Episode 43: The Cursed

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!



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  • Burchell HB, Digitalis poisoning: historical and forensic aspects. J Am Coll Cardiol. 1983 Feb;1(2 Pt 1):506-16.
  • Burton JL, A Bite Into the History of the Autopsy: From Ancient Roots to Modern Decay. Forensic Sci. Med. Pathol. 1:4:277.
  • Cerda JL. Charles II of Spain, «the bewitched». Rev. méd. Chile  [Internet]. 2008 Feb [cited 2019 Feb 11] ; 136( 2 ): 267-270.
    Cullen W, Nosology. Retrieved online at: https://books.google.com/books?id=3IgUAAAAQAAJ&printsec=frontcover&source=gbs_ge_summary_r&cad=0#v=onepage&q&f=false
  • Foucault, Michel. The Birth of the Clinic: An Archaeology of Medical Perception. New York: Vintage Books, 1975.
  • Gargantilla Madera P. Enfermedades de los reyes de España, los Austrias : de la locura de Juana a la impotencia de Carlos II el Hechizado. Madrid 2005.
    Ghosh SK, “Giovanni Battista Morgagni (1682-1771): father of pathologic anatomy and pioneer of Modern Medicine, Anat Sci Int, 6 Sep 2016.
  • Gruener A. Vincent van Gogh’s yellow vision. Br J Gen Pract. 2013;63(612):370-1.
    Hodge GP. A Medical History of the Spanish Habsburgs: As Traced in Portraits. JAMA. 1977;238(11):1169–1174.
  • Lagay F, The Legacy of Humoral Medicine, Virtual Mentor. 2002;4(7):
  • Lee TC. Van Gogh’s Vision: Digitalis Intoxication? JAMA. 1981;245(7):727–729.
    Lesney MS, Flowers for the heart, ACS, March 2002, Vol. 5, No. 3, pp 46, 48
  • López AG et al, Charles II: From Spell to Genitourinary Pathology. Arch. Esp. Urol. 2009; 62 (3): 179-185.
  • Somberg J et al, Digitalis: Historical Development in Clinical Medicine, The Journal of Clinical Pharmacology, Volume 25, Issue 7
  • Starkstein, S., & Berrios, G. (2015). The “Preliminary Discourse” to Methodical Nosology, by François Boissier de Sauvages (1772). History of Psychiatry, 26(4), 477–491.
    Viale G, The rete mirabile of the cranial base: a millenary legend. Neurosurgery. 2006 Jun;58(6):1198-208.


This is Adam Rodman, and you’re listening to Bedside Rounds, a monthly podcast on the weird, wonderful, and intensely human stories that have shaped modern medicine, hosted in partnership with the American College of Physicians. If you’re a member of the ACP, you can get CME and MOC credit for listening by going to www.acponline.org/BedsideRounds. This episode is called “The Cursed” and it’s about the mysterious death of Charles II of Spain, “El Hechizado,” the last of the Spanish Hapsburgs, whose autopsy famously showed the king had the “heart the size of a peppercorn,” and a body without a single drop of blood. But it’s also an exploration of medical perception, and how the clinical gaze of physicians has affected what doctors see throughout the generations — and continues to shape the way we all approach our patients today. Along the way, we’ll talk about inbreeding coefficients, Michel Foucault and postmodern philosophy, the history of anatomy, and, well, two thousand years of medical history. That’s quite a lift — so let’s get going!


The Hapsburg family ruled Spain from 1516 to 1700, a period in which the peninsular nation would dominate not only Europe but territory over the entire World. The sun truly never set on the Spanish Empire, with territory in North and South America, the Philippines, the Low Countries, France, Germany, as well as the Portuguese Empire. The wealth that flooded the nation brought on the Spanish Golden Age — this is the Spain of Miguel de Cervantes, Diego Velazquez, and El Greco. But this isn’t about the glory of the Spanish Hapsburgs — I want to start with their end, by examining the murky medical mystery surrounding the sickly life and untimely death of Charles II of Spain. The unfortunate life and ignominious end of Charles II was large seen by his contemporaries as a parallel to Spain’s ruling family as a whole. One of the methods of consolidating power and territory for the Hapsburgs had been aggressive intermarriage over two centuries. Unfortunately, this led to increasingly interbred progeny. Alvarez and his colleagues performed an analysis of over 3,000 Hapsburgs, stretching back 16 generations. They used this data to construct a detailed pedigree, and then calculate inbreeding coefficients for each of its members. If you’ve ever gone to prenatal genetic counseling, this is essentially the same process you went through, though on a much more massive scale. Charles II was horrifically inbred; his coefficient was 0.254 — in comparison, this is MORE inbred than the offspring from a parent-child or brother-sister union. If this doesn’t make sense how a person can be more inbred than the product of incest, I’ve posted the pedigree to a thread on Twitter. Inbreeding causes an increased expression of recessive disorders — likely the evolutionary reason for widespread taboos. And as you would expect, the Spanish Hapsburgs were remarkably sickly. 30 percent of children died before one year old — and 50% died before the age of 10. Lest you think this was just a sign of high infant mortality, contemporary Spanish villages, which would have a wide range of socio-economic classes, had an infant mortality rates of only 20%.


All of this is to say, that when Charles was born in 1661, the deck was stacked against him. Within weeks of his birth, concerns were raised about his health, and ambiguous genitalia in particular. The Imperial ambassador to Madrid relayed some of these rumors: “They say quite clearly, among other things, that they do not think Spain has a prince, because he is not male but female.” Louis XIV of France, the Sun King himself, was so concerned that he sent his ambassador to inspect the new prince — though he was not allowed to examine him unclothed. He wrote, “The prince seems extremely weak, both cheeks have a herpes-type rash, the head is covered with scabs, and below the right ear a type of suppurating duct or drainage has formed. We have heard of this through other channels as the bonnet the child usually wears prevents seeing this area.” His childhood fared no better — Charles was plagued by seizures and had developmental delays — he couldn’t stand until age six, and he had difficulty reading and writing. He had the famed underbite of his ancestors — the Hapsburg jaw — and a large tongue at that, which made speech difficult. His looks were revolting to those around him. When he came of age, his privy counsel planned a marriage to a French princess. This prompted the French ambassador to write, “The Catholic King is so ugly as to cause fear.” I’ve posted several paintings of Charles II to my Twitter. Dr. Hodge actually analyzed the royal portraiture of the Hapsburgs, and along with historical data advance the idea that Charles may have had Klinefelter’s syndrome. In any event, he was sterile and unable to produce an heir from two different wives.  


Much of his life, Charles was expected to die shortly, his health was so poor. Throughout his 20s and 30s, his health worsened even further. He started to have recurrent fevers, and on one occasion his fever occurred with hematuria, blood in the urine. Unsurprisingly given Castillian beliefs at the time, his court and his people felt that there was only one explanation for this cluster of unfortunate symptoms — the king must have been bewitched. His privy council sought out a prominent exorcist, who in an elaborate ceremony communed with Satan himself confirming the curse, and that “the spell had been cast in a cup of chocolate on 3 April 1675 and containing the dissolved brain of an executed criminal to take away his reason, intestines to take away his health, and kidneys to corrupt his semen and prevent him from engendering offspring.” Increasingly bizarre exorcisms were held, including exhuming his deceased ancestors and having Charles sleep next to them.


By 1700, the King could barely walk, was blind and bald, and had frequent seizures. During his last few months of life, he suffered from dropsy or edema, constant fevers, and intractable diarrhea. Besides his exorcisms, he was subject to humoral medical treatments from the court physician. Blisters of cantharides were put on his feet; freshly killed pigeons on his head. The steaming entrails of animals were laid out on his stomach. Aquavitae — distilled liquor — was sprinkled upon him. But nonetheless, he died on November 1st, 1700, just short of his 39th birthday. Charles II was the last of his line, and Spanish throne was succeeded by the Bourbons. An autopsy followed, which according to Gargantilla, noted that his body ”did not contain a single drop of blood, his heart was the size of a peppercorn; his lungs corroded; his intestines rotten and gangrenous; he had a single testicle, black as coal, and his head was full of water.


So this brings us to this fascinating medical mystery — what killed poor inbred Charles II? And how can we possibly explain such curious autopsy findings like a heart the size of a peppercorn, and a bloodless body?


I am going to attempt to answer this question in the most me way possible — so sufficed to say, it’s not what you think. But first, we have to start from the very beginning. One of my favorite quotes, which I’ve used on the show before, is from Carl Sagan: if you wish to make apple pie from scratch, you must first create the universe. In this case, I want to go back and examine one of the most fundamental assumptions behind medicine — what constitutes disease, and what is the relationship between a physician and a patient with a disease. This is a harder lift than the normal topics that I usually tackle on Bedside Rounds, so instead of hitting old medical articles, I’m going to rely on the field of philosophy — in particular, the works of Michel Foucault. Foucault, broadly speaking, is a postmodern philosopher most interested in power relationships, but that doesn’t even start to scratch the surface. He had a career spanning decades, various interests, shifting views. He was particularly interested in the generation of scientific knowledge and ideas. If you’re a listener of the show, it should be fairly obvious why I find Foucault so fascinating — this podcast is about the history of medicine, but it’s also about interrogating epistemology — how we as physicians know things.


So let’s talk about “The Birth of the Clinic,” subtitled  “An Archaeology of Medical Perception.”  It’s ostensibly about my favorite period of medical history — the Paris Clinical School, dating from the French Revolution through roughly the middle of the 19th century. In fact, I have dedicated 4 of the last 10 episodes to this period of history, and I 3D-printed a copy of Laennec’s stethoscope and occasionally take it on rounds with me. The reason that Foucault decided to study the Paris Clinical School is the same reason I’m so obsessed with it — many of the fundamental epistemologic and pedagogical precepts that define modern medical practice were developed in this period. It’s a great book — and surprisingly readable, given that it’s a revered philosophical tome — and don’t worry, I’m not going to do a book report. But he discusses two interlocking themes that I think best explain the death — and subsequent autopsy — of Charles II.


The first is “le regard” in French, translated usually as the clinical gaze, or I think generally more accurately as “medical perception”. This is the act of a physician “seeing” and medicalizing a patient, of localizing their disease, of planning treatment and evaluating response.  As part of my day job, I have the joy of working with medical students during their standardized patient settings, which allows me to see the development of a clinical gaze over a period of four years. During the early first year, my students largely relate to their patients like, for lack of a better word, the normal people that they still are — they’re worried about their patient’s  emotional response to their illness and they struggle with development of what we call the “HPI” — history of present illness, twisting a conversation to help illuminate or eliminate hidden sources of disease deep inside the patient’s body. By their fourth year, though, students have mastered the gaze — with just a few questions, they can determine risk for heart attack versus reflux, pneumonia versus pulmonary embolism. But their way of relating and communicating with their patients has changed. The difference could not be more dramatic.


The second idea that Foucault explores in Birth of the Clinic is the “epistemic shift,” though he doesn’t use those words so much as describe one; the word “episteme” comes from his next book “The Order of Things.”  An episteme, simplifying, is the unspoken, unconscious assumptions that frame scientific discourse in an era. 


The easiest way to understand this idea is to understand what it is not. The traditional narrative of science is one of slow progress, with new ideas are added, tested, and either falsified or accepted. This is pretty much the standard version of medical history that we learn. Take for example, this story, which you’ve probably heard a version of many times: deep in the mists of history, ancient societies like the Greeks and the Egyptians realized that disease was natural and understandable, and through astute observation realized that they could understand, and hopefully even treat disease. They described some basic physiology and anatomy, and developed an impressive armament of medical herbs. By the time of the Romans and Galen, this knowledge had largely been codified. As Europe descended into the bleakness of the middle ages, this knowledge was maintained, and even advanced by the Arabs, especially Avicenna. Starting in the 16th century, Europeans started to advance beyond the ancients — Vesalius with his anatomy, Harvey with his physiology, and over the next half millenia innovations and discoveries were gradually made to bring us to our current era of radiology, chemotherapy, and antibiotics.


This should sound pretty familiar to you. Any medical review article basically follows this pattern — a slow accumulation of knowledge, generally starting with the Hippocratics and continuing through the present day. At its most extreme, you get something called “the Chart” which pops up on the internet from time to time — a “graph” showing the accumulation of scientific knowledge, with a big drop during the medieval era, the subtext being that, “if only the Roman Empire hadn’t collapsed, we’d be an interstellar civilization,” or something like that.


And this was the dominant narrative of scientific progress, largely until Thomas Kuhn and his Structure of Scientific Revolutions.  He described another model of scientific change — the paradigm shift. A paradigm is a set of fundamental concepts and assumptions surrounding a scientific theory. Rather than constant progress, he argued, things change when two paradigms conflict, and then one wins out. You can see paradigm shifts frequently in the history of medicine, and I’ve covered some on the show — take, for example, the debate around contagion vivum, germ theory — the idea that disease came from infectious microorganisms which were mostly a theoretical construct at that point, and miasma, or that disease came from foul odors in the air. Both sides had compelling evidence, and etiologies that were plausible given the scientific understanding of the time. They were truly two different paradigms to understand disease — of course, until one gained more data and got the upper hand. 


A Foucouldian epistemic shift is analogous to a paradigm shift, but even more fundamental. In a paradigm, the two sides are at least speaking the same language; William Farr and John Snow both argued about the cause of cholera using the language of statistics and epidemiology. An episteme is all the unconscious assumptions that surround our search for knowledge, the borders that control and constrain our attempts to understand reality. And as you can imagine, epistemes change far less frequently than paradigms.


This is great and all, but how does it relate to the mystery of Charles’ death and autopsy? Don’t worry, dear listener, I’m getting there. But first, I want to show you how epistemic shifts have constrained the clinical gaze throughout history, by taking you on a brief intellectual history of, well, all of Western medicine, focusing on autopsy in particular.


Starting off, we have an episteme that I would call traditional Western medicine, which dates back to the ancients and lasted well into the early modern era. The underlying assumption here is that health is caused by the balance of constituent body fluids — blood, black bile, yellow bile, and phlegm, and that disease is caused by its imbalance. Just as the body lies in the balance of its fluids, the human organism lies in balance with the rest of nature. The humors can be affected by the food, weather, altitude, close contacts, alignment of the stars and planets — and imbalances in any of these can cause disease. These assumptions have important implications. Human health cannot be separated from the environment in which it lives. By definition, medicine needs to be holistic — spending less time with your choleric brother, eating more cabbage, and bloodletting are all appropriate therapies  But diseases are also not unique and discrete entities, and do not have discrete treatments. If a breast cancer and melancholy are both caused by too much black bile, the treatment for each is the same.


This is the episteme in which the autopsy first developed — disease localized in body fluids, and not in particular organs. You can see this in the Egyptians, would would discard organs during the mummification process, and in the Greeks, who based much of their knowledge of anatomy of comparison with similar animals and from surface wounds. But since disease is throughout the body, individual parts are less important — hence why major errors were propagated through classical learning, such as the rete mirabile, the “wonderful net” of arteries and veins that Galen mistakenly thought was in the neck of humans, based on dissection of sheep. The rete mirabile, for what it’s worth, was thought to give rise to the “vital spirit” that would abide in the brain. This view lasted even through the Italian Renaissance in the 16th century and onward, when Vesalius and his successors began dissect actually humans are correct many of the errors propagated by the ancients. These new anatomists were keen observers; for example, Pieter Pauw in 1590 autopsied a young woman who had died of blindness, thirst, and extreme fluid intake. He wrote that he found a “significant vesicle, that had occupied the optic nerves close to their crossing, and when I cut in open half a pound of the clearest of watery material flowed out” — in retrospect, a case of diabetes inspidus caused by an arachnoid cyst. But there was still no sense that disease lay in any specific place; it was still caused by mysterious imbalances in body fluids, and from the life-bringing “pneuma,” or the air of life that was thought to run through the veins. 


But everything starts to change starting in roughly the late 17th century, and really coming of age in the 18th — the episteme of nosology. A new group of physicians, most notably Thomas Sydenham in England, but also Cullen, Sauvages, and Pinel, rejected humoral explanations; they didn’t match up with the complexity that the anatomists and physiologists had shown. Instead, they worked to develop a “garden” of diagnoses; Sydenham in particular was influenced by Linnaeus, who had categorized all of life into classes, orders, genera, and species. Just as a rational God had arrayed the natural world in clusters of species, surely he must have done the same with human disease. And they classified a lot of species — thousands of them, grouped by their symptoms. Sauvages, for example, classified his diseases into 10 classes, 295 genera, and 2400 species. 


A new conceptualization means a new gaze. Disease is now discrete, not a continuum. But a disease is defined by its symptoms. Because we’ve taken many of these terms in our modern parlance, it can be a bit confusing to discuss; it’s hard for modern physicians to abandon their own gaze. So let me give an example from Cullen’s nosology, which I’m picking because of its influence in early American physicians like Benjamin Rush, and the fact that it’s been translated into English (Cullen, despite being Scottish, still wrote in Latin). By the way, in the shownotes I’ve linked to a digital copy of Cullen’s Nosology so you can follow along yourself. Let’s start with gastritis. If I were a late 18th century physician, and I suspect gastritis in a patient, I’d turn to class of Pyrexia, or fevers, in the order of Phlegmasiae. If the patient has acute abdominal pain and “vehement” pyrexia, I’d say that this patient has gastritis phlegmonodea. But if the pain and fever are only slight, I’d diagnose gastritis erythematica. A disease in this sense “takes hold” of an individual. If a fever goes from slight to vehement — the disease itself has changed. Everything is categorized by symptoms. And there are important implications for the doctors and their patients. First and foremost, the patient’s subjective experience is of utmost importance, since it will allow the physician to diagnose, and hopefully treat the disease. And speaking of treatments,  disease is now not a matter of balance; diseases can be fought, and a specific disease might have a specific cure. It is in this period that we first start to get militaristic language in regards to disease.


In this episteme, there also becomes a sense that disease lives somewhere, in particular at the level of the organ. Again, take the class of pyrexia, the order of phlegmasiae, but now the class of cynanche. These refer to diseases that cause “strangulation” and blockage of the airway. Cynanche trachealis, if you’ll remember from episode 37, is the disease the was ascribed to kill George Washington, which was likely acute epiglottitis according to a modern nosology. Cullen describes it as “pyrexia, redness in the face, degluition and swallowing difficulty.” Depending on the location affected in the throat, you could have cynanche tonsillaris, maligna, trachealis, pharyngea, or parotidea. 


You see the same changes happen in autopsy. The most dramatic example was Giovanni Battista Morgagni, a professor of anatomy at Padua. His initial career was very much in the mold of Vesalius, with detailed dissections of cadavers, though he was interested less in gross anatomy and more in the anatomy of individual organs. However, over time, he began to perform autopsies on patients that he himself had treated. He eventually published “De Sedibus,” On the Seats and Causes of Disease, descriptions from 700 patients linking their symptoms while alive to disease in the organs after death. For the first time, the gaze had linked symptoms outside the body to organs on the inside — angina, he could see, came from aneurysms of the heart and its vessels, or from thrombi inside the vessels themselves. With apoplexy, he could see a subarachnoid hemorrhage, or dead brain tissue on the opposite side of the lesion.  


This is bringing us to the third episteme — pathological anatomy. I literally could talk about this forever, and it makes up the bulk of Bedside Rounds. Because of that I’ll try and talk about it the least. This is the period that Foucault is interested in Birth of the Clinic. Roughly from the time of the Paris Clinical School, doctors realized that diseases had specific and characteristic changes within certain body tissues, and realized that these change in fact WERE disease. For example, phthisis, or consumption was characterized by non-caseating granulomas, not only in the lungs, but in other organs where it manifested. I would argue that this episteme has in fact survived until the current day, though with considerable modifications. For example, Virchow showed in the middle of the 19th century that it was the cell, rather than tissues, was the fundamental unit of disease; germ theory gave an important etiological factor; and modern scientific methods have localized some diseases to specific biochemical pathways.


But for the most part, our modern nosology outside of field of psychiatry largely operates on the same set of fundamental assumptions. So, for example, physicians understand disease not so much by knowing their patient but by examining their patient for signs — in the early 19th century, this meant percussion and a stethoscope; now it means MRIs, PET scans, and biopsies. Even the patient’s subjective experience — when the cough started, whether or not you have night sweats, what time a fever happens — are another set of signs for physicians to look for the disease inside. There are important implications here for the patient-doctor relationship; in the first two epistemes, the patient’s subjective experience was the most important to diagnose a disease; now it is the physician’s gaze, leading to the loss of participation in one’s own illness, or “loss of the sick-man from the medical cosmology” as Jewson called it.


So now we’ve gone through 2,000 years of anatomical history and medical perception, and I think we’re  finally read to tackle the final illness of Charles II. How could he have had a heart the size of a peppercorn, a head full of water, and a body completely lacking blood? 


The best way to approach this, I’d argue, is by trying to adopt the gaze of the physician who would have directed the autopsy. We can of course, only speculate, but it is 1700 in Spain, and while Sydenham had already written his Nosology, these ideas certainly had not yet become mainstream. Especially given some of the treatments directed at the poor, dying Charles, it would appear that his fatal disease would have been largely explained in the setting of humoral imbalances, all of which would have been obscured by death. The physician would not yet have had the conception that disease might lay in a person’s organs, let alone specific body tissues. The urgency to complete an autopsy as fast as possible to “catch” the transition between life and death was no longer there; in the Paris Clinical School, with Bichat, the delay could be less than an hour. Undoubtedly, some of the findings were due to putrefaction. But perhaps most importantly, we need to consider the reason for the autopsy. Apparently, it was quite unusual the Charles was even autopsied in the first place; this was not a practice done with royalty in Spain. The reason appears to have been to look for evidence of this curse, the one placed through hot chocolate, the one for which he received his exorcisms. A bloodless body, and an impossibly small heart one have been one more sign confirming a curse.


But what of the physician himself? Vesalius followed a humoral model quite closely, but still made remarkable descriptions of human anatomy. I think it goes without saying that a heart the size of a peppercorn is anatomically impossible; were you or I in the room, we would not have described it that way. So was he lying? Was he embellishing to further his diagnosis of a curse?


Or — and here’s where we’re going to get REALLY postmodern — did he actually see something differently than you or I would? Does a different clinical gaze not only affect how we interpret the world — but what we actually see?


Bare with me for a second, because I want to go back to Foucault, to the introduction of Birth of the Clinic.


Foucault starts his book by describing a detailed case report from Pomme, who cured a woman with hysteria by making her take 10 to 12-hour baths daily for ten months. The intent was to “dessicate” her nervous system and the “heat that sustained” it by providing an appropriately warm and wet environment. At the end of this treatment, he described membranous tissues “like pieces of damp parchment” pass through her urine, including her right ureter. Her intestine too, peeled off like a tunic, and passed through her rectum. The same was true of her esophagus, trachea, and tongue — all these dessicated nervous membranes passing from her body and curing the patient.


Foucault then contrasts this with a description from Bayle, a distinguished anatomist from the Paris Clinical School, who describes a similar case, giving detailed descriptions of the arachnoid and dural space that would be familiar to any modern physician in a patient with meningoencephalitis not fifty years after Pomme.


The question that Foucault asks is this — what did Pomme actually see? Did he truly see a “damp parchment” essentially consisting of the woman’s internal linings pass from the ureter, rectum, and mouth? Let me know if your experience is different, but I’ve never seen anything remotely similar to that in patients that I’ve cared for. This is the subtext for the remainder of the book — how much does our conceptualization of disease affect the very act of seeing?


Now I’m not sure that I completely buy this — and it’s conveniently untestable . But modern neuroscience suggests that there are real differences in perceptions bet ween individuals; is it too much of a stretch to say that two different people from different epistemes — with different unstated rules for interacting with science and reality — might have had such a difference?


That feels like a bit of a cop out, so I should point out that a number of modern physicians have revisited Charles’ case with a distinctly modern clinical gaze to try and diagnose his cause of death. Summing up many of the theories, Gargantilla and Castillo both felt he had Klinefelter’s syndrome due to his phenotype and inbreeding. Klinefelter’s is the most common sex chromosome disorder, usually 47 XXY. This would explain his infertility, though he lacked other traits like gynecomastia and unusual height. Lopez suspected underlying panhypopituitarism and Fragile X syndrome, as well as infantile rickets. This would have explained some of his behaviors and learning disabilities, and the enlargement of the lateral ventricles of the brain could have explained the head full of water.


And as for his death? We know Charles II was struck by malaria in 1693 and treated with cinchona. Ray Bueno suggested that his progressive fatal illness may have been from chronic malaria, presumably much more common in that era. Lopez suggested that given the kidney stones found on exam, a hyperuricosuric state leading to chronic urinary tract infections, then a membranous glomerulonephritis, and finally nephrotic syndrome may have led to his death. I personally would suggest a less fanciful option — Charles’ final days were spent with fevers, a wasting disease, edema, and severe diarrhea. Tuberculous enteritis is common even in the 21st century, and would present similarly as well. A small heart could theoretically be explained by a restrictive pericarditis, and TB meningitis makes a lot of pus, which can plug the cisterns — a “head full of water.” Of course, this is mostly an academic exercise, but it’s helpful to consider how my “gaze” — and my personal experiences — shapes and molds the data that I see in front of me.


Cleary this subject means a lot to me. Recognizing my own clinical gaze has greatly influenced not only my approach to medical history, but also my own care of my patients. First, my approach to history. When I was much younger and just starting this podcast, I would naively read old medical texts and think, “huh, I just don’t GET them,” more of a visceral gut feeling than anything intelligible. For example, when I worked on my first episode on James Lind, and I read his Treatise on Scurvy, I was expecting to find a clear explanation of arguably the first controlled trial in history, where he showed that citrus can be used to cure scurvy. But instead, I found alien descriptions of cool weather, warming foods, ideas about putrefying food clogging up sweat ducts. I’d contrast that to Laennec’s On Mediate Auscultation, a hundred years or so later. Even though Laennec uses some old terminology, he spoke to me completely differently. When he described a patient with an empyema and his clinical course, I could see him in front of me — even though Laennec had no knowledge of germ theory. Now I know it’s because, despite our vastly different societies, Laennec and I share the same set of assumptions about the nature and localization of disease — and Lind and I did not.


But like I said, my recognition of my own clinical gaze has, I think, made me a better doctor. I can’t turn it off — none of us can. When a patient starts telling me their story, I unconsciously start chopping and rearranging the “history of present illness” to illuminate potential diseases deep within their body. If I see a person on the street with a limp, an unusual rash, ridges in the fingernails, or a diagonal earlobe crease my mind immediately starts classifying and risk stratifying. But I try to be aware of my gaze. When a patient rambles in the HPI, my gut is to get them back on track, and to ask directed questions. My gaze wants to limit uncertainty — I want to know where the disease is, and what we can do about it. I think this is a large motivator for over-testing. We want to truly localize disease. But clearly that doesn’t always make for good patient care, and I try to make myself comfortable with uncertainty and discuss this with my patients.


Can you be a good doctor without a recognition of history and philosophy? Of course you can. Most doctors do it every single day. There are those who would argue that this is a good thing — you can and should practice chemistry without ever having read Stahl’s Zymotechnica Fundamentalis about phlogiston theory right? But I would argue, unsurprisingly, that medicine is not a science — or at least, it isn’t totally a science. It’s a cultural practice tied up in centuries of assumptions and traditions. A more historical and philosophical perspective, I think, can help all of us realize and address some of the unconscious baggage we all bring to our practices. 


Okay, that’s it for the show! But first it’s time for a #AdamAnswers! 


#AdamAnswers is the segment on the show where I answer listener questions no matter how obscure or profound. This month, I have a question from Hannah Abrams …..


What a wonderful question for this episode where I’ve been talking about gazes — because now we can talk about the intersection of the artist’s and the clinical gaze!


Vincent Van Gogh, of course, was a Dutch painter from the end of the 19th century with a famously tragic and self-destructive life, and who only achieved fame after his suicide at the age of 37. I’m sure he needs no introduction, but just in case all the paintings I’m referencing will be posted to Twitter. His short and turbulent life, as well as his many encounters with the medical system at the time has been a fascination for paleopathologists; Gruener found over 150 articles, with diagnoses as varied as “bipolar disorder, schizophrenia, neurosyphilis, interictal dysphoric disorder, sunstroke, acute intermittent porphyria, temporal lobe epilepsy precipitated by the use of absinthe in the presence of an early limbic lesion, to Ménière’s disease”. 


His paintings, especially in the period of 1886 to 1890, are full of brilliant colors, yellow chief among them. Take the Reaper. A golden yellow seeps from the canvas, not only in the hayfields, or the clothing of the titutar reaper, but it threatens to overwhelm the rising sun and the blue hills above. This has led, as Hannah references, contemporary physicians to theorize that Van Gogh may have had xanthopsia, or yellow vision, brought on by his medical treatments — and in particular digitalis.


Digitalis, or the foxglove flower, in many ways prefigured the modern pharmaceutical revolution. For at least 400 years it has been known as a potent poison, and appears in many murder mysteries, from Agatha Christie to  today. However, by the 18th century it was not thought to be particularly useful in medicine. In Scotland, it was actually removed from pharmacopoeias because of its danger and perceived lack of efficacy. That is, until 1775, when an English country physician named William Withering became aware of a woman on the verge of death from dropsy, what we’d call edema, likely from congestive heart failure, and found that she had been cured from the tea from an elderly country herbalist. As he recounted, the remedy “had long been kept a secret by an old woman in Shropshire who had sometimes made cures after more regular practitioners had failed.” Withering convinced her to share her brew, which had over 20 ingredients, but the poisonous foxglove caught his attention. Over the next decade, he performed a remarkable series of experiments using digitalis on his patients suffering dropsy. He quickly discovered the toxic side effects of foxglove — notably nausea, vomiting, and xanthopsia, and realized that in high doses digitalis actually hastened death. But with a considerable amount of trial and error discovered that the therapeutic dose was far lower. His results were unequivocal — digitalis allowed treatment of a disease — dropsy — that had previously been invariably fatal. Europe quickly went foxglove crazy. Samuel Hahnemann, the inventor of homeopathy, listed 73 different indications for the drug, including “melancholic thoughts, hypochondria, mental illness, headache, nausea, vomiting, pain in the eyes, swelling of the eyelids, tearing, and inflammation of the eyes.” In the late 19th century, digitoxin was purified from foxglove leaves, making administration even easier, and eventually in the 20th century digoxin, an easy to take oral medication. We now know that digoxin works by inhibiting the Na/K/ATPase in myocardial cells, leaving to increased contractility in the heart. This has made it a potent medication for the treatment of heart failure and atrial fibrillation, especially in the days before beta blockers, and while its use has dwindled compared to thirty years ago — now, just as in the 19th century, its narrow therapeutic index limits its use — you’ll still see it all the time.


But back to Van Gogh. In 1889, he suffered a nervous breakdown and was admitted to an asylum at Saint-Remy, where was diagnosed with “acute mania with generalized delirium,” and “epileptic crisis with visual and auditory hallucinations.” He was placed under the care of Dr. Paul-Ferdinand Gachet. Gachet treated his patient with what was then the standard of care for a patient suffering from a diagnosis of epilepsy — digitalis. In fact, Van Gogh famously painted a portrait of his doctor holding a foxglove flower. Based on these two facts — that digitalis was the standard of care for his condition, and the paintings of Gachet and foxglove, Dr. Lee theorized in JAMA in 1981 that digitalis toxicity leading to xanthopsia was the cause of his preference for yellow. Dr. Lee closes his article, concluding that Van Gogh once asked, “There is something within me, what is it then?” to which Lee concludes — “perhaps digitalis.”


This article, Hannah, appears to be the source for the Step 1 pearl on yellow vision. There’s only one problem — it’s almost certainly not true. Dr. Gruener, whose piece is available in the shownotes, has provided a pretty good demolishment of the myth. Problem number 1: Gachet was a homeopathic physician, and by his own admission used miniscule doses — homeopathic if you will — of the drug. He was well aware of the dangers of digitalis, and in fact wrote, “We understand the physiologic effects of this plant well enough today to be afraid of its dangers, and strongly advise against its use, since it can produce syncope by slowing the heartbeat and it can cause paralysis of that organ.”


Second — in true xanthopsia, white also appears as yellow, and blues would appear as greens. Look at The Reaper again — in the distance, the farm house is a brilliant white, and the hill a pale shade of blue. 


Third — Gachet actually tested Van Gogh’s vision using standardized color-vision materials meant for railway workers — and his vision, including color vision, was complete normal. 


So, Hannah, I hope this answers your question — despite being a good heuristic to remember the side effects of digoxin toxicity, it is almost certainly NOT true that Van Gogh’s love of the color yellow was due to xanthopsia. Rather, it’s an example of Van Gogh’s artistic gaze — he made a conscious decision to favor yellow. Our clinical gaze makes us crave a medical understanding for an artist’s style, because it’s how we see and interpret the world. We can’t turn off our gaze. But neither can artists. Dr. Gruener ends her piece with a quote from Edgar Degas, that sums this up nicely: “Art is not what you see, but what you make others see.”


Thanks so much to Hannah Abrams for this wonderful question. If you don’t know, Hannah is both a medical student and the social media editor for the Curbsiders, which if you don’t listen to it, you should, since it’s basically the internal medicine podcast of record. She also makes some awesome Tweetorials on both her own Twitter feed @HannahRAbrams, and on @thecurbsiders.


And if you have a question, dear listener, that you would like to submit to #AdamAnswers, please Tweet it to me @AdamRodmanMD.


And now that’s really it for the show! This episode was inspired by an r/askhistorians thread I answered a couple months ago about the death of Charles II, and the grand rounds I gave at BIDMC earlier in the fall — I’ve been wanting to do an episode about the clinical gaze for a while, so let me know what you thought! OK, I have a couple on general announcements to make. I’ll start with the exciting one first, and then the REALLY REALLY exciting one second. So I am going to be speaking at the American College of Physicians National Conference this year in Philadelphia, about the history of syphilis. It’s on April 11th at 11:15 AM; I’ll have the link to the agenda on Twitter. And I’m doing in with the King of #MedTwitter, Tony Breu — so it’s definitely going to be good!


And the second announcement — sorry for the one week delay in this episode, but I swear it was for a good reason — because I’m a father now! Three weeks ago, my son Sam was born. He already has strong opinions about Bentham’s panopticon and its utility as a model to understand the power structures that constrain modern life [Sam quote] Foucault would be proud, But I just wanted to share my news with you guys, dear listeners!


If you’re a member of the American College of Physicians, you can get CME or MOC credit by listening to this episode by going to www.acponline.org/BedsideRounds and taking a brief quiz. You can listen to all the episodes of Bedside Rounds on the website at www.bedside-rounds.org, or on Apple Podcasts, Spotify, Stitcher, or the podcast retrieval method of your choice. I’m on facebook at /BedsideRounds, and of course I’m on Twitter @AdamRodmanMD, where I tweet about medical history, evidence-based medicine, and high-value care. I occasionally craft Tweetorials, and there will be a thread to come with all the images I reference in this episode, so check it out!


All of the sources are in the shownotes.


And finally, while I am actually a doctor and I don’t just play one on the internet, this podcast is intended to be purely for entertainment and informational purposes, and should not be construed as medical advice. If you have any medical concerns, please see your primary care provider.