Notwithstanding the extended discussion and scientific research of the last few years, the question as to the definite etiology of pellagra has not as yet been positively settled. The maize or Indian corn theory was first advocated by Mazari in 1810. He believed the symptoms to be due to a deficiency in gluten. Sette in 1826 attributed the disease to a fungus (scimelpige) growing on corn and producing a poison from the oil in the grain. The smut of corn, "Ustilago Maydis," was suggested as a possible factor by Pari in 1860. In 1872 Lombroso formulated his toxic theory: "In pellagra we are dealing with an intoxication produced by poisons developed in spoiled corn through the action of certain microorganisms, in themselves harmless to man." He also announced the discovery of "pellagrosein," a toxic substance extracted from spoiled corn. In 1902 Ceni advanced the theory that the disease was caused by the action of certain moulds such as the aspergillus fumigatus and flavescens. The Illinois Pellagra Commission in 1911 came to the conclusion after an elaborate investigation of the subject that the primary etiological factor involved was a living microorganism of unknown nature, that the probable source of infection was through the intestinal tract and that a deficient amount of animal protein in the diet probably acted as a predisposing cause. Funk in 1914 suggested a vitamin deficiency in the diet brought about by the consumption of overmilled corn. Voegtlin[245] in the same year expressed the opinion that the disease was essentially a chronic intoxication,—"While the agents at work in this intoxication are as yet unknown, I am inclined to believe that toxic substances exist in certain vegetable foods, not necessarily spoiled, which, if consumed by man over a long period of time, may produce an injurious effect on certain organs of the body.... It is probably more than a mere coincidence that the population of that part of the world in which pellagra is endemic lives on a mainly vegetable diet." In 1916 a study was made by Koch and Voegtlin[246] of the chemical changes found in the nervous system in pellagra which was very significant in its results. They found an increase in water with a decrease in proteins and lipoids, the latter reaction being attributed to a degeneration in the white matter. There was also a relative increase in the cholesterol content, looked upon as a compensatory protective function tending to replace the loss in lipoids. The most marked chemical alterations were found in the cord. On feeding monkeys and rats with an exclusive vegetable diet, changes in the chemical reaction of the brain and cord of almost exactly the same type were brought about experimentally.