Walter Reed and the Yellow Fever Experiments
The First Recorded Use of Informed Consent
Aug 25, 2009
Prior to the 20th century, yellow fever was an incurable disease that ravaged populations in tropical and subtropical regions, typically during the spring and summer months. Except for cholera or the plague, few diseases have been as harmful as yellow fever.
What Causes Yellow Fever?
As early as 1879, the United States had sent a commission to Cuba to study yellow fever. Unlike other diseases, however, the symptoms of yellow fever could only be duplicated in humans. Thus, efforts to obtain a vaccine through animal experimentation were useless.
In 1900, the Yellow Fever Commission (YFC) was established with Major Walter Reed as its head. After preliminary investigation, the YFC traced the spread of yellow fever to the female Aedes aegypti mosquito. In order to confirm this hypothesis, however, human subjects needed to be tested by direct and indirect inoculation.
Walter Reed and Informed Consent
As human experimentation was necessary, Walter Reed was determined that volunteers should be obtained in Cuba at any cost. Reed authorized 22 Spanish immigrant workers to be injected with yellow fever. He offered the workers $100 in gold if they agreed to be bitten by mosquitoes and an additional $100 if they contracted the disease.
The yellow fever experiments were noteworthy for being the first instance where informed consent forms (in Spanish and English) were drafted. In return for payment, volunteers were required to be at least 25 years of age, fully informed of the experimental risks, and willing to consent to those risks.
Was Informed Consent Real?
The phrasing of the informed consent form, however, is not quite as altruistic as supporters have suggested. A volunteer was required to acknowledge that if he developed yellow fever, then “he endangers his life to a certain extent.” But as it was “entirely impossible” for any volunteer to avoid yellow fever while in Cuba, “he prefers to take the chance of contracting it intentionally in the belief that he will receive from the . . . Commission the . . . most skillful medical service.”
One of the YFC doctors admitted that the main purpose of the informed consent form was not so much to explain the dangers of the proposed experiment, but to lessen “moral responsibility” to the volunteers. As yellow fever then was incurable, the degree of endangerment was statistically far beyond the “certain extent” standard expressed in the form. Ironically, funeral expenses were not included as part of the payment, and there is a suspicion that the omission was deliberate to keep costs down.
How Much Did the Volunteers Understand?
Only three copies of the informed consent forms exist today. One of the surviving signed forms does not have a signature but only a mark, as the volunteer was illiterate. Thus, it is reasonable to question how much the immigrant workers truly understood.
One of the YFC physicians, Aristides Agramonte, described the selection process in an article he later wrote for Scientific Monthly. According to Agramonte, the YFC physicians would wait for a boat of immigrant workers to arrive in Cuba, and then hire “eight or ten men, as day laborers, to work in our camp.” The only work given to these day laborers, however, was a meaningless activity such as picking up “loose stones from the ground” while the laborers were “bountifully fed,” given a place to sleep, and casually interrogated about their family background and medical histories.
After potential subjects were identified, the experiment was explained to them. The exact nature of what was said is not known. According to Agramonte (1915), the volunteers felt that they would likely contract yellow fever if they stayed in Cuba, so “were not at all averse to allow themselves to be bitten by mosquitoes.”
The Yellow Fever Experiments
In fact, the lack of aversion may have been due less to resignation over the prospects of contracting yellow fever than with the lure of money. According to Pierce (2003), Colonel Jefferson Randolph Kean paid one of the surviving volunteers in gold and then noted how “The poor Spaniard had never seen such great coins or so much money and his joy was that of a child with a new toy.”
But not even money was enough to overcome all obstacles. By the time the fourth case of yellow fever was reported on December 15, 1900, Reed noted wryly that the remaining Spanish immigrants “lost all interest in the progress of science” and promptly fled camp.
Nevertheless, new volunteers were recruited. As before, these immigrant workers were seldom seen as human beings but only as “a new batch of susceptible material.” It is a testament to the care offered that not a single one of the final 22 volunteers died from yellow fever.
The Ethics of the Yellow Fever Experiments
Reed's experiments were successful in that they did bring about a vaccine for yellow fever. For the first time, it was recognized that volunteers needed to be informed about the nature of an experiment and agree to participate in it.
Yet, for all the benefits, the volunteers were vulnerable immigrant workers whose understanding was limited and who likely participated solely for financial reasons. Although treated well, they were patronized and dehumanized in the process. Sadly, this attitude has persisted in science ever since.
References
Agramonte A. 1915. The inside history of a great medical discovery. Scientific Monthly. 1:209–37.
Guereña-Burgueño F. 2002. The centennial of the Yellow Fever Commission and the use of informed consent in medical research. Salud Publica Mex. 44(2):140–44.
Pierce JR. 2003. “In the interest of humanity and the cause of science”: the yellow fever volunteers. Military Medicine. 168(11):857–63.
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