Bartholomew - Japanese Nobel Candidates in the First Half of the Twentieth Century

Japanese Nobel Candidates in the First Half of the Twentieth CenturyAuthor(s): James R. BartholomewReviewed work(s):Source: Osiris, 2nd Series, Vol. 13, Beyond Joseph Needham: Science, Technology, andMedicine in East and Southeast Asia (1998), pp. 238-284Published by: The University of Chicago Press on behalf of The History of Science SocietyStable URL: http://www.jstor.org/stable/301885 .

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Japanese Nobel Candidates in the First Half of the Twentieth Century

By James R. Bartholomew*

F IFTY YEARS HAVE PASSED since Yukawa Hideki in 1949 became the first Japanese scientist to win a Nobel Prize (in physics, for his meson particle the-

ory); in the meantime, he has been joined by four other Japanese laureates in science and medicine. Tomonaga Shin'ichiro won in physics (1965), as did Esaki Reona (1973). Fukui Ken'ichi received the prize in chemistry (1981), while Tonegawa Susumu became the first Japanese recipient in physiology or medicine (1987). (Only Tonegawa and Yukawa received unshared awards.) Though Japan is one of just eight nations to have won Nobels in every category of natural science, many believe that five prizes is a modest harvest for so large and wealthy a country. But is this assumption correct? It certainly would be if Nobel awards were only a function of important contributions to science. In fact, they reflect a great many things: the nature of education in particular places, personal connections among scientists, the financial pri- orities of government and private business, and such "cultural" variables as individual skills at self-presentation.

A continuing focus on the history of science in established centers like Britain, Germany, France, and the United States tends to obscure some of these factors in scientific success because modem science is quite obviously a product of Western culture, and many assume that the features of science in Western Europe and the United States have been replicated everywhere. Japan's experience with the Nobel Prizes is a good test of this point of view because, despite recent problems, Japan has been spectacularly successful in reproducing other cultural and economic forms associated with the rise of the West in the last few centuries. But successful or not, there remains the fundamental question of whether, or to what degree, Japan was fully integrated into the world system of science during the first half of the twentieth

* Department of History, Ohio State University, Columbus, Ohio 43210. I would like to thank the over two dozen scholars, graduate students, archivists, and librarians who

generously assisted me during the course of this research. At the Royal Swedish Academy of Sciences (Stockholm), Tore Frangsmyr and Julia Lindqvist; at the Karolinska Institute (Stockholm), Nils Ringertz, Margaretha Petrini, and Gudrun Franzen; at the Hungarian Academy of Sciences (Buda- pest), Eva Apor; at the Semmelweis Museum (Budapest), Laszlo Magyar; at Kitasato University (Tokyo), Kato Ei'ichi and Kuramoto Hiroyuki; at Tokyo University (Tokyo), Hashimoto Takehiko and Matsumura Yoshiaki; at the CNRS (Strasbourg), Elisabeth Crawford; at the University of Cin- cinnati, Thomas Sakmyster; at the University of Minnesota, Mariann Tiblin; at Harvard University, Suzy Conway; and at Ohio State University (Columbus), Marilyn Blackwell, Maureen Donovan, Jeffrey Lewis, Edward Riedinger, Alice Risko, Carole Rogel, Leila Rupp, Birgitta Soland, Mark Spicka, and Barbara Van Brimmer. Any errors are mine.

?) 1999 by The History of Science Society. All rights reserved. 0369-7827/98/1301-0011$02.00

Osiris, 1998, 13:238-284 238



JAPANESE NOBEL CANDIDATES 239

century, before the era of jet airplanes, personal computers, advanced telecommuni- cations, and the seemingly ubiquitous use of English.

These questions matter because the Nobel Prizes have come to be intimately related to matters of prestige, nationalism, and even power. For better or worse, the scientific community, the universities, the government, the mass media, and the edu- cated public of Japan (like counterparts elsewhere) all follow the prizes' annual announcement with great interest and draw conclusions with significant consequences. Yukawa's 1949 prize conferred major advantages on the Japanese research community in theoretical physics, even at a time when money was scarce. Tomona- ga's 1965 award brought additional resources for physics. And the late Fukui Ken'- ichi's 1981 prize in chemistry resulted in a $30 million private gift for an entirely new institute.' Prior to his death in January 1998, Fukui was involved with the other living Japanese Nobel laureates (Esaki, Tonegawa, and Oe Kenzaburo, who won in literature) in a well-supported, formal program designed to attract public attention to the Nobel Prizes. Known as the "Japan Forum of Nobel Prize Recipients," this project annually brings foreign Nobel laureates to Japan for public lectures, while Japan's own Nobelists participate in a series of special programs aimed primarily at young people. The forum's sponsors have made it clear that the purpose of their initiative is to publicize the prizes, to improve the climate for creative research, and to enhance Japan's cultural and scientific prestige.2

My purpose here is to explore the issue of Japan's integration with international science during the first half of the century as a key to understanding its record in the Nobel competitions. I focus on this period because the Nobel archives follow a fifty- year rule of access, and archival materials are essential to understanding how particular candidates fared and why. The Nobel Prizes have always been influenced by many factors; important contributions to science (in this case), however essential, are just one. It is clear from studies done since the Nobel archives were opened in 1974 that candidates' connections with other scientists and how candidacies were presented and by whom has affected the results in particular cases. To win a Nobel Prize, one must first be nominated-and the nomination system itself has privileged candidates from certain countries (not only Scandinavia) while tending to handicap others. The invitation enjoyed by Nobel laureates to submit nominations at any time is one reason for this imbalance.3

How, then, have the Japanese fared? How and why did their record evolve as it did? Although the fifty-year rule precludes an archivally based examination of recent

' For details on the boost Yukawa's award brought to physics see Hara Genkichi, Kagaku kenkyt hi: sono naritachi to hensen (The science research grants: Their origin and evolution) (Tokyo: Ka- gaku Shimbun Sha, 1982), pp. 114-115. Tomonaga appealed for increased expenditures for scientific research almost immediately after his Nobel Prize was announced. While some enhancement of research funding would probably have occurred in any case, one can safely assume that his prize forwarded the cause. See James Bartholomew, The Formation of Science in Japan: Building a Re- search Tradition (New Haven, Conn./London: Yale Univ. Press, 1989), pp. 279, 354-355. On the $30 million gift see Matsuo Hiroshi, unpublished MS, 1995. The funds for the Institute for Fundamental Chemistry, directed by Fukui, were provided by the Kao Soap Company.

2 See, e.g., Noberu shd jushosha o konomufuoramu nijuisseiki e no kdzd (Toward the twenty-first century: A forum honoring Nobel laureates) (Tokyo: Yomiuri Shimbun Sha, 1993). The forum has been held every year but one since 1987.

3 For a discussion of the nominating system see Elisabeth Crawford, The Beginnings of the Nobel Institution: The Science Prizes, 1901-1915 (Cambridge: Cambridge Univ. Press, 1984).



240 JAMES R. BARTHOLOMEW

candidacies, those from the first half of the century can be studied in this fashion. I will present three case studies of Japanese candidacies for the Nobel Prize: Kitasato Shibasaburo in 1901, Yamagiwa Katsusaburo in 1927, and Kato Gen'ichi in 1935. A century ago, Kitasato was one of the world's leading medical researchers because of his work on tetanus and plague and his role in the discovery of natural immunity. Yamagiwa was responsible for a major advance in medicine's understanding of cancer. And Kato was among the world's most important nerve physiologists. It was no accident that all three were candidates for the prize in physiology or medicine. In Japan at the time, medicine enjoyed the advantages of generous public support, relatively good research facilities, eminent practitioners, and distinguished achievements. Physics and chemistry had few of these assets on any level before World War I and began to achieve even a rough parity with medicine only in the 1930s.4

Although Japan was clearly viewed as marginal in science when the Nobel Prizes began in 1901, the Swedish Nobel authorities had some understanding of medicine's relative stature there: in 1907 medicine became the first discipline in which a Japa- nese scientist was invited to propose candidates for a Nobel Prize with the naming of Ito Hayazo, professor of surgery at Kyoto University. Similar recognition for Japanese physics came in 1910, when Tanakadate Aikitsu, a professor at Tokyo University, was named. But it was 1927 before a Japanese nominator was selected in chemistry: Machida Shokichi, also from Tokyo University. The sequence of these dates reflects, very roughly, the relative strength of the three disciplines in Japan at the time. The timing of the invitations also suggests that the Swedish Nobel authorities were alert to other contexts of power: 1907 is conspicuously close to Japan's victory over Russia in the Russo-Japanese War (1905) and follows remarkably closely on the heels of Japan's 1906 invitation to join the International Association of Academies at Vienna, an event precipitated by the victory over Russia.5

Swedish understanding of the Japanese research establishment should not be ex- aggerated, however. For unknown reasons, the only Japanese nominators who were invited to serve in the first half of the century held academic posts, a practice not followed elsewhere. Scientists employed at nonacademic research laboratories had no opportunity to nominate candidates. This reliance on professorial nominators excluded such major figures as Nishina Yoshio, Shiga Kiyoshi, and Kitasato Shiba- saburo, all of whom were among the country's most distinguished researchers. Ni- shina, who worked with Niels Bohr in Copenhagen in the 1920s, is known for the Klein-Nishina formula in physics. He headed a laboratory at Japan's most important scientific research facility of the interwar period, the Research Institute for Physics

Bartholomew, Formation of Science in Japan (cit. n. 1). On Ito's appointment see Nobelkommiteten, P M. Forsandelser och Betdnkanden, 1907 (Stock-

holm: Karolinska Institutet, 1907 (hereafter, volumes of this series will be cited by title and date, e.g., P M. Forsandelser och Betankanden, 1907). Ito proposed his European mentor, Theodor Kocher of Switzerland, who did receive a Nobel Prize two years later. For Tanakadate see Kunliga Vetenskapa- kademien, Vetenskapakademiens Protokoll 1910 ANG. Nobelarenden (Stockholm: Kunliga Vetens- kapakademien, 1910) (hereafter, volumes of this series will be cited by title, e.g., Vetenskapakade- miens ProtokollANG. Nobeldirenden). For Machida see Vetenskapakademiens Protokoll 1927ANG. Nobeldrenden. See also Elisabeth Crawford, John Heilbron, and Rebecca Ullrich, The Nobel Popula- tion, 1901-1937 (Berkeley: Office for the History of Science, Univ. California, 1987), p. 242. On the political context see Sakurai Joji, Omoide no kazukazu (Various memories) (Tokyo: Herald Sha, 1939), pp. 70-71.




and Chemistry. Shiga is remembered today as the discoverer of the dysentery pathogen that bears his name, Shiga bacillus.6

It is an equally puzzling fact about the nomination system that operated in Japan that none of the three scientists I focus on in this essay was ever invited to nominate candidates. The Nobel archives show that in Europe and the United States, in contrast, nominators and nominees were often the same people in this period. We know from the pioneering studies of Elisabeth Crawford that American and European scientists could "exchange" nominations; even if such reciprocity was not explicitly planned, scientists who had done something significant might expect that colleagues or friends would submit their names. It is clear from the archival records that this was not the case among the Japanese in the first half of the century. Fukui Ken'ichi has attested to the fact that even in recent years the Japanese nomination system has had certain peculiarities. His fellow laureate Esaki asked Fukui, a professor in Ky- oto's Faculty of Engineering when he received his Nobel award, if he had ever nominated in chemistry before winning the prize himself. Fukui said that he had not: in Japan, such invitations would go only to chemists in a faculty of science, never to chemists in an engineering unit. The latter have been numerous in Japan.7

Another particular, and consequential, feature of the Japanese research system in the first half of the century was its intense factionalism, at least in medicine. What- ever one may think about the proclivity of physicians or medical researchers elsewhere toward factional behavior, it reached particular heights (or depths) in Japan during this period. Some reports have it that medical people in the military constituted a faction. Others stress the factional orientation of many (though not all) professors of medicine at the imperial universities (Tokyo, Kyoto, Tohoku, Kyushu, and Hok- kaido), Tokyo's case being the most widely discussed. Factionalism is sometimes considered an inherent, "cultural" feature of Japanese academic and professional life.8 But it should be emphasized that the factional patterns that influenced Japanese Nobel nominations had a specific historical origin, associated with Kitasato's early career.

In 1888 Kitasato wrote a short, mildly worded letter (in German) to a medical journal in which he criticized an article by a professor of hygiene at Tokyo Univer- sity, Ogata Masanori. Ogata had mistakenly imputed a bacterial origin to beriberi and claimed to have isolated a pathogen. Kitasato was studying at Berlin University with Robert Koch at the time, and some sources say that he was urged to write by Friedrich Loeffler, another Koch associate. He was in any case entirely capable of taking such an initiative on his own, without prompting. Whatever its genesis, Kita- sato's letter infuriated certain people at Tokyo University, not only because the criticism could adversely affect the institution's reputation, but also because Kitasato

6 For essays on all three scientists see Tsuneishi Keiichi, Nihon kagakusha den (Biographies of Japanese scientists) (Tokyo: Shogakkan, 1996).

7 Elisabeth Crawford, Nationalism and Internationalism in Science, 1880-1939 (Cambridge: Cam- bridge Univ. Press, 1992), pp. 51-54; and Shadan Hbjin KyWd6 Tsushinsha, Kagaku to ningen o kataru: Fukui Ken'ichi to Esaki Reona (A conversation about science and human beings: Fukui Ken'i- chi and Esaki Reona) (Kyoto: Shadan Hajin Kyod6 Tsushinsha, 1982), pp. 19-20.

8 On factionalism in medicine see Renee C. Fox, "Medical Scientists in a Chateau," Science, 1962, 136:476-483; and Eliot Friedson, Profession of Medicine: A Study of the Sociology of Applied Knowledge (New York: Harper & Row, 1970), pp. 192-197. On the "inherent" factionalism of Japa- nese academic and professional life see Nakane Chie, Japanese Society (Berkeley/Los Angeles! London: Univ. California Press, 1970), pp. 10-29, 42-43, passim.




had graduated from the university after Ogata and could thus be seen as his junior in the Japanese status hierarchy. Ogata himself was not greatly exercised, but others were. Continuing resentment from the beriberi controversy was one reason why Ki- tasato never became a faculty member at Tokyo even after he became world famous.9 He took a radically different course, serving as director, first, of the Institute for Infectious Diseases (1893-1914) and then of the privately operated Kitasato Insti- tute (1915-1918); in 1918 he became professor and dean at the new medical school of Keio University, a leading private institution.

Kitasato's fame, international reputation, and experience in both academic and institutional politics had a large impact on Japanese medicine and even on parts of the physical sciences. Initiatives he took with respect to the bureaucratic affiliation of the Institute of Infectious Diseases (in 1914) and reaction to them by members of parliament and government officials were among the reasons why the Research Institute for Physics and Chemistry, founded in 1917, never became an academic facility.'0 His presence continued to have a polarizing effect in the medical community. Resentment of Kitasato is one of the reasons why Kato, his protege, received no support from any imperial university professors for his own Nobel candidacy in 1935. Similarly, none of the scientists in Kitasato's camp did anything to advance Yamagiwa's prospects for a Nobel Prize. Though himself disengaged from these quarrels, Yamagiwa was a professor in the Faculty of Medicine at Tokyo University.

Yamagiwa, Kitasato, and Kato are particularly good subjects for a series of case studies because their achievements were especially important scientifically, because their careers were to some degree intertwined, and because they represented the two major camps in the Japanese medical research community of this era. In principle, one would like to examine the case of a physics or chemistry candidate from this period as well. But prior to Yukawa in 1939-1949 there simply were no Japanese candidates who had even a remote prospect of receiving a Nobel Prize. Hata Sa- hachiro, codiscoverer with Paul Ehrlich of Salvarsan 606, a specific for syphilis, was nominated (for the 1911 prize in chemistry) by a Nobel laureate (Theodor Kocher of Switzerland);" but Hata's work was credited to Ehrlich by most people outside Japan and generated no interest at all in Stockholm. I do not take up Yukawa's case fully here, partly because the archival materials pertinent to his award are not yet entirely open, but also because he will be the subject of a future research project. However, Yukawa's candidacy is discussed briefly in the epilogue.

9 For the letter see Kitasato Shibasaburo, "Ueber die Reincultur eines Spirillum aus faulendem Blute, Spirillum concentricum n. Sp.," Centralblatt ffir Bakteriologie und Parasitenkunde, 1888, 3(3):76-78. A Japanese-language version also appeared: "Zai Doitsu-koku Igakushi Kitasato Shiba- saburo Shi shokan," Chuigai iji shimpo-, 25 Jan. 1889, no. 212, p. 105. For an angry reaction see, e.g., Mori Ogai, "Tokei ni tsuite no bunso," Tokyoi iji shinshi, 8 June 1889, no. 562, p. 2. For other details see James R. Bartholomew, "The Acculturation of Science in Japan: Kitasato Shibasaburo and the Japanese Bacteriological Community, 1885-1920" (Ph.D. diss., Stanford Univ., 1971), pp. 163-169.

10 Bartholomew, Formation of Science in Japan (cit. n. 1), p. 216. 11 Vetenskapsakademiens Protokoll 1911 ANG. Nobeldrenden. Hata was also nominated in medi-

cine, in 1912 by Hirai Ikutaro of Kyoto University and in 1913 by Osawa Gakutaro of Tokyo Uni- versity. See P M. Forsdndelser och Betdnkande, 1912; and P M. Forsdndelser och Betdnkande, 1913.



JAPANESE NOBEL CAN'DIDATES 243

m-a}

__- Figure 1. Kitasato Shibasaburo. circa 1920.

KITASATO'S NOBEL CANDIDACY. 1901

As noted earlier. Kitasato Shibasaburo (I1852-1931) was one of the preeminent figures in medicine around the turn of the century. (See Figure 1.) Graduating eighth in his class from Tokyo Universitv's Facultv of Medicine in 1883. Kitasato worked for two years in Japan's Bureau of Sanitation and then received the opportunity to study with Robert Koch. one of bacteriology's two founding figures. at the expense of the Japanese government. His six years at Koch's laboratory in Berlin University (December 1885-Januar- 1892) were. to say the least. productive. In 1887 he did useful work on the bacillus of typhus and the cholera vibrio. and in 1888 he studied blackleg in cattle. In 1889 he managed the technically difficult feat of isolating the bacillus of tetanus in a pure culture. In the course of his studies of the tetanus bacillus. Kitasato discovered tetanus toxin: in 1890 he claimed the mantle of codiscoverer of natural immunitv the fundamental notion that there exist in the bloodstreams of all organisms substances that are capable of neutralizing foreign materials. The Japanese scientist had a colleague in this achievement: Emil Behring. another

researcher in Koch's laboratory, who had been studying the diphtheria bacillus. To- gether. Behring and Kitasato published their epoch-making paper in the 4 Decem- ber 1890 issue of the Delutsche Medizinische Wochenschrift-a paper in which Behring's name appeared first and Kitasato's second. This article became the foundation for the development of serum therapy and indeed constitutes the initial step toward the establishment of humoral imrnunolorv.' As such. it became the principal

" Emil Behring and Shibasaburo Kitasato. "Ueber das Zustandekommen der Diphthenre- Immunitat und der Tetanus-Immunitat bei Thieren." Deutsche Mfedizinische Wochenschrfti. 4 Dec.




scientific argument for awarding the 1901 Nobel Prize in Physiology or Medicine- to Emil Behring. There has been considerable resentment in Japan ever since that this first Nobel award went to Behring alone, with no acknowledgment of Kitasato at all. It is my task here to show that the Japanese criticism has considerable merit.

A closer review of Kitasato's scientific work in Germany is the place to begin. When Kitasato first arrived in Berlin in late December 1885, Koch was clearly skeptical of his scientific abilities, though impressed by his fluency in German. For the first several months Kitasato worked in the laboratory of Friedrich Loeffler, improv- ing his technical capabilities in bacteriological investigation. Then he was on his own. His first independent work (in 1887) added useful details about the relationship between acidity and alkalinity in the media used to cultivate the typhus bacillus and the cholera vibrio. In a study published in 1889 he identified the causative agent of blackleg in cattle, Clostridium chauvoei, and noted its anaerobic nature, that is, its ability to flourish only in the absence of oxygen. A notable achievement in the course of this work was Kitasato's ability to grow the bacterium in a solid medium sur- rounded by a hydrogen atmosphere. His experience with anaerobic microorganisms would pay major dividends when Koch asked him to take on an even more challeng- ing assignment: to produce a pure culture of the tetanus bacillus. Tetanus had been shown to be an infectious disease and its causal organism tentatively identified several years before. But conclusive proof was lacking; and several prominent researchers had failed in attempts to produce the tetanus bacillus in a pure culture, most recently Koch's friend Carl Flugge, a professor of hygiene at the University of Gdt- tingen. Kitasato, however, believed that the problem could be solved, and he was concerned that failure to achieve the pure culture offered ammunition to the still- influential critics of the germ theory of disease.'

In approaching the challenge of tetanus Kitasato was able to draw on his prior experience with anaerobic bacteria. He began by noting the anaerobic character of the tetanus bacillus from the fact that it did not produce colonies in the upper layer of the agar-agar medium but, rather, formed colonies only in a deeper layer. Kitasato also called on the improved culturing techniques he developed in his work with blackleg. A principal difficulty encountered by earlier investigators of the suspected tetanus pathogen was that they had been able to grow it only in symbiosis with other bacteria. Hence Koch's challenge. Kitasato found that the spores of the tetanus bacillus were far more resistant to heat than some fourteen other microorganisms that appeared in the same culture medium. By heating the entire culture to 80 degrees Celsius for close to an hour, he managed to kill everything except the tetanus bacilli. He then cultivated the bacillus in a hydrogen atmosphere and reported his findings to Koch, who understandably insisted on animal trials before accepting Kitasato's claims.14

1890, 16(49): 1113-1114. See also Thomas D. Brock, Robert Koch: A Life in Medicine and Bacteriol- ogy (Madison, Wisc.: Science Tech, 1988), p. 226.

13 For Kitasato's work under Koch see Miyajima Mikinosuke, Kitasato Shibasaburo den (Tokyo: Iwanami Shoten, 1931), pp. 34-35 (Loeffler's lab), 44-45 (tetanus bacillus). On his success in grow- ing Clostridium chauvoei see Tsunesaburo Fujino, "Shibasaburo Kitasato'" in Dictionary of Scien- tific Biography, ed. Charles C. Gillispie, 18 vols. (New York: Scribners, 1970-1986), Vol. 7, p. 391.

14 See Nakamura Teiri, "Seiji to jinmyaku ga karanda saikingakusha no jush6" (A bacteriologist's Nobel Prize suffused by politics and personal connections), in Noberu sh& no hikari to kage (Triumph and shadows of the Nobel Prize), ed. Kagaku Asahi (Tokyo: Asahi Shimbun Sha, 1981), pp. 134- 135; Fujino, "Shibasaburo Kitasato," p. 391; and Miyajima, Kitasato Shibasabur6 den, p. 46.




Strong proof that the claims were legitimate was not long in coming. Indeed, after Kitasato produced the pure culture of tetanus, he achieved a major research advance in the treatment of tetanus by demonstrating the existence of tetanus toxin. He presented the evidence in his 1889 paper "Ueber den Tetanusbacillus," published in the Zeitschriftfuir Hygiene. Kitasato reported that when fluid from the pure culture from which the bacilli had been removed was injected into laboratory mice, they contracted tetanus and died. Thus it was clear that the tetanus bacillus itself must be producing a toxic substance, namely, the tetanus toxin. This was not a surprising discovery, since the existence of such a toxin had been predicted by other researchers, including Behring. Kitasato's contribution was the definitive proof of the toxin's existence and pathogenic effects.15

Kitasato's achievements included the development of a better filter for extracting the tetanus bacilli from the culture fluid and determining a dosage regimen for testing and evaluation. He approached the second problem by adopting an analogy from medical experience with cocaine. By using small amounts of cocaine and gradually increasing the dosage, it was known that a recipient could gradually become used to the cocaine and remain for a time relatively unaffected by the poison. Kitasato suspected that the same might be true for the tetanus toxin, and he pursued his research on the basis of this assumption. Despite the limited understanding on which it was based, the analogy proved useful. Kitasato diluted the tetanus toxin by degrees and injected varying amounts first into mice and then into rabbits. He then diluted the fluid further and gradually determined the minimum amount needed to cause death. Continued, calibrated increases of toxin in the fluid led to a finding of the maximum amount an animal could receive without showing ill effects. Finally, he was able to show that an animal receiving repeated, gradually increased injections would display no symptoms of the disease, even when more toxin was injected than would be required to kill an untreated animal. This suggested the presence in the animal of a substance that had rendered the toxin harmless. After publishing these findings with his coworker, Theodor Weyl, Kitasato turned his attention to the fundamental questions of what this substance might be and how it worked.16

Kitasato's close associate in this important project was, of course, Emil Behring. In 1887, after extended years of service as a military physician and some independent research efforts on disinfectants, Behring began a formative apprenticeship at the Pharmacological Institute of Bonn University under Carl Binz. Through his military experience, he was familiar with the use of the chemical iodoform in treating wounds, a procedure introduced in 1880. He began to wonder if it might be possible to attack infectious diseases as they manifested themselves inside the body by a similar kind of "disinfecting" procedure. In 1881 he published a small paper on sepsis and antisepsis that incorporated this presumption; in an 1882 paper he noted that iodoform's toxic effect on the organisms studied was stronger than its disinfecting influence on the targeted bacteria. But Behring was undeterred, and he chose to study with Binz because of the latter's considerable interest in such chemical disinfectants. Behring's studies at Bonn on iodoform and acetylene gave him

15 Kitasato Shibasaburo, "Ueber den Tetanusbacillus," Zeitschriftfiur Hygiene, 1889, 7:225-234. See also Nakamura, "Seiji to jinmyaku ga karanda," p. 135.

16 Kitasato Shibasaburo and Theodor Weyl, "Zun Kenntniss der Anaeroben," Z. Hygiene, 1890, 8:97-102. See also Miyajima, Kitasato Shibasaburn den (cit. n. 13), pp. 49-50.




valuable knowledge in toxicology and research experience with animals appropriate to that specialty. Most of these studies had little clinical value with respect to infectious diseases. But he did ascertain that the serum of white rats immune to tetanus contained a substance that neutralized the anthrax bacillus, a subject with which Koch had begun his own career in bacteriology.17

Behring was not a classically trained bacteriologist in the tradition of Pasteur or Koch but had an essentially chemical or pharmacological orientation to the study of disease. Nonetheless, in 1889 he entered the Hygiene Institute of Berlin University as a paid assistant to Koch, at about the time Kitasato was beginning his work on tetanus. His principal assignment was to work on diphtheria, not only because it was a major medical threat at the time, especially to children, but also because, following Loeffler's isolation of the diphtheria pathogen in 1884, the institute had a tradition of work on the subject. Drawing on his earlier training in toxicology and pharmacology, Behring began by attempting to discover suitable "systemic disinfecting agents," testing iodine and compounds of gold and zinc on laboratory guinea pigs injected with the diphtheria bacillus. 8 But only with iodine trichloride did he manage to keep a few of the infected animals alive.

At this point the paths of the two investigators converged more directly. By most reports, Kitasato, working on tetanus, and Behring, working on diphtheria, simultaneously found not only that there was something in blood that neutralized the two disease toxins under particular conditions but that the injected blood serum of an immune animal could create immunity for the recipient. These were the findings presented in the Deutsche Medizinische Wochenschrift. These same reports call attention to Behring's paper in the same journal one week later, ostensibly demonstrating his independent role in the discovery of diphtheria antitoxin, as evidence for his leading contribution to this notable achievement in basic medicine.19

It is possible, however, to challenge aspects of this account on the basis of facts long known to medical researchers and medical historians in Europe and the United States. In the first place, most of the direct evidence for the conclusions about natural immunity presented in the 4 December paper concerns tetanus, Kitasato's research topic, rather than diphtheria, where Behring had been active. (It adds little to the credibility of claims for Behring's uniquely important role to emphasize, as most narratives do, that the major discoveries about immunity were based on tetanus because of the particular strength of the toxin it produced.) Second, even Behring's paper of 11 December summarized major findings with reference to tetanus. Third, while Behring did, to be sure, present some details in support of his claim to have extended the findings about tetanus to diphtheria, his account has been described by one historian of biology as "vague" and by an American microbiologist at the Uni- versity of Wisconsin as "not completely convincing."20

Japanese medical historians, relying in part on testimony from longtime scientific

17 Hans Schadewaldt, "Emil von Behring," in Dictionary of Scientific Biography, ed. Gillispie (cit. n. 13), Vol. 1, p. 575.

18 On Behring's orientation see Nakamura, "Seiji to jinmyaku ga karanda" (cit. n. 14), p. 136. See also Schadewaldt, "Emil von Behring," p. 575.

19 Joanne H. Whallon, "Emil Adolph von Behring," in The Nobel Prize Winners, ed. Frank N. Magill, Physiology or Medicine, Vol. 1 (Pasadena, Calif./Englewood Cliffs, N.J.: Salem, 1991), pp. 35-36.

20 Nakamura, "Seiji to jinmyaku ga karanda" (cit. n. 14), p. 134; and Thomas D. Brock, ed., Mile- stones in Microbiology (Englewood Cliffs, N.J.: Prentice-Hall, 1961), p. 144.




colleagues of Kitasato-which no doubt reflected Kitasato's own view-have suggested a far more plausible interpretation of the discovery of natural immunity than is typically found in Western medical histories. First of all, it is a simple matter to confirm what Nakamura Teiri has pointed out: shortly after Kitasato and Behring published their classic joint paper, the Japanese researcher published his own follow- up, a longer report in the Zeitschrift ffir Hygiene in which he quotes extensively, almost word for word, from the Deutsche Medizinische Wochenschrift essay.21 More- over, the material he quotes in his own piece in a discussion of the immune serum's effects is very nearly identical with the portions of the earlier paper that report on the actual experiments ostensibly performed by the two bacteriologists. We may take this as direct evidence that it was Kitasato who wrote these crucial sections of the first paper and that it was he, not Behring, who was actually responsible for the major findings about natural immunity. In all likelihood, apart from the famous concluding line about the nature of blood as a "very unusual fluid," Behring's main contribution to the original paper was probably to argue-correctly-that Kitasato's findings about tetanus have a general immunological significance.

Of course, this interpretation is inconsistent with the appearance of Behring as first author and Kitasato as second author at the top of the article. Indeed, there appears to be no explanation as to why Behring's name appeared first-unless he actually was the major contributor. However, three scientists who knew Kitasato well and worked closely with him insist that Behring was not; they also claim that Behring achieved his success with diphtheria at this point only because Koch, when Kitasato produced the pure culture of tetanus, diverted Behring from his earlier em- phasis on chemical approaches to diphtheria and insisted that he focus instead on the possible role of blood serum. Apart from any direct evidence presented by Kitasato's colleagues in Japan, this version of events seems plausible in light of Behring's own training and previous approaches to disease.

Accounts left by the three Japanese scientists differ in nuance but agree on the essential point that Koch told Behring to adopt the approach to diphtheria that Kita- sato had been following in his study of tetanus. Recounting Kitasato's report to Koch of his findings on the tetanus toxin, Miyajima Mikinosuke, a 1935 Nobel nominator, wrote in 1932: "[Koch] called in Behring, who had charge of research on the diphtheria bacillus, and ordered him to do the same kind of research .. . according to Kitasato's methods." In 1961 Takano Rokuro, director of the Kitasato Institute at the end of the 1940s, stated: "Koch ordered Behring to adopt Kitasato's methods in his own research; finally [Behring] was able to get the same kind of [immunizing] results." Both Miyajima and Takano see the "basic principle that serum therapy is possible" as having been "discovered by Kitasato." However, the most authoritative statement is probably that of Hata Sahachiro, a closer contemporary of Kitasato than Miyajima or Takano and a Nobel nominee himself. Hata's 1931 lecture eulogiz- ing Kitasato discusses, among other matters, his research on the tetanus toxin: "When [Kitasato] mixed the toxin with the blood serum, it became clear that this blood serum was counteracting the effects of the toxin. This was all before Behring

21 Shibasaburo Kitasato, "Experimentelle Untersuchungen uber das Tetanusgift," Z. Hygiene, 1891, 10:267-305; see esp. pp. 299-300. Nakamura Teiri first pointed out the nearly identical word- ing in this paper and the Deutsche Medizinische Wochenschrift essay; see Nakamura, "Seiji to jinmyaku ga karanda," p. 133.




discovered how to nullify diphtheria toxin by using the blood fluid of animals who were diphtheria-immune. Dr. Kitasato is thus the founder of today's serum therapy."22

Why, then, was the 4 December 1890 article coauthored? And why was Behring's name listed first? The only direct testimony we have on the first question is that of Hata: "To avoid bad feelings between [Kitasato and Behring], Koch had them write a paper under their two names in which they simply reported on the immunity work regarding diphtheria and tetanus. What one did first, the other used. Kitasato had discovered an antitoxin in the blood fluid, so Behring used it in his research. Because the discovery was so important, the [scientific] reporting should not be divided, [Koch believed], but [should] rather be announced by the two of them together." Regarding the second question, Takano writes, "This [research on immunity] should have been reported [in the Deutsche Medizinische Wochenschrift] as the discovery of Kitasato with Behring listed as the second author. Scientists in Japan have been unable to determine why it appeared as a dual-authored paper." 23

That fact, however, has not prevented some from speculating. The historian of biology Nakamura Teiri believes that Behring, recognizing the enormous significance of the basic medical findings and fully aware of the potential prospects for clinical treatment, pressured Koch to have his name listed first. There is, to be sure, no direct evidence for this assertion; but the allegation is fully consistent with what has long been known about Behring's personality and professional dealings with colleagues. He feuded with Koch, came to be despised by his erstwhile friend, the Nobel laureate Paul Ehrlich, and has been described by a recent authority on his career as "one of the great solitary figures in the history of medicine." There is, further, indirect evidence for this view of Behring even in the Nobel archives of the Karolinska Institute, where one discovers that among the dozen or so scientists who proposed Behring's name for the Nobel Prize, not one came from his native Germany.24

If, in fact, Behring did ask to have his name listed first, despite a number of indications that Kitasato's contribution to the paper was notably more substantial, why might Koch have acceded to such a request? Nakamura offers a somewhat plausible explanation. It has to do with the tuberculin fiasco in which Koch became embroiled in the autumn of 1890, after his speech on the subject at the Tenth International Medical Congress, held in Berlin in August. Koch not only indicated that he had discovered an important substance elaborated by the tubercle bacillus-he called it tuberculin-but also hinted that this substance might actually cure the disease. In the weeks and months that followed, it gradually became clear that tuberculin, despite its valuable diagnostic properties, was in no sense a cure. After this unfortunate turn of events Koch was-unfairly-the target of bitter attacks and denunciations from disappointed tuberculosis patients and uncomprehending physicians. Naka-

22 Miyajima, Kitasato Shibasaburo- den (cit. n. 13), p. 50; Takano Rokuro, Kitasato Shibasaburo (Tokyo: Nihon Sh6bo, 1965), pp. 39, 37-38; and Hata Sahachiro, "Gakusha to shite no menboku" (His reputation as a scientist), in Miyajima, Kitasato Shibasaburo den, p. 284.

23 Hata, "Gakusha to shite no menboku," p. 284; and Takano, Kitasato Shibasaburo, p. 40. Here and elsewhere, translations are mine unless otherwise indicated.

24 Nakamura, "Seiji to jinmyaku ga karanda" (cit. n. 14), p. 137; and Schadewaldt, "Emil von Behring" (cit. n. 17), p. 577. Regarding Behring's relationship with Ehrlich see Martha Marquardt, Paul Ehrlich (New York: Schuman, 1951), pp. 34-35. On the Nobel proposals see H. Schuck et al., Nobel: The Man and His Prizes (Norman: Univ. Oklahoma Press, 1951), p. 182.




mura argues that during this highly volatile period Koch's professional status was falling just as Behring's star was rising; he suggests that under the circumstances Koch might have acceded to pressure from Behring that he be designated first author of the joint essay.25

Although Nakamura does not mention them, at least three other factors could have played a role in Behring's name being listed ahead of Kitasato's. One is the fact that Behring was serving as Koch's paid assistant, whereas Kitasato-obviously not a German national-would have been unable to hold such a post even had Koch wished to appoint him. (Given the close personal and professional relationship that existed between Koch and Kitasato by this time and continued until Koch's death in 1910, this would not have been an unlikely development had Kitasato held German citizenship.26) A second factor has little or nothing to do with Koch. Despite Kita- sato's reputation in medical research, due to his work on tetanus, the 4 December article was his first appearance in the Deutsche Medizinische Wochenschrift. Beh- ring, however, had published there before and was therefore better known to its readership-and, as Koch's paid assistant, of higher status than Kitasato. Finally, given the fact that, because of its prevalence, diphtheria was a greater challenge to clinical medicine than the less common (though more lethal) tetanus, it is possible that the journal editors decided to list Behring as first author because of the exciting possibility that there might now be a genuine cure for diphtheria. Whether or not anything like this happened, the Nobel archival materials, together with numerous published accounts, clearly accent the importance of the medical triumph over diphtheria as a reason to honor this work with a Nobel Prize.27

Important as it was from a scientific perspective, the discovery of natural immunity might not have been so honored had Behring, Kitasato, and others not managed to improve the efficacy of blood serum therapy. The details of this effort have often been related and need not be repeated here. But two points may be noted. Serum producers faced enormous difficulties initially in generating the amounts required for the treatment of human patients. Mice, guinea pigs, rabbits, and other small mammals proved quite inadequate for this purpose; Emile Roux's convincing demonstration in 1894 that the blood system of the horse was suitable for serum production finally solved that problem. Similarly, Paul Ehrlich, working with Behring-at the time his close friend-in the mid 1890s developed useful mathematical techniques for determining the proper serum dosages for diphtheria patients and other victims of infectious diseases; this achievement made the new serum therapy effi- cient, predictable, and, above all, effective.28

Full appreciation of the sociopolitical context within which the first Nobel Prize selection committee considered the discovery of immunity and serum therapy in 1901 requires us to note that Kitasato left Berlin shortly after Christmas 1891 and returned to Japan in May 1892. He resided permanently in Tokyo thereafter but

25 Nakamura, "Seiji to jinmyaku ga karanda'" p. 138. 26 Victor Robinson, Pathfinders in Medicine (New York: Medical Life, 1929), p. 743: "Koch's

pupils were not limited to his country or race, and perhaps no disciple gave him sincerer gratification than Kitasato."

27 See Schadewaldt, "Emil von Behring" (cit. n. 17), p. 577 (Behring had published in the Deutsche Medizinische Wochenschrift in 1882); and Schtick et al., Nobel (cit. n. 24), pp. 182-183.

28 On Roux's work see Brock, Robert Koch (cit. n. 12), pp. 226-227; on Ehrlich and Behring's mathematical techniques see Marquardt, Paul Ehrlich (cit. n. 24), pp. 30-32, 34-35.




visited Europe on various occasions. According to Miyajima, Budapest was Kita- sato's favorite European city, and he visited it on every European trip. His particularly extensive travels of 1891-1892 involved site visits to public health-related facilities in France, Italy, Britain, the Netherlands, and the United States. Discus- sions about possible employment at Cambridge University and at the University of Pennsylvania are an indication of his international reputation. While visiting The Hague he was told that every Dutch physician knew his name. But the most enthusiastic reception came in France. Leading newspapers in Paris announced his month- long visit. Louis Pasteur spent considerable time with him, and "nowhere did he receive a warmer welcome than at the Pasteur Institute."29

Behring, of course, remained in Germany, and despite technical difficulties with serum production and administration he enjoyed a successful career. An 1892 contract with Hoechst brought him lucrative returns from the sale of serums. Despite conflict with Koch over the terms of this contract (and later over tuberculosis), Beh- ring was named associate professor of hygiene at Halle in 1894; in 1895 he moved to a full professorship at Marburg. As if foreshadowing the later pattern of nominations for the Nobel Prize-in which those who knew Behring best liked him least- the Marburg appointment went forward despite major opposition from the Faculty of Medicine. In 1898 Behring was appointed to the German nobility and named a privy councillor. While much of this success was directly due to the active support of the minister of education, Friedrich Althoff, it was also a reflection of popular acclaim for Behring's triumphs over diphtheria and other infectious diseases. It is not irrelevant to understanding Behring's career to observe that Kitasato enjoyed similar success-including the acquisition of great wealth-in Japan.30

When the Swedish authorities began considering possible recipients for the first Nobel Prize in Physiology or Medicine, they decided, understandably, to recognize an achievement that was already well known and widely acclaimed. There was, moreover, a conviction in the committee that the first award should recognize a basic medical advance that also had significant clinical importance. The discovery of natural immunity and the subsequent development of serum therapy met these criteria perfectly; five letters arrived in Stockholm recommending an award for these achievements. One came from the Netherlands, one from Switzerland, two from Norway, and one from Hungary. The nine signatories from Leiden, the two separate correspondents from Christiania (Oslo), and the one from Berne mentioned only Behring. However, the letter from Budapest proposed an award to Kitasato as well as Behring and indicated that other colleagues at Budapest also favored the idea of a prize for the two investigators.3'

29 Miyajima, Kitasato Shibasaburo- den (cit. n. 13), pp. 57-59; the quotation is from pp. 58-59. 30 On Behring's achievements see Brock, Robert Koch (cit. n. 12), p. 235; Schadewaldt, "Emil von

Behring" (cit. n. 17), p. 576; and Takano, Kitasato Shibasaburd (cit. n. 22), p. 41. On Kitasato's success see Miyajima, Kitasato Shibasabur5 den, pp. 210-220. Here Miyajima notes that Kitasato spent 50,000 yen-a very substantial sum at the time-on a hot spring at Izu, inspired by one he had patronized in Budapest. He also paid for a foreign tour by a Japanese sumo wrestler. He was named to the House of Peers in 1917 and enobled as Baron Kitasato in 1924.

31 SchUck et al., Nobel (cit. n. 24), p. 182 (Behring only); and P M. Forsdndelser och Betdnkanden, 1901 (Kitasato and Behring). The official nominator, Arpad de Bokay, wrote on 27 Jan. 1901: "J'esp6re donc avoir l'essentiment de mes collegues en proposant de decerner le prix a Messieurs Behring et Kitasato, deux savants dont le m6rite inconteste a pour toujours une place dans l'histoire de la m6decine."




Why Behring alone was proposed by most of the European nominators is to some degree a matter of conjecture. Diphtheria was a major disease, of course, and there were major epidemics in Europe before Behring came along. Moreover, "Behring was regarded as a savior by the general public, and this reception was one basis for awarding him the first Nobel prize." By contrast, "Kitasato's tetanus was not so major a disease in humans, and since it was often contracted through unclean wounds, the public reception of his success in treating it was more prosaic." But it is equally probable that in moving back to Japan Kitasato sacrificed his visibility; despite periodic visits, he simply dropped out of the sight of many Europeans. Indeed, a recent Japanese commentator who has authored a book and a widely known article on the Nobel Prizes refers to their obvious European origin and describes Kitasato as from "remote Japan" and, in a phrase redolent of nineteenth-century positivism, a "victim of the maldistribution of civilization" !32

Despite the peculiar terminology, this explanation is not as far-fetched as it might seem. Behring may have been disliked by many German medical colleagues, but he retained some powerful assets. One was the affinity felt by many Swedish academics for German culture generally and German academic culture in particular, a theme well developed in the important studies of Elisabeth Crawford. One senses these affinities in a biased, rather implausible report written on behalf of Behring's candidacy by Ernst Bernhard Almquist for the Karolinska prize committee in 1901. Alm- quist concedes that Behring admitted to "a kind of inadequacy" in his research capabilities and draws attention to what others have characterized as the candidate's chemical or pharmacological approach to disease. At the same time, he insists that the discovery of a means of immunizing against diphtheria was "essentially Beh- ring's own [achievement]." Moreover, Behring "came to the right path from his earlier study of diphtheria and thereafter turned to . .. tetanus because. .. it more easily gave results. He therefore joined forces with Kitasato who was already in charge of tetanus. [However], it will be generally recognized that neither Koch nor Kitasato had any significant role in Behring's project." But if this were true, why did Behring and his partisans go to such trouble to slight Kitasato's contributions? In view of the German scientist's experience, training, and basic orientation to disease, the claim that neither Kitasato nor Koch played any "significant role" strains credibility.33 At the least, a Nobel award for the discovery of natural immunity and the principles of serum therapy should have been shared by Kitasato and Behring.

An equally intriguing question is, Why did the letter from Budapest, unlike the others, propose both Kitasato and Behring? There are several possibilities. One is certainly professional affinity. That letter was signed by Arpad de Bokay (1856- 1919), professor of pharmacology at the University of Budapest and a member of the Hungarian Academy of Sciences. De Bokay probably leaned toward the joint candidacy because of his interest in drug therapy, illustrated by his authorship of

32 Takano, Kitasato Shibasaburo (cit. n. 22), p. 41; Yano Toru, Noberu sho (Nobel Prizes) (Tokyo: Chioi Koron Sha, 1988), p. 133; and Yano, "Maboroshi no Nihonjin Noberu sho jushoshatachi" Chau Koron, May 1988, 103(5):171.

33 Ernst Bernhard Almquist, "Blodserumterapiens uppkomst och utveckling,"' in P. M. Forsandelser och Betankanden, 1901, pp. 1, 2. For another work that slights Kitasato's contribution see Heinz Zeiss and Richard Bieling, Behring: Gestalt und Werk (Berlin/Grunewald: Schultz, 1941), pp. 54-55, 58-60. On behalf of Kitasato and Koch see Nakamura, "Seiji to jinmyaku ga karanda" (cit. n. 14), p. 136; and Brock, Robert Koch (cit. n. 12), p. 295. Brock writes: "Without Koch before him, Beh- ring's work would have never been possible." He further describes Behring as "a much lesser figure."




Figure 2. Robert Koch in kimn

o

visit to Japan. 1908.

sexveral books on this subject. He may also haxve had a personal affinity for Kitasato. It is possible that they met durnng Kitasato's xvell received visit to the Pasteur Insti- tute. since de Bokax is knoxxvn to haxve xvisited there often. They could also have met in Budapest. xxhere Kitasato xvisited on a number of occasions (one of his objectives was to enjoy the renowned Turkish baths). In 1895. 19031. and 1909 he attended international medical congresses in Budapest. and he could certainly have met de Bokav on one of these visits (though of course only the first could have mattered with respect to the Nobel Prize nomination.

A final possibility is ethnic or cultural considerations. De Bokav, may have nomi'- nated Kitasato partly because his Hungarian ethnicity gave him a greater affinity xvith things relating to Asia than most European medical or scientific personalities in this period. Robert Koch spent sexeral wveeks in Japan in 1908 and even had his photograph taken in a Japanese kimono: but he was atypical of European scientists in his appreciation for Asia. (See Figure 21.) Hungary. hoxvever. is a country xvhose founders came from Asia. Its languag~e xvas once believed to haxe linguistic ties to Japanese. And it is rumored that in 1919. wvhen an independent Hungarian monarchy xvas being organized under a regent. one of the candidates for the throne considered

On de Bokay see .Arpdd de B6kayW. in Ma gyar Elerro-izi Lexikon. Vol. 1 i Budapest: Akaderniai Kiado. 196-T. p. 236: and .Arpid Bo'kay." in Mat gnar MVxikn. Vol. 2 iBudapest: Akadmiiai Kiado. 199-5 . p. 229. I am crateful to Tfhomas Sakmrster oIf the University- of Cincinnati and Eva Apor of the Hungarian Academr of Sciences. Budapest. for bringing these references to my attention. Alice Risko. a graduate student in the Department of Germanic Langauges at Ohio State Universitv. kindly- translated the materials for me.) On the medical congresses in Budapest I have consulted Ldszld A. Marvar of the Semmelweis Museum. Budapest ppnvate communication. 9 Sept. 1997T. Ma!gvar ki ndlx gave me a list of de Bokavs publications on drug therapy and other matters.




by power brokers in Budapest was the brother of Japan's Meiji Emperor, Prince Fushimi.

For whatever reasons, it was Arpad de Bokay of Budapest who most vigorously stated the case for a Nobel award that involved Kitasato: "The work of Messrs Beh- ring and Kitasato marks the beginning of a new era in research."35

YAMAGIWA'S NOBEL CANDIDACY, 1926-1927

Yamagiwa Katsusaburo (1863-1930) was nominated for the Nobel Prize on four occasions; by some indications, he came close to receiving the 1926 prize, actually awarded in 1927. He did not win, however, despite having strong admirers in Japan as well as abroad. He was respectfully backed by Tokyo University nominators, especially his longtime friend and younger colleague Nagayo Mataro. Even more enthusiastic supporters included Alexander Maximow of the University of Chicago, Ludwig Aschoff of the University of Freiburg, William Cramer of Washington Uni- versity in St. Louis, and, most influential of all, Folke Henschen of the Karolinska Institute in Stockholm. Maximow and Aschoff each nominated Yamagiwa formally, and Henschen wrote a report for the selection committee that was explicitly designed to get him a Nobel Prize.

But it was to no avail. The committee decided instead to award the 1926 prize solely to Johannes Fibiger of Copenhagen, mostly because Fibiger had apparently discovered how to use parasites to generate cancers in rats two years before Yama- giwa showed how to induce cancers in rabbits by applying coal tar to their skin. The committee believed that Fibiger's work was very important and had been carried out earlier than Yamagiwa's; thus, they reasoned, it deserved the award. In fact, it was Yamagiwa's work that proved to have lasting value for oncology, and there is now wide agreement that Yamagiwa should have received a share of the prize. Others would say that he alone deserved the Nobel.

Yamagiwa's achievement, which unfolded over many months in the course of World War I, had an extended prehistory, beginning with his medical studies in Tokyo and Berlin. (See Figure 3.) After graduating from Tokyo University's Faculty of Medicine in 1889, he took an assistantship in the university's pathology graduate program and advanced to the rank of assistant professor after only two years. In May 1891 the ministry of education decided to send a three-member delegation of Tokyo professors, including Yamagiwa, to Robert Koch's institute in Berlin for the purpose of learning more about the newly discovered tuberculin. The visit began badly because Koch considered it a slight to Kitasato by the ministry, which had recently terminated the Japanese bacteriologist's funding (later reinstated). This chilly reception gave Yamagiwa little incentive to remain at Koch's laboratory.36 He found Ru- dolf Virchow's highly regarded program in pathology more to his liking in any case, and in January 1892 he began studying under Virchow.

His sixteen months at Virchow's institute (January 1892-April 1894) proved to be one of the two most decisive periods of Yamagiwa's career, not because of any

35 EM. Firsdndelser och Betdnkanden, 1901. Miyajima, Kitasato Shibasabur5 den (cit. n. 13), contains a copy of the Koch photograph between pages 198 and 199. For a sense of Hungarian affinities with Asia see the brochure entitled "The Path from the Orient to Our Present Homeland," Fact Sheets on Hungary (Budapest: Ministry of Foreign Affairs, 1997).

36 Miyajima, Kitasato Shibasabur& den, p. 55.



54 JAMES R. BARTHOLONIEWV

|~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~. . .. ...

Figure 3. l.amagiwa KarAzit rO.

important research contribution he made at the time but becaus.e of the intellectual foundation he laid for later work. While he ultimately made a reputation for his work on cancer. Yama~-iwa did not s;tudy- cancer to any signiticant extent while resident in Berlin. In fact. he did not s;pecialize at all during his;, time with Virchowv but. rather. immersed hims,;elf in general pathology,. These efforts- included studies of cells. morphological changes in inflamed tiss,-;ue. regeneration phenomena. and all kinds of chancels in cells. Asa morphologist. he was,, able to do the research on artificial cancer [later] because he had managed to lay such a durable foundation."'

Yamnagiwvas; relationship w-ith Virchow was quite different from that of Kitasato with Koch. The two bacteriologzists wvere only a few years- apart in aL-e: but Virchowx was, almost forty years- ;senior to Yamnagiwa. and they never became pers-onally close. Moreover. Yamagiwva contracted pulmonary tuberculosis in 1899 and wJas- never again able to leave Japan. wvhile Virchovv died in 1902. But they wvere compatible in thir intellectual approach to medicine. -Many years earlier Vir'chowv had 2ained re- nown for his cellular theory of pathology. according to which "~everythinc, relating to cells comes- from cell~s.' Virchowv offered a ye ar-long pathology demonstration course. through wvhich Yamna!-iwa fully absorbed this pesetv nd one of its cor- ollaries;,. Virchow's- equally wxell known but unproven contention that cancer can be

-~ Nagavo aMatar5. -arm \z a K s ui ; u> bur Seiei sho den rA shorz biora phx of Pro-fessor N-a- Marxva Katsusabur5 in TjAc-GJ jt f71-C:; Dcz7ctc^; BIF'r: ..?-; K,5's::; o&'. n: , Fift-'ear hi- ton oft the Patholo!: Institnte of Tok--o Imperial 1iniversirt e;. Na ga~o Tok-v: Thkx-) Teikoku Da~i~aku. 193-9,. VT.- 1. p. 236.




caused by a chronic, repetitive external stimulus.38 It is uncertain exactly when Ya- magiwa got the idea of trying to prove Virchow's theory of cancer, but there is reason to think the seed was planted in Berlin.

However, Yamagiwa did not begin working on cancer immediately after returning to Tokyo. Instead, he spent several years on plague, beriberi, pulmonary distomiasis, Japanese blood fluke disease, and several other diseases that were prominent in Ja- pan. He and Virchow kept in touch; for example, Virchow published Yamagiwa's 1895 study of plague, carried out during a Taiwan epidemic, in a special supplement to the Virchow Archiv, a signal honor given the journal's worldwide reputation. In February 1899 Yamagiwa contracted tuberculosis, and there is no doubt that this strongly affected the timing of his work on cancer. The intensification of his latent interest in cancer may well have come during the difficult early months of his illness; certainly by 1905 he was fully committed to a program of research, and a few months later he founded his own journal of cancer studies, Gann [Cancer], a publication that still appears regularly.39

Yamagiwa's illness left him bereft of energy for long periods, sometimes months at a time. (He spent most of 1910 at the university hospital in Kyoto, where he had taken sick while returning from a conference in Osaka, too weak even to return to Tokyo.) As a result, he was heavily dependent on the cooperation of others. Assistant professors often delivered his university lectures, and in the laboratory he had to rely on a series of assistants. The most important of these was Ichikawa Koichi, a twenty-five-year-old graduate in veterinary medicine from Tohoku University who joined Yamagiwa's staff in 1913. Some reports suggest that Ichikawa's association with Yamagiwa was largely accidental. In fact, Yamagiwa almost certainly hired him because of his expertise with animals and because he had earlier completed a study of parasites. Fibiger's 1913 announcement that he had used the nematode Spiroptera parasite to generate cancer in rats surely made Ichikawa's experience with animals in general and parasites in particular all the more valuable to Yamagiwa.40 Their partnership was to prove enormously productive.

A sophisticated knowledge of pathology and long years of research activity guar- anteed Yamagiwa's role as the intellectual leader of the effort to produce cancer artificially in the laboratory. Ichikawa's relative youth and inexperience should not obscure the importance of his contribution, however. Yamagiwa was in precarious health and could perform the necessary research tasks himself only occasionally. It was therefore Ichikawa whose physical labor assured the success of their plan; one indication of the contribution he made is his own, albeit unsuccessful, nomination for a Nobel Prize after Yamagiwa's death, in 1936.

Yamagiwa was by no means the first investigator who had hoped to prove Vir- chow's contention that chronic, local irritation could generate cancer. Many others

38 Guenter B. Risse, "Rudolf Carl Virchow," in Dictionary of Scientific Biography, ed. Gillispie (cit. n. 13), Vol. 14, p. 41 (quotation); and Maruyama Kosaku, "Ayamari datta 'kiseichui hatsugen setsu' de jusho" (Mistaken Nobel Prize for the "parasite thesis"), in N5beru sh5 no hikari to kage, ed. Kagaku (cit. n. 14), p. 19.

39 Irisawa Tatsukichi, "Yamagiwa kun no omoide" (Some memories of Mr. Yamagiwa), in Tokyo5 Teikoku Daigaku Byorigaku Kyoshitsu, ed. Nagayo (cit. n. 37), p. 115; and Nagayo, "Yamagiwa Katsusaburo Sensei sho den" (cit. n. 37), p. 236.

40 OnYamagiwa's illness and its consequences see Irisawa, "Yamagiwa kun no omoide," p. 116. On his partnership with Ichikawa see Maruyama, "Ayamari datta 'kiseichiu hatsugen setsu' de jusho" (cit. n. 38), pp. 21, 18.




in France, Germany, Italy, and elsewhere-had taken up the challenge, using several different types of laboratory animals and a range of chemical substances. Long- term, tedious experiments that ultimately produced the artificial cancer began at the end of the summer in 1913; one account says on 31 August, another targets 1 Sep- tember. They were far from straightforward in the earliest phase. Rabbits had not previously been used in cancer experiments, but Yamagiwa decided to work with them because they had a relatively long life span, because they were not susceptible to cancer in their natural environment, and because their long ears offered conve- niently accessible epithelial tissue. Ichikawa first tried either external applications or injections of a form of olive oil in a small number of animals, producing nothing of interest. Creosote or wood tar applications and injections were no more successful, and neither were mechanical methods of irritation-crushing or twisting the skin with tweezers. The investigators then decided to test coal tar-sources disagree as to who proposed it-because of prior medical findings that exposure to coal tar had been implicated in the cancers of some factory workers. This was a fortunate, if somewhat casual, choice; the agent in the coal tar that made the experiments work, 3,4-benzpyrene, was not fully identified until many years later.41

Yamagiwa and Ichikawa divided the rabbits into two groups: one group would receive both external coal tar applications and internal injections of a skin- regenerating medicine every other day; the other group received coal tar and skin- regenerating medicine on alternate days. The investigators then divided each of the larger groups into two subgroups: one subgroup was subjected to mechanical manip- ulations as well, given small wounds or cuts on the skin with a knife or tweezers; the other, control, subgroup was not. After two months of these procedures, all the rabbits' skin became inflamed and showed considerable swelling; but microscopic examinations showed that no cancer was present.42

A new phase in the project began in the early spring of 1914. On 2 April the investigators delivered a paper to the Tokyo Pathology Society that reported the appearance of a neoplasm akin to a malignant growth on the rabbits' skin after 112 days of coal tar applications. This report elicited much criticism. Members of the audience were well aware that earlier efforts of this sort had all failed, and several of those in attendance contended that Yamagiwa and Ichikawa had produced nothing more than a new type of inflammation. At this point the two pathologists obtained private funding from the (Japanese) Cancer Research Society and purchased sixty additional rabbits for continued experimentation. Unfortunately, the rabbits' cages were mostly placed adjacent to each other; during the June rainy season, the Coxsid- ium protozoan attacked the animals, killing most of them by early September.43

As fortune would have it, however, two (or, by other accounts, three) animals not only survived but showed wartlike growths, shaped like grains of rice or millet, on their skin. Yamagiwa bought more rabbits, and in mid December he decided to add

4' On Yamagiwa and Ichikawa's work see Maruyama, "Ayamari datta 'kiseichu hatsugen setsu' de jusho," pp. 20-21; and Ichikawa Koichi, "Gan no gen'in ni kansuru kenkyu no tsuikai, Onshi Yama- giwa Sensei no tsuioku" (A eulogy for my teacher, Professor Yamagiwa Katsusaburo: An account of our research on the origin of cancer), in Toky6 Teikoku Daigaku Byorigaku Kyoshitsu, ed. Nagayo (cit. n. 37), Vol. 2, p. 172. On the identification of 3,4-benzpyrene see Alexander Haddow, "Cancer Research," in Encyclopedia Britannica (Chicago: William Benton, 1972), Vol. 4, p. 776.

42 Maruyama, "Ayamari datta 'kiseichui hatsugen setsu' de jusho," pp. 21, 23. 43 Ichikawa, "Gan no gen'in ni kansuru kenkyu no tsuikai" (cit. n. 41), p. 173.




black rabbits to the experimental pool, which hitherto had contained only white rabbits. The coal tar and skin-regenerating treatments continued. On 1 March 1915 benign tumors or papillomas had appeared on the skin of the black rabbits; on 25 March holes opened up in their ears. Finally, on 13 May the white rabbits displayed the papillomas as well. When the papillomas first appeared, the coal tar and skin- regenerating treatments were discontinued so the researchers could analyze the developments. Yamagiwa and Ichikawa concluded that the papillomas, with their strongly evident keratosis, were indeed tumors, not mere neoplasms. By mid May, microscopy studies indicated that the former papillomas on the black rabbits were now fully developed carcinomas. On 11 June, three white rabbits also displayed the carcinomas; so far as Yamagiwa was concerned, the chronic irritation theory of cancer first formulated by Virchow had now been proven.44

As is often true for fundamental discoveries, Yamagiwa and Ichikawa had to allay important criticisms and clarify certain issues before their claims won broad acceptance. Some challenges involved issues of fact, others points of interpretation, and still others matters of methodology. Their first effort to present and support their claims came in the summer and fall of 1915. Kikuta Kichisaburo was hired to produce the necessary microphotographs of the lesions; and his efforts were precise and thorough enough that a September presentation by the two investigators before the Tokyo Medical Society came off successfully. Immediately following this presentation, Yamagiwa published an account of their work in the society's journal, Tokyo Igakkai Zasshi, and a similar report in the Journal of Cancer Research. Word of their apparent triumph spread overseas by these and other means, including timely visits to Tokyo in August and December by Simon Flexner of the Rockefeller Insti- tute and William H. Welch of Johns Hopkins University.45

Not everyone was immediately persuaded, however; and by the spring of 1916 Yamagiwa and Ichikawa were troubled by the observations of various colleagues to the effect that the rabbit tumors seemed to have undergone no further morphological changes. Were the surface skin tumors true horny adenocarcinomas? By this time Ichikawa had accepted a position at Tohoku University (whose Faculty of Agricul- ture was then located in Sapporo), so Yamagiwa hired another youthful assistant, Murayama Koshichiro, to help with a new but related project. The goal was to prove that the skin tumors were significant by injecting the mammary glands of rabbits with a mixture of coal tar and lanolin in the hope of producing another set of tumors. Murayama's own account reveals in some detail the single-minded determination with which Yamagiwa approached this new research effort. On one occasion the senior pathologist made him stand absolutely still in the laboratory for nearly an hour because he had not administered the injections to the rabbits quickly enough; the younger man felt as though he were back in elementary school!46 In due course, however, the project succeeded in producing fibrous sarcomas in the rabbits, thus vindicating and extending the original claims.

14 Maruyama, "Ayamari datta 'kiseichu hatsugen setsu' de jusho" (cit. n. 38), p. 24. " Ichikawa, "Gan no gen'in ni kansaru kenkyu no tsuikai" (cit. n. 41), pp. 174-175, 176. Both articles were cited in 1966 by the British cancer researcher James F. Riley: "Mast Cells and Cancer in the Skin of Mice," Lancet, 31 Dec. 1966, 2(7479):1457-1459, on p. 1457.

46 Ichikawa, "Gan no gen'in ni kansaru kenkyu no tsuikai," pp. 175-176; and Murayama Koshi- chiro, "Kaiko" (Reminiscence), in Tokyo Teikoku Daigaku By5rigaku Kydshitsu, ed. Nagayo (cit. n. 37), Vol. 2, pp. 380-384, on p. 382.




While World War I was still under way, two important medical delegations from the United States arrived at the Pathology Institute of Tokyo University. Flexner and Welch made a second trip late in 1917, while H. Gideon Wells of the University of Chicago led a separate American delegation in 1918. Both groups informed the Japa- nese pathologists that Yamagiwa's success was creating quite a stir in the United States and to some extent in Europe. Yamagiwa and Ichikawa took encouragement from these reports as they began to prepare a lecture to be delivered at the Imperial Academy of Sciences in August. Yamagiwa was so worried that some mishap or disaster might occur that he made Ichikawa memorize the entire talk and present it to him ahead of time. Not surprisingly, the lecture came off perfectly.47

In the meantime, efforts were under way to replicate the original work of the two pathologists. In the spring of 1918 Yamagiwa's former pupil, Tsutsui Hidejiro of the Chiba Medical College, followed the methods of his teacher in applying coal tar to the skin of mice. This particular study was so carefully conceived and executed that it established the standard technique for generating cancer in the laboratory, used worldwide. In 1920 and 1921 Fibiger himself undertook a similar project in Copen- hagen, following the original Yamagiwa-Ichikawa methods as modified by Tsutsui. His results were equally successful. Other scientists in the United States and Europe did similar work with favorable outcomes.48

In fact, the discovery that coal tar, consistently applied to the skin in a laboratory setting, can cause cancer set off another chain of research activity directed at finding the cancer-causing chemical component. Chemists and medical researchers alike in Britain, Switzerland, and the United States-undertook to isolate the critical substance. Early work by B. Bloch and W. Dreyfus in Zurich in the 1920s indicated that the crucial agent probably belonged to the class of cyclic hydrocarbons. In 1932 E. L. Kennaway and J. W. Cook of the Cancer Research Institute of London were able to identify 3,4-benzpyrene as the causative agent. "These advances were not merely of utmost importance in themselves but had immediate and lasting repercus- sions on every aspect of experimental cancer research throughout the world."49 In- deed, the entire field of chemical carcinogen research received an enormous boost from the epoch-making triumph of Yamagiwa and Ichikawa.

However, these assessments were rendered many years after the original events. Any prospect of a Nobel Prize in the 1 920s would require the act , support of well- placed scientists in Europe, the United States, and Japan in this relatively early period. The early indications were quite favorable. Ichikawa spent two years in Europe, 1923-1925, demonstrating the Japanese methods of cancer production for skeptical colleagues in Paris, Berlin, and elsewhere; it is clear from testimony of the period that he made some converts. Folke Henschen of the Karolinska Institute was impressed, and so was Otto Warburg of the Kaiser Wilhelm Institute for Biology. (War- burg himself won a Nobel in 1931.) In September 1924 the noted German pathologist Ludwig Aschoff of the University of Freiburg visited Japan and met with Yamagiwa. Aschoff had previously received a number of young Japanese researchers

47 Ichikawa, "Gan no gen'in ni kansaru kenkyd no tsukai," pp. 176-177. 48 On Tsutsui's work see Maruyama, "Ayamari datta 'kiseichl hatsugen setsu' de jush6" (cit. n. 38),

p. 24, and SchUck et al., Nobel (cit. n. 24), p. 247. On Fibiger's use of these techniques see Paul Madden, "Johannes Fibiger,' in Nobel Prize Winners, ed. Magill, Physiology or Medicine (cit. n. 19), Vol. 1, pp. 267-274, on p. 273.

49 Haddow, "Cancer Research" (cit. n. 41), p. 776.




at his institute, among them Yamagiwa's friend Nagayo Mataro, and he was clearly impressed by the accomplishments of the Japanese cancer researchers. Indeed, Aschoff was sufficiently impressed that in December 1925 he proposed Fibiger and Yamagiwa as joint candidates for the 1926 Nobel Prize in Physiology or Medicine.50 Unfortunately, none of these developments was quite enough.

Fibiger's prominence, the evaluation of his work by some external referees, and the perceptions of both held by the Karolinska Institute faculty were the problem in Stockholm. By 1927 there was broad agreement that Yamagiwa-and Fibiger-had done something important. But there was never a possibility that Yamagiwa could receive an unshared Nobel Prize; it would at best be shared with Fibiger. Between 1923 and the fall of 1927 the Danish scientist received a total of fourteen nominations, while Yamagiwa obtained six. The nominators' institutional affiliations and countries of origin are revealing. Fibiger was very much a Scandinavian favorite son, earning two recommendations from Norway, two from Denmark, two from Sweden, and one from Finland. In addition, three scientists from Germany submitted his name, along with one each from Austria, Belgium, Switzerland, and the United States. By contrast, support for Yamagiwa came primarily from Japan-four colleagues from Tokyo University, each writing separately; he also had one nomination from Germany and one from the United States.5' None of the Japanese nominators made reference to Fibiger in their letters; eight of the Fibiger nominators mentioned Yamagiwa.

The Fibiger Nobel Prize of 1927 has for many years been regarded as one of the few major blunders ever committed by a Nobel Prize committee in science. Begin- ning in 1913, Fibiger had contended that tumors in the stomach linings of certain rats were directly due to the presence of the Spiroptera neoplastica worm, a small organism the rats ingested when they devoured a particular form of cockroach in a Copenhagen sugar refining mill. When he collected these cockroaches and fed them to normal white mice in the laboratory, most became infected with the worms and a

50 For evidence that Ichikawa made some converts see Yamagiwa Katsusabur6 to Nagayo Mataro, 26 Dec. 1923, in Tokyo Teikoku Daigaku Byorigaku Kyoshitsu (cit. n. 37), Vol. 2, p. 161. Henschen's support is clear from Folke Henschen, "Betankande angaende J. Fibiger och K. Yamagiwa," 31 Aug. 1926, in Karolinska Institutet, Medic. Nob. Kom. 1926 P. M. Fbrsdndelser och Betdnkanden (Stock- holm: Karolinska Institutet, 1926) (hereafter, volumes of this series will be cited by title, e.g., Medic. Nob. Kom. 1926 P M. Forsandelser och Betinkanden), pp. 1-13. See also K. J. H. Bergstrand, "Betankande anga'ende J. Fibiger och O. Warburg," 1 Sept. 1927, in Medic. Nobel Kom. 1927 P M. Fdrsdndelser och Betdnkanden, pp. 1-5. In this report Bergstrand, rector of the Karolinska, wrote: "It is significant that Otto Warburg in a lecture held in 1926 says that Yamagiwa's experiments had shown that the old clinical and pathological-anatomical understanding of chronic stimulation as the reason for cancer is true." On Aschoff's interest see Nagayo Hakushi Kinen Kai, ed., Nagayo Matare den (Biography of Nagayo Matar6) (Tokyo: Nagayo Hakushi Kinen Kai, 1944), p. 110. A photograph of Aschoff and Nagayo taken in Tokyo is in the front section of the book. For Aschoff's letter propos- ing Fibiger and Yamagiwa, dated 9 Oct. 1925, see Medic. Nob. Kom. 1926 P. M. Fdrsdndelser och Betdnkanden, pp. 1-2.

51 Fibiger's Scandinavian nominators were Valdemar Bie and Thorvald Madsen (Denmark), Francis Harbitz and Vilhelm Schaldemose (Norway), Ulrik Quensel and Folke Henschen (Sweden), and Axel Wallgren (Finland). Others included Max Askanazy (Switzerland), Georg Gruber (Austria), Frans Daels (Belgium), and Alexander Maximow (United States) and Ludwig Aschoff, Friedrich Kopsch, and Erich Opitz (Germany). For details see the appropriate volumes of the Karolinska Institute's archival materials for 1923, 1925, 1926, and 1927. For Yamagiwa's nominating letters see Medic. Nob. Kom. 1925 P. M. Firsdndelsen och Betdnkanden, for the letters from Japan by Nagayo Mataro, Hayashi Haruo, Yokote Chiyanosuke, and Kure Shuzo; Med. Nob. Kom. 1926 P M. Fbrsdndelsen och Betdnkanden, for Aschoff's letter; and Med. Nob. Kom. 1928 R M. Fbrsdndelsen och Betdnkan- den, for Maximow's letter.




significant number contracted cancer. Fibiger was even able to transfer the stomach cancers seemingly caused by the worms to other mice.52 For many years these findings were seen by most researchers as a clear confirmation of Virchow's chronic irritation theory of cancer, and for a time they were accorded temporal and intellectual priority over the later-but much more important-discoveries of Yamagiwa and Ichikawa.

Unfortunately, the pertinent facts had not all been brought into proper focus when the Nobel committee and the Karolinska Institute faculty began considering the possibility of a Nobel Prize for achievements in cancer studies. Gunnar Hedren, professor of pathological anatomy at the Karolinska, had tried to slow things down in 1923, writing in a confidential report: "Researches on the basic value of Fibi- ger's investigation ... have still not yielded any result.... I have an obligation to insist ... that people need time to reach a more definitive judgment about the worthi- ness of Fibiger's work for a Nobel prize." But few were willing to listen; it was only in 1928 and 1929, after the prize had already been awarded to Fibiger, that evidence was presented that the tumors were probably not caused by the worms at all but, rather, associated with a deficiency of vitamin A in the diet of the rats and laboratory mice.53

The real mystery is why so few were willing to accept Hedren's caution. Ever more favorable evaluations of Yamagiwa and Ichikawa's work were appearing by the latter part of the 1920s; and the more favorable reports on the Japanese findings became, the more vigorously Fibiger's champions espoused their claims for his intellectual priority. In 1923 Folke Henschen had proposed only Fibiger for the Nobel; by late 1926 he was arguing that Yamagiwa and Fibiger deserved to share a prize. "The reservations expressed in 1922 and in 1923 were reasonable, but at this point they no longer are," he wrote on 31 August 1926. "It should rightly be established that the prize be divided between Fibiger, who first delved into the carcinoma research, and Yamagiwa, the discoverer of the experimental tar carcinoma."954 Hen- schen's view was shared by Maximow of Chicago and by Aschoff of Freiburg.

Why, then, was a shared prize not proffered? The official history of the Nobel Prizes published in 1950 reports that the pertinent considerations at the time were that the cancer-producing properties of coal tar had supposedly been discovered earlier from observations on human beings-thus Yamagiwa's work was not really that original-and that Fibiger's experiments had initiated the entire process of discovery in any case.55 These judgments were mistaken, of course; among the contrib- uting factors were a tactical error by Yamagiwa himself, a similar blunder by his supporters in Japan, Yamagiwa's physical inability to travel to Europe to defend his claims, and the unmistakable chauvinism of certain European referees who participated in the Nobel nomination process.

Yamagiwa's mistake-an understandable one-was to have praised Fibiger ex- cessively in print. In 1930 the Lancet, in its obituary for Yamagiwa, reminded readers

52 Madden, "Johannes Fibiger" (cit. n. 48), pp. 267-273. 53 Gunnar Hedren, "Betankande angaende J. Fibiger," 31 Aug. 1923, in Medic. Nob. Kom. 1924

P. M. Fdrsdndelser och Betankanden. See also Claude R. Hitchcock and E. T. Bell, "Studies on the Nematode Parasite, Gongylonema neopolasticum," Journal of the National Cancer Institute, June 1952, 12:1345-1387.

54 Henschen, "Betankande angdende J. Fibiger och K. Yamagiwa" (cit. n. 50), p. 13. 55 Schfick et al., Nobel (cit. n. 24), p. 235.




that in one of his earliest reports on the tar carcinoma work the Japanese pathologist had attributed his decision to launch his cancer studies in the first place to the "glorious achievement of Fibiger." It is probably true, as the British medical weekly noted, that "rarely has a scientific worker paid a more generous tribute to another"; it was certainly a blunder in the context of the Nobel Prize. In his Nobel nomination letter of 29 January 1927 for his University of Copenhagen colleague, Thorvald Madsen, director of Denmark's State Serum Institute, seized on Yamagiwa's words as a major reason to accord Fibiger sole priority.56 Other European referees presented a mis- leading view of events. Georg Gruber of the University of Innsbruck described Ya- magiwa and Ichikawa as having "followed Fibiger's path" but then inconsistently noted, in reference to Fibiger's researches of 1920-1921, that he and his assistant had developed effective methods of cancer production by following the methods of Yamagiwa and Ichikawa. Gruber held that Fibiger alone deserved the prize. To his credit, K. J. H. Bergstrand, rector of the Karolinska Institute, flatly denied Gruber's claim that the Japanese investigators had followed Fibiger's path in a referee's report dated 1 September 1927.57

In this intensely political evaluation process, Yamagiwa was to some extent a victim of both his own physical infirmity and the lack of political sophistication of the well-meaning colleagues at Tokyo University who submitted his name to Stock- holm. The debilitating effects of his tuberculosis meant that Yamagiwa could rarely travel even in Japan, let alone accept the many European invitations that the late 1920s brought to his laboratory. In 1929 the German government gave him an important decoration for his work, the Sophie Nordhoff-Jung Prize; but the ceremony had to be conducted in Tokyo by the German ambassador because of Yamagiwa's precarious health. And almost certainly he attracted the support of Alexander Max- imow and Ludwig Aschoff because these two scientists were able to visit him in Tokyo. Aschoff, in fact, explicitly stated in his letter of nomination for Yamagiwa that his backing had resulted from what he had learned when he visited the Tokyo pathologist in 1924.58

Nor were Yamagiwa's prospects much enhanced by the literary character and the modest tone of the four letters sent to Stockholm by his Tokyo colleagues. In recent years there has been a lively debate in Japan about what is required to win a Nobel

56 "Katsusaburo Yamagiwa" Lancet, 17 May 1930, 218:1084; and letter of Thorvald Madsen, 31 Jan. 1927, in Medic. Nob. Kom. 1926 P. M. Fcrsdndelser och Betdnkanden, p. 10. Madsen wrote (in Danish): "Fibiger brought cancer studies from a stage where they were dead in the water. His work's [importance] is underscored by the work of Yamagiwa and Ichikawa who first achieved the [tar cancer]. [They wrote]: 'Encouraged by Fibiger's glorious achievement, we have been doing experimental work on cancer since last fall."'

57 For Gruber's letter, dated 22 Jan. 1927, see Medic. Nob. Kom. 1927 P. M. Forsdndelser och Betdnkanden, p. 7. Gruber wrote (in German): "Yamagiwa and Ichikawa recently followed the path already trodden by Fibiger, producing cancer by painting coal tar [on a rabbit's ear] inspired by the recognized successes of Fibiger who dealt with spiroptera research. They led [us] to methodologies rich in results. Fibiger and Bang also made successful use of these methodologies." For Bergstrand's report see Bergstrand, "Betankande angaende J. Fibiger och 0. Warburg" (cit. n. 50), pp. 2-3. Berg- strand wrote: "Both [Yamagiwa and Ichikawa] admit that they were stimulated by Fibiger's successful experiment. But to claim that Yamagiwa's work is just a continuation of Fibiger's seems to me to go entirely too far! There is a considerable difference between developing cancer through a parasitiz- ing worm and through a chemically effective means."

58 Yamagiwa Katsusaburo to Nagayo Mataro, 30 Mar. 1929, in Tokyo Teikoku Daigaku Byorigaku Ky6shitsu go]a nen shi, ed. Nagayo (cit. n. 37), Vol. 2, pp. 166-168; and Aschoff's letter to the institute, 9 Oct. 1925 (cit. n. 50), p. 2.




Prize, and in 1994 a prominent official in the Science and Technology Agency complained that Japanese scientists have often been too modest in promoting their own achievements. Perusal of the letters dispatched by Yamagiwa's colleagues in Decem- ber 1924 offers support for the STA official's claim. Nagayo Mataro, Hayashi Haruo, Yokote Chiyanosuke, and Kure Shuzo all wrote very straightforward, factual expositions in German, with never a hint of enthusiasm or a single word of extrava- gant praise. Worse still, though they wrote separately and in accordance with their particular views of Yamagiwa's work, each used a remarkably humble and almost certainly formulaic closing statement-and they were nearly identical: "In closing, I am asking the highly honorable chairman that the committee for the Nobel Prize ... undertake an exact evaluation of the work of Yamagiwa; and I hope that the committee will endorse my recommendation."5s The contrast between these letters and the sometimes boastful letters about Fibiger from Europe is painfully evident.

It has often been noted that the Nobel Committee for Physiology or Medicine was deeply embarrassed by the 1926 prize fiasco; one consequence was its refusal to confer another prize for achievements in cancer studies over the next four decades. For a time, the committee tried to defend the Fibiger award-for example, in the official histories of 1950 and 1962. This strategy was finally abandoned in 1972, when the official history stated flatly: "It certainly seems strange that the 1926 Nobel Prize should have been awarded to Johannes Fibiger." Fibiger died early in 1928, witnessing few of the attacks that were to come. Yamagiwa died not long thereafter, in March 1930; and some of the embarrassment was already evident. In the Lancet obituary William Cramer of Washington University wrote: "It is impossible to over- estimate the importance of Yamagiwa's discovery for the study of cancer." To this day, Yamagiwa's classic papers are regularly cited by cancer researchers from around the world. In 1966 an aged Folke Henschen delivered a memorial lecture on Yama- giwa in Tokyo in which he recalled the events of forty years earlier and reminded the audience that even in 1926 he had thought that Fibiger and Yamagiwa should share the Nobel Prize. Perhaps to suggest that this view was now widely held in Scandinavia and elsewhere, he approvingly quoted a researcher in Belguim: "The man who solves the enigma of cancer does not need a Nobel Prize."60

KATO'S NOBEL CANDIDACY, 1935-1936

Kato Gen'ichi's candidacy in the mid 1930s is a more ambiguous case than the earlier candidacies of Kitasato and Yamagiwa. In the early 1920s Kato (1890-1979) announced his so-called decrementless theory of nerve conduction, and in 1934 he published a detailed monographic account of how researchers working under his

59 Medic. Nob. Kom. 1925 P. M. Fbrsdndelser och Betdnkanden, pp. 3-9. For the recent complaint see Atarashi Kinju, "Nijilisseiki no 'Kagaku gijutsu rikkoku' mezasu: kis6 kenkyO jUshi no seisaku tenkai" (How to create a nation strong in science and technology: Emphasize the importance of basic research), Keizai Seisaku JohJ (Science policy information), 20 June 1994, no. 114, p. 1. At the time Atarashi was chief of the Technology Promotion Bureau in the Science and Technology Agency.

60 H. Schtick et al., Nobel: The Man and His Prizes (New York/London/Amsterdam: American Elsevier, 1972), pp. 188-189. For earlier attempts to justify the award see SchUck et al., Nobel (cit. n. 24), pp. 234-236; and H. SchUck et al., Nobel: The Man and His Prizes (Amsterdam/London/ New York: Elsevier, 1962), pp. 246-247. For implied or explicit criticisms see William Cramer, "The Late Prof. Yamagiwa," Lancet, 20 May 1930, 218:1155; and Folke Henschen, "Yamagiwa's Tar Can- cer and Its Historical Significance," Gann, Dec. 1968, 59:451.



JAPAINESE NOBEL CAN'DIDATES 263

Mainichi Shimbun.

close superx ision had managed to isolate single muscle and nerve fibers and perform valuable expeniments on them. Several of the experiments established the existence of reflex inhibitonv nen es and reflex excitatory nerves. These latter achievements. especialiy. w ere x% idelv heralded and formed the principal basis for Nobel nominations on his behalf bv INan Pavlov (Lenin-grad). Mariano R. Castex (Buenos Aires). and sev eral colleagues at Keio University. Indeed. Kato was a verv credible nominee for a Nobel Prize, as subsequent events wvere to show. But this is not to say that he should haxe receixed a prize. In medicine, especially. there are nearly alw~ays more deserv ing, possible recipients than can ever be officially acknowledged. Kitasato and Yamagiwxa should haxe received prizes: particular Nobel committees had judged certain results prizew~orthy: though their work met the committees' criteria. the two Japanese grot no share of the awards because their achievements were misconstrued or inappropniatelx credited to others. Kato. in contrast. had not produced work of the kind for xxhich a prize was explicitly conferred. although the 1932 award to Edgar Adrian of Bnitain was cited by one Nobel referee as preempting a possible award to Kato. (See Figure 4i Whatever the menits of Kato's case. his candidacy and the events leading to it are

instructive because of the extraordinarv light they shed on the intricate politics that Nobel candidacies can sometimes engender. Friends and supporters in the scientific community naturally took steps to promote his cause. and so did high officials of the Japanese government. There was, in fact. some collusion between the two camps. At the age of tw~enty -eight-under unusual circumstances-Kato became a pro- t~g6 of Kitasato. Keio University's first medical school dean who recruited him for the Keio faculty in 1918. In the face of significant opposition, Kitasato went to remarkable lengths to promote Kato's career. Kato himself was less accomplished




in Japanese medical politics than his powerful mentor, but he was more than skillful on the international stage. Indeed, he took steps to position himself as favorably as possible. That his efforts and those of others ultimately came up short is a poignant illustration of the difficulties of the task at hand: the plethora of deserving Nobel candidates, the continuing-though diminishing-isolation of Japan from Europe, and the intense, destructive factionalism of the Japanese medical research community in this period.

If a Nobel Prize in medicine were one's ultimate goal, Kato was better placed than most to achieve it. Born in 1890 to the family of a socially prominent ophthalmolo- gist in Okayama Prefecture, he grew up in affluence and received the best education Japan had to offer. His father's practice attracted patients from as far away as Ky- ushu, two hundred or more miles to the west of their home. After graduating from the prestigious First Higher School in Tokyo, Kato enrolled in medicine at Kyoto University, rather than at the institution-Tokyo University-for which the First Higher School had prepared him, in order to be close to his father, whose health had begun to decline. He received a gold watch from Kyoto University upon graduating as valedictorian in 1916 and entered the university's graduate program in physiology. His graduate supervisor was Ishikawa Hidezurumaru, with whom he came to have a troubled, tumultuous relationship.

It is no simple matter now to disentangle the elements that produced the bitter conflict between them. Ishikawa came from a far less prominent background than Kato and, while just twelve years older, insisted on a degree of deference that Kato was disinclined to extend. There are indications that the two had very different tem- peraments. Moreover, Ishikawa was part of the last Japanese cohort to pursue advanced medical studies in Germany before World War I, while Kato never studied in Europe at all.62 At bottom, however, the problems between them reflected intense intellectual differences.

Ishikawa was one of two prominent Japanese pupils of Max Verworn, a professor of physiology at Gottingen during the first decade of the twentieth century and after 1910 head of the Physiology Institute at the University of Bonn. Verworn was considered one of the world's leading physiologists at the time, and Ishikawa studied with him between November 1908 and July 1912. A good deal of evidence exists to show that Verworn and Ishikawa became and remained close, especially in a professional context. Verworn was a leading advocate of cellular physiology and was inter- ested in the most basic physiological processes of living organisms.63 But it was his opinions in the field of nerve physiology that most deeply affected Ishikawa and, later, Kato.

At least from the time of Johannes Muller (1801-1858) and Emil Du Bois- Reymond (1818-1896), nerve physiologists had debated the relationship between

61 Yoshimura Hisako, "Kato Gen'ichi," in Ky6do no jimbutsu fud6ki (A gazeteer of prominent personalities from the region), ed. Niimi Shimin Kaikan (Niimi, Okayama Prefecture: Niimi Shimin Kaikan, 1989), pp. 152-165, esp. pp. 153-155.

62 "Ishikawa Hidezurumaru," in Dai Nihon hakase roku (Biographical dictionary of Japanese doc- torate holders), ed. Iseki Kur6 (Tokyo: Hattensha, 1922-1930), Vol. 2, p. 298. Ishikawa came from a commoner background in an era when the majority of academics were former samurai.

63 K. E. Rothschuh, "Max Verworn," in Dictionary of Scientific Biography, ed. Gillispie (cit. n. 13), Vol. 14, p. 2.




nerve stimuli-mechanical or electrical-and nerve responses. For some, Du Bois- Reymond had appeared to settle the issue when he formulated the so-called all-or- none law. This principle incorporated three major arguments: that above a minimum threshold level, there is no connection between the strength of a nerve stimulus and the strength of the response; that the intensity of excitation in a medullated nerve under normal conditions remains unchanged during the time of transmission; and that the rate of conduction also remains constant at all distances from the point of stimulation. Verworn, however, dissented from part of this paradigm on the basis of his studies of certain rhizopods from the Red Sea, especially Difflugia; he reported that in these rhizopods the conduction of nerve excitation takes place "with a decrement of intensity and rapidity" that becomes larger with the distance "from the point of stimulation until the wave of excitation is obliterated." These and other findings gave Verworn considerable prominence, to the point that in 1911 he was invited to deliver the prestigious Silliman Lectures at Yale University. Ishikawa remained a faithful adherent of Verworn's nerve physiology, dissenting from his teacher only on certain details.64

With World War I precluding the possibility of study in Germany, Kato spent two crucial years after his graduation from Kyoto University, December 1916-December 1918, working under Ishikawa. During this period the younger physiologist developed many of the laboratory techniques and much of the problem awareness that would subsequently guide his professional work. Reacting to the research of Friedrich W Frolich, another student of Verworn's at Bonn, Ishikawa determined to show that nerve excitability and nerve conductivity were separate phenomena. Kato, in his first year of graduate study, was instructed to replicate the experiments of another German physiologist, P. F. F Grutzner, regarding the effects of the halogens on nerve conduction. These salts-chlorine, bromine, iodine, and fluorine-were believed to increase the rhythm-making ability of nerves, which displayed a pattern of increased excitability, spontaneous contraction, and paralysis when exposed to them. Kato confirmed these findings, as well as Grutzner's claim that chlorine produced the most intense effects. During these same months he also studied the effect of sarcolactic acid on the rhythm-making ability of nerves, measuring the intensity and duration of the contractions that resulted.65

Kato's subsequent studies under Ishikawa were more or less a continuation of these projects. The Japanese toad, Bufo vulgaris, was frequently used for research purposes in Ishikawa's laboratory, and the senior physiologist instructed Kato to study the rhythm-making ability of a toad nerve and to investigate whether there was an increase in excitability under varying conditions of narcosis. Did these effects depend on the length of the narcotized segment? Various narcotics were employed, especially alcohol, urethane, and morphine. In half the cases Kato found that there was no increase in excitability. He also sought to discover which anesthet- ics were most powerful in increasing a toad nerve's rhythm-making ability when

64 Gen'ichi Kato, The Theory of Decrementless Conduction in Narcotised Region of Nerve (Tokyo: Nankodo, 1924), p. 3; Max Verworn, Irritability: A Physiological Analysis of the General Effect of Stimuli in Living Substance (New Haven, Conn.: Yale Univ. Press, 1913', pp. 128-129, 127 (quotation); and Hidezurumaru Ishikawa, Studies in the Fundamental Phenomena of Life (Kyoto: Institute of Physiology, 1924), pp. 110-112.

65 Ishikawa, Studies in the Fundamental Phenomena of Life, pp. 4-5, 112, 116-117.




applied in concentrations sufficient to paralyze the nerve trunk. Ammonia and alcohol were found to be the most effective, cocaine the least effective, of the substances studied.66

These particular studies tended to confirm Ishikawa's basic views, but those that Kato carried out between April and November 1918 were to sow the seeds of long- term conflict between the two Japanese physiologists. One would not suspect this from the original published record, perhaps because Kato was still working under Ishikawa's firm hand and was not in a position to defy his mentor in print. During these months Ishikawa asked Kato to study the apparent phenomenon of decremental nerve conduction under varying conditions of narcosis, again using Bufo vulgaris for the research. Max Verworn had called attention to decremental nerve conduction in his Difflugia studies, and Ishikawa viewed Kato's assignment as an opportunity to gather evidence in support of his German mentor's opinions. Thus Kato was asked to examine electrical conductivity when various narcotizing substances-ether, chloroform, alcohol, morphine, urethane, chloral hydrate, sulphonol, cocaine, car- bonic acid, and ammonia dissolved in Ringer's solution-were applied to a nerve segment.

Judging from the report of Kato's studies published in the Kyoto medical faculty's in-house journal, the project achieved its ostensible goal. After testing the various narcotics and graphing the nerve conduction curves they produced, Kato ascertained that the so-called E curve, measured at a point within the narcotized nerve segment, "first ascends temporarily and then descends gradually." According to Ishikawa, this finding amounted to a "definite confirmation of the fact that the real excitability [of the nerve] never increases, but gradually decreases on affection [with narcosis]." In short, the results confirmed Verworn's belief in the decremental theory of nerve conduction. The problem was that this interpretation of the evidence did not reflect Kato's settled judgment of the matter. Kato had completed most of the work while Ishikawa was away from the campus for an extended period; when his supervisor returned, Kato announced his suspicion that Verworn's claims were in error. Ac- cording to one report Ishikawa exploded in anger, calling Kato an "impudent appren- tice" and accusing the younger man of defying him.67

This incident can be seen in retrospect as the defining event in Kato's long career. He suffered at first because Ishikawa adopted an attitude toward him that vacillated between indifference and overt antagonism. But an unexpected intervention by Kita- sato soon altered Kato's prospects. Despite his estrangement from many leading medical specialists at Japan's imperial universities, Kitasato had carefully main- tained particular friendships from this group; one of them was with the noted pathologist Araki Torasaburo, who in 1918 was serving as president of Kyoto University. Kitasato was in the process of organizing Keio's new medical school and needed to assemble a faculty. He asked Araki if he knew of any bright younger "men with backbone"; the Kyoto president responded by telling him of an advanced graduate student who had "quarreled with a professor." Kitasato appears to have recognized a kindred spirit, and in December he offered Kato a lectureship at Keio that was gratefully accepted.68

66 Ibid., p. 99. 67 Ibid., pp. 73, 74; and Yoshimura, "Kato Gen'ichi" (cit. n. 61), p. 156. 68 Yoshimura, "Kato Gen'ichi," p. 156.




Events gradually revealed that Kitasato's commitment to Kato went far beyond anything most younger scientists could hope for. In February 1919, after just two months of employment, Kitasato raised Kato to the rank of full professor with a salary to match. When other professors complained, the dean simply told them that the young physiologist was unusually promising and would fulfill the highest professional expectations in ten years' time. Like other Keio faculty members, Kato had entirely new equipment and research facilities as good as any in Japan. Even then, he became known for "borrowing" resources from the rest of the medical school. Kato's reputation and the favorable treatment he received did not go unnoticed by aspiring younger scientists, and within two or three years he had attracted more than a dozen research associates to his laboratory. By 1926 he had twenty researchers working under his direction.69

After his move to Keio University, Kato did not immediately return to the basic research on nerve conduction that had occupied him during his last months with Ishikawa. Apart from the demands of organizing his laboratory and recruiting a staff, he was at first involved in a project on the neurological aspects of beriberi. This was a topic that had engaged Japanese medical researchers for more than forty years and to which Takagi Kanehiro had made a major contribution by demonstrating that the incidence of beriberi could be drastically reduced by dietary modifications. Kato's work led to coauthored publications in 1921 and 1924; beriberi remained an interest for some years.70 But from the summer of 1921 research on nerve conduction occupied most of his time.

Unfortunately, no record shows the exact sequence of research-related events pertaining to this topic in Kato's laboratory. Internal evidence from publications, together with other material, shows that most of the work leading to the theory of what came to be called decrementless nerve conduction was completed between January 1922 and March 1924. In September 1921 Kato left Japan on an eleven-month in- spection tour of medical research facilities in the United States and Europe, paid for by the university; prior to leaving, he consulted extensively with his principal assistant, Maki Ryokichi, about projects to be pursued in his absence. At least since the autumn of 1918 Kato had been suspicious of claims by Verworn, Keith Lucas, Edgar Adrian, and others that the intensity of nerve transmissions declines gradually when the nerve impulse encounters an impaired nerve segment, typically created by exposure to narcotics, asphyxia, or a mechanically induced injury. He gave Maki some suggestions about how to proceed, but the extent of his guidance is difficult to gauge since much of the work was repeated by the two of them after Kato returned to Tokyo in August 1922.71

Kato had learned certain research techniques from Ishikawa and from close reading of the literature. He had adopted the contemporary nerve physiologists' practice of soaking nerve-muscle preparations in Ringer's solution and of employing cir- cuitry with properly positioned electrodes and a narcotizing chamber. In some cases

69 Ibid.; and Gen'ichi Kato, Further Studies on Decrementless Conduction (Tokyo: Nankodo, 1926), p. 1.

70 Robert R. Williams, Toward the Conquest of Beriberi (Cambridge, Mass.: Harvard Univ. Press, 1961), pp. 19-26. In Japanese see Nagai Tamotsu, Takagi Kanehiro den (Tokyo: Tokyo Jikei Kai Ika Daigaku Soritsu HachijUgo Nen Kinen Jigy6 Iinkai, 1965), pp. 93-122. See also Kato, Theory of Decrementless Conduction (cit. n. 64), p. 129.

71 Yoshimura, "Kato Gen'ichi" (cit. n. 61), p. 157.




the narcotizing chamber contained subchambers of differing lengths through which the same or different nerve fibers were passed. For the most part, the narcotizing substances employed-ether, cocaine, alcohol, urethane, and the like-were standard among practitioners. Kato gradually introduced some of his own procedures, among which the simultaneous examination of nerve segments of differing lengths taken from the same animal (rather than from different animals) was probably the most important. All of Kato's coworkers employed these procedures as appropriate.

Maki's research, replicated by Kato, focused on four issues. One was the influence of the length of a piece of unnarcotized nerve between two narcotized nerve segments and its effect on the depth of narcosis required for either to lose conduction. Another had to do with a claim in the literature that a strong electric stimulus to a narcotized segment of nerve would sometimes elicit a response from an attached muscle, even when a stimulus from an electrode external to the narcotized region could not cause a contraction response. Was this response generated, as some claimed, within the narcotized segment? The third question concerned the relative effects of a mechanical stimulus and an electrical stimulus, instigated externally and internally, on a narcotized nerve-muscle preparation. And the last focused on a threshold value for the total loss of conductivity within a narcotized segment. Would this point be reached gradually at electrodes positioned at various distances from the distal end of the narcotized chamber, or would the loss of conduction occur simultaneously at all the points?73

Having created a narcotizing chamber with several points of internal stimulation and two points of external stimulation, Maki prepared two nerve segments of differing lengths attached to muscles from the same toad (Bufo vulgaris) and subjected them to various narcotics-ether, chloroform, alcohol vapor, urethane in Ringer's solution, chlorohydrate, and cocaine. Decrement theory held both that conduction within the narcotized region should fail gradually, according to the distance of the recording electrode from the distal end of the chamber, and that a longer stretch of narcotized nerve should lose conduction sooner than a shorter one. Maki found, however, that length was irrelevant to the outcome and that all points within the region of narcosis lost conduction simultaneously, a result signifying the absence of any decrement in nerve conduction intensity.74

Two other assistants contributed to Kato's formulation of the decrementless nerve conduction theory in this period. Otsuka Tokichi showed experimentally that a full-sized nerve impulse can travel just as rapidly through a long narcotized nerve segment as through a short narcotized segment provided the depth of narcosis is uniform. Similarly, Otsuka Kunio studied the intensity of muscle contractions instigated by stimuli of identical strength at different distances from the muscle. The belief that muscles contracted differently in this situation had been an important piece of evidence in support of decrement theory. But the younger Otsuka's work removed it. By a complex series of tests and measurements, he was able to show that earlier findings of differing muscle contraction heights were due to experimen-

72 Kato, Theory of Decrementless Conduction (cit. n. 64), pp. 13-14. Kato criticized Max Verworn's disciple F. W Frolich for taking measurements from the nerves of different toads and averaging the results.

73 Ibid., pp. 73, 79, 89, 92. 74 Ibid., pp. 71-79.




tal error and that in fact stimulus distance played little or no role in the nature of the contractions.75

In April 1923 the Kato team felt ready for a first public presentation of their work and journeyed to Fukuoka in Kyushu for the national meeting of the Japanese Physi- ological Society. Their lecture and demonstration were scheduled for the morning session of the meeting's first day and seemed at first to go well. Then Ishikawa asked to be heard at the beginning of the question period. After a few innocuous remarks, he launched into a vehement public denunciation of the entire project, calling Kato's research "infantile" and "worthless." He claimed that a thorough airing of the evidence would show that Verworn's theories could explain all the findings and asked the program officials for two hours to prove it. After the deeply abashed Kato and his three associates had left the lecture hall, Ishikawa even moved formally that Keio University be expelled from the Physiological Society!76

Not surprisingly, this proposal failed: Keio was not expelled, and the Kato group remained physiologists in good standing. But Ishikawa's antagonism continued un- abated. In a 1924 publication he attacked his former pupil for a supposed lack of attention to temperature controls in some experiments and for putative inadequacies in data recording. Throughout the period 1924-1926 he made it impossible for most Japanese physiologists to discuss Kato's work on the programs of professional meetings, even though the research was gaining international attention. And in 1927 Ishi- kawa held up for months, and nearly succeeded in preventing, a well-deserved acco- lade for Kato-the Imperial Academy Prize for his theory of decrementless nerve conduction. It is notable that this bitter relationship was sometimes reported in the press. The marine biologist and emperor of Japan, Hirohito, was one of Kato's admirers. In 1988 he recalled the events of 1927, reporting the opposition as having said, "How dare they give this prize for something not fully accepted by the scientific community!" He also noted that Kato's opponents finally backed down.77

Opposition failed because Ishikawa's attacks goaded Kato into an absolutely re- lentless commitment to detail and thoroughness in his work that finally persuaded everyone concerned that his claims were correct. This process of vindication took about twelve years, 1923-1935; it began back at Keio in the difficult weeks following the events in Fukuoka. Kato informed his staff that Ishikawa's opposition was making it impossible to find a suitable venue for reporting their work in Japan. The logical course was to present the nerve conduction project at meetings overseas, beginning with the Twelfth International Congress of Physiology, scheduled for Au- gust 1926 in Stockholm. But such a venture faced formidable difficulties. Travel on the Trans-Siberian Railroad through the Soviet Union would be time consuming, and conditions in the area were still somewhat unsettled. There was the logistical difficulty of transporting the necessary laboratory animals, and it would be necessary to provide hotel accommodations and food for the Keio delegates for a period of several weeks. Here one sees .the most striking evidence of Kitasato's commitment

75Ibid., pp. 137-144, 108-112. 76 Yoshimura, "Kato Gen'ichi" (cit. n. 61), pp. 158-159. 77 Ishikawa, Studies in the Fundamental Phenomena of Life (cit. n. 64), pp. 87-88; and "Gakushin

onshish6 enki: rokujifichi nen mae mo toraburu Tenn6 Heika seikaku na omoide" (Postponement of the Imperial Academy Prize: His Majesty's precise recollection of a problem occurring sixty-one years ago), AERA, 21 June 1998, no. 5, p. 26. See also Yoshimura, "Kato Gen'ichi," p. 160.




to his promising young faculty member. The dean simply contacted several Keio graduates well placed in the business community, asking them to support this important university project, and they did.78

Kato and his staff had much work to complete before any demonstration in Stock- holm could hope to succeed. He began by dividing various research tasks among the members of the staff. Maki Ryokichi, Otsuka Tokichi, and Otsuka Kunio continued with their previous projects. Nakazawa Tsunesaburo was asked to study nerve conduction in warm-blooded animals (chickens, in this case) as a complement to the work on the cold-blooded toads. Fukui Tatsuoki investigated conduction when nerve segments were impaired by asphyxiants-nitrogen, hydrogen, or potassium cyanide-as opposed to narcotics. Harashima Susumu performed many of the narcotization tests using the delicate nerves of the frog rather than the more robust nerves of the toad. Kajikawa Jin'ichi performed narcotization studies using the toad's sensory nerves instead of the more commonly employed motor nerves. Ha- riya Junji worked to explain how and why the rate of nerve conduction dropped considerably within a narcotized segment when conduction was stopped from an outside electrode. And Uchimura Ryoji repeated some of Maki's experiments, revealing that the phenomenon of current spread from outside the narcotized chamber could sometimes elicit a muscular response even when a substantial segment of intervening nerve had been completely deadened by narcotics.79

Projects carried out by Kubo Moritomi and Minami Norio are especially notable since they broke new ground regarding the applicability of the all-or-none law to different kinds of nerve impulses. Two of the most influential European physiologists, Keith Lucas of Cambridge University and his student Edgar Adrian, while accepting the all-or-none law for fresh medullated nerves, supported decrement theory in other contexts. They had, in fact, argued that nerve impulses of subnormal intensity would not obey the all-or-none law and thus that conformity to the law or the lack of it-could be used to measure the strength of a nerve impulse. How- ever, under Kato's direction, Kubo developed a technique for generating subnormal nerve impulses by running the nerve preparations through an accessory chamber containing a 2 percent urethane-Ringer's solution before they passed into the main narcotizing chamber. Minami then employed this technique to show that subnormal nerve impulses are not fundamentally different from other nerve impulses and do indeed obey the all-or-none law.80

Symptomatic of Kato's determination to answer every possible criticism and tie up every loose end was his continued work and that of his staff on decrementless nerve conduction even after the 1924 monograph appeared. Maki Ryokichi had previously studied the sciatic nerve of Bufo vulgaris. But in 1925 Kato had him repeat most of the earlier experiments using the tibialis, abdominalis, and cutaneous dorsi nerves, this time assisted by Otsuka Kunio. In fact, most of the 1924-1925 projects involved two or three investigators working together or in parallel. Uchimura Ryoji and Kajikawa Jin'ichi studied conductivity in and the effects of heating and cooling on sympathetic and vagus nerve fibers. Miura Torao investigated postganglionic

78 Yoshimura, "Kato Gen'ichi," p. 160; and Kato Ei'ichi, "Chichi, haha, shi o kataru: Kitasato Sensei, Chichi, Keio Gijuku" (Discussion of my father, mother, and teacher: Dr. Kitasato, father, and Keio University), Yoshisha Shinfuoni, Nov. 1988, 40(3), p. 106.

79 Kato, "Chichi, haha, shi o kataru," pp. 129, 116, 124, 103, 83, 86. 80 Ibid., p. 61; and Kato, Theory of Decrementless Conduction (cit. n. 64), pp. 36, 49-56.




fibers using the sciatic nerve of the frog. Kajikawa studied preganglionic sympathetic fibers in the toad. And Uchimura used the heart of a rabbit to study vagus nerve fiber conduction.8'

Kato felt that an insufficient understanding of the phenomenon of current spread from a normal nerve segment to one impaired by narcosis was a major reason why many physiologists had believed in decremental conduction. So he saw it as essential to explain current spread fully and demonstrate its precise effects. Miura, Tama- mura Hideaki, and Hayashi Takashi were all assigned to work on the phenomenon and had some success. Using a new technique devised in Kato's laboratory, latent period determination, the three showed that current spread was actually of two types-external (operating on a nerve surface) and internal (operating within the nerve's axis cylinder)-and that the internal type was more important. Hayashi, the senior investigator of the three, organized work on current spread not only in normal nerves but in narcotized nerve segments as well. His study showed that both the extent of current spread and the speed of conduction diminished with narcosis, while the starting point of a nerve impulse moved nearer the stimulating electrode.82

Hayashi was the principal investigator in two other studies crucial to the theory of decrementless conduction. One was the determination of the so-called limit length. While Kato argued that the length of a narcotized nerve segment was irrelevant to the timing of its loss of conduction, Hayashi refined this claim. He found that, below 6 mm, length did matter-because of current spread from the normal segment of nerve. Assisted by Adachi Kimio, Hayashi was also instrumental in clari- fying an important phase of nerve conduction called the relatively refractory period. (A refractory period is a temporary period of reduced responsiveness to stimuli immediately following a response.) Kato was eventually able to show that the all-or- none principle held for this phase of conduction as well. He was concerned enough about this detail that he set two teams of investigators, Hayashi and Adachi, and Nakajima Kenjiro and Nakazawa Tsunesaburo, to study it. Following very different strategies, both teams ultimately met the senior physiologist's expectations and showed that the all-or-none law did indeed apply to the relatively refractory period.83

These investigations of decrementless conduction appeared in a second monograph in early 1926, but the 1924 studies were already making a splash. Late in December that year, four physiologists from the Harvard Medical School reported at the national meeting of the American Physiological Society that they too had reopened the question of decrement in nerve conduction and had found it completely absent in the narcotized peroneal nerve segment of a cat. They called attention to the work of the Kato group, carried out simultaneously, noting that the Keio physiologists had not only provided valuable corroboration for their own efforts but had actually found the "sources of error which had [earlier] led to the inference of [decremental] conduction'" Their more detailed report, which appeared in the American Journal of Physiology a year later, was even more eloquent in praise of Kato. Led by Hallowell Davis, the Harvard authors called the tests performed in Kato's laboratory "ingenious" and said that the Japanese team had shown the "experimental evidence underlying the concept of decrement [to be] unsound." One member of the Harvard

81 Kato, Further Studies on Decrementless Conduction (cit. n. 69), pp. 32, 97-101, 97, 95, 101. 82 Ibid., pp. 60-64, 69-74, 84. 83 Ibid., pp. 50-51, 111-112.




group did something even rarer in science, acknowledging previous error. Davis revealed that he had been a collaborator of Edgar Adrian, whom the Kato team had criticized for adherence to decrement theory. Davis also declared in the American Journal of Physiology article that he now considered many earlier experiments on nerve conduction to be "valueless" and the conclusions drawn from them "unjustified." He made it plain that these evaluations extended to some of the projects he himself had carried out with Adrian.84

Recognition at this level created a favorable context for Kato's trip to Sweden in the spring and summer of 1926. Accompanied by Uchimura Ryoji, Miyake Ryoi- chi, Matsuyama Satoru, and 150 toads to be used for lectures and demonstrations, Kato arrived in Stockholm at the end of April but stayed only long enough to en- sconce the toads in suitable storage facilities at the Karolinska Institute. On 31 May the group returned to the city from a tour around Europe and began preparing for the congress, which began on 2 August. Their preparations included replacing the Japanese toads, which had all died, with a different kind of toad from the Nether- lands. They also involved rehearsals for the lecture and demonstration, as well as interviews with the Stockholm newspapers. Kato attracted substantial press attention and made it clear that this was not his first but, rather, his third visit to Sweden. He clearly saw his visit as career enhancing, relished the attention, and told one reporter to write that Stockholm is "the most beautiful city on earth"!85

Events at the congress seemed to indicate that Kato's strategy of presenting his work outside Japan was going to succeed. His morning lecture in English and after- noon demonstration were presented on the third day of the meetings; he had prac- ticed the lecture several times, so it went smoothly. The demonstration, in which he was assisted by Uchimura, seemed less compelling from his own point of view, but he received many favorable comments and an invitation to speak at the University of Berlin nonetheless. For Kato, however, the highlight of the congress probably came a day later, when he and Edgar Adrian together held forth on the implications of the new research for science's understanding of the all-or-none principle and its importance in explaining nerve conduction. This spontaneous event produced a "long and lively discussion" among the physiologists present and led Stockholm's influential daily, Dagens Nyheter to publish a photograph of Kato with several other scientists in its 5 August edition.86

From this point on Kato's career trajectory moved ever more sharply upward. He and his colleagues returned to a flag-waving reception at Tokyo Station, with Kita- sato present, in September. In October 1926 Physiological Reviews published a

84 Hallowell Davis, Alexander Forbes, David Brunswick, and Ann McHenry Hopkins, "Conduction without Progressive Decrement in Nerve under Alcohol Narcosis," American Journal of Physiology, Mar. 1925, 72(1):177-179; and Davis et al., "Studies of the Nerve Impulse," ibid., Apr. 1926, 76(2):448-471, on pp. 450, 461. Davis's acknowledgment is on p. 450. The text reads as follows on this point: "The present author whose work with Adrian is here referred to, now believes the experiments in question to be valueless because of lack of proper control of current spread, and the conclusion drawn from them unjustified."

85 Yoshimura, "Kato Gen'ichi" (cit. n. 61), p. 160; "Japan-landet dir all vilja bli lakare: Prof. Kato, nervfysiologen fratn Tokio, om sina ron och sitt lands forha'llanden," Svenska Dagbladet, 29 July 1926, p. 1; and "Eliten Av All Virldens Fysiologer Samlad Till Kongress I Stockholm," Social- Demokraten, 3 Aug. 1926, no. 207, p. 1.

86 Yoshimura, "Kato Gen'ichi," pp. 161-162; and "M6dosam Onsdag for Fysiologer och f6rsoks- djur-Efter dagens hundra fdredrag ger Stockholms stad bankett I Gyllene salen," Dagens Nyheter, 5 Aug. 1926, no. 209, p. 1.




lengthy essay, "The Conduction of the Nerve Impulse," that featured Kato's work prominently and criticized Ishikawa for attacking him. The following spring he received the Imperial Academy Prize, despite Ishikawa's efforts to prevent it. And in late October his colleagues Hata Sahachiro and Kitajima Ta'ichi wrote to Stock- holm by invitation and nominated Kato for the Nobel Prize.87 This initial nomination had no immediate effect. Nonetheless, Kato continued to work, continued to attract attention, and gradually made himself a stronger candidate.

In fact, his Nobel candidacy in the mid 1930s depended much more on what he accomplished after returning from Stockholm than on any of his earlier work. Be- tween 1927 and 1929 Kato's associates continued to study muscle contractions in Bufo vulgaris, identified three stages of narcosis and three distinct kinds of contractions, and clarified the exact applicability and limitations of the all-or-none law. In 1927 Miura showed that very strong electrical or mechanical stimuli applied to a narcotized region of the toad's sartorius muscle resulted in what came to be called postnarcotic contractions. Three years later Hashida Kunihiko discovered the phenomenon of localized contraction, the small, limited contractions seen at the group of stimulating electrodes attached to single muscle fibers.88 The kind of contraction that the Kato team had been studying for some years was distinct from postnarcotic and localized contractions because it would conduct nerve and electrical impulses (hence their term for it, "conducted contraction"). To conducted contraction, and to it alone, did the all-or-none law apply.

Hashida's work in particular was made possible because Kamaya Tadashi had managed to isolate a single muscle fiber in December 1929. This was no simple task: the fibers were delicate and fine; the micromanipulator proved useless, and Kamaya succeeded only when he was able to use his own hands instead. Kato also directed several staff members to attempt the isolation of a single fiber from the sciatic nerve of a toad, a task that proved even more difficult. However, in May 1930, having developed a special apparatus for the purpose, Shimizu Tadao isolated a single motor nerve fiber from a sciatic tibialis flexor digitorum preparation. After describing the apparatus in a December 1934 monograph, Kato noted that Shimizu's achievement "required by far [a] finer technique than [did] the isolation of a single muscle fiber." Kato had relatively little to boast about when he traveled to the United States in the summer of 1929, since these important achievements were still in the future. But he was still prominent enough to have his lecture at Johns Hopkins Uni- versity reported in the New York Times. 89 And in August he spent a week in Boston as a delegate to the Thirteenth International Congress of Physiology, hosted by Harvard.

It was his team's isolation of the single muscle and nerve fibers, together with the studies this achievement made possible, that finally raised Kato's reputation to the highest international level. In 1929 he and Ivan Pavlov were both present at the

87 Hallowell Davis, "The Conduction of the Nerve Impulse," Physiological Reviews, Oct. 1926, 6(4):547-595, on p. 552. Davis wrote: "Ishikawa (1924) offers certain criticisms of Kato's work, but it is difficult to follow the logic of his argument or to evaluate his observations from the meager descriptions available." On the Imperial Academy Prize see Yoshimura, "Kato Gen'ichi," p. 162; for the nomination letters see Medic. Nob. Kom. 1928 P. M. Fbrsdndelser och Betdnkanden. Hata Sahachiro's letter is dated 27 Oct. 1927, Kitajima Ta'ichi's 31 Oct. 1927.

88 Gen'ichi Kato, The Microphysiology of Nerve (Tokyo: Maruzen, 1934), pp. 53-54, 47. 89 Ibid., pp. 4-5, 5-6 (quotation); and "Says Nerve Responses Go 3 Miles a Minute: Professor

Kato Holds Superior Brain Is Secret of Ty Cobb's and Bobby Jones's Success," New York Times, 2 July 1929, p. 28.




Boston International Congress, but they probably did not meet. However, in August 1932 Kato attended the Fourteenth International Congress in Rome, where he dem- onstrated the techniques that had made the isolation of the single fibers possible; Pavlov is said to have been deeply impressed. By this time, the availability of single nerve and muscle fibers for close scrutiny and precise experimentation was yielding valuable new information that Kato and his associates were uniquely able to exploit. Between 1930 and 1932 Kamaya, under Kato's direction, showed unequivocally that the all-or-none principle applied without exception to narcotized, asphyxiated, or impaired segments of nerve just as it did to fresh nerves. Ogawa Asayoshi, Ono Kohei, and Tomita Tsuneo used single fibers to show that Joseph Erlanger and E. A. Blair's argument about localized action potential at the seat of stimulation of a nerve when the investigator employed an electrical stimulus also applied when a mechanical stimulus was used.90 And several other Kato associates described and clarified the role in conduction of tiny nerve structures called "nodes of Ranvier."

Prior to the isolation of single muscle and nerve fibers that made their investigation possible, physiologists knew little about these nodes, small breaks in the myelin sheath covering a nerve fiber. Kato thus set Hayashi Yoshio and Shimizu Tadao to measuring them in various animals-toads, frogs, rats, dogs, cats, cattle, and humans. This inquiry showed that the nodes are farther apart in smaller animals than in larger ones and in cold-blooded than in warm-blooded animals. Kubo Moritomi and Ono then showed that a nerve fiber is highly susceptible to electric stimulus at any node of Ranvier; initially they theorized that the nerve axon also had higher excitability at the nodes than elsewhere. Further study proved this speculation false. In fact, the threshold strengths needed to produce muscular contractions were shown to be weakest at the nodes and gradually to increase between one node and another, being strongest at the midway point. Moreover, a reversal of the direction of the current caused a strikingly different threshold strength to be needed. "The nerve is excited with far weaker stimuli when the cathode is placed on the Ranvier node than when the anode is attached to it," Kato wrote.9'

What could explain such peculiar phenomena, especially since the myelin sheath covering a nerve fiber is of almost uniform thickness? Another Kato staff member, Tasaki Iji, offered an explanation. He assumed that the myelin sheath is completely insulating; thus the effect of electric current as regards excitation "is determined by the potential differences between the Ranvier nodes, and a current excites a nerve fiber as it flows through a Ranvier node directing outwards?" Moreover, an electric stimulus "excites the nerve fiber only at the nodes. . . When an electric stimulus is applied to a nerve, the impulse is set up always at the nodes ... regardless of the seat of [the] electrodes."92 On the basis of this explanation, Kato and his associates used their data to work out logarithmic formulas for expressing the nerve current flows.

90 Pavlov's presence in Boston was mentioned in newspaper reports: "Lowell Welcomes Scientists' Group," New York Times, 20 Aug. 1929, p. 3. Regarding Kato's presence see Yoshimura, "Kato Gen'ichi" (cit. n. 61), p. 162. On Kato's attendance at the conference in Rome see Professor Tsukada, Committee Chairman of the Memorial Service for Prof. Kato, "Obituary: Professor Genichi Kato (1890-1979)," Keio Journal of Medicine, 1979,28:5. For the work described see Kato, Microphysiol- ogy of Nerve (cit. n. 88), pp. 29-31, 63-65.

91 Kato, Microphysiology of Nerve, pp. 66-67, 72 (quotation). 92 Ibid., pp. 74-76.




By some standards, the most important accomplishment of Kato's laboratory in the early 1930s was its discovery and explication of reflex inhibitory and reflex excitatory nerves. Following the publication of Sir Charles Sherrington's Reflex Ac- tivity of the Spinal Cord in 1932, Kato came to believe that there had to exist special- ized nerve fibers in the vagus nerve trunk, for otherwise a vital organ like the heart would be overwhelmed and paralyzed by an excess of nerve impulses, as impulses from one nerve were blocked by the refractory periods of other nerves. He set a staff member from China, Ho Wen-yan, and a Japanese associate, Nakamura Jiro, to work on this topic. Using decapitated toads, Ho and Nakamura exposed sciatic nerves and a gastrocnemius muscle, as well as the "entire course of the ipselateral peroneal nerve ... with the tibialis anterior muscle and a piece of skin of the dorsal part of [the] foot attached." They then applied induction shocks or pinches with a pincette as direct stimuli to the muscle, skin, or nearby nerves. Analysis of the findings showed that stimulation of the muscle and skin produced very different effects, suggesting that there must be "two kinds of nerve fibers which control the spinal reflex."93

In 1933 it fell to Sugiyama Ryoji to identify a single inhibitory fiber and to Inoue Sei to isolate a single excitatory fiber. Sugiyama's preparation exposed peroneal nerves, gastrocnemius and tibialis anterior muscle, and a piece of skin from the dorsal part of a toad's foot. Upon isolating a single nerve fiber from part of the peroneal nerve, he examined its function by stimulating the nerve, the muscle, or the skin with various electrodes and determining the effect on the extension reflex. He reasoned that any effects on the existing reflex responses when stimuli were applied at the parts distal to the isolated region must be due to the isolated fiber, since impulses had to have been transmitted through it. He then measured the diameters of the single fibers excised and, after repeating these procedures fifty-seven times, ascertained a distinct relationship between the "sizes of the fibers and their func- tions." Ultimately, the reflex inhibitory fibers were shown to be 9-10 microns, the reflex excitatory fibers 6-7 microns, in diameter.94

Inoue's project followed much the same procedure-but with certain differences. He made a preparation of the ipselateral tibial nerve and the ramus cutaneous tibialis magnus plus a piece of skin from the latter. Before attempting the nerve fiber isolation he made a preliminary test, applying stimuli to the cutaneous nerve or skin with electrodes in order to confirm that these either produced reflex contractions when applied alone to the spinal cord at rest or gave summation (displayed added intensity) when applied during the reflex contraction in the gastrocnemius muscle. When they did so, he isolated single fibers from the cutaneous nerve and applied stimuli of different strengths at certain points to see whether this had any effect on muscles. Excitatory fibers proved to be recognizable not only by their small diameters but also from the reflex contractions they evoked in some hind limb muscles of the toad when the spinal cord was in a state of rest. In due course, Inoue and Kato showed that reflex excitatory fibers originate in the skin, whereas reflex inhibitory fibers originate in the muscles.95

Studies of reflex inhibition in the spinal cord constituted the last major body of

9 Ibid., pp. 84-90. 94Ibid., pp. 107-113. 95Ibid., pp. 111-114.




work reported in Kato's December 1934 monograph. Inspired in part by Sherring- ton's research, Kato and his associates began looking for the location of an inhibitory center in the brain of Bufo vulgaris. He assigned part of this project to Wakai Eijiro, who dissected out the toad's central nervous system and began his investigation by stimulating its contralateral peroneal nerve using a newly designed needle electrode containing a pair of fine insulated copper wires. Wakai examined the effect of stimu- lations to various parts of the brain on the reflex contractions of the gastrocnemius muscle. He determined that stimulating a particular region of the anterior end of the lamina terminalis contralateral "caused remarkable inhibition" and designated it the "inhibitory center." Then he sought to ascertain the location of the inhibitory center for other muscles of the toad. His experiments indicated that "all the muscles are inhibited by stimuli applied at the same spot of the brain, although the extent of inhibition . . . differed according to the muscles." Masuda Ryota investigated muscular inhibition associated with a single motoneuron, showing that such motor nerve cells are connected to many inhibitory as well as excitatory fibers. Finally, other staff members' research revealed that a localized stimulus to different points of the spinal cord will produce either a reflex inhibition or a summation, depending on the influence of an inhibitory or an excitatory nerve path.96

Events relating to Kato's Nobel candidacy unfolded with remarkable speed following the official publication of The Microphysiology of Nerve on 17 December 1934. Although Kitasato had died in June 1931, his longtime colleague and biogra- pher, Miyajima Mikinosuke, was still an active member of the Keio faculty and had received an official Nobel request to nominate a few weeks earlier. Miyajima and twenty-three other Keio faculty members each proceeded to write identically worded letters of nomination for Kato on the very date of the book's publication. The Keio professors wrote in English, mentioning the isolation of single muscle and nerve fibers, together with the discovery of reflex inhibitory and excitatory nerves, as the primary reasons to recognize Kato. About a month later, in a French-language communication dated 25 January 1935, Ivan Pavlov made essentially the same argument. Nearly two years passed before Mariano Rafael Castex of the University of Buenos Aires also wrote to nominate Kato. His brief letter of 12 December 1936, written in French, merely referred to Kato's "beautiful researches in microphysiology" as a reason to award him a Nobel Prize and almost certainly arrived too late to influence events in Stockholm.97

Others were determined to do what they could in the interim. Shortly before the publication of Kato's 1934 monograph, Miyajima made arrangements to meet with Togo Shigenori, chief of the Bureau of European and Asian Affairs in the Japanese foreign ministry-and later minister of foreign affairs-to discuss his plan to nominate Kato. Miyajima had clearly become aware that Pavlov was going to nominate two Japanese physiologists for the Nobel Prize, the other candidate being Kure Ken, a member of the Faculty of Medicine at Tokyo University and, like Kato, a nerve

96 Ibid., pp. 123-127, 130; quotation from p. 127. See also Hans Gertz, "Betdnkande angfiende Genichi Kato," 23 Aug. 1935, in Medic. Nob. Kom. 1935 P. M. FRrsindelser och Betdnkanden, pp. 1-7, on p. 6.

97 Medic. Nob. Kom. 1935 P M. Fbrsindelser och Betdnkanden, pp. 30, 53-54. The only letter actually included in the archival materials is one signed by M. Karasawa, dated 17 Dec. 1934. How- ever, the actual nomination request had gone to Miyajima. This letter can be found in the archives of the Ministry of Foreign Affairs in Tokyo.




physiologist. Kure's work was not closely related to Kato's, and his candidacy cannot be treated extensively here. He had been a favorite of medical colleagues at Japan's four oldest imperial universities (Tokyo, Kyoto, Tohoku, and Kyushu) and had been proposed to Stockholm on two previous occasions, beginning in 1930. Pavlov was innocent of any knowledge of Japanese medical politics, and in his letter of nomination he incorrectly situated both Kato and Kure at Tokyo University.98

Judging from official documents in the archives of the Ministry of Foreign Affairs, Miyajima felt that the Kure candidacy was prejudicial to Kato's prospects unless some kind of agreement could be reached between Keio and Tokyo. He managed to persuade Togo to "mediate between the two candidacies." The desired outcome of this mediation was never spelled out; but it seems that Miyajima and Togo were hoping to obtain unanimous support from the two medical faculties for both Kato and Kure. It was not to be. Shortly after Togo met with various professors, his office sent a remarkable letter to Shiratori Toshio, Japan's minister to Sweden. The letter informed Shiratori that the mediation had been unsuccessful and that the two universities "would proceed with the aforementioned candidacies independently." It also explained why this result was especially unfortunate. "We have been informed by a member of the Nobel committee for medicine and physiology that [over the years] quite a few candidates have been nominated from the Japanese medical science community, but that he considered this [occasion] an exceedingly good opportunity for someone from Japan to receive the prize." The foreign ministry then asked Shiratori to see what could be done but conceded, "In the face of this [factional] situation it may be difficult for you to do anything." Closing with a rueful comment about "never seeing any meeting of the minds in the Japanese medical science community," the letter nonetheless urged Shiratori to "give us any advice . . . as to whether there is any possibility that a scientist from Japan could be selected."99

This letter raises intriguing questions, not all of them answerable at present. Did Shiratori actually approach any officials of the Nobel Foundation to lobby for Kato-or for Kure? Could he have been the conduit of a communication from a Swedish member of the Nobel committee? Certainly a lobbying initiative of this kind would have been fully in character for him; historians have rightly considered Shiratori an "atypical diplomat." And Joseph Grew, the U.S. ambassador in Japan during the 1930s who knew him well, noted in his memoirs that Shiratori always inclined toward actions that would enhance Japan's prestige and that he could not be intimidated by his superiors. 100 It is almost certain, moreover, that a Nobel committee member did tell someone from Japan-Shiratori, Togo, or Miyajima-about the numbers of earlier Japanese candidates. Prior to the opening of the Nobel archives

98 Kure was nominated in late Dec. 1930 by Itagaki Masami (Kyushu University) and again in Dec. 1932 by Kimura Onari and Nasu Seizaburo, both of Tohoku University. See Medic. Nob. Kom. 1931 P. M. Fiirsdndelser och Betiinkanden, p. 26; and Medic. Nob. Kom. 1933 P. M. Fiirsdndelser och Betiinkanden, p. 41. On Pavlov's nomination letter see Medic. Nob. Kom. 1935 P M. Forsindel- ser och Betinkanden, p. 30.

99 For these documents see "'NMberu' heiwa sh6kin kankei ikken," in Gaimusho Kiroku S5- Mokuroku, ed. Gaimush6 Gaik6 Shiryokan, Vol. 2 (Tokyo: Hara Shobb, 1992). Despite the title, which suggests an item relating to the Nobel Peace Prize, these documents have nothing to do with the peace prize but, rather, concern the Nobel Prize in Physiology or Medicine.

100 Tobe Ryoichi, "Gaik6 ni okeru 'shisoteki riky6' no shinkyt: Shiratori Toshio no kod6 gaik6 ron" (Intellectual divorce in diplomacy: On the diplomatic posture of Shiratori Toshio), in Nihon Gaikd no Shis6 (Intellectual history of Japanese diplomacy), Aug. 1982, 71:124-140; and Joseph C. Grew, Ten Years in Japan (New York: Simon & Schuster, 1944), pp. 34, 64-65.




in 1974, only committee members had access to them. So unless a member disclosed such information it could not have become known.

Nobel committees always maintain strict confidentiality, and certainly Kato and his supporters were completely unaware of developments at the time. In the winter of 1935 Kato received an official letter from Moscow inviting him to attend the Fifteenth International Congress of Physiology, to be held in the Soviet Union, as an official state guest. Pavlov, with his imposing official connections, was behind this initiative. Though Pavlov died at about the time of the congress, Kato's presentation was deemed a great success; his return to Tokyo in the late spring of 1936 was greeted by posters in department store windows that hailed a "Keio University Doc- tor of Science in Medicine who might be given the Nobel Prize." The same posters proclaimed a "great welcome for a Japanese triumph!" 101 In actual fact, Kato's candidacy had by this point run its course and was not to be revived.

Archival records show that the crucial event occurred in August 1935, when Hans Gertz of the Karolinska Institute faculty submitted a report on Kato's accomplishments. A longtime professor of physiology at the University of Lund, Gertz had come to the Karolinska in 1928 and was serving in 1935 as a member of the prize committee. Nerve physiology was a specialty for him. His report of 23 August 1935 was thorough, precise, detailed, and appreciative-but also ambivalent. He recalled Kato's 1928 candidacy, observing that the decrementless nerve conduction studies had served as its basis. Indicating familiarity with that work, he said he had not deemed it prizeworthy at the time. Thus, his 1935 evaluation was to be based entirely on the 1934 monograph and a few of Kato's articles, though in actual practice he ignored the latter. Most of his text summarized the book. Gertz paid particular attention to the work on the nodes of Ranvier, the claims about the reflex inhibitory and excitatory fibers, and the study of reflexes pertaining to the spinal cord. He said that Kato's inquiries into the nerve transmission system "constituted a substantial body of strongly plausible arguments for the existence of the nerve structures described [by the author]."'02

However, what he found most crucial was the same thing that had captivated Pav- lov and many others: Kato's isolation of individual muscle and nerve fibers and the methodological contributions these accomplishments made to nerve physiology in general. "It will be evident," Gertz wrote, "that the purely methodological achievement of experimentally isolating a nerve and muscle fiber when both are in functioning contact, can ... be considered a prizeworthy discovery as such. It should be acknowledged that this achievement is both beautiful and important." But having conceded this much, the Swedish physiologist went on to argue that while isolating a functioning nerve element was "something recent," as a practical matter it had been done "several times before." In support of this claim he referred to the fact that Edgar Adrian and another physiologist had isolated "impulses from detached muscle receptors" and that Kato himself had acknowledged precursors-one of them Adrian, a point that Gertz stressed. As for the "harvest of results which a systematic

'?' Yoshimura, "Kato Gen'ichi" (cit. n. 61), p. 162. A copy of the poster is reproduced in this source. 102 Gertz, "Betankande angaende Genichi Kato" (cit. n. 96), p. 7. On Gertz see Gdran Liljestrand,

ed., Karolinska Mediko-Kirugiska Institutets Historia, 1910-1960, Vol. 2 (Stockholm/Gbteborg/ Uppsala: Almqvist & Wiksell, 1960), p. 110.




application of the method [had] produced," he felt that they needed "more detailed confirmation"-despite his own belief that the findings were "strongly plausible." 103

On the basis of the available archival sources and other material, it is impossible to say how close Kato may have come to receiving a Nobel Prize. The claim in the Japanese foreign ministry archives that a Swedish committee member talked to someone from Japan about the prospect of a Japanese Nobel recipient for 1935 is both striking and believable, not only because of what is known about Nobel procedures but also because of the Fibiger-Yamagiwa fiasco a few years before. It was obvious to knowledgeable authorities by 1935 that Yamagiwa and not Fibiger should have received the prize in 1927, and we can surmise that in the wake of this injustice the 1935 Nobel committees were particularly sensitive to strong Japanese candidates. Though he never explicitly mentioned Adrian's 1932 Nobel (shared with Sher- rington) in discussing Kato, Gertz's references to the Cambridge physiologist are also suggestive. Even if Adrian and Kato were never strictly in competition-a highly likely surmise-their work could be seen as closely enough related that an award to one precluded a later award to the other. Kato certainly respected Adrian and his mentor Keith Lucas, despite their commitment to decrement theory. He used such terms as "careful," "ingenious," and the like in describing their experiments. Kato was also deeply aware of the advantages of spending time and being well known in Stockholm. But Adrian had already bested him in this "race": he had a substantial working relationship with scientists from the Karolinska several years prior to receiving his Nobel, a political and scientific opportunity that would certainly have counted for more than Kato's brief visits.'04

One is left with the general impression that Japan in the mid 1930s was still too far from the European centers of science and had a research community too internally divided to win a Nobel Prize, at least in medicine. The strategy of having the entire Keio medical faculty write two dozen identically worded letters would not have made the best impression. Nor would any initiative by Japanese officials. I cannot say whether Ambassador Shiratori attempted to lobby anyone in Stockholm, even if some foreign ministry officials back in Tokyo thought he should. A lobbying effort would have been fully in character for Shiratori. It would also have made a terrible impression and would surely have had results exactly contrary to those desired. Kato himself probably did everything that could have been done. He was a resourceful, intelligent scientist of enormous energy and dedication, typical in many ways of the most successful medical research scientists of the present day. But none of this was enough to win him a Nobel Prize.

GENERAL REFLECTIONS

Nobel Prizes, to say the least, are not easy to win. One must first do something important. One must also be nominated and then hope the contribution is not considered premature, unbelievable, or wholly outside informed consensus about how nature works. Prizes have sometimes been awarded to scientists whose findings were

103 Gertz, "Betiinkande angatende Genichi Kato," pp. 6-7, 7. 10 Ronald E. De Meersman, "Edgar Douglas Adrian," in Nobel Prize Winners, ed. Magill, Physiol-

ogy or Medicine (cit. n. 19), Vol. 1, pp. 351-355, on p. 353.




at first seen as improbable or even bizarre; an example is Francis Peyton Rous's 1966 award for showing in 1911 that a virus can cause sarcoma in chickens. But even if one's achievements are considered believable and important, there are no assurances of a forthcoming prize. Sir Charles Sherrington made contributions in nerve physiology that met both criteria. But he was nominated 132 times by scientists from thirteen countries before he shared the 1932 award with Edgar Adrian at the age of seventy-five. And Ernst Ruska was eighty in 1986, when he finally received part of the prize in physics for contributions to the development of the electron microscope made in the early 1930s.'05 Longevity is generally acknowledged as increasing one's prospects for a Nobel award!

Scientists also recognize a category of eminent colleagues called "occupants of the forty-first chair." This phrase alludes to the maximum number of forty who can belong to the French Academy of Letters at any one time; in the natural sciences, it designates people widely but incorrectly believed to have won a Nobel Prize or those seen as deserving to have won. On occasion, Nobel authorities have even mentioned names of particular scientists who did something prizeworthy but never won. The list has usually included Oswald Avery, who discovered that DNA is the carrier of heredity; Josiah Willard Gibbs, a leading mathematical physicist early in this century; and Dmitri Mendeleev, author of the periodic table. Some would cite others: Rosalind Franklin for her role in elucidating the structure of DNA, or Freeman Dy- son for his contributions to quantum electrodynamics (QED).106 Dyson's case is notable because the 1965 physics prize was awarded to three physicists for their work in QED, Tomonaga from Japan among them. Three is the maximum number to share a single prize, and Tomonaga's inclusion (with Richard Feynman and Julian Schwinger) is almost certainly the only time in the history of the Nobel awards when an American or an Englishman lost out to a Japanese.

One could scarcely imagine a case of this kind in the years before World War II. Japanese scientists were not wholly isolated from science's European and American centers: Kitasato and Kato traveled extensively and were reasonably well known to foreign colleagues, and even Yamagiwa, too unwell to travel, had important overseas visitors. But by doing their work in an "out-of-the-way" country, they missed the opportunity for frequent interactions with people who controlled the nominations. This conclusion emerges clearly when their candidacies are compared with that of the period's best-known Japanese scientist, Noguchi Hideyo (1872-1928). Noguchi was once believed to have found the causative organisms of yellow fever and a number of other diseases. But many of his claims were discounted even while he was still living, and only his discovery of the spirochete of paresis is still universally acknowledged. Nonetheless, he had the considerable advantage of working as a

105 Harriet Zuckerman, Scientific Elite: Nobel Laureates in the United States (New York: Free Press, 1977), pp. 47 (Rous), 40 (Sherrington); and Byron D. Cannon, "Ernst Ruska$" in The Nobel Prize Winners, ed. Frank N. Magill, Physics, Vol. 3 (Pasadena, Calif./Englewood Cliffs, N.J.: Salem, 1989), pp. 1315-1321.

106 On the names listed by Nobel authorities see Zuckerman, Scientific Elite, pp. 42-44. The historian of science Donald Fleming once described the absence of Gibbs and Mendeleev from the roster of Nobel laureates as "unpardonable": Fleming, "Nobel's Hits And Errors," Atlantic, Oct. 1966, 218:53-59, on p. 57. On Mendeleev see Stephen Brush, "The Reception of Mendeleev's Periodic Law in America and Britain," Isis, 1996, 87:595-628. On others see Anne Sayre, Rosalind Franklin and DNA (New York: Norton, 1975), p. 24; and Silvan S. Schweber, QED and the Men Who Made It: Dyson, Feynman, Schwinger, and Tomonaga (Princeton, N.J.: Princeton Univ. Press, 1994), p. 575.




research associate of the Rockefeller Institute. The Nobel archives show that he received eighteen nominations on nine occasions from fifteen colleagues in seven different countries. In New York he became acquainted with many influential people, including the Nobel laureate Alexis Carrel, who submitted his name four times.'07 Nomination, of course, could not assure a prize-and in Noguchi's case it did not. But it was a necessary condition, and New York was a better venue than Tokyo for anyone with Nobel hopes.

Japan clearly was, so to say, "off the beaten track" in science before World War II. Travel to and from the country was time consuming and difficult by the standards of the postwar era. Only one significant international scientific meeting was held there in this period, the Pan-Pacific Science Congress of 1924. And only a modest number of distinguished scientists came to Japan in those years, though the list includes Albert Einstein (1922), Werner Heisenberg (1929), Paul Dirac (1929), and Niels Bohr (1937), besides several others mentioned earlier.'08 There was a lack of political sophistication among some of the Japanese who participated in the nomination process. Idiosyncratic factors like Yamagiwa's health and perhaps clumsy lobbying by agents of the Ministry of Foreign Affairs may also have had an effect. And few, if any, Japanese scientists had an opportunity to become personally well known in Sweden.

To what extent, if at all, did the form of the nominations matter? Nobel authorities of this period have said that the number and quality of nomination letters are incon- sequential and have never made a difference to anyone's chances. But would this have been true of Japanese candidates? Most were probably unknown to prize committee members and sometimes lacked supporters who were well known themselves. On the other hand, Yamagiwa came close to winning a prize without knowing anyone in Stockholm, without the support of any Nobel laureate behind him, and without being able to travel. Had he gone to Europe, as Ichikawa did, and defended his work face to face, the 1927 outcome might well have been different. Fibiger won, in part, because his supporters, heavily Scandinavian, were numerous, vigorous, aggressive-and partisan. Yamagiwa lost, in part, because his Tokyo colleagues were modest, quiet, and unassuming. He also had no support from the "Kitasato faction," just as Kato had none from the Tokyo professors. This might not have mattered in a major center of science-Germany, perhaps, or Britain; but the Japanese needed to mobilize all their assets, and an inability to do so was harmful.

That Kitasato faced particular obstacles is obvious in retrospect. To begin with, 1901 was the very first year of the prizes; the procedures were new, and perhaps background investigations of candidates were less thorough than they later became. Behring's achievements seemed so well known and his work so widely acclaimed

107 Isabel Plesset, Noguchi and His Patrons (Rutherford, N.J.: Fairleigh Dickinson Univ. Press, 1980), pp. 130, 187, 271-272. Noguchi was nominated in 1913, 1914, 1915, 1920, 1921, 1922, 1924, 1925, and 1926. His supporters included four scientists from Japan, three from the United States, two each from France, Spain, and Germany, one from Russia, and one from Australia. Carrel nominated Noguchi in 1915, 1920, 1922, and 1926. See Medic. Nob. Kom. P M. Forsdndelser och Betdn- kanden for the appropriate years.

108 For photographs of the visits by Dirac and Heisenberg (who came together) and by Bohr see Tamaki Hidehiko and Egawa Hiroshi, Nishina Yoshio (Tokyo: Misuzu Sh6b6, 1991). Einstein's visit has been treated extensively in Kaneko Tsutomu, Einstein Shokku, 2 vols. (Tokyo: Kawade Shob6 Shinsha, 1991). Regarding Koch's visit see Miyajima, Kitasato Shibasaburo den (cit. n. 13); this book includes a photograph of Koch dressed in a Japanese kimono.




as to vitiate most reasoned objections. Moreover, he clearly benefited from the affinities of many Swedish academics for Germany and its academic culture. Several years ago Elisabeth Crawford showed how determined Swedish academics were to preserve Germany's role in international science after World War I, when the former Allied powers were seeking to curtail or reduce German influence. The Nobel committees for physics and chemistry went well out of their way, in the face of foreign criticism, to recognize German achievements with Nobel Prizes that some considered, at the very least, ill-timed. 109 Moreover, Swedish is a Germanic language; and Sweden's academic traditions have much in common with those of Germany. Ex- cluding the possibility of personal connections at present unknown, how else can one explain Almquist's uncritical reading of the scientific evidence in 1901, his views as to what Behring did or did not do and the substantive nature of his scientific work?

Yet neither the difficulties of winning in general, the remoteness of Japan, the forms of Japanese nomination letters, Japanese factionalism, nor even Swedish cultural proclivities seem quite adequate as a general explanation for the failure of Japanese candidates in the first half of this century. A more fundamental point would seem to be that before Yukawa, all of Japan's strongest Nobel candidates were competing in medicine. But medicine was surely the most competitive of the three science categories-and probably remains so today. The worldwide volume of significant medical research and accomplishment is surely greater than that in physics or even chemistry, a reality that has made it difficult for Nobel committees to reach a measured consensus. Should they favor cancer studies over surgical breakthroughs, biochemistry over nerve physiology? For what reasons? There are usually too many excellent choices. Moreover, political factors of the sort I have mentioned must be taken into account. Medicine is the only scientific field in which significant errors of judgment have ever reasonably been charged against a Nobel committee (aside from the Fibiger case, the committee erred in 1923 by recognizing J. J. R. Macleod as a codiscoverer of insulin, when in fact he did very little).'10 In the highly competitive world of medicine, it seems to have been especially difficult for those from "outlying" countries (outside Europe or the United States) to prevail in Stockholm. Bernardo Houssay of Argentina was the first, in 1947. And the only Japanese is Tonegawa Susumu-for work done mostly in Switzerland.

EPILOGUE

Yukawa Hideki finally proved that it was possible for a Japanese scientist to win a Nobel Prize when the Royal Swedish Academy of Sciences announced his award for physics on 3 November 1949. In the fall of 1934 Yukawa had proposed a new theory of nuclear forces that postulated "a new sort of quantum" intermediate in mass between an electron and a proton. The particle was eventually termed the meson. Yukawa noted that mesons would not be emitted in ordinary nuclear transforma- tions but suggested that they could materialize in nuclear processes like those occurring in cosmic ray interactions. The theory had a complicated reception over the

109 Elisabeth Crawford, Nationalism and Internationalism in Science, 1880-1939 (Cambridge: Cambridge Univ. Press, 1992), pp. 67, 74, passim.

110 Becky Johnson, "John J. R. Macleod," in Nobel Prize Winners, ed. Magill, Physiology or Medi- cine (cit. n. 19), Vol. 1, pp. 246-248. See also Fleming, "Nobel's Hits and Errors" (cit. n. 106), p 56.




next fifteen years. It was completely ignored for the first two years following its publication in January 1935. Then it was actively debated following an important discovery in 1937 by Carl Anderson and Seth Neddermeyer. Using a Wilson cloud chamber, the two Cal Tech experimentalists found a particle that appeared to fit the general description of the one predicted by Yukawa. This was enough to make Yu- kawa famous and to secure him an invitation to the aborted 1939 Solvay conference. But subsequent investigations revealed that Anderson and Neddermeyer's mu-meson (or muon) did not, after all, conform to Yukawa's particle, and interest in his theory waned.'11

New technology developed by physicists in Britain finally provided vindication. Between 1939 and 1945, Cecil Frank Powell of the University of Bristol perfected the photographic emulsion method for recording the tracks of particles found in cosmic radiation. In 1947 he and Guiseppe Occhialini, employing the new technology, identified a particle, which they called the pi-meson, or pion, that exactly matched the predicted features of the Yukawa meson. Their investigation showed that bringing the slightly heavier pions to rest in the emulsions caused the ejection of muons. In effect, muons were the decay product of Yukawa's pi-meson. The pions had been all but undetectable by older methods for tracking particles because of their short lifetimes and propensity to decay in flight.112 Powell's triumph set the stage for two Nobel Prizes: Yukawa received the first, in 1949, and Powell himself the next, in 1950.

The pattern of Yukawa's Nobel nominations conformed in notable degree to the general sequence of events just described. Nagaoka Hantaro, a Tokyo University physicist, was the first to recommend Yukawa's work; this was not surprising, since he had been an informal mentor to Yukawa, though never one of his teachers. Na- gaoka had been invited to nominate far more often than anyone else in Japan, serving in 1914, 1930, 1932, 1934, 1936, and 1938. He had never suggested a Japanese candidate; but on 15 December 1939 he wrote to propose one of his own countrymen for the Nobel Prize, for the first time and "with full confidence." Five weeks later, Dirk Coster of Groningen University in the Netherlands became the first European scientist to nominate Yukawa, in a Swedish-language letter dated 22 January 1940. On 12 November Matsumoto Toru of Kyoto University also wrote in support of Yukawa.113 Yukawa was not proposed in 1941 or 1942; few others were either, because of the war. No prizes were awarded in those years or the next.

However, the Nobel Foundation deemed it essential to restore the prizes, most of which were awarded in 1944 and thereafter. On 23 January 1943 Louis de Broglie, the 1929 laureate in physics, wrote to nominate Yukawa. He proposed Yukawa again

I Hideki Yukawa, "On the Interaction of Elementary Particles, I," Proceedings of the Physical- Mathematical Society of Japan, 1953, 17:49-58, on p. 49. The text of this paper has also been reproduced in Yukawa's long autobiographical essay, "Tabibito," the Traveler, trans. Laurie Brown and R. Yoshida (Singapore: World Scientific Publishing, 1982), pp. 209-218, on p. 210. See also Brown, "Yukawa's Prediction of the Meson," Centaurus, 1981, 25(1-2), pp. 71, 72, 73; and M. F Soto, "Hi- deki Yukawa," in Nobel Prize Winners, ed. Magill, Physics (cit. n. 105), Vol. 2, pp. 563-569, on p. 568. On Anderson and Neddermeyer's findings see Bulent I. Atalay, "Carl David Anderson," ibid., Vol. 1, pp. 439-447, on pp. 443-444.

112 Atalay, "Carl David Anderson," p. 444; and Genevieve Slomski, "Cecil Frank Powell' in Nobel Prize Winners, ed. Magill, Physics, Vol. 2, pp. 573-578, on p. 577.

113 Letter from Nagaoka Hantaro, 15 Dec. 1939, Vetenskapsakademien Protokoll 1940 ANG. Nobeldrenden, Sec. 5, p. 52.




in the following year (11 January 1944). Later the same year (2 November) Maurice de Broglie, the laureate's older brother, also recommended Yukawa, as did another French scientist, Jean Thibaud of the University of Lyon (15 December). In the early postwar era, Yukawa's candidacy attracted the support of Gregor Wentzel of Zurich (1 January 1946).114 But then the nominations stopped; there were no moves to recognize Yukawa in 1947. This should not be surprising, since Anderson and Nedder- meyer's muon had never conformed entirely to the characteristics of his postulated particle, and experiments reported that year by three Italian physicists did further short-term damage. Nobel committee authorities had already expressed caution. In concluding a lengthy report on Yukawa, Ivar Waller, professor of physics at the Uni- versity of Uppsala, wrote on 19 June 1945: "It does not seem to me that any certain judgment about the significance of Yukawa's prediction of the meson can be given at present." 115

Complete access to all archival materials relating to Yukawa is still some months away; but the public record already shows that the discovery of the pi-meson by Powell and Occhialini produced a strong consensus that the Japanese physicist deserved a Nobel. And there may well have been in 1948 or 1949 a flood of nominations from previously skeptical colleagues for whom the case was now fully convincing. One case study does not sustain a general argument, but the contrast with medicine is still suggestive. Yukawa had the considerable advantage of working in physics, where intellectual consensus was not only possible, but even quite likely. Kitasato, Yamagiwa, and Kato made disparate contributions to a very broad field, competing with many others, some of them equally deserving. It has ever been so with the Nobel Prizes.

114 Letter from Louis de Broglie, 23 Jan. 1943, in Vetenskapsakademien Protokoll 1943 ANG. No- beldrenden, p. 32; letter from Louis de Broglie, 11 Jan. 1944, in Vetenskapsakademien Protokoll 1944 ANG. Nobeldrenden, p. 22; letter from Maurice de Broglie, 2 Nov. 1944, in Vetenskapsakade- mien Protokoll 1946 ANG. Nobeldrenden, p. 29; letter from Jean Thibaud, 15 Dec. 1944, ibid., pp. 68-69; and letter from Gregor Wentzel, 1 Jan. 1946, in Vetenskapsakademien Protokoll 1946 ANG. Nobelarenden, pp. 45-46.

115 Ivar Waller, "Kompletterande utredning anghende H. Yukawa," in Vetenskapsakademien Proto- koll 1945 ANG. Nobeldrenden, p. 39. On the problems Yukawa's theory confronted ca. 1947 see Arthur Strong Wightman, "Particles, Elementary," in Encyclopedia Britannica (Chicago: William Benton, 1972), Vol. 17, p. 416. Wightman notes that the experiment of Marcello Conversi, Ettore Pancini, and Oreste Piccioni on meson absoption was an "apparently stunning blow to the Yukawa theory of mesons."



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Bartholomew - Japanese Nobel Candidates in the First Half of the Twentieth Century

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