Walter Reed and the Scourge of Yellow Fever

Walter Reed and the Scourge of Yellow Fever

Editor’s note: Even an institution as historic as the University of Virginia – now entering its third century – has stories yet to be told. Some are inspiring, while the truths of others are painful, but necessary for a fuller accounting of the past. The President’s Commissions on Slavery and on the University in the Age of Segregation were established to find and tell those stories. Here are some of them, written by those who did the research. One in an occasional series:

 

At midnight on Dec. 31, 1900, Major Walter Reed, an 1869 alumnus of the University of Virginia, sat down in his quarters in Cuba and wrote to his wife:

“Here I have been sitting reading that most wonderful book-La Rouche on Yellow Fever-written in 1853-Forty-seven years later it has been permitted to me and my assistants to lift the impenetrable veil that has surrounded the causation of this most dreadful pest of humanity and to put it on a rational and scientific basis-I thank God that this has been accomplished during the latter days of the old century-May its cure be wrought out in the early days of the new century!”1

Walter Reed had good reason to celebrate that New Year’s Eve. He and his colleagues had proven that yellow fever was spread by mosquitoes, providing hope that one day humanity would control one of its most frightening diseases.

Today, most Americans have little knowledge of Walter Reed or his role in the fight against yellow fever. However, his story was once widely known.

Walter Reed was born in Virginia in 1851. At the age of 15, Reed enrolled in the University of Virginia, and after two years of study earned an M.D. In that time, he took James Lawrence Cabell’s course in physiology and surgery, John Staige Davis’s course in anatomy, and James Harrison’s course in medicine.2 Beyond a listing of the courses he took at the University, little is known about Reed’s time at UVA.

Related Story

Walter Reed at the University of Virginia, circa 1868; Reed’s 1869 diploma declaring him a Doctor of Medicine; the Anatomical Theater served as UVA’s medical education building in the 19th century. (Photos courtesy of the University of Virginia Library)

Reed continued his studies in New York City, earning a second medical degree from the Bellevue Hospital Medical College. Then, in 1875, Reed became a doctor in the U.S. Army Medical Corps, where he spent the rest of his career.

For nearly 20 years, Reed served as an army surgeon stationed in various military posts across the Western states and territories of the United States. Around the age of 40, Reed abandoned his life as a practicing clinician to focus on biomedical research, and in a short time, he became well-respected in the Army for his research on a wide range of infectious diseases. At the end of his career, he become famous for his work with yellow fever, a disease that had plagued Americans for centuries.3

Yellow fever, like Walter Reed, is not well-known in the United States today. In the 18th and 19th centuries, though, outbreaks of yellow fever were common in this country. While other maladies were more prevalent and more deadly, few could generate as much terror. It spread rapidly and could kill 20% of a city’s population in just two to three months.

A series of yellow fever outbreaks in Philadelphia in the 1790s famously shut down the federal government and killed nearly 10% of the city’s population.4

As terrible as those Philadelphia outbreaks had been, they were not even the deadliest in U.S. history. The deadliest outbreak of yellow fever occurred in the summer and fall of 1878, infecting 120,000 and killing between 13,000 and 20,000 Americans in the lower Mississippi Valley.5

These outbreaks and others in the United States were especially frightening to Americans because no one could explain the cause of yellow fever or how it spread.

At the end of the 19th century, a growing community of medical researchers, including Walter Reed, worked relentlessly to provide answers. Most of them believed that yellow fever was caused by bacteria and spread by fomites – objects soiled with human blood and excrement. However, after decades of research, there was no scientific evidence to support this theory.6

Many white physicians and scientists moreover believed that individuals of African descent were less susceptible to the disease than other populations.

There was no scientific evidence to support this theory, but it became popular among Europeans in the 18th century who were trying to legitimize African enslavement in areas where yellow fever was endemic.

African Americans from at least the 1790s onward published several works that dispelled this longstanding race-based theory. While there is evidence that Walter Reed held racist views, it is not yet known what he thought of this idea or other race-based theories.7

Meanwhile at the fringes of the biomedical community, a Cuban physician by the name of Carlos Finlay proposed a radically different theory, arguing that yellow fever was spread by mosquitoes.

Finlay was correct, but he could not produce experimental results that were conclusive enough to challenge the beliefs of the mainstream scientific community.

He acknowledged the uphill battle he faced, remarking in 1881:

“I understand too well that nothing less than an absolutely incontrovertible demonstration will be required before the generality of my colleagues accept a theory so entirely at variance with the ideas which have until now prevailed about yellow fever.”8

Nineteen years later, Reed and his associates on the U.S. Army Yellow Fever Commission would finally provide an “incontrovertible demonstration” to prove Finlay’s theory, only after a U.S. public health campaign in Cuba based on the fomite theory failed to control the spread of yellow fever.

After the Spanish-American War, Spain transferred control of Cuba to the United States, and it was agreed that the island would remain a U.S. protectorate until the United States decided to grant Cuba its independence. During the first U.S. occupation of Cuba, from 1899 to 1904, U.S. authorities on the island prioritized funding for yellow fever in Cuba – committing unprecedented amounts of money to the study and control of the disease.

This focus on yellow fever was not altruistic, it first and foremost served U.S. national interests. Historically, while most native Cubans contracted yellow fever as children and survived the disease with a lifelong immunity, adult foreigners in Cuba succumbed to the disease in great numbers.

The United States feared that without effective yellow fever controls, the 50,000 troops it had stationed on the island were in great peril and might spread the disease to the mainland.9

The U.S. occupation government, confident that the unproven fomite theory was correct, implemented a massive public health campaign to improve sanitation on the island. Although the campaign facilitated the decline of other infectious diseases in Cuba, it did not impact yellow fever.10

In May 1900, the U.S. Army, frustrated by this failure, formed the U.S. Army Yellow Fever Commission to gather data in Cuba that might inspire improvements in the public health campaign. A little-known medical army medical researcher, Major Walter Reed, was appointed to lead the group.

The Army appointed three physicians to serve on the commission under Reed’s direction: James Carroll, Reed’s longtime research assistant; Arístides Agramonte y Simoni, an Army contract surgeon who had been studying yellow fever in Cuba since the beginning of the occupation; and Jesse Lazear, another Army contract surgeon who was studying the causes of yellow fever outside of Havana.

Physicians James Carroll, Aristides Agramonte y Simoni and Jesse William Lazear served on the U.S. Army Yellow Fever Commission under Reed’s direction. Carroll volunteered to become a test subject himself. Lazear died from yellow fever in 1900.

U.S. Army Surgeon General George Miller Sternberg first ordered the commission to investigate potential bacterial causes of yellow fever. In June and July of 1900, Reed and his colleagues tested the blood of infected yellow fever patients, but could find no bacterial agent. They observed in their studies that exposure to fomites did not seem to have any relation to yellow fever infection. With no evidence to support the popular theories about yellow fever, Walter Reed concluded that:

“[A]t this stage of our investigation it seemed to me, and I so expressed the opinion to my colleagues, that the time had arrived when the plan of our work should be radically changed”11

At this time, most likely at the urging of Jesse Lazear, the commission turned its attention to Finlay’s mosquito theory. New discoveries encouraged them to pursue this avenue of research. Recently, it had been proven by Britain’s Ronald Ross that malaria was spread by mosquitoes, showing that it might be possible that other diseases are spread by the insect. While another researcher, University of Virginia alumnus Henry Rose Carter, had recently discovered that there was a delay of 10 to 17 days between the first infection of yellow fever in an outbreak and its spread to secondary hosts. Carter’s discovery suggested that Carlos Finlay’s attempts to prove his mosquito theory may have failed because his experiments were not designed in a manner that accounted for this delay.

In August of 1900, Walter Reed temporarily returned to Washington, D.C., while Jesse Lazear and James Carroll began conducting experiments with mosquitoes in Havana’s Las Animas Hospital. After several failed attempts to infect volunteer subjects with yellow fever, Carroll decided to experiment on himself and contracted yellow fever from an infected mosquito. Carroll survived the infection, but would suffer from complications of yellow fever for the rest of his life.12

Four days after Carroll was bitten, a U.S. soldier, William Dean, volunteered to subject himself to the experiment and contracted yellow fever. Dean would also survive.

Dean and Carroll became infected while the other volunteers remained healthy because the commission allowed for the disease to incubate longer in the mosquitoes that bit Dean and Carroll, which was consistent with the discovery made by Henry Rose Carter.

News of Carroll and Dean’s infections reached Walter Reed in Washington, D.C. After hearing that Carroll would survive, on Sept, 7, 1900, Reed excitedly wrote to his longtime assistant:

“Hip! Hip! Hurrah! God be praised for the news from Cuba today—“Carroll much improved—Prognosis very good!” I shall simply go out and get boiling drunk!13

After sealing the letter, Reed scribbled on the envelope one final remark:

“Did the Mosquito DO IT?”14

Excitement and joy would soon give way to tragedy. On Sept. 18, Jesse Lazear contracted yellow fever, and died from the disease on Sept. 25.15

For over 100 years, historians have debated the circumstances that led to Lazear’s death. In Lazear’s notebook, he records that he administered a bite from an infected mosquito to a test subject known as “Guinea Pig No. 1” around Sept. 18. It has been widely believed that “Guinea Pig No. 1” was in fact Lazear himself.16

The infection of Carroll and Dean suggested that Finlay, long mocked by his colleagues as the “Mosquito Man,” was right. However, these preliminary experiments would not be enough to upend the popular fomites theory. After Reed presented the early results at a conference in October 1900, an editorial was published in the Washington Post that ridiculed the findings:

“Of all, the silly and nonsensical rigmarole about yellow fever that has yet found its way into print — and there has been enough of it to load a fleet — the silliest beyond compare is to be found in the arguments and theories engendered by the mosquito hypothesis.”17

Walter Reed set out to design a series of experiments that would incontrovertibly prove Finlay’s theory.

First, the surviving members of the commission ordered the construction of an isolated experimental camp outside of Havana “in order to exercise perfect control over the movements of those individuals who were to be subjected to experimentation, and to avoid any other source of infection.”18 The facility was named Camp Lazear in honor of their deceased colleague.

The isolated, experimental “Camp Lazear” outside of Havana, where the commission continued experiments “in order to exercise perfect control over the movements of those individuals who were to be subjected to experimentation.” (Photo courtesy of Wellcome Images via Creative Commons)

Then, the commission began to recruit human test subjects for the experiments.

Human experimentation at that time was not uncommon in medical research, but the way it was generally practiced in the 19th century would be considered abhorrent today. Many researchers experimented on enslaved persons, the incarcerated, orphans and other vulnerable populations without their consent or knowledge.

The Yellow Fever Commission did not engage in these practices. Instead, they put out calls for U.S. soldiers and recent Spanish immigrants to volunteer for the study. The commission wanted non-immune subjects who had no history of previously being infected with yellow fever.

The men who volunteered were informed about the experiments beforehand and compensated monetarily for their contribution. Then, for the first time in history, all of the volunteers were given written contracts to sign that contained the terms of their involvement in the study. The Spanish volunteers were given two copies of the contract, one written in Spanish and the other in English, to ensure that they understood the agreement.19 The experiments would not begin until all the volunteers had given their written consent.20

Nearly everyone involved with the experiments understood the gravity of their work. Several of the U.S. soldiers who volunteered refused monetary compensation and exposed themselves to yellow fever to help advance “medical science.” Later, in a recommendation for one of the soldiers who volunteered without pay, John Moran, Walter Reed wrote:

“A man who volunteered, as he did, without hope of any pecuniary reward, but solely in the interests of humanity and medical science, to enter a building purposely infected with yellow fever … should need no word of recommendation from any one.”21

On Nov. 20, 1900 preparations were complete and experiments began at Camp Lazear.

In the first experiment, a group of volunteers received bites from mosquitoes that had previously bitten yellow fever patients. Four of the volunteers contracted yellow fever.22

In the second experiment, four volunteers were injected with the blood of patients who had been infected with yellow fever. Three of the volunteers contracted yellow fever suggesting that the disease could be transmitted through direct contact with fresh blood.23

In the third experiment, the commission hoped to put to rest the fomites theory. Two buildings, personally designed by Walter Reed, were constructed; in the first building, three volunteers were sealed in a room and asked to sleep in linens covered with the excrement and dried blood of patients who had died of yellow fever and wear the clothes of the deceased patients. Although the three volunteers in this room had a very unpleasant experience, none of them contracted yellow fever.24

In the other building there were two rooms. The commission released infected mosquitoes into one room, and kept the second room completely empty. Volunteers who spent time in the mosquito room contracted yellow fever while the volunteers in the empty room did not.25

Combined, the three experiments provided strong proof for Carlos Finlay’s theory, and remarkably none of the infected volunteers died during the study.

The occupation government was now eager to put the findings of the Yellow Fever Commission to practical use. Major William Gorgas, the chief sanitary officer of Havana, admitted that after the preliminary experiments, he was skeptical of the mosquito theory, but the experiments at Camp Lazear convinced him otherwise. In December 1900, as the results at Camp Lazear began to be known, Gorgas wrote to Henry Rose Carter:

“So I think if you want to be in at the killing, you had better come down [to Cuba] this winter. I think we are about to make a historic campaign against yellow jack in Havana next summer, and such a seasoned old veteran as you ought to have a part in such a climax.”26

Gorgas was right – the public health campaign of 1901 was historic. The occupation government instituted an unprecedented mosquito control program in Havana. Brigades of Cuban workers fumigated houses, eliminated sources of standing water, and quarantined infected yellow fever patients in rooms protected by mosquito nets.

The results were dramatic. In less than a year, yellow fever had been virtually eradicated in Havana, providing the ultimate demonstration that Finlay’s mosquito theory was correct.

In the years that followed, mosquito control campaigns eradicated yellow fever in North America and the Caribbean. Generations of people were spared the terror and suffering that came with a yellow fever epidemic, and the disease has become largely forgotten in Walter Reed’s native country.

The yellow fever experiments catapulted Walter Reed to the heights of fame. After his death in 1902, Reed was widely memorialized and soon became more a myth than a man. U.S. journalists, artists and educators, looking for a single heroic figure to symbolize the promise of modern medicine, embellished their stories about Reed. In the drive to make him a hero, Americans too often diminished the vital contributions of Carlos Finlay, Jesse Lazear, James Carroll, Arístides Agramonte y Simoni, and the experimental volunteers.

Also, too often, popular accounts diminished the serious questions surrounding the use of humans in medical experimentation. When Reed first presented the commission’s findings to an audience of his colleagues, he received both praise and criticism. The first comment on the commission’s monumental paper came from Dr. Louis Perna of Cienfuegos, Cuba, who “criticized the methods employed by the commission in making experiments on human beings and is entirely opposed to such experiments.”27 Reed’s Cuban and American colleagues in attendance strongly defended the commission experiments against Perna’s critique, praising the high standards set by this work. Reed himself defended the commission’s efforts by noting that his decision to employ human experimentation was not taken lightly, and he assured those in attendance that “all experiments were performed on persons who had given their free consent.”28

The experiments that Walter Reed and his colleagues designed did not reach the higher ethical standards that have been established for modern experiments, but they were an improvement over what came before. Their work provided an example for how medical research could be done with greater respect for human dignity. This, with the confirmation of Finlay’s theory, are the greatest legacies of Walter Reed and his colleagues’ work in Cuba.

 

Dan Cavanaugh is the Alvin V. and Nancy Baird Curator of Historical Collections at the Claude Moore Health Sciences Library.

 

__________________________

Notes

1. Letter from Walter Reed to Emilie Lawrence Reed, December 31, 1900. Philip S. Hench Walter Reed Yellow Fever Collection, 1806-1995. Box-folder 22:62. Historical Collections, Claude Moore Health Sciences Library, University of Virginia.

2. University of Virginia. (1869). Catalogue of the University of Virginia, 1868-1869. Baltimore: The Sun Book and Job Printing Establishment. p. 14.

3. For a more comprehensive biography of Walter Reed see: Bean, William B. (1982). Walter Reed: A Biography. Charlottesville: University of Virginia Press.

4. Carey, Mathew. (1794). A Short Account of the Malignant Fever: Lately Prevalent In Philadelphia… To Which Are Added, Accounts of the Plague In London and Marseilles. 4th ed., improved. Philadelphia: Printed by the author. and Jones, Absalom, Richard Allen, and Matthew Clarkson. (1794). A Narrative of the Proceedings of the Black People, During the Late Awful Calamity In Philadelphia, In the Year 1793: and a Refutation of Some Censures, Thrown Upon Them In Some Late Publications. Philadelphia: Printed for the authors, by William W. Woodward, at Franklin’s Head, no. 41, Chesnut-Street.

5. Carrigan, Jo Ann. (1961). The Saffron Scourge: a History of Yellow Fever In Louisiana, 1796-1905. 1961. Thesis–Louisiana State University of Agricultural and Mechanical College. pg. 184. Other more recent works about the 1878 epidemic include: Bloom, Khaled J. (1993). The Mississippi Valley’s Great Yellow Fever Epidemic of 1878. Baton Rouge: Louisiana State University Press. and Crosby, Molly Caldwell. (2006). The American Plague: the Untold Story of Yellow Fever, the Epidemic That Shaped Our History. New York: Berkley Books.

6. Reed, Walter. (1911). “The propagation of yellow fever — observations based on recent researches,” in United States Senate Document No. 822, Yellow Fever A Compilation of Various Publications. Washington: Government Printing Office. p. 92.

7. Letter from Walter Reed to Laura Reed Blincoe, April 4, 1902. Philip S. Hench Walter Reed Yellow Fever Collection, 1806-1995. Box-folder 140:20. Historical Collections, Claude Moore Health Sciences Library, University of Virginia.

8. Finlay, Carlos J. (1881). “The Mosquito Hypothetically Considered as the Agent of Transmission of Yellow Fever.” Translated by Carlos J. Finlay. Trabajos Selectos Del Dr. Carlos J. Finlay: Selected Papers of Dr. Carlos J. Finlay. Habana, Cuba, 1912. pg 42. Reprint of an article by Carlos J. Finlay that was first published in: Anales de la Academia de Ciencias Médicas, Físicas y Naturales de la Habana, Volume 18, 1881.

9. In her study on the relationship between yellow fever and Cuban independence, Mariola Espinosa argued that the U.S. Army occupation government’s efforts to control yellow fever in Cuba were largely motivated by a concern about the spread of the disease to the United States. See Espinosa, Mariola. (2009). Epidemic Invasions: and the Limits of Cuban independence, 1878-1930. Chicago: University of Chicago Press.

10. See Havard, V. (1901). “Sanitation and yellow fever in Havana, report of Major V. Havard, Surgeon U.S.A.” In Civil Report of Major General Wood, Military Governor of Cuba 1900, Vol. 4. Havana: United States Government. p. 12-13.

11. Reed, Walter. (1911). “The propagation of yellow fever — observations based on recent researches,” in United States Senate Document No. 822, Yellow Fever A Compilation of Various Publications. Washington: Government Printing Office. p. 94.

12. Reed, Walter; Carroll, James; Agramonte, Aristides; and Lazear, Jesse W. (1900). “The etiology of yellow fever — a preliminary note,” Proceedings of the Twenty-eighth Annual Meeting of the American Public Health Association Indianapolis, Indiana, October, 22, 23, 24, 25, and 26, 1900.

13. Letter from Walter Reed to James Carroll, September 7, 1900. Philip S. Hench Walter Reed Yellow Fever Collection 1806-1995. Box-folder 153:12. Historical Collections, Claude Moore Health Sciences Library. The originals of these letters remain in a private collection.

14. Ibid.

15. Fever Chart for Jesse Lazear, September 19, 1900-September 25, 1900. Philip S. Hench Walter Reed Yellow Fever Collection, 1806-1995. Box-folder3:47. Historical Collections, Claude Moore Health Sciences Library.

16. Crosby, Molly Caldwell. (2006). The American Plague: The Untold Story of Yellow Fever. The Epidemic that Shaped Our History. New York City: Berkley Books. pp. 191-197.

17. November 2, 1900. “The Mosquito Hypothesis.” The Washington Post. pg. 6.

18. Reed, Walter; Carroll, James; and Agramonte, Aristides. (1911). “The etiology of yellow fever — an additional note,” in United States Senate Document No. 822, Yellow Fever A Compilation of Various Publications. Washington: Government Printing Office. pp. 70-89. p. 70.

19. For a copy of the Spanish contract see: Informed consent agreement between Antonio Benigno and Walter Reed, November 26, 1900. Philip S. Hench Walter Reed Yellow Fever Collection 1806-1995. Box-folder 70:3 [oversize].  Historical Collections, Claude Moore Health Sciences Library, University of Virginia. For an English translation of the contract see: English translation [from Spanish] of informed consent agreement between Antonio Benigno and Walter Reed, November 26, 1900. Philip S. Hench Walter Reed Yellow Fever Collection 1806-1995. Box-folder 70:4 [oversize].  Historical Collections, Claude Moore Health Sciences Library, University of Virginia.

20. Letter from Walter Reed to Emilie Lawrence Reed, December 2, 1900. Philip S. Hench Walter Reed Yellow Fever Collection 1806-1995. Box-folder 22:24. Historical Collections, Claude Moore Health Sciences Library, University of Virginia.

21. Moran, John J. (circa 1950). Memoirs of a Human Guinea Pig. [unpublished autobiography]. p. 1. Philip S. Hench Walter Reed Yellow Fever Collection 1806-1995. Box-folder 25:71.

22. Reed, Walter; Carroll, James; and Agramonte, Aristides. (1911). “The etiology of yellow fever — an additional note,” in United States Senate Document No. 822, Yellow Fever A Compilation of Various Publications. Washington: Government Printing Office. pp. 70-89. pp. 71-81.

23. ibid, p. 82.

24. ibid, pp. 83-87.

25. ibid  

26. Letter from William C. Gorgas to Henry R. Carter, December 13, 1900. Philip S. Hench Walter Reed Yellow Fever Collection 1806-1995. Box-folder 22:37. Historical Collections, Claude Moore Health Sciences Library.

27. Reed, Walter; Carroll, James; and Agramonte, Aristides. (1911). “The etiology of yellow fever — an additional note,” in United States Senate Document No. 822, Yellow Fever A Compilation of Various Publications. Washington: Government Printing Office. pp. 70-89. pp. 87-88.   

28. Ibid, pp. 88-89.

 

Photo at of Camp Lazear published under Creative Commons.

Media Contact

McGregor McCance

Associate Vice President for Communications and Executive Editor, UVA Today Office of University Communications