Metabolic Control Analysis Shows How Aneuploidy Causes Cancer

Over loo years ago aneuploidy, a numerical abnormality of chromosomes, was proposed as the cause of cancer (von Hansemann, 1890; Boveri, 1914). Since about 1970, the aneuploidy hypothesis has lost support over the years because it was unable to provide a specific mechanism for how the characteristic phenotypes of cancer cells could be generated without gene mutation. However, it is becoming increasingly apparent that the prevailing gene-mutation hypothesis of cancer is incapable of explaining the complexity and diversity of cancer-specific phenotypes, including dedifferentiation, invasiveness, metastasis, abnormal morphology and metabolism, genetic instability, and progression to malignancy (Duesberg & Schwartz, 1992). The failure of the gene-mutation hypothesis to explain cancer led us to re-examine the aneuploidy hypothesis in order to investigate how cancer could be caused without gene mutations (Li et al., 1997; Duesberg et al., 1998; Rasnick & Duesberg, 1999; see also Chapter 9 in this book).