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.   Sources (WARNING -- LONG LIST):   Swain, K. ‘Extraordinarily arduous and fraught with danger’: syphilis, Salvarsan, and general paresis of the insane. Lancet Psychiatry 5, (2018).   Kępa, M. et al. Analysis of mercury levels in historical bone material from syphilitic subjects – pilot studies (short report). Kępa Małgorzata 69, 367-377(11) (2012).   Forrai, J. Syphilis - Recognition, Description and Diagnosis. (2011). doi:10.5772/24205   Parascandola, J. From mercury to miracle drugs: syphilis therapy over the centuries. Pharm Hist 51, 14–23 (2009).   Eisler, C. Who Is Dürer’s ‘Syphilitic Man’? Perspect Biol Med 52, 48–60 (2009).   Rothschild, B. M. History of Syphilis. Clin Infect Dis 40, 1454–1463 (2005).   Schwartz, R. S. Paul Ehrlich’s Magic Bullets. New Engl J Medicine 350, 1079–1080 (2004).   Fee, E. The wages of sin. Lancet 354, SIV61 (1999).   O’Shea, J. ‘Two Minutes with Venus, Two Years with Mercury’-Mercury as an Antisyphilitic Chemotherapeutic Agent. J Roy Soc Med 83, 392–395 (1989).   Mahoney, J., Arnold, R., Sterner, B. L., Harris, A. & Zwally, M. Penicillin Treatment of Early Syphilis: II. Jama 251, 2005–2010 (1984).   Waugh, M. Role played by Italy in the history of syphilis. Sex Transm Infect 58, 92–95 (1982).   Thorburn, A. Fritz Richard Schaudinn, 1871-1906: protozoologist of syphilis. Sex Transm Infect 47, 459–461 (1971).   CROSBY, A. W. The Early History of Syphilis: A Reappraisal. Am Anthropol 71, 218–227 (1969).   Clark, E. G. & Danbolt, N. The Oslo study of the natural history of untreated syphilis An epidemiologic investigation based on a restudy of the Boeck-Bruusgaard material a review and appraisal. J Chron Dis 2, 311–344 (1955).   MUNGER, R. S. Guaiacum, the Holy Wood from the New World. J Hist Med All Sci IV, 196–229 (1949).   Thomas, E. & r, W. Rapid Treatment of Early Syphilis with Multiple Injections of Mapharsen. J Nerv Ment Dis 99, 88 (1944).   WIEDER, L., FOERSTER, O. & FOERSTER, H. MAPHARSEN IN THE TREATMENT OF SYPHILIS: FURTHER EXPERIENCES. Arch Dermatol Syph 35, 402–413 (1937).   THON, L. SHOULD THE INTERNIST KNOW SYPHILIS? J Amer Med Assoc 97, 994–996 (1931).   Sarton, G. The Earliest Printed Literature on Syphilis, being Ten Tractates from the Years 1495-1498. Karl Sudhoff , Charles Singer , Henry E. Sigerist. Isis 8, 351–354 (1926).   COLE, H., GERICKE, A. & SOLLMANN, T. THE TREATMENT OF SYPHILIS BY MERCURY INHALATIONS: HISTORY, METHOD AND RESULTS. Arch Dermatol Syph 5, 18–33 (1922).   Mason, U. Observation: Use and Abuse of Salvarsan. J Natl Med Assoc 3, 340–3 (1911).   Fleming, A. & Colebrook, L. ON THE USE OF SALVARSAN IN THE TREATMENT OF SYPHILIS. Lancet 177, 1631–1634 (1911).   Evans, A. The Treatment of Syphilis by Salvarsan (Dioxy-diamido-arseno-benzol). Brit Med J 1, 617 (1911).   Boeck, W. History, Theory and Practice of Syphilisation. New Engl J Medicine 73, 20–25 (1865).   Veale, H. Remarks on Syphilis and Its Treatment. Edinb Medical J 10, 10–26 (1864).   LaFond RE and Lukehart SA, Biological Basis for Syphilis. Clinical Microbiology Reviews 2006.   Secher L et al, Treponema pallidum in peripheral nerve tissue of syphilitic chancres. Acta dermato-venereologica 1982.  Hollander DH, Turner TB, The role of temperature in experimental treponemal infection. American journal of syphilis, gonorrhea, and vener