By Nancy Marie Brown

Murray Korc likes to be baffled and busy. He likes puzzles and problems and figuring out what makes the body tick. "Look at a Tyrannosaurus rex," he says, leaning back in his chair and lacing his fingers together in his lap. "Look at his bone structure: He has a femur, a pelvic bone, and he stands on his toes! Just like we do. Those genes have been conserved over many, many years. Or look at a giraffe, with its long neck. How many [neck] vertebrae does it have? Seven. All mammals have seven [neck] vertebrae—a cat, a dog, a giraffe, or us. Isn't it amazing?"

Equally amazing is where this schoolboy fascination with anatomy has led Korc: into endocrinology—the treatment and study of hormone-related disorders, including diabetes, pancreatic cancer, and osteoporosis.

"I wound up liking every single clinical rotation I went through—psychology, surgery, ob-gyn," he says of choosing a specialty in the late 1970s. "But in medicine you needed to make an initial diagnosis when it wasn't apparent early on what the problem was. Belly pain could be caused by something benign, something major, or something very unusual. Trying to play detective was what made it interesting to me. I chose endocrinology, finally, because of the really unusual presentation of diseases."

Take the case of the tall young man, apparently healthy, who had lost three and a half inches in height in just nine months. Korc determined that he had severe osteoporosis, so his vertebrae were collapsing. But what was the cause? It turned out that a tumor in his pituitary gland had metastasized to his liver, where it produced the hormone corticotropin-releasing factor (CRF). The hormone coming from the liver was normal and natural—but there was way too much of it. The cancer cells had no "stop" mechanism.

"Hormones are controlled by a feedback loop," Korc explains. Since his postdoctoral days at the University of California at San Francisco, where he researched the physiology of pancreatic cancer cells, he has studied the signaling pathways of these control loops. "If the normal gland produces too much, there's a signal that says, 'Make less.'" In a cancer cell, that signal never comes. Production of the hormone runs amok.

The result? Cacophony, says Korc. "I look at it as a large symphony orchestra. Music is a combination of many signals, coming from many instruments, played by many maestros. Are they all doing the same thing? No. But it's all music. That's where I see the connection to cancer. When cancer cells hijack the making of hormones, they don't make music, they make a cacophony of signals." The work of the doctor is to fix the piano—or teach

the pianist to play better—so the music of the body can resume.

As he talks about his work, Korc exudes a sense of calm optimism. He's relaxed but alert. "It's kind of difficult for me to call what I do 'work,' since I enjoy it so much," he wrote in in an essay titled "The Joy of Discovery" for the July 2006 issue of Cancer Biology and Therapy. "Or," he continued, "is that the definition of a workaholic?"

He had wanted to call his essay "The Ecstasy of Discovery," but the editor thought that word choice was a little too emphatic. Yet Korc is emphatic—albeit in a quiet, professorial way. He calls his academic career "an accidental joyride" and refers to the "seductive" pleasures of research. He finds it "exhilarating" to be the chair of medicine at Dartmouth, a position he took in 2003, after 14 years at the University of California at Irvine.

At DHMC, Korc practices clinical medicine, seeing mostly osteoporosis patients (though in California his emphasis was on diabetes), and he also runs a very active research lab, focusing on pancreatic cancer. He has published more than 230 scientific papers in peer-reviewed journals, plus over 50 book chapters and numerous reviews, and has given nearly 100 invited talks. He is a member of the Association of American Physicians, the premier society for

physician-scientists. At Dartmouth, in 2006, he was instrumental in the creation of the Program in Experimental and Molecular Medicine to train more physician-scientists, seeing it as a way to more quickly translate research findings into patient care. A former president of the American Pancreatic Association, Korc founded the Dartmouth Pancreas Club in 2004 to improve the diagnosis and treatment of pan creatic diseases by fostering collaboration among clinicians and researchers.

Anything else? "I used to be a soccer referee, but I don't seem to have enough time to do that now," he says.

He is also married to Antoinette Korc, M.D.—a DHMC dermatologist who specializes in surgical treatments for skin cancer—and they have three children, the eldest of whom is in his last year of medical school.

How is Korc able to accomplish so much? "I only sleep five hours a night," he quips. Then he gives a more serious answer: "Tenacity, serendipity, hard work, intellectual curiosity, and the desire to help." It was a feeling of helplessness that inspired him to combine research with clinical practice in his first years out of medical school. He realized, he wrote, that "in spite of many wonderful scientific advances, there was still so much more that we did not know or understand.