Gene Sleuth. By Kevin Cool
Patricia Davis Murphy '68 tracks down a cancer-causing genetic mutation
Patricia Davis Murphy's sister, Barbara, was 21 years old in 1974 when she was diagnosed with ovarian cancer. Three years later, she was dead. Murphy '68, who had two small children of her own, cared for her sister after her second surgery at Thanksgiving 1976, enduring the pain of her decline and eventual death and the frustration of a family blind-sided by a disease they assumed they had no reason to fear. She wanted answers.

"I decided that I would go into human genetics and that I was going to find out the basis of her disease," Murphy said. "It was a way of coping."

Barbara's death still tugs at Murphy; if only she knew then what she knows now perhaps her sister's life could have been extended. Murphy believes Barbara inherited a mutation of BRCA1, a cancer-fighting gene that checks the growth of tumors. A quarter century after burying her younger sister, Murphy is busy saving the lives of persons carrying those mutations.

Until recently scientists could only guess whether cancer was inherited, and there was no reliable method for testing persons whose family histories suggested they might be candidates for the disease. That changed when Murphy's research team two years ago made a revolutionary breakthrough. At Oncormed, a Gaithersburg, Md., company that develops and provides gene-based diagnostic and information services, Murphy headed the team that developed a process of testing for gene mutations that can lead to breast, ovarian and prostate cancer.

Murphy's work capitalized on previous research that had mapped some of the human genome. BRCA1 and BRCA2, identified in the mid-'90s, are genes that produce proteins that are important for the normal function of cells. A mutation in either of these genes can alter the protein and degrade its ability to fight tumors. The risk that a woman with a mutated BRCA1 gene will develop breast cancer can be as high as 87 percent, according to Murphy. Risks for ovarian cancer also are high in women with this genetic mutation, and men who have the mutation are at higher risk for prostate and colon cancer.

Murphy's team wanted a way to check BRCA1 genes for irregularities that might indicate a predisposition for cancer. They first had to figure out what a normal BRCA1 gene looked like--the sequence of "code" in a gene's DNA that can tell a scientist whether the gene is correct or flawed. This required isolating the DNA, then interpreting its biochemical structure. Their data allowed Murphy and her team to produce a blueprint of a healthy BRCA1 gene in the spring of 1996. Now, by comparing the profile of the normal BRCA1 gene with a patient's BRCA1 gene--taken from a blood sample--geneticists could identify mutations that signaled a risk of cancer. Murphy was thrilled.

"I knew this was going to save people's lives," she said.