Ever wondered how when you hike up a difficult trail, you feel out of breath? The reason this happens is that your body is trying to take in more oxygen to fuel your muscles.
But when you stop to think about it -- how does our body really know when to take in more oxygen?
A trio of scientists has discovered how cells sense and respond to changing oxygen levels- a feat that won them the 2019 Nobel Prize in Physiology or Medicine! Cancer researcher William Kaelin, physician Peter Ratcliffe, and geneticist Gregg Semenza have not only advanced our understanding of how oxygen levels affect the human body but identified the exact mechanism our cells use to recognize changing oxygen levels.
We know that oxygen is needed by our bodies to convert food into energy by cells -- specifically, the mitochondria. When oxygen levels go low (a condition called hypoxia), our body responds automatically by producing red blood cells and forming new blood vessels. The production of red blood cells is controlled by a hormone called EPO (hormone erythropoietin).
Semenza and Ratcliff showed that when oxygen levels fall, the cells in the body are flooded with a protein complex called HIF (hypoxia-inducible factor). This HIF complex triggers the production of the EPO hormone, which in turn increases the production of oxygen-carrying red blood cells. The scientists also identified the genes that encode two proteins that together make up the HIF protein complex.
Meanwhile, Kaelin was studying a hereditary condition called Hippel-Lindau disease and the role of a gene called VHL. He noticed that patients with defective VHL gene were at an increased risk for cancer. However, what surprised him was that cancer cells with the defective gene also had high genes for hypoxia -- this meant that the cancer tumors were tricking the body "for their own evil purposes", according to Kaelin, and asking for more oxygen to grow!
Impact Of Discovery
This discovery has revolutionalized our understanding of cell behavior and medicine and is helping in the development of drugs to treat diseases. Since we know that cancer cells produce more HIF to feed themselves nutrients and oxygen, drugs can suppress this ability to prevent the growth of tumors. In people with anemia (a condition where the body is deficient in red blood cells), drugs can do the opposite -- trigger the cells into low oxygen condition to boost the production of red blood cells.
These scientists have shown us how science and research can save lives. So the next time you prepare for a hike, take a moment to appreciate the Noble Prize awardees and their discovery of HIF!
This fun TED video shows how oxygen gets into and around inside our bodies!
Sources: Nobelprize.org, NY Times, Guardian. Nature, John Hopkins University