Darwinian ideas about cancer Professor Harold Varmus (Memorial Sloan-Kettering Cancer Centre, New York, USA) Summary: Charles Darwins ideas about natural selection were developed through meticulous observations about species variation, based on the appearance and behaviour of intact organisms and their visible components. Advances during the past century in cell biology, molecular biology, genetics and pathology have produced new ways to apply Darwinian principles to diseases, especially infectious diseases and cancers. Mutations (genetic variations) are the underlying events in cancers; some of these are inherited, but most are somatic (occurring after birth). Selection for cells that bear such cancer-predisposing or cancer-causing mutations is based on a growth advantage. This favours the cells at the expense of the organism (which commonly dies from the cancer), raising interesting questions about why certain cancer-predisposing versions of genes (alleles) persist in human populations. In addition, because cancer cells are usually found to have multiple mutations, additional Darwinian questions arise: Is the rate of variation (mutation) higher in cancer cells than in normal cells? If so, is the higher rate due to defects in mechanisms, such as DNA repair, that normally protect our chromosomes from damage during life? Do cells that undergo sequential mutations also undergo selection in the context of a tumour, producing an evolutionary process that favours the dominance <b>...</b>