While waiting in lodgings to join H.M.S. Beagle just before Christmas 1831, Charles Darwin suffered chest pain and heart palpitations. On his return to England he began to suffer from a range of gut problems and systemic symptoms around the body, which were to plague him for the rest of his life. At least 40 conditions have been proposed to explain Darwin's illness, which left him disabled, sometimes for weeks on end. Here we show that lactose and food intolerance is the only condition that explains all his symptoms. Furthermore, there is now a molecular basis to account for these, based on metabolic toxins produced by microbes in the intestine. This mechanism has important implications in several other diseases, including diabetes, inflammatory bowel disease, Parkinson's disease and some cancers. Lactose intolerance also has fascinating things to tell us about molecular evolution – the origin of lactose, the unique sugar in milk; why white humans were able to invade the plains of Europe after the last ice thaw, some 10 000 years ago; and one of the most intriguing problems in evolution – the origin of a new enzyme such as lactase, the enzyme responsible for cleaving lactose into its constituents monosaccharides, galactose and glucose