The world before anesthesia was brutal -- surgeons inflicted torture on largely conscious patients, hoping to finish an operation as quickly as possible. But all of that changed with the introduction of inhaled ether. This episode covers the context behind the discovery of etherization, with myths about screaming medicinal plants, a “missing recipe” of medieval general anesthesia, 19th century recreational drug use, and a controversy carved in granite.

Sources:

1. Brown, M. The Palgrave Handbook of the History of Surgery. 327–348 (2017). doi:10.1057/978-1-349-95260-1_16 
2. Dorrington, K. & Poole, W. The first intravenous anaesthetic: how well was it managed and its potential realized? Bja Br J Anaesth 110, 7–12 (2013). 
3. Robinson, D. H. & Toledo, A. H. Historical Development of Modern Anesthesia. J Invest Surg 25, 141–149 (2012). 
4. Chidiac, E. J., Kaddoum, R. N. & Fuleihan, S. F. Mandragora. Anesthesia Analgesia 115, 1437–1441 (2012). 
5. Vargas, I. Ether Frolic: The Day Pain Stopped. Bulletin Anesthesia Hist 28, 53–56 (2010). 
6. Whalen, F. X., Bacon, D. R. & Smith, H. M. Inhaled anesthetics: an historical overview. Best Pract Res Clin Anaesthesiol 19, 323–330 (2005). 
7. Prioreschi, P. Medieval anesthesia – the spongia somnifera. Med Hypotheses 61, 213–219 (2003). 
8. Stallings, S. & Montagne, M. A chronicle of anesthesia discovery in New England. Pharm Hist 35, 77–80 (1993). 
9. Litoff, J. & Pernick, M. S. A Calculus of Suffering: Pain, Professionalism, and Anesthesia in Nineteenth-Century America. Am Hist Rev 91, 176 (1986). 
10. Leake, C. D. Letheon: The Cadenced Story of Anesthesia. Science 199, 857–860 (1978). 
11. CRAWFORD W. LONG (1815-1878) DISCOVERER OF ETHER FOR ANESTHESIA. Jama 194, 1008–1009 (1965). 
12. Riches, E. Samuel Pepys and His Stones. J Urology 118, 148–151 (1977). 
13. CWRIGHT, F. The early history of ether. Anaesthesia 15, 67–69 (1960). 
14. Insensibility during Surgical Operations Produced by Inhalation. New Engl J Medicine 35, 379–382 (1846). 
15. SURGICAL HUMBUG. Lancet 5, 646–647 (1826). 

Locations in Boston:

Ether Monument (https://www.atlasobscura.com/places/ether-monument)

Ether Dome (https://www.atlasobscura.com/places/ether-dome?utm_source=atlas-forum&utm_medium=referral)

Warren Anatomic Museum (https://www.atlasobscura.com/places/warren-anatomical-museum)

Because of dad brain, the original musical tracks for episode 48 were offset by almost 30 seconds (even more embarrassing, because I actually LISTENED to it before uploading). I've fixed the audio for the original episode, but anyone who downloaded it already is stuck with the bad audio version. Because of limitations in the podcasting medium, the only way I can get a new episode to those who have downloaded but haven't listened yet is to release a new episode to the feed. Eventually (maybe after a month or so) I will delete this, so only the fixed original remains.

Sorry for the inconvenience guys! 

Germs are regarded today with a combination of fear and disgust. But mankind’s first introduction to the microbial world started off on a very different foot. In this episode, as part of a larger series contextualizing germ theory, we’ll talk about the discovery of animalcules and how they forever changed our conception of the natural world -- and what causes disease. Plus, a new #AdamAnswers about the influence of Bayes Theorem on medicine!

Sources:

• Albury WR, Marie-Francois-Xavier Bichat, Encyclopedia of Life Science, 2001. 
• Ball CS, The Early History of the Compound Microscope, Bios, Vol 37, No2 (May 1966).
• Findlen P, Athanasius Kircher: The Last Man Who Knew Everything. 
• Feinstein AR, “An Analysis of Diagnostic Reasoning,” Yale Journal of Biology and Medicine, 1973.
• Forsberg L.Nature's Invisibilia: The Victorian Microscope and the Miniature Fairy, Victorian Studies 2015.
• Gest H. The discovery of microorganisms by Robert Hooke and Antoni van Leeuwenhoek, Fellows of The Royal Society. Notes and Records of the Royal Society of Lond, 2004. 
• Hall, GH, The Clinical Application of Bayes Theorem, The Lancet, September 9, 1967. 
• Howard-Jones N, Fracastoro and Henle: A Re-Appraisal of their Contribution to the Concept of Communicable Diseases,” Medical History, 1977, 21: 61-68.
• Lane N, The unseen world: reflections on Leeuwenhoek (1677) ‘Concerning little animals’. Philosophical Transactions of the Royal Society, 19 April 2015. 
• Lawson I, Crafting the microworld: how Robert Hooke constructed knowledge about small things, Notes and Records of the Royal Society of Lond, 2015.
• McLeMee S, Athanasius Kirchehr, Dude of Wonders, The Chronicle of Higher Education, May 28, 2002. 
• Van Leeuwenhoek A, Observations, communicated to the publisher by Mr. Antony van Leewenhoeck, in a dutch letter of the 9th Octob. 1676. here English'd: concerning little animals by him observed in rain-well-sea- and snow water; as also in water wherein pepper had lain infused (https://royalsocietypublishing.org/doi/10.1098/rstl.1677.0003)
• “Little worms which propagate plague,” J R Coll Physicians Edinb, 2008. 
• Van Zuylen J, “The microscopes of Antoni van Leeuwenhoek,” Journal of Microscopy., 1981.

Music from https://filmmusic.io, "Wholesome," “Pookatori and Friends,” and  by Kevin MacLeod (https://incompetech.com). License: CC BY

Bedside Rounds is on a summer vacation! In the meantime, I'm joined by journalist Dan Weissmann of the podcast An Arm and a Leg to talk about the tawdry history of the discovery of insulin. 

Can we ever know what causes a chronic disease? In this episode, I’m joined again by Dr. Shoshana Herzig to finish a three-part miniseries on Bradford Hill and Doll’s attempts to prove that smoking caused lung cancer. We’ll talk about the first prospective cohort trial in history, 1960s “Fake News” from tobacco companies, public spats with the most famous statistician of the 20th century, and the development of the Bradford Hill Criteria, a guideline, however imperfect, that gives doctors a blueprint to finally figure out what causes diseases.

Sources:

• Crofton J, The MRC randomized trial of streptomycin and its legacy: a view from the clinical front line. J R Soc Med. 2006 Oct; 99(10): 531–534.
• Daniels M and Bradford Hill A, Chemotherapy of Pulmonary Tuberculosis in Young Adults, Br Med J. 1952 May 31; 1(4769): 1162–1168.
• Dangers of Cigarette-smoking. Brit Med J 1, 1518 (1957).
• Doll, R. & Hill, B. A. Lung Cancer and Other Causes of Death in Relation to Smoking. Brit Med J 2, 1071 (1956).
• Doll, R. & Hill, B. A. Smoking and Carcinoma of the Lung. Brit Med J 2, 739 (1950).
• Hill, A. The Environment and Disease: Association or Causation? J Roy Soc Med 58, 295–300 (1965).
• HOFFMAN, F. L. CANCER AND SMOKING HABITS. Ann Surg 93, 50–67 (1931).
• Keating C, Smoking Kills: The Revolutionary Life of Richard Doll. 2009.
• Morabia, A. Quality, originality, and significance of the 1939 “Tobacco consumption and lung carcinoma” article by Mueller, including translation of a section of the paper. Prev Med 55, 171–177 (2012).
• Ochsner, A. & bakey. Primary pulmonary malignancy: treatment by total pneumonectomy; analysis of 79 collected cases and presentation of 7 personal cases. Ochsner J 1, 109–25 (1999).
• Ochsner, A. My first recognition of the relationship of smoking and lung cancer. Prev Med 2, 611–614 (1973).
• Parascandola, M. Two approaches to etiology: the debate over smoking and lung cancer in the 1950s. Endeavour 28, 81–86 (2004).
• Phillips, C. V. & Goodman, K. J. The missed lessons of Sir Austin Bradford Hill. Epidemiologic Perspectives Innovations 1, 1–5 (2004).
• Proctor, R. Angel H Roffo: the forgotten father of experimental tobacco carcinogenesis. B World Health Organ 84, 494–495 (2006).
• Wynder, E. RE: “WHEN GENIUS ERRS: R. A. FISHER AND THE LUNG CANCER CONTROVERSY”. Am J Epidemiol 134, 1467–9 (1991).

Does smoking cause lung cancer? How could you ever know? The second in a three-part series on causality, I’m joined by Dr. Shoshana Herzig to discuss how Austin Bradford Hill and Richard Doll set out to try and answer this question -- and along the way revolutionized the way we think about what causes disease. In this episode, we’ll talk about the first double-blinded randomized controlled trial, the long shadow of tuberculosis, and why epidemiology is beautiful. Plus, a brand new #AdamAnswers about chest compressions!

Please support Bedside Rounds by filling out the listener demographic survey: https://survey.libsyn.com/bedsiderounds

Sources:

• Bost TC. Cardiac arrest during anaesthesia and surgical operations. Am J Surg 1952;83: 135-4
• Council, T. Tobacco Smoking and Lung Cancer. Brit Med J 1, 1523 (1957).
• Crofton J, The MRC randomized trial of streptomycin and its legacy: a view from the clinical front line. J R Soc Med. 2006 Oct; 99(10): 531–534.
• Daniels M and Bradford Hill A, Chemotherapy of Pulmonary Tuberculosis in Young Adults, Br Med J. 1952 May 31; 1(4769): 1162–1168.
• Dangers of Cigarette-smoking. Brit Med J 1, 1518 (1957).
• Doll, R. & Hill, B. A. Lung Cancer and Other Causes of Death in Relation to Smoking. Brit Med J 2, 1071 (1956).
• Doll, R. & Hill, B. A. Smoking and Carcinoma of the Lung. Brit Med J 2, 739 (1950).
• Hill, A. The Environment and Disease: Association or Causation? J Roy Soc Med 58, 295–300 (1965).
• HOFFMAN, F. L. CANCER AND SMOKING HABITS. Ann Surg 93, 50–67 (1931).
• Hurt R, Modern cardiopulmonary resuscitation—not so new after all. J R Soc Med. 2005 Jul; 98(7): 327–331.
• Keating C, Smoking Kills: The Revolutionary Life of Richard Doll. 2009.
• Keith A, Three Hunterian Lectures ON THE MECHANISM UNDERLYING THE VARIOUS METHODS OF ARTIFICIAL RESPIRATION PRACTISED SINCE THE FOUNDATION OF THE ROYAL HUMANE SOCIETY IN 1774. (1909). The Lancet, 173(4464), 825–828.
• Kouwenhoven WB et al, Closed-chest cardiac massage, JAMA, JAMA. 1960;173(10):1064-1067.
• Morabia, A. Quality, originality, and significance of the 1939 “Tobacco consumption and lung carcinoma” article by Mueller, including translation of a section of the paper. Prev Med 55, 171–177 (2012).
• Ochsner, A. & bakey. Primary pulmonary malignancy: treatment by total pneumonectomy; analysis of 79 collected cases and presentation of 7 personal cases. Ochsner J 1, 109–25 (1999).
• Ochsner, A. My first recognition of the relationship of smoking and lung cancer. Prev Med 2, 611–614 (1973).
• Parascandola, M. Two approaches to etiology: the debate over smoking and lung cancer in the 1950s. Endeavour 28, 81–86 (2004).
• Phillips, C. V. & Goodman, K. J. The missed lessons of Sir Austin Bradford Hill. Epidemiologic Perspectives Innovations 1, 1–5 (2004).
• Proctor, R. Angel H Roffo: the forgotten father of experimental tobacco carcinogenesis. B World Health Organ 84, 494–495 (2006).
• Wynder, E. RE: “WHEN GENIUS ERRS: R. A. FISHER AND THE LUNG CANCER CONTROVERSY”. Am J Epidemiol 134, 1467–9 (1991).

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):

1. Swain, K. ‘Extraordinarily arduous and fraught with danger’: syphilis, Salvarsan, and general paresis of the insane. Lancet Psychiatry 5, (2018).

1. 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).

1. Forrai, J. Syphilis - Recognition, Description and Diagnosis. (2011). doi:10.5772/24205

1. Parascandola, J. From mercury to miracle drugs: syphilis therapy over the centuries. Pharm Hist 51, 14–23 (2009).

1. Eisler, C. Who Is Dürer’s ‘Syphilitic Man’? Perspect Biol Med 52, 48–60 (2009).

1. Rothschild, B. M. History of Syphilis. Clin Infect Dis 40, 1454–1463 (2005).

1. Schwartz, R. S. Paul Ehrlich’s Magic Bullets. New Engl J Medicine 350, 1079–1080 (2004).

1. Fee, E. The wages of sin. Lancet 354, SIV61 (1999).

1. 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).

1. Mahoney, J., Arnold, R., Sterner, B. L., Harris, A. & Zwally, M. Penicillin Treatment of Early Syphilis: II. Jama 251, 2005–2010 (1984).

1. Waugh, M. Role played by Italy in the history of syphilis. Sex Transm Infect 58, 92–95 (1982).

1. Thorburn, A. Fritz Richard Schaudinn, 1871-1906: protozoologist of syphilis. Sex Transm Infect 47, 459–461 (1971).

1. CROSBY, A. W. The Early History of Syphilis: A Reappraisal. Am Anthropol 71, 218–227 (1969).

1. 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).

1. MUNGER, R. S. Guaiacum, the Holy Wood from the New World. J Hist Med All Sci IV, 196–229 (1949).

1. Thomas, E. & r, W. Rapid Treatment of Early Syphilis with Multiple Injections of Mapharsen. J Nerv Ment Dis 99, 88 (1944).

1. WIEDER, L., FOERSTER, O. & FOERSTER, H. MAPHARSEN IN THE TREATMENT OF SYPHILIS: FURTHER EXPERIENCES. Arch Dermatol Syph 35, 402–413 (1937).

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

1. 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).

1. COLE, H., GERICKE, A. & SOLLMANN, T. THE TREATMENT OF SYPHILIS BY MERCURY INHALATIONS: HISTORY, METHOD AND RESULTS. Arch Dermatol Syph 5, 18–33 (1922).

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

1. Fleming, A. & Colebrook, L. ON THE USE OF SALVARSAN IN THE TREATMENT OF SYPHILIS. Lancet 177, 1631–1634 (1911).

1. Evans, A. The Treatment of Syphilis by Salvarsan (Dioxy-diamido-arseno-benzol). Brit Med J 1, 617 (1911).

1. Boeck, W. History, Theory and Practice of Syphilisation. New Engl J Medicine 73, 20–25 (1865).

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

1. LaFond RE and Lukehart SA, Biological Basis for Syphilis. Clinical Microbiology Reviews 2006.

1. Secher L et al, Treponema pallidum in peripheral nerve tissue of syphilitic chancres. Acta dermato-venereologica 1982.
2.  Hollander DH, Turner TB, The role of temperature in experimental treponemal infection. American journal of syphilis, gonorrhea, and venereal diseases, 1954

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.

1. Kampmeier RH, Syphilis therapy: an historical perspective. Journal of the American Venereal Disease Association 1976.

1. Pachner AR, Spirochetal Diseases of the CNS. Neurologic clinics, 1986.

1. Sell S et al, Experimental syphilitic orchitis in rabbits: ultrastructural appearance of Treponema pallidum during phagocytosis and dissolution by macrophages in vivo. Laboratory investigation; a journal of technical methods and pathology, 1982.

1. Taylor SH, Diuretics in cardiovascular therapy. Perusing the past, practising in the present, preparing for the future. Zeitschrift für Kardiologie, 1985.

1. Ovchinnikov NM, [Treponema pallidum in peripheral nerves of rabbit syphiloma]. Vestnik dermatologii i venerologii, 1975.

1. Cheek DB, Wu F, The Effect of Calomel on Plasma Epinephrine in the Rat and the Relationship to Mechanisms in Pink Disease, Archives of Disease in Childhood, 1959

1. Vogl A, The discovery of the organic mercurial diuretics, American Heart Journal, 1950

1. Schwemlein GX et al, Penicillin and fever therapy in early syphilis, Journal of the American Medical Association, 1948.

1. Stringham JS, On the Diuretic Effects of Mercury in a Case of Syphilis. The Medical and physical journal, 1807

1. Evanson RL et al, Effect of mercurial diuretics on tubular sodium and potassium transport in the dog. The American journal of physiology, 1972

1. Sell S and Salman J, Demonstration of Treponema pallidum in Axons of Cutaneous Nerves in Experimental Chancres of Rabbits, Sexually Transmitted Diseases, 1992

1. Penn CW, Avoidance of Host Defences by Treponema pallidum in Situ and on Extraction from Infected Rabbit Testes, Microbiology 1981.

1. Beutler B and Munford RS, Tumor Necrosis Factor and the Jarisch–Herxheimer Reaction, The New England Journal of Medicine 1996.

1. Radolf JD et al, Treponema pallidum: doing a remarkable job with what it's got. Trends in Microbiology, 1999

1. Tight RR, Perkins RL, Treponema pallidum infection in subcutaneous polyethylene chambers in rabbits. Infection and immunity, 1976

1. Salazar JC et al, Treponema pallidum Elicits Innate and Adaptive Cellular Immune Responses in Skin and Blood during Secondary Syphilis: A Flow-Cytometric Analysis. The Journal of Infectious Diseases, 2007

1. Azevedo BF et al, Toxic Effects of Mercury on the Cardiovascular and Central Nervous Systems. Journal of Biomedicine and Biotechnology 2012,

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

1. Bleich HL et al, The Role of Regional Body Temperature in the Pathogenesis of Disease, The New England Journal of Medicine, 1981

1. Vander Veer JB et al, The Prolonged Use of an Oral Mercurial Diuretic in Ambulatory Patients with Congestive Heart Failure. Circulation 1950

1. Cox DL et al, The outer membrane, not a coat of host proteins, limits antigenicity of virulent Treponema pallidum. Infection and immunity, 1992.

1. Fildes P, The Mechanism of the Anti-bacterial Action of Mercury. Br J Exp Pathol, 1940

1. Clarkson TW, THE MECHANISM OF ACTION OF MERCURIAL DIURETICS IN RATS; THE METABOLISM OF 203Hg‐LABELLED CHLORMERODRIN. British Journal of Pharmacology and Chemotherapy, 1965

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

1. Belum GR et al, The Jarisch–Herxheimer reaction: Revisited. Travel Medicine and Infectious Disease, 2013

1. Arando M et al, The Jarisch–Herxheimer reaction in syphilis: could molecular typing help to understand it better? Journal of the European Academy of Dermatology and Venereology, 2018.

1. Butler T, The Jarisch–Herxheimer Reaction After Antibiotic Treatment of Spirochetal Infections: A Review of Recent Cases and Our Understanding of Pathogenesis. The American Journal of Tropical Medicine and Hygiene, 2016

1. Carlson JA et al, The Immunopathobiology of Syphilis: The Manifestations and Course of Syphilis Are Determined by the Level of Delayed-Type Hypersensitivity. The American Journal of Dermatopathology 2011.

1. Aronson IK and Soltani K, The enigma of the pathogenesis of the Jarisch-Herxheimer reaction. The British Journal of Venereal Diseases, 1976

1. Sellato TJ et al, The Cutaneous Response in Humans to Treponema pallidum Lipoprotein Analogues Involves Cellular Elements of Both Innate and Adaptive Immunity, The Journal of Immunology 2001

1. Spiller HA, Rethinking mercury: the role of selenium in the pathophysiology of mercury toxicity. Clinical Toxicology 2017

1. Sell S et al, Reinfection of chancre-immune rabbits with Treponema pallidum. I. Light and immunofluorescence studies. The American journal of pathology 1985.

1.  Grant SS and Hung DT, Persistent bacterial infections, antibiotic tolerance, and the oxidative stress response, Virulence 2013

1. Lant AF, Modern diuretics and the kidney. Journal of Clinical Pathology, 1981

1. Kamath SU et al, Mercury-based traditional herbo-metallic preparations: a toxicological perspective, Archives of Toxicology 2012.

1. Yeter et al, Mercury Promotes Catecholamines Which Potentiate Mercurial Autoimmunity and Vasodilation: Implications for Inositol 1,4,5-Triphosphate 3-Kinase C Susceptibility in Kawasaki Syndrome. Korean Circulation Journal 2013

1. Wöβmann W et al, Mercury intoxication presenting with hypertension and tachycardia. Archives of Disease in Childhood, 1999

1. Giacani L et al, Identification of the Treponema pallidum subsp. pallidum TP0092 (RpoE) Regulon and Its Implications for Pathogen Persistence in the Host and Syphilis Pathogenesis. Journal of Bacteriology 2013.

1. Edwards AM, From tooth to hoof: treponemes in tissue‐destructive diseases. Journal of Applied Microbiology, 2003

1. Wolgemuth CW, Flagellar motility of the pathogenic spirochetes. Seminars in Cell & Developmental Biology 2015.

1. Solomon HC and Kopp I, Fever Therapy. The New England Journal of Medicine 1937.

1. Rice KM et al, Environmental Mercury and Its Toxic Effects. Journal of Preventive Medicine and Public Health 2014.

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

1. McNeely MC et al, Cutaneous secondary syphilis: Preliminary immunohistopathologic support for a role for immune complexes in lesion pathogenesis. Journal of the American Academy of Dermatology 1986.

1. Borenstein LA et al, Contribution of rabbit leukocyte defensins to the host response in experimental syphilis. Infection and immunity 1991.

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

1. Farhi D, Dupin N, Origins of syphilis and management in the

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

1. Frith J, “Syphilis – Its early history and Treatment until Penicillin and the Debate on its Origins,” Journal of Military and Veterans’ Health, 20(4), retrieved online at: http://jmvh.org/article/syphilis-its-early-history-and-treatment-until-penicillin-and-the-debate-on-its-origins/

1. Howes OD et al, “Julius Wagner-Jauregg, 1857-1940,” American Journal of Psychiatry, April 2009 Volume 166 Number 4, Volume 166, Issue 4, April, 2009, pp. 409-409.

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.

1. Simpson WM, “Artificial fever therapy of syphilis,” JAMA. 1935;105(26):2132-2140.

1. Tsay CJ, “Julius Wagner-Jauregg and the Legacy of Malarial Therapy for the Treatment of General Paresis of the Insane,” Yale J Biol Med. 2013;86(2): 245–254

1. Wagner-Jauregg J, “The history of malaria treatment of general paralysis.” Am J Psychiatry. 1946;02: 577-582

1. Shafer JK et al, Untreated syphilis in the male Negro: A prospective study of the effect on life expectancy. Public Health Rep. 1954 Jul; 69(7): 684–690.

1. Abara WE et al, Syphilis Trends among Men Who Have Sex with Men in the United States and Western Europe: A Systematic Review of Trend Studies Published between 2004 and 2015. PLoS One. 2016; 11(7): e0159309.

1. Nutton V, The Reception of Fracastoro's Theory of Contagion: The Seed That Fell among Thorns? Osiris, Vol. 6, Renaissance Medical Learning: Evolution of a Tradition (1990)

1. Tsaraklis A, Preventing syphilis in the 16th century: the distinguished Italian anatomist Gabriele Falloppio (1523-1562)  and the invention of the condom. Le Infezioni in Medicina, n. 4, 395-398, 2017.

What was behind the mysterious increase in lung cancer deaths at the turn of the 20th century? The first of a three-parter investigating the cigarette-smoking link and causality, this episode looks at that early debate, which largely focused on environmental pollution. Along the way, we’re going to talk about toxic vapors -- and not Miasma theory, but the actual literal Great Smog of London in 1952 that killed over 10,000 people -- as well as the birth of the case-control study, Nazi attempts at tobacco control programs, and the rather prosaic beginnings of a debate that rages to this day. Plus a new #AdamAnswers about the medical cause of Game of Thrones greyscale featuring Dr. Jules Lipoff!

Sources:

• Bell, M. L., Davis, D. L. & Fletcher, T. A retrospective assessment of mortality from the London smog episode of 1952: the role of influenza and pollution. Environ Health Persp 112, 6–8 (2003).
• Brunekreef B, Air Pollution and Life Expectancy: Is There a Relation? Occupational and Environmental Medicine, Vol. 54, No. 11 (Nov., 1997), pp. 781-784.
• Des Voeux HC, Smoke and Fog, The Lancet, 1679-1680 (1904).
• Logan WPD, Mortality in the London Fog Incident, 1952. The Lancet, 336-338 (1953).
• Heirdorn KC, The Weather Doctor's Weather Almanac: The Infamous London Smog of 1952, 2012.
• HOFFMAN, F. L. CANCER AND SMOKING HABITS. Ann Surg 93, 50–67 (1931).
• Morabia, A. Quality, originality, and significance of the 1939 “Tobacco consumption and lung carcinoma” article by Mueller, including translation of a section of the paper. Prev Med 55, 171–177 (2012).
• Ochsner, A. My first recognition of the relationship of smoking and lung cancer. Prev Med 2, 611–614 (1973).
• Ochsner, A. & bakey. Primary pulmonary malignancy: treatment by total pneumonectomy; analysis of 79 collected cases and presentation of 7 personal cases. Ochsner J 1, 109–25 (1999).
• Parascandola, M. Two approaches to etiology: the debate over smoking and lung cancer in the 1950s. Endeavour 28, 81–86 (2004).
• Press, D. J. & Pharoah, P. Risk Factors for Breast Cancer. Epidemiology 21, 566–572 (2010).
• Proctor, R. Angel H Roffo: the forgotten father of experimental tobacco carcinogenesis. B World Health Organ 84, 494–495 (2006).
• Proctor, R. N. The anti-tobacco campaign of the Nazis: a little known aspect of public health in Germany, 1933–45. Bmj 313, 1450 (1996).
• Proctor, R. On playing the Nazi card. Tob Control 17, 289–290 (2008).
• Winkelstein, W. Vignettes of the History of Epidemiology: Three Firsts by Janet Elizabeth Lane-Claypon. Am J Epidemiol 160, 97–101 (2004).
• Proctor R, The history of the discovery of the cigarette–lung cancer link: evidentiary traditions, corporate denial, global toll. Tobacco Control. 21:2 (2013).

What killed Charles II of Spain, the inbred monarch whose autopsy famously showed a heart the size of a peppercorn, a head full of water, and a bloodless body? This episode addresses that medical mystery by not only delving deep into Charles’ unfortunate past, but by exploring some of the fundamental assumptions physicians have made about the nature of disease. Along the way we’ll walk about inbreeding coefficients, postmodern philosophy, and two thousand years of anatomy and autopsy. Plus a new #AdamAnswers about whether Vincent van Gogh’s love of the color yellow was caused by digitalis poisoning!

Sources:

• Alvarez G, Ceballos FC, Quinteiro C (2009) The Role of Inbreeding in the Extinction of a European Royal Dynasty. PLoS ONE 4(4): e5174. https://doi.org/10.1371/journal.pone.0005174
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Florence Nightingale stands as one of the most important reformers of 19th century medicine -- a woman whose belief in the power of reason and statistical thinking would critically shape the both the fields of epidemiology and nursing. This episode discusses the fascinating story of Nightingale’s legacy -- how modern nursing was born out of the horrors of war, medical theories about poisonous air, the outsize influence of the average man, the first graph in history, and how a woman who died over a century ago presciently foresaw some of the most important scientific and social issues in medicine that are still with us today. Plus, a new #AdamAnswers about the doctor-nurse relationship.

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