ACT I: Before Unraveling the Enigma

@Kitasatofs achievements concerning his research with tetanus were numerous. He was the discoverer of: 1) the fact that tetanus is caused by the tetanus bacillus (isolation of the tetanus bacillus, 1889), 2) the fact that tetanus symptoms are induced by an exotoxin produced by the tetanus bacillus (demonstration of pathogenicity, 1890), 3) the fact that the toxin can be neutralized and rendered nontoxic (discovery of the immune reaction due to antitoxin antibody, 1890), 4) the fact that the mother's immune antibodies are passed on to the offspring (discovery of fetomaternal immunity and maternal antibodies, 1890), and 5) the establishment of a treatment for tetanus using antitoxic blood serum (discovery of serum therapy, 1891). So much is established historical fact and requires no further elucidation here. These were great discoveries which, were they made today, would earn him the Nobel Prize many times over.

An even more astonishing fact is that it appears that Kitasato performed these discoveries in far less time than Robert Koch or even Louis Pasteur carried out their own great discoveries. Herein lies one of the enigmas of Kitasatofs achievements. This provides the dramatic intrigue for the plot of his story of discovery.

At a rough estimate, Koch required about five years of research from the isolation of the tuberculosis bacillus to the discovery of tuberculin, and Pasteur needed almost 10 years from fixation of the rabies pathogen in rabbits to the development of a rabies vaccine. How much time, then, did Kitasato spend in going from success in isolating the tetanus bacillus, which had eluded all previous researchers, to this series of major discoveries?

According to gSaikingaku wo Tsukutta Hitobitoh (Creators of Bacteriology) in Kitasato Medical News (1984), Kitasato's research on tetanus began in 1887, but this may be an error for 1889. The grounds for this view require some explanation, and are based on the following facts. On September 28, 1885 the director of the Interior Ministry's Hygiene Bureau submitted the request for Kitasato to study in Germany to the Minister. This was approved on October 6, and Kitasato received his orders from the Interior Ministry on November 4. On December 5, 1885, Kitasato left Yokohama aboard the French steamer Menzare and after some 40 days at sea landed at Marseilles in January 1886. He traveled via Paris, reaching Berlin late in January, where he started to work under Robert Koch, who had been appointed professor of Hygiene at the University of Berlin in 1885, carrying out research in the laboratory of the Institute of Hygiene. During the first three years, Koch had Kitasato attend two series of lectures and seminars on hygiene and bacteriology, starting on March 25, 1886 and March 4, 1887 and lasting for a total of a year and several months. The topics that Kitasato was assigned to investigate covered S. typhi, isolated in 1884 by Gaffky, V. cholerae, discovered in 1884 by Koch, and B. anthracis, discovered in 1876 by Koch. The results of this research are documented in papers that he wrote, appearing in Z. Hyg. (founded in 1886) 3:404-426,1888; 5:134-40,1889; 5:484-90, 1889; 5:491-96, 1889; and 6:1-10, 1889.

As the three-year period for which his study was approved drew to a close, Kitasato was not ready for a finale to the act, but rather a new scene. He petitioned the Interior Ministry for a two-year extension, according to his handwritten letter dated January 16, 1888, which probably was within the original three-year period, and this was granted. I would like to discuss this point further since it is necessary to identify the time at which the three-year study period ended to determine when Kitasato began his research on tetanus. The period could have equally well been counted from the date of approval (November 11, 1885), the date of departure from Japan (December 5) or the date of arrival in Berlin. In general, scholars would return to Japan within three years from the date of approval or of departure. In records made at the time of Kitasato's return in 1892, however, the end of his study period is put at January 1892, placing the expiration of the first three-year period in late January 1889. Thus his fourth year in Germany would have begun in February 1889 and so it may be assumed for our present purpose that he started his new research on tetanus on or after January 16, 1889.

One of the most important events on the stage of Kitasatofs life occurred only some three months later, on April 27, 1889, at the 18th Congress of the German Surgical Association. Kitasato announced the isolation of the tetanus bacillus. This was an astonishingly short time, but he also announced in academic journals evidence of the toxin of the tetanus bacillus, the discovery of the immune phenomenon and fetomaternal immunity in 1890, the establishment of serum therapy in 1891, etc.

On analogy with the above events, it would seem that a period of about three months at the most would be ample for cultivation a pure strain of tetanus bacillus, and that a year's research would suffice for establishing a method for the prevention of infectious diseases based on immune antibodies (establishment of fetomaternal immunity using maternal antibodies). But did Kitasato in fact spend a full year and some months on the experiments? Normally one can assume that such a period did not afford the time to perform follow-up experiments and confirm the results. The reason that we may consider this questionable is that before he started his research, Kitasato had thought through the experiment as a whole, selected the experimental sequencing and procedure, and considered in detail the results expected; he did not begin research until he had developed an optimum experimental protocol. Therefore when he began his experiments he already had a clear idea of the objective he wished to reach. Thus it was that the research that Kitasato began with such confidence could be completed in such a short time.

A later episode in Kitasatofs life that serves as a good example of this is the discovery of the organism causing plague--the dreaded Black Death. Kitasato left Yokohama on June 5, 1894, reaching Hong Kong on June 12. He began his research two days after his arrival, and on the 15th confirmed discovery of the plague bacillus. On the 18th he observed the results of experiments with infected animals, and after confirming that gKoch's Three Principlesh were satisfied in every particular, he cabled news of his discovery to the Interior Ministry and announced it to the local English-language press. On July 7 he dispatched a paper on discovery of the plague bacillus to London, and articles on the discovery appeared in The Lancet on Aug. 8 and 25, 1894 gThe plague at Hong Kongh, (Lancet 2:325) and gThe bacillus of bubonic plagueh (Lancet 2:428-30). In order that no one would challenge him, he presented truly excellent results based on the Koch principles, with photographs attached.