Hideyo Noguchi

Born(1876-11-09)November 9, 1876
DiedMay 21, 1928(1928-05-21) (aged 51)
Resting placeWoodlawn Cemetery, New York City, USKnown forsyphilis
Treponema pallidumScientific careerFieldsbacteriology Japanese nameKanji野口 英世Hiraganaのぐち ひでよ

Transcriptions
Romanization	Noguchi Hideyo

Hideyo Noguchi (野口 英世, Noguchi Hideyo, November 9, 1876 – May 21, 1928), also known as Seisaku Noguchi (野口 清作, Noguchi Seisaku), was a prominent Japanese bacteriologist who in 1911 discovered the agent of syphilis as the cause of progressive paralytic disease. Noguchi was one of the first Japanese scientists to gain international acclaim and recognition.

Noguchi Hideyo, whose childhood name was Seisaku Noguchi,^[1] was born to a family of farmers for generations^[1] in Inawashiro, Fukushima prefecture in 1876. When he was one and a half years old, he fell into a fireplace and suffered a burn injury on his left hand. There was no doctor in the small village, but one of the men examined the boy. "The fingers of the left hand are mostly gone," he said, "and the left arm, the left foot, and the right hand are burned; I don't know how badly."^[2]

In 1883, Noguchi entered Mitsuwa elementary school. Thanks to generous contributions from his teacher Kobayashi and his friends, he was able to receive surgery on his badly burned hand. He recovered about 70% mobility and functionality in his left hand through the operation.

Noguchi decided to become a doctor to help those in need. He apprenticed himself to Dr. Kanae Watanabe (渡部 鼎, Watanabe Kanae), the same doctor who had performed the surgery. He entered Saisei Gakusha, which later became Nippon Medical School. He passed the examinations to practice medicine when he was twenty years old in 1897. He showed signs of great talent and was supported in his studies by Dr. Morinosuke Chiwaki. In 1898, he changed his first name to Hideyo after reading a Tsubouchi Shōyō novel of college students whose character had the same name—Seisaku—as him. The character in the story was an intelligent medical student like Noguchi but became lazy and ruined his life.^[3]

In 1900, Noguchi travelled on the America Maru to the United States.^[4] In part, his move was motivated by difficulties in obtaining a medical position in Japan, as prospective employers were concerned that his hand deformity would discourage potential patients.^[4] Noguchi went to Philadelphia and obtained a job as a research assistant with Dr. Simon Flexner at the University of Pennsylvania and later at the Rockefeller Institute of Medical Research.^[4] Flexner put him under guidance from Philadelphia physician Silas Weir Mitchell and dealt with venomous snakes. In 1907, the University of Pennsylvania awarded Hideyo Noguchi an honorary degree.^[4]

In 1909, Noguchi published a monograph, Snake Venoms: An Investigation of Venomous Snakes with Special Reference to the Phenomena of Their Venoms, which bolstered his scientific reputation.^[4] Noguchi was invited to the Serum Institute in Copenhagen, Denmark, where he continued his research on serology and co-wrote several papers with fellow scientist, Toval Massen.^[4]

At the Rockefeller Institute, he thrived in this environment.^[5] He and his peers learned from their work and from each other. In this period, a fellow research assistant in Flexner's lab was Frenchman Alexis Carrel, who would go on to win a Nobel Prize in 1912.^[6] Hideyo Noguchi would later be nominated numerous times for a Nobel Prize.

In 1913, Noguchi demonstrated the presence of Treponema pallidum (syphilitic spirochete) in the brain of a progressive paralysis patient, proving that the spirochete was the cause of the disease and the neurological connection.^[7] Dr. Noguchi's name is remembered in the binomial attached to another spirochete, Leptospira noguchii.^[8]

In 1917, Noguchi was released from the hospital after having typhoid fever. Noguchi and his wife, Mary Dardis, went to Shandaken in the Catskills to recover.^[4] They got a room at the Glenbrook Hotel.^[4] The nature and mountains reminded Noguchi of his hometown, Inwashiro, and the Bandai foothills.^[4] The nearby lake was similar to lake Inawashiro. During that time, he decided to build his house in Shandaken alongside the Esopus.^[4] Hideyo and Mary would spend most of their summers in Shandaken on Old Route 42.^[4]

Dr. Noguchi was gifted a box of oil paints from his close friend and neighbor, Ichiro Hori, a Japanese photographer and artist.^[4] He brought these to Shandaken. Eventually, he painted a portrait of his wife and mother.^[4] His paintings are held in the Hideyo Noguchi Memorial Infectious Disease Museum.^[9] His other hobbies include shoji, chess, and fishing in the Esopus, located outside his house.^[4]

In addition, Hideyo Noguchi was an amateur photographer. He might have been one of the first documented color photographs of a Japanese person using autochrome lumière in a letter, dated August 8th, 1914, to his childhood mentor, Dr. Sakae Kobayashi.^[10] The photograph is presumed to have been taken the same year.^[10]

Hideyo Noguchi wrote in the letter,

"The natural color was obtained by the imaging method discovered by Mr. Lumière, and it was taken at the villa of my friend Dr. Gates.."^[10]

In 1918, Noguchi traveled extensively in Central America and South America working with the International Health Board to conduct research to develop a vaccine for yellow fever, and to research Oroya fever, poliomyelitis and trachoma. In 1923, Noguchi was credited with producing an effective antiserum against Rocky Mountain spotted fever, a disease when left untreated can become life-threatening.^[11]

In the 21st century, the Nobel Foundation archives were opened for public inspection and research. Noguchi was nominated several times for the Nobel Prize in Physiology or Medicine: in 1913–1915, 1920, 1921 and 1924–1927.^[12] Some of Noguchi's prize nominations and work on a pure culture of syphilis and yellow fever attracted scrutiny.^[13][4] He published over 200 papers on various infectious diseases, one of the most prolific scientists, and gave lecture tours throughout Europe.^[4] In 1921, he was elected as a member of the American Philosophical Society.^[14]

Noguchi believed that yellow fever was caused by spirochaete bacteria instead of a virus. He worked for much of the next ten years trying to prove this theory. His work on yellow fever was widely criticized as taking an inaccurate approach that was contradictory to contemporary research, and confusing yellow fever with other pathogens as it was highly debated scientific topic topic. Four years after Noguchi's death, the electron microscope was developed in 1931, which clearly see the differences between the diseases.^[15][4] It turned out he had confused yellow fever with leptospirosis.^[4] Noguchi's vaccine he developed against "yellow fever" was successfully used to treat the latter disease.

In 1911 and 1912 at the Rockefeller Institute in New York City, Noguchi was working to develop a syphilis skin test similar to the tuberculin skin test, which could provide a useful diagnostic procedure to complement the Wassermann test in the detection of syphilis.^[16] Professor William Henry Welch, Board of Scientific Directors at the Rockefeller Institute for Medical Research, urged Noguchi to conduct human trials.^[16] The subjects were gathered from clinics and hospitals in New York. In the experiment, the Rockefeller Institute staff injected an inactive product of syphilis, called luetin, under the skin on the upper arm of the subject.^[16] Skin reactions were studied, as they varied among healthy subjects and syphilis patients, based on the disease's stage and its treatment. The lutein test gave a positive reaction almost 100 percent for congenital and late syphilis.^[17] Of the 571 subjects, 315 had syphilis.^[18] The remaining subjects were controls; some of which were orphans between the ages of 2 and 18 years.^[18] Most were hospital patients being treated for diseases, such as malaria, leprosy, tuberculosis, and pneumonia, and the subjects did not did not realize they were being experimented on and could not give consent. ^[18]

Critics at the time, mainly from the Anti-vivisectionist movement, noted that the Rockefeller Institute violated the rights of vulnerable orphans and hospital patients. There was concern on the part of the anti-vivisectionists that the test subjects had contracted syphilis from Noguchi's experiments, even though that was not possible.^[16][19] Much of the information came from newspapers that sensationalized it, which did not consult doctors or scientists, ignoring the science behind the trials.^[16] Although, none of subjects were infected with syphilis, Noguchi's experiment still tested on patients without their consent, which was unethical human experimentation.^[16]

In Dr. Noguchi's defense, Noguchi had performed tests on animals to ensure the safety of the luetin test.^[16] Rockefeller Institute business manager Jerome D. Greene wrote a letter to the Anti-Vivisection Society, which had pointed out that Noguchi had tested it on himself and his fellow researchers before administering it.^[16]

In a letter to District Attorney Charles S. Whitman, Greene said

""What public institution would not welcome a harmless and painless test which would enable it to decide in the case of every person admitted whether that person was afflicted with a venereal disease or not?" ^[16]

Furthermore, Greene mentioned the steps Rockefeller scientists had taken to ensure the inactive extract's sterility.^[16] At the time, Greene's explanation was considered a demonstration of the care that doctors were taking in research even though it ignored a patients right to informed consent. In May 1912, the New York Society for the Prevention for Cruelty to Children asked the New York district attorney to press charges against Noguchi, but he declined. ^[20] Even though none of the subjects were injured in the experiment. Albert Leffingwell, a physician, social reformer, and advocate for vivisectionist restrictions, said in response to Jerome D. Greene in advocating for informed consent.^[16]

"If insurance could have been given that the luetin test implied no risk of any kind, might not the Rockefeller Institute have secured any number of volunteers by the offer of a gratuity of twenty or thirty dollars as a compensation for any discomfort that might be endured?"^[16]

The United States did not develop sufficient consensus about human experimentation for laws to be passed about informed consent and the rights of patients until the late 20th century, and consent were by no means customary.^[19][16] For instance, often considered the fathers of microbiology, Robert Koch operated medical concentration camps in Africa in 1906 to 1907 to find a cure for sleeping sickness, doubling the doses and blinding some of his patients with atoxyl, a substance known to be toxic, and Louis Pasteur experimented on 9-year-old Joseph Meister without a medical license and was suspected to have lied about conducting animal trials.^[21][22] While Hideyo Noguchi had commited a wrong, it was 'a wrong without injury.' It does not justify his choices to pursue human experimentation, but putting it into perspective of the early 19th century, it was not unlike other scientists at the time.^[16]

Following the death of British pathologist Adrian Stokes of yellow fever in September 1927,^[23] it became increasingly evident that yellow fever was caused by a virus, not by the bacillus Leptospira icteroides, as Noguchi believed.^[4]

Feeling his reputation was at stake, Noguchi hastened to Lagos to carry out additional research. However, he found the working conditions in Lagos did not suit him. At the invitation of Dr. William Alexander Young, the young director of the British Medical Research Institute, Accra, Gold Coast (modern-day Ghana), he moved to Accra and made this his base in 1927.

However, Noguchi proved a very difficult guest and by May 1928 Young regretted his invitation. Noguchi was secretive and volatile, working almost entirely at night to avoid contact with fellow researchers. Possibly his erratic and irresponsible behavior was caused by the untreated syphilis with which he was diagnosed in 1913, and which may have progressed to neurosyphilis.^[4] The diaries of Oskar Klotz, another researcher with the Rockefeller Foundation,^[24] describe Noguchi's temper and behavior as erratic and bordering on the paranoid. His methods were haphazard.

According to Klotz, he inoculated huge numbers of monkeys with yellow fever, but failed to keep proper records. Noguchi might have believed himself immune to yellow fever, having been inoculated with a vaccine of his own development. ^{[citation needed]}

Despite repeated promises to Young, Noguchi failed to keep infected mosquitoes in their secure containers. In May 1928, having failed to find evidence for his theories, Noguchi was set to return to New York after spending six months in Africa, but was fallen ill in Lagos.^[4]

He boarded his ship to sail home, but on 12 May was put ashore at Accra and taken to a hospital with yellow fever. After lingering for some days, he died on 21 May.^[25]

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."^[26]

Seven days later, despite exhaustive sterilisation of the site and most particularly of Noguchi's laboratory, Young himself died of yellow fever.^[27]

Noguchi was influential during his lifetime. Although, his later research was not able to reproduce many of his claims, including having discovered the causes of polio, rabies, trachoma, and yellow fever.^[28] His mental state deteriorated as he suffered from neurosyphilis, prone to amnesia and personality changes. His finding that Noguchia granulosis causes trachoma was questioned within a year of his death, and overturned shortly thereafter.^[29][30] Alongside his identification of the rabies pathogen,^[31] because the medium he invented to cultivate bacteria was seriously prone to contamination.^[32] A fellow Rockefeller Institute researcher said that Noguchi "knew nothing about the pathology of yellow fever" and criticized him for being unwilling to issue retractions for his claims.^[33] Another criticism are the flaws inside the Rockefeller Institute's system of peer review.^[34]

Noguchi's most famous contribution is his identification of the causative agent of syphilis (the bacteria Treponema pallidum) in the brain tissues of patients with partial paralysis due to meningoencephalitis.^[35] Other lasting contributions include the use of snake venom in serums, the identification of the leishmaniasis pathogen and of Carrion's disease with Oroya fever. His claim to have grown a culture of syphilis though is considered irreproducible.^{[citation needed]}

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

Washington, D.C.: Carnegie Institution. [OCLC 2377892]

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

Washington, D.C.: Carnegie Institution. [OCLC 14796920]

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

Philadelphia: J. B. Lippincott. [OCLC 3201239]

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

New York: P. B. Hoeber. [OCLC 14783533]

Noguchi was honored with Japanese and foreign decorations. He received honorary degrees from a number of universities.

Noguchi was self-effacing in his public life, and he often referred to himself as "funny Noguchi." Those who knew him well said that he "gloated in honors."^[36] 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."^[37]

• Kyoto Imperial University, Doctor of Medicine, 1909.^[38]
• Knight of the Order of Dannebrog, 1913 (Denmark).^[39]
• Commander of the Order of Isabella the Catholic, 1913 (Spain).^[40]
• Commander of the Order of the Polar Star, 1914 (Sweden).^[41]
• Tokyo Imperial University, Doctor of Science, 1914.^[41]
• Order of the Rising Sun, Gold Rays with Rosette, 1915.^[42]
• Imperial Award, Imperial Academy (Japan), 1915.^[43]
• Central University of Ecuador, 1919, (Ecuador).^[44]
• National University of San Marcos, 1920, (Peru)
• Medicine School of Merida, "Doctor Honoris Causa en Medicina y Cirugía", 1920 (México)
• University of Guayaquil, 1919, Ecuador.^[44]
• Yale University, 1921, (United States).^[37]
• Knight of the Legion of Honour of France, 1924^[45]
• Senior fifth rank in the order of precedence, Japanese government, 1925^[45]

Noguchi's remains were returned to the United States and buried in Woodlawn Cemetery in the Bronx, New York City.^[46]

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.^[47]

In 1979, the Noguchi Memorial Institute for Medical Research (NMIMR) was founded with funds donated by the Japanese government^[48] at the University of Ghana in Legon, a suburb north of Accra.^[49]

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.^[50]

Dr. Noguchi's portrait has been printed on Japanese 1000-yen banknotes since 2004.^[51] 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.^[52]

A 2.1 km street in Guayaquil, Ecuador downtown is named after Dr. Hideyo Noguchi.

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.^[53] The Prize is awarded to individuals with outstanding achievements in combating various infectious diseases in Africa or in establishing innovative medical service systems.^[54] The presentation ceremony and laureate lectures coincided with the Fourth Tokyo International Conference on African Development in late April 2008.^[55] 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.^[56]

The Prize is expected to be awarded every five years.^[57] The prize has been made possible through a combination of government funding and private donations.^[58]

• List of medicine awards
• Max Theiler - completed Noguchi's work, yellow fever vaccine (1926)
• Human experimentation in the United States
• Tōki Rakujitsu - Japanese film

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