Episode 45: The French Disease at 500


In 1495, a mysterious and deadly plague struck the city of Naples. Over the next 500 years, the medical attempts to understand and treat this new disease — syphilis — would mold and shape medicine in surprising ways. In this episode, Tony Breu and I will perform an historical and physiological biography of syphilis, covering the development of germ theory, epic poetry, mercury saunas, intentionally infecting patients with malaria, magic bullets, and lots and lots of experiments on poor rabbits. This presentation was performed live at the American College of Physicians’ national meeting in Philadelphia on April 11, 2019.




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  1. THON, L. SHOULD THE INTERNIST KNOW SYPHILIS? J Amer Med Assoc 97, 994–996 (1931).


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  1. Mason, U. Observation: Use and Abuse of Salvarsan. J Natl Med Assoc 3, 340–3 (1911).


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  1. Veale, H. Remarks on Syphilis and Its Treatment. Edinb Medical J 10, 10–26 (1864).


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  1. Eagle H, et al. The effect of hyperpyrexia on the therapeutic efficacy of penicillin in experimental syphilis. American journal of syphilis, gonorrhea, and venereal diseases, 1947.


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  1. Clarkson TW and Magos L, The Toxicology of Mercury and Its Chemical Compounds, Critical Reviews in Toxicology 2008.


  1. Fitzgerald TJ, The Th1/Th2-like switch in syphilitic infection: is it detrimental? Infection and immunity, 1992


  1. Batterman RC et al, THE SUBCUTANEOUS ADMINISTRATION OF MERCAPTOMERIN (THIOMERIN®): Effective Mercurial Diuretic for the Treatment of Congestive Heart Failure. Journal of the American Medical Association, 1949


  1. Batterman RC, The status of mercurial diuretics for the treatment of congestive heart failure. American Heart Journal, 1951


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  1. Engelkens HJ et al, The localisation of treponemes and characterisation of the inflammatory infiltrate in skin biopsies from patients with primary or secondary syphilis, or early infectious yaws. Genitourinary Medicine, 1993


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  1. Drusin LM, Electron microscopy of Treponema pallidum occurring in a human primary lesion. Journal of bacteriology 1969.


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  1. Cabot RC et al, Case 51-1976 — Bicentennial CPC — Syphilis, Diarrhea and Death in the 1820’s. The New England Journal of Medicine 1976.


  1. Hobman JL and Crossman LC, Bacterial antimicrobial metal ion resistance. Journal of Medical Microbiology 2015


  1. Gelpi A and Tucker JD, After Venus, mercury: syphilis treatment in the UK before Salvarsan. Sexually Transmitted Infections 2015.


  1. MacHaffie et al, A study of the effectiveness of mercurial diuretics in treatment of cardiac decompensation. The American Journal of Cardiology 1958


  1. Aberer W et al, Ammoniated mercury ointment: outdated but still in use. Contact Dermatitis 1990


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immunocompetent patient: Facts and controversies. Clinics in Dermatology (2010) 28, 533–538


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  1. Karamanou M et al, “Julius Wagner-Jauregg (1857-1940): Introducing fever therapy in the treatment of neurosyphilis.” Psychiatriki. 2013 Jul-Sep;24(3):208-12.


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