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A Maryland-trained doctor studying yellow fever in Cuba just after the Spanish-American War received a most promising bug bite exactly 100 years ago last week. Because he deliberately permitted the Aedes Aegypti mosquito to bite him, and because it nearly killed him, Dr. James Carroll is today heralded as a pioneer in solving an epidemic that ravaged the U.S. coasts and killed hundreds of thousands of Americans in the 18th, 19th and early 20th centuries.

Carroll’s yellow fever research—done in collaboration with U.S. Army colleagues Walter Reed, Jesse Lazear and Aristides Agramonte—is considered a landmark of medical history. A letter from Reed, who was Carroll’s chief at the U.S. Yellow Fever Commission, that followed the near-fatal bite poses the question that ultimately drove scientists to a cure. “Did the mosquito do it?” Reed asks in the letter on display at the University of Maryland School of Medicine in Baltimore. Undoubtedly, yes. The rest, as they say, is history.

“For someone to be so committed to an idea that they would be willing to suffer these abhorrent conditions to advance the hypothesis, that’s remarkable,” said Susan Lederer, a professor of the history of medicine at Yale University. “It was quite heroic to live there at the time and to experiment under those conditions.”
Few illnesses conjure up the gruesome symptoms that yellow fever inflicts on its victims: vomiting, nausea, diarrhea, cramps, and in many cases, death. Yet despite the risks, Carroll allowed a fever-filled mosquito to light on his forearm and deliver its deadly bite. “He knew that (the mosquito) had fed on several yellow fever patients before and that it had been fully incubated,” said Theodore Woodward, a scholar and professor emeritus at the University of Maryland School of Medicine, where Carroll took his medical degree in 1879.

Woodward has collected more than 40 personal letters detailing the work of the Yellow Fever Commission, including the one from Reed to a recovering Carroll dated Sept. 7, 1900. Reed was so moved by Carroll’s courage—and so relieved at his survival—that he penned the following note in his own handwriting: “Hip! Hip! Hurrah! God be praised for the news from Cuba today—‘Carroll much improved, prognosis very good.’”

Indeed, one of the ironies of the yellow fever studies, Lederer said, is that while Reed received most of the credit for the groundbreaking research, it was Carroll, Lazear and Agramonte who risked their lives by exposing themselves to the disease. Reed never exposed himself to the deadly yellow fever mosquitoes because scientists thought he was too old to survive a bite. “He had been called back to Washington when they all decided to start experimenting on themselves,” said Michael Rhode, archivist of the National Museum of Health and Medicine at the Walter Reed Army Medical Center in Washington.

The scientists’ relationship later soured because Carroll felt slighted by the media and others who credited Reed solely for the breakthrough, Woodward said. “He was an irascible character,” he said. So consumed were Americans by yellow fever and the scientists who solved it that a Broadway play, and later a movie, were made from the story. “Yellow Jack,” as the disease was commonly called, drew audiences nationwide.

“It was a particularly terrifying disease,” Rhode said. “Besides establishing an undisputed link between mosquitos and disease, the scientists’ work also set the standard for informed consent using human subjects in medical research,” Rhode said. After infecting themselves with the disease, the scientists recruited U.S. soldiers to participate in controlled studies where their findings about the transmission of yellow fever gained further credence.

The severity of yellow fever also led to the creation of the U.S. Public Health Service, which mobilized after a series of yellow fever outbreaks killed thousands in cities like New Orleans, Charleston, S.C., Norfolk, Va. and Mobile, Ala. “In some cities, the disease killed one in every 10 people who contracted it,” said Margaret Humphreys, a Duke University professor and author of a recent book about the disease. 

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