Malaria Therapy

Researchers once used malaria in an attempt to cure syphilis

By Harriet Washington

“Paresis” is a forgotten word, but it was once a familiar madness, a diagnosis given to one in every five inmates of New York City’s mental asylums. Also known as dementia paralytica and “general paralysis of the insane,” the disease was first described by Anton Bayle in 1822. He noted that paretics, as they were called, experienced a coarsening of the personality followed by mania, vivid delusions and dementia with “rapid and complete mental decay.”

For 70 years after Bayle described it, doctors thought paresis was caused by the usual suspects: trauma, overwork, anxiety, and intemperance. But in 1857, Johannes Friedrich Esmark and W. Jessen suggested that paresis might be caused by syphilis and they backed up this hypothesis with statistical compilations of the number of patients who suffered from the venereal disease and developed paresis. Moreover, tests for syphilis were positive in paretics and researchers who looked found the spirochete form of the bacterium Treponema pallidum— the cause of syphilis—in the bodies of paretics.

By the mid 19th century, many researchers thought of paresis as the tertiary stage of syphilis and sometimes referred to it as neurosyphilis. This knowledge held out hope that if syphilis were ever cured, paresis could be, too.

But no cure was forthcoming.

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Julius Wagner-Jauregg, pioneer of malariatherapy. (Wikimedia Commons)

Then in June 1917 Julius Wagner-Jauregg, of the University of Vienna Hospital for Nervous and Mental Diseases, undertook a radical approach. He fought fire with fire by turning one disease against another. Wagner-Jauregg decided to try suppressing the symptoms of paresis by infecting its sufferers with malaria.

Wagner-Jauregg reasoned that the infamous high fevers of malaria might kill the syphilis spirochetes, or at least inactivate them, because many bacteria can operate only within a very narrow temperature range. Wagner-Jauregg hoped that malarial fevers would raise the paretics’ body heat above the spirochetes’ survival zone. He inoculated an unknown number of Austrian subjects at various sites “on a large scale” with malaria-infected blood and was rewarded with fevers that soared to 106° F. In the end, Wagner-Jauregg recorded dramatic clinical improvements, if no cures.

The medical establishment was so gratified by the apparent success of malaria therapy that Wagner-Jauregg became the first psychiatric researcher to win the Nobel Prize in 1927.

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Mark F. Boyd. (University Texas Medical Branch)

In 1931 Mark F. Boyd began a malariatherapy investigation at the august Rockefeller Foundation. This eponymous philanthropic organization, founded in 1913 by the Rockefeller family, was technically separate from, but had close connections to, the Rockefeller Institute for Medical Research, which was often called just the “Rockefeller Institute.” The institute was America’s answer to such European temples of medical research as Berlin’s Robert Koch Institute and the Institut Pasteur in Paris. Rockefeller researchers developed the first antibiotic, showed that genes are structurally composed of DNA, discovered blood groups, were the first to show that viruses can cause cancer, demonstrated the existence of autoimmune disease, and first cultured the infectious agent associated with syphilis.

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The Rockefeller Institute in 1931. (New York Public Library Digital Collections)

Boyd set to work in New York and in an institute satellite in the South where he infected black and white paretics with malaria by having them repeatedly bitten by mosquitoes. (He maintained a reservoir of infected mosquitoes by maintaining a group of untreated malaria-infected subjects for mosquitoes to bite.) Boyd had at least two strains at his disposal: the plasmodia strain, which had a low fatality rate, and the falciparum strain, which was lethal in 40 percent of those who got it.

Boyd used plasmodia on his white subjects, and the deadly falciparum only on his African American subjects. He did this because many African Americans patients resisted infection by the plasmodia strain. (Some people of African descent—as well as others of Mediterranean, Middle Eastern, and Asian descent—enjoy a degree of resistance to certain strains of malaria.)

But when some of his African-American subjects died, Boyd resorted to deceit: In his notes, he disguised causes of death and distorted death rates. He also falsified other information in his reports, and historians still debate his motives for doing so. Some assume he did so “to protect” his subjects. In the absence of accurate data, we simply cannot know. But a desire to protect subjects seems to run counter to a willingness to inject them with a deadly form of malaria, and the racial disparity in apportioning risk is equally troubling. In the end, Boyd concluded that malariatherapy works well, but in the face of falsified data, it is impossible to know.

Boyd was not the only researcher to draw erroneous or unsupported conclusions from malariatherapy research. “Double-blinding” studies and other techniques we currently rely upon to yield a bias-free study interpretation were not in common use in that era. So whether they meant to or not, it was easy for researchers to see what they wanted to see—that their paresis patients were being helped by infection with a chronic, debilitating disease. Inspired by Wagner-Jauregg’s Nobel and buoyed by the clinical benefits touted in Boyd’s work, malariatherapy experiments continued and investigators praised the clinical results for another decade.

Then, in 1943, John F. Mahoney demonstrated that penicillin cures syphilis. Injections of penicillin arrested paresis, too, restoring to health those whose disease had not progressed too extensively and proving that paresis, now all but vanished from the U.S., was indeed the terrible legacy of an infection.

The question of malariatherapy’s effectiveness became clinically moot, but it was not forgotten. Until the FDA condemned the procedure in 2004, Henry Heimlich, originator of the Heimlich maneuver, tested malariatherapy’s effectiveness against HIV on patients in Africa and China. His research drew wide criticism and even his research associates disagreed about whether the results were promising. The enigmatic prospect of using one disease to fight another lingers as an unanswered question of medical history.

 

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