As beriberi extended its geographical range, incidence, and prevalence in the second half of the nineteenth century, it attracted increasing attention from medical investigators, who began the long process of causal research that extended into the first decades of the twentieth century. Hirsch, in his great Handbook of Geographical and Historical Pathology, first published between I860 and 1864, gave many pages to a description of the disease and to a review and analysis of etiologic possibilities. He found it necessary to discard as principal causes climate, soil, lifestyle, and occupation, among other factors. He could only conclude that beriberi must arise as a result of some intoxication, that is, exposure to a poison. Later the idea emerged that beriberi might appear because of infection, and, until late in the century, theorizing was directed principally to these two causal possibilities.
The search for an infectious agent or a chemical poison, probably in food, continued throughout the remainder of the nineteenth century, but no one interested in beriberi and diet in this period considered the possibility of a deficiency of some specific substance (Williams 1961:16).Two naval officers (the Dutch naval doctor, F S. van Leent, and the chief of the Japanese naval medical service, K. Takaki) were successful in reducing the incidence of beriberi on shipboard by broadening diets previously limited largely to rice (Jansen 1956; Williams 1961). These achievements, pointing clearly to some dietary factor in beriberi, were not widely known or acknowledged at the time.
The first step toward the recognition of the role of thiamine deficiency in beriberi came in 1890 with the publication of a report by Christiaan Eijkman, a Dutch military surgeon in Java, of his studies of polyneuritis in domestic fowl. His experiments were initiated to uncover a presumed infectious cause of the disease by inoculating laboratory chickens with supposedly infectious material from beriberi patients. These birds, fed on crude rice, remained healthy, but when they were later switched to a diet of boiled and polished white rice, left over from the hospital, they began to show signs of polyneuritis not unlike that in human beriberi.
Still later, the chickens were returned to a crude rice diet, after the hospital chief forbade the use of the polished luxury rice for laboratory animals. The neuritis soon disappeared. Intrigued by this change, Eijkman fed two groups of fowl, one with crude rice, the other with polished rice. The latter group developed the same beriberi-like neuritis. The result of this simple experiment was decisive, not only in the history of beriberi but also as the beginning of the much wider field of research on vitamins and specific nutritional deficiencies. Eijkman expanded his investigations in Java until 1896, when he returned to Holland, eventually to a professorial appointment and to the award in 1929 (one year before his death) of a Nobel Prize in Physiology and Medicine, “for his discovery of the antineuritic vitamin.’’
Eijkman’s experimental work with fowl in Java was continued by another Dutch scientist, Gerrit Grijns, who soon became the first to express the theory “that in food there occur in small quantities unknown organic substances essential for health" (Jansen 1956). Grijns called them protective substances. He was able to extract such a substance, soluble in water, from rice bran and to employ it in the treatment of human beriberi. Later Casimir Funk coined the name “vitamine" (later shortened to “vitamin") for a protective substance, an amine that he had isolated and assumed (wrongly as it turned out) to be the same as that studied by Eijkman and Grijns (Byron 1951; Jansen 1956).
The studies in Java were confirmed and extended in Malaya early in the new century (Byron 1951).W L.
Braddon, who published much evidence to show that the cause of beriberi was connected intimately with the consumption of polished white rice, could only explain his findings as due to a poison in the rice. His work provided a foundation for three scientists, H. Fraser, A. T. Stanton, and W Fletcher, at the Institute for Medical Research in Kuala Lumpur. During the decade following 1905, in their studies of road workers (and in Fletcher’s study of patients at an asylum), these investigators further demonstrated the significance of rice polishing in the causation of beriberi. Fraser and Stanton also failed in all attempts to isolate a poison from rice, and they concluded, as Grijns had earlier, that the answer to the problem of beriberi must lie in a nutritional defect, that is, in the absence of an essential protective substance. Fraser and Stanton were never able to isolate the substance, but their studies led them to call for, and advocate, practical measures to cure and prevent beriberi - measures that were to prove very successful. After 1911, the use of polished white rice was prohibited in all Malayan government institutions, the danger of polished rice consumption was widely publicized, and government rice mills began to produce undermilled rice for use in hospitals and public institutions, including prisons and asylums. These actions served to lower dramatically the incidence of beriberi in Malaya within just a few years.
After 1910, as the results of the Malayan studies and preventive actions became known, E. B. Vedder and others in the Philippines started similar programs for the prevention and treatment of the disease. Vedder also encouraged Robert Williams, a scientist at the Bureau of Science in Manila, to begin studies that were to lead, in 1933, to the isolation and final chemical characterization of the protective substance. Some years earlier, in Java, Jansen and W. F. Donath had succeeded in isolating crystals of the antiberiberi factor, but their chemical analysis, limited by the apparatus then at hand, was incomplete, missing the presence of sulfur in the molecule (Jansen 1956). After the final synthesis, in 1936, Williams named the chemical “thiamin.” The spelling was later changed to thiamine, but Williams’s original spelling is still often used.
World History
