Pellagra in the United States: A Historical Perspective

Search for Cause and Cure

In 1912, the pellagra malady was at its peak. An estimated 25,000 cases of pellagra had been diagnosed since 1907, with a mortality rate of 40%.^[15] Despite widespread pellagraphobia, a sincere plea for help came from all quarters. The US Public Health Service and the privately funded Thompson-McFadden Pellagra Commission began to study the pellagra problem.

The Thompson-McFadden Pellagra Commission^[16] surveyed over 5,000 people living in a pellagrous area of Spartanburg County, SC, and found no relationship between diet and occurrence of pellagra. Most pellagrous patients lived in cotton mill villages. Women between the ages of 22 and 44 years, children between the ages of 2 and 10 years, and elderly people were the most frequently affected. Pellagra was uncommon among children younger than 2 years of age, postpubertal adolescents, and active men. Cases of pellagra were seen in clusters. In 80% of pellagra cases, close contact to a preexisting case could be established. The researchers attributed such clustering to an unknown infectious agent transmitted from person to person by an unknown mechanism.

C. H. Lavinder, MD, headed the United States Public Health Service investigations.^[17] However, attempts to establish the basis of an infectious etiology by animal experiments were unsuccessful. R. M. Grimm, MD, did the field survey for the Public Health Service. He studied 25 southern communities: 3 coal mine districts in Kentucky, 7 cotton mill villages in South Carolina, and 15 sharecropping communities in Georgia.^[8] These initial epidemiologic observations established the association of poverty and poor sanitation with occurrence of pellagra.

Pellagra was stripped of its mystery and myth by Joseph Goldberger. Born in Hungary in 1874, he emigrated with his parents to the United States at 7 years of age. He grew up in New York City's East Side, started a college education in civil engineering, then transferred after 2 years to study medicine at Bellevue Hospital Medical College.^[18] After graduation in 1895, Goldberger attempted private practice for a few years. Unsuccessful and bored, he joined the US Public Health Service in 1899. Goldberger found enough challenge and excitement in his new career. By sheer hard work, he was able to establish a name for himself as an astute clinical epidemiologist. It was that reputation that led him to the pellagra problem. Surgeon General Rupert Blue invited Goldberger to head the Public Health Service's pellagra investigations in February 1914.

In 1914, the commonly held opinion was that pellagra was an infectious and communicable disease. Goldberger was not biased by the preexisting opinions. He arrived with a perceptive and a receptive mind. Within 3 months of beginning his investigations, Goldberger convincingly hypothesized the epidemiology of pellagra. By observation and review of the literature, he concluded that pellagra was a dietary disease and not an infectious disease.^[19] His supposition was based on the fact that pellagra occurred only among the inmates of mental institutions and not among the nurses and attendants who had cared for those inmates. The difference between the two groups was in the diet. The nurses and attendants' diet was varied and better. The patients' diet was predominantly based on vegetables and cereals and lacked fresh animal foods. Goldberger was also aware that pellagra was a rural disease associated with poverty, occurring in people who consumed a monotonous "3-M diet" of meat (fat-back), cornmeal, and molasses. Despite not knowing the true dietary cause of pellagra, Goldberger suggested that increased consumption of fresh meats, eggs, and milk could be preventive. Soon, Goldberger was able to prevent and induce pellagra by dietary modification.

Goldberger chose two orphanages in Jackson, Miss, and a Georgia state sanitarium to conduct pellagra prevention studies.^[20] Pellagra had been endemic in these institutions for several years. The diets at the three institutions were modified with a liberal intake of fresh animal foods and legumes beginning in September 1914. The following spring, there was only one case of recurrence among the 172 pellagrins from both the orphanages, and no new cases of pellagra occurred. In the Georgia sanitarium, after dietary modification there was no recurrence of pellagra among the 72 pellagrins, though the recurrence rate was 50% among controls. During the study period, the sanitary conditions of the orphanages and the asylum remained unchanged. With these studies, Goldberger was convinced that pellagra was a preventable dietary malady.

Goldberger's next human experiment was more innovative and radical. With the promise of pardon from Governor Earl Brewer of Mississippi, 12 convicts were recruited from the Rankin Farm of the Mississippi State Penitentiary to participate in a study.^[21,22] The hypothesis was that pellagra is inducible in previously healthy men by consumption of a monotonous cereal-based diet. The subjects were healthy white men. None had pellagra. All other persons living at the farm were observed as controls. The subjects were housed in a clean building and segregated from other convicts. They were expected to work but had shorter work periods and fewer work hours. During the first 10 weeks of the study, there was no difference in diet or lifestyle between the subjects and the controls. During the second phase of the study, for 6 months, the diet was markedly different for the study subjects. They were given a monotonous diet, which was of low caloric and protein value. Of the 12 volunteers, 11 completed the study. Upon completion, 6 of 11 had pellagra. There were no cases of pellagra among the controls. With the success of the Rankin Farm experiments, Goldberger had cured, prevented, and induced pellagra by dietary manipulation.

Goldberger's simplistic and convincing approach to pellagra was not acceptable to southern physicians and politicians.^[8] Implication of the "3-M faulty diet" causing pellagra shifted the focus on the existing poverty in the South, which hurt southerners' pride. Pellagra had come during the era of the microbiologists. Infectious cause had been ascribed to several illnesses. The role of insect vectors in the transmission of malaria and yellow fever had been established.^[23,24,25] Hence, it was only fashionable for the critics of Goldberger to think that pellagra was a transmissible infectious illness. To prove to his critics that pellagra was not transmissible, Goldberger exposed 16 volunteers, including his wife, to blood, urine, feces, and epidermal scales of pellagrous lesions, and pellagra did not develop in any of the volunteers.^[26] Now Goldberger was even more convinced that pellagra was due to a faulty diet and was linked to the prevailing economic conditions in the South.

The next phase of Goldberger's work involved establishing the socioeconomic epidemiology of pellagra. Seven cotton mill villages in South Carolina were chosen. The entire population was screened for pellagra, and meticulous dietary data for all households were collected. Pellagrous households had restricted intake of animal protein.^[27] There was no association with consumption of corn or sanitary conditions to development of pellagra.^[28] Pellagrous households were all poor.^[29] The poverty and diet of those affected could be linked to cotton. Cotton was the king among the cash crops, and the sharecroppers and tenant farmers cultivated cotton at the expense of other crops. Lack of diversification and the speculative nature of cotton prices during the depression made the tenant farmer and the sharecropper vulnerable to poverty, poor diet, and pellagra.^[18] Goldberger had now concluded that pellagra was a socioeconomic malady, and its occurrence in epidemic proportions in the South reflected the extent of southern poverty.

Such a conclusion touched the nerves of the prideful southerners and caught the attention of President Warren Harding.^[8] Harding responded by promising legislative action and wrote to the surgeon general, "Famine and plague are words almost foreign to our American vocabulary, save as we have learned their meaning in connection with afflictions of lands less favored and toward which our people have so many times displayed large and generous charity. . . . The nation could not wait a single day to take action. It must save its own."^[8] Such a statement from the president angered the southern public and politicians. In protest, the citizenry of a Georgia city telegraphed their senator, "When this part of Georgia suffers from a famine the rest of the world will be dead."^[8] The political backlash from the South dampened President Harding's enthusiasm for solving the problem.

The year was 1921; it was 7 years since Goldberger had started his pellagra research. He now began in earnest to study the pellagra-preventive action of various foods and to identify the specific nutritional deficiency that was etiologic for pellagra. Goldberger and Tanner^[30] speculated that pellagra was due to amino acid deficiency. They showed resolution of skin lesions in pellagrins treated with cysteine and tryptophan. However, supplementation of good-quality proteins such as soy and casein failed to cure pellagra; but a diet supplemented with dried yeast and poor in protein was dramatically effective in achieving cure.^[31,32] They concluded that a dietary factor independent of protein was effective in prevention of pellagra. They called it the "pellagra-preventive factor" (P-P factor). Goldberger and his coworkers found dogs to be an ideal animal model for the study of pellagra by showing that black tongue in dogs was similar to pellagra in humans. By 1926, on the basis of animal experiments, Goldberger and his colleagues concluded that P-P factor was the heat-resistant part of "water soluble vitamin B."^[33] Goldberger found dried yeast to contain the highest amount of pellagra-preventive vitamin. In 1927, on Goldberger's recommendation, the American Red Cross distributed dried yeast to Mississippi flood victims and successfully prevented a pellagra epidemic.^[8] The Mississippi flood experience convinced Goldberger that pellagra in the South was preventable only if the prevailing agricultural practices and economic conditions were to change.^[34] He recommended abandoning the cotton monoculture, keeping home gardens for fresh vegetables, and owning milking cows for fresh milk as ways to eliminate the pellagra problem.

Despite his quest to delineate the exact nature of the P-P factor, Goldberger did not succeed; he died of cancer in 1929. The scientific community pursued the search for the isolation of antipellagra factor across the world. In 1937, Conrad A. Elvehjem, an agricultural chemist at the University of Wisconsin, found nicotinic acid to be highly effective for curing black tongue in dogs.^[35] Soon clinical trials followed and confirmed that nicotinic acid (niacin) was indeed the elusive P-P factor.

South Med J. 2000;93(3) © 2000 Lippincott Williams & Wilkins

Cite this: Pellagra in the United States: A Historical Perspective - Medscape - Mar 01, 2000.