Beyond the Dome

Published in Aequanimitas - Aequanimitas Summer 2020

William “Bill” Kaelin Jr., M.D., 2019 Nobel laureate; Sidney Farber Professor of Medicine at the Dana-Farber Cancer Institute and Brigham and Women’s Hospital; Professor of Medicine, Harvard Medical School; and Howard Hughes Medical Institute Investigator.

At 4:40 a.m. on Oct. 7, 2019, Bill Kaelin (Osler, 1983; assistant chief of service, Thayer Firm, 1986) was jolted awake by a phone call. The secretary of the Nobel Prize Committee informed him that he’d won the Nobel Prize in Physiology or Medicine. But Kaelin was confused — he'd just dreamt that no one from the committee called. “It was surreal when I picked up the phone,” he recalls. “I thought it was another dream.”

Kaelin shares the prize with Johns Hopkins scientist Gregg Semenza and University of Oxford’s Peter Ratcliffe for their groundbreaking discovery of the molecular pathway all multicellular animals use to sense and adapt to changes in oxygen levels.

Kaelin’s research focuses on von Hippel-Landau (VHL) disease, in which mutations in the VHL gene increase the risk for kidney cancer and other tumors. During the 1990s, Kaelin found that tumors with VHL gene mutations produce large amounts of molecular distress signals normally generated only when tissues are starved of oxygen. He and others went on to discover the molecular switch VHL uses to control the oxygen-sensitive protein hypoxia-inducible factor (HIF), which controls such distress signals. Since then, he’s been developing therapeutic strategies to target these molecules and others implicated in cancer.

A native of Rockville Centre, Long Island and Fairfield, Connecticut, Kaelin earned his M.D. from Duke University before matching at Johns Hopkins. After serving for a year as an assistant chief of service, he went on to complete an oncology fellowship at Dana-Farber, where he continues his research.

Though he was ecstatic about winning the Nobel, the news was bittersweet. His wife, Carolyn Scerbo — renowned breast cancer surgeon at Dana-Farber and founder of the Comprehensive Breast Health Center at Brigham and Women’s Hospital — couldn’t celebrate with him. She died in 2015, at age 54, from complications of brain cancer. The couple met at Johns Hopkins when she was a fourth-year medical student and he was an ACS. They married, had two children and settled in Boston.

What and who inspired you to become a physician-scientist? In high school and college, I gravitated toward math and computer science. I liked solving puzzles but didn’t want to sit in a back room on a computer. By choosing internal medicine, I thought I could apply my skills to clinical challenges and do good work. At Johns Hopkins, we saw lots of rare diseases. I credit Victor McKusick (Osler, 1946; founder of the Division of Medical Genetics, and later, chairman of the Department of Medicine and physician in chief at The Johns Hopkins Hospital) for solidifying my appreciation for medical history and genetics. I also benefited from attending a lecture oncologist Bert Vogelstein gave about applying molecular biology to colon cancer. At Dana-Farber, I had the privilege of working in David Livingston’s lab. He was at the forefront in studying so-called tumor suppressor genes. This prepared me to study the VHL tumor suppressor gene in my own lab.

Any other standout memories from your time at The Johns Hopkins Hospital? I remember the sense of history that permeates Hopkins. I felt proud to be a house officer and enjoyed great rapport with my colleagues. And, of course, that’s where I met my wife. From the moment I saw her at the Cooley Center, I knew she was the woman I would marry. Months later, I saw her walking into a utility room on Halsted 4, where specimens were kept. I followed her inside, introduced myself and asked her out on a date.

What might surprise people about how you reached this juncture? As a young clinician working in oncology in the 1980s, I realized there wasn’t much we could do for many of my patients, most of whom had been diagnosed before being referred to me. The joy of solving puzzles in the laboratory slowly replaced the joy I'd once experienced in my clinical diagnostic work. My clinical training, however, often provided clues that guided questions we asked in the lab and hypotheses we tested. It’s a great joy to solve scientific puzzles, especially when the answer turns out to be beautiful and elegant. When that knowledge actually touches a patient, it’s especially gratifying.

What advice would you give trainees who have a strong interest in becoming physician-scientists? The first lesson is that you don’t have to have a Ph.D. to do research. I am a physician-scientist, but I’m not an M.D./Ph.D. If you were smart enough to get into medical school, and have some residual curiosity (after all your memorization in medical school!), you might want to consider this path.

Whats been the best part about having won the Nobel? Sharing it with the people in my life who made it possible: friends, family, teachers, mentors, colleagues and trainees. Seeing how much pride and joy it has given them has been priceless.