History of Medicine

BERIBERI: AN INFECTION?

      Today we know that the cause of a disease of rice-eating countries, beriberi, is a deficiency of thiamine. During the latter part of the nineteenth century, however, the source of this mysterious disease that afflicted workers in Asian countries, bedeviled thousands in military services, and devastated prison inmates, was unknown. Numbness, muscular weakness, and cardiac insufficiency were its hallmarks, and the fatality rate was in the range of 30-35 percent. A British medical officer, William Anderson, an instructor in the Japanese Naval College (using British advisors) in Yedo, where the disease was known as kakké, reported on it in 1877. He considered factors such as overcrowding (common on ships), atmospheric conditions, geography, general hygienic conditions, and diet as possible causative factors. But he did not consider it an infectious or contagious disease.

Beriberi patient (National Library of Medicine)

     The year of that report, a young Japanese, Kanehiro Takaki, was in London studying medicine. Born into a samurai family, Takaki grew up learning Chinese, fencing, and riding. He read

medical books translated from Dutch  and served as a medic under the Prince of Satsuma in the civil wars following the fall of the shogunate. Disturbed by the poor treatment the wounded soldiers received, Takaki resolved to study medicine. He learned Dutch and English while studying under an English physician, William Willis, who encouraged further education in England. Takaki spent five years at St. Thomas School of Medicine in London, where he received several prizes and a gold medal.

     Returning to Japan, in 1880, as a medical officer in the

Kanehiro Takaki (National Library of Medicine)

Japanese Navy, he was confronted with a high prevalence of kakké among the sailors. Using techniques acquired in England, Takaki noticed that the nitrogen (a marker of protein) to carbon ratio was lower than an accepted value. Persuading the Navy brass to enrich the sailors’ diet for an upcoming cruise, identical to one on which kakké broke out, Takaki all but eliminated the scourge. He dismissed the idea that an infection caused the problem, noting the excellent state of hygiene on the ships. Later, barley or mungo beans added to the diet proved as effective as bread and meat. Barley had been discovered when prison authorities, to save money, partially substituted barley for rice, and watched beriberi disappear. The Navy was never troubled with kakké again.

     Japan’s medical schools, however, had invited German advisors, who focused on an infectious agent. Beriberi’s tendency to outbreaks and predilection for the summer season invited this speculation in an age of emerging germ theory. The Japanese Army doctors, also trained by Germans, also rejected the dietary hypothesis and concentrated on microbes.

     So did the Dutch. In 1886, the Dutch halted the suppression of a revolt in Sumatra due to alarming rates of beriberi among their troops. An investigating commission was formed whose leader, the pathologist Cornelis Pekelharing, was sent to study in Robert Koch’s laboratory before embarking. There he met

Christiaan Eijkman (Wikipedia)

Christiaan Eijkman, another Dutchman studying with Koch, and took him to Sumatra. Perhaps unsurprisingly, looking for an infecting agent, they isolated a micrococcus from patients but only with difficulty could they produce nerve changes. Pekelharing left after eight months and, probably for economy, Eijkman switched from mammals to chickens as an experimental animal. By chance, cooked rice left over from an Army kitchen was substituted for the usual chicken feed and the chickens developed the neuropathy characteristic of beriberi. Eijkman turned to dietary studies, eventually determining that the skin covering the rice grain, removed in the rice-polishing procedure, contained the necessary ingredient to prevent the disease in rice eaters.

      Japanese Army doctors pursued an infectious cause but in spite of exemplary hygienic measures, Beriberi devastated the Japanese soldiers during the 1904-5 Russo-Japanese War. Estimates of 80,000 to over 200,000 cases are available.    

     Beriberi also plagued the Philippines during the American occupation following the Spanish-American War of 1898. Soldiers, civilians, and prisoners were all affected. An American, Maximilian Herzog, was dispatched from Manila to the Japanese Army kakké hospital in Hiroshima to meet with Surgeon Major Kokubo, who, significantly, was a professor of infectious diseases in Tokyo. He also had isolated a coccus from patients. Herzog studied the coccus at the Army Research Center in Manila but could do nothing with it. Meanwhile, in 1905, General Terauchi, Japanese Minister of War, finally ordered barley added to Army rice rations, almost eliminating the disease in troops.

     In 1910, the Americans convened a conference in Manila, the First Congress of the Far Eastern Association for Tropical Disease. At the conference two British investigators, Henry Fraser and Thomas Stanton, presented convincing dietary studies carried out in Malaya, showing again that polished rice was the culprit.  Still, after much discussion the conference failed to pass a resolution stating that beriberi was due to a continuous diet of polished rice. The resolution slipped through later, though, at a final business meeting with fewer members present.

     Even so, the French Société de Pathologie Exotique, unconvinced, appointed yet another study commission. Only at the Second Congress, in 1912, was a firm resolution implicating polished-rice diets agreed upon. The notion of infection had finally expired.

Casimir Funk (Wikipedia)

     Takaki was appointed Navy Surgeon General in 1885 and was made a baron in 1905. Eijkman received the Nobel Prize in 1929 for his work. Casimir Funk coined the term “vitamine” in 1912 (later shortened to “vitamin”), and Robert R. Williams synthesized thiamine in 1935. In Japan, vials of liquid thiamine were sold as “Beriberol”, injected by civilians and military alike during WWII.

SOURCES:

Carpenter, Kenneth J. Beriberi, White Rice, and Vitamin B: A disease, a Cause, and a Cure. 2000; Univ of California Press.

Strong, R and Crowell, B. “The etiology of beriberi.” 1912; Philippine Journal of Science 7B: 271-411.

Heiser, V G. “Practical experience with beriberi and unpolished rice in the Philippines.” 1911;  JAMA 56: 1237-8.

Sugiyama, Y and Seita, A, “Kanehiro Takaki and the control of beriberi in the Japanese Navy.” J Royal Society of Medicine 106 (8): 332-4.

Hawk, B A, “The great disease enemy, kakké (beriberi) and the Imperial Japanese Army.” 2006; Military Medicine 171: 333-9.

Anonym, “The Far Eastern Association of Tropical Medicine.” BMJ April 23, 1910, pp 999-1000.

Fraser, H and Stanton, A T, “The etiology of beriberi.” Trans Royal Society Tropical Med and Hygiene 3(5): 235-67.

Herzog, M. “Beriberi in the Japanese Army during the late war: The kakké coccus of Okata-Kokubo.” 1906; Philipp J Science 1: 169.

Edit, “Baron Kanehiro Takaki.” 1906; Medicine 12: 241-3.

Bay, Alexander. Beriberi in Modern Japan: The Making of a National Disease. 2012; Univ of Rochester Press.