REVIEW
Modern Japanese medical history and theEuropean in¯uence
Yoshio Izumi and Kazuo Isozumi1
Department of Neurology, Tokai University School of Medicine, Kanagawa
1 Department of Neurology, Ashikaga Red Cross Hospital, Tochigi, Japan(Received for publication on January 19, 2001)

Abstract. Before the ®rst European visited Japan in 1549, traditional Chinese medicine was mainly
employed in Japan. Francisco de Xavier, a missionary of the Society of Jesus, tried to promote theintroduction of Christianity by providing a medical service for Japanese citizens. However, Japan
implemented a national isolation policy in 1639 and cut off diplomatic relations with the rest of theworld, except Holland and China. For over 200 years, until the American admiral Matthew Perry
forced Japan to open its doors in 1853, Japan learned about western medicine only from doctors of the
Dutch merchants' of®ce or from Dutch medical books. After 1853, Western medicine was rapidly
introduced into Japan, and great achievements by Japanese medical doctors soon followed, such as theserum therapy for tetanus, the discovery of the plague and dysentery bacilli, the invention of Salvarsan
for the treatment of syphilis, and the demonstration of the neurosyphilis spirochete. (Keio J Med 50 (2):91±99, June 2001)
Key words: Kaitai-Shinsho, Seishu Hanaoka, Siebold, Pompe, Shibasaburo Kitasato

Obtaining the permission of the feudal lord of Satsuma,
Shimazu, he engaged in missionary work in the westernparts of Japan. According to the record of NipponSeikyo-Shi (History of Western Religion in Japan),
Xavier nursed sick persons during his missionary work.
In 1557 Macao was ceded to Portugal by the Chinese
Ming dynasty as compensation for the subjugation of
pirates, and Portugal used Macao as a base for tradewith Japan.
Xavier had medical skill only at the nursing level.
However, Luis de Almeida (1525±1583) brought thefull scope of European medicine to Japan. Almeida
came to Japan in 1555, and provided medical treatment
to local people to encourage their conversion to Christianity. Almeida carried out medical treatment andsurgery outdoors, partly because lighting was poor indoors, but also because he wished to avoid the rumor
that southern barbarians (Nanban-Jin) sucked out people's lifeblood and ate human ¯esh. According to therecommendation of Almeida, Sourin Ohtomo (1530±
1587), the feudal lord of Bungo, constructed a relief
facility (a hospital, misericordia) in 1557 in the city ofOita. The surgery, which was done mainly by Spaniards

Xavier's Visit to Japan and``Southern Barbarian Style Surgery''
The God of medicine in Europe is Asclepius, but theperson honored as the founder of medicine is Hippocrates, who was born around 460 B.C. However, after
Hippocrates and Galenus (130±201?), there was little
development of medicine in Europe; such progressas there was, occurred in Arabia. Later, during
the Renaissance in Europe, Andreas Vesalius (1514±1564) developed anatomy greatly. In the same period,
Ambroise PareÂ (1510±1590) served as the chief surgeon
for four French kings and left the saying, ``I dressed him
and God healed him (Je le pansay et Dieu le guarist).''Hospitals were being built in Europe in accordancewith Christian teaching. These hospitals cared not only
for acutely sick persons, but also for the poor or physically handicapped, and also the chronically sick. This
was the background of the Europeans who came to
Japan, where traditional Chinese medicine was mainly
practiced.
Francisco de Xavier (1506±1552), a missionary of theSociety of Jesus (Iezusu-Kai), visited Japan in 1549.

Reprint requests to: Dr. Yoshio Izumi, Department of Neurology, Tokai University School of Medicine, Bouseidai, Isehara-shi, Kanagawa
259-1193, Japan
91

92

Izumi Y and Isozumi K: Japanese medical history

and Portugueses, was called ``southern barbarian stylesurgery'' (Nanban-Ryu-Geka). In comparison with thepolitically sensitive missionary work of the Society ofJesus, the Society of Francisco adopted an aggressively
evangelistic approach. Hideyoshi Toyotomi (1536±
1598), the Japanese ruler, became annoyed; in 1587 thefathers were deported (Bateren-Tsuihou) and in 1596,
26 missionaries were executed as martyrs.
``Red Hair Style Surgery'' and Touyou Yamawaki
Formal diplomatic relations between Japan and
Holland started in 1608, more than 50 years after theestablishment of a western style hospital by Almeida.
The policy of Japan in those days was strictly to prohibit Christian missionary work but to promote trade.
The Spaniards and Portugueses were forced to retire
from the entry-port (Dejima) in Nagasaki, because they
propagated Christianity under cover of Christian medical treatment, and also because of their rumored intention to occupy Japan.
In this way, ``southern barbarian style surgery'' cameto an end, and ``red hair style surgery'' (Koumou-RyuGeka)'' started on Nagasaki's 13,000 m 2 entry-portisland. Dutchmen were called ``red hair persons''(Koumou-Jin) because of the color of their hair. Caspar
Schamberger, a doctor of the Dutch merchants' of®ce,
played an active part in the early stages, and his work
was called ``Caspar style surgery''. The import of medical books was prohibited by the national isolation
policy (Sakoku-Rei) in 1639. However, Japanese doctors, who were eager to learn European medicine,
wrote down what Dutch surgeons said, observed theoperations and imitated them. During the 250 years of
the Edo period about 100 Dutch doctors were stationed
at the merchants' of®ce. Hoan Arashiyama (1633±1693)
learned surgery from Dutchmen at Nagasaki's entryport island for 6 years from the age of 28, and wrote 6
volumes of ``Learning Records of Red Hair Style Surgery (Koumou-Geka-Souden)''.
Touyou Yamawaki (1705±1762), a doctor who questioned the traditional Chinese concepts of anatomy, got
hold of an anatomical textbook by Johan Vesling, published in Holland. In 1754 he observed the dismemberment of the corpse of a criminal in Kyoto, and was
surprised at the accuracy of the textbook. Touyou
Yamawaki could not understand Dutch, but he eventually published ``Records of Dissection'' (Zoushi) (Fig. 1)
in 1759.
Cancellation of the Embargo on the Import ofDutch Books and Gempaku Sugita
The Shogun, Yoshimune Tokugawa (1684±1751),
cancelled the embargo on the import of Dutch books

Fig. 1 Original ®gures of ``Records of Dissection'' (Zoushi) written
by Touyou Yamawaki in 1759.

in 1720 (Bansho-Kaikin-Rei). Dutch studies (Rangaku)
developed rapidly, and the famous ``Kaitai-Shinsho''(New Textbook of Anatomy)'' (Fig. 2) was published.
Gempaku Sugita (1733±1817) (Fig. 3) was a doctorof a feudal clan. Young Sugita wanted to take the bestof Japanese, Chinese and Dutch medicine, and published ``Accomplishment as a Surgeon'' (Youka-Taisei).
Later, he read ``Tabula Anatomica'', a Dutch translation of an illustrated textbook of anatomy (1731version) written by the German anatomist, Johan
Kulumus. He observed the dismemberment of the corpseof a criminal in 1771, and, like Yamawaki before him,
was astonished by the accuracy of the textbook. He
then studied with Ryoutaku Maeno for four years, and®nally published Kaitai-Shinsho.
Ryoutaku Maeno and Kaitai-Shinsho
Ryoutaku Maeno (1723±1803), who lost his parents
in childhood, was brought up and educated by his uncle,
Zentaku Miyata, a doctor of a feudal clan. His uncle's
precepts were (1) if you are doing only what otherpeople are doing, you will stay fruitlessly behind themfor your entire lifetime, and (2) any man worthy ofthe name should originate at least one thing and become a leader. At the age of 47, Ryoutaku became thepupil of Konyou Aoki (1698±1769), who was the Shogunate's book-magistrate (Bakufu-Shomotsu-Bugyo),Keio J Med 2001; 50 (2): 91±99

93Fig. 3

Gempaku Sugita in 1812 (80 years old).

Fig. 2 Cover ®gure of ``Kaitai-Shinsho'' (New Textbook of Anatomy) in 1775.

Seishu Hanaoka and Tusensan
and learned Dutch. Ryoutaku Maeno followed the advice of his adoptive father by publishing Kaitai-Shinsho,
which was an illustrated textbook of anatomy in classical Chinese writing. On the opening page of the KaitaiShinsho three names following Gempaku were listed,
but the name of Ryoutaku Maeno was not included,
even though he had played the greatest role in its
translation.
Gempaku, et al. found dif®culty in the translation of
Dutch words which had no Chinese equivalents. Theytranslated cartilage as Nankotsu, nerve as Shinkei,
the portal vein as Monmyaku, and so on, creating
new Chinese words. A translation of pancreas was notmade, and Suizou was named later by Genshin Udagawa (1769±1834). Gempaku described these painstaking efforts in his reminiscences ``Rangaku Kotohajime''(The Beginning of Dutch Studies). Rangaku Kotohajime was reissued to commemorate the ®rst generalacademic medical meeting in Japan in 1890, and Yukichi Fukuzawa (1835±1901) provided an introduction.

In the era of Gempaku Sugita, a surgeon could only
apply a plaster, suture a wound and lance an abscess.
Seishu Hanaoka (1760±1835) (Fig. 4) developed surgery in Japan. He came to Kyoto at the age of 23, andlearned old Japanese medicine and ``Caspar style surgery''. Although Seishu himself could not understandDutch, he combined Chinese and Dutch medicine
and established ``Hanaoka style surgery''. He used thenames Sakou for aproctia and Sain for gynatresia. He
performed operations for breast cancer, gangrene,
hemorrhoids, and palatoschisis. He published a book``Youka Hiroku'' (Secret Notes for Surgery). This was
actually written by his pupils, based on notes of what hehad said.
After 20 years of investigation, Seishu developed theanesthetic ``Tusensan'', whose main ingredients are
Korean morning glory and aconite. During this 20
years, his mother Otugi and his wife Kae devoted
themselves to his research. His mother died without
knowing of his success and his wife unfortunately losther sight.

94

Izumi Y and Isozumi K: Japanese medical history

Fig. 4

Seishu Hanaoka (60 years old).
Fig. 5The ®rst operation for breast cancer was on a 60year-old woman named Kan. Since her sisters had diedmiserably of breast cancer, she asked for the operation
without hesitation. The operation was performed on
October 13, 1804, and Kan survived for 4 months afterwards, dying on February 26, 1805. In America, surgery to remove cervical neoplasm under ether anesthesia was ®rst done by Morton at the Massachusetts
General Hospital in 1846. Thus, Seishu invented andutilized an anesthetic 42 years earlier than the ®rst use
in America. However, it was not known to the world
because of Japanese isolation policy and Seishu's secret.
Siebold and the Narutaki Cram School
Engelbert Kempfer (1651±1716), a doctor in the
Dutch merchants' of®ce, wrote ``The Natural History ofJapan'' (Nippon-Shi), describing Japan as it was in the
18th century. In this book, there is a picture of Kempfer
singing a love poem in front of the Shogun, Tsunayoshi(1646±1709), in Edo castle. Kempfer also introduced
acupuncture and moxibustion in Japan.
Philipp von Siebold (1796±1866) (Fig. 5), a German
ophthalmologist, stayed in Japan for six years from1823. Siebold was born in a prestigious family in 1796;
his grandfather, father and uncle were all medical professors. He had a wide knowledge of many subjects,
such as natural history, ethnology, geography, history
and language. Siebold had the title of surgeon lieuten-

Siebold in his later years.

ant commander, but actually, he was given the task ofgeneral investigation of Japan by the Dutch government.
The reasons for Siebold's prominent place in Japanese medical history are (1) he had a great passion forJapan, and (2) there were already many scholars of
Dutch studies in Japan who could translate even scienti®c books, because a half century had passed since
the publication of Kaitai-Shinsho. Siebold opened the
Narutaki Cram School (Narutaki-Juku) within a year
after his arrival in Japan. A number of pupils studiedDutch there, and observed Siebold's clinical work.
Siebold performed vaccination against smallpox,
bloodletting, abdominocentesis, tylectomy, surgery forcataract, optical iridectomy, etc. (Fig. 6). However, it isuncertain whether his school provided a systematic
medical education or not. Siebold gave themes to hisbest pupils, and let them submit their graduation thesis
in Dutch (Dissertatio inauguralis). From these Dutch
papers Siebold gathered a wide range of information
about Japan. Papers which Chouei Takano and Ryousai
Kou submitted include ``Japanese Diseases'' (NipponShippei-Shi), ``The Outline of Moxibustion Method''(Kyuhou-Ryakusetsu) and ``Questions and Answers on
Japan Obstetrics'' (Nippon-Sanka-Mondou). Siebold
copied the university system in Germany and awardeda degree quali®cation (Doctor-Diplom), though it
was purely a private one. However, most of his pupils

Keio J Med 2001; 50 (2): 91±9995translation ``Ophthalmology Convenience'' (GankaBinyou) and ``Essentials of Ophthalmology'' (GankaHitsudoku), but Genseki did not know this.
Siebold later approached the Shogunate's geographer, Kageyasu Takahashi (1785±1829), and offered to
exchange a world map for a map of Japan, which was astate secret. Kageyasu agreed to this proposal, but was
found out, and this became known as the second Siebold Affair. Kageyasu died in prison. Siebold was sentenced to deportation and the map was seized, but Siebold had already sent copies to Holland. After this, theNarutaki Cram School closed and the pupils scattered.
After his return home, Siebold was considered
Europe's top expert on Japan, and he wrote many
books such as ``Japan'', ``Japanese Plants (Flora
Japonica)'' and ``Japanese Animals''. Much of the information was based on the Dutch papers presented by
Siebold's pupils. Siebold cooperated with the Russianemperor Nikolai, who was pressing Japan to open the
country, and helped Nikolai to prepare the draft of acommercial treaty between Japan and Russia (NichiroTsusho-Jouyaku). Also, he asked to accompany Matthew Perry's Japanese expedition, but Perry rejected
this proposal because Siebold was under sentence ofbanishment in Japan. This was later lifted, and Siebold
re-visited Japan in 1859.
Fig. 6

Surgical equipment that Siebold used.

wished to gain this quali®cation, and struggled to write
papers in Dutch on the themes given by Siebold.
The Siebold Affair and the Natural History of JapanThe staff of the Dutch merchants' of®ce at Nagasaki's entry-port island were given an audience with the
Shogun every ®ve years. On the way to Edo, there were
proposals of interview from many doctors and wealthy
persons, and they offered huge presents to the staff.
Also the staff could get much information from them.
Genseki Habu (1768±1854), who was an ophthalmologist in the Shogunate, approached Siebold in order tolearn the secret of the mydriasis agent, belladonna,
which was mandatory for cataract operations. Siebold
asked Genseki to get him some cloth bearing the mallow crest (Ai-No-Monpuku), which was the of®cial
cloth of the Shogunate, in exchange. Genseki did so,
but the act was discovered, and this became known as
the ®rst Siebold Affair. Genseki received a heavy punishment, ``deprivation'', but he was pardoned later. In
the Edo period, deprivation was a lighter punishment
than Hara-Kiri (Seppuku), but heavier than house arrest (Chikkyo). Incidentally, Siebold's pupil, Ryousai
Kou, had already described this mydriasis agent in the

Ryoujun Matsumoto and Pompe's Visit to Japan
Taizen Satou (1804±1872), a Dutch style surgeon,
originally wished to become a pupil of Chouei Takano(1804±1850), who was a pupil of Siebold but was later
imprisoned with Kazan Watanabe (1793±1841) underthe Bansha-No-Goku (imprisonment of scholars for
European studies). The request was refused, but Taizen
Satou stayed in Nagasaki for three years to study. After
returning to his hometown, he opened the Sakura Juntendo which was the ®rst private hospital in Japan, offering smallpox vaccination and operations for ovariancysts. Ryoujun Sato, who was the second son of Taizen,
entered the family of Matsumoto (Shogunate's physician) as a son-in-law, and changed his name to Ryoujun
Matsumoto (1832±1907). Taizen's successor was Shunkai Yamaguchi, who later changed his name to Shouchu
Sato, and founded the Juntendo Clinic.
A warship was presented by Holland to the Shogunate in 1855. It was equipped with six big guns and the
Shogunate named it ``Kankou-Maru''. Kaishu Katsu(Rintaro, 1823±1899), followed by dozens of the Shogunate's samurai, was sent to Nagasaki as the ®rst naval
student (Kaigun-Denshu-Sei). Two years later (1857),
Kanrin-Maru, which the Shogunate had ordered toHolland, entered the port of Nagasaki. On this warship,a 28-year-old second-class military surgeon, Pompe
van Meerdervoort (1829±1908) (Fig. 7) was embarked.

96

Izumi Y and Isozumi K: Japanese medical history

cation. Pompe ordered a human body model ``Kunstlijk'' from Paris and used it to educate students. For
anatomy education, Pompe himself conducted dissection and explained each part. Since the principle of
excluding foreigners (Joui-Ron) was popular during
this period, a foreigner's dissection of a Japanese bodywas considered outrageous. Therefore, the dissection
was performed under a guard of 150 soldiers. The lectures were carefully programmed by making simple
guidebooks in all subjects, distributing them to thestudents, and providing verbal explanations based onthem. Most Japanese in the medical world in the Meiji
era were pupils of Pompe, and many excellent doctors
graduated from his medical school.
Nagasaki Recuperation Place and the
Return Home of Pompe

Fig. 7

Pompe in his youth.

Further naval students were recruited and Ryoujun
Matsumoto was sent to Nagasaki.
Pompe's visit to Japan was the result of a special invitation by the Shogunate, and he became the surgeonof the navy teaching group. After taking up his new
post Pompe immediately set about the preparation of
medical lectures. Lectures on Western medicine were
given at the western Nagasaki magistrate's of®ce todozens of students, including Ryoujun Matsumoto. In
fact, Ryoujun Matsumoto was the only of®cial medical
student, and the other naval students were consideredfollowers. As the number of students increased, a
medical school (Igaku-Denshu-Jo) was established, andeach feudal clan sent selected students. This was theforerunner of today's Nagasaki University Medical
School.
During his term of of®ce Pompe educated 350 surgeons and issued 133 graduation certi®cates. Medical
education by Pompe was based on the idea of advancing to clinical medicine after thoroughly learning basic
medicine, and in this respect, resembled modern edu-

The second important achievement of Pompe inJapan was the establishment of the Nagasaki recuperation place (Nagasaki-Youjou-Sho) which was the ®rst
Western style hospital in Japan. This was founded by
the Shogunate in response to the request of the Dutch
merchants' of®ce and Pompe. The dimensions of this
hospital were 25 meters east to west, and 8 meters northto south, with two-story Western style architecture in
the shape of an H. It had 128 beds, of which about 70
were generally occupied.
Cholera was endemic in the whole country in 1858,and it was said that there were 260,000 deaths in
the Edo area alone. Pompe predicted the outbreak ofcholera in Japan based on information from Java,and suggested countermeasures to the Nagasaki magistrate's of®ce (Nagasaki-Bugyo-Sho). Based on his
report, the magistrate's of®ce prohibited eating fresh
foods and distributed a julep which was recommended
by Pompe. This julep consisted of quinine and opium,and for this purpose, doctors bought the whole stock ofquinine in Osaka.
Pompe returned to his home country in 1862 after 5
years in Japan. In 1863 the Shogunate sent six persons
to study at Leiden in Holland for the ®rst time. Ryojun
Matsumoto was advanced in rank from his Shogunate
post to be the ®rst surgeon general of the army, and wascreated a baron by the Meiji government.
Adoption of German Medicine and the Hiring of
Foreigners to Assist Medical Education
When Pompe returned home, the Dutch government
sent Anthonius Bauduin (1822±1885) as his successor.
Bauduin had been a professor of Utrecht Army Surgeon School for 15 years. On the other hand, an English
doctor William Willis (1837±1894) helped the Meiji
government in the war of Bakumatsu restoration. It wasKeio J Med 2001; 50 (2): 91±99

clear that Western medicine, especially surgery, wassuperior to the traditional Chinese-Kampo medicine inJapan. The new government wavered in choosing between the English medicine of Willis and the Dutch
medicine of Bauduin. Finally, the government accepted
the opinion of Guido Verbeck (1830±1898), a Dutch
missionary, and decided to adopt German medicine in
1869. After that, medicine in Japan was predominantly
German-in¯uenced until the end of World War II.
After the Meiji government had adopted German
medicine, Willis went to Kagoshima and founded Kagoshima Medical School with the aid of Takamori Saigou(1827±1877).
Medical education by hired foreigners was started,and in 1871, Benjamin MuÈller (1822±1893), a surgeonof the German army, and Theodor Hoffmann (1837±1894), a specialist in internal medicine from the German navy, visited Japan. Also, the Tokyo University
School of Medicine was established at the Kaga feudalclan mansion at Hongo in 1876. Erwin von BoÈlz (1849±
1913) came to Japan in 1876 to take charge of internal
medicine and obstetrics, and Julius Scriba (1848±1905)
came in 1881 to take charge of surgery and dermatology.
In 1879 Tokyo University School of Medicine sent
the best of its ®rst graduate students to study in Germany. When they returned to Japan, they were successively installed as professors in place of the foreign
medical teachers. By 1903, all the professors of Tokyo
University School of Medicine were Japanese, and theJapanese medical world had achieved independence.
The continuation of traditional Chinese-Kampo medicine was prohibited in 1895 by the Diet.
Rintaro Mori and the Beriberi Argument
After his graduation from Tokyo Imperial University, Rintaro Mori (Ougai, 1862±1922) studied in Germany. After he returned to Japan, he became the army
surgeon general. He is now remembered in the medical
world for his mistaken advice about beriberi to thearmy. Beriberi was common mainly in cities, from the
middle of the Edo era, and was called ``Edo disease'' or``Osaka swelling''. The 14th Shogun, Iemochi, died ofberiberi. When Pompe and Bauduin examined thesepatients, they con®rmed that the disease was ``beriberi'', which is common in southeastern Asia, but not inWestern countries. It is now known to be a de®ciency
disease of vitamin B1 and causes muscle weakness,sensory disturbance and heart failure due to peripheral
neuropathy. Vitamin B1 is not contained in polishedrice, but is contained in unpolished rice and wheat.
Rintaro Mori insisted that a polished rice-based dietwas excellent for soldiers from the viewpoint of nutrition. On the other hand, the navy adopted bread as a

97

Fig. 8

Shibasaburo Kitasato in 1892 (41 years old).

part of the diet on the advice of the navy surgeon general Kanehiro Takagi, and beriberi decreased sharply
among naval personnel. However, the army entered the
Russo-Japanese War without changing the diet at insistence of Rintaro Mori, the army surgeon general, andaccordingly suffered severely from disease. It was after
the Battle of Houten, the hardest land battle of the
Russo-Japanese War, in 1905 that a rice and wheat
mixed diet was adopted throughout the army.
Shibasaburo Kitasato and Koch
The 19th century was the time of the rise of microbiology. The true nature of infectious diseases was discovered by Louis Pasteur (1822±1895) in France andRobert Koch (1843±1910) in Germany, and there wasgreat competition between nations to establish treatments. Shibasaburo Kitasato (Fig. 8) was the ®rst Japanese to join the world leaders in medicine.
Kitasato graduated from the Tokyo University
School of Medicine in 1883, and was sent to Germany
to study in 1885, when he was 32 years old. Koch wasastonished by the ¯uent German of Kitasato when hevisited the Koch Research Institute. Kitasato was acommitted student; he had never walked along any
road except the one from his lodging to the research
institute even after he had been in Berlin for a year.

98

Izumi Y and Isozumi K: Japanese medical history

Kitasato succeeded in the anaerobic cultivation of
Clostridium tetani. Moreover, he discovered that thecause of tetanus is a toxin released by the bacteria, notthe bacteria itself. Emil von Behring (1854±1917), who
was working in the same institute as Kitasato, obtained
a similar result with Corynebacterium diphtheriae, andthese two investigators published a joint paper on serum therapy. They won high praise throughout theworld, and Behring later won a Nobel prize. However,regrettably, Kitasato did not.
Kitasato originally planned to study abroad for three
years, but this was extended to ®ve years. In 1893,
Cambridge University invited Kitasato to be presidentof a newly established research institute of microbiology. However, Kitasato declined the invitation,saying, ``I have to go back to Japan and rescue mycountrymen from illness and repay my obligation to theEmperor.''However, unexpectedly, Japan did not welcome him.
Tokyo University closed its gates, and the Ministryof Education, Science and Culture ignored Kitasato.
Yukichi Fukuzawa at the Keio Gijuku founded a private infectious disease research institute, and Kitasato
began to work there. The government granted a subsidy to this institute every year, but as the importanceof research on infectious diseases grew, the institutebecame a national one under the Ministry of Domestic
Affairs. Kitasato became head of the national research
institute. When the school of medicine was establishedin 1920 in Keio Gijuku, Kitasato did not forget the helpof Fukuzawa and became the ®rst dean of the school of
medicine.
In 1908 Koch visited Japan and stayed over 70 days.
He gave a memorial lecture in the auditorium of Ueno
Music School, at which Kitasato himself served as theinterpreter. At the evening theater party, Ougai Moriundertook to translate the outline of the play. Koch fellin love with Japan and wanted to take a Japanese maidback to Germany. Kitasato asked a girl called Ohanasan to go to Germany, and she faithfully cared for Kochfor two years until he died.
Kiyoshi Shiga and Ehrlich
Kiyoshi Shiga (1870±1957) discovered the dysentery
bacillus in 1898, and studied abroad under Paul Ehrlich
from 1901. Ehrlich (1854±1915) discovered passive immunity by serum injection and active immunity by toxin
injection. Moreover, he discovered that toxins do not
lose their immunogenicity even after they have losttheir toxicity by heating, and he was awarded a Nobel
prize in 1908. Many new dyes were being developed inPrussia, and Ehrlich suggested that Shiga should try
the administration of these dyes to Trypanosomatidae.
Hundreds of dyes were tested, and at last in 1904, Shigafound that the dye Trypanrot had an anti-Trypanosomatidae effect. Ehrlich and Shiga described this method
as dye therapy (Farbentherapie), and it can be regarded
as the precursor of later techniques of chemotherapy.
Sahachiro Hata and Salvarsan
In 1908 Sahachiro Hata (1873±1938) went to study in
Ehrlich's own research laboratory. Hata examined theanti-spirochete effects of thousands of chemical compounds. Treponema pallidum had only been discoveredin 1905, but as early as 1909, Hata discovered thatcompound No. 606 was effective against syphilis Treponema pallidum. This compound, arsphenamine, wasput on sale under the name of Salvarsan in 1910. After
that, Ehrlich in Germany and Hata in Japan worked to
introduce and improve this new medicine.
In addition, Umetaro Suzuki (1874±1943), who had
been studying the nutritional value of rice, solved themechanism of beriberi, and succeeded in extracting
oryzanin (vitamin B1 ) from rice bran in 1910.
The Life of a Hero, Hideyo Noguchi
Hideyo Noguchi (1876±1928, Fig. 9) is more popularthan Shibasaburo Kitasato, and more famous than
Sahachiro Hata. Many biographies of him have been
written and bronze statues of him can be seen in many
places in Japan.
Noguchi was the son of a poor farmer in Aizu, andwas born in 1876. At the age of one and a half years, he
put his left hand into the ®re by mistake and severely
burned it. He went to Tokyo in 1896 and eventually
graduated from the Saiseisha medical school. However,clinical activities were dif®cult with his damaged left
hand. Therefore he specialized in microbiology. He
entered Kitasato Research Institute of Infectious Diseases in 1898, but all the other staff were graduates ofTokyo University and Noguchi felt like an outsider.
One day, an American researcher visited the institute.
Noguchi got on well with him, and in 1899, the 23-yearold Noguchi got on board ship to America. He spent all
his time working at the research laboratory, and people
were always asking, ``When does Noguchi sleep?'' Hebecame a director of the Rockefeller Research Instituteas a result of his studies on snake venom and the syphilis spirochete. He succeeded in the demonstration of
the existence of syphilis spirochetes in the cerebral tissue of a neurosyphilis patient, which is considered his
greatest achievement.
In 1915, Noguchi returned to Japan. The Japanese
victory in the Russo-Japanese War had led to the rise ofnationalism, and Noguchi's world-beating achievements
made him a hero in Japan. However, when he visited
America again, America was ®ghting with Spain, andKeio J Med 2001; 50 (2): 91±99

99

scope. So, Noguchi, looking for a new challenge, went
to Accra in Africa, where yellow fever was endemic.
This brought Noguchi's life to a close at the age of 53,
because he himself got yellow fever. His last words
were, ``I don't understand.'' The following sentence waswritten on Noguchi's tombstone in New York.
THROUGH DEVOTION TO SCIENCEHE LIVED AND DIED FOR HUMANITY
Selected References

Fig. 9Hideyo Noguchi in 1920 (44 years old).

more American soldiers died of yellow fever than in the
war itself in Cuba. The pathogen of this disease isactually a virus which passes through bacterial ®lters,
and it could not be seen with Noguchi's optical micro-

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Tokyo, 1991 (in Japanese)
4. Inoue K: Igakushi Gaisetsu. Uchida Roukakuho, Tokyo, 1971
(in Japanese)
5. Souda H, Kamohara H, Nagatoya Y, Ishida J: Igaku Kindaika
To Rainichi Gaikokujin. Sekai Hoken Tsushin Sha, Osaka, 1988
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6. Sugimoto T: Zuroku Rangaku Kotohajime. Waseda Daigaku
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7. Koike I: Zusetsu Nihon No I No Rekishi, Ouzora Sha, Tokyo,
1993 (in Japanese)
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9. Katagiri K: Rangaku Kotohajime To Sono Jidai. Nihon Housou
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10. Ninomiya R: Igakushi Tanbou. Nikkei BP, 1999 (in Japanese)
11. Itou Y: Iryou To Rekishi. Medica Shuppan, Osaka, 1994 (inJapanese)
12. Magner LN: A history of medicine. Marcel Dekker (Inc.), New
York, 1992
13. Bynum WF, Porter R: Companion encyclopedia of the history of
medicine (Vol. 1, 2). Routledge, London, 1993
14. Duin N, Sutcliffe J: A history of medicine. Simon & Schuster,London, 1992