Yellow fever is an acute viral hemorrhagic disease that has historically plagued tropical and subtropical regions across the globe. Determining where it was discovered is complex because it involves two distinct moments: the disease’s origin as a biological entity and the specific locations of the scientific breakthroughs that revealed its cause and mode of transmission. The identification of its mechanism and pathogen required modern laboratory science.
The Historical Geography of Yellow Fever’s Emergence
The evolutionary origins of yellow fever are traced back to West and Central Africa, where the virus likely circulated for centuries in a sylvatic, or jungle, cycle among non-human primates and forest-dwelling mosquitoes. Phylogenetic analyses suggest the virus originated in this region, eventually making the jump from monkeys to humans. Because the virus was endemic to this area, many indigenous African populations had developed a degree of immunity.
The disease’s spread to the Americas was a direct consequence of the transatlantic slave trade, which began in the 17th century. Infected people and the primary urban vector, the Aedes aegypti mosquito, were inadvertently transported across the ocean on slave ships. The earliest documented outbreaks in the New World occurred in the Caribbean, with cases recorded on the island of Barbados in 1647 and Guadeloupe in 1648.
Once established, the virus and its mosquito vector found ideal conditions in the tropical and subtropical port cities of the Americas. Epidemics subsequently ravaged major urban centers, becoming a recurring and devastating presence. The disease, often referred to as “Yellow Jack” or “black vomit” (vómito negro) due to the jaundice and internal hemorrhaging it caused, became a defining plague of the New World for over two centuries.
Havana and the Discovery of Mosquito Transmission
The most significant step in understanding how yellow fever was spread occurred in Havana, Cuba, at the turn of the 20th century. Cuban physician and epidemiologist Carlos Finlay first proposed in 1881 that the disease was transmitted by a mosquito, which he identified as Culex fasciatus, now known as Aedes aegypti. His hypothesis, presented at the International Sanitary Conference, was largely ignored by the medical establishment for nearly two decades.
The definitive proof came in 1900 with the arrival of the U.S. Army Yellow Fever Commission, led by Major Walter Reed, tasked with investigating an outbreak among American troops stationed in Cuba. The commission, operating near Havana, refined and tested Finlay’s theory through a series of controlled human experiments conducted at a facility named Camp Lazear.
The researchers proved two crucial facts that confirmed the mosquito’s role. First, they established that the Aedes aegypti mosquito was the sole vector responsible for transmitting the disease from a sick person to a healthy one. Second, they determined the required extrinsic incubation period. They showed the mosquito needed to bite a patient during the first three days of illness, and then wait approximately 12 days before it could transmit the infection to a new host. This groundbreaking work shifted the focus of disease control from sanitation to aggressive mosquito eradication, dramatically reducing the incidence of yellow fever in Cuba and later enabling the successful construction of the Panama Canal.
Identifying the Viral Cause
While the Havana experiments proved the mode of transmission, they did not identify the causative agent itself. Reed’s team performed filtration experiments that suggested the agent was a “filterable virus,” meaning it was small enough to pass through a filter designed to trap bacteria. The final scientific discovery of the yellow fever pathogen took place nearly three decades later, in a laboratory setting.
The definitive isolation of the yellow fever virus occurred in 1927 by researchers from the Rockefeller Institute for Medical Research, working in West Africa and the United States. Scientists were able to isolate the virus from the serum of a patient in Ghana by inoculating rhesus monkeys, which proved susceptible to the disease. The virus, an RNA virus belonging to the Flavivirus genus, was confirmed to be the agent responsible for the illness.
This identification distinguished the yellow fever virus as the first human virus ever isolated, marking a pivotal moment in virology and tropical medicine. The ability to study the virus in a laboratory setting paved the way for the development of a highly effective vaccine, achieved by Max Theiler in the 1930s.