History and Geography
Most historical studies of beriberi have been concerned not with its occurrence or impact, but with the developments in medical science that led to an understanding of its etiology, treatment, and prevention.
The geography of the disease has been closely bound to the rice-eating peoples of Asia, although the disease has never been limited to them.In the nineteenth century, beriberi was common among troops and institutionalized people around the globe. What appeared to be epidemics occurred on British ships in the Bay of Bengal, Dutch ships in the East Indies, Norwegian whalers, ships plying the China trade in the Sea of Japan, and ships bringing “coolies” home to India from labor in the French Antilles (Hirsch 1885). The broader epidemiology was very puzzling.
The Search for the Etiology
August Hirsch (1885) noted many contradictions as he described the changing pattern of beriberi in the latter half of the nineteenth century. In a few places, notably Japan and the Malay archipelago and the state of Minas Gerais in Brazil, the disease was endemic. The disease had first appeared in Bahia in Brazil in 1866, and then had spread to Sao Paulo and Rio Grande do Sul by 1874, along the Brazilian seacoast, and into the interior provinces and on into Paraguay. Similarly, the disease had been known on the coast of Japan, but had now spread into interior towns. Earlier opinion had held that a distance of 40 to 60 miles from a seacoast or great river was enough to give immunity, but the disease now occurred hundreds of miles into the interior of Burma and India as well as Brazil. Its appearance in new places showed that it was not caused by climate, which had not changed, and yet it was associated with the rainy season and hot, humid weather. It seemed associated with a period of acclimatization, since people from the interior who moved to the coast as well as new troops usually did not develop the disease for 8 months to a year.
It afflicted people in the prime of life, and wealth and high position did not grant immunity. People who led sedentary lives, such as scholars and teachers, were prone to the disease but so were soldiers and laborers. Tainted water was contraindicated. Clearly people who lived in crowded and poorly ventilated quarters were at risk. The evidence for a dietary cause was confusing. There seemed to be an association with insufficient diet, especially lack of fat and albumin, and with preponderance of rice and dried fish in the diet. Rice, however, was eaten widely in places where beriberi did not occur, and cases had been observed in Borneo where troops eating beef and eggs contracted the disease whereas laborers on a diet of rice and fish did not. Hirsch concluded from the global evidence that the cause of beriberi was sui generis, a peculiar and specific poison and not the climate, weather, soil, manner of living, or diet. It is instructive to contemplate the complexity of the disease, which was not clarified until the concept of a nutritional deficiency, lack of a vitamin, (or mineral) was developed and replaced the idea of a positive poison, in the twentieth century. Then three factors could explain Hirsch’s observations quite simply: the monotonous, restrictive diets of certain populations such as prisoners, troops, and coolies; the metabolic needs of heavy labor; and, notably, the spread of steam-driven milling to supply the urban grain needs. The power mills, first established along coasts and at great ports, then spread along transportation routes through the urban system. They intensified and spread an ancient problem in East Asian populations, and introduced it to plantation societies and booming cities in Latin America and Africa. Power milling practices continued to widen and to cause beriberi in Asia especially until into the 1970s.Ship beriberi was serious among the fishing fleets of New England, Norway, Great Britain, and Canada. There were epidemics in the asylums of Arkansas, and among convicts in South Carolina.
It was reported along the entire coast of South America from Venezuela to Argentina, but was especially serious in Panama City and among the Brazilian navy. In Africa, where there was little rice consumption, it affected troops in Senegal, Sierra Leone, Gabon, the Congo, and Angola. Seven epidemics along the Ivory Coast killed 80 percent of 1,100 known afflicted. It afflicted especially those who ate diets based on bananas, corn, and yams.Robert R. Williams (1961) has best described the importance of the disease as he first encountered it in the Philippines in 1910 (25 years after Hirsch’s description) by summarizing some of the numerous papers and presentations of Edward B. Vedder. In Asia, beriberi was one of the leading causes of death. In what is now Malaysia, British doctors estimated that in 20 years they had treated 150,000 hospitalized cases, of whom 30,000 had died out of a total population of 1,250,000. In the hospitals of Kuala Lumpur between 1895 and 1910, 8,422 admissions out of 33,735 were for beriberi; 20 percent died (Williams 1961). In Japan, where white rice was popular, mortality increased from 20 per 100,000 to over 30 per 100,000 in the early 1920s (Shimazono and Katsura 1965). General morbidity among the Japanese population is not known, but in the Russo- Japanese War of 1904—5 more than 20,000 cases among the troops made beriberi “the only ravaging epidemic.”
There were early suspicions that diet was responsible. K. Takaki observed as a student in Europe the low incidence of beriberi among European navies. In 1885, as surgeon general of the Japanese navy, he altered the diet on the ship where sailors had previously been much afflicted with beriberi, and in so doing provided convincing evidence of beriberi’s nutritional etiology. He subsequently ordered the protein ration increased for all naval personnel, and barley was added to their diet.
By the late nineteenth century, the Dutch in Indonesia had also become convinced that diet was somehow to blame for beriberi.
Experiments were carried out among the penitentiaries of Java in which locally hand-milled rice was substituted for white rice, and beriberi almost disappeared among the prisoners. In 1890, Christian Eijkman, a Dutch officer in Java, discovered that a paralytic disease with nerve damage characteristic of beriberi could be induced in chickens fed polished rice. He and his successor, Gerrit Grijns, demonstrated in 1900 that this condition could be prevented or cured by feeding rice bran. Later Grijns extracted the water-soluble factor from the bran and used it to treat people.These Dutch efforts were the first experimental characterization of nutritional deficiencies, and they developed an animal model that was essential for later nutritional work. Their immediate impact was limited, however, because American and Japanese physicians did not read Dutch. The belief continued across much of the globe that beriberi must be due to some toxin or microbe, although none could be found, or to food spoilage. After the work of Louis Pasteur, the assumption was that every disease must have a positive etiology, an active cause.
Isolation of the Active Factor
In 1910 in the Philippines, Vedder, a U.S. Army captain, began treating beriberi cases with an extract from rice bran, and enrolled the efforts of Williams, a new scientist at the Bureau of Science in Manila, to isolate the active factor. A Filipino doctor, Jose Albert, was then able to identify infantile beriberi: Recognizing that in Europe, breast feeding was protective compared to artificial feeding of babies, but that in the Philippines two-thirds of the mortality occurred in breast-fed infants, he made the connection linking the mothers’ eating habits to the disease.
In 1911, Casimir Funk at the Lister Institute in London isolated a crystalline substance, which he erroneously thought was the active antiberiberi factor and called it a “vitamine” after its amine function. In 1926, two Dutch chemists in Java, B.C.P.
Jansen and W. F. Donath, succeeded in isolating and crystallizing the active substance from rice bran. They mischaracterized it, however, by missing its sulfur atom, and other scientists were unable to repeat the isolation.Williams, now a chemist at Bell Laboratories working on marine cables, continued on his own time and money at home to isolate the active factor and succeeded in 1933. He and those working with him characterized it chemically, and finally, in 1936, completely synthesized it and proved their active synthetic material to be biologically and chemically identical to the antiberiberi factor. Williams named it thiamin, to which research councils later added a final e. Taking out a patent whose royalties funded the Williams-Waterman Fund for the Combat of Dietary Disease, Williams interested Merck & Company in developing a commercial process. Production of thiamine increased from 100 kilograms in 1937 to 200,000 in 1967 (Gubler 1984) until, as Williams remarked with satisfaction, synthetic thiamine was cheaper than that which could be extracted from any natural source (Williams 1961).
Prevention of Beriberi
In the final stage, from his position on the Food and Nutrition Board of the National Academy of Science’s National Research Council, Williams pioneered and supported the enrichment of grain with synthetic thiamine. Russell M. Wilder led the effort to enrich flour, which General Mills supported, and in 1941, the first definitions and standards for enrichment were established. The principle espoused was to raise thiamine to “high natural levels” in the milled flour. Because it was a standard and not a requirement, enrichment of bread in the United States was not fully accomplished until a popular movement was organized during World War II.
Other methods of preventing beriberi had been practiced for decades in Asia. There was considerable success in both Japan and Indonesia in limiting the extent of milling so that bran remained on the rice.
These efforts involved the large, central mills of major cities rather than isolated rural enforcement. Professionals involved in public health generally believed in the importance of educating the public and improving diet to prevent beriberi. Williams, who repeatedly traveled to Asian countries campaigning for the prevention of beriberi, noted that there was opposition on the part of British nutritionists and their Asian pupils to any artificial enrichment of cereals because of a viewpoint that “any commercial intent is suspect with respect to any public health measure” (Williams 1961). The result was that even as beriberi spread through the Southeast Asian countryside as an epidemic following the spread of power rice milling and development, the United Nations and its Food and Agriculture Organization continued to ignore efforts at rice enrichment. Finally, in the 1970s the government of Thailand undertook heavy invest. ments, and others followed their example until the agencies of the United Nations became supportive. It was difficult to treat rice grains with synthesized vitamins (locally deficient) and seal them with a protective coating against washing and excess cooking water, let alone to distribute tons of the enriched rice to be mixed with deficient rice at thousands of small mills extending into the most remote areas, and then to regulate and enforce the system. Nonetheless the success of recent efforts portends that, although marginal and Subclinical beriberi may persist forever, the scourge of beriberi is ended.Melinda S. Meade