Tracing genes to fight pancreatic cancer
Scientific fame might have eluded Dr. Teresa Brentnall of the University of Washington if she hadn't tried to help a patient who claimed he was cursed.
That was back in 1996. Brentnall's patient, a 40-year-old Olympia resident, felt doomed because his grandfather, father, four uncles and three cousins had all died of pancreatic cancer. A swift and lethal disease, it's the fourth leading cause of cancer deaths in the U.S. and Europe.
"I had been concentrating on colon cancer before that guy walked into my clinic," Brentnall says, of the meeting that turned her life around. "But colon cancer is usually curable by surgery. Pancreatic cancer is uniformly lethal.
"I had this idea that over your life as a researcher, you can probably answer only two or three significant questions. You have to be very careful about what you choose to work on or you could put on your hat, start working and 20 years could go by. I realized that if I could make any headway on pancreatic disease, that would be significant because everyone who has it dies."
Using her patient's family as a starting point, Brentnall assembled a team of researchers from around the world to solve the mystery of "Family X." What accounted for their spectacularly bad luck?
After 10 years of detective work, the team had its answer, announced with fanfare at Radio City Music Hall. They discovered that a mutated gene called palladin can cause pancreatic cancer in families.
Like any success story, this one involved a bumpy ride, especially when it came to funding. Few researchers were looking into pancreatic cancer when Brentnall started. It's a difficult disease to study, because patients usually die within a year after diagnosis. And the pancreas, unlike the breast, is buried deep within the body. It's difficult to get a good look.
"We didn't have a lot of support for this research at first," says Brentnall. "People said we were crazy, that our surveillance would give patients a terrible choice if precancerous cells were found. The terrible choice was that the patient could either wait to see if a cancer occurred or have the pancreas removed and develop insulin-dependent diabetes."
A breast cancer survivor herself, Brentnall persevered because her patients wanted her to. Eventually, her team discovered precancerous cells in nine members of Family X. All but two of them had their pancreases removed, including the original patient.
"I think the people who criticized us had never worked in a clinic," says Brentnall, who divides her time between her clinical work and teaching at the UW School of Medicine in gastroenterology. "My interest is in helping people with their problems. I've never been interested in information for information's sake."
Brentnall, who's raising two sons in addition to her day job, now is working with her team to develop a simple blood test that can detect pancreatic cancer in its early stages.
She is optimistic that her team can accomplish that goal in five years or fewer. But she's philosophical about the setbacks that accompany any ambitious enterprise.
"You just land on your feet and keep going," she says. "Bad luck is just a reminder that there are always interesting things ahead of you, no matter what corner you're turning."
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