Warburg hypothesis

From Wikipedia, the free encyclopedia

Warburg's hypothesis was postulated by the Nobel laureate Otto Heinrich Warburg in 1924.^[1] He hypothesized that cancer, malignant growth, and tumor growth are caused by the fact that tumor cells mainly generate energy (as e.g. adenosine triphosphate / ATP) by non-oxidative breakdown of glucose (a process called glycolysis). This is in contrast to "healthy" cells which mainly generate energy from oxidative breakdown of pyruvate. Pyruvate is an end-product of glycolysis, and is oxidized within the mitochondria. Hence, according to Warburg, cancer should be interpreted as a mitochondrial dysfunction. Warburg reported a fundamental difference between normal and cancerous cells to be the ratio of glycolysis to respiration; this observation is also known as the Warburg effect.

It is now known that cancer is caused by mutations or increased expression of oncogenes in a process called malignant transformation, resulting in an uncontrolled growth of cells.^[2][3] The metabolic differences observed by Warburg are thought by orthodox oncology to be an adaptation of cancer cells to the hypoxic (oxygen-deficient) conditions inside solid tumors, and therefore not the cause, as he claimed, but an effect of cancer; however, realizing that normal aerobic cellular respiration provides the ATP energy for continual gene repair, as well as controlling gene expression, Warburg's hypothesis, which indicates production of less ATP through anaerobic glycolysis than through normal aerobic respiration, and thereby less ability to maintain normal DNA repair and protein expression, can be reconciled with current understanding of oncogene mechanisms of cancer etiology.

Warburg articulated his hypothesis in a paper entitled The Prime Cause and Prevention of Cancer which he presented in lecture at the meeting of the Nobel-Laureates on June 30, 1966 at Lindau, Lake Constance, Germany. In this speech, Warburg presented evidence in support of the claim that anaerobiosis was a primary cause of cancerous cells. Put in his own words, "the prime cause of cancer is the replacement of the respiration of oxygen in normal body cells by a fermentation of sugar."^[4]