18
Microbiological Process Discussion A View of Microbiological Science in Japan, J. W. FOSTER Department of Microbiology, The University of Texas, Austin, Texas Received for publication November 18, 1960 During 10 weeks of the summer of 1960, I had a free lance opportunity to visit and observe micro- biological establishments in Japan. Altogether, I visited a few dozen such places and conferred with scores of persons concerned with microbiological science in that country. The majority of places visited were in central Japan on the main island of Honshu, but lab- oratories on the islands of Shikoku and Hokkaido were also included. The breadth of the perspective obtained may be judged from the fact that site visits included most of the outstanding university, government, and industrial laboratories of Japan and also a great many other places. Laboratories engaged in pure medical mi- crobiology were visited less frequently, this area pro- fessedly lying outside my competence. Some national scientific conventions were attended. In addition to technical people in the above-named places, exten- sive consultations were had with university and insti- tute administrators, management officials of fermen- tation companies, journal editors, government officials in the Ministries of Public Health and Welfare, and of Education, and science writers and editors of some leading Japanese newspapers and magazines. The impressions gained and the assessments made from an experience of this nature are, of course, strictly subjective and, hence, represent a purely personal viewpoint. Nevertheless, for the most part I dealt with scientific territory in which I felt completely at home, and I inquisitively sought an evaluation of the status of microbiological science in Japan. Since I experienced many unexpected and novel revelations, a review of my mission and my analysis of the micro- biological situation in Japan will be of interest to Western scientists. A useful facet of this mission was the excellent posi- tion I was in to observe the progress of microbiological science in Japan since the last war. For 7 months in 1946-47, as civilian consultant to General MacArthur's headquarters in Tokyo, I had the responsibility of working with scientists from various parts of Japan toward modernizing and stimulating general micro- biological science through promotion of the produc- ' A report to the National Science Foundation under grant G12886. tion of penicillin. In course, I was able to obtain a good picture of the microbiological situation existing through- out Japan at that time. Thus, the recent visit afforded an excellent position from which to judge the progress made in the last 13 years. At the same time, I was able to discern trends that may indicate something of the future. Perhaps the most important advantage derived from my former visit to Japan was the acquaintances made. I had the chance to consult again, and to com- pare notes, so to speak, with a great many of the scientists I worked with in 1946-47, including many prominent individuals. As the last item of this introduction I would like to take up a matter frequently asked about upon my return to the United States, namely, the language prob- lem for an American in Japan. I would say that there is no language barrier as far as English is concerned, but there very definitely is a communication barrier for occidentals in Japan. English is taught as the second language almost universally in Japan, and some high school graduates acquit themselves conversa- tionally adequately in the ordinary amenities of a meeting between people. College-educated people are, of course, more skillful and, in my experience, wherever I went in the scientific world of Japan I found the English sufficient to establish rapport and to ascertain what was going on. Japanese-speaking occidentals are rarities and so it is revealing that scientific intercourse in Japan is not fundamentally handicapped for an English-speaking person. In fact, one of the surprising incidental things that I discovered was the large num- ber of persons from many parts of Japan able to main- tain a better than elementary English conversation, persons who had never before conversed with an English-tongued individual. Certainly they were more fluent than the so-called English-speaking employees in the western style hotels throughout Japan! These remarks should, however, be qualified by mentioning that an American would naturally come in contact with English-speaking Japanese; but, if they are a minority, they are a ubiquitous minority, and serve as interpreters for others. I should also mention the high frequency with which a scientist meets Japanese counterparts who have sojourned to the United States 434 on April 8, 2020 by guest http://aem.asm.org/ Downloaded from

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Page 1: Microbiological Process Discussion View of …pare notes, so to speak, with a great many of the scientists I worked with in 1946-47, including many prominent individuals. As the last

Microbiological Process Discussion

A View of Microbiological Science in Japan,

J. W. FOSTER

Department of Microbiology, The University of Texas, Austin, Texas

Received for publication November 18, 1960

During 10 weeks of the summer of 1960, I had afree lance opportunity to visit and observe micro-biological establishments in Japan. Altogether, Ivisited a few dozen such places and conferred withscores of persons concerned with microbiological sciencein that country. The majority of places visited were incentral Japan on the main island of Honshu, but lab-oratories on the islands of Shikoku and Hokkaido werealso included. The breadth of the perspective obtainedmay be judged from the fact that site visits includedmost of the outstanding university, government, andindustrial laboratories of Japan and also a great manyother places. Laboratories engaged in pure medical mi-crobiology were visited less frequently, this area pro-fessedly lying outside my competence. Some nationalscientific conventions were attended. In addition totechnical people in the above-named places, exten-sive consultations were had with university and insti-tute administrators, management officials of fermen-tation companies, journal editors, government officialsin the Ministries of Public Health and Welfare, andof Education, and science writers and editors of someleading Japanese newspapers and magazines.The impressions gained and the assessments made

from an experience of this nature are, of course, strictlysubjective and, hence, represent a purely personalviewpoint. Nevertheless, for the most part I dealtwith scientific territory in which I felt completely athome, and I inquisitively sought an evaluation of thestatus of microbiological science in Japan. Since Iexperienced many unexpected and novel revelations, areview of my mission and my analysis of the micro-biological situation in Japan will be of interest toWestern scientists.A useful facet of this mission was the excellent posi-

tion I was in to observe the progress of microbiologicalscience in Japan since the last war. For 7 months in1946-47, as civilian consultant to General MacArthur'sheadquarters in Tokyo, I had the responsibility ofworking with scientists from various parts of Japantoward modernizing and stimulating general micro-biological science through promotion of the produc-

' A report to the National Science Foundation under grantG12886.

tion of penicillin. In course, I was able to obtain a goodpicture of the microbiological situation existing through-out Japan at that time. Thus, the recent visit affordedan excellent position from which to judge the progressmade in the last 13 years. At the same time, I was ableto discern trends that may indicate something of thefuture. Perhaps the most important advantage derivedfrom my former visit to Japan was the acquaintancesmade. I had the chance to consult again, and to com-pare notes, so to speak, with a great many of thescientists I worked with in 1946-47, including manyprominent individuals.As the last item of this introduction I would like to

take up a matter frequently asked about upon myreturn to the United States, namely, the language prob-lem for an American in Japan. I would say that thereis no language barrier as far as English is concerned,but there very definitely is a communication barrierfor occidentals in Japan. English is taught as thesecond language almost universally in Japan, and somehigh school graduates acquit themselves conversa-tionally adequately in the ordinary amenities of ameeting between people. College-educated people are,of course, more skillful and, in my experience, whereverI went in the scientific world of Japan I found theEnglish sufficient to establish rapport and to ascertainwhat was going on. Japanese-speaking occidentals arerarities and so it is revealing that scientific intercoursein Japan is not fundamentally handicapped for anEnglish-speaking person. In fact, one of the surprisingincidental things that I discovered was the large num-ber of persons from many parts of Japan able to main-tain a better than elementary English conversation,persons who had never before conversed with anEnglish-tongued individual. Certainly they were morefluent than the so-called English-speaking employeesin the western style hotels throughout Japan! Theseremarks should, however, be qualified by mentioningthat an American would naturally come in contactwith English-speaking Japanese; but, if they are aminority, they are a ubiquitous minority, and serveas interpreters for others. I should also mention thehigh frequency with which a scientist meets Japanesecounterparts who have sojourned to the United States

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MICROBIOLOGICAL SCIENCE IN JAPAN

or Europe and, thereby, acquired more or less facilitywith English. An even larger number of Japanese profes-sional people comprehend spoken English in spite of in-effectuality in speech. I lectured in English in manyuniversities and industrial companies and was alwaysimpressed by the obvious comprehension of my au-dience, evidenced, among other ways, by assiduousnote-taking.

However, communication of concepts or abstractionsby most English-speaking Japanese is much less suc-cessful; in fact, this was an omnipresent obstacle of thehighest formidability to exchange of information andformulation of ideas. Linguistic experts have variousexplanations for this but my explanation is thatJapanese words and phrases are vague in meaning;they take particular sense from the context of thesentence. Nor is Japanese thought ordered in thesame way that the occidental mind operates. Thus,ambiguities and misinformation are encountered reg-ularly even though sentences may be expressed quiteliterately. For factual information I found the use ofsimple English words and short, even incomplete,sentences most successful. Abstract information andover-all pictures had to be synthesized from answers topersistent, systematic interrogation, point by point.Unless one knows exactly what kind of informationhe seeks, and insistently digs it out piece by piece,step by step, like a cross-examination lawyer, he mightjust as well attempt to penetrate the Bamboo Curtain.A proper inference from this is that it takes a hard-working English-speaking specialist to get really worth-while information from his Japanese counterparts. Imarvel at the success many Americans, from govern-ment, industry, and academics, fancy that they achievein surveying broad areas of Japanese endeavor onquick forays to that country. The accuracy of theassessments and the degree of authoritativeness derivedby these frequent "10- to 14-day flying wonders,"as the Japanese describe them, are unimpressive to anyoccidental who has had intimate association withJapanese people on their own grounds.

STATUS OF MICROBIOLOGY

The postwar economic recovery of Japan has beenamply documented, but much less appreciated is theeven more remarkable progress in microbiologicalscience since the war. This is evident not only in theamount of activity and the scope of interests in uni-versity, government, and industrial laboratories; it isevident in the record of solid accomplishments and in anational enthusiasm for the power of the microbe.Japan today is a leading microbiological nation and

in certain respects is rapidly gaining supremacy, if thatis not already an accomplished fact. To informedscientists the world over the imposing microbiologicalstature of Japan is evident from the number, variety,

and quality of technical publications flowing fromJapanese laboratories into the stream of scientificjournals. However, it is also evidenced in anotherinteresting way. Until a few years ago, Japanese in-dustries went to Western countries, particularly theUnited States, for information of new microbiologicaldevelopments and to secure licenses to manufactureunder American patents. Today, the situation has be-come a two way affair. American companies nowregularly send teams of experts to Japan to learn of thelatest Japanese progress. What is more indicative ofthis progress is that many recently discovered andpatented Japanese fermentation processes are nowbeing licensed to American and other Western com-panies.Some interesting reasons account for the unmis-

takable emergence of Japan as a microbiological worldpower.

First, successful microbiology is part art, part science.The art of working with microbes is especially highlydeveloped, and an awareness of microorganisms wide-spread in Japan, because of the traditional importanceof many kinds of fermented foods and alcoholic bever-ages in the diet and culture of Japan. The climate ofJapan is warm and humid, particularly during therainy season in early summer. These conditions arefavorable for microbial growth and activities, especiallyfor molds, in uncontrolled environments. Microbes areintimately and widely connected with Japanese foods,and fermented foods constitute an important part ofthe Japanese diet. Almost every morning, miso soup isdrunk at breakfast. The principal ingredient of miso issoybean which is fermented through enzymatic re-actions of a mixed flora of molds, yeasts, and bacteria.Sh5yu (soy sauce) is indispensable for Japanese mealsand is also the product of a mixed flora fermentation.Koji (moldy cereal grains) plays a key role in thefermentative processing of a variety of Japanese agri-cultural products, especially for industrial alcohol andfermented beverages. Until quite recently, most farmersmade their own miso and sh3yu and, secretly, evensake (rice wine). Even today most Japanese wivesprepare many kinds of popular pickled foods whichalso involve microbial activities.

Second, microbiology is one of Japan's most im-portant national resources. It is an especially significantone for Japan because that country is a nation oflimited material national resources. This, like the ap-prehensions about atomic bombs, is a specter everpresent in the immediate background in Japanese think-ing and policies. In the context of Japan I found thisto be much more compelling than in the United States.Microorganisms offer a potential means of manufac-turing an almost unlimited variety of chemical andbiological products from a few cheap substances thatare abundantly available in Japan, especially sweet

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J. W. FOSTER

potato starch and imported Formosan, Phillipine, orCuban molasses. In this way microorganisms upgradethe value of raw materials and, thereby, create newindustries, each utilizing the same few raw materialsand contributing new products to the domestic andexport economy.Apart from the fermented foods described above,

microbiological industry, through alcoholic beverages,occupies a central role in the over-all economy ofJapan. There are over 4,000 manufacturers of naturalsake in Japan and 15 beer breweries. In 1958, the taxeson alcoholic beverages amounted to 16.6 % of the entiregovernment tax revenue for that year. It is, therefore,not surprising that fermentation research and thetraining of technical experts in this field are stronglysupported by industries and government alike. A simi-lar emphasis has now become apparent in the new di-rections of applied microbiology.

Third is the dexterity and manual skill of Japanesetechnical workers in the laboratory and in productionplants. Unquestionably, these talents contribute im-portantly to microbiological progress.

Fourth is the vitality and diligence of Japanese indi-viduals. These result in the necessary quality of sys-tematic thoroughness. American laboratories whichhave had visiting Japanese scientists are well acquaintedwith these characteristics.

Fifth is an eagerness to learn, to emulate, and tobecome expert in the newest developments publishedin other countries.

Sixth is a proportionately large emphasis on micro-biological science and technology. This is evident inthe number of universities, hospitals, industrial compa-nies, and government and private institutes in whichvarious aspects of microbiology are emphasized and arestrong. A majority of Japanese universities which haveagricultural colleges has Chairs of Fermentation.

Seventh is the existence of several universities, withoutstanding microbiological professors, which alreadyhave a tradition of training and inspiring young menfor careers in microbiological science.

Eighth, the spectacular impact of the antibiotic ageon Japan's vital statistics has intensified the alreadyexisting public awareness and focused attention onmicrobiology as a glamor subject. Submerged penicillinwas introduced to Japan in 1946 and less than 3 yearslater Japanese fermentation plants had satisfied thedomestic penicillin requirements and this drug was anitem for export trade. The remaining antibiotics cameinto full production in rapid succession, and progressin this line culminated in the Japanese discovery ofkanamycin, which is looked upon with a sort of nationalpride. Through the occupation authorities, immediatelyafter the war many improvements in medical scienceand public health were introduced to Japan, all ofwhich contributed to the improvement of Japanese

credit for the fantastic increase in human longevity inJapan. In 1947 the life expectancy of Japanese men was

50.1 years and women, 54.0 years. Twelve years laterthe corresponding figures were 65.2 and 69.9 years, a

spectacular 15.5-year increase in life expectancy. Fewindividuals in Japan are unaware of this impact on thehealth and lives of their families.

GRADUATE EDUCATIONGraduate students, especially in the major Japanese

universities, are products of a rigorously selective edu-cational system. Nine years of schooling are required forall Japanese youths. Only a small number of highschools in the major cities of Japan provides the qualityof preparation needed to secure admission to the hardcore of preferred universities. The order of success ofthese high schools has led to a numerical ranking oftheir accepted quality and consequent exclusiveness.For example, Hibiya High School in Tokyo, regardedas no. 1, has an esteem and function comparable toBoston Latin School in Boston, Massachusetts. En-trance to these few top-ranked high schools is based on

citywide examinations, with most superior students inthe cities competing, since this is the best insurance foradmission to the few choice universities. Even so, thenationwide university examinations are so stiff thatonly about 30 % of the admissions to Tokyo Universitycomprise graduating high school seniors. The rest ismade up of high school graduates who pass the exami-nations only after 1 or 2 years of postgraduate highschooling. Approximately one out of seven applicantsis accepted to these universities under this system.Academic standards, entrance examinations, limitedscholarship support, and physical limitations on en-

rollments combine to effect a strict selectivity of studentmaterial.

Preparation for microbiological professions is avail-able principally in certain of the 72 government-sup-ported national universities. The foremost of these are

the prewar Imperial universities, namely, Tokyo, Kyoto,Osaka, Tohoku, Hokkaido, Kyushu, and Nagoya Uni-versities. They are generally ranked in this order. N\oneof the other national universities is in this class, havingbeen elevated after the war from the level of junior or

agricultural college to university status by little more

than a government decree. In the seven universitiesmentioned are concentrated most of the outstandingscientists, microbiological and otherwise, and they,together with their staffs and students, are regarded as

the scientific elite of Japan. By far the major part ofJapanese microbiological scholarship emanates fromthese universities and affiliated institutes. As regardsprivate institutions, two in particular, Waseda Uni-versity and Keio University, both in Tokyo, are gener-ally thought to provide good training for professionalbiology, among other things.

well-being. However, antibiotics are given the main

436 [VOL. 9

After the war 7 the graduate-training system was

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MICROBIOLOGICAL SCIEN-CE IN JAPAN4

rather abruptly shifted from the former German styleto one resembling the American system. Departmentsstill have only one professor. Other academic personnelin the department, namely assistant professors, areunder the authority of the professor, and this includestheir research activities, which are directed by theprofessor. In other words, departments are strictly oneman affairs, and assistant professors are literally as-sistants to the professor. Before the war, graduatetraining in microbiology was taken for granted to in-volve a long period of research servitude to the pro-fessor. When the latter adjudged that the graduateassistant had enhanced his mentor's reputation suf-ficiently, he was permitted to take his Ph.D. degree.Eight-, ten-, or even twelve-year stints of full timeresearch assistance were common.The United States occupational authorities revolution-

ized the entire educational system in Japan, especiallyin the graduate and professional sciences. The normalperiod of study now for the Master's degree is 2 years,with 3 additional for the Ph.D. The M.S. degree in-variably is taken by a Ph.D. candidate. The first 2years in college (junior course) cover general educationin liberal arts and culture. The last 2 years of theBachelor's degree program (senior course) provideknowledge in more specialized fields. The postwar pro-gram stresses, more than the former program did,supporting courses in subjects allied to microbiology.However, strong compartmentalization is still a charac-teristic of most graduate training, and even research,in Japan. From talks with a great many Japanesescientists, especially younger ones, I obtained the im-pression that the breadth of interests and scope ofliterature knowledge are substantially less with themthan with comparable American scientists.The organization of graduate training and research

along strictly vocational lines fosters the professionalisolation found so commonly in Japan. For example,breadth in microbiological scholarship is under-standably restricted in an academic system in whichonly pathogenic microbiology is taught and investigatedin the Faculty of Medicine; industrial and soil micro-biology in the Department of Agricultural Chemistry,Faculty of Agriculture; plant pathology in the Depart-merit of Agriculture, Faculty of Agriculture; dairyand animal pathogenic microbiology in the Departmentof Veterinary Science, Faculty of Agriculture; andgeneral microbiology and mycology in the Departmentof Botany, Faculty of Science. The opportunity for thefusion of the various facets of microbiology with sup-porting biological, chemical, and physical training disci-plines essential for the production of scholars withsophisticated outlooks in basic microbiology does notexist in Japan, even for the student who aspires to thisend. Interdisciplinary training and intercourse wouldgo a long way toward broadening the base for an ap-proach to microbiology as a fundamental academic

subject, with an appreciation of the biological andchemical problems which are unique to microorganismsand which in microorganisms illustrate general bio-logical principles. But the emphasis on the practicalapplications of microorganisms would also have to beabated, or compensated for by matching alternatives.Ironically, history attests to the fact that the surestway to new areas of practical developments is throughbasic research uncommitted and, seemingly, imprac-tical.

Microbiology in Japan is, without question, mostrobust in the applied aspects. Undoubtedly, the peculiarfitness of microbiological industries for the Japaneseeconomy, as mentioned above, accounts for this inpart. It seems probable that inculcations from vo-cational emphasis also orient students in practical di-rections. However, the special qualities of the Japanese,which endow them with mastery of and success withthe screening, development, testing techniques, andrationale upon which so much of modern industrialmicrobiology is based, also help account for the empha-sis on exploitation of the microbe. Partly for thesereasons, and partly for the tradition of utilizing micro-organisms in processing agricultural products, one findsthat a large fraction of microbiological science in theuniversities in Japan today is done in departments ofagricultural chemistry, and, as well, in the other clas-sical lines mentioned above.One other important explanation of the widespread

preoccupation of academic people with potentiallypractical microbiological problems has to do with re-search funds, as well as academic salaries. As discussedlater, funds for support of basic research are pitifullysmall in Japan. On the other hand, applied research inuniversities receives industrial support. Moreover, theprospects of research support from royalty income frompatented developments is a mirage which spurs im-poverished laboratories to applied objectives or pro-grammatic research.The Ministries of Public Health and Welfare and of

Education are the main sources of scholarships andfellowships in Japan. These are woefully inadequate innumbers and in value of the stipends. Undergraduatesmay receive government scholarships; in Tokyo Uni-versity's Department of Agricultural Chemistry lastyear, 70 % of the undergraduates received EducationMinistry scholarships averaging 3,000 yen ($8.33) permonth. Master's candidates received 6,000 yen ($16.33)per month, and Ph.D. candidates up to 10,000 yen($27.77) per month. According to the Ministry of Edu-cation, student living expenses in Tokyo today are6,000 to 10,000 yen per month. Recipients of thescholarships disagree.A program of competitive predoctoral and post-

doctoral fellowships is supported by the NationalScience Foundation of Japan, a government agency.These predoctoral fellowships, ordinarily renewable for

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J. W. FOSTER

only 1 or 2 years at the most, carry 15,000 yen ($42)per month. Postdoctorate fellowships, of which thereare very few, carry 20,000 yen ($56).

Partly because of the limited fellowship support inJapan, and partly because of the relatively few uni-versities which offer the desired training in microbio-logical science, the annual Fulbright Fellowships are ingreat demand and are highly prized. Training in anAmerican laboratory or that of another western countryhas prestige value in Japan aside from the training valueitself. The Japanese Fulbright Committee usuallyawards fellowships to about one of every two or threeapplicants and the standards employed are high. Thefellowships cover only round trip travel to the foreigncountry and, in the usual case, the fellow receives localsupport in the destination laboratory to cover livingexpenses in that country. Some fellowships are awardedunder both the Fulbright and the Smith-Mundt Acts,in which case living expenses are also provided.

SALARIES

In terms of dollar values, in Japan the cost of livingaccording to American standards is about % to /1 thatin the United States, but salaries for technical andacademic people are disproportionately less. It mayinflate the ego of American professors to learn that atleast one Japanese college professor confessed to methe sincere belief that his American colleagues make$40,000 a year on the average! Yet this may seem to beour status from the extremely low salary vantage pointsof academic people in Japan. A-cademic people tra-ditionally are relatively poorly paid; in Japan this is aspeciality. One of Japan's most distinguished uni-versity professors, in microbiological science, who alsois Dean of his Faculty (College), receives a salary of82,000 yen ($228) per month; take home pay aftertaxes is 55,000 yen ($153). The government's salaryscale, as it was published on August 9, 1960, is recordedin Table 1.

Salary scales for nonacademic scientists in the gov-ernment research institutes are even lower, perhaps by10% , than for scientists of comparable rank or staturein the teaching profession.

Aside from the indignity that such salaries engender,academic persons are obliged or tempted to supplementtheir incomes with extracurricular activities such asconsulting, performance of applied research for in-dustry, and book writing. These practices are wide-spread among most individuals with some reputation.They are a leading cause of preoccupation with practicalmicrobiology and a deterrent to basic research. Thegovernment from time to time promises improvedsalaries for college professors, but the latter are resignedto such promises and little accomplishment in thisregard. Education Minister Masuo Araki proposed to a

budget for 1961 raise the pay of professors "to prevent

them from trading their ivory towers for businesscareers."

The salary situation is complicated by the fact thatmerit does not enter into salary considerations; equaldistribution is made to all 72 national (government-supported) universities on the basis of the number ofprofessors. Thus, to achieve a material improvement inthe salary status of a minority of outstanding anddeserving professors, a vast majority of mediocre andother professors also have to be raised. The EducationMinistry is definitely in an unenviable position. How-ever, it should be noted that, according to EducationMinistry sources, if the next fiscal budget does notallow pay boosts for all professors at the 72 government-operated universities, professors at institutions offeringpostgraduate courses will be given priority. This is a

breach in the rigid system that previously did notallow recognition of the need to reward talent selec-tively, and in essence, is a device to concentrate extra

support in Tokyo, Kyoto, Osaka, Tohoku, Hokkaido,Kyushu, and Nagoya Universities.Each university determines its own retirement age,

which is relatively low, probably a carry-over from thetraditionally short life expectancy in Japan. As men-

tioned above, the expectancy now is approaching thatof the United States, and that may lead to an increasein the retirement age. At Tokyo University, 60 is theretirement age; at Kyoto and Osaka Universities, 63.At retirement age, full professors receive a lump re-

tirement sum amounting to 200,000 to 300,000 yen,

depending on length of service. In addition, the fullprofessor receives for life a monthly pension of from

TABLE 1. Basic wages by vocation (government employees)

Title Wages earned per month

yen dollars

Addministr ativeBureau Director ...................... 51,200 142

Section Chief ......................... 39,000 108

Assistant Section Chief ............... 29,000 81

Sub-Section Chief ..................... 23,500 65

Starting pay (university graduate) .. 10,800 30Starting pay (senior high school

graduate) ........................... 7,400 21

EducationalProfessor (top) ....................... 67,900 190

Professor (middle) ........ ............ 50,100 139Assistant Professor (middle) .......... 36,500 101Lecturer (middle) ......... ............ 27,200 76Assistant (master's degree) ........... 13,500 38

MedicalDeputy Hospital Head, Veteran ChiefDoctor ............................. 49,300 137

Department Head..................... 41,300 115

Starting pay .......................... 14,500 40

cabinet meeting on August 3, 1960, that the national

438 [VOL. 9

* Exchange rate: 360 yen = 1 United States dollar.

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1MICROBIOLOGICAL SCIENCE IN JAPAN4

40 to 70 % of his last salary. After his death his wifeor dependents also receive a pension.

SUPPORT AND CONDITIONS

The plight of Japanese basic research is vividly ap-parent from the physical environment in which it isconducted. By American standards, most of the labora-tories in universities and institutes are old and dilapi-dated, with little evidence of maintenance, past orpresent. There are, of course, some exceptions, buteven new buildings are underdesigned and stark. As arule, laboratories and classrooms of microbiological orother science are poorly lighted, inadequate in furnitureand fixtures, and, in general, stand as incongruitiesagainst the requirements of modern science. Again withcertain exceptions, the drabness, dinginess, and mar-ginal facilities of most laboratories must surely castdepression on their inhabitants. There are some showplaces, of course, but it takes a systematic survey toimpress a visitor that such well-known centers of at-traction are as unrepresentative of the laboratorybuilding conditions in Japan as the Potemkin villageswere of the Russia of Catherine the Great.

Similar comments apply to equipment. There is muchgood laboratory equipment of Japanese manufacture,such as microscopes, infrared and ultraviolet spectro-photometers, Warburg respirometers, fraction collectors,centrifuges, autoclaves, jar fermentor assemblies, andelectron microscopes. Indeed, one wonders why thefine quality instruments and apparatus, costing lessthan one-half, and frequently less than one-third, ofthe United States articles, are not exported to theUnited States in larger numbers. However, laboratorieswell-equipped by American standards are very muchin the minority and, here again, these are the relativelyfew strong centers of microbiological activity. Thoselaboratories concerning themselves with some phase ofapplied or programmatic microbiology appear to be byfar the best equipped. Time and again the matter ofinadequate budgets restricting the acquisition of moreor less standard modern apparatus, radioactive chemi-cals, and other material requirements was brought up,especially in laboratories seeking to concern themselveswith nonprogrammatic research.

This situation broadens farther the already wide gulfbetween a small number of well-fixed centers and therest of the academic laboratories throughout the lengthand breadth of Japan. The good get better throughtheir attraction of outside support, and the betterstudents and researchers of the country become concen-

trated in a few places. Not the least of the reasons

talented students gravitate to a very few universitiesin Japan is that these institutions are the habitualsources whence originate key personnel for academic,professional, business, and government positions. This

which transcends the Ivy League dogma in the UnitedStates. Graduation from one of the very small numberof top-ranked Japanese universities is almost a sine quanon qualification for a leadership career in all walks ofJapanese life.Japan is paradoxical to an occidental in many ways.

In spite of the booming economy that is one of theeconomic marvels of the international scene, the pro-fessional, educational, and basic research systems of thecountry have been sadly neglected. The problem ofbudget is, of course, the prime factor. Yet, the few-months-old new Japanese government of Prime MinisterIkeda has already planned and promised nationwidetax reductions for the next fiscal year. A concertedeffort to strengthen and broaden graduate educationand basic research in natural sciences is a pressing needof Japan today. A new building program to abolish thedismaying decrepitude would be a tremendous advance,as well as a powerful morale factor. Pleasant laboratoryenvironments would also provide attraction for young,talented people to careers in science.

PROFESSIONAL CAREERS

Poor salaries and poor working conditions are, ofcourse, traditional deterrents to young talent in pursuitof academic or other basic research positions in science.In Japanese universities there is the added dissuasionintrinsically bound up with the one professor per de-partment system. The incentive of recognition andpromotion based on individual merit can hardly expressitself when death or resignation of "the Professor"is the only opportunity for an assistant professor, andthen only one in a department, to acquire independentstature. Obviously, that event might not transpire formany years, during which time the status of competentor outstanding department members changes little.

However, one other practice, which is novel toAmericans, also works seriously against the inflow ofyoung talent to microbiological and other technicalprofessions and careers. This is the extraordinary andtime-honored practice in industry of having salaryscales based primarily on the age and years of experi-ence of the employee. Degree of technical education,training, and individual talent or merit count for littlein determining the beginning salary available forpersons joining a commercial laboratory. Regardless ofBachelor, Master's, or Doctor of Philosophy status,the "age ladder" determines starting salaries. Thus,one may witness commonly the strange situation inwhich a bright, young Ph.D. receives the same, orlittle more, salary than an ordinary Bachelor orMaster's person of the same age. Currently, a freshBachelor of Science employed in a pharmaceuticalfermentation company begins at about 15,000 yen ($42)per month, a Master of Science at 18,000 yen ($50),and a Doctor of Philosophy at 22,000 to 25,000 yen

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($61 to $70). During the 5 to 7 years it takes to earnthe Ph.D. degree, the B.S. employee meanwhile israised to 22,000 to 25,000 yen. Salarywise, the experi-ence with the company is rated equivalent to the uni-versity advanced degree training. Automatic annualraises are the rule, and after several years the Ph.D.gradually pulls ahead. Frequently, the "bonus" systemis used to confer salary distinction without, however,changing the entrenched salary lines. The main basisfor salary distinction comes through increased super-visory responsibilities, promotion to laboratory chiefcarrying with it the first real salary superiority forsuperior individuals.

Another important facet of this situation is the cus-tom of lifetime commitment of a worker to one com-pany. Jockeying for an improved position in anothercompany and hiring another company's man are re-garded as unethical and are practically unknown. Theage ladder system is so strong that the second companywould not break the salary line anyway. A traditionof implied loyalty to one's company for a lifetime,together with the failure of other companies to competefor an employee's services, perpetuates the age laddersystem. The longer an employee works for one company,the larger his stake in retirement provisions, which aresacrificed by a change of position to another employer.The insidious consequences of these Japanese values

are apparent to the American way of thinking. Theautomatic salary increase with age, with its equalityof mediocrity and talent, engenders stagnation; itevokes fealty on the part of the employee, and, for itspart, a company rarely discharges a technical person.But the most pernicious consequence of this system thatrates age and years of experience over creative talentand competence of the individual is the demoralizinginfluence on Ph.D. graduate programs in technicalfields. The economic plight of the average Ph.D. candi-date being what it is, coupled with the scarcity of gradu-ate fellowship support, understandably causes many apotential Ph.D. candidate to weigh the merits of de-voting a minimum of 5 Spartan years to study for theprivilege of obtaining a salary in industry not signifi-cantly higher than he can obtain with a Bachelor degree.The incentive of a higher standard of living based onsalaries in proportion to training and competence,which is the foundation of the American enterprisesystem, is absent in Japan. Under this Japanese system,the incentive for a great many people to submit to thediscipline involved in obtaining the Ph.D. is undoubt-edly removed. It is obvious that one is confronted herewith the very heart of any program designed to attractand strengthen the pool of personnel with advancedtraining in microbiology and other technical professions.Such a doctrinaire practice curtails, of course, thecreative potential of the country.

In lieu of salary inducements, the companies are,nevertheless, successful in luring people from, and com-peting with, teaching and basic research careers. First,the laboratory surroundings and equipment in most ofthe established companies are vastly superior to whatis available in most universities or noncommercial re-search institutes. For essentially the same salary, youngpeople are, therefore, attracted to the working con-ditions in industrial laboratories. Second, a curiouskind of commensalism has evolved between industrieswith a surplus of Ph.D. potential material holdingBachelor or Master's degrees and certain practicallyoriented university laboratories. The industry arrangesfor a suitably qualified employee to conduct Ph.D.dissertation research in a convenient university. Theproblem is selected by the supervising professor; itmay or may not pertain to the company's interestsand objectives. The student receives company salaryduring the arrangement, the university laboratory re-ceives some financial contribution, the professor mayreceive consulting compensation, and the companyreceives an exclusive or preferred position with respectto patentable inventions. In this way the companiessecure the talented guidance and supervision of a pro-fessor in a field of his special competence. Employeesmay eventually earn the Ph.D. degree in this way, buta great deal of importance is also placed on 1-yearprograms of this nature, to acquire the training andresults involved without completion of Ph.D. require-ments. Thus, the industry-sponsored training systemcompensates somewhat for the premature hiring ofpersons interested in and capable of doing Ph.D. levelwork. Probably the industries sense the shortcomingsof the age ladder system without choosing to break thesystem.The situation is ripe for a means of effectively break-

ing this custom in Japan. An ideal way would be forsmall companies, incapable of matching their big com-petitors in numbers of research personnel and scale oflaboratory facilities, to outcompete in certain fields bysecuring basic patents developed by outstanding per-sonnel. Creative talent could be purposely attracted tothe small companies by exceptional salaries, and theimpact of their contributions undoubtedly would befelt within several years. Small companies with out-standing talent could, thereby, compete with a betterthan even chance against the large companies in fieldsin which ideas pay off. In self defense, the large com-panies would be forced to vie for superior talent, andthe merit barrier would be broken, to the indirect greatstimulation and improvement of technical strengththrough all levels of Japanese endeavor. I regard thissituation to be one of the main problems and, at thesame time, major opportunities for Japanese sciencetoday.

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RESEARCH INSTITUTES

Cognizance of the power of the microbe in theeconomy and welfare of Japan is illustrated by theactivities of a number of government-sponsored re-search institutes which, in scope, correspond roughlyto the United States National Institutes of Health andthe regional laboratories of the Department of Agri-culture. Indeed, the National Institute of Health ofJapan, in Tokyo, is patterned somewhat after thatUnited States organization. Other noted centers ofresearch in medical microbiology are the Institute ofInfectious Diseases of Tokyo University and the OsakaUniversity Research Institute for Microbial Diseases.

Criticisms are common against bureaucratic ineptnessand shortsightedness in the Ministry of Public Healthand Welfare's programs and the disproportion in budg-etary allotments to administration versus laboratoriesand researchers. The impact of the impressive statisticson human longevity in Japan already cited is made lesssatisfying by the discomforting incidence of mass out-breaks of food poisoning reported in the daily pressin the summer of 1960, and by the monumental govern-ment administrative bungling in polio vaccine adminis-tration culminating in the polio epidemic disaster inHokkaido in the summer of 1960. This situation was

as perplexing in Japan as the Cutter incident was inthe United States. Salk vaccine knowhow has beenavailable for over 5 years, and ample supplies were

available for import from the United States, but vaccinewas desperately unavailable during the most severepolio epidemic in Japan's history. In the wide publi-cizing of the offer of the Russian government to donateSalk vaccine at the height of the emergency, the inci-dental information that the donation was good onlyfor some 1,200 doses was not often revealed.

Privately supported institutes devoted to medicalmicrobiology are best represented by the Kitasato In-stitute for Infectious Diseases (Tokyo). In laboratoryfacilities, the dilapidation of which at first sight dis-tresses an American, this institute, headed by the sonof the famed S. Kitasato, manages to maintain broadresearch programs in medical microbiology. Supportcomes mainly from the Institute's commercial produc-tion division which sells all kinds of vaccines, and alsofrom research grants. The first new construction sincethe founding of the Institute is nearing completion inthe form of a separate, medium-sized facility for themanufacture of Salk polio vaccine. A sizable antibioticscreening program has been conducted for 15 yearsunder the direction of Dr. T. Hata, the son of S. Hatawho collaborated with Ehrlich in the discovery ofsalvarsan. Culture filtrates of some 36,000 isolates ofactinomycetes have been screened for activity in bac-terial, viral, parasitic, fungal, and cancer test systems.

Eleven antibiotics have been discovered: luteomycin,leucomycin, carzinophilin, mitomycin, melanomycin,amaromycin, ascaricidin (anti-Ascaris), protomycin(anti-Entamoeba histolytica), cephalomycin (anti-en-cephalitis virus), cerulenin (anti-Candida albicans), and"No. 339" (anti-acites and solid tumors).

In medical microbiology outside of Tokyo, the Re-search Institute for Microbial Diseases, a branch ofOsaka University, must be mentioned as an outstandingcenter. The broad scope of the activities in this Instituteis exemplified by the sections in the Institute and thetype of work currently done: Pathology (virology),Virology (epidemiology), Bacteriology (medical my-cology), Immunology (immunological chemistry), Para-sitology (microbial genetics), Chemotherapy (biochemi-cal pharmacology), Tuberculosis (section I, bacterialphysiology; section II, acid-fast microorganisms), Clini-cal Research (cancer clinic), Preventive Medicine (vir-ology), and Leprosy (bacteriology and chemotherapy).

In the nonmedical areas, the principal governmentmicrobial establishments are two: the Brewing Experi-ment Station (Tokyo) and the Fermentation ResearchInstitute (Inage, Chiba Prefecture). The Brewing Ex-periment Station, an agency of the National TaxAdministration Agency, Ministry of Finance, was organ-ized in 1904 for the purpose of investigating off-fermen-tation and spoilage of sake and improving its qualityfor "the purpose of securing a liquor tax imposed onliquor makers." Some 50 persons are concerned inseven research sections: analysis and appraisal of allalcoholic liquors; raw materials; manufacture and stor-age of sake; taxonomy and ecology of fermenting mi-crobes; physiology of fermenting microbes; manufactureand storage of distilled liquors; and manufacture andstorage of compounded liquors. This institute has largescale production equipment and provides many tech-nological services for commercial brewers.Through a foundation organized for this purpose, the

Institute annually distributes over 50,000 bottles ofselected starter strains of sake yeast inoculum to sakemanufacturers all over Japan. Each year it also oper-ates a 3-month training course for some 40 techniciansfrom the beverage fermentation companies.

Rice mash prepared by saccharification with koji,rice molded with Aspergillus oryzae, is fermented bythe yeast to an alcohol content of 18 to 20%. Ordi-narily today, the filtered liquid is diluted with twoparts of 50% ethyl alcohol to yield the commercialproduct with an alcohol content of 15 to 16 %.One of the most intriguing developments in this

connection is the popularity of synthetic sake. Interestin this started about 25 years ago for the purpose ofconserving food rice. However, the greatest develop-ments have taken place in recent years concurrent withthe refinement in modern methods of separation, iso-

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lation, and identification of complex mixtures ofcompounds in natural materials, especially minor com-ponents. A number of taste-, flavor-, and bouquet-lending pure chemicals, among which may be mentionedsuccinic and lactic acids, minerals, glycine, leucine,alanine, and glutamic acid, are blended with industrialalcohol produced from sweet potato starch or molassesto yield a product surprisingly similar to the naturalfermentation beverage. As more constituents of naturalsake are identified, the synthetic version improves. Im-portant research on this subject is also conducted in theInstitute of Physical and Chemical Research in Tokyo.Enzymatically hydrolyzed soybean powder or caseinhave been found to improve materially the taste andflavor of artificial sake. Additional verisimilitude isachieved by a small proportion of natural sake. Arti-ficial sake is gaining wide popular acceptance, the 35million gallons sold in 1959 representing about one-fifthof total sales in Japan. Its cost is about one-half thatfirst class natural sake and only little less than theprice of second class natural sake. Artificial sake istaxed at the same rate es the natural product, on thebasis of alcohol content.The government's augmented tax take through the

development of artificial sake may boomerang in anunexpected way. The success of artificial sake has ledto study of the components of beer responsible for itsdistinctive qualities, and, through the liberal use ofcheap substitute materials mixed with alcohol belowthe taxable limits, potable products claimed to resemblenatural beer are being marketed. Untaxed, they sellfor a small fraction of the cost of the regular productand the several manufacturers of the artificial products,for which there are various formulas, expect eventuallyto capture an appreciable portion of the beer market.The emphasis given to beverage fermentation science

and technology is further indicated by the existence ofDepartments of Fermentation Technology in severaluniversities, especially Osaka, Yomanashi (Kofu), andHiroshima Universities, and in Tokyo Agricultural Uni-versity, a private institution. Also, almost all of thenational universities which have agricultural collegeshave at least one Chair or Professor of Fermentation.The Fermentation Research Institute at Inage, Chiba

Prefecture, is wholly government-supported and illus-trates the importance attached to microorganisms forthe economy and special talents of the Japanese. Thisinstitute, established in 1940, has 46 technically trainedpersons studying industrial applications of micro-organisms, excluding beverages, foods, and pharma-ceuticals. Essentially, it is concerned with production ofchemicals by fermentation. Its main objective originallywas increasing the efficiency of the industrial ethylalcohol fermentation of sweet potato starch. Develop-ments made in this institute on the Amylo saccharifi-cation and fermentation stages have been adopted by

all of the industrial alcohol companies. In the last 10years, the amount of raw sweet potatoes required toyield 1,000 kiloliters of ethanol has been reduced from7,000 to 5,000 kg.

In extremely poor physical circumstances, practicaldevelopments in the following main lines are intensivelypursued currently: microbial production of rubber; in-duced amylase synthesis; development of new mutagensfor molds; reductive bacteria, especially the bacterialproduction of soluble leucoindigo from insoluble plantindigo; submerged production of ustilagic acid as araw material for chemical syntheses; laccase productionas drying agents for the lacquer industry; dipicolinicacid production by filamentous fungi; microbial muci-lages and thickening agents; vitamin B12 production bycombined methane fermentation and activated sludgeprocess; new antifungal agents to prevent deterioration;and unfermentable sugars in barley.Government support is also provided for research in

food fermentations, notably miso (soybean mash) andsh5yu (soy sauce), in one of the divisions of the govern-ment Institute of Food Research (Tokyo).Some well-known private institutes capitalized partly

with government funds also engage in microbiologicalresearch. Perhaps the largest is the Institute of Physicaland Chemical Research, most of the senior staff mem-bers of which are professors in Tokyo University. Es-tablished in 1919 by the Emperor Meiji, the Institutewas patterned after the Kaiser Wilhelm Institute inGermany. Over the past 2 years, approximately 60%of the budget was borne by the national governmentand 40 % came from patent income and industrial re-search contracts. Six of the many sections are concernedwith microbiology and biochemistry. New antibiotics,the physiology and biochemistry of microorganisms re-lated to the beverage fermentation industries, hydro-lytic enzymes of many kinds, and bioengineering com-prise the principal programs.

Undoubtedly, the strongest aggregation of peopledevoted exclusively to general and applied microbiologyis found at the Institute of Applied Microbiology ofTokyo University. Organized only in 1953, this instituteis, like the Rutgers University Institute of Microbiology,a center of basic microbiological research and scholar-ship. Here, too, support is derived from governmentbasic research grants and industrial research grants.Its chief scientific staff has academic ranks in TokyoUniversity and graduate student research training isconducted in the Institute. The Institute was organizedby the first director, Professor Emeritus K. Sakaguchi,and is presently headed by Professor T. Asai, dis-tinguished fermentation authority. Because of the apicalposition and influence that the Institute has in Japanesemicrobiology, some information on its organization andactivities will be of interest. As of fiscal 1960, thepermanent staff numbered 74, including ten professors,

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11 assistant professors, and the rest technicians andadministrators. In addition, more than ten graduatestudents were pursuing dissertation research towardadvanced degrees, and, in May 1960, some 40 visitinginvestigators, mainly employees of industry on a train-ing basis, were also engaged in research in the Institute.There are 11 divisions of the Institute; the main prob-lems conducted in each as of September 1960, are listedbelow.

First division. Zymomycology. Professor K. Kitahara,director, who in 1960 received the Prize of the JapanAcademy for his outstanding work on racemases ofthe lactic acid bacteria. Nutrition of hiochi lactic acidbacteria; fermentative utilization of xylans; "trans-crystallization" of a 50% suspension of ammoniumfumarate to crystalline aspartic acid by strains ofEscherichia coli; filament formation by vitamin B12-deficient cells of Lactobacillus bifidus; fermentative pro-duction of D-lactic acid from glucose by Rhizopus oryzae.

Second division. Genetics. Professor Y. Ikeda, director.Improvement of technologically important strains ofproteolytic and saccharifying organisms by mutations,genetic recombination, and heterocaryosis; transfor-mation and transduction approaches to the geneticbackground of amylase formation by Bacillus subtilis;parasexual cycle in A spergillus oryzae; role of D-glutamicacid in cell wall synthesis in B. subtilis.

Third division. Taxonomy and type culture collection.Assistant Professor H. lizuka, director. Maintenanceand delivery of stock cultures; research on classificationand taxonomy of microorganisms of cereal grains andof organisms utilizing petroleum fractions and naturalgas; also research and taxonomy of organisms carryingout steroid oxidations.

Fourth division. Physiology. Professor T. Asai, di-rector. Aerobic bacterial oxidations (Japan AcademyPrize); direct fermentative production of amino acids;fermentative production of isoascorbic acid; fungal re-duction of 5-ketogluconic acid to L-idonic acid; micro-biological transformation of steroids; bacterial spores;microbioassays; red pigment formation by interactionof strains of Penicillium and Trichoderma.

Fifth division. Enzymology. Professor B. Maruo, di-rector. Protein synthesis (exocellular amylase) by Ba-cillus subtilis; amine factor released from ribonucleicacid by ribonuclease and which stimulates amylasesynthesis; function of exocellular ribonuclease of B.subtilis; immunological specificity of mold, bacterial,and animal amylases; endoamylase synthesis in cell-freeextracts of Pseudomonas.

Sixth division. Antibiotics. Professor Y. Sumiki andProfessor H. Umezawa, directors. Chemical isolation,characterization, and structure determination on newantibiotics. This laboratory works closely with Dr.Umezawa's laboratory in the National Institute of

and animal testing furnish the antibiotic culture fil-trates for the chemical program in this division. Mainemphasis is on antitumor substances: griseolutein, hela-mycin, peptimycin, raromycin, blastocidin S (antiriceblast disease caused by Piricularia oryzae), cytomycin,angustmycin.

Seventh division. Biosynthesis I. Professor H. Tamiya,director. Synchronous division of Chlorella ellipsoidea;sulfur-containing peptide nucleotide compounds fromChlorella; role of sulfur in cell division of Chlorella;effect of inhibitors on life cycle of Chlorella.

Eighth division. Chemistry. Professor K. Tsuda, di-rector. Microbiological transformations of steroids:conversion of cortisol to prednisolone by Bacillus pul-vifaciens; conversion of progesterone to 73, 1513-dihy-droxyprogesterone; conversion of progesterone to 15-hydroxyprogesterone by Helminthosporium sativum.Chemistry of steroids: conversion of 4,4-dimethylcho-lesterol and lanosterol to 4, 4-dimethylcholecalciferoland lanocalciferol by photochemical reaction of theA5'7-diene; chemistry of the 10-isosteroid group; ringinversions and ring transformations of steroids.

Ninth division. Biophysics. Assistant Professor S.Koga, director. Optical studies on unicellular suspen-sions; ionic characteristics of unicellular suspensions;kinetics of killing by ultraviolet light; automatc re-cording apparatus for microbial cultures.

Tenth division. Biosynthesis II. Professor A. Wata-nabe, director. Maintenance of stock culture collectionof algae (500 strains). Physiology and biochemistry ofalgae: nitrogen metabolism especially nitrogen fixationby blue-green algae; phycobilin pigment from blue-green and red algae; carbohydrates synthesized byHormidium; heterotrophic (dark) cultivation of algae.

Eleventh division. Bioengineering. Professor Y. Oyama,director. Air filtration; oxygen transfer and absorptionin aerated cultures; microbiological treatments ofsewage and industrial wastes; agitation of aerobic cul-tures.Two other places should be mentioned in the category

of institutes, both playing important roles in algalphysiology and the development of mass production ofChlorella pyrenoidosa. Japan, preoccupied with the prob-lem of feeding its high density population, is more ad-vanced than any other nation in respect to evaluatingthe use of dried algae as a proteinaceous and vitaminsupplement to various staple dishes. Certain kinds offood algae appeal to the Japanese palate and are com-mercially farmed in the ocean coastal regions; also,intensive efforts are made to produce Chlorella undersemicontrolled conditions. Basic research on algal physi-ology has been and is still conducted by Dr. H. Tamiyain the Tokugawa Institute for Biological Research, afamous private institute in which basic research inseveral areas of biology is conducted. Technologicalstudy and semilarge scale commercial production of

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Chlorella are underway at the Microalgae ResearchInstitute of Japan in a suburb of Tokyo. This institutewas established with government funds but is nowself-supporting from the sale of some 500 kg monthlyof dried Chlorella grown continuously with naturalillumination by the "open circulation system." Thisfactory consists of nine open air, circular sweep, shallowconcrete tanks 20 meters in diameter, with a liquiddepth of 10 cm. A significant part of the output is usedto prepare an extract of Chlorella which is sold tocompanies producing yogurt. The algae extract is saidto stimulate greatly the rate of the bacterial fermen-tation and reduce production costs correspondingly.

FOUNDATIONS

As indicated previously, the great bulk of support forbasic research in Japan depends on government funds.Private foundations do assist to some extent. For ex-ample, in 1959 the Rockefeller Foundation awardednine research grants totaling $356,600 to various insti-tutions and laboratories in Japan, several of which aredirectly concerned with microbiology. Of particularinterest to micrGbiologists is the support of basic re-search by two private foundations, the funds of whichare derived exclusively from the royalty income fromlicenses to industry for the production of fermentationproducts. The Waksman Foundation of Japan supportsseveral fellowships in microbiological science each yearfrom the income from streptomycin patents in Japan.An important new development for Japanese micro-biology took place in 1959 with the establishment ofthe Microbial Chemistry Research Foundation withroyalty income from worldwide sales of the antibiotickanamycin under Dr. Hamao Umezawa's (NationalInstitute of Health and Tokyo University) patent.These funds will enable construction and equipment ofa new modern research institute, together with pilotplant fermentation and chemical facilities, and are ex-pected to support broad research training and edu-cational progress in various aspects of microbiology.Dr. Umezawa will be the scientific director of theFoundation, the directors of which comprise repre-sentatives of universities, government, and industry.Construction of the building is scheduled to begin in1961 in Tokyo.

STOCK CULTURE COLLECTIONS

There are several major collections of microorganismsin Japan which maintain type cultures and function asdistribution centers for stocks. The Institute for Fer-mentation, affiliated with Takeda Pharmaceutical Com-pany, Ltd., in Osaka, is an agency of the World HealthOrganization and distributes cultures upon request,free of charge. Its 1956 catalogue lists 1,303 molds,474 wild yeasts, 280 technological yeasts, 81 actino-mycetes, 239 bacteria, and 14 protozoa. The culture

collection of algae and other microorganisms of theInstitute of Applied Microbiology is made availablethrough a foundation associated with the Institute forthat purpose. In April 1960, this collection consistedof 2,538 strains of fungi, 687 bacteria, 878 yeasts, and398 actinomycetes. During calendar 1959, the collec-tion furnished 2,430 cultures to laboratories in Japanand 152 to foreign laboratories. Organisms particularlyrelated to technological fields are also distributed fromthe collections of the Nagao Institute (Tokyo), aprivate foundation, and from the Department of Fer-mentation Technology, Osaka University. An exten-sive collection of brewing yeasts is maintained in theDepartment of Fermentation Technology, HiroshimaUniversity. A large collection of yeasts and fungiisolated from fruits and foods is kept by Dr. Y. Sasaki,Department of Agricultural Chemistry, Hokkaido Uni-versity. Organisms of human pathogenic significanceare stocked at the Institute for Infectious Diseases,Tokyo University. Apparently no major collectionsof protozoa, viruses, or tissue cultures are establishedas centers for the purpose of distributing stocks.

INDUSTRIAL MICROBIOLOGYAs implied earlier in this report, the amount, variety,

and quality of microbiological research conducted byindustry in Japan are very impressive. Noted alreadyhas been the excellence of the buildings, facilities,and staffs in many industrial companies which may behighly competitive, and yet which manage to live to-gether in periods of microbiological crisis, such as byagreeing to production quotas during periods of na-tional overproduction of penicillin. One of the moststriking postwar developments has been the evolutionin many companies of teams of specialists and firstclass pilot plant facilities capable of improving andcarrying new microbiological reactions to large scaleproduction efficiently and in a relatively short time.This type of coordinated research embodying theintegrated activities of a variety of technologicalspecialties was virtually unknown in Japan prior tothe postwar era. Several of the larger companies supportseparately organized laboratories as nonprofit append-ages. Two outstanding illustrations are the TakedaResearch Institute, affiliated with Takeda Pharm-aceutical Industries, Ltd., in Osaka, and the NodaInstitute for Scientific Research, affiliated with NodaShoyu Company, in Chiba Prefecture.The vigor of industrial microbiology in Japan,

especially in antibiotics, which, of course, with theexception of beverages and solvents, is by far themajor single aspect of the industry, derives in sub-stantial part from transfusions from American com-panies. Over the past 10 years, development of foreignmanufacturing subsidiaries has been a major trend ofAmerican companies. Access to expanded markets and

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profits, better even than from a corresponding capitalinvestment in the United States, has accelerated thistrend. Earlier mention was made of the licensing ofJapanese companies to produce under American pat-ents. Invariably, a license results in an intimate rela-tion between the companies concerned. The complexityof a modern fermentation process for the industrialmanufacture of an antibiotic being what it is, licensingarrangments invariably include technical engineering,microbiological and chemical instruction, and trouble-shooting services in fulfillment of contractual agree-ments to have the Japanese factory operating at apredetermined efficiency. These things usually requirethe sending back and forth of teams of American andJapanese specialists among their employers' factories.Usually, contractual provision is made for continuingexchange of improvements in processes as they aremade subsequently in both companies. Fundamentally,all commercial aerobic fermentations are alike in equip-ment, design, and operation. In consequence, acquisi-tion of knowhow of one process is tantamount tomanufacturing competence in the entire field, andsuccess in one product soon leads to eager independentexploration in other directions. Coming to maturityrather late on the modern industrial fermentation scene,many Japanese companies have elected to acquirelicensed knowhow for the manufacture of the olderantibiotics, and it is not unusual to find one Japanesecompany with license arrangements for different prod-ucts with several American companies. Most often thesearrangements are simple royalty agreements. However,in some cases, jointly owned new subsidiary companiesare formed with the capital investment and manage-ment from the American and Japanese co-owners.

Certain notable instances illustrate that Japanesecompanies have proved to be apt students. For ex-ample, under American patents, dihydrostreptomycinis produced by chemical hydrogenation of streptomycin.One Japanese company discovered and manufacturesdihydrostreptomycin by direct fermentation. Anothercompany circumnavigated the same patents by dis-covering and producing deoxystreptomycin by directfermentation. This product is said to be at least equiva-lent clinically to streptomycin or dihydrostreptomycin.Another case in point is steroid oxidation, in whichJapanese companies succeeded in obtaining bacterialdesaturation of ring A of cortisone and hydrocortisoneto form prednisone and prednisolone, thereby eludingAmerican patents covering the same transformation.In one case, the rather extraordinary achievement wasmade whereby a suspension of crystalline substratesteroid in a concentration of 50 g per 100 ml of mediumcan be bacterially tranformed to 50 g of crystallineproduct in 2 days. The term "pseudocrystalline fer-mentation" is used to describe this conversion (see

The prowess of Japanese microbiology has not gone

unnoticed by Asian nations. The Russians have re-

cently sent a microbiological mission to Japan and, inexchange, a group of Japanese scientists will go toMoscow. Pakistan has contracted with Kaken Chemi-cal Company, Ltd., Tokyo, one of Japan's leadingindustrial fermentation companies, for the design,construction, and start-up of a new streptomycinfermentation plant.

Allusion has already been made to the Americanacknowledgment in the key phase of new antibioticdiscoveries, namely, screening in its broadest sense.

Awareness of another important aspect of screening inJapan-its surprisingly low cost compared to screeningin the United States-is already becoming widespread.The apparent competence of the Japanese in turningup new antibiotics by systematic screening, coupledwith the costly constant drain on research budgets ofAmerican companies for screening programs that havehad less than spectacular success, has led to a system of"farming out," whereby screening is conducted inJapanese laboratories under contract with Americancompanies who pay all or most of the operating costs.A typical arrangement might specify that patentrights in Japan to any commercial process resultingfrom this "partnership" are vested in the Japaneselaboratory, whereas rights in the United States wouldbe assigned to the American company. At least one

prominent American pharmaceutical-manufacturingcompany has discontinued its own screening and reliesentirely on the program it supports in Japan. A new

antibiotic, antimicrobial or anticancer, is broughtthrough the mouse toxicity and the curative or tissueculture tests in the Japanese laboratories; the sub-sequent development work is done in the Americancompany. The tremendous cost of such programs inthe United States almost certainly will turn otherAmerican companies to examining the potentials ofthe Japanese "farm system."The situation is ideal for this rapport for a reason

other than the compelling fact of research economy

that one United States dollar will screen five to tentimes as many cultures in Japan as it will in the UnitedStates. There is also the desperate shortage in Japanof research funds and laboratory support which causes

many excellent researchers in various nonindustriallaboratories to be found hungering for support which isunattainable from Japanese sources. Thus, financialsupport is now given by American companies to anti-biotic research in several university and institutelaboratories in Japan. Contractual or not, this supportimplies that the supporting company receives a favoredposition with respect to information obtained and to anycommercially useful results. But the conduct and direc-tion of research are solely those of the responsible

"transcrystallization" of ammonium fumarate).

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Until Japanese sources of research support are forth-coming on a much larger scale than presently-anunlikely prospect-modest American funds of the typedescribed are having an increasing impact on antibioticand microbiological research in Japan. The reason isthat screening in Japanese laboratories is much morethan a unidirectional, unswerving pursuit of new,useful drugs. Their habit in Japan, it seems to me, is toconsider screening not as a streamlined mechanicaloperation, but as research problems in techniques,microorganisms, and chemistry. Screening is undertakencomprehensively, and fans out in the directions ofinterest to the chief investigator. This scientificallyproductive approach undoubtedly also is an importantfactor in the discovery of new antibiotics. SeveralAmerican friends have inquired about the secret of thesuccess of the Japanese in uncovering new antibiotics.To furnish a complete answer to this question un-doubtedly would require an astuteness greater thanany one person has, but I think a good part of theanswer is to be found somewhere in the foregoingconsideration. The fixity of purpose which obviouslymust guide an industrial screening program evidentlyis not felt by noncommercial screening laboratorieswhich, in the aggregate, bring flexibility and the origi-nality and imagination of many individuals workingindependently and uninfluenced by one another. Es-sentially, the answer is to be found in the greatervariety of means and ends in the noncommerciallaboratories.

It may be noted that, in the United States, systematicantibiotic screening research is conducted in very fewnoncommercial laboratories and in practically no uni-versity laboratories. As subjects for professorial re-search and graduate student dissertations, this researchhas fallen into disrepute and become out of vogue; uni-versities have defaulted to industry in this area. InJapan the situation is reversed. True, the pharma-ceutical industries there conduct extensive antibioticscreening programs, but so do several nonindustriallaboratories, and the latter have been conspicuousfor the leadership in new antibiotic research in thatcountry, a fact readily acknowledged by researchersin industry .

ASSOCIATIONS

Companies with common interests in commerciallyimportant fields are usually allied through member-ship in "associations." Among the major associationsin the microbiological realm are the Japan PenicillinManufacturers Association, the Japan Antibiotics Re-search Association, The Fermentation Association, andthe newly formed Association of Amino Acid Fer-mentation. These associations meet periodically, usuallymonthly, for the purpose of exchanging informationon problems of mutual concern and for the presentation

of scientific reports in formal sessions. Membership iscomposed largely of industrial scientists, but also in-cludes persons from government, universities, and otherlaboratory institutions. These associations sponsorsymposia and publications in their specialized fields.Some details about the important and influential

Japan Antibiotics Research Association are warrantedsince it has such a vital function in microbiologicalscience in Japan and illustrates the nature of the manyassociations. This organization has its own office build-ing (a converted dwelling) in Shinagawa-ku, Tokyo.There is a staff of eight, headed by an exceptionallyable permanent managing director, Dr. Y. Yagisawa,who has held this office since the inception of the Asso-ciation in 1946. It is supported by levies assessed prorata, according to the antibiotic sales of the respectivecompanies. This office edits the Japanese (Series B)and the English (Series A) editions of the Journal ofAntibiotics. It functions as a clearing house for thedissemination of information to members, such as thechanging government regulations covering antibiotics,and it usually is the spokesman and go-between for theindustry and the various agencies of the Ministry ofPublic Health and Welfare. It publishes news of in-terest to the membership about developments, events,individuals, and organizations concerned with antibioticscience and medicine. It also plays an important role inpublishing popular articles about antibiotics in the laypress, and in providing information for writers, re-porters, and so forth. The Association also providesmembers, upon request, title and literature surveys onany subject related directly or indirectly to antibiotics.An enormous card file of literature abstracts, cross-indexed by subject and by authors, has been compiled.Every article related to antibiotics is abstracted from400 different Japanese periodicals and 150 foreignjournals which are received regularly either on sub-scription or on an exchange basis. The title of every oneof these articles, including patents, is published in theJournal of Antibiotics, Series B. For example, theFebruary and the June 1960 issues listed, respectively,341 and 310 current references. This source is the mostcomplete published bibliography of antibiotic literaturein the world.The managing director advises the members on

matters of policy and administrates patents for uni-versity professors and others from nonindustrial lab-oratories. In the event of royalties, 50 % reverts to theinventor, 25 % is set aside for support of basic researchin nonprofit laboratories, and 10% for administrativecosts in connection with the patent. In instances oflarge royalty income, 15 % is set aside to accumulatetoward construction of future laboratory facilities forthe inventor. The Association also arranges for sup-port of basic research with research grants receivedfrom Japanese and American companies.

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OTHER MICROBIAL RESEARCHA complete picture of microbiological research in

academic institutions in Japan must include at leastseveral other places. The following list is not complete,but includes most of the important laboratories.

Tokyo University. Department of Agricultural Chem-istry, Laboratory of Fermentation Technology, Pro-fessor K. Yamada. Acid-resistant dextrinizing a-amylase and saccharogenic amylase from submergedcultures of Aspergillus awamori; influence of physicalenvironment on morphogenesis of submerged moldmycelium; oxygen transfer in submerged cultures;acid-resistant lipase from Penicillium sp.; chemicaldifferences between young and wood-aged whiskies.Laboratory of Microbiology, Professor K. Arima.Hiochi (mevalonic) acid and its role in lipid metabolism;microbial degradation of aromatic compounds; pep-tidases and proteinases; D-amino acid oxidation; aminoacid production; allo-isocitric acid fermentation; mecha-nisms of drug resistance in bacteria; bacterial degrada-tion of dipicolinic acid.

Tohoku University, Sendai. Department of Bac-teriology, Faculty of Medicine, Dr. M. Kuroya. Isola-tion and biochemistry of Bacillus pertussis endotoxin.Dr. N. Ishida. Anticancer antibiotic screening, carzino-statin most promising, active against several kinds ofsolid tumors by all routes except oral. Department ofAgricultural Chemistry, Faculty of Agriculture, Pro-fessor T. Uemura. Ecology of sake flora; soil micro-biology; excretion of nucleic acid by yeasts; bacterialbiosynthesis of isoleucine from a-aminobutyric acid.Institute of Agricultural Microbiology, Professor C.Furusaka. Soil microbiology, microbial ecology.Hokkaido University, Sapporo. Department of Agri-

cultural Chemistry, Professor T. Sasaki. Taxonomy offungi; ecology and classification of yeasts; aerobicproduction of gluconic acid by species of Candida;riboflavin formation by strains of Candida robusta;survey of aerobic carbohydrate metabolism of new yeastisolates.Niigata University, Niigata. Department of Bac-

teriology, Faculty of Medicine, Professor T. Ito. Newantibiotic screening against medical and plant patho-gens; classification of actinomycetes. Department ofAgricultural Chemistry, Faculty of Agriculture, Pro-fessor K. Tamari. Biochemical basis of rice blast disease;a-picolinic acid from germinating spores of Piriculariaoryzae; isolation and characterization of piricularin, atoxin for plants with antioxidase enzyme activity;mechanisms of plant resistance to piricularin, e.g.,chlorogenic acid.Osaka City University, Osaka. Department of Bac-

teriology, Faculty of Medicine, Professor S. Otani.Biochemistry of gramicidin J, including biosynthesisand mechanisms; biochemical aspects of sporulation in

Kyoto University, Kyoto. Department of AgriculturalChemistry, Professor H. Katagiri. Biosynthesis ofriboflavin; transglycosidations by flavin enzymes; en-zyme group transfer in microorganisms; fermentativeproduction of L-malic acid from glucose by Aspergillusoryzae (55 % weight yield); aerobic acetone-butanolproduction by mutant strains of Clostridium aceto-butylicum; oxidative production of pyruvic and a-ketoglutaric acids from glucose by Escherichia coli;carbon dioxide assimilation by Thiobacillus thiooxidans;energy transfer during oxidation of elemental sulfur;mechanisms of synthesis in amino acid direct fermenta-tions.

Tokushima University, Tokushima. Faculty of Medi-cine, Department of Bacteriology, Professor N. Yonedaand Assistant Professor T. Hashimoto. Electron mi-croscopy of bacterial spores; mechanisms of spore forma-tion and heat resistance.

Chiba University, Chiba. Institute of Food Micro-biology, Dr. T. Yanagita. Biochemical aspects ofconidiospore germination; choline sulfate in conid-iospores; halophilic microorganisms. Dr. T. Arai. Anti-cancer antibiotic screening.Osaka University, Osaka. Department of Fermenta-

tion Technology, Professor G. Terui. Bioengineering;citric acid formation in submerged Aspergillis nigercultures; germination of conidiospores. Professor S.Teramoto. Oxidative fermentations; glutamic acid bio-engineering; special aspects of shoyu brewing.Kagoshima University, Kagoshima. Professor M.

Kanie. Mechanism of lactic and fumaric acid formationby fungi.Osaka University, Research Institute for Microbial

Diseases. Chemotherapy Section, Dr. J. Kamamato.Mechanisms of action of actinomycins. BacteriologySection, Dr. M. Yoneda. Iron and toxin productionby Corynebacter diphtheriae; immunochemistry of ex-tracellular proteins of Mycobacterium tuberculosis;impermeability barrier, acid-fastness, and biochemistryof bacterial spores.Kyushu University, Fukuoka. Department of Agricul-

tural Chemistry, Professors I. Yamasaki and M. Hongo.Acetone-butanol fermentation, high butanol-acetoneratio strains; amylases for raw starch.Although conducted in an industry-affiliated lab-

oratory, namely, the Takeda Institute for Fermenta-tion, Osaka, there should be mentioned the 20-yearinvestigation by Dr. M. Abe of the biosynthesis ofergot alkaloids in pure cultures of species of the moldClaviceps.

MAJOR FRONTS

Thanks to the names Kitasato, Shiga, Hata, andNoguchi, the first strength of experimental microbiologyin Japan came through the medical area in the early1900's. Today the strength is unquestionably con-

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centrated in the applied and technological area, ex-emplified by antibiotics, amino acids, hydrolytic en-zymes, and food algae. Japan can well claim leadershipin these particular fields at the present time, and, fromthe impressive amount of research on other micro-biological topics, it would not be surprising if the list isextended in the near future. Certainly, if a new fieldof application is portended by any particular experi-mental developments, a number of competent lab-oratories are literally poised to exploit the subjectmatter. The prominent competitive spirit which isfelt widely ensures a multipronged attack on the sub-ject with dispatch.

1) Antibiotics. Two well-defined directions have be-come apparent. One is the search for anticancer agents.This effort seems to be something of a national objective.New agents are discovered with encouraging frequencyin the screening programs discussed earlier in this re-port. Thereafter, chance determines the toxicity,efficacy, and usefulness of the compounds. In the earlydays, claims for remarkable successes with certainantibiotics proved to be premature and unverifiablein other countries. However, antibiotic science in thelaboratory and in the clinic today in Japan is as dis-criminating as it is anywhere, and the description ofnew anticancer agents is apt to be conservative andbased on adequately controlled experimental evalua-tion. A governmental committee evaluates new anti-biotics in a manner analogous to the governmentalcommittees in the United States. When signal promise isindicated, almost certainly it will be learned in theUnited States, if for no other reason than that many ofthe major laboratories, especially the industrial, havetie-ins with United States companies, as describedearlier.The second major antibiotic effort is directed to the

control, of crop diseases in practical agriculture. Amajor breakthrough appears to have been achievedrecently in the protection of the rice plant againstdamage by the rice blast fungus, Piricularia oryzae.This pathogen is airborne and infects stems, leaves, andinflorescences of the rice plant. Blasticidin S, an anti-biotic produced by Streptomyces griseochromogenes, is avery effective inhibitor of P. oryzae. It was discoveredin the Department of Agricultural Chemistry, TokyoUniversity, and process patents are held by ProfessorsY. Sumiki and H. Umezawa. In the summer of 1960,some 40 field experiments on the control of the diseaseunder practical farm conditions were conducted inmany sections of Japan. Depending on the locality andthe year, rice blast causes from 3 to 10 % loss in riceyields. These field trials were supervised by the NationalInstitute of Agricultural Science (equivalent to theDepartment of Agriculture in the United States).Private farms were used and the plants cultivated bythe farm owners in the usual way. I inspected one of

the field experiments just prior to harvest. The resultsof this experiment were striking. The treated plotshad virtually no infection whereas control untreatedplots had a very significant incidence of infection, asrevealed by a complex scoring system based on ex-amination of a large number of individual rice plants.Blasticidin S is applied as an emulsion spray threetimes during the growing season. Effective inhibitoryconcentration in solution is 10 to 20 ppm of the anti-biotic. In efficacious concentrations, the antibiotic itselfdoes not reduce the yield of rice, nor is the antibiotictranslocated to the grain.

Equally as important as the control achieved underfield conditions is the indication that blasticidin S canbe manufactured commercially and sold at a pricepractical for the agricultural economy in Japan. Thefungicide employed in recent years for rice blast isphenylmercuric acetate. Because of the accumulationof residual mercury in soils, the government hasannounced a ban on the use of mercury fungicides forrice, and blasticidin S is the most promising candidatefor its successor. Cost projection based on large scaleproduction of blasticidin S indicates that the agricul-tural product will sell for approximately the same asthe mercury fungicide, i.e., about 10 yen (2.8 cents)per g of 0.2% agricultural powder. The low cost ofblasticidin S is ascribable to the relatively high cur-rent yield, 3 g per liter of broth in 4 days, and thesimplicity of the purification process. It is sold as thehydrochloride salt. Improvements in the process areexpected and the chemical constitution of blasticidinS is under study. The antibiotic is a water-soluble base,with an empirical composition of C14H2005N6. Themolecule contains cytosine. In 1961 it is expected that10 tons of pure blasticidin S will be manufactured foragricultural use, and in 1963 or 1964, 30 tons, theestimated total annual requirement for the country.Larger production is envisioned for export to thesoutheast Asian countries.The bright promise for blasticidin S in practical

agriculture has evoked incentive for screening pro-grams for other antibiotics useful in agriculture.Blasticidin S may well be only a forerunner. The bulkof the royalties expected to accrue from the com-mercialization of blasticidin S will be used to promotebasic research in this field in a new research institute.

2) Amino acid fermentations. Japan's leadership inthis field is acknowledged. The industrialization ofbacterial glutamic acid production was initiated byDr. S. Kinoshita in Kyowa Fermentation Company,Ltd.; in 1960, he received the Prime Minister's Prizefor this contribution to Japan's economy. The bacterialprocess gives a 50 % yield of L-glutamic acid fromsugar in about 2 days. The principal use of monosodiumglutamate is as a flavor-enhancing agent for variousfoods. In the Orient, the trade name "Ajinomoto" is

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practically the common word for monosodium glu-tamate; in the United States, the popular trade nameis "Accent."The success of fermentation glutamic acid has

generated a lively research interest in the microbio-logical production of a second important flavor andtaste chemical for the Japanese palate. Inosinic acid, amononucleotide derived from adenylic acid, was iso-lated and identified in 1913 by Kodama as the majortaste component of "katsuobushi," a favorite driedtuna fish. Its commercial manufacture from driedyeast nucleic acid was recently announced by twoJapanese companies. The lure of direct fermentativesynthesis of inosinic acid is responsible for micro-biological screening programs in several places. Inosinicacid combined in a proportion of 1 to 10-40 parts ofmonosodium glutamate is said to represent a verydesirable seasoning.The glutamic acid fermentation spurred research

which has resulted in a number of one or two stepmicrobial processes for commercially important yieldsof other amino acids. Attention is currently directedto developing industrially useful fermentations for theproduction of each of the amino acids essential formammalian growth. Lysine, produced by a mutantstrain of the glutamic acid bacterium, is, like glutamicacid itself, already in commercial production in theUnited States, under license from the Japanese patent.The low cost fermentative production of L-glutamic

acid has directed attention to the potentially enormousutilization of this and other amino acids as industrialchemicals. Particular interest is being shown in thepolymerization of glutamic acid or alanine to fibersfor textiles. In Japan, as well as in Western countries,close research rapport is being maintained between thelarger synthetic fiber companies and the major sup-pliers of fermentation glutamic acid. A practical de-velopment of this kind would usher in a tremendousnew era for fermentation technology in Japan.

3) Hydrolytic enzymes. This subject has alwaysloomed large in technological microbiology because ofthe cardinal role these enzymes play in saccharifica-tion for the industrial alcohol and beverage fermenta-tions, particularly sake. In addition, the vital functionof proteolytic enzymes in the shOyu and miso fermenta-tions helps explain the interest in these enzymes.K-ji, the traditional molded rice of the Orient, repre-sents an accumulation of hydrolytic enzymes in a massof moist cereal bran cultured with Aspergillus oryzae.The world-famous "Takadiastase," a partly purifiedconcentrate extracted from koji-like cultures, is stillan important commercial product employed in in-dustry and sold as a digestive aid in Japan. TheJapanese have demonstrated skill in crystallizing agreat many hydrolytic enzymes, including nucleases;and the factors controlling synthesis of these enzymes,

and the search for new enzymes with particular prop-erties suiting them for specialized functions, are fieldsin which impressive progress is being made.

4) Mass cultivation of food algae. This subject hasalready been discussed.

SCIENTIFIC LITERATURE

The tremendous amount of microbiological activityin Japan inexorably expresses itself in publications.The major microbiological publications from Westerncountries are widely found in university and institutelibraries in Japan, so access to foreign literature is noproblem. As mentioned earlier, facility with English iscommon among professional scientists, especially read-ing facility.However, the reverse, namely, communication of

Japanese research to the occidental world, is seriouslyhampered by the language problem. Of course, to theoccidental way of thinking, the most practical solutionto this problem is for Japanese scientists to publish inEnglish. Unquestionably, there is a definite trend inthis direction, but only a small fraction of all of theJapanese microbiological literature appears in English.This is true in spite of the universal aspiration ofJapanese scientists to have their works known to theirWestern contemporaries, and to be recognized by them.This attitude I found to be virtually a national charac-teristic. It is also true that in recent years there hasoccurred a noticeable increase in Japanese-authoredpapers in American journals.The main reason for this publication problem ob-

viously is the inability to write in English. It is un-likely that this situation will change appreciably inthis or even the next generation. And yet, a vastamount of important microbiological literature is pub-lished in innumerable Japanese language journals.This log jam is about to be broken.The United States National Science Foundation

has recently stationed two scientific representativesin the American Embassy in Tokyo. In cooperationwith the Science Attach6, they handle all interestsof the National Science Foundation in Japan, amongwhich is the selection of Japanese science literaturefor translation. This will include microbiological science,and a program is being developed for the publication ofthe English translations. In some respects, this programis comparable to American efforts to cope with theRussian literature of science.

Nevertheless, it should be emphasized that Japanesescientists have made admirable progress in publishingin English many excellent journals with microbiologicalcontent. Incongruously, most of these are more widelycirculated and better known in Japan than they arein Western countries. There are two reasons for this.First, English journals originating in Japan are notadvertised and have not heretofore been widely es-

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teemed in Western libraries for the importance andquality of their content. Second, there is the commonpractice for the individual faculties and institutes topublish regularly English language journals or bulletinsrepresenting the collected scientific contributions ofonly the members of those organizations. In fact, inmost such places, publication in the institutionalorgan is mandatory. This is the usual practice of re-search institutes, college faculties, and industrial com-panies alike, and in the aggregate comprises an im-pressive volume and variety of papers. Moreover,practically all of these journals are distributed freeto foreign individuals and libraries. Just how themailing lists for these periodicals are made up isdifficult to ascertain, but usually the lists contain anarbitrary selection of individuals who are noteworthyin the particular fields or who have personal or pro-fessional contacts with the staff members at the source.When applicable, an exchange of periodicals is solicitedon a reciprocal basis. Unfortunately, this system islittle more than a private circulation and does notreach a large circle of potentially interested readers.The Journal of General and Applied Microbiology isregularly mailed to 600 addresses abroad.The problem of communications is highlighted, for

example, by the absence of the very excellent Englishissue (Series A) of the Journal of Antibiotics from manyAmerican college libraries. Actually, there are only 220addresses to which this outstanding journal is mailedoutside Japan, 100 paid and 120 gift subscriptions.Also, I was somewhat chagrined to discover the ex-istence, only after I arrived in Japan, of the excellentEnglish-printed Japan Journal of Microbiology, theorgan of the Japan Bacteriological Society. Un-doubtedly, a great many Western scientists and stu-dents would desire the contents of numerous Englishlanguage Japanese journals and would undertake toarrange their delivery, at least to their own libraries,if they were aware of the existence of these journals.An important service would be filled if a list of allEnglish language journals with microbiological contentpublished in Japan were made available to Westernscientists, such as through publication in Science andin Nature.Another conspicuous gap: the strength and the

impact of modern Japanese microbiology, both basicand applied, imply that the Japanese approaches andpoints of view would be valuable source material forWestern science. At least, the Japanese certainly de-serve to be heard. Their versions of the field, andparticularly the basic treatises on characteristicallyJapanese microbiological practices, would be valuablefor Western specialists and graduate students. Inspite of their acknowledged prowess in microbial arts,sciences, and technology, not a single Japanese referenceor textbook has been made available to Western

microbiology through English translation. A number ofauthoritative works in the field should be published inEnglish editions and distributed through Americanpublishers, whose efficiency in getting books to theattention of interested persons is well-known.A large majority of the journals and bulletins in

Japan dealing with microbiological science and technol-ogy is, as mentioned, essentially collections of worksperformed in the respective organizations, and pub-lished by those organizations. Another large fraction ofscientific papers appears in association-sponsored pub-lications. Both practices conduce a continuation of theparochialism already described for Japanese micro-biology. An important salutory influence on micro-biological science in Japan would be the wider practiceof publication of journals sponsored and published byacademic or professional societies, containing variedbasic research papers and open to individuals from anylaboratory. The quality of the contribution would bethe main criterion for acceptance, this being determinedin the best-known method for accomplishing it, namely,through boards of competent editors. Such a systemwould aid substantially in counterbalancing the spe-cialized, vocational, and technological complexion ofJapanese microbiological science today.

SCIENCE NEWS

In Japan the lay press is very conscious of science;newsworthy developments in microbiology receive theirshare of publicity, and readers their information. Theincidence of science news in the daily newspapersperhaps exceeds the coverage in the American press,and weekly and monthly magazines include everyimaginable phase of science and technology. One out-standing publication of the later kind is a counterpartof the Scientific Monthly, namely, the Asahi ScienceMonthly. Others are Nature, Science, and ScienceGraphic. Not only do these enjoy wide popular circula-tion, but they are extensively used in the primaryschools.The quality of the science coverage in the daily press

is evidenced by the staff of the science section of theAsahi Shimbum, the largest and most influential dailynewspaper in Japan. The morning daily circulation ofthe paper is 4 million, the evening, 3 million, and anEnglish edition is also printed. This staff is comprised offive reporters, all college-trained with science majors.

PERSPECTIVE

In spite of the impediments of compartmentalizationin training and research, and of the accent on pro-grammatic and vocational aspects, microbiology inJapan has prestige as an independent science. Inattitudes, education, research, and technology, it hasits position of equality and respect in the front line of

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recognized professions. As a profession, it is regardedtoday as an end in itself and not, as is often the case

in the occidental world, simply a handmaiden tomedicine, chemistry, and biology. These factors, to-gether with the organization of microbiological sciencein institutes, conduce an orientation to an image ofmicrobiology as a profession and a science; added to theconscious mobilization for the exploitation of themicrobe, these give one an appreciation of the forcesaccounting for the size, strength, and vigor of micro-biological science in Japan today.And it must be said that the situation is a founda-

tion of recent fabrication, the full impact of which hasonly begun to assert itself. The emphasis is mainlytechnological, because of its present fruitfulness and

the scarcity of funds for support of basic microbio-logical research. In the long run, success in technologydepends on the discoveries of the independent funda-mental researcher and on the flow of persons trainedin breadth from the universities. The need for greatlyincreased financial support for both of these inter-dependent aspects on a broader base throughoutthe colleges and universities of Japan is becomingincreasingly critical.

ACKNOWLEDGMENT

Financial assistance through grants from the Micro-bial Chemistry Research Foundation (Japan) and theNational Science Foundation (United States) is grate-fully acknowledged.

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