Kitasato, Shibasaburo

Kitasato, Shibasaburo

(b. Oguni, Kumamoto, Japan, 20 December 1852; d. Nakanojo, Gumma, Japan, 13 June 1931)

bacteriology.

Kitasato, one of the foremost Japanese bacteriologists, was born sixteen years before the Meiji Restoration in a country village in the mountains of Kumamoto prefecture. He was the eldest son of Korenobu Kitasato, the mayor of the village. In 1872 he enrolled at a newly founded medical college in the city of Kumamoto, where he met a Dutch physician, C. G. van Mansvelt, who had been invited to the school as the principal advisor for medical education. Kitasato became greatly devoted to the Dutch scholar, who in turn recognized his pupil’s ability. Mansvelt invited Kitasato to his own home almost every evening, and gave private tutoring to Kitasato not only in the medical sciences but in Western history and culture.

When Mansvelt left Kumamoto, he suggested to Kitasato that he pursue a medical education at the University of Tokyo and then go to Europe for further study. Kitasato received his medical degree from the University of Tokyo in 1883. He then worked as a government officer at the new Public Health Bureau. There he became a research assistant to Masanori Ogata, associate professor at the University of Tokyo, who had just returned from Germany and had opened a new laboratory of bacteriology at the bureau; the first such laboratory in Japan, it was equipped with German microscopes and other apparatus.

Kitasato married Torako Matsuo in 1884. In the same year during an outbreak of cholera at Nagasaki, Kitasato is said to have demonstrated the presence of comma bacillus, the causative bacteria of the disease, under a microscope. Following the recommendation of the chief of the Public Health Bureau, Kitasato went to Germany for further study at Robert Koch’s laboratory (1886-1891).

Many of Kitasato’ papers are milestones in the history of bacteriology. In 1889 he published a paper on his method of culturing the anaerobic bacterium Clostridium chauvoei, the causative agent of blackleg in cattle; Kitasato found that the bacterium could grow in solid media surrounded by a hydrogen atmosphere. In the same year he published a paper on the bacillus that causes tetanus. It had been thought impossible to get a pure culture of Clostridium tetani, which had hitherto been grown in symbiosis with other bacteria. But Kitasato thought otherwise and discussed his belief with Koch and other colleagues. He found that the spores of the bacillus, strongly heat-resistant, could be heated to 80°C. without perishing. He utilized this property to obtain a pure culture: he heated a mixed culture of Clostridium tetani and other bacteria at 80° C. for forty-five to sixty minutes and then cultivated them in a hydrogen atmosphere. He thereby derived the first pure culture of Clostridium tetani.

In 1890, with Behring, Kitasato published a paper on immunity to diphtheria and tetanus, the section on diphtheria being written by Behring and the greater part of the paper, on tetanus, by Kitasato. This report opened a new field of science—that of serology—and provided the first evidence that immune serum can serve in the curing of an infectious disease.

The existence of tetanus toxin in the culture filtrate of clostridium tetani was unknown until Kitasato found it. By diluting the toxin and injecting it into rabbits, he established the minimum lethal dose. He then injected nonlethal doses and found that the animals contracted no symptoms of tetanus, and that repeated injections with an increasing amount of toxin made them immune. Moreover, Kitasato found that subsequent injection of a large amount of toxin—much more than the normal minimum lethal dose—did not kill the immune animals. He also demonstrated that serum containing antitoxin taken from immune animals could neutralize (inactivate) the toxin, and that injection of such serum in nonimmune animals had a prophylactic and therapeutic effect against tetanus infection.

In 1894 there occurred an outbreak of bubonic plague at Hong Kong, and Kitasato was dispatched to the city by the Japanese government. He identified there the causative bacterium of the plague, Pasteurella pestis. In one paper, in collaboration with James A. Lowson, a British naval surgeon, he presented several photographs of the isolated bacterium. In a later paper he described its nature in detail. Kitasato sent his Hong Kong strain to Koch’s laboratory and in 1897 published a third paper, in Japanese, on plague bacteria. Unknown to him, however, the bacterium described in this paper was quite different from that which he had isolated at Hong Kong. Two years later, Kitasato realized his error and published a correction. Based upon his papers published in Lancet and on the strain he sent to Koch’s laboratory, the strain he isolated (at Hong Kong), Pasteurella pestis, has been generally accepted as being the causative bacterium of bubonic plague. During the same Hong Kong outbreak, Yersin discovered the same bacterium independently.

During a final period of his stay in Germany, Kitasato worked on tuberculin, which had been discovered by Koch in 1890. (During this period Kitasato’s stay was supported by the Imperial household of Japan, not by the Japanese government.) When he returned home from Germany in 1892, he found no laboratory where he could work satisfactorily. But two people proved helpful to Kitasato at this juncture: Yukichi Fukuzawa, founder of Keio University and president of a large newspaper company, and Ichizaemon Morimura, a businessman. Together they founded the Institute for Infectious Diseases, and Kitasato became its director. In 1899, this institute became part of the Public Health Bureau of the government. In 1914, when it was suddenly transferred from the Bureau to the Ministry of Education, Kitasato and the entire research staff left the institute protesting the sudden change in its bureaucratic affiliation. Kitasato founded the Kitasato Institute the same year and most of his researchers rejoined him there.

In 1917 Kitasato became the first dean of the school of medicine of Keio University in Tokyo. In the same year he was appointed a member of the House of Peers by the Japanese government. In 1923, when the Japanese Medical Association was founded, he was elected its first president. The following year, he was created baron by the emperor, then a supreme honor for a Japanese scientist. In 1925 he was awarded the Harben Gold Medal by the Royal Institute of Public Health.

Among Kitasato’s notable disciples were Kiyoshi Shiga, the discoverer of Shigella dysenteriae, the cause of bacillary dysentery; and Sahachiro Hata, who found with Ehrlich the antisyphilitic effect of Salvarsan. The Prussian government made Kitasato a professor; he was decorated by the governments of Prussia, Norway, and France, and was elected an honorary member of national academies and scientific societies of various countries.

In 1908 Koch visited Japan at the invitation of Kitasato and was officially welcomed by the Japanese government. After Koch’s death on 27 May 1910, Kitasato built a small shrine in front of his laboratory in honor of the German bacteriologist and deposited there a strand of Koch’s hair and a fingernail, which he had secretly obtained during Koch’s stay in Japan. In 1931 Kitasato died of a stroke and was laid to rest in the shrine of his respected teacher. Each year, on the anniversaries of Koch’s and Kitasato’s deaths, many people pay their respects at the shrine. The notable friendship between Koch and Kitasato is well remembered in Japan as an example of the close bond possible between teacher and pupil.

Kitasato left behind him the memory of a pioneer, of gratitude to his teachers and colleagues, of wisdom carried into practice, and of indomitability. Thus inspired, the Kitasato Institute has remained active in the fields of bacteriology, serology, and virology. In 1967, on the fiftieth anniversary of the Institute, Kitasato University was founded.

BIBLIOGRAPHY

Among Kitasato’s important papers are “Über den Rauschbrandnadbacillus und sein Culturfahren,” in Zeitschrift für Hygience und Infektionskrankheiten, 6 (1889), 105-116; “Über dem Tetanusbacillus,” ibid., 7 (1889), 225-234; “Über das Zustandekommen der Diptherie-Immunität und der Tatanus-immunität bei Thieren,” in Deutsche Medizinische Wochenschrift, 16 (1890), 1113-1114, written with Email von Behring; “The Plague at Hong Kong,” in Lancet (11 August 1894), p. 325; and “The Bacillus of Bubonic Plague,” ibid. (25 August 1894), p. 428-430.

Tsunesaburo Fujino