In 1914, Mississippi recorded almost 1,400 deaths from pellagra (aka "the red flame"), a disease that causes "diarrhea, dementia, dermatitis and death." The following year, the Rankin State Prison Farm becomes an experimental site for Dr. Joseph Goldberger, who is working for the U.S. Public Health Office (formerly the U.S. Marine Hospital Service).

Known as the "Pellagra Squad," tests are performed on twelve incarcerated men, who are offered pardons in exchange for participating, for one year to identify the cause of the disease, which Goldberger has hypothesized as being a nutritional deficiency. After feeding a nutrient-rich diet to children in Mississippi orphanages and to inmates at the Georgia State Asylum and discovering that these people did not contract pellagra, Goldberger feeds a nutrient-deficient, corn-based diet to the incarcerated men at Rankin. More than half of them contract pellagra.

As such, Goldberger determines that the condition is caused by poverty and malnutrition rather than infectious disease. He also hosts "filth parties," where he and guests consume skin scrapings and excrement in pills to prove "pellagra" is not infectious. While he proves that poverty and diet can cause a disease state, he also exploits the social position of the people in his experiments and violates their autonomy.