This led to the disease being known as "Asturian leprosy", and it is recognized as the first modern pathological description of a syndrome. It was an endemic disease in northern Italy, where it was named, from Lombard, as "pell agra" (agra = holly-like or serum-like; pell = skin) by Francesco Frapolli of Milan. With pellagra affecting over 100,000 people in Italy by the 1880s, debates raged as to how to classify the disease (as a form of scurvy, elephantiasis or as something new), and over its causation. In the 19th century, Roussel started a campaign in France to restrict consumption of maize and eradicated the disease in France, but it remained endemic in many rural areas of Europe. Because pellagra outbreaks occurred in regions where maize was a dominant food crop, the most convincing hypothesis during the late 19thcentury, as espoused by Cesare Lombroso, was that the maize either carried a toxic substance or was a carrier of disease. Louis Sambon, an Anglo-Italian doctor working at the London School of Tropical Medicine, was convinced that pellagra was carried by an insect, along the lines of malaria. Later, the lack of pellagra outbreaks in Mesoamerica, where maize is a major food crop, led researchers to investigate processing techniques in that region. Pellagra was studied mostly in Europe until the late 19th century when it became epidemic especially in the southern United States. In the early 1900s, pellagra reached epidemic proportions in the American South.
Goldberger experimented on 11 prisoners (one was dismissed because of prostatitis). Before the experiment, the prisoners were eating the prison fare fed to all inmates at Rankin Prison Farm in Mississippi. Goldberger started feeding them a restricted diet of grits, syrup, mush, biscuits, cabbage, sweet potatoes, rice, collards, and coffee with sugar (no milk). Healthy white male volunteers were selected as the typical skin lesions were easier to see in Caucasians and this population was felt to be those least susceptible to the disease, and thus provide the strongest evidence that the disease was caused by a nutritional deficiency. Subjects experienced mild, but typical cognitive and gastrointestinal symptoms, and within five months of this cereal-based diet, 6 of the 11 subjects broke out in the skin lesions that are necessary for a definitive diagnosis of pellagra. The lesions appeared first on the scrotum. Goldberger was not given the opportunity to experimentally reverse the effects of diet-induced pellagra as the prisoners were released shortly after the diagnoses of pellagra were confirmed. In the 1920s, he connected pellagra to the corn-based diets of rural areas rather than infection as contemporary medical opinion would suggest. Goldberger believed that the root cause of pellagra amongst Southern farmers was limited diet resulting from poverty, and that social and land reform would cure epidemic pellagra. His reform efforts were not realized, but crop diversification in the Southern United States, and the accompanying improvement in diet, dramatically reduced the risk of pellagra. Goldberger is remembered as the "unsung hero of American clinical epidemiology".