Hideyo Noguchi

, also known as , was a Japanese bacteriologist at the Rockefeller Institute during its foundation under Simon Flexner and known for his work on syphilis and contributing to the long term understanding of neurosyphilis.

During the emergence of the field of serology, he began as a research assistant to American physician Silas Weir Mitchell in his studies on snake venom at the University of Pennsylvania in 1901. Mitchell and Noguchi presented the results before National Academy of Science.

Later in his career, Noguchi developed the first serum to give partial immunity to Rocky mountain spotted fever, a notoriously lethal disease before treatment was discovered. He also suggested the name for the genus Leptospira in 1917.

Posthumously, his work on yellow fever was overturned alongside his claims of discovering the causative agent of rabies, poliomyelitis, trachoma and his culture of syphilis could not be reproduced. His research with his colleague Evelyn Tilden after his death proved that Carrions disease and verruca peruana were the same species.

His name is attached to the spirochete, Leptospira noguchii. His mother Shika worked to maintain the family farm and restore the Noguchi name to the honor it once had, the family having been descended from samurai in the days of Noguchi's great grandfather.

Childhood accident

Noguchi was two years old when he was left with his deaf grandmother who had poor eyesight alongside his four year old sister, Inu, while his mother worked in the rice fields. In 1898, Noguchi changed his first name to Hideyo after reading a novel by Japanese author Tsubouchi Shōyō about a college student whose character had the same name as him. The character in the story, Seisaku, was an intelligent medical student but became lazy and ruined his life.

Noguchi received a position at the Kitasato Research. Although, he was an outsider as one of the few doctors to have not graduated from the Imperial University. Kanae Watanabe, the doctor who performed surgery on his hand, and Morinosuke Chiwaki, who helped fund his travel to the United States.

Leaving Japan

Noguchi was inspired to go to the United States, partly motivated by difficulties in obtaining a medical position in Japan as it required expensive schooling. Flexner, who was visiting to see research being made on dysentery from foreign scientists, gave polite words of encouragement to his desire to work in the United States.

Noguchi decided that was that and bought a ticket on the America Maru. Chiwaki took a loan to pay for it. Noguchi hosted a party to celebrate, spending most of his money before leaving. He surprised Flexner at his position at the University of Pennsylvania. In spite of their brief encounter, Noguchi requested a position but he said the university had no funds. Although, Flexner did want to hire an assistant to investigate snake venoms. The day after he arrived, Flexner asked, "Have you ever studied snake venom?" Flexner was impressed. Dr. Mitchell spoke during the presentation but Noguchi handled the specimens.</blockquote>Although, Dr. Mitchell was concerned about his acceptance into larger Western society. Nonetheless, Mitchell recommended him for the Carnegie Fellowship. Noguchi was accepted and became an official researcher and received funding from both the Carnegie Institute and National Academy of Science. On July 9, 1907, the University of Pennsylvania awarded Hideyo Noguchi an honorary degree.</blockquote>

State institute and advocate for antivenom

French scientist Albert Calmette was the first to produce an antitoxin for venomous snake bites in 1895. Mitchell had made attempts to produce a serum for rattlesnakes, but was unsuccessful and encouraged his protege.

Major publications

Between 1905 and 1908, Noguchi produced 28 papers and reports on his work with snake venoms and the routine observations of immunologic relationships, as well as tetanus. In 1907, he wrote the chapter on venoms in William Osler and Thomas McCraes Modern Medicine. thumb|Statens Serum Institute in CopenhagenIn 1909, Noguchi released a comprehensive monograph on snake venom, Snake Venoms: An Investigation of Venomous Snakes with Special Reference to the Phenomena of Their Venoms. In the preface, it stated,<blockquote>“No single work in the English language exists at this time which treats of the facts of zoological, anatomical, physiological, and pathological features of venomous snakes, with particular reference to the properties of their venoms." Noguchi moved to Lexington Avenue in New York City. He was introduced to another medical student Norio Araki, who was roommates with Hideyo Noguchi for three years.

Career at the Rockefeller Institute

thumb|359x359px|Hideyo Noguchi's laboratory at Rockefeller InstituteIn 1905, Treponema pallidum was first identified as the cause of syphilis by Fritz Schaudinn and Erich Hoffmann. Noguchi conducted a study to find whether if jaundice, specifically in the context of Weil's disease, which often spreads through the urine of the infected rats, is found in the bodies of American rats as it does in European rats. During his research, Noguchi notices the spirochete is unlike previous he has encountered. In 1917, he suggests the name of the new genus Leptospira meaning slim spiral. Physicians reported finding the test more sensitive. During the distribution to hospitals, doctors reported, “Noguchi had prepared for us all the antigen and ambocepter tests that we used. He also spent about two weeks at our laboratory and helped us materially by making many of the tests."

In particular, it was effective at diagnosing neurosyphilis as it detected 90 percent of cases of general paralysis. Although, the test was used less as more refined tests were developed and it was technically demanding and required more specialized expertise.

In 1909, he published twelve papers on syphilis.

Controversial pure culture of syphilis

Dr. Flexner told him to focus his efforts on obtaining a pure culture of the spirochete. Flexner wrote in his diary, “Once he was started on a problem he would pursue it to the bitter end." Noguchi set up hundreds of tubes for his cultures and used thousands of microscopic slides in his lab.

In February 1911, Noguchi believed that he had grown a pure culture and wrote to his childhood mentor Kobayashi, “I feel as if I am dancing in heaven." He thought it might eradicate of syphilis.

Presence of Treponema pallidum in paresis

thumb|Hideyo Noguchi's personal microscope used to identify syphilis

Wards Island State Hospital, located on an island in the East River, held the New York State Pathologic Institute and was located opposite of the Rockefeller Institute. Staff members at the Rockefeller Institute, Phoebus Levene and James B. Murphy worked at the Pathologic Institute and were well aware of the issue of paresis and brought this up in conversation with Hideyo Noguchi. Some researchers held out some hope that understanding the pathophysiology of paresis could lead to a cure for late stage neurosyphilis.

Noguchi decided to remove the doubt and demonstrate the presence of caustive agent in paretic brains. He began collecting samples from spinal cords and brains of paretic patients to determine its relationship to syphilis. Eventually, he discovered the presence of Treponema pallidum in the spinal cord of a patient. Consequently, this discovery proved the homogeneity of a mental and physical disease and demonstrated that an organic agent could cause psychosis. In 1925, Association of American Physicians granted him its prized Kober Medal for this discovery.</blockquote>When compared to a genius, he said, "there was no such thing as genius. There was only the willingness to work three, four, even five times harder than the next man". His record for numbers of published papers in a single year was an unheard of nineteen submitted to journals. Noguchi published over 200 paper and gave lecture tours throughout Europe during his career.

Noguchi rarely read extensively before his experimentation. He wanted to learn through his failure. He report in a letter to his mentor,<blockquote>"Theories are not to be taught by anybody outside of ourselves. We are the best teachers of the truth — I mean by this that we ought to convince ourselves chiefly by our own experiences and own experiments."</blockquote>Although, he tended to draw premature conclusions. During a lecture on the transmission of syphilis to rabbits, he had been successful in only one out of thirty-six cases. Noguchi did not label his test tubes, he insisted he had it memorized. His friend Okumura witnessed Noguchi drank and smoked a great deal, but was stunned at how Noguchi could get along without sleep. He could be irresponsible with his specimens. Once he swallowed solution of jaundice while pipetting a culture.

When he met Evelyn Tilden, an English major, in Massachusetts, she was hired as his secretary. Tilden was profoundly impactful to the writing of his research papers. Eventually, Tilden became his apprentice and Noguchi encouraged her to enroll in courses in biology and organic chemistry at Columbia University. Eventually, she received a doctoral degree in 1931 and made a career for herself, becoming professor at the North Western University. Both came from a background of poverty. Mary, nicknamed Maize, called her husband, Hidey. Flexner opposed his marriage to an American. Flexner felt he should marry someone of Japanese descent. Noguchi worried his marriage would put his promotion at risk because she would have to be added to his pension and the taboo of having an interracial marriage. He would turn the kitchen into a laboratory, leaving bacterial specimens in the refrigerator, have microscopes holding germ cultures on the dinner table, and put test tubes in the oven.

thumb|Letter from Hideyo Noguchi to his wife Mary Dardis

Noguchi would often be caught at the laboratory at night and people would ask him why he was not at home? His usual reply was, "Home? This is my home." Some people thought he was escaping from his relationship but it is revealed through letters their marriage brought great satisfaction. Mary provided a refuge and inspiration.

Suzanne Kamata has discussed how American women, such as Mary Dardis, have played a large part in the success of their Japanese husbands but have often gone unnoticed due to their nationality. She states "her assistance may have even helped to prolong his life."

Since he was notoriously bad with money, he often got paid in two separate checks, one to hand on to his wife who paid the bills and the other to keep so that he would have something to spend it on. Mary could have stopped him from entering financial ruin.

His mother, Shika, who was notably illiterate, wrote, “Please come home soon, please come home soon, please come home soon, please come home soon.

His mother's health declined. Noguchi sent an unsubtle telegram to Hoshi and asked for enough money to return home. Hoshi was generous and immediately sent him enough to return to Japan Noguchi bought a ticket and sailed to visit her and accept the Imperial Prize on September 5, 1915. He greeted his mentors Chiwaki and Kobayashi at the Imperial Hotel. Noguchi presented them with golden watches as gifts. Noguchi spent another ten whole days with his mother, but returned to the United States, and this would be the last time he would be back in Japan. Earlier Noguchi was told he had enlarged heart from his irregular intense activity after a physical examination. Mary called an ambulance since he refused to go to the hospital and was brought to Mount Sinai hospital. He claimed it was jaundice after accidentally digesting. His fever worsened and Mary and those around him thought he might die.thumb|Portrait of Hideyo Noguchi using color photography|263x263px

Hobbies

Noguchi was gifted oil paints from Ichiro Hori and he started painting in Shandaken.

Noguchi was an amateur photographer. It was said that there is no scientific researcher who likes photography more than Noguchi. He achieved this through using autochrome lumière. He sent this in a letter, dated August 8, 1914, to his childhood mentor, Sakae Kobayashi.

Professor William Henry Welch, Board of Scientific Directors at the Rockefeller Institute for Medical Research, urged Noguchi to conduct human trials. While his diagnostic test was effective, it never had a reliable supply from the organism in pure culture form, never yielding practical results. The remaining subjects were controls; some of which were orphans between the ages of 2 and 18 years.

In Dr. Noguchi's defense, Noguchi had performed tests on animals to ensure the safety of the lutein test. Although, none of subjects were infected with syphilis, the Rockefeller Institute did test on patients without consent. They received far less scrutiny on their legacy.

Later career

thumb|Noguchi decorated with medals

In July, 1914, Flexner made Noguchi a full member of the Institute. He wrote in a letter,<blockquote>"I am almost exhausted and I feel the weight of my situation, because every one working at this Institute is expected by the outsiders to do something. Yet, as you know, we cannot find a new thing every day!"</blockquote>

Successes in tropical diseases

Noguchi began to tackle Rocky mountain spotted fever, similar to another disease Tsutsugamushi present in Japan, where deaths were common among rice planters and farmers. Furthermore, he began researching jaundice after two Japanese scientists announced a discovery of a spirochete appearing in the liver of a guinea pig demonstrating jaundice.

In June of 1918, Noguchi became chief investigator on a commission of the International Health Board traveled throughout Central America and South America to conduct research to develop a vaccine for yellow fever. In the meantime, Noguchi published a revision of Serum Diagnosis of Syphilis with assistance from Evelyn Tilden in 1922, Laboratory Diagnosis of Syphilis, which aided in the diagnosis and treatment of the disease.

During his time in Peru and Ecuador, between 1925 to 1927, he worked on Carrions disease and verruca peruana, which was widespread in the regions, and proved the infections were due to the same species, Bartonella bacilliformis. Noguchi sometimes lost his temper and scolding his assistants, but outside of the laboratory, Noguchi was a different and more open person. He would invite him to restaurants and speak Japanesesomething he never did at the Rockefeller Institute.</blockquote>

Controversial research on yellow fever

thumb|Hideyo Noguchi dissecting a crocodile along the Rio Grande

Noguchi decided to focus on yellow fever, which some of his colleagues died researching because of his experience with syphilis and spirochetes. He thought the disease could have been a spirochete after traveling to Merida, Mexico and seeing patients demonstrate symptoms of Weil's disease, but similar to yellow fever. He identified it as Leptospira icterohemorrhagiae Noguchi worked much of the next ten years to prove his theory that it was from spir bacteria. He even thought he developed a vaccine against it, unknowingly for Weil's disease. it became increasingly evident that yellow fever was caused by a virus, not by the bacillus Leptospira icteroides, as Noguchi believed. describe Noguchi's temper and behavior as erratic and bordering on the paranoid. One reason might be he had untreated syphilis, for which he was diagnosed in 1913, but it could have progressed to neurosyphilis, prone to personality changes.

During his last letters to Mary, he writes<blockquote>“I spend every moment of every day waiting for a telegram from you. When I am dispirited or tired, you are the one thing that raises my spirits. I am always thinking of you. It is rare that I dream but when I do, it is always of you.” </blockquote>

In a letter home, Young states, "He died suddenly noon Monday. I saw him Sunday afternoon – he smiled – and amongst other things, said, “Are you sure you are quite well?" "Quite." I said, and then he said "I don’t understand." His obituary was featured in The New York Times.

Legacy

Noguchi was profoundly influential during his lifetime. He brought newfound attention to obscure and tropical diseases, such as trachoma, affecting a large part of developing countries in Africa, often ignored by western scientists.

Furthermore, Noguchi and Tilden's identification of the leishmaniasis pathogen and proving Carrion's disease and Oroya fever one of the same. He was applauded for his discovery in South America and had a 2.1 km street in Guayaquil, Ecuador named after him.

Posthumous retractions

With the electron microscope, which was invented two years after his passing, some of his discoveries became understood as mistaken.

Some of his research, including his discovery of polio, rabies, trachoma, and yellow fever's cause were not able to be reproduced. His finding that Noguchia granulosis causes trachoma was questioned within a year of his death. His identification of Leptospira icterohemorrhagiae as yellow fever was disproven after Max Theiler discovery. Furthermore, his rabies pathogen medium to cultivate bacteria was prone to contamination.thumb|200px|Statue of Hideyo Noguchi in [[Ueno Park]]A Rockefeller Institute researcher criticized him for being unwilling to issue retractions for his claims, but others said it was more flaws inside the system of peer review at the Institute.

Selected works

1904: The Action of Snake Venom Upon Cold-blooded Animals.

:::Washington, D.C.: Carnegie Institution.

1909: Snake Venoms: An Investigation of Venomous Snakes with Special Reference to the Phenomena of Their Venoms.

:::Washington, D.C.: Carnegie Institution.

1911: Serum Diagnosis of Syphilis and the Butyric Acid Test for Syphilis.

:::Philadelphia: J. B. Lippincott.

1923: Laboratory Diagnosis of Syphilis: A Manual for Students and Physicians.

:::New York: P. B. Hoeber.

Honors during Noguchi's lifetime

Noguchi was honored with Japanese and foreign decorations. He received honorary degrees from a number of universities.thumb|200px|The bust of the Japanese scientist and doctor Hideyo Noguchi was inaugurated on June 22, 2018, outside the Crystal Palace in [[Guayaquil]]Noguchi was self-effacing in his public life, and he often referred to himself as "Funny Noguchi" as noted in Times Magazine. When Noguchi was awarded an honorary doctorate at Yale, William Lyon Phelps observed that the kings of Spain, Denmark and Sweden had conferred awards, but "perhaps he appreciates even more than royal honors the admiration and the gratitude of the people."

Kyoto Imperial University, Doctor of Medicine, 1909.
Knight of the Order of Dannebrog, 1913 (Denmark).
Commander of the Order of Isabella the Catholic, 1913 (Spain).
Commander of the Order of the Polar Star, 1914 (Sweden).
Tokyo Imperial University, Doctor of Science, 1914.
Imperial Award, Imperial Academy (Japan), 1915.
Central University of Ecuador, 1919, (Ecuador).
National University of San Marcos, 1920, (Peru)
Medicine School of Merida, "Doctor Honoris Causa en Medicina y Cirugía", 1920 (México)
John Scott Medal, 1921, (United States)
University of Guayaquil, 1919, Ecuador.
Senior fifth rank in the order of precedence, Japanese government, 1925

In 1928, the Japanese government awarded Noguchi the Order of the Rising Sun, Gold and Silver Star, which represents the second highest of eight classes associated with the award.

In 1979, the Noguchi Memorial Institute for Medical Research (NMIMR) was founded with funds donated by the Japanese government at the University of Ghana in Legon, a suburb north of Accra.

In 1981, the Instituto Nacional de Salud Mental (National Institute of Mental Health) "Honorio Delgado – Hideyo Noguchi" was founded with founds of the Peruvian Government and the JICA (Japan International Cooperation Agency) in Lima – Perú.

Dr. Noguchi's portrait has been printed on Japanese 1000 yen banknotes issued since 2004. In addition, the house near Inawashiro where he was born and brought up is preserved. It is operated as part of a museum to his life and achievements.

Noguchi's name is honored at the Centro de Investigaciones Regionales Dr. Hideyo Noguchi at the Universidad Autónoma de Yucatán.

Hideyo Noguchi Africa Prize

thumb|The footstone of Hideyo Noguchi in [[Woodlawn Cemetery (Bronx)|Woodlawn Cemetery, New York City]]The Japanese Government established the Hideyo Noguchi Africa Prize in July 2006 as a new international medical research and services award to mark the official visit by Prime Minister Jun'ichirō Koizumi to Africa in May 2006 and the 80th anniversary of Dr. Noguchi's death. The Prize is awarded to individuals with outstanding achievements in combating various infectious diseases in Africa or in establishing innovative medical service systems. The presentation ceremony and laureate lectures coincided with the Fourth Tokyo International Conference on African Development in late April 2008. In 2009, the conference venue was moved from Tokyo to Yokohama as another way of honoring the man after whom the prize was named. In 1899, Dr. Noguchi worked at the Yokohama Port Quarantine Office as an assistant quarantine doctor.

The Prize is expected to be awarded every five years. The prize has been made possible through a combination of government funding and private donations.

Notes

References

D'Amelio, Dan. Taller Than Bandai Mountain: The Story of Hideyo Noguchi. New York: Viking Press. (cloth)
Flexner, James Thomas. (1996). Maverick's Progress. New York: Fordham University Press. (cloth)
Kita, Atsushi. (2005). Dr. Noguchi's Journey: A Life of Medical Search and Discovery (tr., Peter Durfee). Tokyo: Kodansha. (cloth)
Lederer, Susan E. Subjected to Science: Human Experimentation in America before the Second World War, Johns Hopkins University Press, 1995/1997 paperback
Sri Kantha, S. "Hideyo Noguchi's research on yellow fever (1918–1928) in the pre-electron microscopic era", Kitasato Archives of Experimental Medicine, April 1989; 62(1): 1–9.

External links

Noguchi Memorial Institute for Medical Research, University of Ghana, Legon
Japanese Government Internet TV: streaming video, "Hideyo Noguchi Africa Prize," 2007/04/26 (5 mins.)
Fukushima Prefecture: "The Dreamer, Hideyo Noguchi," slide show
Cabinet Office, Government of Japan: Hideyo Noguchi Africa Prize
Japan Society for the Promotion of Science (JSPS): Purpose and Description of the Noguchi Prize
National Diet Library: NDL portrait
Yomiuri Shimbun: Noguchi – slightly less than 90% name recognition amongst primary school students in Japan, 2008.