"In the interest of humanity and the cause of science": The yellow fever volunteers

Military Medicine, Nov 2003 by Pierce, John R

AMSUS History of Military Medicine Essay Award 2001

This essay award should have been published in 2002 but was inadvertently omitted. Military Medicine regrets the oversight.

The scientific discoveries of the U.S. Army Yellow Fever Board of 1900 are well known as are the Army physicians who led the board. Walter Reed, of course, is the best known, but James Carroll, Aristides Agramonte, and Jesse Lazear are also known, if not nationally, to their local communities. This article deals not with the known but with the unknown, meaning the volunteers who subjected themselves to the ravages of yellow fever and the real possibility of death. The year 1900 was known as a "yellow fever year" among the locals in Cuba because in the preceding year the epidemics had been relatively mild. Beginning its work in June 1900 in the midst of a deadly epidemic, the board conducted a truly remarkable set of experiments that set a benchmark for controlled clinical trials and informed consent. Because no animal model was known to be susceptible to yellow fever, they used human volunteers for their experiments. These volunteers were recruited from among Spanish immigrants and were accepted from soldiers and two civilians who volunteered. Over 30 men participated in the experiments, and 22 developed yellow fever. With expected death rates of 20% to 40%, it is incredible that none of these volunteers died. In 1929, the U.S. government honored the Americans who volunteered by placing their names on a Roll of Honor published annually in the Army Register. The successes of the 1900 U.S. Army Yellow Fever Board were truly remarkable, and many of the successes were made possible by the men who volunteered, some repeatedly, to risk their lives "in the interest of humanity and the cause of science."

Introduction

The scientific discoveries of the U.S. Army Yellow Fever Board of 1900 are well known.1-5 Led by Major Walter Reed, their conclusions have stood the test of a century of time, having never been disproved or even modified in any significant way. Their most significant discoveries were: (1) a domestic mosquito, now known as Aedes aegypti, serves as the intermediate host for the agent of yellow fever, (2) yellow fever is transmitted to the nonimmune individual by means of the bite of a mosquito that has previously fed on the blood of those sick with this disease, (3) an interval of about 12 days or more after contamination appears to be necessary before the mosquito is capable of conveying the infection, (4) yellow fever can also be experimentally produced by the subcutaneous injection of blood and blood filtrate taken from the general circulation during the first and second days of this disease, (5) yellow fever is not conveyed by fomites (contaminated clothing and bedding), and hence disinfection of clothing, bedding, or merchandise, supposedly contaminated by contact with those sick with this disease, is unnecessary, and (6) the spread of yellow fever can be most effectually controlled by measures directed to the destruction of mosquitoes and the protection of the sick against the bites of these insects.

We know much of the Army doctors who were on the board (Walter Reed, James Carroll, Jesse Lazear, and Aristides Agramonte)5-8 (Fig. 1, No. 1, 2, 3, and 4), but what of the human volunteers for their experiments? Because no animal model had been found that was susceptible to yellow fever, human volunteers had to be used. Early in the experiments James Carroll volunteered to be bitten and nearly died from the subsequent illness.1,5-8 Jesse Lazear did die from yellow fever, but he was not an experimental subject. On his deathbed, he told the others that his case was naturally acquired, but the circumstances of his acquisition of yellow fever were mysterious and never fully understood.1,5-8 Neither the genius of their experimental design nor the brilliance of their thoroughness could have bequeathed the board the extraordinary luck they had, for not a single one of their volunteers died.

Reed asked Governor-General Leonard Wood (Fig. 1, No. 6) to seek approval from the Spanish Consul for the board to recruit volunteers from the local population of Spanish immigrants. Volunteers were to receive payment ($100.00 in gold and another $100.00 if they became ill) and the best care possible if they became sick. General Wood, also a physician, recognized the significance of their work and as a military leader knew the importance of its completion. He eagerly offered his support and $10,000 or more, if needed, to finish the job.5-8

Although Reed did not actively seek volunteers among the U.S. soldiers, a young private (John R. Kissinger) stepped forward and volunteered. He refused to accept any payment, stating that his actions were "solely in the interest of humanity and the cause of science."9 A former corpsman and then civilian clerk, John J. Moran, quickly followed suit. Despite the fact that they were not specifically recruited, many other soldiers also volunteered. In fact, more Americans volunteered, 18 all together (1 officer, 15 enlisted men, and 2 civilians), than Spaniards. There were seven Spanish volunteers who contracted yellow fever. Several others volunteered, but because they did not become ill, they were not specifically identified.1-4