Gerrit Grijns’s proposal that beriberi is caused by a nutritional deficiency in a diet of polished rice led to the concept of vitamins.
Beriberi is a disease caused by a deficiency of vitamin B1, thiamine, in the diet. The name of the disease, which is Sinhalese for “I cannot,” came from the fact that people afflicted with severe beriberi are too sick to do even the simplest things. Beriberi was endemic to the Far East in the nineteenth and early twentieth centuries. Its symptoms include stiffness of the lower limbs, paralysis, severe pain, gradual breakdown of the muscles, anemia, mental confusion, enlargement of the heart, and death resulting from heart failure.
By the end of the twentieth century, the incidence of severe beriberi was much lower; the disease was found mostly in undernourished people in the rice-eating nations of Asia, Indonesia, and Africa. In industrialized nations, beriberi is seen most often in chronic alcoholics because their limited diets—which consist mostly of alcohol—are deficient in vitamins in general, including thiamine. Very severe thiamine deficiency in alcoholics results in Wernicke-Korsakoff syndrome,
Despite the fact that the human body’s need for thiamine has been known for many years, a significant proportion of Americans are believed to ingest barely enough thiamine in their daily diets. By the end of the twentieth century, manufacturers enriched many foods inherently low in thiamine (such as white bread, breakfast cereal, pasta, and white flour) with the vitamin as a health precaution. The best natural sources of thiamine are whole-grain cereals, nuts, and cooked fish (raw fish contains an enzyme that can destroy thiamine). Excessive consumption of tea can lead to thiamine-deficiency symptoms because tea contains a chemical that antagonizes the actions of this vitamin.
Beriberi has been known for thousands of years. For example, reference to a disease with its symptoms is found in the Chinese medical literature of 2700
In 1887, an important early observation on the dietary origin of beriberi was reported by Takagi Kanehiro, director-general of the Japanese navy. Kanehiro became interested in beriberi because one-third of all Japanese sailors had the disease. After careful study, Kanehiro became convinced that the cause of the beriberi was the standard navy diet—polished rice and fish—which was low in protein. He ordered the addition of red meat, vegetables, and whole-grain wheat to the sailors’ diet. After the changes were made, beriberi became rare in the navy.
Around the same time, the work of Christiaan Eijkman and his assistant, Gerrit Grijns, began. The Dutch East Indies (now Indonesia) was becoming a dangerous beriberi zone. The disease was spreading in epidemic proportions in the armed forces, prisons, and general population. Conditions were so bad in Javanese prisons, for example, that a jail sentence was considered to be almost a death sentence. In some afflicted people, cardiac insufficiency and massive edema (swelling) of the legs, symptoms of “wet beriberi,” predominated. In patients with “dry beriberi,” the main problem was progressive paralysis of the legs. Because of the apparent epidemic nature of the disease, a bacterial origin was suspected. Consequently, the Dutch government appointed a commission composed of two physicians, Cornelius Pekelharing and Clemens Winkler, to study beriberi firsthand. A third commissioner, Eijkman, was appointed after Winkler and Pekelharing asked Robert Koch to join their expedition. Koch demurred but suggested the substitution of Eijkman, a physician who had just completed training in bacteriology with him.
The commissioners arrived in the East Indies in 1886 and immediately began their studies. Within two years, they had shown that beriberi is a result of inflammation of the nerves (polyneuritis). Because they isolated a bacterium from the blood of beriberi victims, the commissioners were satisfied that the disease was of bacterial origin. Winkler and Pekelharing returned to the Netherlands, and Eijkman stayed behind to continue the research and to direct the Javanese Medical School.
Fortuitously, Eijkman observed a disease similar to beriberi in chickens. The diseased animals developed spontaneously all the symptoms of beriberi. Eijkman named the disease polyneuritis gallinarum. In the course of studying the birds, Eijkman had them moved to new quarters. Strangely, the disease disappeared inexplicably. Upon examination, reflection, and study, Eijkman determined that the food given to the birds after they were moved had changed in one important respect: Originally, the birds had been fed on leftover boiled white rice from the officers’ ward in the military hospital, but after their relocation they were given unpolished rice because the cook at the new site “refused to give any military rice to civilian fowl.”
On the strength of this observation, Eijkman set out to determine whether the polished rice was the cause of the disease. He found this to be the case, because the feedings of unpolished rice cured the disease. Eijkman postulated that a chemical—perhaps a toxin from intestinal bacteria—was the actual causative agent. Although this concept was not correct, Eijkman’s efforts began the scientific research that later showed that thiamine taken from the outer layer (the pericarp) of unpolished rice protected against beriberi.
In 1896, Eijkman left Java and returned to the Netherlands because of ill health. At that time, Grijns took over the study of beriberi. In 1901, Grijns proposed that the disease results from the lack of some natural nutrient substance that is found in unpolished rice and in other foods (that is, a nutritional deficiency). Many scientists now view the work that Eijkman began and Grijns continued as the basis for the modern theory of vitamins.
In 1917, Grijns likewise returned to the Netherlands. By 1921, he had become a professor of animal physiology at the State University in Wagenigen. In 1940, he was awarded the Swammerdam Medal for his development of the concept of nutritional deficiency.
Eijkman was appointed professor of public health at the University of Utrecht in 1898. He retained that position for thirty years and completed many other important research efforts during his tenure at the university. In 1929, Eijkman and Frederick Hopkins shared the Nobel Prize in Physiology or Medicine for their roles in the discovery of vitamins.
Eijkman’s observations that beriberi was caused by excessive dietary use of polished rice and that it could be cured by the feeding of unpolished rice were extremely important to the understanding of nutrition. His work set into motion a sequence of events that led to the development of many aspects of modern nutrition theory, the evolution of biochemical explanations for several very serious nutritional diseases, and the virtual eradication of beriberi.
Eijkman believed incorrectly, however, that a curative material in unpolished rice prevented the action of toxins present in the polished grain. In 1901, Grijns was the first to interpret correctly the action of this unknown substance. Grijns proposed that beriberi developed because diets that used polished rice only lacked an essential substance that was required for the appropriate function of the nervous system. Grijns and other researchers soon showed that many foods contain the antiberiberi factor and proved that these foods could be used to treat beriberi.
Further studies were conducted in an effort to identify the chemical nature of the substance involved. In 1912, Casimir Funk
The availability of the pure vitamin allowed examination of its metabolic rate and actions. It soon became clear that thiamine is an essential component (coenzyme) required for the biological action of a great many important enzymes (biological catalysts). The lack of function of these catalysts was shown eventually to be the cause of beriberi. Very similar results with other vitamins led to the concept that vitamins are coenzymes or parts of coenzymes and that the deficiency diseases produced by their absence are diseases resulting from enzyme inactivation. Thus Eijkman’s and Grijns’s endeavors to understand beriberi led eventually to the establishment of many basic precepts of nutrition and to the current understanding of the roles of vitamins.
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Bicknell, Franklin, and Frederick Prescott. The Vitamins in Medicine. 3d ed. New York: Grune & Stratton, 1953. Chapter 3 describes concisely the history, the chemistry, and many medical aspects of thiamine up to 1952. A valuable source for readers who desire historical perspective on thiamine and its medicinal attributes. Includes pictures of beriberi victims and 953 references on the vitamin, its isolation, and its use. -
Carpenter, Kenneth J. Beriberi, White Rice, and Vitamin B: A Disease, a Cause, a Cure. Berkeley: University of California Press, 2000. Provides a comprehensive account of the history and treatment of beriberi. Includes appendixes, illustrations, and references. -
Lehninger, Albert L. Biochemistry. 2d ed. New York: Worth, 1975. Chapter 13 of this college textbook contains a summary of the chemistry and biochemistry of thiamine and describes briefly aspects of thiamine enzymology, production of thiamine deficiency, and thiamine isolation. Several useful references appear at the end of the chapter. -
Lindeboom, Gerritt A. “Christiaan Eijkman.” In Dictionary of Scientific Biography, edited by Charles Coulston Gillispie. New York: Charles Scribner’s Sons, 1971. This brief biographical sketch is one of the few sources of information on Eijkman written in the English language. It focuses on his career, providing some insight into his life and his impact on both medicine and the science of nutrition. Includes information on some Dutch sources of biographical information. -
McCollum, Elmer V. A History of Nutrition. Boston: Houghton Muffin, 1957. Chapter 16 of this interesting book is especially valuable to readers who wish to trace the evolution of the understanding of the chemical nature of the vitamin and the biochemical basis for its actions. Twenty-eight references are cited. -
_______. The Newer Knowledge of Nutrition. 2d ed. New York: Macmillan, 1922. Chapters 9 and 10 contain useful information on thiamine and beriberi, including the history, symptoms, and treatment of the disease. These chapters discuss the work of Kanehiro, Grijns, and Eijkman; Funk’s isolation of thiamine; and aspects of the work of Williams (who later synthesized thiamine). -
Smith, Emil L., et al. Principles of Biochemistry. 7th ed. New York: McGraw-Hill, 1983. Chapter 21 of this excellent biochemistry text contains a brief description of thiamine and beriberi. Aspects of thiamine biochemistry, metabolism, deficiency, and distribution are addressed. Several references to more technical sources are included. -
Sure, Barnett. Vitamins in Health and Disease. Baltimore: Williams & Wilkins, 1922. Chapter 21 of this basic nutrition text describes the symptoms of different types of beriberi and their treatment as well as aspects of the nutrition, distribution, and medicinal properties of vitamin B1. A useful source for readers who desire a simple approach. -
Williams, Robert R. “The Chemistry of Thiamine (Vitamin B1).” In The Vitamins, a Symposium, edited by Morris Fishbein. Chicago: American Medical Association, 1939. This article describes the synthesis and chemical characterization of thiamine, credits isolation of the vitamin from natural sources, describes Williams’s chemical synthesis and characterization of thiamine, and inventories several aspects of the first evidence for the coenzymatic nature of the vitamin. Includes forty-six references.
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