Prostate link was all in the families Hopkins scientists culled a 'gold mine' of genetic histories

November 23, 1996|By Jonathan Bor | Jonathan Bor,SUN STAFF

The discovery by Johns Hopkins scientists of a hereditary link to prostate cancer was not simply a triumph of brains -- but a logistical feat that depended on the telephone, overnight mail, genealogical charts and sheer persistence.

It was also a demonstration that ordinary people yielding vials of blood and family histories can play a pivotal role in the slow and often tedious grind of science. Ninety-one families -- 600 people from three nations -- provided the raw material for a discovery that could soon lead to a test for genetic susceptibility.

"We had what no one else had -- the families," said Dr. William B. Isaacs, a Hopkins molecular biologist who shared in making the announcement Thursday. "They were our gold mine."

The families were recruited because they were hit hard by prostate cancer, with afflicted sons, cousins, fathers and uncles scattered across the generations. When scientists scanned their DNA for evidence of a common defect, they struck pay dirt: a marker on the first chromosome that almost surely will point the way to the faulty gene.

Dr. Patrick Walsh, the surgeon who heads Hopkins' Brady Urological Institute, became famous for developing a way to remove diseased prostates without sacrificing sexual function or urinary control. But his interests transcend surgery, encompassing such questions as what causes the disease and whether some men are born predisposed.

Doctors had long observed that the disease seems to run in some families. Utah's Mormons, among the most ardent of the world's genealogists, reported in medical literature that they had noticed this in the family trees of church members.

But nobody had determined whether clusters were because of genetic inheritance or a common environmental exposure such as diet or pollution.

That task would be left to Walsh, who in 1986 saw a 49-year-old cancer patient with a compelling family history. Every man in his immediate family had died of the disease -- his father, his father's three brothers and his grandfather.

The man sparked more than curiosity. Walsh mobilized his department to find the genes, if any, that pass the disease from generation to generation.

Walsh took family histories of 700 patients who had come to him for the removal of diseased prostates. He discovered that men with one or more first-degree relatives -- fathers and brothers -- had an elevated risk of prostate cancer. The greater the number of afflicted relatives, the higher a man's risk.

The disease did not run in most of the families. But where it did, it appeared in different generations, and it didn't matter where they lived. This suggested that the disease was a matter of inheritance. An environmental cause would probably be limited to geographic regions or certain generations.

From this study, he estimated that 10 percent of all prostate cancers are inherited. But to find the gene or genes, he would need a larger collection of families.

Four years ago, his department mailed letters to the 8,000 physicians belonging to the American Urological Association, asking them for help in obtaining blood samples and histories from patients who had at least three affected family members.

Sally Isaacs, a behavioral scientist who had spent several years studying hereditary links to learning disabilities, was chosen to command a logistical enterprise that could challenge the Census Bureau.

Her interest was more than casual. Her father was a prostate cancer survivor. Her husband, Dr. John Isaacs, was a Hopkins tumor biologist studying ways to control the growth of prostate cancers. And his brother, William Isaacs, was a molecular biologist looking at the genetic basis.

"The brothers are constantly talking this stuff," Sally Isaacs said. "That's all I hear."

Walsh's appeal generated a huge response, as did his appearance on "The Phil Donahue Show" and coverage in mass-market publications such as Parade.

Some 2,500 families responded, enough to give Sally Isaacs the luxury to skim those in which prostate cancer had taken the heaviest toll. She chose 91 families -- 79 from the United States and Canada and 12 from Sweden. (The Swedes were recruited at Umea University.)

She telephoned the patients and their relatives, asking them to answer questionnaires with details about their health, occupation and family history. The patients later went to their local doctors and submitted blood samples that were sent to Hopkins by overnight mail.

"We were very structured," she said. "The blood samples could only be drawn on Monday, Tuesday or Wednesday. That would allow 24 hours to get back to us before the weekend when the lab closed.

"I could depend on getting one or two bloods every day. And there were phone calls, many many phone calls."

One of the patients was Henry Hicks, a high school principal in Winston-Salem, N.C. Four years ago, his 68-year-old father was diagnosed with prostate cancer. Tests showed the cancer had spread, so it was useless to operate. He soon died.

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