[7] His most notable achievement was discovering the causative agent of syphilis Treponema pallidum in the infected brain and spinal cord tissue of a patient with general paresis, establishing the conclusive link between the mental and physical disease.

He had three main benefactors, Sakae Kobayashi, his elementary school teacher and father figure,[19] Kanae Watanabe, the doctor who performed surgery on his hand,[20] and Morinosuke Chiwaki, who later aided in funding his travel to the United States.

[3][2] Flexner left for San Francisco to investigate an outbreak of the plague, leaving Noguchi for three months under the guidance of Dr. Silas Weir Mitchell.

[2] When the Wasserman test was announced in 1906, Noguchi began working on refining it as it utilized serum reactions, which he was familiar from the course of his research of snake venom.

[47] 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."

Noguchi began collecting samples from spinal cords and brains of patients that died from tabes dorsalis or of paresis to determine its relationship to syphilis.

[50] In collboration with J. W. Moore, a psychiatrist at Wards Island, Noguchi discovered the presence of Treponema pallidum in the spinal cord of a patient with tabes dorsalis and paresis.

[8][50] His friend and neighbor, Ichiro Hori, reported he bursted into his apartment in the middle of the night, dancing and wearing nothing but his underwear, shouting, “I found it!

Noguchi proved that general paresis and tabes dorsalis are late stages of tertiary syphilis of the brain and spinal cords.

[63] 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.

[65] 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.

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.

[75] Professor William Henry Welch, Board of Scientific Directors at the Rockefeller Institute for Medical Research, urged Noguchi to conduct human trials.

[77] Most were hospital patients being treated for diseases, such as malaria, leprosy, tuberculosis, and pneumonia, and the subjects did not realize they were being experimented on and could not give consent.

[77] Critics at the time, mainly from the anti-vivisectionist movement, noted that the Rockefeller Institute violated the rights of vulnerable orphans and hospital patients.

[75] 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.

[75]"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?

[78] The United States did not develop sufficient consensus about unethical human experimentation until the late 20th century, which brought laws about involving informed consent and the rights of patients to pass.

"[75] He made a wrong doing with his experiments, not obtaining consent, but he might have received more criticism due to his race and the perpetuated stereotype of yellow peril.

[12] Noguchi felt compelled to make more discoveries and pressure from his boss Simon Flexner and home country to bring respect and honor to his fellow Japanese.

"[84]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.

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.

[23] He began preparing to travel to Accra, Gold Coast (modern-day Ghana) to study yellow fever and get closer to specimens.

The diaries of Oskar Klotz, another researcher with the Rockefeller Foundation,[96] describe Noguchi's temper and behavior as erratic and bordering on the paranoid.

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.

[101] In addition to his lasting contributions to the use of snake venom and serums for Rocky Mountain spotted fever.In the 21st century, the Nobel Foundation archives were opened for public inspection and research.

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" as noted in Times Magazine.

[121] In 1979, the Noguchi Memorial Institute for Medical Research (NMIMR) was founded with funds donated by the Japanese government[122] at the University of Ghana in Legon, a suburb north of Accra.

[127] The Prize is awarded to individuals with outstanding achievements in combating various infectious diseases in Africa or in establishing innovative medical service systems.

[128] The presentation ceremony and laureate lectures coincided with the Fourth Tokyo International Conference on African Development in late April 2008.