Comparing the Guatemala and Tuskegee Projects

The revelations of the barbaric Guatemalan project have brought back into the news another sordid episode in American medical history, the infamous study of “Untreated Syphilis in the Male Negro,” popularly known as the Tuskegee Project. In this thirty year effort, PHS researchers observed a population of 400 poor, black men from rural Alabama who were infected with syphilis to see how the disease affected their health

That the two studies were close cousins is borne out by the fact that the lead investigator on the Guatemalan effort, John C. Cutler, was also an active member of the Tuskegee team.  Comparing the two projects is instructive. Unlike the Guatemalan project, the Tuskegee study subjects were never infected with syphilis; by contrast, most of the Guatemalan subjects did in fact receive treatment (including penicillin) while the Tuskegee subjects were intentionally left untreated. These differences went back to the reason each study was designed in the first place: the Guatemalan researchers, working from 1946-48, wanted a well-controlled test of the effectiveness of a revolutionary new therapeutic, penicillin, as a syphilis treatment; the Tuskegee researchers, beginning in 1932 before the 1944 discovery of penicillin’s therapeutic application to syphilis, wanted to observe the natural course of syphilis infection in patients who were left untreated.

As the Guatemalan study has been disclosed, the ethical lapses of these two syphilis studies have been treated as indistinguishable. At the time, however, they were seen quite differently. The Guatemalan project was never disclosed and never published. Those involved discussed their discomfort openly. Cutler’s supervisor wrote in 1948, ““I am a bit, in fact more than a bit, leery of the experiment with the insane people. They cannot give consent, do not know what is going on, and if some goody organization got wind of the work, they would raise a lot of smoke.”

By contrast, the Tuskegee team was immensely proud of their work. They published twelve papers in peer reviewed journals between 1936 and 1964: the last two of these were published in journals of the American Medical Association. And the research team was clearly proud of their work, praising themselves for their “quality of dedication to the ideal of a long-term study based upon love of and respect for the dignity of the individual within the group, and upon the satisfaction of making a single, valuable contribution to the increment of knowledge, without concern for credit…”

It took many years (from the late 1950s, at the latest, to 1972) for the PHS to realize that withholding penicillin from a black man infected with syphilis wasn’t respectful of his dignity.

Judging the Ethics of Medical Experiments in Hindsight

Looking back, the Tuskegee Project is indefensible in virtually every respect. But there is one intriguing feature of the study design that has long been overlooked. Before it became obvious that penicillin stopped the syphilitic spirochete, treponema pallidus, in its tracks, the act of keeping approved treatments away from syphilis patients actually did them less harm than good. Because for centuries, the standard of care for syphilis treatment involved the internal administration of an extremely toxic compound, mercuric chloride, a practice that continued into the 1950s.

Yes, you heard that right. So let’s say it again.

For centuries, syphilis doctors gave their patients mercuric chloride as a medicine. First they gave it as a liquid. Then, starting in the 1860s, frustrated that their patients kept dying, doctors began administering mercuric chloride injections to their syphilis patients.

Nowhere in the Frieden and Collin’s JAMA editorial is this practice, so obviously barbaric today, condemned or even mentioned. Yet there is little doubt that the toll of human suffering (many thousands of fatalities) at the hands of the medical profession from mercuric chloride, the approved standard of care for syphilis at the time, was far greater in comparison to the victim count of the despicable PHS experiments, mere hundreds of syphilis-infected Guatemalans and untreated Alabamans.

One might be tempted to say that at least one bright ethical line here was the act of infection itself: that any doctor who deliberately infected a patient with a dangerous microbe violated their oath as a physician. Yet oddly enough, even the deliberate introduction of a dangerous microbe was fair territory for syphilis doctors in those days. Indeed, Julius Wagner-Jauregg won the 1927 Nobel Prize in Medicine for his idea of infecting syphilis patients with malaria. Wagner-Jauregg’s proposal (which may actually have helped in some cases) was that the high fevers of malaria could kill the syphilitic spirochete in the brain when mercuric chloride (and also arsenic) medicines couldn’t reach that far.

Today, treatments of mercuric chloride and malaria are treated by the medical profession not with public apologies but rather a kind of embarrassed silence. As one historian notes, the idea of breeding “colonies of malarial mosquitoes with which to infect tertiary syphilitics and so burn the offending parasites from their brains” doesn’t look very good with the benefit of hindsight. As we argue in our book, The Age of Autism: Mercury, Medicine and a Manmade Epidemic, most historic uses of mercury don’t look very good either.

So what’s the real difference between therapies that merit a Nobel Prize and those that elicit public apologies from our countries’ top medical leaders? Interestingly, the Tuskegee Project, which for a time mostly benefited its subjects by withholding the approved therapies of arsenic and mercury injections, has come under fire largely because of its failure to treat the infected men regardless of the safety or efficacy of the approved treatment.  So what does that tell us about how the medical profession distinguishes between ethical and unethical acts?

The main distinction appears to be whether or not the medical profession approved of the treatment at the time.

Seen this way, should the assurances offered by Frieden and Collins persuade us that “the basic ethical principle of respect for persons” is so well entrenched that we are now safe from human experiments designed by the medical profession? What about the largest human experiment ever conducted in America: the unprecedented, uncontrolled, untested expansion of the childhood immunization program that started around 1990? When it comes to ethics, it would appear we are safe only from those experiments of which the doctors who set today’s medical standards don’t approve. For those approved treatments that we learn many years later to be barbaric, the watchword remains, “buyer beware.”

As for the current experiment--one that dwarfs Guatemala and Tuskegee in both its scale and its hubris--it would appear that medical authorities are content to continue the experiment as long as they can convince themselves (as they did for years with arsenic and mercuric chloride injections for syphilis) that it is unethical to measure rigorously the overall impact of the experiment: by comparing total health outcomes in untreated patients with those who are treated. Unfortunately for the subjects of the experiment, these doctors believe that “respect for persons” requires that otherwise healthy American infants receive every single ounce of treatment  new medical technology can provide them.

Dan Olmsted is Editor and Mark Blaxill is Editor-At-Large of Age of Autism. They are co-authors of The Age Of Autism Mercury, Medicine and a Manmade Epidemic.