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William Kaelin

Nobel Prize in Physiology or Medicine

2019

Scientists have known for many years that oxygen is needed for the conversion of food into useful energy. But how cells adapt to changes in oxygen levels has long been unknown until it was finally unlocked in large part through research done by Professor William G. Kaelin Jr., MD. He identified a molecular machinery by which different oxygen levels regulate fundamental physiological processes. This discovery may lead to new treatments for anaemia, cancer, and many other diseases.

 For his work, Prof. Kaelin was awarded the Nobel Prize in Physiology or Medicine in 2019, together with Sir Peter Ratcliffe and Dr. Gregg Semenza. 

He came to his discovery from his research done at his lab at Dana-Farber Cancer Institute on tumour suppressor gene mutations and how they cause cancer. He had focused on a rare, hereditary syndrome called von Hippel-Lindau disease, which is caused by defects in the tumour-suppressor gene VHL. These tumours over-produce chemical distress signals that are characteristic of cells starved for oxygen. This results in the production of red blood cells, the formation of new blood vessels, changes in cellular metabolism and more.

Prof. Kaelin showed that cells lacking the VHL gene, and hence the protein it encodes, are incapable of sensing oxygen. His long term goal is to lay the foundation for new anti-cancer therapies based on the biochemical functions of such proteins. 

One disease he is working on is kidney cancer, where the VHL gene is critical.  Some new kidney cancer drugs have emerged based on knowledge of the VHL gene, but he says that curing this disease will probably take a combination of three to four drugs. Scientists have already found that a combination of two drugs is more effective than a single agent, he said. 

New agents are being tested and they might become the third or fourth drug. “I don’t know how long this will take, but I certainly hope it is in my lifetime.”

He advises young scientists interested in research to find a mentor they like to work with. “A lot of learning is through apprenticeship so finding a mentor to help you become a good scientist will be helpful.”

When a researcher applies to work in his lab, he tries to get a sense of the kind of person he or she is and whether he or she would respond to constructive criticism and challenge. 

“We are about scientific rigour, learning to think clearly and logically, to be self-critical at the way we look at our results and not immediately gravitate to the obvious.”

Prof. Kaelin is currently the Sidney Farber Professor of Medicine at the Dana-Farber Cancer Institute and Brigham and Women’s Hospital, Harvard Medical School, and a Howard Hughes Medical Institute Investigator. He has received numerous awards in recognition of his scientific contributions, including the 2016 Albert Lasker Basic Medical Research Award and the 2010 Canada Gairdner International Award, both shared jointly with his fellow 2019 Nobel laureates.