On October 7, 2019, three scientists – Dr. William G. Kaelin Jr., Dr. Gregg L. Semenza and Dr. Peter J. Ratcliffe – shared a Nobel Prize in physiology and medicine for unlocking a critical mechanism of oxygen sensing. This research is groundbreaking, especially in cancer, because this will lead us to understand how cells use oxygen and how cancer cells develop. The scientists shared a SEK 9 million prize, rewarded by the Nobel Institute in Stockholm.
Cells experience different levels of oxygen depending on their environment. For instance, if the body is exposed to oxygen deficient environments, then the oxygen level in the body cells would decrease. In addition, wounds can also affect oxygen levels in the cells, since the immune system is adapted to fight infections. There are different oxygen levels depending on the types of cells. When cells progress into cancer or tumor cells, the cell’s characteristics and functions change to benefit the cancer cells. For example, cancer cells will disrupt the blood supply to neighboring cells and instead redivert it to the cancer cells.
The three Nobel laureates identified the mechanism that allows cells to detect when oxygen levels decrease. Cells will activate different pathways to maintain high oxygen levels in the blood. When oxygen levels drop in the body, cells will activate the biosynthetic pathway for erythropoietin (EPO), a protein that targets the bone marrow to synthesize more red blood cells. The production of extra red blood cells is crucial, because red blood cells contain hemoglobin, which can bind to oxygen. Thus, if cells increase the level of red blood cells, it can also increase the oxygen level in the body.
Drs. Semenza, Ratcliff and Kaelin Jr. each contributed to elucidating the mechanism for sensing oxygen levels. Dr. Semenza discovered the hypoxia-inducible factor (HIF), which is a molecule that turns on the activity of genes of EPO synthesis. Dr. Ratcliffe found out that the kidneys make an excess of HIF, but in the presence of adequate levels of oxygen, the cells destroy HIF. Dr. Kaelin Jr. discovered that cancer cells produce EPO, which means that oxygen levels are low.
This research has various applications, such as in biological systems and in drug development. We can better understand how the cells utilize oxygen and the pathways and mechanisms that the cells use oxygen in metabolism. This research is important for developing new drugs to combat cancer. Cancerous cells can thrive in oxygen deficient environments. Scientists are currently making new drugs that help manipulate oxygen levels in the cells in order to starve cancer cells of proper oxygen levels. Scientists are one step closer to figuring out a cure for cancer that targets the problem at a genetic level. In addition, other applications of this research is to develop pills to help people with chronic kidney disease and to aid heart attack and stroke patients.
It is interesting to note that although the three scientists share the Nobel prize together, they did not directly collaborate. They did their own research independent of each other. However, the work of the three scientists was all interconnected, as one part of the research helped them understand and discover other areas of cell biology. The scientists met at conferences and exchanged their findings. Thus, while they did not research the issue of oxygen in cell biology together in the same laboratory, they nonetheless shared their ongoing research, which allowed them to efficiently figure out this issue.
Drs. Semenza, Ratcliffe and Kaelin Jr. discovered the pathway that detects oxygen levels and the reaction mechanisms to maintain adequate levels of oxygen in cells. This research has far-reaching effects in biology, especially in the field of cancer research. This research shows a promising step towards unlocking the mysteries of cancer development and treatment.