History and Geography Europe

Pellagra has always been associated with maize or corn, a grain native to America and the staple food of the American Indians. Carried to Europe as early as the third voyage of Christopher Columbus, maize was at first of interest chiefly to herbalists investigating the medicinal properties of plants. By the middle of the seventeenth century, however, at least one herbalist observed that the grain might have a deleterious rather than a sanguine effect if consumed in large quantities. An herbal of Caspar Bauhinus, published posthumously in 1658 at Basel, described how boys of the Guineas roasted and burned the grains and ate them in place of bread: "[I]f they take it a little too often [they] cannot rid themselves of the itch, since the plant produces blood that is too hot and virtually burned."

Despite this caveat, the obvious advantages of maize ensured its spread beyond the botanical gardens of Europe and into the fields. Its ease of cultivation and prolific yields made it an attractive substitute for wheat, barley, or millet. By the end of the eighteenth century, maize was widely grown in Italy, and from there spread into what is now Yugoslavia and into France, Austria, and Hungary. The ruling Hapsburgs of Austria-Hungary actively fostered its production not only because maize provided a staple food for the peasants, but because its greater yields meant larger tithes for the royal coffers.

Pellagra was first identified by Casal, a physician at the royal court of Spain. In 1735 in the town of Oviedo in the Austrias, he first noticed a kind of leprosy the peasants called mal de la rosa. "Since I never saw a more disgusting indigenous disease," he wrote, "I thought I should explain its characteristics." There followed the description of the disease with its extreme weakness, sensations of burning, crusts on the skin, and melancholia. Casal noted that victims of the disease lived primarily on maize, and he emphasized that the "rose" could be treated by adding to the diet milk, cheese, and other foods seldom seen by the poor. Thiéry, then a physician at the court of Spain, read Casal's manuscript and wrote a brief description of the disease for a French journal, published in 1755. Casal's own work, Historia natural y médica de la principado de Austrias, was not published until 1762, 3 years after his death. In it, the section on mal de la rosa is set apart from other diseases discussed. It contains the volume's only illustration and is written in Latin rather than Spanish. Within 10 years, the disease was noted in Italy and given the name pellagra by Frapolli.

Accounts of pellagra in Spain are scarce after Casal's report, but by the nineteenth century the disease was rampant in northern Italy and southwestern France. Estimates were that 5 percent of the population of Lombardy was affected and that in the worst areas, the ratio was 1:5. In Milan in 1817, a visiting English physician found that about 66 percent of the inmates of a mental institution were pellagrins. The lack of reports of the disease from Spain during this period puzzled the French physician Théophile Roussel; visiting Spain in the 1840s, he determined that some diseases called by various other names were indeed pellagra, and thus published a report to this effect. Although Spanish physicians resented his interference in their medical affairs, Roussel's insistence that there was unity in endemic pellagra-like diseases was a step forward.

In retrospect, it is possible to see why pellagra spread as it did with the cultivation of maize. It was not the grain itself that was to blame for the malady, but the social and economic conditions that forced the poorest segment of the populace to eat an increasingly monotonous diet. In Spain, for example, the disease occurred in the region where the once powerful guild that controlled the raising of Merino sheep had lost its influence. There were 321 different sheep taxes in 1758, and the formerly prosperous sheep industry was badly crippled. Peasants were left to fend for themselves. In Italy, a system of land tenure called mezzadria kept peasants impoverished, half their crops going to the landowner to pay rent. In southern France, maize was not an important crop until the late eighteenth century, and its production in the environs of Paris was not encouraged until 1829, the year the first pellagra case was reported in the country. The peasants who fell victim to the disease were primarily sheep herders. Their land was poor, and money and food were so scarce that they ate an exclusively vegetable diet. The French, however, were luckier than their neighbors. They benefited from the work of Roussel, who believed so strongly that pellagra was caused by eating maize that he encouraged reforms to improve the food supply and the working and living conditions of the peasants. He wrote two books on pellagra, the second appearing in 1866. In this volume, he wrote that the problem of pellagra would be solved not by scientific discovery but through social progress. His arguments were persuasive enough for the French government to decrease maize cultivation for human food and encourage animal husbandry. By the turn of the century, pellagra had virtually disappeared from France.

Few people were willing to accept the idea that a disease as horrible as pellagra was caused by economic conditions. Many, however, were ready to associate it with maize. The proponents of this view were called Zeists, from zea mays, the botanical name of maize. They were led by an Italian physician, Giovanni Battista Marzari, who suggested that there were two problems with the corn diet of pellagrins. The grain was picked before it was ripe and molded in storage. More important, he believed that corn was lacking in certain nutritive elements. His followers tended to accept the spoiled corn theory and for years searched diligently for a toxin. Lodovico Balardini thought he had found it in copper-green molds growing on corn. Cesare Lombroso of Turin, who was as much interested in criminology as medicine, spent a quarter of a century studying these molds. The spoiled corn theory was used to explain why pellagra broke out in Yucatan in 1882, when locusts destroyed the Indian corn crop and the grain had to be imported from New York. Brought in the holds of ships as ballast, the grain spoiled en route. The poorer classes ate it anyway, and pellagra followed. When corn crops failed again in the early years of the twentieth century, corn was again imported to Yucatan. Again it arrived spoiled, and there were outbreaks of pellagra.

Not everyone was convinced that corn was responsible for pellagra. The Anti-Zeists thought that heredity played a part, that bad air was responsible, or that the disease was caused by some unseen organism, which they termed a virus. In the nineteenth century, however, the Zeists were for the most part triumphant, and when they were able to persuade governments to act in curtailing the consumption of corn, as they were in France, they met with a measure of success.

America and the Third World

For a century and a half after pellagra was first described, the magnitude of the problem outside Europe was not appreciated. Not until the 1890s, when the British epidemiologist Fleming Sandwith went to Egypt to serve on the staff of a hospital in Cairo, was anything about pellagra written in English. Sandwith found that many of his hookworm patients had pellagra, and he later discovered that they suffered from malaria and syphilis as well as other ailments. Sandwith noted that the disease was principally "country-bred," and he associated it with a diet of corn. He believed, however, that diseased corn, not good corn, was responsible. During the Boer War, when he was surrounded by poor Bantu people living on maize, he expected to find pellagra among them and he did, although the medical men of South Africa assured him that no such disease existed there.

When pellagra was identified in the southern United States, Sandwith was not surprised. Because this was an area where much corn was eaten, he had long suspected that the disease must be present. He expressed the "confident hope" that long unsolved pellagra problems would be mastered in the United States. The chief threat he saw to eventual success was that "enterprising" people in the South would diagnose everything as "doubtful pellagra." If that happened, he thought, the whole question of pellagra's etiology would fall into disrepute. Both his hopes and his fears were realized.

Pellagra came to the attention of the American medical profession in the spring of 1907 with the diagnosis of an epidemic at a mental hospital in Alabama. The mortality rate was a shocking 64 percent. In the months that followed, hundreds and then thousands of cases were identified, and there was a frantic search for a cause and a cure. The Zeists had their advocates in America, as in Europe, but there was also much interest in looking for an insect vector. The Simulium fly appeared to be the most likely suspect. This theory, advanced by Louis Sambon of the London School of Tropical Medicine, was greeted with relief by agriculturists in the United States. Because of the discovery that malaria, yellow fever, and Rocky Mountain spotted fever had insect vectors, pellagra might well have one, too. Some American physicians blamed foodstuffs other than corn, notably cane sugar and cottonseed oil.

While the search for a cause was underway, so was one for a cure. More than 200 remedies are recorded in the literature. Those most frequently tried were various arsenic compounds, both inorganic and organic, the most popular being Salvarsan, used in the treatment of syphilis.

The U.S. Public Health Service began its work on pellagra soon after the first cases were diagnosed in Alabama, but it was not until 1914, when Joseph Goldberger was assigned to the problem, that real progress was made. In a matter of weeks, Goldberger identified the essential cause of the disease: Something was missing in the diet. In a logical systematic way, he did what no one before him had done. He proved his case and found the missing element, although he did not specifically identify it.

Only 3 weeks after Goldberger began his work, he completely revamped the pellagra investigations of the U.S. Public Health Service and set them on a course that yielded fruitful results. His most important innovation was to introduce a new diet into selected institutions where pellagra was prevalent to see if the disease would disappear. Succeeding in that experiment, he then induced pellagra with a poor diet in a population of volunteer prisoners. To boost acceptance of the then novel idea that a disease could be caused by a dietetic deficiency and to squelch his critics, Goldberger next attempted to transmit the disease to himself and several colleagues. In several experiments over a course of 2 months in 1916, he used all the time-honored ways of experimentally transmitting a disease: blood, nasal secretions, epidermal scales from skin lesions, urine, and feces. Neither he nor anyone else got pellagra.

While these "filth parties" were underway, Goldberger began a study of the relationship of pellagra to economics. He noted that rural victims of the disease were sharecroppers and tenant farmers caught in a cycle of poverty tied to a one-crop agriculture. They grew little but cotton and used their meager share of profits to buy the "3 M" dietary articles which were all they could afford. Few grew much in the way of foodstuffs or kept a cow. Most were chronically in debt. In the mill villages, wages were kept notoriously low so as to attract industry into the so-called New South arising out of the debacle of Civil War. It was in the company-owned South Carolina mill villages that Goldberger demonstrated that poverty begets disease. Conducted over a period of 2 or 3 years, this epidemiological study conclusively proved that pellagrins were sick because they were poor. The study itself became a model in epidemiology. Victims of pellagra in the mill villages were poorer than those who escaped the disease.

In the 1920s, Goldberger turned from epidemiological studies to a search for the specific cause of pellagra. Working at the Hygienic Laboratory in Washington, D.C., a forerunner of the National Institutes of Health, he began a systematic search for the specific element missing in the pellagrin's diet. He was aided in this work by two fortuitous events. He got an animal model for his studies when research workers at Yale University determined that black tongue in dogs is an analogue of human pellagra, and, almost accidentally, he and his associates found one of the richest sources of the missing pellagra-preventive factor. In an effort to improve the dogs' appetite for the monotonous pellagra-producing diet, they added a cake of commercial yeast to the daily ration. The results were magical. Within 4 days after a dog with pellagra was given yeast, its condition had markedly improved.

The efficacy of yeast in preventing and treating pellagra was dramatically proved during the flood of the Mississippi River in the spring of 1927, when thousands of people were driven from their homes and forced to subsist on a diet even more restricted than usual. With Goldberger's help and encouragement, the American Red Cross distributed tons of yeast to flood victims. Distribution of yeast became a standard feature of aid to people during the depression of the 1930s. It was from yeast and liver extracts, also found to be an effective pellagra preventive, that the missing dietary element was finally isolated.

Goldberger was studying liver extracts at the time of his death in 1929. That year there were probably more than 200,000 cases of pellagra in the United States, and the mortality rate was 33 percent. Ironically, it was in the years of economic depression which followed that the incidence of pellagra began to decrease in the United States as both the economy and government programs forced Southerners to grow something other than cotton. With diversification of agriculture and government programs that provided jobs, distributed surplus commodities, and encouraged people to grow more foodstuffs and preserve them for winter use, the disease began to disappear.

After Goldberger's work, the next scientific breakthrough in conquering the disease came from laboratories at the University of Wisconsin, where in 1937 nicotinic acid, later named niacin, was found to be the pellagra-preventive factor. Conrad A. Elvehjem and his associates found that a deficiency of nicotinic acid caused black tongue in dogs. Subsequently, they learned that nicotinamide is as effective in treating black tongue as is nicotinic acid.

Numerous studies were made to transfer the results of this research on dogs afflicted with black tongue to humans with pellagra. Tom Spies used nicotinic acid to treat pellagra patients with considerable success at a hospital in Cincinnati and later extended and expanded his work to Alabama. Commenting on the work of Elvehjem and Spies and fellow workers, the New York Times noted that "an ailment which has baffled medicine for centuries has at last been relegated to the curable diseases and . . . American Medicine has to its credit a triumph comparable with the conquest of yellow fever."

The incredible complexity of pellagra has provided years of work for researchers. Grace A. Goldsmith and her co-workers at Tulane University proved that the amino acid tryptophan is a precursor of niacin, and she helped establish the recommended dietary allowances for that vitamin. Physicians in India have been responsible for the observation that pellagra is associated with the consumption of millet.

Coluthur Gopalan linked the high incidence of pellagra on the Deccan Plateau to consumption of millet and to the grain's high leucine content. Another Indian physician, P. S. Shankar, also noted the association of millet with the disease and found that the drug isoniazid, given for treatment of tuberculosis, may precipitate pellagra.

The disappearance of pellagra from so much of the world where it was once endemic is due as much to economic and social factors as to advances in medicine. In the southern United States, enrichment of bread and flour with vitamins, begun in World War II, has certainly played a part in eliminating the disease, but so has burgeoning prosperity. The example of France in the late nineteenth century showed that government policy that encouraged a varied agriculture could result in important health benefits. Pellagra was finally brought under control in Italy by the 1930s, probably because of a rising standard of living.

From the time when pellagra was first described in the eighteenth century, members of the upper classes have tended either to deny the existence of the disease or to blame its appearance on the inherent moral weaknesses of its victims. In the American South, pellagra became a political and social issue. Its presence bespoke a distinctiveness for the region that many Southerners did not welcome. In the late twentieth century, the disease appears in only isolated pockets in Egypt, Lesotho, and India. Its victims are poor, just as were the Spanish peasants who consulted Don Gaspar Casal in Asturias in 1735.

Elizabeth W. Etheridge

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