Search for a Cure

 The medical mystery of pellagra dates back to 1736, when Spanish royal physician Pedro Casal first described the disorder in Oviedo, Spain. He noted its association with poverty and corn, but believed the cause to be contamination of the corn  ^1.

A distinctive symptom of pellagra still known as Casal's necklace or the Casal collar

The idea that an infectious agent in spoiled corn carried pellagra remained prominent among Western doctors and politicians for the next two hundred years.
 

James Jackson Jarves, a correspondent to the New York Times in 1881 writing about Italy, expresses the common range of insight and confusion about pellagra prior to its final cause being determined:

Hitherto cretinism has appeared to be the most frightful misery that could afflict humanity as a disease, but it is limited as to locality and extent. Compared to the pellagra it is child's play in its capacity of torturing and destroying humanity. And yet Governments and communities can prevent the rise and spread of the latter on the easiest terms of nature, practically enforced in the spirit of justice and love of your neighbor in the Christ-sense. Bad food and bad lodging are the exciting causes of pellagra; good nourishment the remedy and preventive. But if the peasant's chief or exclusive diet is cornmeal, good or bad, as he obtains it in Italy, he seems to be marked out as the victim of the pellagra, while a change to wheaten flour, slightly cooked meat, and pure light wine either prevents, cures, or alleviates it. It would be interesting to know if an exclusive diet of sound corn-meal in American would produce the same disease there as in Italy. If maize be eaten unripe, rotten, or otherwise injured, as with any other spoiled food, it is to be expected that disease of some kind will ensure. In Italy the prevailing opinion now is that corn-meal or any quality as an exclusive diet is the chief exciting cause of pellagra, and a change of food the prevention or remedy.

In Jarves's view, pellagra is caused by an exclusive corn diet of whatever quality, or maybe by spoiled corn and bad lodging, and in any case “the same misery, innutritious, scanty diet, filthy habitations, foul water, damp or chilly climate, prevail alike in two places, and one is afflicted with the plague and the other is free.” ^2 The correlations of pellagra with poverty and corn consumption are clear, but the details are vague, and the exact cause uncertain. 

 

An early 20th century epidemic in the US stimulated medical investigation that finally revealed the true cause of pellagra. The first US cases were reported by Dr. George H. Searcy in 1907. In scarcely over a decade, the epidemic reached a hundred thousand annual reported new cases ^3.

Like other observers, Searcy noted the connection between pellagra and diet. His institutionalized “colored insane” patients never infected the hospital staff, and the dietary link was confirmed when he substituted wheat and potatoes for the molasses and corn products fed to the inmates ^4.

The American medical institution responded to the epidemic, organizing a conference on the subject that met in late 1908 with the support of the governor of South Carolina. The Second National Conference on Pellagra the following year spawned the National Association for the Study of Pellagra ^5. The political attention to the disease was not always helpful, however, since political pressure as well as trends in medical research insisted upon an infectious cause, rather than a nutritional and economic one--Dr. James Babcock, co-organizer of the first National Conference on Pellagra, was fired by the state government in 1914 for damaging the state's reputation by publicizing the disease ^6. An infectious cause would be more palatable to politicians than emphasis on the clear association with poor diet and poverty.

Researchers were biased for a more level-headed reason: infectious microbes usually were the answer. During the time period, medicine was discovering the causes of “typhoid fever, lobar pneumonia, tuberculosis, cerebrospinal meningitis, syphilis, Asiatic cholera, malaria, amebic dysentery, scarlet fever, tetanus, and diphteria” ^7. With so many major diseases caused by the presence of something tiny--rather than the absence of something smaller--infection seemed likely. Add to that the rapid spread of the US epidemic and the conclusions of the Thompson-McFadden Pellagra Commission, which concluded that cases appeared in proximity to other cases and under poor sanitary conditions (ignoring the correlation of these factors with a cheap, monotonous, corn and molasses-based diet), and an infectious disease seemed plausible ^8.

Dr. Joseph Goldberger (image from history.nih.gov)

When in 1914, Dr. Joseph Goldberger replaced his infection-focused predecessor as the Surgeon General's pellagra-research appointee, a new direction of research opened up. A yellow fever and dengue fever survivor and epidemiologist, Goldberger used his own and others' observations of staff immunity in pellagra-plagued institutions like orphanages and insane asylums to rule out a communicable infectious agent ^9. He honed in on dietary inequities between affected and non-affected, and from there experimented on increasing variety of diets in institutions and thus curing pellagra there. Although his findings supported hypothesis, the Southern Medical Association and the Association for the Study of Pellagra responded with hostility. He responded by experimentally inducing the disease in inmates by dietary changes and later failing to induce the disease in himself and colleagues who injected or consumed potentially-infectious body materials from pellagrins. For all his pains and feces-eating, skeptics remained ^10.

However, by establishing that pellagra was a dietary deficiency disease, Goldberger was on the path to ending the epidemic--even when a healthy, balanced diet was not available. A series of accidental discoveries involving canine pellagra led Goldberger to brewer's yeast as a treatment and prophylactic: he had the Red Cross provide yeast to prevent an outbreak among victims of the Great Flood of 1927 ^11. Yeast became a popular clinical treatment, followed by injections in the late 1930s ^12.

Niacin was finally identified as the specific nutrient lacking in pellagrins in 1938 ^13. This time the embarrassment of politicians about having malnourished populations was productive: state laws ordered the enrichment of many common foods with niacin and other nutrients commonly involved in deficiencies ^14.

The United States solved pellagra not by ameliorating the inadequacies in the processing methods they invented and applied to a crop adopted from other cultures, nor by directly addressing the inequities of food distribution and the problem of monoculture in their societies, but by extending their reliance on science and technology through vitamin supplementation. The emphasis on scientific explanations eventually solved the mystery of pellagra and produced several treatment paths, but for a while helped block treatment through varying diet because of a narrow-minded focus on infectious agents.

Cereal box showing supplementation with niacinamide to 25% RDA of niacin

1. Alfred J. Bollet, Plagues and Poxes: The Impact of Human History on Epidemic Disease. (New York: Demos Medical Publishing: 2004.), 156.
2. James Jackson Jarves, "Italy and Her Dark Side: A Frightful Scourge Poverty Has Caused
There," The New York Times, June 19, 1881. Accessed at http://query.nytimes.com/mem/archive-free/pdf?res=9B05EEDE103CEE3ABC4152DFB066838A699FDE
3. Bollet, 158.
4. Ibid., 158.
5. Ibid., 160.
6. Ibid., 161.
7. Ibid., 162.
8. Ibid., 162.
9. Ibid., 163.
10. Ibid., 163-4.
11. Ibid., 166-7.
12. Ibid., 167.
13. Waldemar Kaempffert, "Authorities Sure of Pellagra Cure; New Tests Confirm Finding That Nicotinic Acid Offers a Reliable Specific," The New York Times, March 20, 1938. Accessed at http://select.nytimes.com/gst/abstract.html?res=F60A16F93D55157A93C2AB1788D85F4C8385F9&scp=1&sq=pellagra+kaempffert&st=p
14. Bollet, 167.