Did We Get Pasteur, Warburg, and Crabtree on a Right Note?

Antoine Lavoisier (eighteenth century) demonstrated that living organisms consume oxygen to slowly burn the fuels in their bodies to release energy (1). Louis Pasteur (2) in an epoch making discovery, recognized as “the Pasteur effect,” declared “fermentation is an alternate form of life and that fermentation is suppressed by respiration” [reviewed in (3–5)]. Yet another observation of Pasteur, that yeast cells consume oxygen to multiply, is debated less among cancer biologists. This nevertheless, forms the first scientific observation that proliferating cells need oxygen to divide. Pasteur was involved in a path breaking debate with Liebig on whether fermentation is a chemical or a biological process? By 1880s Pasteur could establish that fermentation is a physiological process, and oxygen, considered to be a putrefying factor by Liebig and others, was a growth promoting factor [reviewed in (3)]. Six decades later, Warburg (6) proposed that damaged respiration and enhanced fermentation of glucose is the prime cause of cancer formation. It became popular as “aerobic glycolysis” and a counter to “the Pasteur effect.” Warburg was uncompromising and was intolerant to any alternate theory on cancer formation and declared to the German Central Committee for Cancer control in 1955 at Stuttgart “… there is today no other explanation for the origin of cancer cells, either special or general. From this point of view, mutation and carcinogenic agent are not alternatives, but empty words, unless metabolically specified…” (7). Crabtree (8), a contemporary of Warburg, suggested that pathological over growths use aerobic glycolysis as a source of energy and glucose uptake and glycolytic activity has a depressive effect on oxygen consumption. His conclusion gained the popularity as the “inverted Pasteur effect” or the “Crabtree effect” (9). Several authors in the middle of twentieth century reported that glucose is a negative regulator of respiration. These reports indicate that there is an initial stimulation of oxygen consumption for about 20–120 s following glucose consumption followed by an inhibitory period, which after equilibration stabilizes to a constant of about 30% of the endogenous rate until all the glucose was consumed [reviewed by (9)].