DR. JOHN MULVIHILL was working quietly in his office at the University of Pittsburgh in the fall of 1989 when the telephone rang.
The caller was somber and to the point: "Mrs. Spann's got it."
For a moment, the words didn't register. "Got what?" Mulvihill asked. But then, even before the question mark had formed at the end of his sentence, he knew. Mulvihill was stunned.
Gloria Carter Spann, the sister of former President Jimmy Carter, had pancreatic cancer.
She was the fourth member of the family to have the disease. Her father, James Earl Carter Sr., died of pancreatic cancer in 1953 when he was 58. Her sister, evangelist and faith healer Ruth Carter Stapleton, died of it in 1983 at 54, and brother Billy in 1988 when he was 51. Among the children, only the former President is untouched. So far.
When he heard the news about Spann, Mulvihill could barely contain his shock--and his growing fascination. He knew it meant another tragedy in the Carter family--in fact, Gloria Carter Spann died of pancreatic cancer last March--but he also hoped that something positive could come from Spann's unfortunate diagnosis.
Since 1970, geneticist and epidemiologist Mulvihill has delved into the mysteries of cancer in general and, recently, pancreatic cancer in particular. Families like the Carters are his primary research tools. Although few cases of pancreatic cancer seem to run in families, Mulvihill is convinced that studying those that do can provide answers to some of the toughest questions about this cancer--and others.
"Families share environment, diet and lifestyle, and they share genes as well," Mulvihill says. "We study the family to see if a common thread emerges to explain the cancers. If that thread can be identified in the family, then we can test it in the most common sporadic cancers, those that aren't necessarily family-related."
"Family disease studies provide a lot of knowledge," agrees Dr. Samuel Broder, director of the National Cancer Institute. "They speak to some kind of gene, or exposure, or custom, or practice that figures in the causes or workings of an illness." Mulvihill's family-based pancreatic cancer study at the National Cancer Institute in Bethesda, Md., had already begun when, in 1988, he learned that Billy Carter was being treated for the disease there. Mulvihill remembered that one of Carter's sisters and his father had died from pancreatic cancer.
"That clinched it," he says. "There were already too many cases in that family."
He wrote a letter to the Carter family physician, describing his study and asking for their participation. It didn't take long for the family to agree to cooperate.
Mulvihill conferred with Billy Carter's doctor and took blood and tissue samples. Then he went to Plains, Ga., where he took similar samples from the surviving family members, including the former President. Through interviews with them and their family physician, Mulvihill was able to put together a complete medical genealogy. Then, five months into the study, Billy died. Mulvihill had only the few samples he had taken previously to compare with those of the healthy family members.
When the call came about Spann, Mulvihill was flabbergasted. In a way, she actually defied the odds. "We thought with Billy, that's enough," he says.
Mulvihill considers the Carters an invaluable resource.
"If something is going to be found that accounts for clusters, then it's going to be found in this spectacular cluster," he says.
MULVIHILL'S PANCREATIC cancer study is just one of several dozen family-based medical studies in progress across America. Many, perhaps most, are focused on diseases with clear family associations: hereditary conditions such as Huntington's disease, Tay-Sachs disease or cystic fibrosis. But more and more, like Mulvihill's study, are focused on problems where the family connection, and all aspects of the disease, is more mysterious.
That illness can have a family component is hardly a new idea. As far back as the writing of the Talmud--which recognized hemophilia when it proscribed circumcision in families in which two sons had already died from bleeding--such connections have been observed. Nor is the use of afflicted families as a medical microcosm revolutionary. The family "lab" developed when medical knowledge advanced enough to combine genealogies with the basics of genetics to provide explanations for diseases such as hemophilia and more benign inherited conditions such as the "Hapsburg lip," which plagued Austria's monarchs for generations.
Once a hereditary component has been identified, families continue to be important in going further into the causes and mechanics of a disease. Through family studies, scientists have been able to pinpoint where in the genetic makeup--sometimes down to the specific gene and its location on a specific chromosome--the inherited problem originates.