Voluntary Paid Human Experimentation versus Yellow Fever

In case you’ve never had yellow fever, here’s what to expect:

Yellow fever begins after an incubation period of three to six days. Most cases cause only a mild infection with fever, headache, chills, back pain, fatigue, loss of appetite, muscle pain, nausea, and vomiting. In these cases, the infection lasts only three to six days.

But in 15% of cases, people enter a second, toxic phase of the disease characterized by recurring fever, this time accompanied by jaundice due to liver damage, as well as abdominal pain. Bleeding in the mouth, nose, the eyes, and the gastrointestinal tract cause vomit containing blood, hence one of the names in Spanish for yellow fever, vómito negro ("black vomit"). There may also be kidney failure, hiccups, and delirium.

Among those who develop jaundice, the fatality rate is 20 to 50%, while the overall fatality rate is about 3 to 7.5%. Severe cases may have a mortality greater than 50%.

Surviving the infection provides lifelong immunity, and normally results in no permanent organ damage.

For comparison, the overall fatality rate for unvaccinated Covid is under 1%. Unlike Covid, healthy young people are, if anything, especially vulnerable to yellow fever.

But fear not! In 1901, medical researchers figured out how yellow fever spreads. The answer, in case you haven’t heard, is mosquitos. Vaccines didn’t come until the 1930s, but many countries managed to practically eliminate yellow fever simply by eliminating the insects that carry the disease. The critical question really was simply “How does yellow fever spread?”

How, you may ask, did researchers pin the blame on the humble mosquito? By the power of Voluntary Paid Human Experimentation! This 2009 piece by Akhil Mehra in the AMA Journal of Ethics begins with the standard story:

At the termination of the Spanish-American War in 1900… the American Surgeon General dispatched Major Walter Reed and a team of young doctors to investigate the diseases, particularly the pathogenic mechanism of yellow fever. Reed’s team pursued a program of human experimentation by intentionally exposing human subjects, team members included, to potentially deadly virulent material. Despite several prominent fatalities during the experiment’s run, Reed’s experiments were a scientific success and instrumental in establishing that yellow fever was a mosquito-borne illness… For years following the experiments, the honor, bravery, and heroism of the volunteers were extensively celebrated in publicity campaigns, charity drives, a government-published “Yellow Fever Roll of Honor,” popular books, a movie, and a Broadway play.

How does the standard story fall short? It fails to show us the money - and money was a critical ingredient for the investigations’ success.

There were three phases of the experiments. In Phase I, the researchers were still dismissive of the mosquito theory. They tested it primarily to eliminate mosquitos as a possible disease vector, using volunteer soldiers and the researchers themselves as subjects. Johns Hopkins doctor Jesse Lazear inoculated himself with infected mosquitos twice, and died the second time around.

At this point, Phase II began - and so did cash payments:

The volunteers were now paid $200 to participate and $500 if they contracted yellow fever. This substantial payment, made in gold, would approximate $8,000 and $20,000, respectively, in today’s dollars. Recent Spanish immigrants to Cuba were also sought as volunteers and were likewise well-compensated.

Phase II was the crucial part of the research:

Reed was angry with his colleagues for the conduct of the first phase of the experiments. His major contribution was in the second phase, during which he designed the ingenious set of rigorously controlled experiments that satisfied international scientific criteria. But the diversity of volunteers was notable. Both Americans and Spaniards may well have been motivated by monetary inducement and fears that they were likely to get yellow fever regardless.

A Phase III followed, but the article doesn’t clearly state whether monetary payments for volunteers continued. Either way, one of the greatest historic triumphs of medicine clearly relied heavily on paying volunteers. Sure, the volunteers were heroes. But what’s so awful about giving heroes large cash rewards? If it’s OK to pay firefighters or bodyguards for risking their lives to save the vulnerable, why not participants in dangerous medical experiments?

Though some bioethicists will no doubt be eager to square this circle, they honestly don’t know what they’re talking about. Resistance to Voluntary Paid Human Experimentation is one of the clearest-cut cases of anti-market bigotry. If paying volunteers to risk their lives for the greater good is wrong, what isn’t?!