Dr. William Kaelin of Harvard Medical School and Dana-Farber Cancer Institute went to sleep at his usual bedtime on Oct. 6, but any hope of a peaceful rest was interrupted by a vivid dream: of waking up, seeing “5:45” on his clock, and knowing that the Nobel committee had not phoned him with good news. (Such calls tend to come about an hour earlier, Eastern time, or 11 a.m. in Stockholm.) But when Kaelin woke up for real at 2:30, he realized he had been dreaming, and went back to sleep.
When his phone rang at 4:50 and Thomas Perlmann, secretary of the Nobel Committee, told him he had won the 2019 Nobel Prize in physiology or medicine (along with two other scientists), all Kaelin could think was, “Is this the dream part or the awake part?”, he told a roomful of colleagues and reporters later that morning at Boston’s Dana-Farber Cancer Institute, where he has his lab. “It was surreal, like an out-of-body experience.”
Kealin made his breakthroughs nearly 20 years ago. He was studying a hereditary condition called von Hippel-Lindau disease, in which mutations in the VHL gene dramatically increase the risk of cancer. A normal VHL gene encodes a protein that prevents cancer, Kaelin and his colleagues discovered.
That seemed pretty straightforward. Weirdly, however, cancer cells missing a healthy VHL gene also express abnormally high levels of genes associated with hypoxia, or dangerously low levels of oxygen, he discovered. And VHL tumors overproduce a “distress signal” that cells short of oxygen also emit. It was as if the tumors were calling for reinforcements: send more oxygen.
These tumors use the hypoxia pathway “for their own evil purposes,” Kaelin said, summoning red blood cells and blood vessels to boost their oxygen supply and thereby grow and proliferate with abandon.
“Every scientist in the world dreams of this possibility, but if you’re realistic you don’t think it’s really going to happen,” Kaelin told the Nobel Foundation. His only regret is that his wife, cancer surgeon Dr. Carolyn Kaelin, a breast cancer survivor, died of brain cancer in 2015 at age 54. “There were a couple of years after I lost her, when I thought, please, no prize this year” without his wife to celebrate it with him. “But now I’ve reached a point where … [I imagine her] looking down, saying, see, I told you this would happen.”
The archived chat is available for download here.