The 2019 Nobel Prize in Medicine was shared among three scientists: Dr. William Kaelin, Dr. Gregg Semenza, and Sir Peter Ratcliffe. Each had his own separate research; without any coordination, they worked in strange harmony, effectively completing each other’s work. The three researches addressed the adaptation of cells to the level of oxygen in the blood from a distinctive aspect, until the three scientists were able to solve the puzzle.
Cells use oxygen to turn food into energy; this process takes place in the cell’s mitochondria through enzyme control. This discovery was awarded the 1931 Nobel Prize. Corneille Heymans was awarded the 1938 Nobel Prize for discovering that the oxygen level in the carotid artery controls the respiration rate by sending signals to the brain directly. Also, there is the carotid body, which stimulates the production of erythropoietin in the case of hypoxia by producing more red blood cells. However, the mechanism of stimulating the erythropoietin hormone in case of lack of oxygen was still unidentified. Knowing this mechanism helps in controlling the level of oxygen in certain diseases; such as: anemia, heart-attack, angina, and cancer.
Sir Peter Ratcliffe discovered that the mechanism for making erythropioetin is found in all body cells; this discovery was the first step. Dr. Gregg Semenza studied the gene responsible for stimulating the erythopoietin hormone, and how it varies according to oxygen concentration in the blood. Using a genetically-modified rat, he attached a distinct DNA to the gene responsible for erythropoietin production to facilitate monitoring the effect of hypoxia on it. He discovered a protein complex (protein synthesis) connected to the distinct DNA in case of hypoxia or hyperoxia; he named it the Hypoxia-Inducible Factor (HIF). He found two types of this complex (synthesis), but he focused his studies on the first type, HIF-1.
He began to decipher the mechanism of stimulating the erythropoietin hormone as HIF-1 increases with hypoxia and vice versa, then rapidly decomposing in normal conditions or in the cases of hyperoxia. Yet, how can the body protect this factor from decomposition in case of hypoxia? Dr. William Kaelin answered this question during his study of the VHL genetic disease, which increases the probability of cancer.
He found out that cancer cells with a deficiency in the gene responsible for the VHL disease have high levels of the hormone controlling oxygen; when the deficient gene is returned, the oxygen levels become normal. As such, the gene responsible for the VHL disease controls the cell’s response to hypoxia or hyperoxia. It became clear that gene linkage with the protein complex HIF-1 leads to its decomposition in normal conditions.
We now know how to regulate the different levels of oxygen, and how this adaptation allows the cells to perform its vital processes, even during hypoxia, such as what happens to the muscles while exercising. This happens through the production of more red blood cells and blood vessels. Now that these promising researches have come to light, it is up to pharmaceutical companies to develop a medicine that controls the mechanism of cells adaptation to oxygen levels, whether by inhibition or activation according to each disease and what suits it.
References
nobelprize.org
nytimes.com
qz.com
*The original article was published in SCIplanet, Winter 2020 Issue.