Breakthrough Research from Winners of the 2019 Nobel Prize in Medicine


Dr. Gregg L. Semenza of Johns Hopkins, Dr. William G. Kaelin Jr. of Harvard and Dr. Peter J. Ratcliffe at Oxford in London shared the 2019 Nobel Prize for discovering how your body responds when you can’t meet your needs for oxygen. Their groundbreaking research is now being used to treat certain cancers, strokes, infections, anemia, heart attack risks, and some eye diseases that can cause blindness.

You need oxygen for your cells to convert food to energy. When you can’t get enough oxygen, your body makes extra red blood cells to carry oxygen, makes new blood vessels to bring the oxygen to your cells, and switches to ways to convert food to energy without using oxygen. These researchers have shown how to turn genes on and off to increase or decrease oxygen levels. By decreasing available oxygen, you can:
• kill cancer cells,
• stimulate new growth of blood vessels for a person prone to heart attacks,
• stimulate the bone marrow to make new red cells to treat anemia.
By increasing oxygen levels, you can treat kidney diseases.

Applications for Cancer Treatment
Cancer cells need lots of oxygen to keep on growing, so researchers are now trying to stop cancer from spreading by blocking their supply of oxygen through blocking production of new blood vessels. Scientists have known for many years that low oxygen levels cause the kidneys and liver to make a hormone called erythropoietin (EPO), that causes the bone marrow to increase production of new red blood cells. Both Drs. Semenza and Ratcliffe showed that low oxygen levels cause all the cells in the body to make large amounts of a protein called HIF-1a that stimulates the body to increase production of blood vessels and red blood cells that increase a cancer’s chance of spreading.

Dr. Kaelin studied people who suffered from von Hippel-Lindau syndrome (VHL), an inherited disease in which patients have a very high risk of pancreatic and kidney cancers. The same gene that increases their cancer risk also increases the oxygen supply to cancer cells, so their cancers can grow and spread through the body. Since high levels of oxygen increase (and low levels decrease) the risk of cancer spreading through the body, blocking HIF-1a can treat cancer by preventing cancer cells from increasing oxygen supply by making new blood vessels. An angiogenesis blocker, Avastin (bevacizumab), treats brain, kidney, lung and colon cancers by blocking cancer cells from stimulating the growth of new blood vessels they need to obtain oxygen and nutrients. On the other hand, increasing HIF-1a production can increase production of red blood cells to treat anemia.

The Recipients
William G. Kaelin, Jr., is professor of medicine at Harvard Medical School. He earned his bachelor’s degree in math and chemistry at Duke University where his laboratory instructor wrote, “Mr. Kaelin appears to be a bright young man whose future lies outside of the laboratory.” He went to Duke Medical School and took his residency in internal medicine at Johns Hopkins. He then went to Harvard where he studied a genetic disorder, VHL, that is characterized by high risk for cancer. He found that the disease was characterized by high levels of a hormone called erythropoietin, and showed that these people have a gene that causes high oxygen levels that cause cancers to spread through the body.
Gregg L. Semenza is professor of pediatrics, radiation oncology, biological chemistry, medicine, and oncology at the Johns Hopkins University. He credits his interest in science to his high school biology teacher, Rose Nelson, in Sleepy Hollow, N.Y. He went to college at Harvard and medical school at the University of Pennsylvania, where he also got a PhD. He took a pediatrics residency at Duke University Hospital and then went to Johns Hopkins where he did his breakthrough research that is now used to treat patients with cancers and heart attacks.
Peter J. Ratcliffe is the director of the Target Discovery Institute at Oxford University in London, UK. In high school, he wanted to be an industrial chemist. The headmaster showed up in his chemistry classroom and told him, “Peter, I think you should study medicine.” The next day he changed his university application form to medical school at Cambridge University. He has specialized in kidney diseases with studies involving EPO, the hormone that is released when oxygen levels are low to cause the bone marrow to make more red blood cells

Checked 10/5/20