1901 – Theory that yellow fever is transmitted by the Aedes Aegypti mosquito proved

In 1900 Reed was appointed head of an army board to investigate the causes of yellow fever, which had broken out among American troops in Cuba. In the United States yellow fever was an annual scourge; the disease swept up the eastern seaboard and often spread to the Gulf states and up the Mississippi River valley. The places in which it occurred, the season of its occurrence, and the temperature coordinates of its spread were predictable and well known but not understood. No one knew what caused it, and the terror that accompanied it was equaled only by the misapprehension of its nature. A few lucky guesses had been made before Reed took up his work; as early as 1848 the Alabama physician Josiah No had suggested that an insect—perhaps the mosquito—caused the disease, although he had only tenuous evidence, and in 1881 Carlos Finlay, working closely with the United States Yellow Fever Commission in Havana, suggested that yellow fever was transmitted by Culex fasciatus (now called Aëdes aegypti ).

Upon arriving in Havana, Reed and his co-workers pursued further investigations of Sanarelli’sBacillus icteroides and concluded that it was the hog-cholera virus. They then turned to the theory of the mosquito as the vector of yellow fever. Finlay had been conducting experiments along these Lines, and provided them with mosquitoes, mosquito eggs, and instructions for raising the insects in the laboratory. Since there was no laboratory test for yellow fever, Finlay also aided them in the clinical verification of the disease. Reed then designed and conducted the experiments that elucidated the means of transmission of the disease once and for all. He used human subjects of necessity, and Lazear, who was accidentally bitten by an infected mosquito, contracted yellow fever and died; Carroll also became ill with the first experimental case of the disease but recovered. Using soldier volunteers. Reed and his team produced twenty-two other experimental instances of yellow fever, of which none was fatal. These experiments, coupled with the notes that Lazear had left, led Reed and his co-workers to the discoveries about the disease that resulted in its eradication.

Reed and his colleagues discovered that the female Aëdes aegypti mosquito can become infected by biting a victim of yellow fever only during the first three days of the course of the illness; she does not become infectious for two weeks thereafter, but may then remain infectious for up to two months in a warm season. The mosquito does not herself become ill, nor do her eggs, which remain infertile until she has fed on blood, harbor an infection that will affect the brood. The period of incubation of yellow fever is three to five days after the victim has been bitten by an infected mosquito, and having had the disease provides excellent immunity against subsequent attacks. Through experimentation Reed and his group established that whole blood taken from a patient early in the course of the disease will, upon injection into a susceptible person, cause yellow fever. They also determined that blood from an infected person could be passed through a Pasteur filter and still remain infectious; this was thus the first known filterable virus causing a human infection.