Pellagra was first identified among Spanish peasants by Don Gaspar Casal in 1735. A loathsome skin disease, it was called ‘mal de la rosa’ and often mistaken for leprosy. Pellagra has sometimes been called the disease of the four Ds – dermatitis, diarrhoea, dementia and death. In 1937 it was discovered that pellagra was caused by a deficiency of the B vitamin niacin (nicotinic acid). The body's synthesis of this vitamin depends on the availability of the essential amino acid tryptophan, which is found in milk, cheese, fish, meat and eggs. Two decades before the discovery of niacin, however, epidemiological and clinical research done by Joseph Goldberger and his colleagues had identified that pellagra could be prevented by improved diet. By 1912, the state of South Carolina alone had reported 30,000 cases of pellagra, with a case fatality rate of 40%. The disease was not confined to Southern states, however, and the US Congress asked the Surgeon General to investigate the disease. In 1914 he appointed Joseph Goldberger (1874–1929), a medical officer in the US Public Health Service, to lead the investigation. Even though some scientists such as Theophile Roussel1 and Casimir Funk2 argued that pellagra was caused by something inadequate in the diet, the disease was generally thought to be due to an unidentified germ. This opinion had received strong support in 1914 by the Thompson-McFadden Pellagra Commission. This Commission, which had been set up by the US government, had conducted a house-to-house survey of pellagra cases in the cotton mill districts in South Carolina and concluded that the disease was unrelated to diet. Goldberger had a different opinion. He had observed that, in mental hospitals and orphanages, the disease affected inmates but never staff. Also, well-to-do people seemed never to develop the condition. Goldberger believed that an infectious disease was unlikely to distinguish between inmates and employees or so systematically between rich and poor, and he favoured the hypothesis that a superior diet protected people from pellagra. He had also in mind the case of beri-beri, a disease which had recently been shown to be responsive to dietary interventions.3–5 In 1914 Goldberger designed and implemented two experiments to assess whether improving the diet of institutionalized children and adults would prevent pellagra. The first set of institutions studied were two orphanages with a high incidence of pellagra in Jackson, Mississippi. Goldberger and his colleagues noted that the disease affected only children between 6 and 12 years of age and observed that ‘after a detailed inquiry, the only explanation that could be found for the remarkable restriction of the disease to this group was a difference in the diet of the resident groups’.6 Their diet was poor in lean meat or other animal protein food. A parallel and analogous experiment was conducted in two women's wards (one for black patients, the other for white patients) in the Georgia State Sanitarium, the largest asylum in the South. This institution admitted a large number of patients with pellagra every year, but the objective of the study was to assess the effects of the dietary intervention in preventing recurrence of the condition, not for treatment.