Hideyo Noguchi. Courtesy of the National Library of Medicine.

26 The Pharos/Autumn 2011 Hideyo Noguchi Controversial microbe hunter

Don K. Nakayama, MD, MBA The author (AΩA, University of California, San Francisco, Atsushi Kita presents Noguchi as a lonely scientist in a foreign 1977) is the Milford B. Hatcher Professor and Chair of land who reached success through hard work, deference, and the Department of Surgery at Mercer University School of perseverance, characteristics highly valued in Japan.2 Isabel Medicine in Macon, Georgia. Plesset, in her 1980 book, Noguchi and His Patrons, details the debates that surrounded his work and the relentless ero- ideyo Noguchi (1876–1928) at the time of his death sion of his assertions as conflicting evidence accumulated.3 was one of the world’s foremost medical researchers Plesset shows Noguchi as a scientist who holds a hypothesis during the heroic “microbe hunter” era of medicine, long after others have demonstrated it to be wrong, a failing knownH for his work with syphilis, yellow fever, and tropical afflicting researchers throughout history. In her 1985 mono- diseases in Mexico, South America, and Africa. While his graph on Noguchi, Susan Eyrich Lederer, an authority on the reputation in Japan as one of its greatest scientists continues ethics of human experimentation, recounts the researcher’s today, he is nearly a forgotten figure in his adopted coun- human tests with syphilis and the public controversies that try, the United States, where he did the work that earned surrounded them.4 While his experiments used noninfective him international renown. There are few figures in modern extracts that were first tested on fellow researchers and him- medical history whose reputation is as dichotomous as that self, Noguchi was caught in the rising human antivivisection of Noguchi. movement of the times.* His story is both inspirational and tragic. The son of a Through these three works, we see the character strengths peasant woman, his hand disfigured from burns suffered in that made Noguchi a hero in his native Japan, the human infancy, he immigrated penniless to the United States and rose weaknesses that blinded him to the flaws in his science, and to international fame in one of the West’s most technological the historical happenstance that gave him an early role in a and competitive fields, biomedical research. His staggering major controversy in medical ethics. Plesset’s and Lederer’s capacity for work and drive for recognition, however, led works were published more than twenty-five years ago, but to unethical science: premature publication of findings that they give an added Western perspective to a present-day hero could not be duplicated, clinical application before adequate in Japan and Africa. verification, and questionable human experimentation. His Noguchi’s mother Shiga worked in the rice paddies while untimely death at fifty-one from yellow fever was the result his father did odd jobs and often lost himself in drink. The in part of his unshakable belief—arising from his own faulty infant Hideyo, unattended while Shiga was planting rice, experiments—that the infective agent was a spirochete, not a crawled into the burning coals of the open hearth that warmed virus. Despite being little more than a footnote in U.S. medical the living quarters and cooked the family meals. By the time history, Noguchi’s portrait graces Japan’s basic unit of cur- Shiga heard his screams and rescued him, he had horribly rency, the 1,000 yen note, he is honored with a statue in front burned his left hand. With poultices and home remedies the of Tokyo’s National Museum of Nature and Science in Ueno only treatment for the burns, the boy’s hand healed virtually Park, and a major research institute for tropical diseases in 1 Ghana is named after him. The discrepancy in legacies could * Lederer’s paper, “Hideyo Noguchi’s luetin experiment and the not be more different and defies easy explanation. antivivisectionists,” explains the movement against human experi- In a 2003 book translated into English in 2005, Dr. mentation that arose from the original opposition to animal vivisec- Noguchi’s Journey: A Life of Medical Search and Discovery, tion.4

The Pharos/Autumn 2011 27 Hideyo Noguchi

fingerless, with its thumb fused to the wrist. It was clear that nearest railway station in Koriyama. he would never become a farmer, one of the few realistic fu- Tokyo was already the world’s largest city when Noguchi tures for a son of peasants. arrived in 1896. It provided a multitude of distractions, par- ticularly in the seedy Yoshiwara entertainment district where But Hideyo was bright and excelled in the village school. impoverished medical students lived. Noguchi likely had his His oral examinations impressed the proctor, Sakae Kobayashi, second encounter there with spirochetes, this time through who was also the schoolmaster at a more advanced private the usual means with local prostitutes. Noguchi discovered school. Touched by the boy’s injury and poverty, Kobayashi that he had syphilis some seventeen years later in the United offered admission to his school tuition-free. It was a difficult States when a physical examination uncovered aortic insuffi- choice for Shiga. Neighbors and friends warned against over- ciency from an inadequately treated infection, a secret he held reaching and predicted disappointment because a peasant had until his own postmortem examination.3 little use for education. It offered the possibility, however, that Noguchi attended a proprietary medical school, Shiga’s one-handed fourteen-year-old son might be able to Saiseigakusha, where students crammed for the national ex- make a living using his sharp mind. aminations. The lectures were given by assistants from the Although Kobayashi’s students were destined for agricul- nearby Tokyo University Medical School in their spare time. ture and small rural business rather than university study, They consisted of recitations from texts from start to finish, they nevertheless learned English. Hideyo’s command of the then rereading them until students felt that they had learned language would later provide the opportunity for emigration enough to take the national exam or their money ran out, of- to America. His schoolmates teased him about his hand, call- ten the cause of discontinuing a medical education. Noguchi’s ing him tembo, an epithet meaning “arm like a stick.” 2p16 A diligent study paid off—within a year he had passed both writing assignment that allowed him to poignantly express his exams, one of only four passing the second clinical test. Still frustration and shame over his deformity moved the school- his future was far from assured. He was awkward and crude master to collect contributions from teachers and students to in society, always without money, and painfully sensitive of his pay for surgery for the boy’s hand. Kanae Watanabe, a physi- dress. He and his instructors worried that patient reactions to cian trained at the University of California who lived in nearby his deformed hand could limit his success as a clinician. Wakamatsu, surgically freed the thumb and what was left of While earning pocket money translating German medical Hideyo’s fingers to allow a rudimentary grasp. texts Noguchi came upon a section on bacteriology that he The experience inspired Hideyo to become a doctor. did not understand. A conversation with one of his instruc- Watanabe took the boy in as an apprentice, a practice more tors for more information kindled an interest in the field. The characteristic of medieval Japan than appropriate to a U.S.- instructor suggested that Noguchi seek a job as a research as- trained physician.3 Hideyo cleaned the rooms and floors of sistant at the Institute for the Study of Infectious Diseases, the the combination clinic-household, helped compound medica- top research facility in the country. An obstacle to obtaining tions, assisted with patients, and when the chores were done a position there was the Institute’s preference for graduates studied long hours into the night. Watanabe’s library had of the University of Tokyo, with which it had an affiliation. texts in English, German, and French, so Hideyo’s facility with Noguchi pestered his instructors into recommending him languages was an advantage. One day Watanabe showed the to Shibasaburo Kitasato, founder of the Institute, who had boy spirochetes with his new German microscope. Fascinated, trained in Berlin under two giants in bacteriology, Robert Hideyo took far longer than his appointed time watching the Koch and Emil Adolph von Behring. In 1898 Noguchi joined creatures. The other apprentices in their impatience and jeal- the Institute as a library assistant at the age of twenty-one.3 ousy taunted that he would never be able to use a microscope with his disabled hand, taunts that fed his resolve to become Noguchi in the United States a success. Noguchi dreamed of emigrating to the United States and Watanabe gave his approval for Noguchi to take his medi- Europe for medical training, plans that at the time appeared cal examinations, a demanding two-part examination in hopelessly ambitious. In 1899 the means to achieve his aspi- Tokyo. To pay for the necessary months of study in the capital rations arrived when Simon Flexner visited Kitasato and the Noguchi borrowed money, an annoying habit of begging that Institute.3 Flexner, an authority on infectious diseases and would plague his friends and contacts long after his later ar- an assistant to William Welch, dean of the Johns Hopkins rival in the United States. Before departing he carved a vow Medical School, was part of a scientific delegation to the on a wooden pillar in his home: “I will not set foot in this Philippines. Noguchi was chosen to guide the Americans place again until I have achieved all my goals.” The inscription, because of his fluency in English. Noguchi earnestly in- along with Noguchi’s boyhood home, is preserved today as his quired about coming to the United States to study. Flexner memorial.2 Dressed in his provincial peasant garb he walked remembered his response to Noguchi as polite but far from twenty-five miles over footpaths through the mountains to the encouraging. What Noguchi heard, however, was an outright

28 The Pharos/Autumn 2011 English, so it was no use trying to explain anything complex.3 Noguchi was at first uncertain whether he would be retained at Penn for more than an academic year. Over time, however, his work progressed and he became well published, with twenty scientific articles and a chapter on snake venoms for a leading medical text. Flexner and Mitchell brought Noguchi to the meeting of the National Academy of Science in November 1902, introduced him to elite academic society, and successfully sponsored him for a grant from the Smithsonian Institution.3 To his mentors in the United States, Noguchi was a tireless worker and “utterly charming” despite his near- unintelligible English and awkward social manners.3p83 In 1901 Flexner was appointed to head the newly an- nounced Rockefeller Institute for Medical Research, the first biomedical research center in the United States, and he planned to take Noguchi with him.3 In prepara- tion he sent Noguchi in 1903 to study bacteriology in Copenhagen. One year later Noguchi joined Flexner in New York. In 1907 Flexner set Noguchi to work on syphilis, a highly competitive field appropriate to the mission of the new institute and the ambitions of its founder.2 The agent causing syphilis, Treponema pallidum, had just been discovered in 1905 by Fritz Schaudinn and Erich Hoffman; one year later the famous complement fixation test was developed by August Paul von Wassermann. Hideyo Noguchi. Noguchi worked long into the nights, chain-smoking ci- Courtesy of the National Library of Medicine. gars, which he considered stimulants. During this period he made the discovery that is now considered his most important contribution to medical science: the discovery invitation to come to Philadelphia, where Flexner was about of T. pallidum in the brain tissue of patients who had suffered to transfer to the University of Pennsylvania. A year and a half paresis from tertiary syphilis, the first demonstration of an later on a cold December day in 1900 Flexner was astonished organic cause for psychosis.6,7 to find Noguchi at his office door, nearly penniless, declaring that he was ready to begin work.2 Problems and controversies The child of Jewish immigrants from Germany, Flexner had Noguchi’s work with syphilis led to his first major contro- attended a proprietary medical school in Kentucky, won a re- versy, his claim in 1911 of growing T. pallidum in pure culture. search position at Johns Hopkins despite his modest training, While T. pallidum inoculated into a susceptible mammalian and had become a trusted protégé of Welch. Flexner had no host clearly produced the disease, researchers had never been funds for another laboratory assistant, but found a project for able to obtain the organism in pure culture. A pure culture of his unexpected visitor with Silas Weir Mitchell, an authority the organism would allow the development of antisera with on snake venoms, who needed someone to develop antitoxins. potentially important diagnostic and therapeutic uses: specific Noguchi threw himself into the work, reviewing the English, diagnostic serological tests, antiserum-based therapy, and vac- German, and French literature, learning necessary immuno- cine development. logical techniques, and learning to handle venomous snakes.3 We now know that Noguchi could not have done what he Noguchi was lonely, homesick, and isolated. His English claimed. A major barrier to research in the disease is that the was woefully inadequate for daily use. He no doubt felt the organism cannot be cultured in vitro and survives only in live sting of racism and racial discrimination, even though he mammalian hosts.9 Others trying to duplicate Noguchi’s re- settled on the East Coast, away from the hotbed of anti-Asian sults were understandably unsuccessful and became skeptical sentiment on the West Coast.5 At Noguchi’s first seminar, of the claims in his publications. With firsthand knowledge one senior scientist joked that no one could understand his of the chaotic, disorganized, and frenetic manner in which

The Pharos/Autumn 2011 29 Hideyo Noguchi

he worked, his own laboratory technicians questioned his legal complexities of obtaining consent.4 techniques and scientific rigor.3 Test tubes went unlabeled; In using noninfective material that was tested on himself Noguchi insisted that he knew the contents of each one. Based and other coworkers, Noguchi’s use of human subjects are of on this work he was promoted to directorship of his own labo- an entirely different category than later egregious violations ratory and nominated for the Nobel Prize.3 of biomedical ethics such as the Tuskegee syphilis experiment Convinced he had isolated a pure culture of T. pallidum, of 1932 through 1972 and the Willowbrook hepatitis studies of Noguchi continued his work using false material. In 1907 1956 through 1971. Noguchi’s work was an early battle in the Clemens von Pirquet published his work on tuberculin, an developing antivivisection movement that led to modern legal extract of the tubercle bacillus that when injected subdermally restrictions protecting human subjects. detected a patient infected with tuberculosis. Motivated to The luetin affair ended Noguchi’s work with syphilis. find a similar such test for syphilis, Noguchi produced an ex- Noguchi likely was relieved when opportunities came to leave tract from his preparations, which he called “luetin,” after the the country to lecture and receive honors in Europe in the fall common term for the disease, “lues.” 10, 4p35 Noguchi’s prepara- of 1913 and Japan in 1915 (where he fulfilled the vow carved in tions of luetin included steps that he felt rendered it noninfec- the woodwork of his home). Syphilis was not the only disease tive—in fact, it never had been capable of infecting a recipient to receive his attention. In a single year, 1913, he published with syphilis—and proved its safety in animals. Welch, widely discoveries for the infective agents of rabies (Negri bodies considered the dean of American medicine, encouraged being the infective agent, so Noguchi believed),11 anal condy- Noguchi to proceed with human testing. With the assistance loma (a new species of Treponema spriochete),12 and polio (a of New York area physicians Noguchi tested 400 patients, 254 protozoan forming “globoid bodies” that are visible on light known to have syphilis at various stages, 100 adults and chil- microscopy).13 His conclusions were wrong in all three cases. dren with other nonsyphilitic conditions, and 46 normal chil- Noguchi began work on Weil’s disease, a disease that he could dren. Noguchi reported that luetin detected infected patients, characterize completely using the techniques available at that particularly those with tertiary syphilis, where the reaction time.3 In 1917 he nearly died when he acquired typhoid by un- was especially pronounced and where the Wassermann test intentionally aspirating infective organisms through a pipette. was often negative.4 Response in the public health community His convalescence was a hiatus before the turbulent yellow was immediate—requests for luetin flooded the Rockefeller fever research that would kill him. Institute, which considered licensing the compound and con- tracting for its mass production. Yellow fever and the “fatal commitment” The response from antivivisectionists was also prompt. An expedition to Ecuador to study an outbreak of yellow Had human subjects been injected with syphilis? The New fever in 1918 held a natural attraction for Noguchi. Yellow York-based Vivisection Investigation League asked, “Are the fever was another “big disease” appropriate to the ambitions helpless people in our hospitals and asylums to be treated as of Noguchi, Flexner, and the Rockefeller Institute.3 Biographer so much material for scientific experimentation, irrespective Plesset terms it a “fatal commitment.” 3p189 Cuban medical sci- of age or consent?” 4p36 In 1912 John Lindsay, then president entists, among the leading researchers in the field, had made of the New York Society for the Prevention of Cruelty to several basic and important observations: the organism was Children, instituted a formal complaint against Noguchi on carried by the mosquito Aedes aegypti; it was recoverable from charges of assault. Manhattan’s District Attorney declined the bloodstream from infected individuals only during the first to prosecute the case. The fact that children were subjects three to four days after the onset of the disease; and it passed in the experiments—it later emerged that the children were through all known filters and thus was by definition a “virus.” 3 wards of the New York City Board of Charities—plagued the Flexner and William Gorgas, expedition leader and hero of the Rockefeller Institute.4 yellow fever eradication programs in Havana and the Panama Jerome Greene, business manager for the Rockefeller Canal, disagreed and believed that the infective agent was a Institute, argued that Noguchi observed the standards of the spirochete.3 Noguchi shared their bias, based upon the clinical day regarding human experimentation: the preparation had similarity between yellow fever and Weil’s disease.14 not harmed laboratory animals and the researchers had tested Less than a month after his arrival in Ecuador Noguchi the material on themselves.4 Noguchi had neglected to report announced that he had found the infective agent of yellow that he had tested luetin on himself and his collaborators, pos- fever, a goal that had eluded competent scientists for years. sibly to keep secret his own syphilitic condition. In publica- He claimed that it was a new spirochete, Leptospira icter- tions and testimony Greene, Welch, and Flexner emphasized oides, related to the Leptospira agent of Weil’s disease that the overall benefit to mankind from the advances produced he had characterized the previous year. He claimed that the by the work. The Rockefeller briefly considered legal action Leptospira organisms causing the two diseases could be against the the activists on the basis of libel, but decided distinguished immunologically, but his evidence was scant. against a lawsuit because of the public furor and the emerging Noguchi’s Ecuadorian hosts celebrated him as the conqueror

30 The Pharos/Autumn 2011 of yellow fever, honoring him in celebra- tions throughout the country.3 The Cubans, however, were skeptical.3 Mario Lebredo, a Cuban yellow fever spe- cialist who was also part of the Ecuadorian commission, noted that the peasants the commission studied likely had been ex- posed to a number of tropical diseases, including both yellow fever and Weil’s disease. The diagnosis of yellow fever was questionable because many patients were first seen long after the first days of illness when the organism was recoverable. The descriptions of patients suggested Weil’s disease, not yellow fever. Noguchi’s slip- shod laboratory techniques were nearly impossible to duplicate in remote Latin Hideyo Noguchi. SPL/Photo Researchers, Inc. American backwaters. Noguchi’s use of guinea pigs to make the diagnosis of yellow fever was also an issue, as standard lab ani- mals are not susceptible to the disease. At the time, before the use of rhesus monkeys, human volunteers Coworkers in West Africa in 1925 and 1926 were unable to were needed.14 Lebredo worried that unproven methods of isolate L. icteroides from yellow fever patients.3 Refusing to immunization based on Noguchi’s claims would compromise believe he was wrong, Noguchi in 1927 became convinced that mosquito abatement measures, an intervention known to he should go to West Africa himself to reproduce the work he control the disease.3 had done in Ecuador. After one colleague died of yellow fever Noguchi, undeterred, sent doses of immune serum based without evidence of Leptospira, Noguchi felt that his presence upon the supposed L. icteroides organism to public health of- in West Africa was mandatory.3 ficials in Ecuador and Peru,3 as well as to his field staff when His preparations for the trip had the appearance of an in- they fell ill with symptoms of yellow fever.3 Reports, however, tention to commit suicide. He gave Evelyn Tilden, his longtime began to appear that Noguchi’s immune serum was ineffec- lab assistant and later colleague, specific instructions to send tive against yellow fever, and indeed appeared to have activity money to his sister in Japan should he not return. Leaving against Weil’s disease.3 Noguchi explained that the serum nothing to chance, he gave the same instructions to his wife.3 was developed where Weil’s disease was endemic, so activity At the final staff meeting at the Rockefeller Institute the day against that disease also would be expected. Then, tragically, before his departure Noguchi presented some of his work on in 1921 Howard Cross, a young Rockefeller trainee from Johns trachoma. One attendee, Rebecca Lancefield, remembered the Hopkins, died from yellow fever in Mexico despite being im- emotions among those there. Plesset quotes her: munized with Noguchi’s serum.3 By 1924 several prominent researchers, particularly the they now recognized the courage with which he was facing Cubans, began to attack Noguchi’s claims for L. icteroides the real danger as well as the humiliation that lay before him. as the causative agent in yellow fever.14 Two years later They all believed that he had been mistaken about yellow fe- Max Theiler and Andrew Sellards at the Harvard School of ver, and that he knew it at the time of his departure. [Philip] Tropical Medicine did basic serological work that proved McMaster [another Rockefeller Institute staff member] said that Noguchi’s organism and the Weil’s disease agent were Noguchi knew he had been wrong before he left and per- identical,15, 14 revealing Noguichi’s work to be “a red herring haps it would have been worse for him if he had lived.3p255 drawn across the whole field of yellow fever research.” 3p188 Theiler later joined the Rockefeller Institute and, long after Noguchi still took the precaution of taking his yellow fever Noguchi’s death, received a Nobel Prize for the development vaccine before his departure.2 “No matter what anyone says of an ­effective vaccine against yellow fever.16 the icteroides vaccine protects against yellow fever,” he wrote Flexner from Africa.14p139 In October 1927 Noguchi left New Noguchi’s death York. His correspondence from Africa revealed his struggle Noguchi, faced with distrust over his techniques and re- to reconcile his biases with facts. In a December letter to his sults, became protective and secretive about his methods.3 wife he wrote that he knew the organism producing yellow

The Pharos/Autumn 2011 31 Hideyo Noguchi

fever . . . was practically valueless and possibly harmful.” 14p144 A contemporary at the Rockefeller Institute, Thomas Rivers, called Noguchi “neither a great nor an honest scientist.” 14p144 In his memoir, Paul de Kruif remembered the opinion of Frederick Novy of Michigan, the most eminent U.S. bacteri- ologist at the turn of the twentieth century:

Noguchi, a gay little Japanese, had earned fame resting partly on his discovery of a spurious spirochete that turned out, alas, to be definitely not the cause of yellow fever. You forgave Noguchi because he was a nice little guy, but Novy, the master of spirochetes, took Noguchi apart without mercy.3p207

In another excerpt de Kruif called Noguchi “a scientific Trilby . . . the slave of his Svengali, Dr. Simon Flexner.” 3p207 In an interview with Plesset before his death Theiler, who ulti- mately attained Noguchi’s dream of a yellow fever vaccine, re- Statue of Hideyo Noguchi in Ueno Park, Tokyo. Photo courtesy of the author. membered with sadness hearing others disparage the Japanese scientist’s work.3p242 In her words, “Theiler recommended that the whole Noguchi matter be allowed to ‘rest in peace’; he said it was surely a psychological problem.” Such withering opin- ions assured the burial of Noguchi’s reputation in the West. In stark contrast is Noguchi’s status as the literal face of Japanese science with his portrait on the 1,000 yen note, his statue in front of the country’s major science museum, and his more than one hundred biographies.17 His birthplace in Fukushima Prefecture preserves the thatched-roof wooden house where he was born and features a reconstruction of his laboratory, where a robot in Noguchi’s image greets visitors and narrates events in his life.18 Sapporo Breweries in Japan Hideyo Noguchi’s portrait on a 1,000 yen note. Photo courtesy of the author. released a limited edition of its Black Label beer with a cari- cature of Noguchi on its label in 2007. Noguchi is held as an example of medical professionalism in a lecture, “Learn from Hideyo Noguchi,” given to entering students at the Nippon fever in Africa was not the one he had found in Ecuador.3 In Medical School.19 a letter to Tilden he describes “some funny bug, a filterable His reputation has assumed a global dimension in Africa one,” a reference to a viral pathogen, a clear departure from and Ghana, the country where he died. In 1979 the Noguchi his lifelong conviction.14p140 But in a letter to Flexner Noguchi Memorial Institute for Medical Research of the University of announced that he had isolated the bacillary cause of West Ghana was established in Legon. Its nine departments house African yellow fever, his original obsession.14 On May 21 1928, nearly three hundred persons, including more than one hun- barely six months after his arrival in Accra, Noguchi was dead dred scientists, devoted to the study and control of tropical from yellow fever. William Young, a British pathologist work- disease.1 In 2006 the government of Japan established a prize ing with Noguchi, performed the autopsy and confirmed the in his honor, the Hideyo Noguchi Africa Prize, to honor indi- diagnosis of both yellow fever and tertiary syphilis. Befitting viduals for outstanding achievements in medical research and of a microbe hunter of the era, eight days later Young, too, services to combat infectious and other diseases in Africa.20 succumbed to yellow fever.14 Its first awards were made in 2008. It is managed by the Japan International Cooperation Agency, through which the Noguchi’s legacy in the West, Japan, and Africa Japanese government funds 94.7 billion yen of economic de- At the end of Noguchi’s career, leading Western bacteri- velopment projects throughout sub-Saharan Africa. Noguchi’s ologists disregarded his work. Aristides Agramonte y Simoni, legacy includes his native country’s support of economic and a member of the original Reed Yellow Fever Board in Cuba, scientific projects in Africa, a continent beset by endemic wrote, “From 1919 to the day of his decease, his work in yellow tropical diseases, the field to which he gave his life.

32 The Pharos/Autumn 2011 References 1. Noguchi Memorial Institute for Medical Research. Univer- sity of Ghana, Legon. http://www.noguchimedres.org. 2. Kita A. Dr. Noguchi’s Journey: A Life of Medical Search and Discovery. Durfee P, translator. Tokyo: Kodansha International; 2003. 3. Plesset IR. Noguchi and His Patrons. Cranbury (NJ): Fairleigh Dickinson University Press/Associated University Presses; 1980. 4. Lederer SE. Hideyo Noguchi’s luetin experiment and the antivivisectionists. Isis 1985; 76: 31–48. 5. Hosokawa B. Nisei: The Quiet Americans. Boulder (CO): University Press of Colorado; 2002. 6. Whitehorn JC. A Century of Psychiatric Research in Amer- ica. In: Hall JK, editor for the American Psychiatric Association. One Hundred Years of American Psychiatry. New York: Columbia University Press; 1944. 7. Noguchi H. Moore JW. A demonstration of Treponema palli- dum in the brain in cases of general paralysis. J Exp Med 1913; 17: 232–38. 8. Noguchi H. A method for the pure cultivation of pathogenic Treponema palludum (Spirochaeta pallida). J Exp Med 1911; 14: 99–108. 9. LaFond RE, Lukehart SA. Biological basis for syphilis. Clin Microbiol Rev 2006; 19: 29–49. 10. Noguchi H. A cutaneous reaction in syphilis. J Exp Med 1911; 14: 557–68. 11. Noguchi H. Contribution to the cultivation of the parasite of How’d I like that no-salt diet you put me on? rabies. J Exp Med 1913; 18: 314–16. Well, sorta takes the sting outta dyin’. 12. Noguchi H. Cultivation of Treponema calligyrum (new spe- cies) from condylomata of man. J Exp Med 1913; 17: 89–98. Alan Blum, MD 13. Flexner S, Noguchi H. Experiments on the cultivation of the mi- croorganism causing epidemic poliomyelitis. J Exp Med 1913; 18: 461–85. 14. Dolman CD. Hideyo Noguchi (1876–1928): His final effort. Clio Medica 1977; 12: 131–45. 15. Frierson JG. The yellow fever vaccine: A history. Yale J Biol Med 2010; 83: 77–85. 16. The Nobel Prize in Physiology or Medicine 1951: Max Thei- ler. http://nobelprize.org/nobel_prizes/medicine/laureates/1951/. 17. Ishikawa H. Book reviews: Dr. Noguchi’s Journey: A Life of Medical Search and Discovery. N Engl J Med 2005; 353: 2091–92. 18. Hideo Noguchi Memorial Hall Home Page. http://noguchi- hideyo.or.jp/home.htm. 19. Shimura T, Yoshimura A, Saito T, Aso R. Unique medical education programs at Nippon Medical School. J Nippon Med Sch 2008 75: 196–201. 20. Hideyo Noguchi Africa Prize (Fact Sheet)—Hideyo Noguchi Africa Prize–Cabinet Office Home Page. http://www.cao.go.jp/no- guchisho/english/keii/gaiyo.html. From his earliest days as a medical student, Dr. Alan Blum (AΩA, Emory University, 1985), Gerald Leon Wallace MD Endowed Chair in Family The author’s address is: Medicine at the University of Alabama, has captured thousands of patients’ Medical Education–Department of Surgery stories in notes and drawings. The sketches and jottings bring back the essence of a conversation, a detail of personality, and the fragmentary clues Medical Center of Central Georgia patients give their doctor about the experience of illness. Dr. Blum’s address 777 Hemlock Street, MSC 140 is: 26 Pinehurst Drive, Tuscaloosa, Alabama 35401-1148. E-mail: ablum@cchs. ua.edu Macon, Georgia 31201 E-mail: [email protected]

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