Hot brains: manipulating body heat to save the brain.

CONSIDER A DISEASE with high mortality, severe morbidity, unknown pathogenesis, imprecise diagnostic features, and no known cure—in short, a condition with no hope. One can only offer soothing words and symptomatic remedy. Then, there is hope. Anecdotal observations lead to a new hypothesis. A pilot trial indicates that 6 of 9 treated patients “unexpectedly recover.” Larger studies follow and show 30% to 50% improvement. On the basis of what was looked for, the treatment is considered safe, and compared with the desperate condition of the treated, the risks (if any) are deemed tolerable. People the world over begin to offer this exciting therapy. Could there be a Nobel Prize in the horizon for the discoverer? What was the disease, and what was the cure? The disease was not stroke, hepatic coma, or neonatal encephalopathy. It was general paresis of the insane (GPI), the dreaded neurosyphilis, and the magical remedy was “fever therapy,” induced by injecting blood from malaria patients. This idea of “fighting one disease with another” evolved as recently as the 1910s, not in the Dark Ages.1–4 Enter Julius Wagner-Jauregg (1857–1940), a Viennese doctor who specialized in experimental pathology but chose psychiatry because he could not get into internal medicine. The choice, he noted dryly, “harmed neither [himself] nor psychiatry.”1 An interest in the brain led him to study patients with psychiatric and neurologic symptoms. By the mid-1880s, he had discovered a curious association. His psychiatric patients were reporting improved symptoms after recovering from bouts of fever. Wagner-Jauregg studied 30 different patients with typhoid, malaria, smallpox, scarlet fever, and erysipelas and confirmed that a small percentage indeed felt better after having had a fever. He correctly surmised that because at least some mental disorders might have organic causes, one must consider organic remedies for those conditions. He thought of inducing fever by inducing infections. But how does one go about inducing infections, especially choosing donors and recipients? Spirochetes that cause syphilis had been discovered in 1905, and the Wasserman test was developed in 1906. However, diagnosing infectious conditions was difficult, and therapy was empirical. Wagner-Jauregg tried inducing fever by injecting tuberculin, which did not cause fever consistently.3 He continued to think about this issue and waited. In June 1917 there was a break. A soldier with symptoms of malaria was admitted to his clinic. In May of that year, another patient with GPI had been admitted to the same clinic. Because “there was nothing to loose,” on June 14, 1917, Wagner-Jauregg obtained the soldier’s blood and injected it into the arm of the patient with GPI. A photograph taken on a later date depicts the treatment procedure (Fig 1). The patient with GPI promptly developed malaria, and Wagner-Jauregg wrote that “in the course of the following month, there was a gradual improvement” in