by Joe Luna

Picture yourself at the entrance of a prestigious laboratory in Philadelphia, where you hope to be a postdoc. You just arrived from a small village in Japan and you never went to medical school; you instead learned from textbooks (in self-taught English, French and German) enough to pass the Japanese M.D. examination with pure hard work. On top of that, you’re without the use of your left hand due to a childhood fire accident. Perhaps you have a letter of introduction in your attaché, but by all measures you’ve shown up out of the blue, and are hoping, no, praying for a job. As you stand at the threshold, you become suddenly aware that you’re thousands of miles from home. Do you enter the building?

In 1900, a man named Hideyo Noguchi (born 24 November 1876) must have mulled this over before entering the pathology laboratory at the University of Pennsylvania. He could never know it, but he had just embarked on one of the most exciting and tragic scientific adventures of the last century.

Noguchi
Bust of Hideyo Noguchi in the Markus Library at Rockefeller University

Noguchi secured a job as a research assistant under a pathologist named Simon Flexner (recognize him?), who in 1901 became the first scientific director of the newly created Rockefeller Institute for Medical Research. Under Flexner’s guidance, Noguchi blossomed as a scientist, first studying the toxic properties of snake venoms and devising a diagnostic test for syphlilis infections. In 1910, Noguchi tackled the difficult problem of growing the causative agent of syphilis: the spirochete Treponema pallidum (now known as Spirochaeta pallida). And he wasn’t the first to try.

Years earlier in 1905, two German scientists Fritz Schaudinn and Erich Hoffmann reported that the squiggly spirochete could be observed in the brains of patients who died of syphilis. While tantalizing as the potential cause, they failed to cultivate the spirochete and as a result could not definitely prove that Treponema caused the disease. The bacteriology world went into an immediate frenzy, with every lab trying to cultivate Treponema pallidum. By 1910, no one had yet succeeded and it remained an open race.

Noguchi set to work. At the time, Treponema could not be cultivated due to fast-growing contaminating bacteria. Only rabbit testicles would support supple growth of the spirochete, yet still contaminating bacteria were a problem. Noguchi realized that if cultures were placed in a semi-porous ceramic filter, the spirochetes would be able to wiggle their way through the filter while leaving contaminating bacteria behind, thus creating a pure culture. He inoculated dozens of rabbits (poor guys), isolated their rabbithood, filtered their extracts and by using the resulting supernatant to inoculate a second set of rabbits –voila! – the rabbits developed syphilis! Koch’s postulates confirmed!

With this discovery, Noguchi joined the ranks of Pasteur, Reed, and Smith as a microbe hunter. He triumphantly lectured all across Europe and continued to pursue other diseases that could be caused by spirochetes. The Nobel nominations poured in (he received a total of twenty-five over nine years).

In 1918, the now famous Noguchi was invited to Ecuador to find the unknown mosquito-borne agent that caused yellow fever. Almost immediately he came across the spirochete Leptospira icteroides in patient samples. He went on to show using his previous methods that this germ could cause yellow fever-like disease in guinea pigs. (The Ecuadorean government made him an honorary colonel for this discovery). Traveling in the 1920’s to study yellow fever epidemics in Peru and Mexico, Leptospira icteroides kept popping up – the matter seemed almost closed. Another disease, solved by Noguchi!

One slight problem: in African cases of yellow fever, Leptospira icteroides could not be found. Over time, Noguchi’s initial claim was called into doubt, and despite failing health, Noguchi set out for Africa to find out for himself. Sadly he wouldn’t live to seek the answer, in 1928 Noguchi succumbed to yellow fever in Accra, Ghana at age 51.

There are few examples of scientists giving their lives in the pursuit their work; Noguchi’s story is among the most moving. From the humblest of beginnings, to the greatest heights, to a tragic end, the story of Hideyo Noguchi has not gone un-noticed in recent years. Since 2004 Noguchi’s portrait has graced the Japanese 1000 yen note, a national hero. In 2006, the Japanese government established the Hideyo Noguchi Africa Prize, to honor the work of scientists still fighting infectious disease in Africa.

So have you entered the building yet?

 

Sources:

George Washington Corner’s seminal book “A History of the Rockefeller Institute 1901-1953: Orgins and Growth” provides the best account of Noguchi’s scientific life (The Rockefeller Institute Press, New York, 1964). Check it out at the RU library (while you’re there, tip your hat to the bust of Noguchi that flanks the library doors in the main reading room).

Noguchi’s recent biography “Dr. Noguchi’s Journey: A life of Medical Search and Discovery” by Atsushi Kita is an excellent read and gives an honest picture of the man in all his triumphs and faults. From the preface: “When a person shines so brightly, surely his shadows will be equally as dark.” (Kodansha International, Tokyo, 2005).

Nature obituary, June 1928.

Most of Noguchi’s papers were in the Journal of Experimental Medicine, and are fully publicly accessible via Pubmed. (Yay RU press!)

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