Table 1.

Disease driving hypotheses in cancer.

Historic metabolic hypothesis since circa 1950 (Otto Heinrich Warburg) Cancer cells produce energy by a high rate of glycolysis and lactic acid production in the cytosol even if oxygen is plentiful. Historic submolecular hypothesis since circa 1975 (Albert Szent-Györgyi) Cancer is caused by submolecular mechanisms associated with electron transport abnormalities and protein dysfunctions. This hypothesis was overtaken by molecular genomics approaches and gene dysfunctions. Genetic hypothesis since circa 1990 (Harold Eliot Varmus) Mutations in oncogenes and tumor suppressor genes are responsible for cell transformation with metabolic consequences such as the Warburg effect, which are the results of oncogenic signaling and mutations rather than a cause. Metabolic hypothesis since circa 1998 Cancer is caused by abnormal metabolic reaction architectures and gene clustering that alter mitochondrial functions due to enzyme mutations and/or hypoxia. Mutations and oncogenic signaling are not necessary to initiate or maintain oncogenic transformation but the presence of “oncometabolites” is critical. Deuterium hypothesis since circa 1992 - current Cancer is caused by abnormal metabolic reaction architectures that decrease mitochondrial deuterium depletion. The result is DNA deuteration and aneuploidy by strong kinetic isotope effects exerted by deuterium. Deuterium depletion is an effective adjuvant to prevent and treat cancer.