Bedside Rounds

What does it mean when a computer can make better medical decisions than a human? The progress in large language models, and in particular the popularity of ChatGPT, has brought these questions to the forefront in 2023, but we've been discussing this for over 50 years. In this episode, Dr. Shani Herzig and I are going all the way back to the early 1970s with the invention of AAPHELP, the first real clinical decision support system, and the first time doctors had to contemplate working with – or competing against – computer systems.

American doctors spend the majority of their time during the day on the computer, either writing or reading notes about their patients; only a small fraction is spent with the human beings in their care. Technology itself – especially the electronic medical record – has often been blamed for this. But in this episode – a recorded grand rounds that I gave at the San Francisco VA in 2022 – I argue that this alienation has its roots in the way we've decided to organize clinical data, and the assumptions that we've made about the nature of medical care. In particular, I'm going to discuss one of the most influential medical thinkers of the second half of the 20th century, Larry Weed, his invention of the problem-oriented medical record and the SOAP note, and how his insight – that medical documentation fundamentally influences how we think about our patients – changed the way we think about our patients.

What do doctors actually do? Are they Sherlockian detectives, hunting down obscure clues to solve intractable cases? Are they virtuosic experts, training for half a lifetime to bring the latest science to bear to cure disease? Or are they clerks, whose main job is to collect and enter data into the electronic health record? In this episode, Adam is joined by medical and cultural historians Lakshmi Krishnan and Mike Neuss to discuss the stories we tell about our own work – and how this often conflicts with the realities of clinical practice.

Internal medicine physicians like to pride ourselves on our clinical reasoning – the ability to talk to any patient, pluck out seemingly random bits of information, and make a mystery diagnosis. But how does this actually work? In this episode, called The History, I'll be joined by Gurpreet Dhaliwal as we explore the beginnings of our understanding on how clinical reasoning works – starting in the middle of the 19th century with polar tensions between two ways of approaching our patients that are still felt today. Along the way, we'll talk about the American Civil War, Car Talk, Sherlock Holmes, and whether the practice of medicine can ever be considered a science. Sign up for Digital Education 2022 here: https://cmecatalog.hms.harvard.edu/digital-education Sources: Fitzgerald F, Curiosity. https://www.acpjournals.org/doi/full/10.7326/0003-4819-130-1-199901050-00015 Montgomery K, How Doctors Thinks (amazon link: https://www.amazon.com/How-Doctors-Think-Clinical-Judgment/dp/0195187121) Da Costa J, Medical Diagnosis, 1864. https://openlibrary.org/books/OL23402241M/Medical_diagnosis

In the early 19th century, a strange new illness, seemingly unknown to medicine, ravaged settler communities in the American Middle West. As fierce debates about this new disease, now called milk sickness, raged – was it from toxic swamp gasses? arsenic in the soil? infectious microorganisms? from the poor constitutions of the settlers – an irregular medicine woman named Dr. Anna and an indigenous Shawnee healer discovered the cause of the disease and successfully prevented it in their community. But their discovery went unheeded for over a half century. This is a live podcast that I gave to the South Dakota chapter of the American College of Physicians – plus a new Stethospeaks with Dr. Umme H. Faisal on the history of Resusci-Annie's mysteriously serene face! Teepublic store: https://www.teepublic.com/stores/bedsiderounds Sources: DOYLE JT. Milk sickness. N C Med J. 1947 Jul;8(7):404-10. PMID: 20250350. Furbee L, Snively WD Jr. Milk sickness, 1811-1966: a bibliography. J Hist Med Allied Sci. 1968 Jul;23(3):276-85. doi: 10.1093/jhmas/xxiii.3.276. PMID: 4875594. HARTMANN AF Sr, HARTMANN AF Jr, PURKERSON ML, WESLEY ME. Tremetol poisoning--not yet extinct. JAMA. 1963 Aug 31;185:706-9. doi: 10.1001/jama.1963.03060090038014. PMID: 13953145. Niederhofer RE. The milk sickness. Drake on medical interpretation. JAMA. 1985 Oct 18;254(15):2123-5. PMID: 3900448. Pickard ME and Buley RC, The Midwest Pioneer; His Ills, Cures, & Doctors. 1945. Snively WD Jr, Furbee L. Discoverer of the cause of milk sickness (Anna Pierce Hobbs Bixby). JAMA. 1966 Jun 20;196(12):1055-60. PMID: 5327806. Stenn F. Pioneer History of Milk Sickness. Ann Med Hist. 1937 Jan;9(1):23-29. PMID: 33943945; PMCID: PMC7942921. Townsend RB. Milk sickness- a plague on the new west. Scalpel Tongs. 1999 Jan-Feb;43(1):13-5. PMID: 11623628. Walker JW. Milk-sickness. Science. 1886 Dec 10;8(201):540. doi: 10.1126/science.ns-8.201.540. PMID: 17741312.

How can we medically tell whether or not someone is alive or dead? The answer is much more complicated than you'd think. In this episode, which is a live podcast I gave with Tony Breu at the Massachusetts Chapter of the American College of Physicians annual meeting on October 16, 2021, we track the evolution and controversies of the death exam, from a trans-Atlantic scandal surrounding a possible vivisection, a 19th century "X-prize" to determine a technology that could diagnose death, the important distinction between "permanent" and irreversible, and the mysterious Lazarus phenomenon. References: Rodman A, Breu A. The last breath: historical controversies surrounding determination of cardiopulmonary death. Chest. 2021; [online ahead of print August 13, 2021]. https://doi.org/10.1016/j.chest.2021.08.006

What does it mean when different physicians disagree about a diagnosis? I am joined by Dr. Shani Herzig as we explore this issue in the second part of my series on the development of diagnosis. We're going to discuss the advent of signal detection theory in the middle of the 20th century as new diagnostics such as laboratory testing and x-rays started to challenge the classical view of diagnosis. Along the way, we're going to talk about focal infection theory and why it seems that everyone in older generations had their tonsils removed as children, early and very inefficient chest x-rays, British radar operators trying to figure out if they were looking at a flock of geese or a German bomber, and finally probably one of the most important people in medical diagnostics that you've never heard of -- Jacob Yerushalmy. If you want to purchase any Bedside Rounds swag, the store is at https://www.teepublic.com/stores/bedsiderounds.

Words matter. At its best, etymology gives us insight not only into the origins of words, but why they remain so important today, especially in medicine, where we've been accruing jargon for millennia. In this episode, we're delving into four specific words -- doctor, cerebrovascular accident, rounds, and zebras. And along the way, we're going to discuss pre-historical pastoralists on the Eurasian steppes, medieval universities, Octagonal air-ventilated chambers in 19th century Baltimore, and of course, early 21st century sitcoms. Works cited: OSLER W. THE NATURAL METHOD OF TEACHING THE SUBJECT OF MEDICINE. JAMA. 1901;XXXVI(24):1673–1679. doi:10.1001/jama.1901.52470240001001 Fair, A 2014, 'A Laboratory of Heating and Ventilation: The Johns Hopkins Hospital as experimental architecture, 1870–90', The Journal of Architecture, vol. 19, no. 3, pp. 357-81. https://doi.org/10.1080/13602365.2014.930063 Engelhardt E. Apoplexy, cerebrovascular disease, and stroke: Historical evolution of terms and definitions. Dement Neuropsychol. 2017 Oct-Dec;11(4):449-453. doi: 10.1590/1980-57642016dn11-040016. PMID: 29354227; PMCID: PMC5770005. Coupland AP, Thapar A, Qureshi MI, Jenkins H, Davies AH. The definition of stroke. J R Soc Med. 2017 Jan;110(1):9-12. doi: 10.1177/0141076816680121. Epub 2017 Jan 13. PMID: 28084167; PMCID: PMC5298424. An Updated Definition of Stroke for the 21st Century Ralph L. Sacco, MD, MS, FAHA, FAAN, Co-Chair, Scott E. Kasner, MD, MSCE, FAHA, FAAN, Co-Chair, Joseph P. Broderick, MD, FAHA, Louis R. Caplan, MD, J.J. (Buddy) Connors, MD, Antonio Culebras, MD, FAHA, FAAN, Mitchell S.V. Elkind, MD, MS, FAHA, FAAN, Mary G. George, MD, MSPH, FAHA, Allen D. Hamdan, MD, Randall T. Higashida, MD, Brian L. Hoh, MD, FAHA, L. Scott Janis, PhD, Carlos S. Kase, MD, Dawn O. Kleindorfer, MD, FAHA, Jin-Moo Lee, MD, PhD, Michael E. Moseley, PhD, Eric D. Peterson, MD, MPH, FAHA, Tanya N. Turan, MD, MS, FAHA, Amy L. Valderrama, PhD, RN, and Harry V. Vinters, MD on behalf of the American Heart Association Stroke Council, Council on Cardiovascular Surgery and Anesthesia, Council on Cardiovascular Radiology and Intervention, Council on Cardiovascular and Stroke Nursing, Council on Epidemiology and Prevention, Council on Peripheral Vascular Disease, and Council on Nutrition, Physical Activity and Metabolism Harrison F, Roberts AE, Gabrilska R, Rumbaugh KP, Lee C, Diggle SP. A 1,000-Year-Old Antimicrobial Remedy with Antistaphylococcal Activity. mBio. 2015;6(4):e01129. Published 2015 Aug 11. doi:10.1128/mBio.01129-15 Furner-Pardoe J, Anonye BO, Cain R, Moat J, Ortori CA, Lee C, Barrett DA, Corre C, Harrison F. Anti-biofilm efficacy of a medieval treatment for bacterial infection requires the combination of multiple ingredients. Sci Rep. 2020 Jul 28;10(1):12687. doi: 10.1038/s41598-020-69273-8. PMID: 32724094; PMCID: PMC7387442. American Heritage Dictionary of Indo-European Roots, third edition, 2011 Oxford English Dictionary Online Johnson S, Dictionary. Retrieved online: https://johnsonsdictionaryonline.com/doctor-noun/ Riva MA. No renaissance for doctors in Shakespeare's plays. BMJ. 2017 May 22;357:j2223. doi: 10.1136/bmj.j2223. PMID: 28533302.

Diagnosis is arguably the most important job of a physician. But what does it actually mean to make a diagnosis? In this episode, we'll explore this question by tracking the development of the "classical" model of diagnosis and pathological anatomy and discussing three cases over three hundred years. Along the way, we'll ponder the concept of the lesion, iatromechanistic theories of the human machine, the birth of the International Classification of Diseases, and the rise and decline of the autopsy. You can sign up for the iMED Digital Education conference at cmeregistration.hms.harvard.edu/digitaleducation. Sources: Hooper R, The Physician's Vade-Mecum: Containing the Symptoms, Causes, Diagnosis, Prognosis and Treatment of Diseases. 1812. Holdman L et al, The Value of the Autopsy in Three Medical Eras. N Engl J Med 1983; 308:1000-1005. Cabot RC et al. CASE RECORDS OF THE MASSACHUSETTS GENERAL HOSPITALANTE-MORTEM AND POST-MORTEM RECORDS AS USED IN WEEKLY CLINICO-PATHOLOGICAL EXERCISES. Case 9431. Boston Med Surg J 1923; 189:595-599. Shojania KG and Burton EC, The Vanishing Nonforensic Autopsy. N Engl J Med 2008; 358:873-875 Morgagni GB. The seats and causes of diseases investigated by anatomy in five books, containing a great variety of dissections, with remarks. To which are added ... copious indexes. 1769. Retrieved online: https://openlibrary.org/works/OL15821973W/The_seats_and_causes_of_diseases_investigated_by_anatomy Castiglioni A, GB Morgagni and the Anatomico-pathological Conception of the Clinical. Proceedings of the Royal Society of Medicine, November 7, 1934. Thiene G, Padua University: The role it has played in the History of Medicine and Cardiology and its position today. European Heart Journal, Volume 30, Issue 6, March 2009, Pages 629–635. Zampieri F et al, Origin and development of modern medicine at the University of Padua and the role of the "Serenissima" Republic of Venice. Glob Cardiol Sci Pract. 2013; 2013(2): 149–162. Conner, Annastasia (2017) "Galen's Analogy: Animal Experimentation and Anatomy in the Second Century C.E.," Anthós: Vol. 8: Iss. 1, Article 9. Zampieri F et al. The clinico-pathological conference, based upon Giovanni Battista Morgagni's legacy, remains of fundamental importance even in the era of the vanishing autopsy. Virchows Arch. 2015 Sep;467(3):249-54. Ghosh SK, Giovanni Battista Morgagni (1682-1771): father of pathologic anatomy and pioneer of modern medicine. Anat Sci Int. 2017 Jun;92(3):305-312. O'Neal JC, Auenbrugger, Corvisart, and the Perception of Disease. Eighteenth-Century Studies Vol. 31, No. 4, The Mind/Body Problem (Summer, 1998), pp. 473-489 Brown TM, THE COLLEGE OF PHYSICIANS AND THE ACCEPTANCE OF IATROMECHANISM IN ENGLAND, 1665-1695. Bulletin of the History of Medicine Vol. 44, No. 1 (JANUARY-FEBRUARY 1970), pp. 12-30 Roos AM, Luminaries in Medicine: Richard Mead, James Gibbs, and Solar and Lunar Effects on the Human Body in Early Modern England. Bulletin of the History of Medicine Vol. 74, No. 3 (Fall 2000), pp. 433-457 (25 pages) Frith J, History of Tuberculosis. Part 1 – Phthisis, consumption and the White Plague. JMVH. 2014; 22(2). World Health Organization, History of the development of the ICD. https://www.who.int/classifications/icd/en/HistoryOfICD.pdf Laennec RTH, A treatise on diseases of the chest and on mediate auscultation. 1834. Retrieved from: https://archive.org/details/b21987002. Marinker M, Why make people patients? J Med Ethics. 1975 Jul; 1(2): 81–84. King LS, Medical Thinking: A Historical Preface. Princeton University Press, 2016.

The COVID-19 pandemic laid bare the racial health disparities in the United States, with markedly increased mortality especially among Blacks and Native Americans. In this episode, Tony Breu and I discuss the conception of race, racism, and the social determinants of health through three historic plagues in the United States -- from yellow fever in New Orleans, to poliomyelitis, and finally the early days of HIV/AIDS -- and what lessons we can draw for COVID-19. Along the way, we'll discuss the unique social capital afforded by acclimation, immunity passports, the concept of the "original antigenic sin," and constitutionalism and eugenics. This presentation was performed live at the annual meeting of the Massachusetts American College of Physicians, and is only lightly edited. SOURCES: Monath TP, Yellow fever: an update. Lancet Infect Dis. 2001 Aug;1(1):11-20. doi: 10.1016/S1473-3099(01)00016-0. Kallas EG, D'Elia Zanella LGFAB, Moreira CHV, Buccheri R, Diniz GBF, Castiñeiras ACP, Costa PR, Dias JZC, Marmorato MP, Song ATW, Maestri A, Borges IC, Joelsons D, Cerqueira NB, Santiago E Souza NC, Morales Claro I, Sabino EC, Levi JE, Avelino-Silva VI, Ho YL. Predictors of mortality in patients with yellow fever: an observational cohort study. Lancet Infect Dis. 2019 Jul;19(7):750-758. doi: 10.1016/S1473-3099(19)30125-2. Epub 2019 May 16. Erratum in: Lancet Infect Dis. 2019 Nov;19(11):e370. PMID: 31104909. Blake LE, Garcia-Blanco MA. Human genetic variation and yellow fever mortality during 19th century U.S. epidemics. mBio. 2014 Jun 3;5(3):e01253-14. doi: 10.1128/mBio.01253-14. PMID: 24895309; PMCID: PMC4049105. Jelili Ojodu, MPH1, Mary M. Hulihan, MPH2, Shammara N. Pope, MPH2, Althea M. Grant, PhD2,, MMWR, Incidence of Sickle Cell Trait — United States, 2010. IthaMaps, Haemoglobin Epidemiology. https://www.ithanet.eu/db/ithamaps?country=GR Serjeant GR, The natural history of sickle cell disease. Cold Spring Harb Perspect Med. 2013 Oct; 3(10): a011783. Hamosh A, FitzSimmons SC, Macek M Jr, Knowles MR, Rosenstein BJ, Cutting GR. Comparison of the clinical manifestations of cystic fibrosis in black and white patients. J Pediatr. 1998 Feb;132(2):255-9. doi: 10.1016/s0022-3476(98)70441-x. PMID: 9506637. Gershman KD et al, Yellow Fever Vaccine & Malaria Prophylaxis Information, by Country. CDC. Kofler N and Baylis F, Ten reasons why immunity passports are a bad idea. Nature 21 May 2020. NASEM, National Academies Release Framework for Equitable Allocation of a COVID-19 Vaccine for Adoption by HHS, State, Tribal, Local, and Territorial Authorities. Schmidt H et al, Covid-19: how to prioritize worse-off populations in allocating safe and effective vaccines.BMJ 2020; 371 doi: https://doi.org/10.1136/bmj.m3795 (Published 05 October 2020). Siegal FP, Lopez C, Hammer GS, Brown AE, Kornfeld SJ, Gold J, Hassett J, Hirschman SZ, Cunningham-Rundles C, Adelsberg BR, et al. Severe acquired immunodeficiency in male homosexuals, manifested by chronic perianal ulcerative herpes simplex lesions. N Engl J Med. 1981 Dec 10;305(24):1439-44. doi: 10.1056/NEJM198112103052403. PMID: 6272110. Lushniak BD, Surgeon General's Perspectives. Public Health Rep. 2014 Mar-Apr; 129(2): 112–114. Booske BC et al, "Different Perspectives For Assigning Weights to Determinants of Health," University of Wisconsin Population Health Institute. Marc LG et al,HIV among Haitian-born persons in the United States, 1985–2007, AIDS. Author manuscript; available in PMC 2011 Aug 24. Rogers N, Race and the Politics of Polio: Warm Springs, Tuskegee, and the March of Dimes. Am J Public Health. 2007 May; 97(5): 784–795. Curran JW and Jaffe HW, AIDS: the Early Years and CDC's Response. MMWR. Olivarius Kathryn, Immunity, Capital, and Power in Antebellum New Orleans. The American Historical Review, Volume 124, Issue 2, April 2019, Pages 425–455,

The 1889 Russian Flu was the first influenza pandemic in an increasingly globalized world. In this episode, the second of a two-parter on how hydroxychloroquine became a great hope in COVID-19, we'll talk about how quinine became the standard of care for influenza. Along the way, we'll discuss the astrological origins of the flu, the nosological difficulties of identifying past pandemics, conspiracy theories about previous global coronavirus outbreaks, the media panic over the Russian Flu, first year law school cases about Carbolic Smoke Balls, and the first studies into quinine's efficacy in influenza. References Seeler, A. O., Graessle, O. & Ott, W. H. Effect of Quinine on Influenza Virus Infections in Mice. J Infect Dis 79, 156–158 (1946). Barberis, I., Myles, P., Ault, S. K., Bragazzi, N. L. & Martini, M. History and evolution of influenza control through vaccination: from the first monovalent vaccine to universal vaccines. J Prev Medicine Hyg 57, E115–E120 (2016). Ewing, E. T. La Grippe or Russian influenza: Mortality statistics during the 1890 Epidemic in Indiana. Influenza Other Resp 13, 279–287 (2019). Gold, E. Pandemic Influenza 1700-1900: A Study in Historical Epidemiology. Jama 257, 2656–2656 (1987). Rice, G. W. & Palmer, E. Pandemic Influenza in Japan, 1918-19: Mortality Patterns and Official Responses. J Jpn Stud 19, 389 (1993). Mulder, J., Masurel, N., Deggars, E. M. & Webbers, P. T. PRE-EPIDEMIC ANTIBODY AGAINST 1957 STRAIN OF ASIATIC INFLUENZA IN SERUM OF OLDER PEOPLE LIVING IN THE NETHERLANDS. Lancet 271, 810–814 (1958). Refresher Course for General Practitioners. J Amer Med Assoc 152, 773 (1953). Moore, J. W. The influenza epidemic of 1889–90, as observed in Dublin. Transactions Royal Acad Medicine Irel 8, 56–74 (1890). Textbook of Influenza. (n.d.). Coghill, J. G. S. The Prophylaxis of Influenza. Brit Med J 1, 751 (1895). When early modern Europe caught the flu. A scientific account of pandemic influenza in sixteenth century Sicily. (n.d.). Potter. A history of influenza. Valleron AJ et al, Transmissibility and geographic spread of the 1889 influenza pandemic. PNAS May 11, 2010 107 (19) 8778-8781 Cavallaro JJ and Monto AS. Community-wide Outbreak of Infection with a 229E-like Coronavirus in Tecumseh, Michigan.The Journal of Infectious Diseases. Vol. 122, No. 4 (Oct., 1970), pp. 272-279 Mulder J and Masurel N, Pre-epidemic Antibody Against 1957 Strain of Asiatic Influenza in Serum of Older People Living in the Netherlands. Lancet. 1958 Apr 19;1(7025):810-4 Vijgen L et al. Complete Genomic Sequence of Human Coronavirus OC43: Molecular Clock Analysis Suggests a Relatively Recent Zoonotic Coronavirus Transmission Event. J Virol. 2005 Feb; 79(3): 1595–1604. Saunders-Hastings PR and Krewski D. Reviewing the History of Pandemic Influenza: Understanding Patterns of Emergence and Transmission. Pathogens. 2016 Dec; 5(4): 66. Pappas G et al. Insights into infectious disease in the era of Hippocrates.International Journal of Infectious Diseases Volume 12, Issue 4, July 2008, Pages 347-350. Flint A, Principles and Practice of Medicine. https://collections.nlm.nih.gov/bookviewer?PID=nlm:nlmuid-100894695-bk#page/234/mode/2up/search/influenza Osler W, Principles and Practice of Medicine. https://archive.org/details/principlespract00osle/page/1002/mode/2up Taubenberger JK and Morens DM. Influenza: The Once and Future Pandemic. Public Health Rep. 2010; 125(Suppl 3): 16–26. Shope RE. Influenza: history, epidemiology, and speculation. Public Health Rep. 1958 Feb; 73(2): 165–179. Ewing ET. Will It Come Here? Using Digital Humanities Tools to Explore Medical Understanding during the Russian Flu Epidemic, 1889–90. Med Hist. 2017 Jul; 61(3): 474–477.

Where did cinchona, the first medication to cure malaria, come from? This episode explores the murky history of the bark of the fever tree and its derivative chloroquine with mysterious pre-Columbian Pacific crossings of the plasmodium parasite, Jesuit priests and Inca healers, a Chinese Emperor performing a clinical trial to treat his fever, chemistry leading to the first modern pharmaceuticals, and imperialism on a global scale. This episode is the first of a multi-part series exploring how hydroxychloroquine became the great hope for treating COVID-19. Sources: Jaramillo‐Arango, J. A Critical Review of the Basic Facts in the History of Cinchona. J Linn Soc Lond Botany 53, 272–311 (1949). Smith, N. K. A Cure for Ague. J Roy Soc Med 90, 589–590 (1997). Potter, C. W. A history of influenza. J Appl Microbiol 91, 572–579 (2001). Cunha, C. B. & Cunha, B. A. Brief history of the clinical diagnosis of malaria: from Hippocrates to Osler. J Vector Dis 45, 194–9 (2008). Goss, A. Building the world's supply of quinine: Dutch colonialism and the origins of a global pharmaceutical industry. Endeavour 38, 8–18 (2014). Al-Bari, Md. A. A. Chloroquine analogues in drug discovery: new directions of uses, mechanisms of actions and toxic manifestations from malaria to multifarious diseases. J Antimicrob Chemoth 70, 1608–1621 (2015). Guastalegname, M. & Vallone, A. Could chloroquine /hydroxychloroquine be harmful in Coronavirus Disease 2019 (COVID-19) treatment? Clin Infect Dis (2020) doi:10.1093/cid/ciaa321. Alia, E. & Grant-Kels, J. M. Does Hydroxychloroquine Combat COVID-19? A Timeline of Evidence. J Am Acad Dermatol (2020) doi:10.1016/j.jaad.2020.04.031. Seeler, A. O., Graessle, O. & Ott, W. H. Effect of Quinine on Influenza Virus Infections in Mice. J Infect Dis 79, 156–158 (1946). Savarino, A., Boelaert, J. R., Cassone, A., Majori, G. & Cauda, R. Effects of chloroquine on viral infections: an old drug against today's diseases. Lancet Infect Dis 3, 722–727 (2003). Chakrabarti, P. Empire and Alternatives: Swietenia febrifuga and the Cinchona Substitutes. Med Hist 54, 75–94 (2010). Lonie, I. M. Fever pathology in the sixteenth century: tradition and innovation. Med Hist 25, 19–44 (1981). Luke, T. C. et al. Hark back&colon Passive immunotherapy for influenza and other serious infections. Crit Care Med 38, e66–e73 (2010). Shanks, G. D. Historical Review: Problematic Malaria Prophylaxis with Quinine. Am J Tropical Medicine Hyg 95, 269–272 (2016). Harrison, N. In celebration of the Jesuit's powder: a history of malaria treatment. Lancet Infect Dis 15, 1143 (2015). Gerszten, E., Allison, M. J. & Maguire, B. Paleopathology in South American Mummies: A Review and New Findings. Pathobiology 79, 247–256 (2012). Haas, L. F. Pierre Joseph Pelletier (1788-1842) and Jean Bienaime Caventou (1795-1887). J Neurology Neurosurg Psychiatry 57, 1333 (1994). PROPHYLACTIC QUININE IN INFLUENZA. Lancet 204, 1152 (1924). Gensini, G. F. & Conti, A. A. The evolution of the concept of 'fever' in the history of medicine: from pathological picture per se to clinical epiphenomenon (and vice versa). J Infection 49, 85–87 (2004). Bergman, G. J. The history and importance of cinchona bark as an anti‐malarial febrifuge. Sci Educ 32, 93–103 (1948). Thompson, C. & MBE. The History and Lore of Cinchona. (n.d.). THE HUXLEY MEMORIAL. Lancet 146, 1381 (1895). Urdang, G. The Legend on Cinchona. (n.d.). Castro, M. C. de & Singer, B. H. Was malaria present in the Amazon before the European conquest? Available evidence and future research agenda. J Archaeol Sci 32, 337–340 (2005). Kummu M et al, How Close Do We Live to Water? A Global Analysis of Population Distance to Freshwater Bodies. PLoS One. 2011; 6(6): e20578. Dawson WT et al, IDIOSYNCRASY TO QUININE, CINCHONIDINE AND ETHYLHYDROCUPREINEv AND OTHER LEVOROTATORY ALKALOIDS OF THE CINCHONA SERIES: PRELIMINARY REPORT. JAMA 8 Mar 1930. Bynum WF, Cullen and the study of fevers in Bitain, 1760-1820. Medical History, supplement no 1, 1981. Rodrigues PT et al, Human migration and the spread of malaria parasites to the New World. Nature, 31 January 2018. Achan J et al, Quinine, an old anti-malarial drug in a modern world: role in the treatment of malaria. Malar J. 2011; 10: 144. Norn PH, On the history of Cinchona bark in the treatment of Malaria.Dansk Medicinhistorisk Arbog, 31 Dec 2015, 44:9-30. Cook H (2010). Testing the effects of Jesuit's bark in the Chinese Emperor's court. JLL Bulletin: Commentaries on the history of treatment evaluation (https://www.jameslindlibrary.org/articles/testing-the-effects-of-jesuits-bark-in-the-chinese-emperors-court/)

Plagues have fascinated us since antiquity, but the Antonine Plague stands out because one of the most famous physicians in Western history was present to make detailed observations. In this episode, guest host Liam Conway-Pearson explores what we know -- and what we don't know -- about this plague, which ravaged Rome two millennia ago. Plus a brand new #AdamAnswers about using convalescent plasma to treat the Spanish Flu of 1918! Sources: Adrian Muraru, "On Galen of Pergamum: The Greek Physician and Philosopher of Late Antiquity in the Roman Empire," Agathos 9, no.2 (2018): 7-20. H. Clifford Lane and Anthony S. Fauci, "Microbial Bioterrorism," in Harrison's Principles of Internal Medicine, 20e, ed. J. Larry Jameson et al. (New York: McGraw Hill, 2018), S2. James Greenberg, "Plagued by Doubt: Reconsidering the Impact of a Mortality Crisis in the 2nd C. A.D.," Journal of Roman Archaeology 16 (2003): 413-425. Jennifer Manley, "Measles and Ancient Plagues: A Note on New Scientific Evidence," Classical World 107, no. 3 (Spring 2014): 393-397. J. F. Gilliam, "The Plague under Marcus Aurelius," The American Journal of Philology 82, no. 3 (July 1961): 225-251. John Haldon, Hugh Elton, Sabine R. Huebner, Adam Izdebski, Lee Mordechai, and Timothy P. Newfield, "Plagues, Climate Change, and the End of an Empire. A Response to Kyle Harper's The Fate of Rome (2): Plagues and a Crisis of Empire," History Compass 6, no. 12 (November 2018). Joseph B. Fullerton and Mark E. Silverman, "Claudius Galen of Pergamum: Authority of Medieval Medicine," Clinical Cardiology 32, no. 11 (January 2008): E82-E84. Joseph R. McConnell, Andrew I. Wilson, Andreas Stohl, Monica M. Arienzo, Nathan J. Chellman, Sabine Eckhardt, Elisabeth M. Thompson, A. Mark Pollard, and Jørgen Pender Steffensen, "Lead Pollution Recorded in Greenland Ice Indicates European Emissions Tracked Plagues, Wars, and Imperial Expansion during Antiquity," PNAS 115, no. 22 (May 2018): 5726-5731. J. Rufus Fears, "The Plague under Marcus Aurelius and the Decline and Fall of the Roman Empire," Infectious Disease Clinics of North America 18 (2004): 65-77. Kyle Harper, The Fate of Rome (Princeton NJ: Princeton University Press, 2017), 23-118. Mike Duncan, The History of Rome, Podcast Audio, 2007-2013. https://thehistoryofrome.typepad.com/the_history_of_rome/archives.html R. J. Littman and M. L. Littman, "Galen and the Antonine Plague," The American Journal of Philology 94, no. 3 (Autumn 1973): 243-255. R. P. Duncan-Jones, "The Impact of the Antonine Plague," Journal of Roman Archaeology 9 (1996): 108-136. "Smallpox," CDC, last modified June 7, 2016, https://www.cdc.gov/smallpox/transmission/index.html. Vivian Nutton, "The Chronology of Galen's Early Career," The Classical Quarterly 23, no. 1 (May 1973): 158-171. Yuki Furuse, Akira Suzuki, and Hitoshi Oshitani, "Origin of Measles Virus: Divergence from Rinderpest Virus between the 11th and 12th Centuries," Virology Journal 7, no. 52 (March 2010): 1-4. Catherine Thėves, Eric Crubėzy, and Philippe Biagini, "History of Smallpox and Its Spread in Human Populations," Microbiology Spectrum 4, no. 4 (April 2015): Walter Scheidel, "A Model of Demographic and Economic Change in Roman Egypt after the Antonine Plague," Journal of Roman Archaeology 15 (2002): 97-114.