Trio wins Nobel Medicine Prize for work on how cells adapt to oxygen

STOCKHOLM: Three researchers from the US and Britain on Monday shared the Nobel Medicine Prize for research into how human cells sense and adapt to changing oxygen levels, opening up new strategies to fight common diseases such as cancer and anaemia.

William Kaelin and Gregg Semenza of the United States and Britain´s Peter Ratcliffe split the nine million Swedish kronor ($914,000) award. While the fact that humans need oxygen to survive has been understood for centuries, how the body registers and responds to oxygen was little known prior to the trio´s pioneering work. "They established the basis for our understanding of how oxygen levels affect cellular metabolism and physiological function," the jury said.

Semenza studied a gene known as EPO which causes the body to create more red blood cells and isolated the specific DNA segments that help it to adapt to low oxygen levels. Ratcliffe and Semenza then applied this knowledge to show that the oxygen sensing mechanism was present in virtually all human tissues.

Kaelin identified another gene, present in patients with a genetic disorder that puts them at far greater risk of certain cancers. The gene rewires the body’s ability to prevent the onset of cancer, and it plays a key role in how cancer cells respond to low oxygen levels.

Their work has shed new light on the specific, cell-level processes the body undergoes when low on oxygen — from helping our muscles function during exercise to adapting to life at high altitude. Cells’ oxygen-sensing ability is also essential during foetal development and in creating new blood vessels.

A large number of diseases are linked to EPO, including renal failure and severe anaemia. Cancerous tumours use the body´s oxygen-regulating tools to hijack blood vessel formation and allow the cancer cells to spread.

The Nobel committee said Monday that several trials were underway developing drugs to interrupt this process, potentially short-circuiting tumour growth. "Intense ongoing efforts in academic laboratories and pharmaceutical companies are now focused on developing drugs that can interfere with different disease states by either activating, or blocking, the oxygen-sensing machinery," the jury said.

For treatment of anaemia -- where the body lacks sufficient red blood cells to carry enough oxygen to tissues -- medicines in development seek to stimulate EPO creation.

This essentially tricks the body into thinking it is at higher altitude, prompting the creation of new red blood cells. One drug using EPO-stimulation for anaemia is already on the market in China and others are in the pipeline.

Kaelin, 61, works at the Dana-Farber Cancer Institute in Boston and is a professor at Harvard Medical School in the US. Semenza, 63, is director of the Vascular Research Programme at the Johns Hopkins Institute for Cell Engineering.