From Hookworm to Yellow Fever: Rockefeller Foundation, 1919-1927

The public health movement in the early 1900s was inspired not just by new scientific knowledge, but by a new awareness of connections between health and social problems. Reformers had discovered that poverty, ignorance, and vice often went hand in hand with disease and poor health. Treating and preventing disease, they believed, would eventually decrease poverty and vice in the populations treated. There were not yet any large federal or international health agencies to help fund public health studies and carry out control programs. But the Rockefeller Foundation (RF), established in 1913, had initiated such public health projects in America and abroad to eliminate debilitating diseases such as hookworm infection. The foundation's International Health Division (IHD) provided initial funding and personnel, but required that local governments contribute a portion of these as well, with the ultimate goal of building self-sufficient public health programs. (The RF also funded schools of medicine, nursing, and public health to provide trained staff for public health programs.) Sawyer became acquainted with several of the RF staff in the course of his wartime duties. Impressed with Sawyer's wide-ranging public health experience, the foundation recruited him to direct a new hookworm control program in Australia. He accepted the job in May 1919.

Sawyer and his family sailed to Australia that summer, and settled in Brisbane. For the next several years, Sawyer traveled around Australia assessing different areas for hookworm infection. Most parts of the country, as it turned out, were too arid to sustain the parasites, but the program did reduce hookworm infection in the tropical regions of Queensland. Sawyer also helped establish local public health associations, and helped draft plans for a Ministry of Health. He served as advisor to the ministry from 1922 to 1924. In 1923 Sawyer became Assistant Regional Director for the East, in charge of all IHD projects in Australia. In this post he also assisted Dr. Victor Heiser, Director for the East, inspect RF projects in Indonesia, Thailand, Ceylon, and India.

Sawyer and his family (which now included a son born in 1921) returned to the U.S. in 1924 (by way of India, Egypt, Palestine, and Europe). That fall, he was appointed Director of Laboratories, replacing Dr. Frederick F. Russell, who had become director of the International Health Division. One of the foundation's many missions was to assist in the development of county and municipal public health laboratories in the United States and abroad. These were often, though not always, adjuncts to the RF hookworm and malaria control projects. As Director of Laboratories, Sawyer initiated the establishment of such laboratories and also visited periodically to assess their operations. He also spent considerable time conferring with other public health officials, promoting cooperation between government and private public health organizations, and developing strategies for disease control efforts.

In 1926, Sawyer traveled to Nigeria to serve as director of the RF West Africa Yellow Fever Commission while director Henry Beeuwkes took six months of leave. Although he had not worked on yellow-fever control before, this disease would occupy much of his time for the next decade.

Yellow fever had long been one of the scourges of the tropics; it was characterized by a sudden onset, high fever, severe jaundice (hence "yellow" fever), and black vomit (from internal bleeding). Those who survived it had a permanent immunity to the disease. For many years its cause was unknown. Along with malaria, it had doomed the first attempt to build the Panama Canal in the 1880s, and also took a heavy toll during the Spanish-American War of 1898.

Knowledge of yellow fever improved considerably in 1900-1901, when Walter Reed and his staff, working in Cuba, conducted the first systematic study. That study proved that the disease was carried by mosquitoes, which could pass it to new hosts about twelve days after taking an infectious blood meal, and that the disease could also be produced by injecting blood taken from a yellow fever victim during the first two days of the illness. This knowledge enabled public health forces to nearly eliminate yellow fever from Havana and then from the Panama Canal Zone, mainly by eliminating the mosquito vectors. Also, though they were unable to identify the causative agent of yellow fever--attempts to culture it and establish a line of infection in lab animals failed--Reed and his colleagues did demonstrate that it was a very minute organism, capable of passing through very fine filters. This narrowed the field of possible causative agents by ruling out larger microorganisms.

Yellow fever was still present in South and Central America, however, and the increased trade made possible by the Panama Canal also increased the risk that it could be carried to many Asian countries. Before the canal opened in 1914, the newly established International Health Board (later the International Health Division) of the Rockefeller Foundation appointed a commission, headed by General William Gorgas, to evaluate suspected yellow fever centers in Ecuador, Colombia, Peru, Venezuela, and Brazil. In 1918-1919, Gorgas supervised a campaign that eradicated yellow fever from Guayaquil, Ecuador.

During the same period Hideyo Noguchi, a distinguished Rockefeller Institute scientist, studied the blood of yellow fever patients in Guayaquil. Within several months, he concluded that a spirochete (small spiral-shaped bacterium) found in some samples, which he named Leptospira icteroides, was the cause of the disease. His findings were accepted by many, though they contradicted Reed's earlier work that pointed to a filterable virus as the cause. Noguchi went on to develop a vaccine against it, which was used for a few years, though his proofs left room for doubts.

Noguchi's mistake (and its acceptance) demonstrated how difficult it was to distinguish yellow fever from other tropical diseases that produced some of the same symptoms (e.g., jaundice or hemorrhaging). One of the primary challenges at the time was simply determining what "yellow fever" was, in Africa and in the Americas, and establishing it as a distinct clinical entity. In 1920, the RF established the first West Africa Yellow Fever Commission in Nigeria. Its goals were to determine whether the yellow fever reported there was the same disease seen in the western hemisphere, and to ascertain whether control measures were feasible. Visits to Nigeria and nearby countries did not find any active cases, but there was evidence that yellow fever infection had occurred within the past three years. The commission recommended further investigation and in 1925, a second yellow fever commission, directed by Dr. Henry Beeuwkes, set out to study the characteristics and epidemiology of the disease in Africa; to determine its relationship to the yellow fever seen in the Americas; to isolate the causative organism; to discover the method of transmission, and to identify the areas where the disease was endemic.

During his six months as director of the lab in 1926-27, Sawyer investigated reports of yellow fever cases and continued testing different experimental animals for susceptibility to the disease. (The usual experimental candidates--rats, mice, dogs, cats--did not develop yellow fever, and this had made research difficult.) Shortly before he returned to the United States, there were several outbreaks of yellow fever in the region, and RF physicians were able to obtain blood samples from several infected patients during the early days of their illness. The laboratory had just received a new shipment of animals, which included several rhesus monkeys. These proved to be susceptible to yellow fever when injected with blood from one patient, an African named Asibi. Within the next few months Adrian Stokes, Johannes Bauer, and N. Paul Hudson had confirmed that the disease was caused by a filterable virus; that Aedes aegypti mosquitoes were the vectors, and that the disease could be transmitted between the monkeys, and between the monkeys and humans. (Unfortunately, it was Stokes' death from yellow fever in September 1927 that helped confirm monkey-to-human transmission.) In 1928 Bauer discovered that several other Aedes species (not found in the Americas) could transmit the disease, suggesting that the epidemiology could be more complex than first thought. (The prevailing theory, based on the experiences of Reed and Gorgas, was that yellow fever was carried only by A. aegypti, and was an urban disease, requiring a dense population of non-immune human hosts for its spread. Several years later, Fred Soper's recognition of jungle yellow fever in rural Brazil confirmed a different pattern of infection.)

The discoveries of the West Africa Commission also suggested that Noguchi's Leptospira was not the causative organism, and that African and American yellow fever were the same disease. Noguchi went to Nigeria in November 1927, and did a study attempting to prove that Leptospira icteroides caused African yellow fever or that South American yellow fever was different from the African kind. Several months of hard work proved inconclusive and, tragically, Noguchi contracted the disease and died in May 1928.

For more information about the Rockefeller Foundation's work on hookworm and yellow fever, visit the National Library of Medicine's Profiles in Science exhibit featuring the Fred L. Soper Papers.