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

Japanese Nobel Candidates in the First Half of the Twentieth Century Author(s): James R.
Bartholomew Reviewed work(s): Source: Osiris, 2nd Series, Vol. 13, Beyond Joseph Needham: Science, Technology, and Medicine in East and Southeast Asia (1998), pp. 238-284 Published by: The University of Chicago Press on behalf of The History of Science Society Stable URL: http://www.jstor.org/stable/301885 . Accessed: 17/01/2013 09:56
Your use of the JSTOR archive indicates your acceptance of the Terms & Conditions of Use, available at . http://www.jstor.org/page/info/about/policies/terms.jsp
.
JSTOR is a not-for-profit service that helps scholars, researchers, and students discover, use, and build upon a wide range of content in a trusted digital archive. We use information technology and tools to increase productivity and facilitate new forms of scholarship. For more information about JSTOR, please contact support@jstor.org.
The University of Chicago Press and The History of Science Society are collaborating with JSTOR to digitize, preserve and extend access to Osiris.
http://www.jstor.org
This content downloaded on Thu, 17 Jan 2013 09:56:14 AM All use subject to JSTOR Terms and Conditions
Japanese Nobel Candidates in the HalfoftheTwentieth First Century

ByJamesR. Bartholomew*
IFTY YEARS HAVE PASSED since YukawaHideki in 1949became thefirst scientist towina NobelPrize(inphysics, Japanese for hismeson particle theinthe ory); meantime, hehasbeen joinedbyfour other Japanese laureates inscience and medicine. TomonagaShin'ichiro wonin physics (1965), as did Esaki Reona (1973). Fukui Ken'ichi received theprizein chemistry (1981), whileTonegawa Susumu became thefirst Japanese recipient inphysiology ormedicine (1987).(Only Tonegawa andYukawa received unshared awards.) Though Japan is oneofjusteight tohavewonNobelsin every nations category ofnatural science, many believe that five prizes is a modest harvest for so large andwealthy a country. Butis this assumption correct? Itcertainly would be ifNobelawards were only a function ofimportant contributions In fact, toscience. they reflect a great many things: thenature ofeduinparticular cation places, personal connections among scientists, thefinancial priorities ofgovernment andprivate business, andsuch"cultural" variables as individual skills at self-presentation. A continuing focuson thehistory of science in established centers likeBritain, and theUnited Statestends to obscure someofthesefactors in Germany, France, scientific successbecausemodem is quiteobviously ofWestern science a product of sciencein Western and many assumethat thefeatures culture, Europeand the States havebeenreplicated with theNobel United everywhere. Japan's experience ofthispoint of viewbecause, Prizesis a goodtest recent despite problems, Japan inreproducing forms successful other cultural andeconomic hasbeenspectacularly ornot, with in thelastfewcenturies. Butsuccessful associated theriseoftheWest thefundamental of whether, or to whatdegree, was there remains question Japan ofthetwentieth ofscience thefirst half into theworld fully integrated system during
*Department Ohio 43210. ofHistory, Ohio StateUniversity, Columbus, I wouldliketothank who twodozenscholars, andlibrarians theover graduate students, archivists, ofSciences Atthe ofthis research. meduring the course assisted generously RoyalSwedish Academy Institute at theKarolinska Nils Tore Frangsmyr and JuliaLindqvist; (Stockholm), (Stockholm), of Sciences(Budaat theHungarian and Gudrun Ringertz, Margaretha Petrini, Franzen; Academy at Kitasato Museum(Budapest), Laszlo Magyar; pest),Eva Apor;at theSemmelweis University Takehiko Hashimoto atTokyo Kato Ei'ichiandKuramotoHiroyuki; (Tokyo), University (Tokyo), ofCinElisabeth at theUniversity at theCNRS (Strasbourg), andMatsumuraYoshiaki; Crawford; Mariann at theUniversity ofMinnesota, ThomasSakmyster; cinnati, Tiblin;at Harvard University, Maureen Suzy Conway;and at Ohio StateUniversity (Columbus), Marilyn Blackwell, Donovan, Alice Risko,Carole Rogel,Leila Rupp,Birgitta Jeffrey Lewis, EdwardRiedinger, Soland,Mark aremine. VanBrimmer. Spicka,andBarbara Anyerrors All rights reserved. ?) 1999byThe History ofScienceSociety. 0369-7827/98/1301-0011$02.00 Osiris,1998,13:238-284 238
JAPANESENOBEL CANDIDATES
239
theeraofjet airplanes, advanced century, before telecommunipersonal computers, use ofEnglish. andtheseemingly cations, ubiquitous matter becausetheNobelPrizeshavecometobe intimately Thesequestions reForbetter or worse, and evenpower. latedto matters of prestige, the nationalism, thegovernment, themassmedia, andtheeduscientific community, theuniversities, all follow theprizes'annual catedpublicof Japan (like counterparts elsewhere) withsignificant announcement withgreatinterest and drawconclusions conseon theJapanese Yukawa's quences. 1949prizeconferred research major advantages community intheoretical when physics, evenata time was scarce. Tomonamoney for AndthelateFukui Ken'ga's 1965award additional resources brought physics. ichi's1981prizein chemistry in a $30 million resulted foran entirely private gift newinstitute.' Prior tohisdeath inJanuary wasinvolved with theother 1998,Fukui living Japanese Nobellaureates whowonin (Esaki,Tonegawa, andOe Kenzaburo, in a well-supported, literature) formal to attract program designed publicattention to theNobelPrizes.Knownas the"Japan Forum ofNobelPrizeRecipients," this project annually brings foreign Nobellaureates to Japan forpubliclectures, while ownNobelists in a series Japan's ofspecialprograms participate aimedprimarily at young people.The forum's sponsors havemadeit clearthat thepurpose of their initiative is topublicize theprizes, toimprove theclimate for creative research, and to enhance Japan's cultural andscientific prestige.2 hereis to explore theissueofJapan's My purpose with integration international science during thefirst half ofthecentury as a keytounderstanding itsrecord inthe Nobelcompetitions. I focus onthis period becausethe Nobelarchives follow a fiftyruleofaccess,andarchival year materials areessential tounderstanding howparticularcandidates fared and why. The Nobel Prizeshavealways beeninfluenced by many factors; important contributions to science(in thiscase), however essential, arejustone.It is clearfrom donesincetheNobelarchives studies wereopenedin 1974that candidates' connections with other scientists andhowcandidacies were presented andbywhom has affected theresults in particular cases.To wina Nobel onemust Prize, first be nominated-and thenomination system itself hasprivileged candidates from certain countries (notonlyScandinavia) while tending tohandicap others. Theinvitation enjoyed byNobellaureates tosubmit nominations atanytime is onereason for this imbalance.3 How,then, havetheJapanese fared? How and whydid their record evolveas it did?Although thefifty-year rule precludes anarchivally basedexamination ofrecent
' Fordetails on theboostYukawa's award brought to physics see Hara Genkichi, Kagakukenkyt hi: sono naritachi to hensen (The scienceresearch grants: Theirorigin and evolution) Ka(Tokyo: gakuShimbun Sha, 1982),pp. 114-115. Tomonaga appealed for increased expenditures for scientific research almostimmediately after his Nobel Prize was announced. While some enhancement of research funding wouldprobably haveoccurred in anycase, one can safely assumethat his prize forwarded thecause. See James Bartholomew, TheFormation ofSciencein Japan:Building a ResearchTradition (New Haven, Conn./London: Yale Univ. Press,1989),pp.279,354-355.On the$30 million gift see Matsuo Hiroshi, unpublished MS, 1995.Thefunds for theInstitute for Fundamental Chemistry, directed byFukui, wereprovided bytheKao Soap Company. 2 See, e.g.,Noberu shdjushoshao konomufuoramu nijuisseiki e no kdzd(Toward thetwenty-first A forum century: honoring Nobel laureates) (Tokyo: Yomiuri Shimbun Sha, 1993). The forum has beenheldevery yearbutone since1987. 3 For a discussion ofthenominating system see Elisabeth Crawford, TheBeginnings oftheNobel Institution: TheSciencePrizes, 1901-1915(Cambridge: Cambridge Univ.Press,1984).
240
JAMES R. BARTHOLOMEW
I in this fashion. canbe studied ofthecentury half thefirst from those candidacies, Kitasato the NobelPrize: for candidacies ofJapanese case studies three willpresent in 1935. in 1927,andKato Gen'ichi in 1901,YamagiwaKatsusaburo Shibasaburo because researchers medical leading wasoneoftheworld's ago,Kitasato A century immunity. ofnatural andplagueandhisroleinthediscovery on tetanus ofhiswork ofcanunderstanding in medicine's advance a major for wasresponsible Yamagiwa It wasno nerve physiologists. most important theworld's AndKatowasamong cer. In or medicine. fortheprizein physiology werecandidates that all three accident relapublic support, ofgenerous theadvantages enjoyed medicine atthetime, Japan achieveand distinguished practitioners, eminent facilities, tively good research War World on anylevelbefore assets hadfewofthese andchemistry Physics ments. onlyin the1930s.4 medicine with parity evena rough I andbegantoachieve theNobelPrizes when in science as marginal viewed wasclearly Japan Although ofmedicine's hadsomeunderstanding Nobelauthorities in 1901,theSwedish began a Japain which discipline thefirst became in 1907medicine there: relative stature thenaming for a NobelPrizewith candidates to propose was invited nesescientist for recognition Similar at KyotoUniversity. of surgery of Ito Hayazo,professor at Tokyo a professor came in 1910,whenTanakadateAikitsu, physics Japanese was selected nominator a Japanese Butit was 1927before was named. University, ofthese Thesequence University. Tokyo alsofrom Machida Shokichi, inchemistry: at in Japan ofthethree disciplines strength therelative roughly, very datesreflects, NobelauthoritheSwedish that also suggests oftheinvitations Thetiming thetime. close to Japan's of power:1907 is conspicuously contexts to other tieswerealert remarkably War (1905) and follows overRussia in the Russo-Japanese victory Association tojoin theInternational 1906invitation on theheelsofJapan's closely Russia.5 over bythevictory an event precipitated atVienna, ofAcademies notbe exshould establishment research oftheJapanese understanding Swedish whowere nominators theonly Japanese Forunknown however. reasons, aggerated, not a practice heldacademic posts, halfof thecentury in thefirst to serve invited had research laboratories at nonacademic employed Scientists elsewhere. followed nominators on professorial This reliance candidates. to nominate no opportunity andKitasatoShibaas Nishina ShigaKiyoshi, Yoshio, suchmajor figures excluded Niresearchers. most thecountry's distinguished wereamong all ofwhom saburo, is for in the1920s, known the NielsBohrin Copenhagen with whoworked shina, most atJapan's a important He headed laboratory inphysics. formula Klein-Nishina for Institute the Research Physics interwar ofthe period, research facility scientific
ofScienceinJapan(cit.n. 1). Formation Bartholomew, 1907 (StockochBetdnkanden, P M. Forsandelser see Nobelkommiteten, On Ito'sappointment e.g., anddate, willbe cited series ofthis bytitle volumes 1907(hereafter, Institutet, Karolinska holm: of Kocher Theodor hisEuropean mentor, 1907). Itoproposed ochBetankanden, P M. Forsandelser Vetenskapasee Kunliga ForTanakadate later. a NobelPrizetwoyears whodidreceive Switzerland, 1910ANG.Nobelarenden KunligaVetens(Stockholm: Protokoll Vetenskapakademiens kademien, ofthisserieswillbe citedby title, e.g.,Vetenskapakadevolumes 1910) (hereafter, kapakademien, 1927ANG. Protokoll ForMachidasee Vetenskapakademiens Nobeldirenden). ProtokollANG. miens TheNobelPopulaandRebeccaUllrich, John Heilbron, Crawford, See also Elisabeth Nobeldrenden. 1987),p. 242. On of Science,Univ.California, fortheHistory Office tion,1901-1937(Berkeley: Sha, Herald no kazukazu (Tokyo: memories) (Various Omoide see Sakurai Joji, context thepolitical 1939),pp. 70-71.
241
andChemistry. ofthedysentery as thediscoverer Shigais remembered today pathogenthat bearshisname, Shigabacillus.6 It is an equally fact thenomination puzzling about that in Japan system operated that noneofthethree I focus scientists on inthis ever to was invited nominate essay candidates. in EuropeandtheUnited The Nobelarchives showthat in conStates, trast, nominators andnominees thesamepeopleinthis wereoften We period. know from thepioneering studies ofElisabeth Crawford that American andEuropean scientists could"exchange" evenif suchreciprocity nominations; was notexplicitly planned, whohaddonesomething scientists significant that might expect colleagues or friends wouldsubmit their names.It is clearfrom thearchival records that this was notthecase among theJapanese inthefirst ofthecentury. half FukuiKen'ichi has attested tothefact that eveninrecent theJapanese years nomination has system hadcertain peculiarities. His fellow laureate EsakiaskedFukui, a professor in Kyoto'sFaculty ofEngineering when hereceived hisNobelaward, ifhehadever nominated in chemistry before theprizehimself. winning Fukuisaidthat he hadnot:in Japan, suchinvitations wouldgo onlyto chemists in a faculty of science, never to chemists inan engineering unit. The latter havebeennumerous in Japan.7 Another particular, andconsequential, feature oftheJapanese research system in thefirst halfofthecentury was itsintense at leastinmedicine. factionalism, Whateverone maythink abouttheproclivity ofphysicians or medical researchers elsewhere toward factional behavior, itreached particular heights (ordepths) inJapan duringthis period. Somereports haveitthat medical peopleinthemilitary constituted a faction. Others stress thefactional orientation ofmany (though notall) professors ofmedicine attheimperial universities (Tokyo, Kyoto, Tohoku, Kyushu, andHokkaido), Tokyo's casebeing the most widely discussed. Factionalism is sometimes considered an inherent, "cultural" feature ofJapanese academic andprofessional life.8 Butitshould be emphasized that the factional patterns that influenced Japanese Nobel nominations hada 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 bya professor ofhygiene atTokyo University, Ogata Masanori. Ogatahad mistakenly imputed a bacterial origin to beriberi andclaimed tohaveisolated a pathogen. Kitasato was studying atBerlin University with Robert Koch at thetime, andsomesources saythat he was urged to write by Friedrich Loeffler, another Koch associate. He was in anycase entirely capableof suchan initiative taking onhisown,without prompting. Whatever itsgenesis, Kitasato's letter infuriated certain peopleatTokyo University, notonly becausethecriticismcould adversely affect theinstitution's reputation, butalso becauseKitasato
6 For essayson all three scientists see TsuneishiKeiichi, Nihonkagakusha den (Biographies of Japanese scientists) (Tokyo: Shogakkan, 1996). 7 Elisabeth Crawford, Nationalism andInternationalism inScience, 1880-1939(Cambridge: Cambridge Univ.Press,1992), pp. 51-54; and ShadanHbjin KyWd6 Tsushinsha, Kagaku to ningen o kataru: FukuiKen'ichi toEsakiReona(A conversation about scienceandhuman beings: Fukui Ken'ichi andEsaki Reona) (Kyoto:ShadanHajin Kyod6Tsushinsha, 1982),pp. 19-20. 8 On factionalism inmedicine see ReneeC. Fox,"MedicalScientists ina Chateau," Science,1962, 136:476-483; and Eliot Friedson, Profession of Medicine:A Study of theSociology ofApplied Knowledge (New York: Harper & Row,1970),pp. 192-197.On the"inherent" factionalism ofJapanese academicand professional lifesee Nakane Chie,JapaneseSociety(Berkeley/Los Angeles! London:Univ.California Press,1970),pp. 10-29,42-43, passim.
242
JAMESR. BARTHOLOMEW
hadgraduated from theuniversity after Ogataandcouldthus be seenas hisjunior intheJapanese status hierarchy. Ogatahimself wasnotgreatly exercised, butothers were. Continuing resentment from theberiberi controversy wasonereason why Kitasato never became a faculty member atTokyo evenafter hebecame world famous.9 He tooka radically different course, serving as director, first, of theInstitute for Infectious Diseases (1893-1914)andthen oftheprivately operated Kitasato Institute (1915-1918);in 1918hebecame professor anddeanatthenewmedical school ofKeio University, a leading private institution. Kitasato's fame, international reputation, and experience in bothacademic and institutional politics hada largeimpact on Japanese medicine andevenon parts of thephysical sciences. he tookwith tothebureaucratic Initiatives respect affiliation of Infectious oftheInstitute Diseases (in 1914) andreaction to them bymembers ofparliament andgovernment officials wereamong thereasons whytheResearch forPhysics Institute and Chemistry, founded in 1917,never becamean academic His presence inthemedical continued tohavea polarizing effect commufacility.'0 of Kitasato is one ofthereasons nity. Resentment whyKato,hisprotege, received from for hisownNobelcandidacy in no support anyimperial university professors 1935.Similarly, noneofthescientists in Kitasato's campdid anything to advance from fora Nobel Prize.Though himself these Yamagiwa's prospects disengaged ofMedicine atTokyo quarrels, Yamagiwa wasa professor intheFaculty University. for a series ofcase andKatoareparticularly Yamagiwa, Kitasato, goodsubjects achievements were because studies becausetheir especially important scientifically, thetwo were andbecause their careers tosomedegree intertwined, they represented ofthisera.In principle, medical research major campsin theJapanese community from this or chemistry candidate one wouldliketo examine thecase of a physics in 1939-1949 there wereno Japanese to Yukawa as well.Butprior period simply a NobelPrize.Hata Saofreceiving whohad evena remote candidates prospect for was with ofSalvarsan codiscoverer PaulEhrlich hachiro, 606,a specific syphilis, Kocher nominated the1911prizein chemistry) (for bya Nobellaureate (Theodor to Ehrlich was credited of Switzerland);" butHata'swork bymostpeopleoutside case I do nottakeupYukawa's no interest at all in Stockholm. andgenerated Japan to his award arenotyet materials becausethearchival fully here, partly pertinent of a future research entirely open,butalso becausehe willbe thesubject project. intheepilogue. is discussed Yukawa's However, candidacy briefly
9For theletter aus faulendem einesSpirillum "Ueberdie Reincultur see Kitasato Shibasaburo, 1888, und Parasitenkunde, Bakteriologie n. Sp.," Centralblatt concentricum Blute,Spirillum ffir ShibaKitasato Igakushi "Zai Doitsu-koku also appeared: version 3(3):76-78.A Japanese-language reaction see,e.g., 25 Jan.1889,no.212,p. 105.Foran angry iji shimpo-, Chuigai saburo Shi shokan," details 8 June 1889,no. 562,p. 2. Forother iji shinshi, no bunso," Tokyoi Mori Ogai,"Tokeinitsuite and the Kitasato Shibasaburo of Sciencein Japan: "The Acculturation R. Bartholomew, see James Univ.,1971),pp. 163-169. 1885-1920"(Ph.D. diss.,Stanford Community, Bacteriological Japanese 10Bartholomew, ofScienceinJapan(cit.n. 1), p. 216. Formation 11Vetenskapsakademiens in mediHata was also nominated 1911ANG.Nobeldrenden. Protokoll UniofTokyo andin 1913byOsawa Gakutaro University of Kyoto cine,in 1912byHirai Ikutaro och Betdnkande, 1912; and P M. Forsdndelser och Betdnkande, See P M. Forsdndelser versity. 1913.
JAPANESENOBEL CAN'DIDATES
243
m-a}
__-
Figure1. Kitasato Shibasaburo. circa1920.

KITASATO'S NOBEL CANDIDACY. 1901
Asnoted earlier. KitasatoShibasaburo wasoneofthepreeminent (I1852-1931) figin medicine ures around theturn of thecentury. (See Figure1.) Graduating eighth inhisclassfrom Tokyo Universitv's Facultv ofMedicine in 1883.Kitasato worked for two years in Japan's Bureauof Sanitation andthen received theopportunity to with Robert Koch.one ofbacteriology's twofounding study at theexpense figures. ofthe Japanese government. His six years at Koch'slaboratory inBerlin University (December 1885-Januar1892) were.to saytheleast.productive. In 1887he did useful work on thebacillus oftyphus andthecholera vibrio. andin 1888he studied blackleg in cattle. In 1889he managed thetechnically difficult feat ofisolating the bacillus oftetanus ina pureculture. In thecourse ofhisstudies ofthetetanus bacilKitasato lus. discovered tetanus in 1890heclaimed toxin: themantle ofcodiscoverer ofnatural immunitv thefundamental notion that there existin thebloodstreams of allorganisms substances that arecapableofneutralizing foreign materials. TheJapanese scientist hada colleague inthis achievement: EmilBehring. another researcher in Koch'slaboratory, whohadbeenstudying thediphtheria bacillus. Together. Behring andKitasato their published epoch-making paperin the4 December 1890 issue of the DelutscheMedizinische Wochenschrift-apaper in which
Behring's name first andKitasato's appeared second. Thisarticle became the foundation forthedevelopment of serum and indeedconstitutes theinitial therapy step toward the establishment ofhumoral As such.itbecame imrnunolorv.' theprincipal
" Emil Behringand ShibasaburoKitasato. "Ueber das Zustandekommen der DiphthenreImmunitat undderTetanus-Immunitat bei Thieren." Deutsche Mfedizinische Wochenschrfti. 4 Dec.
244
orMedicinethe1901NobelPrizeinPhysiology for awarding scientific argument eversincethat in Japan resentment Therehas beenconsiderable to EmilBehring. ofKitasato no acknowledgment alone,with to Behring went this first Nobelaward merit. hasconsiderable criticism theJapanese to showthat at all. It is mytaskhere is theplace to begin. in Germany work scientific of Kitasato's A closerreview skep1885,Kochwasclearly inBerlin inlateDecember When Kitasato first arrived Forthe in German. byhisfluency impressed though abilities, ticalofhis scientific improvLoeffler, ofFriedrich inthelaboratory worked Kitasato months several first on his he was Then investigation. in bacteriological capabilities inghis technical the relationship about details (in 1887)addeduseful work independent own.His first and bacillus thetyphus inthemediausedtocultivate andalkalinity between acidity of agent the causative he identified in 1889 published In a study thecholera vibrio. its that is, nature, its anaerobic noted and chauvoei, in cattle, Clostridium blackleg course inthe achievement A notable ofoxygen. inthe absence only toflourish ability sura medium in solid the bacterium grow to was Kitasato's ability of thiswork microorganisms with anaerobic His experience atmosphere. bya hydrogen rounded challengonanevenmore totake when Kochaskedhim dividends would paymajor Tetanus hadbeen the bacillus. of tetanus a pureculture toproduce ingassignment: sevidentified tentatively diseaseanditscausalorganism tobe an infectious shown researchand several was prominent Butconclusive before. proof lacking; eralyears most bacillusin a pureculture, thetetanus to produce ers had failedin attempts Gdtthe of at University a of hygiene friend Carl Flugge, professor Koch's recently he was and could be solved, believed that the problem however, Kitasato, tingen. stillthe to offered ammunition the culture failure to achieve that pure concerned ofdisease.' ofthegerm theory influential critics was able to drawon his prior Kitasato of tetanus thechallenge In approaching of character theanaerobic He beganbynoting anaerobic bacteria. with experience intheupper colonies itdidnotproduce layer thefact that from bacillus thetetanus Kitasato ina deeper colonies formed layer. only medium rather, but, oftheagar-agar in his workwith he developed techniques culturing also called on theimproved ofthesuspected encountered investigators byearlier A principal difficulty blackleg. with in to it able had been was that symbiosis only grow tetanus they pathogen ofthetetanus that thespores Kitasato found HenceKoch'schallenge. bacteria. other other to heatthansomefourteen microorganisms resistant bacilluswerefarmore to 80 detheentire culture medium. in thesameculture By heating that appeared thetetanus tokilleverything he managed except closetoan hour, Celsiusfor grees his andreported thebacillusin a hydrogen cultivated atmosphere bacilli.He then before on animaltrials insisted accepting to Koch,who understandably findings claims.14 Kitasato's
andBacteriolKoch:A LifeinMedicine Robert D. Brock, See alsoThomas 1890,16(49):1113-1114. Wisc.:ScienceTech,1988),p. 226. ogy(Madison, den (Tokyo: Shibasaburo Kitasato Koch see MiyajimaMikinosuke, under work 13 For Kitasato's bacillus).On hissuccessingrowlab),44-45 (tetanus 1931),pp. 34-35 (Loeffler's Shoten, Iwanami in Dictionary ofScienKitasato'" Fujino, "Shibasaburo chauvoeisee Tsunesaburo ingClostridium Vol.7, p. 391. 1970-1986), 18 vols.(New York:Scribners, C. Gillispie, ed. Charles Biography, tific nojush6"(A bacteriologist's ga karanda saikingakusha 14 See NakamuraTeiri, "Seiji tojinmyaku tokage(Triumph inNoberu sh&no hikari andpersonal connections), bypolitics NobelPrizesuffused Sha, 1981),pp. 134AsahiShimbun oftheNobelPrize),ed. Kagaku Asahi(Tokyo: and shadows Shibasabur6 den,p. 46. Kitasato p. 391; andMiyajima, Kitasato," "Shibasaburo 135; Fujino,
245
that theclaims Strong were proof wasnotlongincoming. legitimate Indeed, after he achieved thepure oftetanus, a major Kitasato produced culture research advance in thetreatment of tetanus theexistence of tetanus toxin.He by demonstrating inhis 1889paper"Ueber presented theevidence denTetanusbacillus," published in theZeitschriftfuir Hygiene. Kitasato when fluid that thepureculture from reported from which thebacillihad beenremoved was injected intolaboratory mice,they contracted tetanus anddied.Thusitwasclearthat thetetanus itself bacillus must be a toxicsubstance, producing thetetanus toxin. This was nota surprising namely, sincetheexistence discovery, ofsucha toxin hadbeenpredicted researchbyother ers,including Behring. Kitasato's contribution wasthedefinitive ofthetoxin's proof existence andpathogenic effects.15 Kitasato's achievements included thedevelopment ofa better filter for extracting thetetanus bacillifrom theculture fluid anddetermining a dosageregimen for testingandevaluation. He approached thesecond problem byadopting an analogy from medical with experience cocaine. smallamounts By using ofcocaineandgradually increasing thedosage,it was known that a recipient couldgradually becomeused to thecocaineandremain fora time unaffected relatively bythepoison.Kitasato suspected that thesamemight be true forthetetanus toxin, andhe pursued hisresearch on thebasisofthisassumption. Despitethelimited on which understanding itwasbased, theanalogy proved useful. Kitasato diluted the tetanus toxin bydegrees andinjected amounts varying first intomiceandthen intorabbits. He then diluted thefluid further and gradually determined theminimum amount neededto cause death. Continued, calibrated increases of toxin in thefluid led to a finding of the maximum amount an animal couldreceive without ill effects. showing Finally, he was able to showthat an animal receiving repeated, gradually increased injections would display no symptoms ofthedisease, evenwhen more toxin wasinjected than wouldbe required to killan untreated animal. Thissuggested thepresence in the animal ofa substance that hadrendered thetoxin harmless. After publishing these findings with hiscoworker, Theodor Weyl, Kitasato turned hisattention tothe fundamental questions ofwhat thissubstance might be andhowitworked.16 Kitasato's close associate in thisimportant project was,ofcourse, EmilBehring. In 1887,after extended years of service as a military physician andsomeindependent research on disinfectants, efforts Behring begana formative apprenticeship at the Pharmacological Institute ofBonnUniversity under CarlBinz.Through hismilitary experience, he was familiar with theuse ofthechemical iodoform in treating a procedure wounds, introduced in 1880.He begantowonder ifitmight be possible to attack infectious diseasesas they manifested themselves insidethebodyby a similar kindof "disinfecting" procedure. In 1881 he published a smallpaperon sepsisandantisepsis that incorporated this presumption; in an 1882paper he noted that iodoform's toxiceffect on theorganisms studied was stronger thanitsdisinfecting influence onthetargeted bacteria. ButBehring wasundeterred, andhechose to study withBinz because of the latter's considerable interest in such chemical disinfectants. Behring's studies at Bonnon iodoform and acetylene gavehim
15Kitasato Shibasaburo, "UeberdenTetanusbacillus," Zeitschriftfiur Hygiene, 1889,7:225-234. See also Nakamura, ga karanda," "Seiji tojinmyaku p. 135. 16 Kitasato Shibasaburo and Theodor Weyl,"Zun Kenntniss derAnaeroben," Z. Hygiene, 1890, 8:97-102.See also Miyajima, Kitasato Shibasaburn den(cit.n. 13),pp. 49-50.
246
appropriate with animals experience andresearch intoxicology knowledge valuable toinfecrespect valuewith clinical hadlittle studies Mostofthese specialty. tothat to tetanus ratsimmune ofwhite that theserum tiousdiseases.Buthe didascertain a subject withwhich bacillus, theanthrax neutralized that a substance contained inbacteriology.17 hisowncareer Kochhadbegun or ofPasteur in thetradition bacteriologist trained was nota classically Behring of tothestudy orientation orpharmacological chemical Kochbuthadan essentially University ofBerlin Institute theHygiene in 1889he entered disease.Nonetheless, on his work was beginning Kitasato to Koch,at aboutthetime as a paid assistant becauseitwas notonly ondiphtheria, wastowork assignment His principal tetanus. following but alsobecause, tochildren, especially time, threat atthe medical a major of hada tradition institute the in 1884, pathogen diphtheria ofthe isolation Loeffler's andpharmacology, intoxicology training onhisearlier Drawing subject. work onthe agents," disinfecting "systemic suitable to discover beganby attempting Behring pigsinjected guinea of goldandzincon laboratory iodineandcompounds testing tokeep didhemanage trichloride 8 Butonly with iodine bacillus. with the diphtheria alive. animals a fewoftheinfected more By most directly. converged ofthetwoinvestigators thepaths Atthis point simultaon diphtheria, working andBehring, on tetanus, working Kitasato, reports, thetwo neutralized in bloodthat there was something notonlythat found neously of an bloodserum theinjected butthat conditions under particular diseasetoxins Thesewerethefindings fortherecipient. immunity immune animalcouldcreate
call atThese same reports in theDeutscheMedizinischeWochenschrift. presented
demonstraostensibly oneweeklater, inthesame journal toBehring's paper tention for as evidence antitoxin, of diphtheria rolein thediscovery his independent ting inbasicmedicine.19 notable achievement tothis contribution hisleading on thebasisoffacts ofthisaccount to challenge aspects however, It is possible, andtheUnited in historians Europe andmedical researchers tomedical longknown natural about for the conclusions direct evidence ofthe first Inthe place,most States. research Kitasato's tetanus, in the4 December paperconcerns presented immunity to the had beenactive. (It adds little where than Behring rather diphtheria, topic, as roleto emphasize, most of claimsforBehring's important uniquely credibility bewerebasedon tetanus aboutimmunity discoveries themajor do,that narratives it produced.) of thetoxin Second,evenBehring's strength cause of theparticular totetanus. with reference Third, summarized major findings of 11December paper in support ofhisclaimto have somedetails present whileBehring did,to be sure, hasbeendescribed hisaccount todiphtheria, tetanus by about thefindings extended at theUnian and American as "vague" by microbiologist ofbiology onehistorian as "notcompletely convincing."20 ofWisconsin versity scientific from in on testimony longtime medical relying part historians, Japanese
17 (cit. ed. Gillispie Biography, ofScientific inDictionary "EmilvonBehring," HansSchadewaldt, n. 13),Vol. 1,p. 575. (cit.n. 14),p. 136. See 18 On Behring's ga karanda" "Seiji tojinmyaku see Nakamura, orientation p. 575. "EmilvonBehring," also Schadewaldt, 19 ed. FrankN. in TheNobel Prize Winners, "EmilAdolphvon Behring," H. Whallon, Joanne N.J.:Salem,1991),pp. Cliffs, Calif./Englewood Vol. 1 (Pasadena, or Medicine, Magill,Physiology 35-36. D. Brock, ed.,Mile(cit.n. 14),p. 134; andThomas ga karanda" "Seiji tojinmyaku 20 Nakamura, 1961),p. 144. N.J.:Prentice-Hall, Cliffs, (Englewood inMicrobiology stones
247
Kitasato's own view-have colleaguesof Kitasato-whichno doubtreflected of thediscovery of natural a farmore suggested plausible interpretation immunity inWestern medical histories. found First ofall,itis a simple than is typically matter out:shortly after Kitasato andBehring what haspointed toconfirm NakamuraTeiri hisownfollowresearcher the published their classic joint paper, Japanese published in which he quotesextensively, in theZeitschrift up, a longer report Hygiene ffir the word for from DeutscheMedizinischeWochenschrift almost word, essay.21Moreoftheimmune serum's he quotesinhisownpiecein a discussion thematerial over, theportions oftheearlier on is very identical with effects nearly paperthat report We may theactualexperiments ostensibly performed by thetwobacteriologists. these sections of that itwas Kitasato whowrote crucial takethisas direct evidence it was he, notBehring, for thefirst who was actually paperand that responsible In all likelihood, from thefamous themajor about natural findings immunity. apart thenature unusual main lineabout ofbloodas a "very concluding fluid," Behring's totheoriginal wasprobably Kitasato's contribution toargue-correctly-that paper findings about tetanus havea general immunological significance. Of course, thisinterpretation is inconsistent with theappearance of Behring as first author and Kitasato as secondauthor at thetop of thearticle. Indeed,there to be no explanation as to whyBehring's nameappeared first-unless he appears was themajorcontributor. three scientists who knewKitasato actually However, wellandworked with himinsist closely that Behring was not;they also claimthat achieved hissuccess with Behring diphtheria atthis point only becauseKoch,when Kitasato thepure culture oftetanus, diverted produced Behring from hisearlier emonchemical todiphtheria andinsisted that onthe phasis approaches hefocus instead roleofbloodserum. possible Apart from anydirect evidence presented byKitasato's inJapan, this version ofevents seemsplausible inlight ofBehring's own colleagues andprevious todisease. training approaches Accounts left by thethree Japanese scientists differ in nuance butagreeon the essential that KochtoldBehring toadopt point theapproach todiphtheria that Kitasatohadbeenfollowing inhisstudy oftetanus. Recounting Kitasato's report toKoch ofhisfindings onthetetanus toxin, MiyajimaMikinosuke, a 1935Nobelnominator, wrote in 1932:"[Koch]calledin Behring, whohadcharge ofresearch on thediphKitasato's In 1961Takano Rokuro, methods." director of theKitasato Institute at theendofthe1940s,stated: "Kochordered Behring to adopt Kitasato's methods in hisownresearch; finally [Behring] was able to getthesamekindof [immunizing] results." BothMiyajima andTakanosee the"basicprinciple that serum therapy is as having been"discovered possible" byKitasato." However, themost authoritative statement is probably that of Hata Sahachiro, a closercontemporary of Kitasato than orTakano Miyajima anda Nobelnominee himself. Hata's1931lecture eulogizing Kitasatodiscusses, amongother matters, his research on thetetanus toxin: "When[Kitasato] mixed thetoxin with thebloodserum, itbecameclearthat this bloodserum was counteracting theeffects ofthetoxin. Thiswas all before Behring
21 Shibasaburo Kitasato, "Experimentelle uberdas Tetanusgift," Untersuchungen Z. Hygiene, 1891,10:267-305;see esp.pp.299-300.NakamuraTeiri first pointed outthenearly identical wordinginthis paperandtheDeutsche Medizinische Wochenschrift essay;see Nakamura, "Seiji tojinmyakuga karanda," p. 133.
theriabacillus, and orderedhim to do the same kind of research.. . accordingto
248
wasBehring's Andwhy coauthored? 1890article wasthe4 December Why, then, is that of question we haveon thefirst testimony first? The onlydirect namelisted write Kochhadthem andBehring], between [Kitasato Hata:"To avoidbadfeelings work ontheimmunity they simply reported inwhich their twonames a paper under had theother used.Kitasato Whatone did first, diphtheria and tetanus. regarding Because so Behring useditinhisresearch. bloodfluid, anantitoxin inthe discovered shouldnotbe divided, reporting the [scientific] thediscovery was so important, together." by thetwoof them rather be announced but[should] [Kochbelieved], should onimmunity] writes, "This[research Takano thesecond question, Regarding havebeen Scientists in Japan ofKitasato with listed as thesecondauthor. Behring 23 paper." as a dual-authored itappeared unable todetermine why of The historian somefrom speculating. however, has notprevented Thatfact, signifitheenormous that Behring, recognizing biology NakamuraTeiribelieves prospects for awareof thepotential findings and fully canceof thebasic medical There is,tobe sure, Kochtohavehisnamelisted first. pressured clinical treatment, is fully consistent with what for this buttheallegation no direct evidence assertion; and professional with dealings aboutBehring's personality has longbeenknown the friend, with byhiserstwhile He feuded Koch,cameto be despised colleagues. on his authority and has beendescribed by a recent Nobel laureate Paul Ehrlich, in thehistory of medicine." Thereis, as "one of thegreat solitary figures career ofthe evenintheNobelarchives for this viewofBehring indirect evidence further, who thedozenorso scientists where onediscovers that among Karolinska Institute, his native name forthe Nobel Prize,not one came from Behring's proposed Germany.24 a number ofindicalisted didasktohavehisname first, despite Behring If,infact, was more to thepaper Kitasato's contribution substantial, why notably tionsthat offers a somewhat Nakamura tosucha request? plausible Kochhaveacceded might embroiled fiasco inwhich Kochbecame the tuberculin Ithastodo with explanation. at Tenth International the the on of after his in theautumn 1890, subject speech that he had Koch notonlyindicated in August. heldin Berlin MedicalCongress, it tubercle bacillus-he called the elaborated substance an important discovered by In disease. cure the substance this also hinted that actually tuberculin-but might debecameclearthat itgradually that tuberculin, theweeksandmonths followed, this unfortunate in a cure. After no sense was its valuable properties, diagnostic spite anddenunciations ofbitter attacks Koch was-unfairly-thetarget ofevents turn Nakaand uncomprehending tuberculosis physicians. from patients disappointed
22 Kitasato Shibasaburo Kitasato Shibasaburo-den (cit.n. 13),p. 50; Takano Rokuro, Miyajima, no menboku" to shite "Gakusha NihonSh6bo,1965),pp. 39, 37-38; andHata Sahachiro, (Tokyo: Shibasaburo Kitasato den,p. 284. in Miyajima, as a scientist), (His reputation KitasatoShibasaburo, p. 40. Here p. 284; andTakano, to shiteno menboku," 23 Hata,"Gakusha indicated. aremineunlessotherwise translations andelsewhere, "Emil von (cit. n. 14), p. 137; and Schadewaldt, ga karanda" "Seiji to jinmyaku 24 Nakamura, Marquardt, see Martha Ehrlich with relationship Behring's (cit.n. 17),p. 577. Regarding Behring" etal., see H. Schuck 1951),pp. 34-35. On theNobelproposals (New York:Schuman, Paul Ehrlich Press,1951),p. 182. Univ.Oklahoma Nobel: TheMan andHis Prizes(Norman:
therapy."22
who ofanimals byusing thebloodfluid diphtheria toxin howtonullify discovered of today'sserum Dr. Kitasatois thus the founder were diphtheria-immune.
as thediscovery [in theDeutsche MedizinischeWochenschrift] have been reported
249
thishighly volatile Koch'sprofessional muraargues that status during period was he suggests that falling just as Behring's starwas rising; under thecircumstances Kochmight haveacceded topressure from that hebe designated first Behring author ofthe jointessay.25 mention Although Nakamura doesnot atleastthree other couldhave factors them, a roleinBehring's played namebeing aheadofKitasato's. listed One is thefact that Behring was serving as Koch'spaid assistant, whereas nota Kitasato-obviously German national-wouldhavebeen unableto hold sucha postevenhad Koch wished to appoint him.(Given theclosepersonal andprofessional that relationship existed between KochandKitasato time andcontinued bythis until Koch'sdeath in 1910,this wouldnothavebeenan unlikely hadKitasato heldGerman development citizenship.26) A secondfactor has little or nothing to do with Koch.DespiteKitasato'sreputation in medical research, due to his work on tetanus, the4 December ring, had published however, there before and was therefore better known to its as Koch'spaid assistant, readership-and, of higher status thanKitasato. Finally, given thefact that, becauseofitsprevalence, was a greater diphtheria to challenge clinical medicine than theless common more (though lethal) itis possible tetanus, that the journal editors tolistBehring decided as first author becauseoftheexciting that there possibility nowbe a genuine might curefordiphtheria. Whether or not likethishappened, anything theNobelarchival materials, together with numerous published accounts, clearly accent theimportance ofthemedical triumph over diphtheria as a reason tohonor this work with a NobelPrize.27 Important as itwas from a scientific perspective, thediscovery ofnatural immunity nothavebeenso honored might hadBehring, Kitasato, andothers notmanaged toimprove theefficacy ofbloodserum therapy. Thedetails ofthis effort haveoften beenrelated and neednotbe repeated here.But twopoints maybe noted. Serum producers facedenormous difficulties initially in generating theamounts required forthetreatment of human patients. Mice, guineapigs,rabbits, and other small mammals proved quiteinadequate for this purpose; EmileRoux'sconvincing demonstration in 1894that the bloodsystem ofthehorse was suitable for serum productionfinally solvedthat problem. Similarly, PaulEhrlich, working with Behring-at thetimehis close friend-inthemid 1890sdeveloped useful mathematical techniquesfordetermining theproper serum dosagesfordiphtheria patients andother victims ofinfectious diseases;thisachievement madethenewserum therapy efficient, predictable, and,aboveall,effective.28 Full appreciation ofthesociopolitical context within which thefirst NobelPrize selection committee considered thediscovery of immunity and serum therapy in 1901requires us to notethat Kitasato left Berlin shortly after Christmas 1891and returned to Japan in May 1892. He resided permanently in Tokyothereafter but
Nakamura, "Seiji tojinmyaku ga karanda'" p. 138. Victor Robinson, Pathfinders in Medicine(New York:Medical Life, 1929), p. 743: "Koch's pupilswerenotlimited tohiscountry orrace,andperhaps no disciple gavehimsincerer gratification than Kitasato." 27 See Schadewaldt, "EmilvonBehring" (cit.n. 17),p. 577 (Behring hadpublished inthe Deutsche Medizinische Wochenschrift in 1882); andSchtick etal., Nobel(cit.n. 24), pp. 182-183. 28 On Roux'swork 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.
25 26
articlewas his first appearance in the Deutsche MedizinischeWochenschrift. Beh-
250
was KitaBudapest to Miyajima, According occasions. visited Europeon various trip. His particuEuropean it on every city, andhe visited European sato'sfavorite sitevisitsto publichealth-related of 1891-1892involved travels larlyextensive DiscusStates. and theUnited theNetherlands, Britain, Italy, in France, facilities of andat theUniversity University at Cambridge employment possible sionsabout The Whilevisiting reputation. of his international are an indication Pennsylvania enthusiButthemost hisname. knew physician Dutch every Haguehe wastoldthat hismonthinParisannounced newspapers Leading cameinFrance. asticreception did he him,and "nowhere timewith considerable spent longvisit.Louis Pasteur Institute."29 at thePasteur than welcome a warmer receive with difficulties technical anddespite in Germany, remained ofcourse, Behring, An 1892concareer. a successful he enjoyed andadministration serum production Despite himlucrative from thesale of serums. returns with Hoechst brought tract Behover tuberculosis), (andlater ofthis contract Kochover theterms conflict with at Halle in 1894;in 1895he moved ofhygiene professor associate was named ring ofnominapattern thelater As ifforeshadowing atMarburg. toa full professorship him leastbestliked Behring whoknew those for theNobelPrize-in which tions from theFaculty opposition went forward major despite theMarburg appointment a andnamed nobility to theGerman was appointed In 1898Behring of Medicine. dueto theactive support Whilemuch ofthissuccesswas directly councillor. privy of popular it was also a reflection Friedrich of education, Althoff, of theminister infectious diseases.It is andother overdiphtheria triumphs acclaimforBehring's Kitasato that career to observe enjoyed Behring's to understanding notirrelevant ofgreat wealth-inJapan.30 theacquisition success-including similar for thefirst recipients possible authorities beganconsidering WhentheSwedish torecognize understandably, or Medicine, decided, they NobelPrizeinPhysiology Therewas, and widelyacclaimed. well known was already that an achievement a basic award should that thefirst inthecommittee recognize a conviction moreover, ofnatuThediscovery clinical alsohadsignificant importance. advance that medical criteria met these of serum therapy development andthesubsequent ralimmunity an awardforthese in Stockholm arrived recommending fiveletters perfectly; twofrom from one theNetherlands, Switzerland, One came from achievements. the two from The ninesignatories Leiden, separate andonefrom Hungary. Norway, Bernementioned only from Christiania (Oslo), and theone from correspondents as well to Kitasato an award from proposed theletter Budapest However, Behring. theideaof also favored at Budapest other that andindicated colleagues as Behring thetwoinvestigators.3' a prizefor
pp. 58-59. is from den(cit.n. 13),pp. 57-59; thequotation ShibasaburoKitasato Miyajima, "Emilvon Koch(cit.n. 12),p. 235; Schadewaldt, Robert see Brock, achievements On Behring's (cit. n. 22), p. 41. On Kitasato's KitasatoShibasaburd (cit. n. 17), p. 576; and Takano, Behring" Kitasato notesthat den,pp. 210-220. HereMiyajima KitasatoShibasabur5 successsee Miyajima, at Izu, inspired by one he sumat thetime-on a hotspring substantial 50,000yen-a very spent He was sumowrestler. tour by a Japanese He also paid fora foreign in Budapest. had patronized in 1924. as BaronKitasato to theHouse ofPeersin 1917andenobled named ochBetdnkanden, only);andP M. Forsdndelser etal.,Nobel(cit.n. 24),p. 182(Behring 31 SchUck The official Arpadde Bokay,wroteon 27 Jan. 1901: nominator, 1901 (Kitasatoand Behring). le prixa Messieurs de decerner de mes colleguesen proposant doncavoirl'essentiment "J'esp6re uneplace dansl'histoire a pourtoujours inconteste le m6rite dont deuxsavants et Kitasato, Behring de la m6decine."
29 30
251
oftheEuropean nominators Why is tosome Behring alonewasproposed bymost was a major ofconjecture. ofcourse, andthere a matter degree Diphtheria disease, camealong.Moreover, in Europebefore weremajorepidemics Behring "Behring as a savior andthis was onebasisfor wasregarded bythegeneral public, reception him wasnotso major the first Nobelprize." "Kitasato's tetanus awarding Bycontrast, a diseaseinhumans, andsinceitwasoften contracted unclean the through wounds, of his successin treating it was moreprosaic." But it is equally publicreception probable that inmoving backtoJapan Kitasato sacrificed hisvisibility; despite periodicvisits, he simply outofthesight ofmany a recent dropped Europeans. Indeed, Japanese commentator whohas authored a bookanda widely known on the article NobelPrizes refers totheir obvious anddescribes Kitasato as from European origin "remote Japan" and,ina phrase redolent ofnineteenth-century a "victim positivism, ofthemaldistribution ofcivilization" !32 Despite thepeculiar this is notas far-fetched terminology, explanation as itmight seem.Behring havebeendisliked may German medical bymany buthe colleagues, retained somepowerful assets. Onewastheaffinity felt Swedish bymany academics forGerman culture andGerman academic generally culture in particular, a theme well developed in theimportant of Elisabeth studies Crawford. One sensesthese affinities in a biased, rather implausible report written onbehalf ofBehring's candidacybyErnst Bernhard for theKarolinska Almquist in 1901.Almprize committee quist concedes that to"a kind Behring admitted ofinadequacy" inhisresearch capabilities and drawsattention to whatothers havecharacterized as thecandidate's chemical orpharmacological approach todisease.At thesametime, he insists that thediscovery of a meansof immunizing against diphtheria was "essentially Behown[achievement]." ring's Moreover, Behring "cametotheright path from hisearHe therefore gaveresults. joinedforces with Kitasato whowas already incharge of tetanus. it willbe generally [However], recognized that neither Koch norKitasato hadanysignificant roleinBehring's project." Butifthis were true, why didBehring andhispartisans go tosuchtrouble toslight Kitasato's contributions? In viewofthe German scientist's experience, training, andbasic orientation to disease, theclaim that neither Kitasato norKochplayed any"significant role"strains credibility.33 At theleast, a Nobelaward for thediscovery ofnatural immunity andtheprinciples of serum therapy should havebeenshared byKitasato andBehring. An equallyintriguing question is, Whydid theletter from Budapest, unlike the bothKitasato others, propose andBehring? Thereare several possibilities. One is certainly professional affinity. Thatletter was signed byArpadde Bokay(18561919),professor ofpharmacology at theUniversity of Budapest and a member of theHungarian of Sciences.De Bokayprobably Academy leanedtoward thejoint candidacy becauseof his interest in drugtherapy, illustrated by his authorship of
32 Takano, Kitasato Shibasaburo (cit.n. 22), p. 41; Yano Toru, Noberu sho(NobelPrizes)(Tokyo: ChioiKoronSha, 1988),p. 133;andYano,"Maboroshi no Nihonjin Noberu shojushoshatachi" Chau Koron, May 1988,103(5):171. 33 Ernst Bernhard Almquist, "Blodserumterapiens uppkomst ochutveckling,"' inP. M. Forsandelser och Betankanden, 1901, pp. 1, 2. For another workthatslights Kitasato's contribution see Heinz Zeiss andRichard Bieling, Behring: Gestalt undWerk (Berlin/Grunewald: Schultz, 1941),pp.54-55, 58-60. On behalf of Kitasato and Koch see Nakamura, "Seiji tojinmyaku ga karanda" (cit.n. 14), p. 136; andBrock, Robert Koch (cit.n. 12),p. 295. Brockwrites: "Without Kochbefore him, Behring's work wouldhavenever beenpossible." He further describes Behring as "a much lesser figure."
lierstudy of diphtheria and thereafter turned to . .. tetanus because. .. itmoreeasily
252
Figure2. RobertKoch in kimn

visit to Japan. 1908.
sexveral books on thissubject.He mayalso haxve had a personalaffinity forKitasato. It is possible thattheymetdurnng Kitasato'sxvellreceivedvisitto thePasteurInstito haxve xvisited thereoften. They could also havemet tute.since de Bokax is knoxxvn in Budapest.xxhere Kitasatoxvisited on a number of occasions (one of his objectives was to enjoy the renownedTurkishbaths). In 1895. 19031. and 1909 he attended international medical congressesin Budapest. and he could certainly have metde Bokav on one of these visits(thoughof course only the first could have mattered withrespectto theNobel Prize nomination. A finalpossibility is ethnicor cultural considerations. De Bokav,mayhave nomi'nated Kitasato partlybecause his Hungarianethnicity gave him a greater affinity xviththings to Asia thanmostEuropean medical or scientific relating personalities in thisperiod.RobertKoch spentsexeral wveeks in Japanin 1908 and even had his takenin a Japanesekimono:buthe was atypicalof European scientists photograph in his appreciation forAsia. (See Figure21.)Hungary. hoxvever. is a country xvhose founders came from Asia. Its languag~e xvasonce believed to haxe linguistic tiesto And itis rumored that in 1919. wvhen an independent Hungarianmonarchy Japanese. xvasbeingorganizedundera regent. one of thecandidatesforthethrone 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 in Mat gnarMVxikn. Vol. 2 iBudapest: Bo'kay." Akadmiiai Kiado. 199-5 . p. 229. I am crateful to Tfhomas Sakmrster oIftheUniversityof Cincinnati andEva AporoftheHungarian Academr ofSciences. for bringing Budapest. these references tomyattention. Alice Risko.a graduate student in theDepartment ofGermanic Langauges at Ohio StateUniversitv. kindlytranslated thematerials forme.) On themedicalcongresses in BudapestI haveconsulted LdszldA. Marvarof theSemmelweis Museum.Budapestppnvate 9 Sept. 1997T. communication. kindlxgaveme a listofde Bokavs publications Ma!gvar on drug andother matters. therapy
253
in Budapestwas thebrother of Japan's by powerbrokers Prince Meiji Emperor, Fushimi. itwasArpadde Bokayof Budapest whomostvigorously Forwhatever reasons, ofMessrs a Nobelaward that involved Kitasato: "Thework stated thecase for Behmarks thebeginning ofa newerainresearch."35 ring andKitasato
YAMAGIWA'SNOBEL CANDIDACY, 1926-1927
fortheNobel Prizeon four YamagiwaKatsusaburo (1863-1930)was nominated he cameclosetoreceiving the1926prize, occasions; bysomeindications, actually in 1927.He didnotwin, awarded inJapan admirers however, despite having strong as well as abroad.He was respectfully backedby TokyoUniversity nominators, his longtime friend andyounger Evenmore especially colleagueNagayoMataro. enthusiastic Maximow included Alexander ofChicago, oftheUniversity supporters oftheUniversity Aschoff ofFreiburg, William ofWashington Ludwig Cramer Uniin St. Louis,and,most of all,FolkeHenschen versity influential oftheKarolinska in Stockholm. Institute Maximow andAschoff eachnominated Yamagiwa formally, and Henschen wrote a report fortheselection committee that was explicitly detogethima NobelPrize. signed But it was to no avail.The committee decidedinstead the1926 prize to award ofCopenhagen, solelyto Johannes becauseFibiger Fibiger had apparently mostly discovered howto use parasites to generate cancers inrats twoyears before Yamahowtoinduce giwashowed cancers inrabbits byapplying coal tar totheir skin. The committee believed that work wasvery Fibiger's andhadbeencarried important out earlier than Yamagiwa's; thus, it deserved they reasoned, theaward. In fact, it was work Yamagiwa's that proved to havelasting valueforoncology, is now andthere wideagreement that should Yamagiwa havereceived a shareof theprize.Others wouldsaythat he alonedeserved theNobel. Yamagiwa's achievement, whichunfolded overmanymonths in thecourseof World WarI, had an extended prehistory, beginning withhis medicalstudies in andBerlin. Tokyo (See Figure 3.) After graduating from Tokyo University's Faculty ofMedicine in 1889,he tookan assistantship intheuniversity's pathology graduate program andadvanced tothe rank ofassistant professor after only twoyears. In May 1891theministry ofeducation decided tosenda three-member delegation ofTokyo professors, including Yamagiwa, toRobert Koch'sinstitute inBerlin for the purpose of learning more aboutthenewly discovered tuberculin. The visit beganbadlybecause Koch considered it a slight to Kitasato bytheministry, which had recently terminated theJapanese bacteriologist's funding (later reinstated). Thischilly receptiongaveYamagiwa little incentive to remain at Koch'slaboratory.36 He found Rudolf Virchow's highly regarded inpathology program more tohisliking inanycase, andinJanuary 1892he beganstudying under Virchow. His sixteen months atVirchow's institute (January 1892-April 1894)proved tobe one of thetwo mostdecisiveperiodsof Yamagiwa's career, notbecauseof any
35EM. Firsdndelser och Betdnkanden, 1901. Miyajima, KitasatoShibasabur5 den (cit. n. 13), contains a copy of theKoch photograph between pages 198 and 199. For a sense of Hungarian affinities with Asia see thebrochure entitled "The Pathfrom theOrient to OurPresent Homeland," Fact Sheets on Hungary (Budapest: Ministry ofForeign Affairs, 1997). 36 Miyajima, Kitasato Shibasabur& den,p. 55.
54
JAMES R. BARTHOLONIEWV
. ..... |~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~.
Figure 3. l.amagiwa
KarAzit
rO.
he made at the timebut becaus.eof theintellectual researchcontribution important forhiswork made a reputation he laid forlaterwork.While he ultimately foundation extentwhile resident cancer to any signiticant on cancer.Yama~-iwadid not s;tudybut.rather. his;, timewithVirchowv at all during in Berlin.In fact.he did nots;pecialize includedstudiesof cells. morThese effortsin generalpathology,. hims,;elf immersed regeneration phenomena.and all kindsof phological changes in inflamedtiss,-;ue. he was,, able to do the researchon artificial chancelsin cells. Asa morphologist. cancer [later]because he had managedto lay such a durablefoundation."' fromthatof Kitasato Virchowwas quite different w-ith Yamnagiwvas; relationship wvere onlya few yearswithKoch. The twobacteriologzists apartin aL-e:butVirchowx close. and theyneverbecame pers-onally ;senior to Yamnagiwa. yearswas,almostforty never contracted Moreover.Yamagiwva pulmonarytuberculosisin 1899 and wJasin died in 1902. But theywvere Virchovv again able to leave Japan.wvhile compatible had 2ainedreyearsearlierVir'chowv thir intellectual approachto medicine.-Many relating accordingto which "~everythinc, of pathology. nown forhis cellulartheory a ye ar-longpathologydemonstration offered fromcell~s.'Virchowv to cells comesnd one of itscorfullyabsorbedthispesetv wvhich course.through Yamna!-iwa thatcancer can be contention knownbut unproven Virchow'sollaries;,. equally wxell
N-arA shorz bioraphx of Pro-fessor ui s u>; bur Seiei shoden \z a K -~ Nagavo aMatar5. -arm o&'. n: , Fift-'ear hi..?-; K,5's::; Dcz7ctc^;BIF'r: jt f71-C:;
Katsusabur5in TjAc-GJ Marxva
Teikoku 1iniversirte;. Naga~o Tok-v:Thkx-) Imperial of Tok--o thePatholo!: Institnte ton oft 193-9,. VT.-1. p. 236. Da~i~aku.
255
external It is uncertain when causedbya chronic, stimulus.38 repetitive Yaexactly Virchow's ofcancer, but there toprove is reason magiwa gottheideaoftrying theory tothink theseedwas planted inBerlin. oncancer after However, didnotbegin Yamagiwa working immediately returning he spent onplague, toTokyo. several Instead, years beriberi, pulmonary distomiasis, bloodfluke andseveral other diseasesthat wereprominent inJaJapanese disease, forexample, Virchow pan.He and Virchow keptin touch; published Yamagiwa's 1895study ina specialsupplement ofplague, carried outduring a Taiwan epidemic, to theVirchow a signalhonor thejournal's Archiv, worldwide given In reputation. is no doubt February 1899 Yamagiwa contracted and there that this tuberculosis, affected thetiming on cancer. strongly ofhiswork The intensification ofhislatent interest incancer wellhavecomeduring thedifficult may months ofhisillness; early to a program certainly by 1905 he was fully committed of research, and a few hefounded months later hisown ofcancer a publicaGann[Cancer], journal studies, tionthat stillappears regularly.39 Yamagiwa's illness left himbereft ofenergy for longperiods, sometimes months at a time. most of 1910at theuniversity (He spent in Kyoto, where he had hospital taken sickwhilereturning from a conference in Osaka,too weakevento return to As a result, he washeavily Tokyo.) onthe dependent ofothers. cooperation Assistant often professors delivered his university and in thelaboratory lectures, he had to on a series ofassistants. rely The most ofthese important was IchikawaKoichi, a in veterinary twenty-five-year-old graduate medicine from Tohoku who University joinedYamagiwa's staff in 1913.Somereports that suggest Ichikawa's association with Yamagiwa waslargely accidental. In fact, Yamagiwa almost certainly hired him becauseofhisexpertise with animals andbecausehe hadearlier completed a study ofparasites. Fibiger's 1913announcement that hehadusedthenematode Spiroptera to generate parasite cancer in ratssurely madeIchikawa's experience with animals in general and parasites in particular all themorevaluableto Yamagiwa.40 Their was toprove partnership enormously productive. A sophisticated ofpathology knowledge andlongyears ofresearch activity guaranteed roleas theintellectual Yamagiwa's leaderof theeffort to produce cancer in thelaboratory. artificially Ichikawa's relative youth andinexperience should not obscure theimportance ofhis contribution, however. Yamagiwa was in precarious health andcouldperform thenecessary research tasks himself onlyoccasionally. It was therefore Ichikawa whosephysical laborassured thesuccessoftheir plan;one indication ofthecontribution he madeis his own,albeit unsuccessful, nomination for a NobelPrizeafter Yamagiwa's death, in 1936. Yamagiwa was by no meansthefirst investigator whohad hopedto prove Virchow's contention that chronic, localirritation couldgenerate cancer. Many others
38 Guenter B. Risse,"Rudolf Carl Virchow," in Dictionary of Scientific ed. Gillispie Biography, (cit.n. 13), Vol. 14,p. 41 (quotation); and Maruyama Kosaku,"Ayamari datta'kiseichui hatsugen setsu'de jusho" (Mistaken Nobel Prizeforthe"parasite in N5berush5 no hikari thesis"), to kage, ed. Kagaku(cit.n. 14),p. 19. 39 Irisawa Tatsukichi, "Yamagiwa kunno omoide"(Some memories ofMr.Yamagiwa), in Tokyo5 Teikoku Daigaku Byorigaku Kyoshitsu, ed. Nagayo(cit. n. 37), p. 115; and Nagayo,"Yamagiwa Katsusaburo Senseishoden"(cit.n. 37), p. 236. 40 OnYamagiwa's illness anditsconsequences see Irisawa, kunno omoide," "Yamagiwa p. 116.On hispartnership with Ichikawa see Maruyama, "Ayamari datta 'kiseichiu hatsugen setsu'dejusho"(cit. n. 38), pp. 21, 18.
256
JAMESR. BARTHOLOMEW
several using taken upthechallenge, andelsewhere-had Italy, inFrance, Germany, Longsubstances. and a rangeof chemical animals different typesof laboratory beganatthe cancer theartificial produced ultimately that experiments term, tedious 1 Septargets another sayson 31 August, in 1913;one account endofthesummer had not phase.Rabbits in theearliest straightforward Theywerefarfrom tember. with decidedto work butYamagiwa experiments, beenused in cancer previously werenotsusceptible becausethey longlifespan, hada relatively them becausethey convelongearsoffered andbecausetheir in their natural environment, to cancer applications external either first tried Ichikawa tissue. epithelial niently accessible nothing producing ofanimals, ofa form ofoliveoil in a smallnumber orinjections successwereno more andinjections Creosote orwoodtarapplications ofinterest. the or twisting of irritation-crushing methods weremechanical ful,and neither coal tar-sourcesdisagree decided totest tweezers. Theinvestigators then skin with to coal tar exposure that findings medical it-because ofprior as to whoproposed Thiswas a fortunate, workers. in thecancers of somefactory hadbeenimplicated work, experiments madethe that inthe coaltar theagent choice; casual, ifsomewhat later.41 many years identified until was notfully 3,4-benzpyrene, would one group therabbits intotwogroups: divided and Ichikawa Yamagiwa of a skinand internal injections coal tar applications receiveboth external received coal tarand skingroup other day;theother every medicine regenerating eachofthe The investigators then divided days. on alternate medicine regenerating to mechanical manipwassubjected onesubgroup into twosubgroups: groups larger knife or on skin with a or cuts the tweezers; as well,givensmallwounds ulations all the ofthese After twomonths procedures, was not. theother, subgroup control, but microscopic considerable swelling; and showed skin became inflamed rabbits' waspresent.42 no cancer showed that examinations of 1914. On 2 Aprilthe A newphasein theproject beganin theearlyspring theapthat totheTokyo reported Society Pathology delivered a paper investigators skin 112 rabbits' after on the akin a to growth malignant of a neoplasm pearance the of criticism. Members elicited much This report of coal tar applications. days andseveral hadall failed, efforts ofthissort earlier that werewellaware audience hadproduced andIchikawa that nothing inattendance contended Yamagiwa ofthose obtained thetwopathologists Atthispoint ofinflammation. more than a newtype andpurchased sixty CancerResearch Society from the(Japanese) funding private therabbits' forcontinued cages rabbits Unfortunately, additional experimentation. theCoxsidtheJune toeachother; season, rainy during were placedadjacent mostly most ofthem theanimals, attacked September.43 byearly killing iumprotozoan not animals two(or,byother three) haveit,however, accounts, would As fortune on ofriceormillet, likegrains wartlike butshowed shaped growths, onlysurvived he decided to add more andinmidDecember skin. rabbits, their bought Yamagiwa
setsu'de datta'kiseichu hatsugen see Maruyama, work "Ayamari andIchikawa's 4' On Yamagiwa YamaOnshi no tsuikai, nikansuru kenkyu "Ganno gen'in pp. 20-21; andIchikawaKoichi, jusho," of An account Katsusaburo: Professor for Yamagiwa myteacher, (A eulogy giwaSenseino tsuioku"
our research on the origin of cancer), in Toky6TeikokuDaigaku ByorigakuKyoshitsu,ed. Nagayo
"Cancer see Alexander Haddow, of 3,4-benzpyrene (cit.n. 37), Vol. 2, p. 172. On theidentification 1972),Vol.4, p. 776. Benton, (Chicago:William Britannica inEncyclopedia Research," pp. 21, 23. setsu'de jusho," hatsugen 42 Maruyama, datta'kiseichui "Ayamari (cit.n. 41), p. 173. no tsuikai" kenkyu ni kansuru "Gan no gen'in 43 Ichikawa,
257
had contained to theexperimental blackrabbits pool, whichhitherto onlywhite treatments continued. On 1 March1915 The coal tarandskin-regenerating rabbits. or papillomas had appeared on theskinoftheblackrabbits; tumors on 25 benign on 13 Maythewhite rabbits March holesopened ears.Finally, up intheir displayed first thecoal tarand skinthepapillomas as well.Whenthepapillomas appeared, so theresearchers treatments werediscontinued couldanalyze thederegenerating thatthe papillomas, withtheir velopments. Yamagiwaand Ichikawaconcluded evident wereindeed notmere strongly keratosis, tumors, neoplasms. By midMay, studies indicated that theformer on theblackrabbits microscopy were papillomas nowfully carcinomas. three white also displayed developed On 11June, rabbits the so faras Yamagiwa wasconcerned, thechronic irritation ofcancarcinomas; theory cerfirst formulated hadnowbeenproven.44 byVirchow As is often true for fundamental andIchikawa hadtoallay discoveries, Yamagiwa criticisms important andclarify certain issuesbefore their claims wonbroad acceptance.Some challenges involved issuesoffact, others ofinterpretation, and points stillothers matters of methodology. Theirfirst effort to present and support their claimscameinthesummer andfallof 1915.KikutaKichisaburo washired toproduce thenecessary of thelesions;and his efforts microphotographs wereprecise andthorough that a September enough presentation bythetwoinvestigators before theTokyo MedicalSociety cameoffsuccessfully. this Immediately following presentation, Yamagiwa an account published of their workin thesociety's journal, oftheir overseas apparent andother triumph spread bythese means, including timely visits toTokyo inAugust andDecember bySimon Flexner oftheRockefeller Institute andWilliam H. Welch ofJohns Hopkins University.45 Not everyone was immediately persuaded, however; and by thespring of 1916 Yamagiwa andIchikawa weretroubled bytheobservations ofvarious colleagues to theeffect therabbit that tumors seemed tohaveundergone nofurther morphological changes. Werethesurface skintumors true horny adenocarcinomas? By thistime Ichikawa hadaccepted a position atTohoku University (whoseFaculty ofAgriculture was then locatedin Sapporo), so Yamagiwa hired another youthful assistant, to helpwitha newbutrelated Murayama Koshichiro, The goal was to project. provethat theskintumors weresignificant by injecting themammary glandsof rabbits with a mixture ofcoal tarandlanolin in thehopeofproducing another set oftumors. Murayama's ownaccount insomedetail reveals thesingle-minded determination with which Yamagiwa approached this newresearch effort. On oneoccasion thesenior madehimstandabsolutely pathologist stillin thelaboratory for an hour nearly becausehe hadnotadministered theinjections totherabbits quickly theyounger enough; manfelt as though he were backinelementary school!46 In due the course, however, project succeeded inproducing fibrous sarcomas intherabbits, thus andextending vindicating theoriginal claims.
" Ichikawa, "Gan no gen'inni kansaru kenkyu no tsuikai" (cit. n. 41), pp. 174-175, 176. Both articles werecitedin 1966bytheBritish cancer researcher James F. Riley:"MastCells andCancer in theSkinofMice,"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;andMurayama Koshichiro, "Kaiko" (Reminiscence), in Tokyo Teikoku DaigakuBy5rigaku Kydshitsu, ed. Nagayo(cit.n. 37), Vol. 2, pp. 380-384,on p. 382.
14 Maruyama, "Ayamari datta'kiseichu hatsugen setsu'de jusho"(cit.n. 38), p. 24.
Tokyo Igakkai Zasshi, and a similarreport in theJournal of Cancer Research.Word
258
from delegations medical twoimportant way, WarI was stillunder WhileWorld and Flexner ofTokyo University. Institute atthePathology arrived States theUnited of WellsoftheUniversity latein 1917,whileH. Gideon trip madea second Welch the informed in 1918.Both American leda separate Japagroups delegation Chicago in theUnited quitea stir successwas creating Yamagiwa's that nesepathologists tookencouragement andIchikawa Yamagiwa in Europe. andto someextent States attheImperial tobe delivered a lecture begantoprepare as they reports these from or somemishap that was so worried Yamagiwa of Sciencesin August. Academy it talkandpresent theentire memorize he madeIchikawa that occur might disaster perfectly.47 off came thelecture Notsurprisingly, tohimaheadoftime. ofthetwo work theoriginal waytoreplicate wereunder efforts In themeantime, ofthe Hidejiro Tsutsui pupil, former of 1918Yamagiwa's In thespring pathologists. tarto in coal teacher of his applying themethods followed ChibaMedicalCollege, that executed and conceived was so carefully study ofmice.Thisparticular theskin used laboratory, the in cancer generating for technique thestandard it established inCopena similar project undertook himself In 1920and 1921Fibiger worldwide. Tsutsui. by modified as methods Yamagiwa-Ichikawa theoriginal following hagen, Europe and States in the United scientists Other successful. were equally His results outcomes.48 with favorable work didsimilar in a laboratory totheskin applied consistently coal tar, that thediscovery In fact, atfinding directed research activity of chain another set off cancausecancer setting, alike researchers medical and Chemists component. chemical thecancer-causing subcritical the to isolate United States-undertook and the Switzerland, inBritain, that indicated 1920s the in Zurich in and W. Dreyfus Bloch B. work by Early stance. 1932 In of cyclic hydrocarbons. to the class belonged probably crucial agent the of Londonwere Institute andJ.W. Cook of theCancerResearch E. L. Kennaway werenot "Theseadvances agent. as thecausative 3,4-benzpyrene able to identify repercusandlasting buthadimmediate inthemselves importance ofutmost merely Intheworld."49 throughout research cancer aspectofexperimental sionson every boost an enormous received research carcinogen field ofchemical deed,theentire andIchikawa. ofYamagiwa triumph theepoch-making from events. theoriginal after years wererendered many assessments these However, ofwelltheact , support require ofa NobelPrizeinthe1920swould Any prospect pein this early relatively andJapan States, theUnited in Europe, placedscientists inEurope, twoyears Ichikawa favorable. spent were indications quite Theearly riod. skeptical for ofcancer production methods theJapanese demonstrating 1923-1925, oftheperiod testimony itis clearfrom andelsewhere; in Paris, Berlin, colleagues was imInstitute of theKarolinska FolkeHenschen he madesomeconverts. that for Institute Wilhelm (WarBiology. oftheKaiser Warburg andso wasOtto pressed, German 1924thenoted patholohimself wona Nobelin 1931.)In September burg visited of Freiburg Japanand metwith of the University gistLudwigAschoff researchers ofyoung a number received Japanese hadpreviously Aschoff Yamagiwa.
pp. 176-177. no tsukai," kenkyd nikansaru "Gan no gen'in Ichikawa, setsu'dejush6"(cit.n. 38), 'kiseichlhatsugen datta "Ayamari work see Maruyama, On Tsutsui's see Paul use of thesetechniques et al., Nobel (cit. n. 24), p. 247. On Fibiger's p. 24, and SchUck orMedicine ed. Magill, (cit.n. 19), inNobelPrizeWinners, Physiology "Johannes Madden, Fibiger,' Vol. 1,pp. 267-274,on p. 273. 49 Haddow, (cit.n. 41), p. 776. "CancerResearch"
47 48
259
them friend athisinstitute, andhe was clearly among Yamagiwa's NagayoMataro, of the Japanese cancerresearchers. impressed by the accomplishments Indeed, inDecember Aschoff was sufficiently that and 1925he proposed impressed Fibiger as jointcandidates for the1926NobelPrizeinPhysiology orMedicine.50 Yamagiwa noneofthese was quiteenough. Unfortunately, developments Fibiger's theevaluation ofhis work prominence, and by someexternal referees, theperceptions ofboth heldbytheKarolinska Institute weretheproblem in faculty Stockholm. By 1927there wasbroad that agreement Yamagiwa-andFibiger-had donesomething Butthere important. was never a possibility that could Yamagiwa receive an unshared NobelPrize;itwouldat bestbe shared with Fibiger. Between 1923andthefallof 1927theDanishscientist received a total offourteen nominawhileYamagiwa tions, obtained six.The nominators' institutional affiliations and of origin countries are revealing. was very mucha Scandinavian Fibiger favorite son,earning tworecommendations from twofrom Norway, Denmark, twofrom andonefrom Finland. Inaddition, Sweden, three scientists from Germany submitted hisname, oneeachfrom alongwith Austria, Belgium, andtheUnited Switzerland, States.By contrast, forYamagiwa support cameprimarily from Japan-four colleaguesfrom Tokyo University, eachwriting separately; he also hadonenomination from Germany andone from theUnited States.5' NoneoftheJapanese nominators made reference to Fibiger in their letters; eightof theFibiger nominators mentioned Yamagiwa. The Fibiger NobelPrizeof 1927has for many years beenregarded as oneofthe fewmajor blunders evercommitted bya NobelPrizecommittee in science. Beginningin 1913,Fibiger had contended in thestomach that tumors linings of certain ratsweredirectly due to thepresence oftheSpiroptera neoplastica worm, a small theratsingested organism whenthey devoured a particular form ofcockroach in a Copenhagen sugar refining mill. When he collected these cockroaches andfedthem tonormal white miceinthelaboratory, most becameinfected with theworms anda
50Forevidence that Ichikawa madesomeconverts see YamagiwaKatsusabur6 toNagayoMataro, 26 Dec. 1923,in Tokyo Teikoku DaigakuByorigaku Kyoshitsu (cit.n. 37), Vol. 2, p. 161.Henschen's support is clearfrom FolkeHenschen, "Betankande J.Fibiger och K. Yamagiwa," angaende 31 Aug. 1926,in Karolinska Institutet, Medic.Nob.Kom.1926 P. M. Fbrsdndelser ochBetdnkanden (Stockholm:Karolinska Institutet, 1926) (hereafter, volumes ofthis series willbe cited bytitle, 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 1 Sept. 1927,inMedic.NobelKom.1927 P M. och O. Warburg," Fdrsdndelser och Betdnkanden, pp. 1-5. In thisreport rector of theKarolinska, Bergstrand, wrote: "It is significant that OttoWarburg in a lecture heldin 1926 saysthat Yamagiwa's experiments had shown that theold clinicalandpathological-anatomical ofchronic understanding stimulation as the reason for cancer is true." On Aschoff's interest see Nagayo Hakushi KinenKai, ed.,NagayoMatare den(Biography ofNagayo Matar6) (Tokyo: Nagayo Hakushi KinenKai, 1944),p. 110.A photograph ofAschoff andNagayo taken inTokyo is inthefront section ofthebook.ForAschoff's letter proposingFibiger andYamagiwa, dated9 Oct. 1925,see Medic.Nob. Kom.1926 P. M. Fdrsdndelser och Betdnkanden, pp. 1-2. Scandinavian 51 Fibiger's nominators were Valdemar Bie andThorvald Madsen(Denmark), Francis Harbitz andVilhelm Schaldemose (Norway), Ulrik QuenselandFolkeHenschen (Sweden), andAxel Wallgren (Finland).Others included Max Askanazy (Switzerland), GeorgGruber (Austria), Frans Daels (Belgium), andAlexander Maximow (United States)andLudwig Aschoff, Friedrich Kopsch, and ErichOpitz (Germany). For detailssee theappropriate volumes of theKarolinska Institute's archival materials for1923, 1925, 1926,and 1927. For Yamagiwa's nominating letters see Medic. Nob.Kom.1925P. M. Firsdndelsen ochBetdnkanden, for theletters from Japan byNagayoMataro, Hayashi Haruo,YokoteChiyanosuke, and Kure Shuzo;Med. Nob. Kom.1926 P M. Fbrsdndelsen ochBetdnkanden, for Aschoff's letter; andMed.Nob.Kom.1928 R M. Fbrsdndelsen ochBetdnkanden,for Maximow's letter.
260
thestomach wasevenabletotransfer Fibiger cancer. contracted number significant findthese Formany years mice.52 toother causedbytheworms cancers seemingly chronic of Virchow's as a clearconfirmation ingswereseenby mostresearchers andintellectemporal wereaccorded they a time andfor ofcancer, theory irritation ofYamagiwa overthelater-butmuchmoreimportant-discoveries tualpriority andIchikawa. when focus proper into hadnotall beenbrought facts the pertinent Unfortunately, the beganconsidering faculty Institute and theKarolinska theNobel committee proGunnar studies. Hedren, incancer achievements ofa NobelPrizefor possibility downin to slowthings hadtried at theKarolinska, anatomy fessor ofpathological on thebasic value of Fibi"Researches report: in a confidential 1923, writing to anyresult.... I havean obligation ... havestillnotyielded ger'sinvestigation worthithe about judgment definitive a more toreach peopleneedtime ... that insist itwasonly tolisten; willing Butfewwere work for a Nobelprize." nessofFibiger's that evidence toFibiger, beenawarded hadalready theprize in 1928and 1929,after at all but, notcausedby theworms wereprobably thetumors that was presented A in thedietoftheratsandlaboraofvitamin with a deficiency associated rather, mice.53 tory caution. Ever to acceptHedren's is whyso fewwerewilling The real mystery by appearing work were and Ichikawa's of Yamagiwa evaluations morefavorable on the findings Japanese reports favorable ofthe1920s;andthemore thelatter part hisinclaimsfor their espoused champions Fibiger's themore vigorously became, for the Nobel; had Fibiger only In Folke Henschen proposed tellectual priority. 1923 a prize. to share deserved that andFibiger Yamagiwa bylate 1926he was arguing butat this point in 1922andin 1923werereasonable, expressed "Thereservations be established 1926."It should rightly he wrote on 31 August no longer are," they redelvedintothecarcinoma whofirst between Fibiger, that theprizebe divided Hentarcarcinoma."954 of theexperimental thediscoverer andYamagiwa, search, ofFreiburg. ofChicagoandbyAschoff viewwas shared byMaximow schen's of theNobel The official history was a shared prizenotproffered? then, Why, at thetimewere considerations that thepertinent in 1950reports Prizespublished beendiscovered of coal tarhad supposedly that thecancer-producing properties work was notreally on human from observations beings-thusYamagiwa's earlier ofdistheentire hadinitiated process experiments that Fibiger's original-andthat thecontribofcourse; were These among mistaken, inanycase.55 judgments covery a similar blunder error by his werea tactical himself, factors byYamagiwa uting his to defend toEurope totravel inJapan, inability physical Yamagiwa's supporters whoparticireferees ofcertain chauvinism European andtheunmistakable claims, process. patedintheNobelnomination exone-was to havepraised Fibiger mistake-anunderstandable Yamagiwa's readers for reminded In 1930the inprint. Yamagiwa, Lancet,initsobituary cessively
(cit.n. 48), pp. 267-273. Fibiger" "Johannes Madden, 31 Aug. 1923,in Medic.Nob. Kom.1924 J.Fibiger," angaende "Betankande Hedren, Gunnar on the andE. T. Bell, "Studies See also ClaudeR. Hitchcock ochBetankanden. P. M. Fdrsdndelser June Journal of theNationalCancerInstitute, neopolasticum," Parasite, Gongylonema Nematode 1952,12:1345-1387. (cit.n. 50), p. 13. och K. Yamagiwa" J.Fibiger angdende "Betankande 54 Henschen, 55 Schfick etal., Nobel(cit.n. 24), p. 235.
52 53
261
NorwereYamagiwa's prospects much enhanced bytheliterary character andthe modest toneofthefour letters sent toStockholm byhisTokyo colleagues. In recent years there has beena lively debate inJapan aboutwhat is required to wina Nobel
56 "Katsusaburo Yamagiwa"Lancet,17 May 1930,218:1084; and letter ofThorvald Madsen,31 Jan.1927,inMedic.Nob.Kom.1926 P. M. Fcrsdndelser ochBetdnkanden, p. 10. Madsenwrote (in Danish):"Fibiger brought cancer studies from a stagewhere they weredeadin thewater. His work's [importance] is underscored by theworkof Yamagiwaand Ichikawa who first achievedthe [tar cancer].[Theywrote]: 'Encouraged byFibiger's glorious we havebeendoingexperiachievement, mental work on cancersincelastfall."' 57 For Gruber's letter, dated22 Jan.1927, see Medic.Nob. Kom. 1927 P. M. Forsdndelser och Betdnkanden, p. 7. Gruber wrote (in German): "Yamagiwa andIchikawa recently followed thepath already trodden byFibiger, producing cancer bypainting coal tar[on a rabbit's ear]inspired bythe recognized successesofFibiger whodealtwith spiroptera research. Theyled [us] to methodologies rich in results. Fibiger andBangalso madesuccessful use ofthese methodologies." ForBergstrand's report see Bergstrand, "Betankande angaende J.Fibiger och 0. Warburg" (cit.n. 50), pp. 2-3. Bergstrand wrote: "Both[Yamagiwa andIchikawa] admit that werestimulated they byFibiger's successfulexperiment. Butto claimthat Yamagiwa's work is justa continuation ofFibiger's seemstome to go entirely toofar! There is a considerable difference between developing cancer through a parasitizingworm andthrough a chemically effective means." 58 YamagiwaKatsusaburo toNagayoMataro, 30 Mar.1929,in Tokyo Teikoku DaigakuByorigaku 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.
in 1924.58 pathologist
work inoneofhisearliest on thetarcarcinoma theJapanese that reports pathologist inthefirst hisdecision tolaunch hiscancer studies hadattributed placetothe"glorious achievement ofFibiger." Itis probably as the British medical true, weekly noted, that has a scientific worker "rarely tribute toanother"; paida more itwas generous certainly a blunder inthecontext oftheNobelPrize.In hisNobelnomination letter of29 January hisUniversity ofCopenhagen 1927for Thorvald colleague, Madsen, director ofDenmark's State Serum seizedonYamagiwa's as a major words Institute, reasonto accordFibiger sole priority.56 Other referees a misEuropean presented leading viewofevents. oftheUniversity GeorgGruber ofInnsbruck described Yamagiwaand Ichikawa as having "followed Fibiger's path"butthen inconsistently in reference noted, to Fibiger's researches of 1920-1921, that he andhis assistant haddeveloped effective methods ofcancer production byfollowing themethods of Yamagiwa andIchikawa. Gruber heldthat Fibiger alonedeserved theprize.To his credit, K. J.H. Bergstrand, rector oftheKarolinska Institute, flatly denied Gruber's claimthat the Japanese investigators hadfollowed ina referee's Fibiger's path report dated 1 September1927.57 In this intensely political evaluation process, Yamagiwa wastosomeextent a victim ofboth hisownphysical andthelackofpolitical infirmity sophistication ofthe well-meaning colleaguesat Tokyo University who submitted his nameto Stockholm. Thedebilitating effects ofhistuberculosis meant that Yamagiwa couldrarely travel evenin Japan, let alone acceptthemany European invitations that thelate 1920sbrought tohislaboratory. In 1929theGerman government gavehim animportant decoration forhis work, theSophieNordhoff-Jung Prize;buttheceremony had to be conducted in Tokyo bytheGerman ambassador becauseofYamagiwa's precarious health. Andalmost certainly he attracted thesupport ofAlexander Maximowand LudwigAschoff becausethesetwoscientists wereable to visithimin in fact, Tokyo. Aschoff, in his letter explicitly stated of nomination for Yamagiwa that hisbacking hadresulted from what he hadlearned when he visited theTokyo
262
comAgency intheScienceandTechnology official Prize, andin 1994a prominent own inpromoting their beentoomodest haveoften scientists that Japanese plained inDecemcolleagues byYamagiwa's dispatched letters ofthe Perusal achievements. Hayashi claim.Nagayo Mataro, forthe STA official's support ber 1924 offers factual straightforward, very andKureShuzoallwrote Chiyanosuke, Yokote Haruo, word ofextravaora single ofenthusiasm a hint with never inGerman, expositions their with andin accordance separately wrote they still, though Worse praise. gant and almost humble each useda remarkably work, viewsofYamagiwa's particular "In closidentical: they werenearly closingstatement-and formulaic certainly fortheNobel that thecommittee chairman honorable thehighly ing,I am asking andI hopethat ofYamagiwa; ofthework an exactevaluation Prize... undertake letters these between Thecontrast willendorse recommendation."5s my committee the evident. is painfully Europe from Fibiger about letters boastful andthe sometimes was orMedicine Physiology for that theNobelCommittee beennoted Ithasoften to was itsrefusal by the 1926 prizefiasco;one consequence embarrassed deeply decades. four thenext studies over incancer achievements prizefor another confer in the award-forexample, theFibiger to defend tried thecommittee For a time, in abandoned 1972, was finally of 1950 and 1962.This strategy histories official that the1926Nobel "Itcertainly seems strange stated flatly: the official history when earlyin 1928, died Fibiger Fibiger." to Johannes havebeenawarded Prizeshould thereafter, not long died Yamagiwa to come. that were fewoftheattacks witnessing the Lancet In evident. was already the embarrassment inMarch1930;andsomeof over"It to wrote: is impossible University ofWashington William Cramer obituary this To of cancer." the for of study discovery theimportance Yamagiwa's estimate around from cancer researchers cited are by classicpapers regularly Yamagiwa's day, on Yamaa memorial lecture delivered In 1966an agedFolkeHenschen theworld. reminded earlier and of events forty years the in he recalled which in Tokyo giwa should andYamagiwa that Fibiger that evenin 1926he had thought theaudience heldin thisviewwas now widely that to suggest theNobel Prize.Perhaps share "The in Belguim: he approvingly quoteda researcher andelsewhere, Scandinavia doesnotneeda NobelPrize."60 ofcancer manwhosolvestheenigma
KATO'S NOBEL CANDIDACY, 1935-1936
earliercandidaciesof Kitasatoand Yamagiwa. In theearly1920s Kato (1890-1979)
case thanthe in themid 1930sis a moreambiguous candidacy Kato Gen'ichi's
andin 1934he ofnerve decrementless conduction, hisso-called theory announced his under of how researchers account working detailed a monographic published
complaint 59 Medic. pp. 3-9. Fortherecent ochBetdnkanden, Nob.Kom.1925 P. M. Fbrsdndelser mezasu:kis6kenkyO rikkoku' jUshino seisaku no 'Kagakugijutsu see AtarashiKinju,"Nijilisseiki ofbasic theimportance andtechnology: Emphasize inscience strong a nation (How tocreate tenkai" 20 June 1994,no. 114,p. 1.Atthetime JohJ (Sciencepolicyinformation), KeizaiSeisaku research), Agency. BureauintheScienceandTechnology Promotion oftheTechnology was chief Atarashi American 60 H. Schtick et al., Nobel: TheMan and His Prizes(New York/London/Amsterdam: etal., Nobel(cit. see SchUck theaward tojustify attempts 1972),pp. 188-189.Forearlier Elsevier, et al., Nobel: TheMan and His Prizes(Amsterdam/London/ n. 24), pp. 234-236; and H. SchUck "The see William criticisms Cramer, orexplicit 1962),pp.246-247.Forimplied Elsevier, NewYork: TarCan"Yamagiwa's 20 May 1930,218:1155;andFolkeHenschen, Lancet, LateProf. Yamagiwa," Gann,Dec. 1968,59:451. Significance," cerandItsHistorical
JAPAINESE NOBEL CAN'DIDATES
263
Mainichi Shimbun.
close isionhadmanaged toisolate single muscle andnerve fibers andperform superx valuable on them. Several oftheexperiments established theexistence expeniments ofreflex nenes andreflex inhibitonv excitatory nerves. Theselatter achievements. w erex% idelvheralded andformed theprincipal basisfor Nobelnominaespecialiy. tions on hisbehalf bv INan Pavlov(Lenin-grad). Mariano R. Castex(BuenosAires). and sev eralcolleagues atKeio University. Indeed. Katowasa verv credible nominee for a NobelPrize, as subsequent events wvere to show. Butthisis notto saythat he should haxereceixed a prize.In medicine, there arenearly more especially. alw~ays ing, deserv than canever be officially acknowledged. Kitasato possible recipients and should haxereceived Nobelcommittees hadjudgedcerYamagiwxa prizes: particular tain results though their workmetthecommittees' criteria. thetwo prizew~orthy: grot no share oftheawards becausetheir achievements weremisconstrued Japanese orinappropniatelx credited to others. Kato.in contrast. had notproduced work of the kind forxxhich a prizewas explicitly conferred. although the 1932 awardto Adrian of Bnitain was citedbyone Nobelreferee as preempting a possible Edgar
award to Kato. (See Figure 4i
Whatever themenits ofKato'scase. hiscandidacy andtheevents leading to itare instructive becauseoftheextraordinarv they shedon theintricate that light politics Nobel candidacies can sometimes engender. Friends andsupporters inthescientific naturally tookstepsto promote his cause. and so did highofficials community of the There was,infact. somecollusion between the twocamps. Japanese government. Attheage of tw~enty unusual circumstances-Kato becamea pro-eight-under ofKitasato. Keio University's first medical schooldeanwhorecruited himfor t~g6 the Keio faculty in 1918. In thefaceof significant Kitasato wentto opposition, remarkable to promote Kato'scareer. Kato himself was less accomplished lengths
264
skillful than buthe wasmore than hispowerful mentor, inJapanese medical politics as himself as favorably toposition he tooksteps Indeed, stage. on theinternational is a poignant cameup short ultimately ofothers andthose Thathisefforts possible. Nobel of deserving of thetaskat hand:theplethora of thedifficulties illustration from Europe, ofJapan diminishing-isolation thecontinuing-though candidates, commuresearch medical oftheJapanese factionalism destructive andtheintense, inthis period. nity placedthan goal,Katowasbetter one'sultimate were Ifa NobelPrizeinmedicine ophthalmoloprominent ofa socially it.Bornin 1890tothefamily toachieve most thebesteducation andreceived up inaffluence he grew Prefecture, gistinOkayama as farawayas Kyfrom patients hadto offer. His father's attracted practice Japan from After graduating home. milesto thewestoftheir ormore twohundred ushu, at Kyoto in medicine Kato enrolled Higher Schoolin Tokyo, First theprestigious whichtheFirst University-for rather thanat theinstitution-Tokyo University, had whosehealth inorder tobe closetohisfather, him, Schoolhadprepared Higher upongraduating Kyoto University from a goldwatch He received todecline. begun inphysiology. program graduate in 1916andentered the university's as valedictorian he cametohave whom with Hidezurumaru, was Ishikawa supervisor His graduate tumultuous relationship. a troubled, that thebitter produced theelements nowto disentangle matter It is no simple than a farless prominent background Ishikawa camefrom between them. conflict that Kato ofdeference insisted on a degree older, years Katoand,while justtwelve temdifferent thetwohadvery that There areindications toextend. wasdisinclined to pursue adcohort of thelastJapanese Ishikawa was part Moreover, peraments. studied World WarI, whileKatonever in Germany before studies medical vanced intense them reflected between theproblems Atbottom, however, inEurope atall.62 differences. intellectual a professor ofMax Verworn, wasoneoftwoprominent pupils Japanese Ishikawa andafter decadeofthetwentieth thefirst century atGottingen during ofphysiology was conofBonn.Verworn Institute at theUniversity 1910headofthePhysiology studied and Ishikawa at thetime, one of theworld's leading physiologists sidered exists to 1912.A gooddealofevidence 1908andJuly November with him between ina profesbecame andremained Verworn andIshikawa close,especially showthat andwasinterofcellular advocate wasa leading Verworn physiology context. sional Butitwashis ofliving basicphysiological organisms.63 processes estedinthemost Ishikawa that mostdeeply affected of nerve and, in thefield physiology opinions Kato. later, Muller(1801-1858)and Emil Du Boisthe timeof Johannes At least from between therelationship had debated physiologists (1818-1896),nerve Reymond
61 of prominent (A gazeteer fud6ki in Ky6dono jimbutsu YoshimuraHisako,"Kato Gen'ichi," NiimiShimin Prefecture: Kaikan(Niimi, Okayama ed. NiimiShimin theregion), from personalities Kaikan,1989),pp. 152-165,esp. pp. 153-155. docofJapanese dictionary (Biographical hakaseroku 62 "IshikawaHidezurumaru," inDai Nihon camefrom Vol. 2, p. 298. Ishikawa 1922-1930), Hattensha, ed. Iseki Kur6(Tokyo: holders), torate samurai. wereformer ofacademics in an erawhenthemajority background a commoner ed. Gillispie (cit.n. 13), ofScientific Biography, inDictionary 63 K. E. Rothschuh, "Max Verworn," Vol. 14,p. 2.
265
nerve stimuli-mechanical orelectrical-and nerve Forsome, Du Boisresponses. hadappeared to settle Reymond theissuewhen he formulated theso-called all-ornonelaw.Thisprinciple three that abovea minimum incorporated major arguments: threshold there is no connection between thestrength level, ofa nerve stimulus and thestrength of theresponse; that theintensity of excitation in a medullated nerve under normal conditions remains thetimeoftransmission; unchanged during and that therateofconduction also remains constant at all distances from thepoint of stimulation. dissented from ofthis Verworn, on thebasisof however, part paradigm hisstudies ofcertain from theRed Sea, especially rhizopods Difflugia;he reported that inthese theconduction rhizopods ofnerve excitation takes a decreplace"with ment ofintensity andrapidity" that becomes with thedistance larger "from the point of stimulation until thewaveofexcitation is obliterated." Theseandother findings gaveVerworn considerable to thepoint in 1911he was invited that prominence, to deliver theprestigious Silliman Lectures at Yale University. Ishikawa remained a faithful adherent ofVerworn's nerve from histeacher physiology, dissenting on only certain details.64 With World WarI precluding thepossibility ofstudy in Germany, Katospent two crucial after hisgraduation years from December Kyoto 1916-December University, 1918,working under Ishikawa. During thisperiod theyounger physiologist develof thelaboratory oped many and muchof theproblem techniques awareness that would subsequently guide his professional work.Reactingto the research of Friedrich W Frolich, another student ofVerworn's atBonn, Ishikawa determined to showthat nerve andnerve excitability were conductivity separate phenomena. Kato, in his first yearof graduate study, was instructed to replicate theexperiments of another German P. F. F Grutzner, physiologist, regarding theeffects ofthehalogens on nerve conduction. These salts-chlorine, bromine, iodine, and fluorine-were believed toincrease therhythm-making ability ofnerves, which displayed a pattern of increased excitability, spontaneous contraction, and paralysis whenexposedto them. Katoconfirmed these findings, as wellas Grutzner's claimthat chlorine producedthemost intense effects. During these samemonths he also studied theeffect ofsarcolactic acid on therhythm-making ability ofnerves, measuring theintensity andduration ofthecontractions that resulted.65 Kato'ssubsequent studies under Ishikawa weremoreor less a continuation of these projects. The Japanese toad,Bufo vulgaris,was frequently usedfor research in Ishikawa's purposes laboratory, and thesenior physiologist instructed Kato to therhythm-making study ability of a toadnerve and to investigate whether there was an increase in excitability under varying conditions of narcosis. Did theseeffects on thelength depend ofthenarcotized segment? Various narcotics wereemployed, especially alcohol,urethane, and morphine. In halfthecases Kato found that there wasno increase inexcitability. He also sought todiscover which anesthetics weremostpowerful in increasing a toadnerve's rhythm-making ability when
64 Gen'ichi Kato, TheTheory ofDecrementless Conduction inNarcotised Region ofNerve (Tokyo: Nankodo,1924),p. 3; Max Verworn, Irritability: A Physiological Analysis oftheGeneral Effect of Stimuli inLiving Substance (New Haven, Conn.:Yale Univ.Press,1913', pp. 128-129,127 (quotation);andHidezurumaru Ishikawa,Studies intheFundamental Phenomena ofLife(Kyoto: Institute ofPhysiology, 1924),pp. 110-112. 65 Ishikawa, Studies in theFundamental Phenomena ofLife, pp. 4-5, 112,116-117.
266
andalcoAmmonia trunk. thenerve toparalyze sufficient inconcentrations applied of thesubcocainetheleasteffective, to be themosteffective, hol werefound studied.66 stances that butthose basicviews, to confirm Ishikawa's tended studies Theseparticular 1918wereto sowtheseedsoflongandNovember April outbetween Katocarried this One wouldnotsuspect physiologists. thetwoJapanese between term conflict under becauseKato was stillworking perhaps record, published theoriginal from During in print. hismentor to defy handandwas notin a position firm Ishikawa's ofdecremenphenomenon theapparent askedKatotostudy Ishikawa months these vulgaris Bufo againusing ofnarcosis, conditions varying under conduction talnerve conduction nerve todecremental hadcalledattention Max Verworn for theresearch. as an opportunity viewedKato'sassignment and Ishikawa studies, in hisDifflugia ThusKatowasasked opinions. mentor's ofhisGerman insupport evidence togather substances-ether, whenvariousnarcotizing conductivity to examineelectrical carcocaine, sulphonol, hydrate, chloral urethane, morphine, alcohol, chloroform, to a nerve applied solution-were in Ringer's dissolved bonicacid,and ammonia segment. faculty's intheKyoto medical published ofKato'sstudies thereport from Judging the testing various goal.After itsostensible achieved theproject in-house journal, Katoascertained they produced, curves the nerve conduction andgraphing narcotics segment, nerve narcotized within the ata point E curve, measured that theso-called this to Ishikawa, According descends gradually." andthen temporarily "first ascends [of the real excitability that the fact of confirmation toa "definite amounted finding narcosis]." [with on affection decreases butgradually increases, never thenerve] ofnerve theory in thedecremental belief Verworn's confirmed theresults In short, reflect not did the of evidence this wasthat interpretation Theproblem conduction. while the work of most had completed Kato the matter. of judgment Kato'ssettled his when supervisor extended for an period; the was awayfrom campus Ishikawa Acclaimswerein error. Verworn's that his suspicion Kato announced returned, apprenan Kato "impudent in calling Ishikawa exploded anger, toonereport cording him.67 manofdefying theyounger tice"andaccusing in Kato'slongcareer. event as the in defining seen be retrospect can Thisincident vacillated himthat toward attitude an Ishikawa adopted because first at He suffered byKitaintervention an But unexpected overt and antagonism. indifference between leading from many his estrangement Kato's Despite altered prospects. sato soon mainhad carefully Kitasato universities, at Japan's imperial medicalspecialists noted with the patholwas one of them this from group; friendships tained particular University. ofKyoto as president whoin 1918was serving ArakiTorasaburo, ogist to schoolandneeded Keio'snewmedical oforganizing was intheprocess Kitasato "menwith younger He askedArakiif he knewof anybright a faculty. assemble himofan advanced graduate bytelling responded theKyoto president backbone"; to haverecognized a professor." Kitasato with appears whohad"quarreled student was at Keio that Kato a lectureship he offered and in December a kindred spirit, accepted.68 gratefully
66
Ibid.,p. 99. (cit.n. 61), p. 156. "KatoGen'ichi" Ibid.,pp. 73, 74; andYoshimura, 68 p. 156. "KatoGen'ichi," Yoshimura,
67
267
Kitasato's commitment revealed that to Kato went Events farbeyond gradually mostyounger scientists couldhopefor. In February anything 1919,after justtwo raisedKato to therankof fullprofessor witha months of employment, Kitasato Whenother to match. thedeansimply salary toldthem professors complained, that wasunusually andwould theyoung fulfill the physiologist promising highest professionalexpectations in tenyears' time. Like other Keio faculty Katohad members, newequipment andresearch facilities as goodas anyin Japan. Eventhen, entirely he becameknown for"borrowing" resources from therestof themedicalschool. Kato'sreputation andthefavorable treatment he received did notgo unnoticed by andwithin twoorthree he hadattracted more aspiring younger than scientists, years to his laboratory. a dozenresearch associates researchers By 1926 he had twenty under hisdirection.69 working After hismoveto Keio University, Kato didnotimmediately return to thebasic on nerve research conduction that had occupied himduring his lastmonths with Ishikawa. from Apart thedemands oforganizing hislaboratory andrecruiting a staff, he wasatfirst involved ina project on theneurological ofberiberi. Thiswas aspects a topic that hadengaged medical Japanese researchers for more than and forty years towhich hadmadea major TakagiKanehiro contribution that the bydemonstrating incidence ofberiberi couldbe drastically reduced bydietary modifications. Kato's work ledtocoauthored in 1921and1924;beriberi publications remained an interest for someyears.70 Butfrom thesummer of 1921research on nerve conduction occupiedmost ofhistime. norecord Unfortunately, shows theexactsequence ofresearch-related events perto thistopicin Kato'slaboratory. taining Internal evidence from topublications, with other gether shows that ofthework material, most tothetheory leading ofwhat cameto be calleddecrementless nerve conduction was completed between January tour ofmedical spection research facilities intheUnited States andEurope, paidfor bytheuniversity; toleaving, prior he consulted extensively with hisprincipal assisMaki Ryokichi, tant, about tobe pursued projects in hisabsence. Atleastsincethe autumn of1918Katohadbeensuspicious ofclaims byVerworn, Keith Lucas,Edgar Adrian, andothers that theintensity ofnerve transmissions declines gradually when thenerve encounters animpaired impulse nerve segment, typically created byexposureto narcotics, or a mechanically asphyxia, induced injury. He gaveMaki some about howtoproceed, suggestions buttheextent ofhisguidance is difficult togauge sincemuchof theworkwas repeated by thetwoof them after Kato returned to inAugust Tokyo 1922.71 Katohadlearned certain research techniques from Ishikawa andfrom closereadingoftheliterature. He hadadopted thecontemporary nerve physiologists' practice of soaking nerve-muscle preparations in Ringer's solution and of employing cirwith cuitry properly positioned electrodes anda narcotizing chamber. In somecases
69 Ibid.; and Gen'ichiKato, Further Studieson Decrementless Conduction (Tokyo:Nankodo, 1926),p. 1. 70 Robert R. Williams, Toward theConquest ofBeriberi (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 KinenJigy6 Iinkai,1965),pp. 93-122. See also Kato, Theory of Decrementless Conduction (cit.n. 64), p. 129. 71 Yoshimura, "KatoGen'ichi" (cit.n. 61), p. 157.
1922 and March 1924. In September1921 Kato leftJapanon an eleven-month in-
268
which through lengths ofdiffering subchambers contained chamber thenarcotizing thenarcotizing werepassed.For themostpart, fibers nerve thesameor different andthelike-were stanurethane, alcohol, cocaine, employed-ether, substances someofhisownprocedures, introduced Katogradually practitioners. dardamong lengths ofdiffering segments ofnerve examination thesimultaneous among which the was probably animals) different from than (rather thesameanimal taken from as appropriate. procedures these employed coworkers AllofKato's important. most Onewastheinfluence issues. onfour byKato,focused Maki'sresearch, replicated segnerve twonarcotized between nerve of a piece of unnarcotized of thelength either tolose conduction. for required ofnarcosis on thedepth anditseffect ments to a stimulus electric a strong that a claimin theliterature hadto do with Another an attached from elicita response wouldsometimes of nerve narcotized segment region to thenarcotized external an electrode from evenwhena stimulus muscle, as some generated, Was thisresponse response. could not cause a contraction therelative concerned question The third segment? within thenarcotized claimed, externally instigated stimulus, and an electrical stimulus of a mechanical effects on a Andthelastfocused preparation. nerve-muscle on a narcotized andinternally, Would a narcotized segment. within valuefor the total lossofconductivity threshold from at various distances at electrodes positioned be reached gradually thispoint occur or wouldtheloss of conduction chamber, thedistalend of thenarcotized at all thepoints?73 simultaneously stimulation ofinternal several points chamber with a narcotizing created Having of diftwonerve segments Makiprepared stimulation, of external andtwopoints and thesametoad(Bufo from vulgaris) subjected attached tomuscles lengths fering in Ringer's urethane alcoholvapor, chloroform, narcotics-ether, them to various conduction held both that andcocaine.Decrement theory chlorohydrate, solution, ofthe to thedistance failgradually, according should region within thenarcotized a of stretch and that the longer end of chamber, the distal from electrode recording a one. Maki than shorter found, conduction sooner lose nerveshould narcotized within the all points and that was irrelevant to theoutcome length that however, of the absence a result signifying conduction simultaneously, lost ofnarcosis region conduction in nerve intensity.74 anydecrement nerve ofthedecrementless toKato'sformulation contributed assistants Twoother thata showedexperimentally in thisperiod.Otsuka Tokichi conduction theory nerve a longnarcotized can travel through nerve justas rapidly full-sized impulse is of narcosis thedepth a short narcotized provided as through segment segment of musclecontractions the intensity Otsuka Kunio studied uniform. Similarly, The themuscle. from atdifferent distances ofidentical strength bystimuli instigated had been an important in thissituation contracted muscles differently that belief work But theyounger Otsuka's of decrement in support theory. pieceof evidence he was able to show and measurements, seriesof tests it.By a complex removed wereduetoexperimencontraction muscle ofdiffering heights earlier that findings
72 Max Verworn's (cit.n.64),pp. 13-14.Katocriticized Conduction ofDecrementless Kato,Theory toadsand averaging of different thenerves from measurements discipleF. W Frolichfortaking theresults. 73 Ibid., pp. 73, 79, 89, 92. 74 Ibid., pp. 71-79.
269
little infact stimulus distance orno roleinthenature talerror andthat ofthe played contractions.75 InApril1923theKatoteam felt for a first oftheir ready work public presentation inKyushu andjourneyed toFukuoka for oftheJapanese thenational meeting PhysiTheir anddemonstration ologicalSociety. lecture werescheduled forthemorning session ofthemeeting's first atfirst togo well.ThenIshikawa dayandseemed asked tobe heard atthebeginning ofthequestion a fewinnocuous After period. remarks, he launched into a vehement denunciation oftheentire public Kato's project, calling research "infantile" and "worthless." He claimed that a thorough oftheeviairing dencewouldshowthat Verworn's theories couldexplain all thefindings andasked theprogram officials fortwohours to prove it.After thedeeply abashedKatoand histhree associates hadleft thelecture evenmoved hall,Ishikawa that Keio formally be expelled from thePhysiological University Society!76 Notsurprisingly, this failed: Keio was notexpelled, proposal andtheKatogroup remained physiologists in goodstanding. ButIshikawa's unantagonism continued abated.In a 1924publication he attacked his former pupilfora supposed lackof attention totemperature insomeexperiments controls andfor putative inadequacies indatarecording. Throughout theperiod 1924-1926 he madeitimpossible for most Japanese todiscuss physiologists Kato'swork ontheprograms ofprofessional meetings, eventhough theresearch wasgaining international attention. Andin 1927Ishikawaheldupfor months, andnearly inpreventing, succeeded a well-deserved accolade forKato-the Imperial Academy Prizefor histheory ofdecrementless nerve conduction. It is notable that thisbitter was sometimes relationship in the reported press. The marine biologist andemperor ofJapan, Hirohito, was one of Kato'sadIn 1988he recalled mirers. theevents of 1927,reporting theopposition as having said,"Howdarethey for givethis prize not something fully accepted bythescientific He also noted community!" that Kato'sopponents finally backed down.77 failed Opposition becauseIshikawa's attacks goadedKato intoan absolutely relentless commitment to detailandthoroughness in hiswork that finally persuaded everyone concerned that his claimswerecorrect. Thisprocess of vindication took about twelve years, itbeganbackatKeio inthedifficult 1923-1935; weeksfollowingtheevents in Fukuoka. Kato informed his staff that Ishikawa's opposition was itimpossible making tofind a suitable venue for reporting their work inJapan. The logicalcoursewas to present thenerve conduction project at meetings overseas, with beginning theTwelfth International Congress ofPhysiology, scheduled for August1926in Stockholm. Butsucha venture facedformidable difficulties. Travel on theTrans-Siberian Railroad through theSovietUnionwouldbe timeconsuming, and conditions in thearea werestillsomewhat unsettled. Therewas thelogistical oftransporting difficulty the necessary laboratory animals, anditwould be necessary to provide hotelaccommodations and foodfortheKeio delegates fora period of several weeks.Hereone sees.the most striking evidence ofKitasato's commitment
75Ibid., pp. 137-144,108-112. 76 Yoshimura, "KatoGen'ichi" (cit.n. 61), pp. 158-159. 77 Ishikawa, Studies intheFundamental Phenomena ofLife(cit.n. 64), pp. 87-88; and"Gakushin onshish6 enki:rokujifichi nenmae mo toraburu Tenn6 Heikaseikaku na omoide"(Postponement of theImperial Academy Prize:His Majesty's preciserecollection of a problem occurring sixty-one years ago),AERA,21 June 1998,no. 5, p. 26. See also Yoshimura, "KatoGen'ichi," p. 160.
270
contacted several The dean simply member. young faculty Keio to his promising this importosupport asking them community, business wellplacedinthe graduates did.78 andthey project, tant university inStockdemonstration before any work tocomplete hadmuch Katoandhisstaff tasksamong research various holmcouldhopeto succeed.He beganbydividing andOtsukaKunioconOtsukaTokichi, Maki Ryokichi, ofthestaff. themembers was askedto study Tsunesaburo Nakazawa projects. previous withtheir tinued case) as a complement in this (chickens, animals in warm-blooded conduction nerve when conduction investigated Fukui Tatsuoki toads. cold-blooded tothework onthe or potassium hydrogen, by asphyxiants-nitrogen, were impaired segments nerve many ofthenarperformed HarashimaSusumu tonarcotics. cyanide-as opposed more robust than the frog rather of the delicate nerves using the tests cotization usingthe studies narcotization performed of thetoad.Kajikawa Jin'ichi nerves Hanerves. motor employed ofthemorecommonly nerves instead toad'ssensory dropped conduction howand whytherateof nerve to explain worked riyaJunji an from was stopped whenconduction segment within a narcotized considerably resomeofMaki'sexperiments, Ryojirepeated AndUchimura electrode. outside chamber thenarcotized from outside spread ofcurrent that thephenomenon vealing of segment even whena substantial response elicita muscular could sometimes bynarcotics.79 deadened hadbeencompletely nerve intervening areespecially notable andMinamiNorio carried outbyKubo Moritomi Projects law to of theall-or-none theapplicability broke newground regarding sincethey European physioloofnerve Twoof themostinfluential impulses. kinds different while and his student EdgarAdrian, University KeithLucas of Cambridge gists, thedecrement lawfor fresh medullated supported theall-or-none nerves, accepting of subnormal that nerve impulses argued contexts. Theyhad,in fact, oryin other tothelaw that law andthus conformity intensity wouldnotobeytheall-or-none Howofa nerve thestrength impulse. orthelackofit-could be usedto measure subnormal a technique for Kubodeveloped generating Kato'sdirection, under ever, chamber an accessory thenerve through preparations by running nerve impulses themain solution before they passedinto a 2 percent urethane-Ringer's containing subnormal this toshowthat then Minami technique employed chamber. narcotizing anddo other from nerve different impulses are notfundamentally nerve impulses law.80 indeed obeytheall-or-none andtie criticism to answer of Kato'sdetermination possible every Symptomatic on decrementless of his staff work andthat loose endwas his continued up every hadpreMaki Ryokichi the1924monograph evenafter appeared. conduction nerve ofBufovulgaris.Butin 1925Katohadhimrepeat nerve thesciatic studied viously dorsi andcutaneous thetibialis, abdominalis, oftheearlier using most experiments ofthe1924-1925 most projects time assisted this byOtsukaKunio.In fact, nerves, Uchimura orinparallel. Ryoji working together twoorthree investigators involved ofheating andcooling inandtheeffects studied andKajikawa Jin'ichi conductivity Miura Toraoinvestigated fibers. and vagusnerve postganglionic on sympathetic
78 Yoshimura, Kitasato haha,shi o kataru: p. 160; and Kato Ei'ichi,"Chichi, "Kato Gen'ichi," and Dr.Kitasato, andteacher: father, ofmyfather, (Discussion Keio Gijuku" mother, Sensei,Chichi, Nov. 1988,40(3), p. 106. Shinfuoni, Yoshisha Keio University), pp. 129, 116,124, 103,83, 86. haha,shio kataru," 79 Kato,"Chichi, 80Ibid.,p. 61; andKato,Theory (cit.n. 64), pp. 36, 49-56. Conduction ofDecrementless
271
of thefrog. fibers usingthesciaticnerve Kajikawastudied preganglionic sympain thetoad.AndUchimura to study used theheart of a rabbit thetic fibers vagus nerve fiber conduction.8' that ofthephenomenon Katofelt ofcurrent an insufficient understanding spread from a normal to oneimpaired nerve was a major segment reason bynarcosis why hadbelieved indecremental many conduction. So he sawitas essential physiologists to explain itsprecise current spread and demonstrate effects. fully TamaMiura, muraHideaki, andHayashiTakashi wereall assigned towork on thephenomenon andhad somesuccess.Usinga newtechnique devisedin Kato'slaboratory, latent perioddetermination, thethree showedthatcurrent of two spreadwas actually on a nerve types-external and internal within (operating the surface) (operating nerve's axiscylinder)-and that theinternal was more the type important. Hayashi, senior ofthethree, work on current investigator notonly innormal organized spread nerves butin narcotized nerve as well.His study showed that boththe segments extent ofcurrent spread andthespeedofconduction diminished with while narcosis, thestarting ofa nerve point moved thestimulating impulse nearer electrode.82 Hayashi was theprincipal in twoother investigator studies crucial to thetheory of decrementless conduction. One was the determination of the so-calledlimit length. WhileKatoargued that thelength ofa narcotized nerve segment was irrelevantto thetiming of itsloss of conduction, refined thisclaim.He found Hayashi below6 mm,length that, did matter-because of current from spread thenormal ofnerve. segment Assisted byAdachiKimio, wasalsoinstrumental Hayashi inclarian important fying phaseofnerve conduction calledtherelatively refractory period. (A refractory is a temporary period ofreduced period to stimuli responsiveness immediately a response.) following Katowas eventually able to showthat theall-ornoneprinciple heldfor this phaseofconduction as well.He was concerned enough aboutthisdetailthat he set twoteamsof investigators, andAdachi,and Hayashi andNakazawa Tsunesaburo, Nakajima Kenjiro to study it.Following differvery entstrategies, both teams ultimately metthesenior physiologist's expectations and showed that theall-or-none lawdidindeed apply tothe relatively refractory period.83 These investigations of decrementless conduction appeared in a secondmonoin early1926,butthe 1924 studies graph werealready making a splash.Late in December that four year, from physiologists theHarvard MedicalSchoolreported at thenational of theAmerican meeting Physiological Societythat they too had reopened the question ofdecrement innerve conduction andhadfound itcompletely absent in thenarcotized peroneal nerve segment of a cat.Theycalledattention to thework oftheKatogroup, carried outsimultaneously, noting that theKeiophysiolhad notonlyprovided ogists valuablecorroboration fortheir ownefforts buthad found actually the"sources oferror which had[earlier] ledtotheinference of[decremental] Their more conduction'" detailed report, which appeared inthe American ofPhysiology Journal a year later, wasevenmore eloquent inpraise ofKato.Led by Hallowell Davis,theHarvard authors calledthetests performed inKato'slaboratory "ingenious" andsaidthat theJapanese team hadshown the"experimental evidence theconcept underlying ofdecrement [tobe] unsound." One member oftheHarvard
82Ibid.,pp. 60-64, 69-74, 84.
81 Kato,Further Studies on Decrementless Conduction (cit.n. 69), pp. 32, 97-101,97, 95,
101.
83 Ibid.,pp. 50-51, 111-112.
272
Davis error. previous acknowledging in science, evenrarer groupdid something had theKatoteam whom Adrian, ofEdgar he hadbeena collaborator that revealed in theAmerican Davis also declared theory. to decrement foradherence criticized on earlier experiments many he nowconsidered that article ofPhysiology Journal "unjustifrom them drawn andtheconclusions to be "valueless" conduction nerve he to someof theprojects extended theseevaluations He madeit plainthat fied." Adrian.84 outwith hadcarried himself to Swedenin forKato'strip a favorable context levelcreated at this Recognition Ryoji, MiyakeRyoibyUchimura of 1926.Accompanied andsummer thespring demonstrations, and lectures and 150toadstobe usedfor chi,MatsuyamaSatoru, to enonlylongenough butstayed at theendofApril in Stockholm Kato arrived May On 31 Institute. attheKarolinska facilities storage sconcethetoadsinsuitable for preparing began and Europe around a tour from to thecity returned thegroup the replacing included preparations Their beganon 2 August. which thecongress, theNetherkindof toadfrom a different had all died,with which toads, Japanese as well as demonstration, and lecture the for rehearsals lands.Theyalso involved attention press substantial attracted Kato newspapers. Stockholm with the interviews He to visit Sweden. his third rather, first but, was not his this it that andmade clear one reporter and told attention, the relished enhancing, his visit as career saw clearly on earth"!85 beautiful city is "themost Stockholm that to write his of presenting Kato'sstrategy that to indicate seemed at thecongress Events afterand in English lecture His morning to succeed. was going Japan work outside he hadpracon thethird dayofthemeetings; werepresented noondemonstration he inwhich Thedemonstration, so itwent smoothly. times, several ticed thelecture but ofview, from hisownpoint lesscompelling seemed byUchimura, was assisted to speakat theUniversity andan invitation comments favorable many he received of thecongress probably thehighlight For Kato,however, of Berlinnonetheless. on theimplications heldforth Adrian together when he andEdgar camea daylater, andits principle oftheall-or-none forscience's understanding ofthenewresearch a eventproduced This spontaneous nerveconduction. in explaining importance andled Stockholm's thephysiologists present among discussion" "longand lively other several ofKatowith a photograph topublish DagensNyheter daily, influential edition.86 in its5 August scientists He evermore moved upward. sharply on Kato'scareer trajectory this point From Kitawith Station, atTokyo to a flag-waving reception returned andhiscolleagues a Reviews published In October1926 Physiological in September. sato present,
"Conduction Hopkins, 84 Hallowell andAnnMcHenry DavidBrunswick, Forbes, Davis,Alexander Journal American ofPhysiology, AlcoholNarcosis," under in Nerve Decrement Progressive without ibid.,Apr. 1926, Mar. 1925, 72(1):177-179;and Davis et al., "Studiesof the NerveImpulse," on readsas follows is on p. 450. The text 76(2):448-471,on pp. 450, 461. Davis'sacknowledgment theexperiis herereferred Adrian with to,nowbelieves whosework author "Thepresent point: this andtheconcluofcurrent control spread, becauseoflackofproper tobe valueless inquestion ments unjustified." them from siondrawn (cit. n. 61), p. 160; "Japan-landetdir all vilja bli lakare:Prof. "Kato Gen'ichi" 85 Yoshimura, Svenska Dagbladet,29 fratn Tokio,om sinaronoch sittlandsforha'llanden," Kato,nervfysiologen SocialI Stockholm," SamladTill Kongress AvAll Virldens Fysiologer 1926,p. 1; and "Eliten July 3 Aug. 1926,no. 207,p. 1. Demokraten, och f6rsoksOnsdagforFysiologer pp. 161-162;and "M6dosam "Kato Gen'ichi," 86 Yoshimura, I Gyllene stadbankett salen," DagensNyheter, gerStockholms fdredrag djur-Efterdagenshundra 5 Aug. 1926,no. 209,p. 1.
273
of theNerveImpulse," that featured "The Conduction lengthy essay, Kato'swork him.The following forattacking he reandcriticized Ishikawa prominently spring Ishikawa's efforts ceivedtheImperial to prevent it.Andin Academy Prize, despite and KitajimaTa'ichiwrote to StocklateOctober his colleagues Hata Sahachiro holm andnominated Katofor the NobelPrize.87 Thisinitial byinvitation nomination hadno immediate effect. Katocontinued towork, continued to attract Nonetheless, a stronger andgradually madehimself candidate. attention, In fact, in themid1930sdepended hisNobelcandidacy much more on what he after from Stockholm than on anyofhisearlier accomplished work. Bereturning tween1927 and 1929 Kato'sassociates continued to study in musclecontractions Bufo vulgaris, identified three ofnarcosis andthree ofcontracdistinct kinds stages tions, andclarified theexactapplicability andlimitations oftheall-or-none law.In 1927 Miurashowed that or mechanical stimuli electrical very strong appliedto a narcotized ofthetoad'ssartorius region muscle in what resulted cameto be called postnarcotic contractions. Three later years Hashida Kunihiko discovered thephenomenon oflocalizedcontraction, thesmall, limited contractions seenatthegroup ofstimulating electrodes attached to single muscle fibers.88 Thekind ofcontraction that theKatoteam hadbeenstudying for someyears wasdistinct from postnarcotic andlocalizedcontractions becauseit wouldconduct nerve andelectrical impulses term (hencetheir for it,"conducted contraction"). To conducted contraction, andto italone,didtheall-or-none law apply. Hashida's workin particular was madepossiblebecauseKamaya Tadashi had to isolatea singlemusclefiber managed in December1929.This was no simple task:thefibers weredelicate and fine; themicromanipulator proved useless,and succeeded Kamaya onlywhenhe was able touse hisownhands instead. Katoalso directed several staff members to attempt theisolation of a singlefiber from the sciatic nerve ofa toad, a task that proved evenmore difficult. However, inMay1930, having developed a specialapparatus forthepurpose, ShimizuTadao isolated a singlemotor nerve fiber from a sciatic tibialis flexor digitorum preparation. After theapparatus ina December describing 1934monograph, Katonoted that Shimizu's achievement "required byfar[a] finer technique than[did]theisolation ofa single muscle fiber." Katohadrelatively little toboastabout when hetraveled totheUnited in thesummer States of 1929,sincethese important achievements werestillin the future. Buthe was still prominent enough tohavehislecture atJohns Hopkins Uni89 versity inthe reported NewYork Times. AndinAugust hespent a weekinBoston as a delegate tothe Thirteenth International Congress ofPhysiology, hosted byHarvard. It was his team's isolation of thesinglemuscleand nerve fibers, together with thestudies thisachievement madepossible, that finally raisedKato'sreputation to thehighest international level.In 1929he andIvanPavlovwereboth present atthe
87 HallowellDavis, "The Conduction of theNerveImpulse," Physiological Oct. 1926, Reviews, 6(4):547-595,on p. 552. Davis wrote: "Ishikawa (1924) offers certain criticisms ofKato'swork, but it is difficult to followthelogic of his argument or to evaluate his observations from themeager descriptions available." On theImperial AcademyPrize see Yoshimura, "Kato Gen'ichi," p. 162; forthenomination letters see Medic.Nob. Kom.1928 P. M. Fbrsdndelser och Betdnkanden. Hata Sahachiro's letter is dated27 Oct. 1927,KitajimaTa'ichi's 31 Oct. 1927. 88 Gen'ichi Kato, TheMicrophysiology ofNerve(Tokyo: Maruzen, 1934),pp. 53-54,47. 89 Ibid.,pp. 4-5, 5-6 (quotation); and "Says NerveResponsesGo 3 Miles a Minute:Professor Kato Holds Superior BrainIs Secretof TyCobb'sand BobbyJones's Success," New York Times, 2 July 1929,p. 28.
274
JAMESR. BARTHOLOMEW
inAugust However, didnotmeet. probably butthey Congress, International Boston he demwhere inRome, Congress International theFourteenth 1932Katoattended possible; of thesinglefibers had madetheisolation that thetechniques onstrated ofsingle theavailability time, By this impressed. is saidtohavebeendeeply Pavlov wasyielding experimentation andprecise for closescrutiny fibers nerve andmuscle abletoexploit. were uniquely Katoandhisassociates that newinformation valuable that showed unequivocally Kato'sdirection, under 1930and1932Kamaya, Between or asphyxiated, to narcotized, exception appliedwithout principle theall-or-none Ono Ogawa Asayoshi, nerves. just as it did to fresh of nerve segments impaired andE. A. Erlanger Joseph that fibers toshow usedsingle Tsuneo andTomita Kohei, ofa nerve attheseatofstimulation potential action localized about argument Blair's a mechaniwhen also applied stimulus an electrical employed when theinvestigator andclarified described Kato associates other Andseveral was used.90 cal stimulus called"nodesofRanvier." structures nerve oftiny therolein conduction investigamadetheir that fibers andnerve muscle ofsingle totheisolation Prior inthemyelin breaks small nodes, these little about knew physiologists tion possible, setHayashiYoshioandShimizuTadaoto fiber. Katothus a nerve covering sheath andhudogs,cats,cattle, rats, in various animals-toads,frogs, them measuring than animals smaller in apart thenodesarefarther that showed Thisinquiry mans. Moritomi Kubo animals. inwarm-blooded than in larger onesandin cold-blooded at stimulus to electric is highly fiber susceptible that a nerve showed andOno then higher axon also had thenerve theorized that they initially anynodeof Ranvier; false. this speculation Further study proved elsewhere. atthenodesthan excitability were shown contractions muscular toproduce needed the threshold strengths In fact, onenodeandanother, toincrease between atthenodesandgradually tobe weakest of the of thedirection a reversal Moreover, at themidway point. beingstrongest is nerve to be needed. "The threshold different strength causeda strikingly current than node on the Ranvier is cathode when the placed weaker stimuli with far excited to it," Katowrote.9' theanodeis attached when sheath sincethemyelin suchpeculiar especially couldexplain phenomena, What Katostaff Another member, thickness? uniform fiber is ofalmost a nerve covering is completely that themyelin sheath He assumed an explanation. Tasaki Iji,offered "is determined excitation by as regards current ofelectric theeffect thus insulating; a nerve and a current excites theRanvier between nodes, differences thepotential an electric outwards?" Moreover, nodedirecting a Ranvier fiber as itflows through is an electric stimulus fiber thenerve onlyatthenodes. . . When "excites stimulus of the at thenodes... regardless is setup always theimpulse appliedto a nerve, Katoandhisassociates On thebasisofthis explanation, electrodes."92 seatof [the] current thenerve forexpressing formulas outlogarithmic datato work usedtheir flows.
Scientists' 90Pavlov's "LowellWelcomes reports: innewspaper was mentioned inBoston presence "Kato see Yoshimura, Kato's presence 20 Aug. 1929,p. 3. Regarding Times, New York Group," Tsukada, inRomesee Professor attheconference (cit.n. 61), p. 162.On Kato'sattendance Gen'ichi" Kato Genichi Professor ServiceforProf.Kato,"Obituary: of theMemorial Chairman Committee see Kato,Microphysioldescribed 1979,28:5.Forthework ofMedicine, KeioJournal (1890-1979)," (cit.n. 88), pp. 29-31,63-65. ogyofNerve 91Kato,Microphysiology pp. 66-67, 72 (quotation). ofNerve, 92 Ibid.,pp. 74-76.
275
themostimportant of Kato'slaboratory By somestandards, accomplishment in theearly1930s was its discovery and explication of reflex and reflex inhibitory thepublication ofSirCharles nerves. excitatory Following AcSherrington's Reflex tivity ofthe SpinalCordin 1932,Katocametobelieve that there hadtoexist specialin thevagusnerve ized nerve fibers for otherwise a vitalorgan liketheheart trunk, wouldbe overwhelmed andparalyzed as impulses byan excessofnerve impulses, from onenerve were blocked ofother He seta staff bytherefractory nerves. periods member from China,Ho Wen-yan, and a Japanese NakamuraJiro, to associate, workon thistopic.Usingdecapitated toads,Ho and Nakamura exposedsciatic nerves anda gastrocnemius as wellas the"entire course oftheipselateral muscle, peroneal nerve thetibialis ... with anterior muscle anda pieceofskin ofthedorsal of [the]footattached." part shocks or pinches with Theythen appliedinduction a pincette as direct stimuli tothemuscle, ornearby skin, nerves. ofthefindAnalysis ingsshowed that stimulation ofthemuscle andskin different produced very effects, that there must suggesting be "twokindsof nerve fibers which control thespinal reflex."93 In 1933itfell toSugiyama Ryoji toidentify a single fiber andtoInoue inhibitory Sei to isolatea singleexcitatory fiber. Sugiyama's preparation exposedperoneal nerves, gastrocnemius and tibialis anterior muscle, and a piece of skinfrom the dorsalpartof a toad'sfoot.Upon isolating a singlenerve fiber from partof the he examined peroneal itsfunction nerve, by stimulating thenerve, themuscle, or theskinwith various electrodes anddetermining theeffect on theextension reflex. He reasoned thatanyeffects on theexisting reflex responses whenstimuli were atthe applied parts distal tothe isolated region must be duetotheisolated fiber, since impulses hadto havebeentransmitted through it.He then measured thediameters ofthesingle fibers excisedand,after repeating these procedures fifty-seven times, ascertained a distinct between the"sizes of thefibers relationship andtheir functions." Ultimately, thereflex inhibitory fibers wereshown to be 9-10 microns, the reflex excitatory fibers 6-7 microns, indiameter.94 Inoue's project followed much thesameprocedure-but with certain differences. He madea preparation oftheipselateral tibial nerve andthe ramus cutaneous tibialis magnus plusa pieceofskin from thelatter. Before attempting thenerve fiber isolation hemadea preliminary test, applying stimuli tothecutaneous nerve orskin with electrodes in order to confirm that theseeither produced reflex contractions when applied alonetothespinal cord atrest orgavesummation (displayed addedintensity) when applied thereflex during contraction inthegastrocnemius muscle. When they did so, he isolatedsinglefibers from thecutaneous nerve and appliedstimuli of different strengths at certain points to see whether thishad anyeffect on muscles. Excitatory fibers proved to be recognizable notonlyby their smalldiameters but also from thereflex contractions they evoked insomehind limb muscles ofthetoad whenthespinalcordwas in a state ofrest. In due course, InoueandKato showed that reflex excitatory fibers originate in theskin, whereas reflex inhibitory fibers inthemuscles.95 originate Studies ofreflex inhibition in thespinalcordconstituted thelastmajor bodyof
9
95Ibid., pp. 111-114.
94Ibid., pp. 107-113.
Ibid., pp. 84-90.
276
bySherringin part Inspired 1934monograph. in Kato'sDecember reported work ofaninhibitory location the for looking began Katoandhisassociates research, ton's toWakaiEijiro, project part ofthis ofBufovulgaris.He assigned inthebrain center by andbeganhisinvestigation system nervous outthetoad'scentral whodissected electrode needle designed a newly using nerve peroneal itscontralateral stimulating ofstimuthe effect Wakai examined wires. copper insulated a pairoffine containing ofthegastrocnemius contractions on thereflex ofthebrain parts to various lations endofthe oftheanterior region a particular stimulating that He determined muscle. itthe anddesignated inhibition" "causedremarkable contralateral terminalis lamina center oftheinhibitory thelocation toascertain Thenhe sought center." "inhibitory are that "all themuscles indicated ofthetoad.His experiments muscles forother of theextent although appliedat thesame spotof thebrain, by stimuli inhibited musinvestigated Masuda Ryota tothemuscles." according . . . differed inhibition nerve suchmotor that showing motoneuron, with a single inhibition associated cular other fibers. Finally, as well as excitatory inhibitory to many cells are connected ofthe points to different a localizedstimulus that revealed research members' staff onthe depending ora summation, inhibition either a reflex cordwillproduce spinal nerve path.96 oran excitatory ofan inhibitory influence speedfolwith remarkable unfolded to Kato'sNobelcandidacy Events relating December 17 on Nerve of Microphysiology The of publication theofficial lowing andbiogracolleague 1931,hislongtime haddiedinJune Kitasato 1934.Although andhad Keio faculty of the member active still an was Mikinosuke, Miyajima pher, and Miyajima a fewweeksearlier. to nominate Nobelrequest received an official to writeidentically each proceeded members otherKeio faculty twenty-three dateof thebook'spublication. forKato on thevery letters of nomination worded and ofsingle muscle theisolation inEnglish, mentioning wrote TheKeio professors nerves, andexcitatory ofreflex inhibitory with thediscovery nerve together fibers, ina French-language a month later, Kato.About torecognize reasons as theprimary thesameargumadeessentially IvanPavlov 25 January 1935, dated communication of RafaelCastexoftheUniversity Mariano twoyears passedbefore ment. Nearly letter of 12 December 1936, Kato.His brief to nominate BuenosAiresalso wrote in microresearches referred to Kato's "beautiful in French, merely written too arrived certainly hima NobelPrizeandalmost toaward as a reason physiology" in Stockholm.97 events lateto influence the before couldintheinterim. Shortly to do what weredetermined they Others with tomeet madearrangements Miyajima ofKato's1934monograph, publication intheJapanese andAsianAffairs ofEuropean oftheBureau chief TogoShigenori, hisplantonomidiscuss affairs-to minister offoreign later ministry-and foreign to nominate Pavlovwas going that becomeaware hadclearly nateKato.Miyajima Kure Ken, candidate the other NobelPrize, the being for twoJapanese physiologists at Tokyo of Medicine and,likeKato,a nerve University of theFaculty a member
96 angfiende "Betdnkande p. 127. See also Hans Gertz, from Ibid.,pp. 123-127,130; quotation pp. och Betdnkanden, Kato,"23 Aug. 1935,in Medic.Nob. Kom.1935 P. M. FRrsindelser Genichi 1-7,on p. 6. 97 Medic.Nob. Kom. 1935 P M. Fbrsindelser pp. 30, 53-54. The onlyletter och Betdnkanden, dated17 Dec. 1934.Howis one signed materials byM. Karasawa, inthearchival included actually of inthearchives can be found Thisletter hadgonetoMiyajima. request theactualnomination ever, inTokyo. Affairs ofForeign theMinistry
277
work wasnotclosely related toKato's, andhiscandidacy Kure's cannot physiologist. here. He hadbeena favorite be treated extensively ofmedical atJapan's colleagues universities andKyushu) andhadbeen four oldest imperial (Tokyo, Kyoto, Tohoku, in 1930.Pavlovwas on twoprevious to Stockholm proposed occasions, beginning ofnominaandinhisletter medical ofJapanese innocent ofanyknowledge politics, situated both KatoandKureatTokyo tionhe incorrectly University.98 inthearchives ofthe ofForeign official documents Judging from Ministry Affairs, unless to Kato'sprospects theKurecandidacy was prejudicial felt that Miyajima He managed to between Keio andTokyo. ofagreement couldbe reached somekind thetwocandidacies." The desired outcome of between persuade Togoto "mediate and Togo were thismediation was neverspelledout;butit seemsthat Miyajima for from thetwomedical faculties bothKato hoping to obtain unanimous support hisoffice with andKure.Itwasnottobe. Shortly after various Togomet professors, minister The letter to Sweden. sent a remarkable letter to Shiratori Toshio, Japan's hadbeenunsuccessful andthat thetwouniverinformed Shiratori that themediation with theaforementioned It also sities"wouldproceed candidacies independently." this result was especially unfortunate. "Wehavebeeninformed explained why bya medicine member oftheNobelcommittee for andphysiology that theyears] [over the quitea fewcandidates have beennominated from medical science comJapanese munity, butthat he considered this[occasion] an exceedingly goodopportunity for someone from Japan toreceive theprize." Theforeign ministry then askedShiratori to see what couldbe donebutconceded, "In thefaceofthis[factional] situation it be difficult for may youtodo anything." with Closing a rueful comment about "never in theJapanese seeinganymeeting of theminds medical sciencecommunity," the that a scientist from couldbe selected."99 anypossibility Japan Thisletter raisesintriguing questions, notall ofthem answerable atpresent. Did Shiratori actually approach any officials of the Nobel Foundation to lobbyfor Kato-or forKure?Could he havebeentheconduit of a communication from a Swedishmember of theNobel committee? Certainly a lobbying initiative of this kindwouldhavebeenfully in character for him;historians haverightly considered Shiratori an "atypical diplomat." AndJoseph Grew, theU.S. ambassador in Japan the1930swhoknewhimwell,noted during in his memoirs that Shiratori always inclined toward actions that would enhance Japan's prestige andthat he couldnotbe 100 intimidated byhissuperiors. It is almost certain, moreover, that a Nobelcommitteemember didtellsomeone from Japan-Shiratori, Togo, orMiyajima-about the ofearlier numbers Japanese candidates. Prior to theopening oftheNobelarchives
98 Kure was nominated in lateDec. 1930 by Itagaki Masami (Kyushu and againin University) Dec. 1932byKimuraOnariandNasu Seizaburo, ofTohoku both University. See Medic.Nob.Kom. 1931 P. M. Fiirsdndelser och Betiinkanden, p. 26; and Medic.Nob. Kom. 1933 P. M. Fiirsdndelser ochBetiinkanden, p. 41. On Pavlov's nomination letter see Medic.Nob.Kom.1935P M. ForsindelserochBetinkanden, p. 30. 99For thesedocuments see "'NMberu' heiwa sh6kinkankeiikken," in Gaimusho KirokuS5ed. Gaimush6 Mokuroku, Gaik6 Shiryokan, Vol. 2 (Tokyo:Hara Shobb, 1992). Despitethetitle, which suggests an item relating to theNobelPeace Prize,thesedocuments havenothing to do with thepeace prizebut, rather, concern theNobelPrizein Physiology or Medicine. 100 Tobe Ryoichi, "Gaik6ni okeru'shisoteki no shinkyt: riky6' Shiratori Toshiono kod6 gaik6 ron"(Intellectual in diplomacy: divorce On thediplomatic posture of Shiratori Toshio),in Nihon Gaikdno Shis6(Intellectual ofJapanese history diplomacy), Aug. 1982,71:124-140;andJoseph C. TenYearsinJapan(New York:Simon& Schuster, Grew, 1944),pp. 34, 64-65.
letter nonetheless urgedShiratori to "give us any advice . . . as to whether thereis
278
JAMESR. BARTHOLOMEW
disclosed a member So unless hadaccesstothem. members committee in 1974, only known. itcouldnothavebecome suchinformation Kato and andcertainly confidentiality, strict maintain always Nobelcommittees In thewinter at thetime. ofdevelopments unaware werecompletely hissupporters the himto attend Moscowinviting from letter an official of 1935 Kato received as to be heldin theSovietUnion, of Physiology, Congress International Fifteenth was behind official connections, with his imposing state Pavlov, guest. an official Kato'spresentacongress, ofthe the time diedatabout Pavlov Though initiative. this of 1936was inthelatespring toTokyo hisreturn a great success; tionwas deemed Doca "KeioUniversity that hailed windows store indepartment byposters greeted The sameposters theNobelPrize." be given whomight torofScienceinMedicine candi101 Kato's fact, Inactual triumph!" a Japanese for welcome a "great proclaimed andwasnottobe revived. itscourse point run dacyhadbythis Hans 1935,when inAugust occurred that thecrucial event records show Archival on Kato'saccomplisha report submitted faculty oftheKarolinska Institute Gertz of Lund,Gertzhad of physiology at theUniversity A longtime professor ments. a member oftheprize in 1935 as in 1928andwas serving cometo theKarolinska 1935 of 23 August him. His report a for was specialty physiology committee. Nerve He recalled also ambivalent. andappreciative-but detailed, precise, wasthorough, studies conduction nerve thedecrementless that observing Kato's1928candidacy, had not said he he that work, with familiarity Indicating basis. as its had served entirely to based was be evaluation his 1935 Thus, at the time. prizeworthy it deemed he in actualpractice though and a fewof Kato'sarticles, on the1934 monograph attenthe book.Gertz paidparticular summarized Mostofhistext thelatter. ignored and thereflex inhibitory theclaimsabout on thenodesofRanvier, tiontothework He saidthat cord. tothespinal ofreflexes andthestudy pertaining fibers, excitatory a substantial "constituted body transmission system intothenerve Kato'sinquiries structures described ofthenerve fortheexistence of strongly arguments plausible [bytheauthor]."'02 Pavthat hadcaptivated wasthesamething most crucial what hefound However, andthe andnerve fibers muscle ofindividual Kato'sisolation others: lov andmany in madeto nerve theseaccomplishments physiology contributions methodological achievethepurely "that Gertz methodological "Itwillbe evident," wrote, general. when areinfunctionfiber both andmuscle a nerve ment ofexperimentally isolating be as such.It should a prizeworthy discovery can ... be considered ingcontact, But having and important." is bothbeautiful thisachievement that acknowledged on to argue that while went isolating theSwedish this physiologist conceded much, it had matter as a practical was "something nerve element recent," a functioning that tothefact claimhereferred ofthis In support times before." beendone"several muscle from detached hadisolated "impulses andanother Adrian physiologist Edgar of them had acknowledged precursors-one and thatKato himself receptors" which a systematic the"harvest ofresults As for stressed. that Gertz a point Adrian,
source. inthis is reproduced poster (cit.n. 61),p. 162.A copyofthe "KatoGen'ichi" '?' Yoshimura, Liljestrand, see Gdran Kato" (cit.n. 96), p. 7. On Gertz Genichi angaende "Betankande Gertz,
102
Historia, 1910-1960, Vol. 2 (Stockholm/Gbteborg/ ed., Karolinska Mediko-Kirugiska Institutets
& Wiksell, 1960),p. 110. Uppsala:Almqvist
279
ofthemethod application he felt that needed"more [had]produced," they detailed hisownbelief that thefindings confirmation"-despite were "strongly 103 plausible." On thebasisoftheavailable archival sources andother itis impossible material, to say how close Kato mayhavecometo receiving a Nobel Prize.The claimin theJapanese archives that a Swedish foreign committee ministry member talked to someone from abouttheprospect of a Japanese Japan Nobelrecipient for1935is both andbelievable, striking notonly becauseofwhat is known about Nobelprocedures butalso becauseof theFibiger-Yamagiwa fiascoa fewyears It was before. obvious toknowledgeable authorities andnot by1935that Yamagiwa should Fibiger havereceived theprize in 1927,andwe cansurmise that inthewakeofthis injustice the 1935 Nobel committees wereparticularly sensitive to strong candiJapanese dates. Though henever mentioned explicitly Adrian's 1932Nobel(shared with Sherin discussing rington) Kato,Gertz's references to theCambridge are physiologist also suggestive. Even if Adrian and Kato wereneverstrictly in competition-a highly likely surmise-their work couldbe seenas closelyenough related that an award to one precluded a later award to theother. Katocertainly Adrian respected andhismentor Keith Lucas,despite their commitment todecrement theory. He used suchterms as "careful," andthelikein describing "ingenious," their experiments. Kato was also deeplyawareof theadvantages of spending timeand beingwell known in Stockholm. ButAdrian had already bested himin this"race":he had a substantial working withscientists relationship from theKarolinska several years to receiving prior his Nobel,a political and scientific that opportunity wouldcertainly havecounted for more than Kato'sbrief visits.'04 One is left with thegeneral that impression in themid1930swas stilltoo Japan farfrom theEuropean centers of scienceandhad a research community toointernally divided to wina NobelPrize, at leastin medicine. The strategy ofhaving the entire Keio medical faculty write twodozenidentically worded letters wouldnot havemadethebestimpression. Nor wouldanyinitiative by Japanese officials. I cannot saywhether Ambassador Shiratori attempted tolobby anyone inStockholm, evenifsomeforeign ministry officials backinTokyo thought he should. A lobbying effort wouldhavebeenfully in character forShiratori. It wouldalso havemadea terrible impression andwouldsurely havehadresults exactly contrary to those desired. Kato himself did everything probably that couldhavebeendone.He was a resourceful, intelligent scientist ofenormous energy anddedication, typical inmany ofthemost ways successful medical research scientists ofthepresent day. Butnone ofthis was enough to winhima NobelPrize.
GENERAL REFLECTIONS
Nobel Prizes,to say theleast,are noteasy to win.One mustfirst do something important. Onemust alsobe nominated andthen hopethecontribution is not consideredpremature, unbelievable, orwholly outside informed consensus about hownature works. Prizeshavesometimes beenawarded to scientists whosefindings were
Gertz, "Betiinkande angatende Genichi Kato,"pp. 6-7, 7. RonaldE. De Meersman, "Edgar DouglasAdrian," inNobel Prize Winners, ed. Magill, Physiologyor Medicine (cit.n. 19),Vol. 1,pp. 351-355,on p. 353.
103
10
280
JAMESR. BARTHOLOMEW
Rous's Peyton is Francis an example or evenbizarre; seen as improbable at first But in chickens. can cause sarcoma a virus in 1911that forshowing 1966 award are no there and important, believable are considered evenif one'sachievements in madecontributions Sherrington prize.Sir Charles of a forthcoming assurances byscien132times Buthe was nominated criteria. metboth that physiology nerve Adrian Edgar with the1932award he shared before countries thirteen from tists in 1986,whenhe finally Ruskawas eighty AndErnst at theage of seventy-five. of the to thedevelopment forcontributions partof theprizein physics received acknowlis generally madein theearly1930s.'05Longevity microscope electron a Nobelaward! for one'sprospects edgedas increasing of called"occupants colleagues of eminent a category also recognize Scientists can who of forty number maximum tothe alludes Thisphrase chair." theforty-first it inthenatural sciences, atanyonetime; ofLetters Academy totheFrench belong those or Prize Nobel a won have to believed incorrectly but peoplewidely designates haveevenmentioned Nobelauthorities tohavewon.On occasion, seenas deserving won.The butnever prizeworthy something did who scientists of particular names of DNA is thecarrier that whodiscovered OswaldAvery, included listhas usually in thiscenearly mathematical physicist Gibbs,a leading Willard Josiah heredity; table.Some wouldciteothers: oftheperiodic author Mendeleev, andDmitri tury; DyofDNA, orFreeman thestructure herroleinelucidating for Franklin Rosalind case is no(QED).106Dyson's toquantum electrodynamics hiscontributions sonfor work for their tothree physicists prizewas awarded tablebecausethe1965physics toshare number is themaximum Three them. among from Japan inQED, Tomonaga and Julian inclusion(withRichardFeynman a singleprize,and Tomonaga's when Nobelawards ofthe inthe time history theonly is almost certainly Schwinger) anAmerican oran Englishman lostoutto a Japanese. WarII. World before in theyears kind a case ofthis imagine One couldscarcely andAmerican science's European from isolated were notwholly scientists Japanese to wellknown andwere reasonably extensively andKatotraveled Kitasato centers: overseas hadimportant totravel, toounwell andevenYamagiwa, colleagues, foreign the missed they country, in an "out-of-the-way" work Butby doingtheir visitors. thenominations. with interactions peoplewhocontrolled forfrequent opportunity of with that arecompared candidacies when their clearly emerges Thisconclusion (1872-1928).Noguchi Hideyo Noguchi scientist, best-known Japanese theperiod's anda numfever ofyellow thecausative organisms tohavefound wasoncebelieved evenwhilehe was of his claimswerediscounted diseases.But many berof other is stilluniversally of paresis of thespirochete and onlyhis discovery stillliving, as a of working advantage he had theconsiderable Nonetheless, acknowledged.
in TheNobel "Ernst D. Cannon, and Byron Ruska$" Press,1977),pp. 47 (Rous),40 (Sherrington); N.J.:Salem, Vol.3 (Pasadena, Cliffs, Calif./Englewood N. Magill, Physics, ed. Frank PrizeWinners, 1989),pp. 1315-1321. Elite,pp.42-44. ThehistoScientific see Zuckerman, byNobelauthorities 106 On the nameslisted from theroster theabsenceofGibbsandMendeleev oncedescribed DonaldFleming rianofscience Oct. 1966, Atlantic, "Nobel'sHitsAnd Errors," as "unpardonable": Fleming, of Nobel laureates Periodic of Mendeleev's "The Reception Brush, see Stephen 218:53-59, on p. 57. On Mendeleev Franklin Rosalind see AnneSayre, Isis, 1996,87:595-628. On others andBritain," Law inAmerica MadeIt: MenWho QED andthe 1975),p. 24; andSilvanS. Schweber, Norton, andDNA (NewYork:
and Tomonaga (Princeton,N.J.: PrincetonUniv. Press, 1994), p. 575. Dyson, Feynman,Schwinger,
105 HarrietZuckerman, ScientificElite: Nobel Laureates in the United States (New York: Free
281
research associateof theRockefeller Institute. The Nobel archives showthat he received on nineoccasions eighteen nominations from fifteen in seven colleagues different countries. In New Yorkhe became acquainted withmanyinfluential people,including theNobel laureate AlexisCarrel, who submitted his namefour times.'07 ofcourse, Nomination, couldnotassure a prize-and inNoguchi's case it did not.But it was a necessary andNew Yorkwas a better condition, venuethan Tokyo for anyone with Nobelhopes. Japan "off clearly was,so to say, thebeaten track" in science before World War II. Travel toandfrom thecountry wastime anddifficult consuming bythestandards of thepostwar era. Onlyone significant international scientific was held meeting there in this period, thePan-Pacific ScienceCongress of 1924.Andonlya modest number ofdistinguished scientists cameto Japan in those thelistinyears, though cludesAlbert Einstein (1922), Werner Heisenberg (1929), Paul Dirac (1929), and NielsBohr(1937),besidesseveral others mentioned earlier.'08 There was a lackof political sophistication among someofthe whoparticipated Japanese inthenominationprocess. Idiosyncratic factors likeYamagiwa's health andperhaps lobclumsy bying byagents oftheMinistry ofForeign Affairs mayalso havehadan effect. And ifany, few, Japanese scientists hadan opportunity tobecome wellknown personally in Sweden. To what ifatall,didthe extent, ofthenominations form Nobelauthorities matter? ofthis period havesaidthat thenumber andquality ofnomination letters areinconsequential and havenever madea difference to anyone's chances. But wouldthis havebeentrue ofJapanese candidates? Mostwere probably unknown toprize committee members andsometimes lacked whowere supporters wellknown themselves. On theother hand, camecloseto winning Yamagiwa a prizewithout knowing anyonein Stockholm, without thesupport ofanyNobellaureate behind andwithhim, outbeingableto travel. Had he goneto Europe, as Ichikawa did,anddefended his work faceto face,the1927outcome might wellhavebeendifferent. Fibiger won, in part, becausehis supporters, heavily Scandinavian, werenumerous, vigorous, aggressive-andpartisan. Yamagiwalost,in part, becausehis Tokyocolleagues weremodest, quiet,and unassuming. He also had no support from the"Kitasato faction," justas Katohadnonefrom theTokyo professors. Thismight nothavemattered in a major center ofscience-Germany, perhaps, orBritain; buttheJapanese needed to mobilize all their assets, andan inability to do so washarmful. ThatKitasato facedparticular obstacles is obvious in retrospect. To beginwith, 1901 was thevery first yearof theprizes;theprocedures werenew,and perhaps background investigations ofcandidates werelessthorough than they later became. Behring's achievements seemedso wellknown andhis 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 wasnominated in 1913,1914,1915,1920,1921,1922,1924, 1925,and 1926. His supporters included four scientists from Japan, three from theUnitedStates, twoeach 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 ochBetdnkanden fortheappropriate years. 108 For photographs of thevisits by Dirac and Heisenberg (who came together) and by Bohrsee TamakiHidehiko andEgawa Hiroshi, Nishina Yoshio (Tokyo: MisuzuSh6b6,1991).Einstein's visit has been treated extensively in KanekoTsutomu, Einstein Shokku, 2 vols.(Tokyo:Kawade Shob6 Shinsha,1991). Regarding Koch's visitsee Miyajima, KitasatoShibasaburo den (cit. n. 13); this bookincludes a photograph ofKochdressed in a Japanese kimono.
282
theaffinfrom benefited heclearly Moreover, objections. most reasoned as tovitiate Several and itsacademicculture. forGermany Swedishacademics itiesof many wereto academics Swedish howdetermined showed Crawford ago Elisabeth years theformer WarI, when after World science roleininternational Germany's preserve TheNobelcominfluence. German orreduce tocurtail wereseeking Alliedpowers way, inthefaceofforeign welloutoftheir went andchemistry physics for mittees someconsidNobelPrizesthat with achievements German to recognize criticism, and language; is a Germanic 109 Swedish Moreover, ill-timed. least, atthevery ered, Exwith thoseof Germany. havemuchin common traditions academic Sweden's howelse can unknown, at present connections of personal thepossibility cluding in 1901,his evidence of thescientific reading uncritical one explainAlmquist's ofhissciennature didordidnotdo andthesubstantive Behring viewsas to what tific work? the of Japan, theremoteness in general, of winning thedifficulties Yet neither culSwedish even nor factionalism, Japanese letters, nomination forms ofJapanese of forthefailure explanation seemquiteadequateas a general proclivities tural would point fundamental more A century. ofthis half first inthe candidates Japanese werecomNobelcandidates strongest all ofJapan's Yukawa, before seemtobe that scithree of the themost competitive was surely Butmedicine in medicine. peting signifiof volume The worldwide today. so remains probably encecategories-and or that in physics than greater is surely andaccomplishment research cantmedical a reach to committees for Nobel made it difficult has a reality that evenchemistry, breakthroughs, over surgical studies cancer favor Should they consensus. measured toomany areusually There reasons? Forwhat nerve over physiology? biochemistry be must I havementioned ofthesort factors political Moreover, choices. excellent errors in which significant field is theonlyscientific Medicine intoaccount. taken (aside a Nobelcommittee beencharged against haveeverreasonably ofjudgment J.J.R. Macleod in 1923byrecognizing erred case,thecommittee from theFibiger competiIn the highly hedidvery infact little).'10 when ofinsulin, as a codiscoverer forthosefrom difficult it seemsto havebeenespecially of medicine, tiveworld in Stockholm. toprevail ortheUnited States) Europe countries (outside "outlying" is in 1947.And theonlyJapanese was thefirst, Houssayof Argentina Bernardo in Switzerland. donemostly TonegawaSusumu-forwork
EPILOGUE
to wina scientist for a Japanese itwaspossible that proved Yukawa Hidekifinally his award of Sciencesannounced Academy NobelPrizewhentheRoyalSwedish a new hadproposed 1949.In thefallof 1934Yukawa on 3 November forphysics in intermediate "a new sortof quantum" forces that of nuclear postulated theory themetermed was eventually Theparticle anda proton. an electron massbetween transformanuclear inordinary not be emitted would that mesons noted son.Yukawa likethoseocin nuclear processes couldmaterialize that they tions butsuggested the over hada complicated The theory reception in cosmic rayinteractions. curring
Univ.Press,1992),pp. 67, 74,passim. Cambridge
109 Elisabeth Crawford,Nationalism and Internationalismin Science, 1880-1939 (Cambridge: 110 ed. Magill, Physiologyor Medi"JohnJ. R. Macleod," in Nobel Prize Winners, Becky Johnson,
"Nobel'sHitsandErrors" (cit.n. 106),p 56. cine(cit.n. 19),Vol. 1,pp. 246-248. See also Fleming,
283
forthefirst twoyears It was completely nextfifteen years. its ignored following in January 1935.Thenit was actively debated an important publication following in 1937byCarlAnderson andSethNeddermeyer. discovery cloud Usinga Wilson to fit thetwoCal Techexperimentalists found a particle that chamber, the appeared to makeYuoftheone predicted Thiswas enough general description byYukawa. kawafamous andtosecure himaninvitation totheaborted conference. 1939Solvay Butsubsequent revealed that Anderson andNeddermeyer's mu-meson investigations to Yukawa's and interest in his the(or muon)did not,after all, conform particle, orywaned.'11 New technology in Britain developed byphysicists vindication. finally provided Between 1939and 1945,Cecil Frank PowelloftheUniversity ofBristol perfected thephotographic emulsion forrecording method thetracks of particles found in In 1947he andGuiseppe cosmic radiation. thenewtechnolOcchialini, employing a particle, whichtheycalled thepi-meson, or pion,thatexactly ogy,identified matched thepredicted features Theirinvestigation of theYukawameson. showed that theslightly in theemulsions bringing heavier pionsto rest causedtheejection ofmuons. In effect, were muons thedecay ofYukawa's product Thepions pi-meson. had been all butundetectable by oldermethods fortracking particles becauseof their short lifetimes and propensity to decayin flight.112 Powell'striumph setthe twoNobelPrizes:Yukawa stagefor in 1949,andPowellhimself received thefirst, thenext, in 1950. The pattern ofYukawa's Nobelnominations in notable conformed degree to the general sequenceof events just described. Nagaoka Hantaro, a Tokyo University was thefirst physicist, torecommend Yukawa's work; this was notsurprising, since he hadbeenan informal mentor to Yukawa, though never one ofhisteachers. Nagaokahadbeeninvited tonominate far more often than anyone elseinJapan, serving in 1914, 1930, 1932, 1934, 1936,and 1938. He had neversuggested a Japanese candidate; buton 15December 1939hewrote topropose oneofhisowncountrymen fortheNobelPrize, forthefirst timeand"with fullconfidence." Fiveweekslater, DirkCoster ofGroningen in theNetherlands University becamethefirst European to nominate scientist Yukawa, in a Swedish-language letter dated22 January 1940. On 12 November Matsumoto Toruof KyotoUniversity also wrote in support of Yukawa.113 Yukawa was notproposed in 1941or 1942;fewothers wereeither, becauseofthewar. No prizes wereawarded inthose years orthenext. theNobelFoundation However, deemed itessential torestore theprizes, most of which wereawarded in 1944andthereafter. On 23 January 1943Louis de Broglie, the1929laureate inphysics, wrote tonominate Yukawa. He proposed Yukawa again
I HidekiYukawa, "On theInteraction of Elementary Particles, I," Proceedings ofthePhysicalMathematical Society ofJapan, 1953,17:49-58,on p. 49. Thetext ofthis paperhas also beenreproducedinYukawa's longautobiographical essay,"Tabibito," theTraveler, trans. LaurieBrown andR. Yoshida(Singapore: World Scientific Publishing, 1982),pp. 209-218, on p. 210. See also Brown, "Yukawa's Prediction oftheMeson,"Centaurus, 1981,25(1-2), pp. 71, 72, 73; andM. F Soto,"HidekiYukawa," in NobelPrizeWinners, ed. Magill,Physics (cit.n. 105),Vol. 2, pp. 563-569,on p. 568. On Anderson and Neddermeyer's findings see BulentI. Atalay, "CarlDavid Anderson," ibid., Vol. 1,pp. 439-447, on pp. 443-444. 112 Atalay, "CarlDavidAnderson," p. 444; andGenevieve Slomski, "CecilFrank Powell' inNobel PrizeWinners, ed. Magill,Physics, Vol.2, pp. 573-578,on p. 577. 113 Letter fromNagaoka Hantaro,15 Dec. 1939, Vetenskapsakademien Protokoll 1940 ANG. Nobeldrenden, Sec. 5, p. 52.
284
(2 November) Maurice inthefollowing year (11 January 1944).Later thesameyear Yukawa, as didanother de Broglie, thelaureate's olderbrother, also recommended In the early French scientist, Jean Thibaud oftheUniversity ofLyon (15 December). Wentzel ofZurich postwar era,Yukawa's candidacy attracted thesupport ofGregor wereno moves torec(1 January 1946).114 Butthen thenominations stopped; there in 1947.Thisshould Yukawa Anderson andNedderognize notbe surprising, since hadnever conformed to thecharacteristics ofhispostulated meyer's muon entirely physicists did further particle, and experiments reported that yearbythree Italian short-term Nobelcommittee expressed caution. In damage. authorities hadalready a lengthy onYukawa, Ivar ofphysics attheUniconcluding report Waller, professor wrote on 19 June anycertain versity ofUppsala, 1945:"Itdoesnotseemtomethat ofthemesoncan be given aboutthesignificance ofYukawa's judgment prediction 115 atpresent." is still materials toYukawa somemonths Complete accessto all archival relating showsthat thediscovery of thepi-meson by away;butthepublicrecord already dephysicist PowellandOcchialini produced a strong consensus that theJapanese ofnominaserved a Nobel.Andthere maywellhavebeenin 1948or 1949a flood forwhom thecase was nowfully contionsfrom previously skeptical colleagues with a general butthecontrast One case study does notsustain vincing. argument, in ofworking Yukawa hadtheconsiderable medicine is stillsuggestive. advantage was notonlypossible, butevenquitelikely. where consensus physics, intellectual to a very broadfield, contributions and Katomadedisparate Kitasato, Yamagiwa, It has ever beenso some of them with competing many others, equallydeserving. theNobelPrizes. with
114 1943ANG.NoProtokoll 23 Jan.1943,in Vetenskapsakademien Louis de Broglie, Letter from Protokoll from Louis de Broglie,11 Jan.1944,in Vetenskapsakademien p. 32; letter beldrenden, 2 Nov. 1944,in Vetenskapsakadefrom de Broglie, Maurice p. 22; letter 1944ANG.Nobeldrenden, 15 Dec. 1944,ibid.,pp. Jean Thibaud, from p. 29; letter 1946ANG.Nobeldrenden, Protokoll mien 1946ANG. Protokoll 1 Jan.1946,in Vetenskapsakademien from Wentzel, Gregor 68-69; andletter pp. 45-46. Nobelarenden, Protoin Vetenskapsakademien 115 Ivar H. Yukawa," anghende utredning "Kompletterande Waller, ca. 1947 see confronted theory Yukawa's p. 39. On theproblems koll 1945 ANG. Nobeldrenden, Britannica in Encyclopedia (Chicago:William "Particles, Elementary," Wightman, Strong Arthur Ettore of MarcelloConversi, theexperiment notesthat 1972),Vol. 17, p. 416. Wightman Benton, stunning blowto theYukawa was an "apparently Piccionion mesonabsoption andOreste Pancini, ofmesons." theory

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

Uploaded by

Document Information

Original Description:

Original Title

Copyright

Available Formats

Share this document

Share or Embed Document

Sharing Options

Did you find this document useful?

Is this content inappropriate?

Copyright:

Available Formats

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

Uploaded by

Copyright:

Available Formats

Japanese Nobel Candidates in the First Half of the Twentieth Century Author(s): James R.

Japanese Nobel Candidates in the HalfoftheTwentieth First Century

Figure1. Kitasato Shibasaburo. circa1920.

theriabacillus, and orderedhim to do the same kind of research.. . accordingto

as thediscovery [in theDeutsche MedizinischeWochenschrift] have been reported

articlewas his first appearance in the Deutsche MedizinischeWochenschrift. Beh-

lierstudy of diphtheria and thereafter turned to . .. tetanus because. .. itmoreeasily

Figure2. RobertKoch in kimn

Katsusabur5in TjAc-GJ Marxva

Tokyo Igakkai Zasshi, and a similarreport in theJournal of Cancer Research.Word

earliercandidaciesof Kitasatoand Yamagiwa. In theearly1920s Kato (1890-1979)

case thanthe in themid 1930sis a moreambiguous candidacy Kato Gen'ichi's

JAPAINESE NOBEL CAN'DIDATES

1922 and March 1924. In September1921 Kato leftJapanon an eleven-month in-

83 Ibid.,pp. 50-51, 111-112.

95Ibid., pp. 111-114.

94Ibid., pp. 107-113.

Ibid., pp. 84-90.

letter nonetheless urgedShiratori to "give us any advice . . . as to whether thereis

Historia, 1910-1960, Vol. 2 (Stockholm/Gbteborg/ ed., Karolinska Mediko-Kirugiska Institutets

& Wiksell, 1960),p. 110. Uppsala:Almqvist

You might also like