxyribonucleic acid--that could enable scientists to pinpoint, with remarkable precision, the presence and location of genes responsible for serious disorders.
Genes are made up of DNA, and DNA and genes are contained by and arranged along chromosomes. The breakthrough process uses enzymes to "snip" DNA into pieces. Specific enzymes always cut DNA at the same place. "Imagine," Mulvihill says, "that the DNA is a sentence, and there is an enzyme that always recognizes a specific string of DNA, or genes, like the letters T-H-E. So it would always cut in places like THE or THERE or THEM. That results in various lengths of DNA--which are called markers--depending on what genes are there."
If researchers can find a string of DNA that's exactly the same in people who have a genetic disease and is absent in people who don't have it, then the disease gene is somewhere around that stretch of DNA.
The search for the right chromosome and the suspect gene--among the 23 pairs of chromosomes contained in every human cell--is almost like looking for a house somewhere in the United States when you don't even know the state the house is in, let alone the city or street. Finding the right marker is like finding a signpost.