Mosquitoes: Finding the Vector

Introduction | Politics | In Cuba | Commission | Mosquitos | New Strategies | Impact | Credits

Two Theories: Fomites or Aedes?

George M. Sternberg (1838-1915)

From the frontispiece of George Miller Sternberg: A Biography by Martha Sternberg (1920)

Sternberg formed the Army Yellow Fever Commission in 1900 with the hope of ending the scientific debate on the cause and spread of yellow fever. Sternberg himself had been deeply involved in the controversy since his work in Cuba in 1879 as chief microscopist of the National Board of Health’s Yellow Fever Commission. He had disproved several popular theories regarding the microbe responsible for yellow fever, but he was not able to find the real culprit. In 1900, the yellow fever germ was still a mystery.

Isolation of the germ was one problem; how the disease spread was another. Many scientists believed that yellow fever spread by direct contact with an infected person or with infected objects (fomites) like clothing, blankets, or luggage: this was called the fomites theory. Sternberg was reasonably certain that the fomites theory was correct, but he needed his four commissioners to erase all doubt.

Henry Rose Carter (1852-1925)

Photo from H. R. Carter Collection, Historical Collections & Services, CMHSL

Dr. Henry Rose Carter (UVa Class of 1873) disagreed. While a quarantine officer with the U.S. Marine Hospital Service, Carter observed that, regardless of contact with infected persons or clothing, approximately two weeks elapsed between the first and second outbreaks of yellow fever in his quarantine camps. His study of a yellow fever epidemic in Orwood and Taylor, Mississippi, in 1898 confirmed his previous observations: a period of 9 to 14 days separated the first series of cases from the second. The yellow fever germ required, as Carter called it, an “extrinsic incubation period” before it could be transmitted.

Carter did not explain how or why this occurred, but his work suggested an intermediate host. Scientists had speculated as early as 1848 that yellow fever was carried by an insect. In 1881, Dr. Carlos Juan Finlay specified the Aedes aegypti mosquito as the vector for the disease.

Carlos J. Finlay (1833-1915)

Ridiculed by his associates as “The Mosquito Man,” Finlay tried for nearly 20 years to win support for his theory.

Hench-Reed Collection, Historical Collections & Services, CMHSL

Born in Cuba and educated in Europe and the United States, Finlay had been among the Cuban scientists chosen to work with Sternberg and the U.S. Yellow Fever Commission of 1879. He was convinced by the commission’s results that the germ was present in the walls of blood vessels and concluded that the disease somehow spread from an infected person’s vessels directly to another’s. Thinking in terms of inoculation, he implicated the long proboscis of Havana’s household mosquito, the Aedes aegypti.

But he could not prove it. Unlike Ronald Ross and Patrick Manson, who had demonstrated in 1897 that the Anopheles mosquito carried malaria, Finlay and his assistant, Claudio Delgado, failed to design an air-tight experiment that might convince the scientific community that a similar connection existed between the Aedes mosquito and yellow fever.

After serving as a contract surgeon with the U.S. Army during the 1898 Santiago campaign, Finlay joined Henry Rose Carter and William Crawford Gorgas on the U.S. Yellow Fever Board in 1899. He offered his services to Walter Reed the following year.

The Death of Lazear

Agramonte, Lazear, and Carroll at Camp Columbia Barracks, July-August 1900. It is likely that Reed was in the United States finishing the typhoid report when this photograph was taken.

Hench-Reed Collection, Historical Collections & Services, CMHSL

On June 25, 1900, Reed and his team met for the first time at Columbia Barracks in Quemados, Cuba, where a yellow fever epidemic had recently begun. Ross’s Anopheles-malaria work and Carter’s extrinsic incubation period convinced the commissioners to test Finlay’s mosquito theory. Finlay himself provided Lazear with the mosquito eggs for the experiments.

After infecting and incubating the mosquitoes, Lazear allowed them to feed on nine American volunteers, none of whom developed yellow fever. Carroll then agreed to be bitten. On August 29, he showed the first symptoms of the disease. Two days later, a second volunteer, Private William Dean of the Seventh Cavalry, showed signs of yellow fever. Lazear noted that Carroll’s and Dean’s mosquitoes had been incubated for at least ten days after having fed on infected persons before the third day of illness. The incubation periods proved to be the key that was missing in Finlay’s experiments.

Jesse Lazear’s gravestone, Loudon Park Cemetery, Baltimore.

Hench-Reed Collection, Historical Collections & Services, CMHSL

While Carroll and Dean recovered, Lazear was diagnosed with yellow fever. How he became infected remains a mystery. Some claimed that Lazear applied infected mosquitoes to his own arm and fell sick, but others, including Lazear himself, said that he was accidentally bitten while attending to patients in the yellow fever hospital. It is possible that Lazear reported his case as “accidental” in order for his family to inherit his life insurance benefits: a self-experimentation “suicide” might have nullified their claim. Lazear died of yellow fever at Columbia Barracks Hospital, September 25, 1900, after just seven days of illness.

Reed was shocked by Lazear’s death, but, with such encouraging results, he felt obligated to continue what Lazear and the rest of the team had begun. With Sternberg’s approval, he presented his team’s preliminary findings on October 23, 1900, at the Annual Meeting of the American Public Health Association in Indianapolis.

Reed’s sketch of the Infected Mosquito Building at Camp Lazear, from a letter to his wife, Emilie, December 1900.

Hench-Reed Collection, Historical Collections & Services, CMHSL

Reed returned to Cuba in November and ordered a new series of experiments that he hoped would convince the remaining skeptics. He secured over $10,000 from Governor-General Leonard Wood to continue research and established an isolated experimental station outside Havana which he named Camp Lazear. There the team not only reinforced the mosquito-yellow fever connection but also disproved the fomites theory. Volunteers confined for nearly three weeks in a small shack full of ”infected” clothing, pillows, and blankets from the yellow fever hospital did not develop the disease.

Las Animas Hospital Ambulance, Havana, ca. 1900.

Hench-Reed Collection, Historical Collections & Services, CMHSL

In addition, the team demonstrated that yellow fever could be induced by direct blood transfusion. They were not able, however, to isolate the causative agent. In August, six months after the Camp Lazear experiments, Carroll returned to Cuba to conduct further research at Havana’s Las Animas Hospital. He produced yellow fever in a volunteer whom he had injected with infected blood that he had first passed through a Berkefeld filter. The mystery as to why no one had been able to positively identify the yellow fever parasite was solved: the germ was filterable, or “ultra-microscopic.” Today Carroll’s “filterable agent” is commonly known as a virus.

Informed Consent

Hospital Corps Detachment at Camp Columbia, Havana, September 1900. Most of the volunteers for the yellow fever experiments came from this unit. Lt. Albert E. Truby, unit commander, is seated in the front row, second from left.

Hench-Reed Collection, Historical Collections & Services, CMHSL

The team needed human subjects in order to test the mosquito theory because, at the time, no one knew of any animals susceptible to the disease. The commissioners agreed to experiment on themselves before requesting volunteers. Agramonte was exempted since his childhood case had made him immune. When Reed departed for Washington to complete the typhoid report of 1898, only Carroll and Lazear were left to share the risk with their volunteers.

Several Spanish immigrants participated in the experiments, but the majority of volunteers came from Lieutenant Albert E. Truby’s Hospital Detachment at Camp Columbia. Governor-General Wood authorized Reed to offer the volunteers a $100 gold piece. To a poor Spanish immigrant or an underpaid army private, this was considerable incentive. Added to this was the likelihood of contracting yellow fever naturally during their assignment in Cuba, a point that Reed emphasized in the consent form. Better, said Reed, to contract yellow fever in a controlled environment where one could receive immediate medical attention from reputable physicians than to unexpectedly develop yellow fever in a remote camp where adequate care was unlikely. Even so, Reed stated the possibility that volunteers might die during the experiment. The members of the Yellow Fever Commission are considered the first advocates of informed consent because of their conscientious approach to human experimentation.

Volunteers

John R. Kissinger (1877-1946)

Hench-Reed Collection, Historical Collections & Services, CMHSL

The first volunteer at Camp Lazear was Private John R. Kissinger. Kissinger, an Ohioan from Truby’s hospital corps, developed yellow fever on December 8, 1900, after being bitten by several infected mosquitoes. He recovered ten days later, but the disease left permanent damage. He was granted a disability discharge the following year. In 1910, Congress rewarded Kissinger with a $100 per month pension for his services.

John J. Moran (1876-1950)

Hench-Reed Collection, Historical Collections & Services, CMHSL

Mr. John J. Moran, a civilian clerk in General Fitzhugh Lee’s headquarters, was bitten just six days after Kissinger, but he did not develop yellow fever. Moran later volunteered to be confined in Camp Lazear’s “Infected Mosquito Building.” There he was bitten repeatedly by 15 contaminated mosquitoes. On Christmas Day, 1900, he fell ill with yellow fever. Moran survived. 40 years later he assisted Dr. Philip S. Hench in his search for the actual site of Camp Lazear.

Clara Louise Maass (1876-1901)

Hench-Reed Collection, Historical Collections & Services, CMHSL

Ms. Clara Louise Maass was the only American woman to volunteer. Maass was a contract nurse with the U.S. Army who volunteered to participate in Dr. Juan Guiteras’s yellow fever experiments at Havana’s Las Animas Hospital in August of 1901. Guiteras hoped that his mosquitoes would cause only mild cases of yellow fever in order to demonstrate that lifetime immunity could be safely produced in a controlled environment. His experiments proved, however, that this was not possible. Several volunteers developed severe cases of yellow fever and died, including Clara Maass. Her death on August 24, 1901, created a public outcry that ended human experimentation in yellow fever research.

Introduction | Politics | In Cuba | Commission | Mosquitos | New Strategies | Impact | Credits