Howard Fischer
Uppsala, Sweden

 

Patient in Kettering hypertherm cabinet undergoing fever therapy. New Orleans, 1937. U.S. Marine Hospital. Works Progress Administration photo. New Orleans Public Library Digital Collections via Wikimedia. Public domain.

“The syphilitic man was thinking hard…about how to get his legs to step off the curb and carry him across Washington Street. Here was his problem: His brains, where the instructions to his legs originated, were being eaten alive by corkscrews.”
– Kurt Vonnegut, The Breakfast of Champions

 

Julius Wagner-Jauregg, M.D. (1857–1940) graduated from the University of Vienna School of Medicine in 1880. He wanted, but did not obtain, a position in internal medicine, so he took one in psychiatry. He and Sigmund Freud had been classmates and maintained respectful relations for most of their lives.¹ In 1927 he became the first psychiatrist to be awarded the Nobel Prize in Physiology and Medicine.²

As a psychiatrist, he had observed a patient who had a febrile attack of erysipelas (a serious skin infection) and then recovered from “severe mental illness.”³ He performed an extensive literature search and learned that in Pinel’s Treatise on Insanity, there was a mention of a patient with malaria and its accompanying fever who recovered from his insanity. Hippocrates described the beneficial effect of malaria on a patient with epilepsy. Epidemics ran through hospitals for the “insane,” and it was reported that typhoid, anthrax, smallpox, and malaria sometimes cured mental illness. Cholera did not, and erysipelas produced the best cure rate.⁴

Jauregg decided to focus his research on treating mental disorders by inducing fever.⁵ He had some success with tuberculin until it was deemed a dangerous substance and became unavailable. He also tried killed staphylococci, which produced fever followed by a very short remission in the patients’ mental disorders.⁶

In 1917, while serving as a military doctor in the Balkans, he injected some blood from a soldier with malaria into a patient with tertiary syphilis. The patient developed malaria and the expected fever, and the mental signs of his tertiary syphilis resolved. He tried the same experiment on nine more patients with tertiary syphilis, and six of the nine improved.⁷ They were then treated with quinine to cure their malaria.

The broad term “neurosyphilis” means a syphilitic infection of the central nervous system. About one year after contracting syphilis, an untreated infection may progress to secondary syphilis with hair loss, rash, anemia, and systemic symptoms. Syphilitic meningitis and involvement of the retina and cornea may occur. Late neurosyphilis appears about six years after the primary infection. The treponema of syphilis infiltrate the blood vessels of the central nervous system, leading to strokes and spinal cord infarction. Years to decades later the organisms invade brain and spinal cord parenchyma.⁸ Chronic syphilitic meningoencephalitis causes progressive degeneration of the central nervous system and a general degradation of mental capacities. This state is variously known as general paresis, general paresis of the insane, or paralytic dementia.⁹ The frontal and temporal cortices are most involved. The posterior columns of the spinal cord demyelinate, producing ataxia and incontinence. At this point the patient is psychotic or demented¹⁰ and death follows.¹¹ The arsenicals and mercuric compounds used to treat early (non-neurologic) syphilis are ineffective in neurosyphilis. The blood-brain barrier lets treponemas in, but not these medications.¹²

It seemed that Dr. Jauregg had developed a way to treat a formerly terminal disease. He published his results, and the initial skepticism was outweighed by the possibility of treating a uniformly fatal disease and having a chance at a cure. Malaria therapy was adopted in Germany in 1920; in the UK, Italy, and Czechoslovakia in 1922; and the following year in the US, the USSR, France, and Denmark. Tens of thousands of patients were treated by injection of the malaria-causing organism Plasmodium vivax between 1917 and the mid-1940s, when penicillin became generally available. About one-half of patients treated worldwide recovered enough to resume normal activities, another 20% had partial remission of symptoms,^13,14 and about 15% died.¹⁵ Jauregg’s Nobel Prize in 1927 was awarded for “his discovery of the therapeutic value of malaria inoculation in the treatment of ‘dementia paralytica’.”¹⁶

If the fever is the cure, reasoned others, then why not induce fever without producing another disease? Other ways of making patients febrile included injections of foreign proteins, injections of sulfur in olive oil, hot baths, heat cabinets, and electric blankets.¹⁷ The general idea was to give the patient a fever of 104^o F (40^o C) to 106^o F (41^o C) for several hours. This constituted one “treatment,” and one approach was ten weekly treatments of five hours each.¹⁸ In vitro the treponema of syphilis can survive at a temperature of 40^o C for three hours, 41^o C for two hours, and 42^o C for one hour.¹⁹

Jauregg criticized heating methods that did not use malaria as the cause of the fever, maintaining that the immune response to the malaria organisms worked synergistically with the fever. However, cure rates produced by non-infectious fever sources were similar to those produced by malaria therapy, without the risk of producing another disease.²⁰

Psychiatrist Jauregg approved of the sterilization of the mentally ill, of criminals, and of “genetically inferior” people. He applauded the German anschluss of Austria in 1938 and requested membership in the Nazi party. He was turned down because his first wife was a Jew, but this did not diminish his adherence to party principles.²¹ While he was responsible for the “earliest triumph of biological psychiatry over psychoanalysis,”²² he has been accused of performing “ethically ambiguous experimentation with fever therapy on non-consenting patients.”²³ Gartlehner and Stepper²⁴ conclude their overview of Jauregg’s work with: “In Austria today, the names of some streets and medical facilities commemorate the medical achievements of Wagner-Jauregg. He continues to be a controversial figure in history, teetering between brilliance and despicableness.”

 

References

1. Lois Magner. “Julius Wagner-Jauregg, 1857-1940,” Encyclopedia.com, ND.
2. Julius Wagner-Jauregg. Wikipedia.
3. Magda Whitrow. “Wagner-Jauregg and fever therapy,” Medical History, 34, 1990.
4. Whitrow, “Wagner-Jauregg.”
5. Julius Wagner-Jauregg. Wikipedia.
6. Whitrow, “Wagner-Jauregg.”
7. Gretchen Vogel. “Malaria as a lifesaving therapy,” Science, 342 (6156), 2013.
8. Neurosyphilis. Wikipedia.
9. Ingrid Ouwens, Elisabeth Lens, et al. “Malaria fever therapy for general paralysis of the insane: A hybrid chart study,” Eur Neurol, 78, 2017.
10. Neurosyphilis. Wikipedia.
11. Cynthia Tsay. “Julius Wagner-Jauregg and the legacy of malarial therapy for the treatment of general paralysis of the insane,” Yale J Biol Med, 86(2), 2013.
12. Joseph Warner. “A critical history of the malaria fever therapy for general paresis,” unpublished masters’ thesis, University of Calgary, Calgary AB, 2000.
13. Whitrow, “Wagner-Jauregg.”
14. Vogel, “Malaria.”
15. Julius Wagner-Jauregg. Wikipedia.
16. Julius Wagner- Jauregg. Wikipedia.
17. Norman Epstein. “Neurosyphilis: Its treatment,” California and Western Med. 44(3), 1936.
18. Howard Morrow, Norman Epstein, et al. “Modern therapy of syphilis,” California and Western Med, 44(4), 1936.
19. Epstein, “Neurosyphilis.”
20. Epstein, “Neurosyphilis.”
21. Julius Wagner-Jauregg. Wikipedia.
22. Tsay, “Julius Wagner-Jauregg.”
23. Tsay, “Julius Wagner-Jauregg.”
24. Gerald Gartlehner and K. Stepper. “Julius Wagner-Jauregg: Pyrotherapy, simultanmethode, and ‘racial hygiene’,” J Royal Society of Medicine, 105, 2012.

 

---

 

HOWARD FISCHER, M.D., was a professor of pediatrics at Wayne State University School of Medicine, Detroit, Michigan.

 

Spring 2022  |  Sections  |  Infectious Diseases