Episode 32: The Humors

 in Podcasts  tagged Galen / hippocrates / history / humors / James Lind / RCT / scurvy by

 

The Four Humors are probably the longest-lasting idea in the history of medicine, even though they’ve been more or less completely abandoned for the past century or so. In this episode, we’ll explore how the ancient Greek idea of disease coming from imbalances in body fluids touched every aspect of medicine for two millennia, well into the modern era. And we’ll discuss how humoral explanations likely hampered adoption of the first clinical trial in history, James Lind’s famous scurvy study. Plus we have a brand new #AdamAnswers about germ theory. Listen to all this and more in Episode 32 of Bedside Rounds, a tiny podcast about fascinating stories in clinical medicine!

Sources:

  • Arikha N, Passions and Tempers: A History of the Humors. 2007.
  • Baron JH, “Sailors’ scurvy before and after James Lind–a reassessment,” Nutr Rev. 2009 Jun;67(6):315-32.
  • Bartholomew M, “James Lind and scurvy: a revaluation,” Journal for Maritime Research. Published online: 08 Feb 2011.
  • Lind J. A Treatise of the Scurvy in Three Parts. Containing an Inquiry into the Nature, Causes and Cure of that Disease, together with a Critical and Chronological View of what has been published on the subject. London: Miller, 1753
  • NLM’s Turning the Pages on the Edwin Smith Papyrus (https://www.nlm.nih.gov/news/turn_page_egyptian.html)
  • Nutton V, Ancient Medicine.
  • Nutton V, “The Fatal Embrace: Galen and the History of Ancient Medicine”. Science in Context 18(1), 111–121 (2005).
  • Shoja MM et al, “Wrong theories on the origin of blood vessels: Polybus and De Natura Hominis.” Int J Cardiol. 2008 Jun 6;126(3):313-5.
  • Sutton G, “Putrid gums and ‘dead men’s cloaths’: James Lind aboard the Salisbury.” J R Soc Med. 2003 Dec;96(12):605-8.
  • Trohler U, “Lind and Scurvy: 1747-1795,” J R Soc Med. 2005 Nov; 98(11): 519–522.
  • West JB, Galen and the beginnings of Western physiology Volume 307 Issue 2 July 2014 Pages L121-L128

Transcript

This is Adam Rodman and you’re listening to Bedside Rounds, a tiny podcast about fascinating stories in clinical medicine. This episode is called “The Humors,” and it’s about how an ancient Greek idea about body fluids ended up shaping pretty much the entire history of medicine, and how it muddied the waters of the first clinical trial in history.

 

So let’s talk again about James Lind, who featured in my episode The First Trial, all the way back in the Bedside Rounds dark ages. So the traditional story goes, the Scottish naval surgeon James Lind revolutionized medicine by performing the world’s first controlled trial to definitively show that citrus, especially oranges and lemons, cured scurvy. Depending on how excitable the storyteller is, his discovery might also be based on a whole-hearted embrace of new ideas about the human body. They might even talk about the Enlightenment, or the Scientific Revolution. And yet it took forty years for Lind’s clarion call to be heeded by an over-bureaucratic Admiralty and issue citrus to its sailors. In the meantime, countless thousands died horrible deaths. This was more or less the story I was told when I was an impressionable young student. The big problem, of course — it’s that it’s not quite true. In fact, in order to tell the whole story of James Lind, his scurvy trial, and why it took so long for doctors to realize the cure for scurvy was under their nose all along, we’re going to have to dive deep and go back to some of the foundational ideas of Western medicine that we don’t really talk about in polite company anymore — the four humors. 

 

But first, let’s talk about the naval world that the young James Lind found himself in in the latter half of the 18th century. It’s hard to overstate the influence that the invention of the humble marine chronometer had on world history — ships were now able to accurately set their position at sea without having to be in sight of land, which allowed for longer and longer sea voyages. Suddenly, European powers could conduct trade, exploration, colonialism, and war on a worldwide scale.

 

Disease mirrors the ebb and flows of our civilization, and as humanity set out to the sea for longer and longer periods of time, a seemingly new menace flourished. Scurvy, we know now, results from a lack of ascorbic acid, or vitamin C, which is found in fresh fruits and vegetables. Fun party fact — the name ascorbic acid comes from Latin for scurvy, scorbutus. In any event, it’s essential in formation of collagen, the main connective tissue in the body. Without it, our gums become diseased, teeth fall out, non-healing ulcer open up all over the skin, old scars will pop open, and eventually infection descends on the weakened body. Untreated scurvy can be fatal. So-called land scurvy had been noted before — in sieges, and also as a seasonal disease in the northern climes on both Europe and North America, where an absence of fresh vegetables in the winter would cause a milder form of the disease. Traditional treatments would be to eat various cresses or a brew tea of spruce leaves, both of which we now know are good sources of vitamin C. In fact, one of these cresses was even called “scurvygrass”.

 

But with massive fleets now patrolling the world, scurvy became a constant companion of the sailor. Lind himself was inspired by the tale of  Lord Anson’s fleet, who was dispatched by the British in 1740 to “annoy and distress” the Spanish by circumnavigating the globe and attacking their possessions during the War of Austrian Succession. Anson left St. Helens with 1,955 men and eight ships. Three years later, his fleet returned with one ship and 145 members of the original crew; almost 1,300 men had been killed by scurvy.

 

James Lind was from a family of merchants, and joined the navy as a surgeon’s mate. By 1747, he had risen to the ship’s surgeon aboard the HMS Salisbury. The Salisbury was assigned to blockade the French from the English channel — as a sense of scale of these 18th century naval engagements, this was the same conflict that Anson had first been dispatched in. After 10 weeks at sea, the crew predictably started to come down with scurvy — almost 80 of the complement of 350, according to Lind. Rather than treat them with the standard of care, he decided to run an experiment comparing the various treatments — the first controlled trial in the history of medicine. He selected 12 of the sickest patients and tried to match the sailors “as similar as I could have them.” He also made sure to give them the same diet, and confine them to the same space — the forehold which served as a sick bay. He then divided them into six different treatment groups of two each — one got 1.1 liters of cider daily, another 25 mL of vitriol (that is, sulphuric acid), another 18 mL of vinegar with meals, another a half pint of seawater, another a medicinal paste of garlic, mustard, and radish, and finally, the last was given two oranges and one lemon daily until Lind ran out of citrus fruits, which was six days. 

 

The effects were dramatic: Lind reported that of the two treated with citrus, one was well enough by six days to return to duty, and the other had improved so much that he could help treat the sick. This was a remarkable moment — not only the first controlled trial in history, but with an astonishingly positive result. And from a military standpoint, the potential was tremendous — if the British could leverage their knowledge about how to treat — and potentially prevent — scurvy, they would have another weapon in their arsenal against the French and the Spanish. So it would speak to reason that Lind’s 1753 publication of his Treatise of the Scurvy, which performed a systematic review of all the previously literature Lind could get his hands on about scurvy, as well as a description of his experiment, should have been a game changer.

 

But that is not what happened. There were some fits and starts of citrus being used in the fleet, but scurvy would continue to kill British sailors until 1795, when the admiralty finally ordered lemon juice for all its ships. In the 20th century, a whole subgenre of counterfactual Lind stories has sprouted to explain why this happened. I’ve got a wonderful article in the shownotes that deals with 21 of them, but some of the more notable or interesting reasons: first, the use of citrus and fresh vegetables like scurvygrass was well-known by mariners, and Portuguese and Spanish fleets had intermittently use fresh fruit for centuries. His proposal just might not have been that revolutionary. Lind was also mislead by his results to develop a “rob” of orange and lemon juice, that was boiled and concentrated so it would last longer. Unfortunately, we know now that the boiling process would have neutralized vitamin C, rendering it useless.  Lind was also not of noble heritage and notoriously unassuming, and likely did not aggressively push his ideas to the aristocratic Admiralty — a reasonable idea, since another Scottish physician Gilbert Blane was eventually able to leverage his personal relationships to get lemon juice assigned. There’s even one scholar who reviewed the logs of the Salisbury and suggested that Lind’s experiment may have been a fabrication and never actually taken place.

 

All of these are likely true to a certain extent — though I’d like to think that Lind did actually perform his experiments — but I actually want to take a step back and ask for a second what Lind actually thought about his results. After all, he wrote a 580 page book about it, which he updated twice over the remainder of his prestigious and productive career.

 

And it turns out that Lind tells a different story about his experiments and findings than we do. According to Lind, scurvy was not caused by dietary factors at all, but by an imbalance of temperature and moisture. The digestive system, he writes, works best in warm and dry conditions. During normal functioning, byproducts of digestion left the body basically by sweating them out — via our pores. But when a sailor encountered the wet and cold effects of the sea, digestion would go haywire and undigested food would start to back up and putrefy, first in the gut, and then in the skin. Even worse, Lind found that cold and wet conditions brought about melancholia in his men, which appeared to be a major risk factor for scurvy. This putrefaction of undigested food in the gut and skin explained the fetid breath, rotten gums, and skin wounds that Lind observed in his sailors.

 

Given this model of scurvy, how did Lind explain his first medical trial in history? Essentially, he writes that food plays a part in disease pathogenesis — when scurvy strikes and digestion is blocked, fresh fruits and vegetables can help restore normal digestion. It’s notable that he doesn’t necessarily single out anything special about vegetables, only that they’re “less oily than meat.”  But it’s only part of the picture. Patients need fresh air, warm and dry conditions, and exercise. In fact, Lind stressed good living conditions as the most important factor in treating the disease.

 

It’s telling that Lind’s experiment takes up only six paragraphs in his voluminous tome, and he intentionally drives home the point that we shouldn’t heed the results too much: “I do not mean to say that lemon juice and wine are the only remedy for the scurvy, he writes.  “This disease, like many others, may be cured by medicines of very different, and opposite qualities to each other, and to that of lemons.” 

 

So this seems a bit, well, odd. Far from being an empirical iconoclast, he shapes and massages his conclusions into an all-encompassing explanation about the effects of weather and moisture on digestion and mood. And while this seems odd to me, and presumably other modern doctors, in fact Lind is cognitively working in a multiple millenia-long medical tradition — probably the longest surviving, and most influential medical idea that we’ve ever had. And that’s the idea of humoralism, or the Four Humors. I’ve danced around humoral concepts before but now, using James Lind as a background, I want to fully embrace the four humors and explain how they became so influential in medicine.

 

First a quick refresher on humoral theory. Though Lind doesn’t mention them by name, the basic idea is that the human body is comprised of four constituent fluids — blood, phlegm, yellow bile, and black bile. Different balances in the amounts of these fluids could explain pretty much anything about an individual — our personality, our relationships, who we would marry, what foods we could eat. The vestiges of these ideas are still present in English — if you’re sanguine, you have a relative excess of blood, and you’re happy and optimistic. If you’re melancholic, you have an excess of black bile, and you’re thoughtful and depressed. Even our word “humor”, used today to talk about liking a good joke, comes from the idea that an individual with “good humor” would be well balanced in his body fluids. Temperature and moisture, as well as diet, were the prime drivers of our humoral imbalances — and therefore of all disease, because in their extremes, imbalances in the humors were what made us sick. The rationale behind many types of medical treatments was to affect the makeup of humors — for example, bloodletting to relieve an excess of blood, and purgatives to either expel yellow or black bile.

 

The theory of the Humors is usually attributed to Hippocrates. But the truth, like most things, is a bit more complicated than that. And in fact, to understand James Lind’s reasoning, we have to go back to the world of the Greece in the fifth century BCE when the idea of the physician first takes root. This was a world far more similar to the pre-industrial developing world than anything that exists today. What we now call “cities” were very small — usually less than 2000 people, and even if you included the surrounding countryside would be no bigger than 6,000. The demographic pyramid likely was skewed young — life expectancy was between 20 and 30, driven by an atrocious infant mortality rate. People lived off the land, and farming was largely subsistence-based, leaving people vulnerable to famines. All of this is to say, to early doctors, life was intimately connected to the natural world. 

 

Now, the practice of medicine has existed presumably as long as homo sapiens have walked the earth. But the idea of a physician has not. The medical fragments we have from other civilizations — especially Babylon and Egypt — show a world where the supernatural and natural mingle freely in human disease. Diseases are curses from gods or spirits, and require prayer and magic as intercession. Somewhere lost in the beginnings of civilization, a more naturalistic view began to take hold. The classic example is the Edwin Smith papyrus, which has been attributed to Imhotep — who, for what it’s worth, Osler considered the first physician. The Edwin Smith papyrus is a list of surgical treatments dating to about 1600 BCE, notable for its naturalistic approach to diagnosis, prognosis, and treatment. However, when cases are mysterious, magic and prayer are still suggested. There’s an awesome interactive papyrus you can explore published by the National Library of Medicine and I’ve put it in the shownotes if you’re interested. During this period, Imhotep, who was very much a real person, began to be worshipped across the Mediterranean as a healing god, and his physician-priests would treat worshippers. In Greece, another healing god named Asclepius was worshipped — sometimes identified with Imhotep, and it is from his priests, the Asclepiads, that we get the first physicians.

 

I am talking about, of course, the Hippocratic school, which arose from the Asclepiads on the island of Kos, a Greek island located off the coast of modern day Turkey.  Among other foundational ideas in medicine, they taught that disease was natural in origin, and therefore had natural treatments. It is from them that we get the idea of health as a mixture of body fluids. That being said, there appears to have been quite a dramatic difference in the makeup of humors, even among the Hippocratic school. Pretty much everyone agreed on phlegm and bile, but there was wide disagreement on the total number — Praxagoras, for example, discussed 11 different fluids. And even though the four humors have been attributed ever since to Hippocrates, the man himself described a completely different system. Similarly, it’s also unclear how much these early doctors actually thought the humors were actually flowing through the human body, rather than more abstract constructs. There appears to be considerable disagreement on these.

 

But despite that, the humors were an extraordinary development in the history of medicine. Body fluids are visible, after all. Sick patients might excrete phlegm, blood, gastric contents, chyle, diarrhea, urine, pus — and I’m only really getting started there. It does not take too much of a logical leap for these first physicians to theorize that the liquids coming out of his are responsible for our health — or even, that we ARE the liquids. And that imbalances in these very real fluids might be the cause of disease, rather than evil spirits, empowers a new type of naturalistic healer — the physician — to prevent and cure disease like never before, without the intercession of any god. 

 

So why are there four? That idea actually comes from Hippocrates’ son-in-law Polybus, first described in his On the Nature of Man. Polybus’ staying power comes from merging humoral theory with a teleological philosophy. Teleology is the ancient idea that phenomena are explained by their purpose, rather than their causes. Modern science has done away with the idea of teleology, but humans are purpose-finding machines like none other and teleological fallacies are alive and well in the modern world; I always like to use the ancient but persistent example of “intelligent design”. Anyway, Polybus took the idea of opposing classical elements described by Empedocles — air, earth, fire, and water — and merged them with body fluids. The blood was hot and wet like air, yellow bile was hot and dry like fire, black bile was dry and cold like earth, and phlegm was wet and cold like water. Merging the humors with the explanatory model of all existence proved to be a potent idea. It also gave doctors a clear mechanism by which to treat patients — different foods and environmental factors had different hot/cold and wet/dry tendencies, which could now be prescribed as medicine.

 

In any event, by the second century CE, Polybus’ view of humoralism was widely accepted, and was attributed to Hippocrates so much so that a contemporaneous scribe wanted to edit Hippocrates’ own words to omit his own humoral theory. That should be said — even in this time period, there were still a number of competing naturalistic theories on medicine that were not based on the  humors. There were the Pneumatists, the Erasitratists, the Methodists, and the Empiricists, among others that we certainly haven’t heard about.  So how did the humours win out?

 

That’s a one word answer — Galen, the elephant in the room of ancient medicine. You can’t really talk about any pre-modern medical history without discussing Galen. So very briefly, Galen was a wealthy and influential physician in the second century CE, a legend in his own time and after. He studied in all the major centers of medical knowledge in the ancient world — Pergamon, his hometown, Alexandria, and Rome. He was the doctor to gladiators and Emperors. And he was famed for helping to treat and stop the Antonine Plague in Rome, which was likely smallpox — so much that the plague is sometimes called the Plague of Galen. Most notably Galen was a prolific writer. He is estimated to have written 500 treatises, and amassed one of the largest medical libraries in the world. One estimate put his output at 10 million words, with over 3 million words surviving today. In comparison, the King James Bible has 783,137 words, and all the Harry Potter books in English have 1,084,170 words. So 10 Harry Potter sagas. In his writings, he describes, develops, and advocates humoral theory, though his writings cover any other number of topics, including anatomy physiology, and the materia medica, or pharmacology. 

 

Galen wrote in Greek, and his works were essentially lost in the Latinate half of the empire after the fall of Rome. But in the Greek speaking East, Galen lived on, where he was preserved and adopted in “Byzantine”, and yes, I’m making a pun here, ways. Many of these areas would fall to the Arabs in the 8th century CE, and it’s here than Islamic civilization adopted and adapted Galen. Galen’s works were translated into Arabic, and were taught in the first universities and medical schools, like the University of Al Quaraouiyine in modern-day Fez, started in 859, arguably the first university. There was considerably innovation within the humoral system in the Arab world, especially with Avicenna, or Ibn Sina, who wrote the Canon of Medicine based on Galen, a medical textbook that was used almost 1,000 years, and Ibn al-Nafis, who described pulmonary circulation. It is from the Arab civilizations that Galen was reintroduced to the West, first translated from Arabic into Latin, and then from the original Greek. Galen was quickly taught in the first Western medical schools, starting in Salerno, and rapidly became doctrinal — taught in universities, and adopted by the Catholic church so much that anti-Galenic ideas were seen as heretical. 

 

By the time of the Renaissance, the four humors were firmly entrenched both in medical thought and in society at large, especially when it came to personality. Shakespeare, for example, made common use of archetypes based on each of the four humors, such as when Brutus tells Cassius in Julius Caesar, Go show your slaves how choleric you are … Must I stand and crouch / Under your testy humour? (JC IV.iii.43)

 

I recommend the book Passions and Temper by Noga Arikha for a examples of how overarching humoralism was to early modern Europeans, but briefly cooking, dating, astrology, mental health, folk medicine– all were explained in an overarching humoral theory. And even in the medical world, where exciting new knowledge was being generated, the humors still reigned supreme. Today, we see Vesalius and Harvey as repudiating Galen and laying the steps of scientific medicine. However, each of these men saw themselves as complementing and improving upon Galen’s humoral model

 

Which pretty much brings us back to Lind in the mid 18th century. There had been plenty of holes poked in the humors and Galen, but humoralism, even if not taken quite so literally as even 100 years earlier, was still alive and well. Galen and Avicenna were still foundational texts in medical school. And despite some alternatives to the Galenic model, most notably the teachings of Paracelsus, none had persisted more than a few decades. Of course Lind was going to interpret his findings in the medical milieu of the day.  And with this context, his views suddenly seem more reasonable. The digestive system, constituted of yellow bile, needed a hot and dry climate to properly operate.. That is why the wet and cold of the sea caused it to malfunction. Meat, which made up a part of a sailors rations, was wet and cold as well. However, hot and dry fruit, especially citrus, could help restore this natural balance, but naturally a hot and dry climate would work best. 

 

So what, then, are we to make of Lind? And does the fact that his attempts to work his findings into a humoral Galenic understanding negate the impact of his famous trial? Of course not. The scientific revolution was a process, and new ideas freely mingled with old. Isaac Newton’s interest in the occult and alchemy doesn’t change the impact of his ideas on physics. And astrology was embraced by many of the physicians who we now reference glowingly. 

 

If anything, understanding Lind’s humoralism helps show how science works — and how slowly paradigms can take to shift. James Lind, brilliant as he was, was speaking a different story than us. If anything, his story should be a caution to all of us who practice the science and art of medicine — science is a process and not just a collection of facts, and we are all a part of it. Thomas Kuhn warned that paradigm shifts are the most dramatic when things seem the most stable. Perhaps it’s happening beneath our feet right now. 

 

Okay, that’s it for the show! But wait, it’s time for a #AdamAnswers! This one is off one of my favorite subreddits r/AskHistorians, from user td4999, who asks: “Germ theory was proposed in the 16th century, but took well over 300 years to get widespread acceptance. What took so long?”

 

OK, so I selfishly chose this question because of its ties to humoralism. So first, this question is a bit of an anachronism. Germ theory was set about by Koch and Loeffler, defined by Koch’s four postulates: first, that a microorganism or pathogen must be present in all cases of a disease, second, that that pathogen can be isolated and grown separately from the organism, third, that the pathogen that was grown must again cause disease when inoculated in a healthy laboratory animal, and finally, that fourth, when the pathogen is again isolated, it must be same as the first.. 

 

The theory from the 16th century introduced the word “germs” but is fundamentally different — it’s Fracastoro’s theory of contagion. 

 

So Fracastoro was an Italian physician, and he was grappling with one of the biggest challenges to Galenic medicine, and that was epidemic disease. So the four humors could explain almost any disease — but they were particularly challenged by epidemics. What environmental or dietary factor was causing a whole population to become sick at once? The Galenic explanation was miasma — bad air, essentially, that would cause many people to fall ill.

However, by the 16th century, physicians had made careful observations of many epidemics, especially syphilis, and it was increasingly clear that some epidemics were spread by physical contact. How could this fit into Galenic medicine and the theory of miasma? It’s in the context that Fracastoro published “On Contagion”, in which we first get the word “germs”. He purposefully based this on the idea of plant breeding. Essentially, he argued that there were chemical substances called germs, and each different disease had a different germ. This substances could travel between person to person and caused “putrefaction” in the individual, making more germs. Contagion became quite popular, and lively contagion versus miasma debates continued well into the 19th century.

 

There’s not a straight line between Fracastoro’s theory of contagion and Koch’s germ theory. Science isn’t that tidy. A couple scientific trends converged in the late 18th century that inspired Koch. The first is the increasing debate on abiogenesis, the idea that life could arise spontaneously. Experiments with maggots showed that life could not come from nothing. This inspired Pasteur in particular that “fermentation” and “inflammation” in disease might be due to microorganisms, and his experiments showed that this was possible. The second is the increasing sophistication of microscopes, which allowed for a visible world smaller than the human eye can see. The third was particularly influential, and that’s the idea of epidemiology — using statistical analysis to study disease. The most influential here is John Snow, who used disease maps to demonstrate that cholera was transmitted through the water — without any knowledge of microorganisms.

 

All this is to say that Robert Koch needed ALL of this to start his famous experiments. He needed the idea of contagion (even though it was in some ways opposed to germ theory). He needed improved technology like microscopes. He needed Snow’s ideas and epidemiology that suggested a variety of ways disease could spread. He needed knowledge of “animalcules” and the microscopic world to give a mechanism for disease to spread. And probably most importantly, he needed Pasteur’s experiments which proved that microorganisms were everywhere, and the mechanisms by which they spread. Were it not for all of this, he would never have done his experiments that identified anthrax, TB, and cholera. And were it not for those identifications, he would not have generated his postulates that define germ theory, and fundamentally changed medicine.

 

So, td4999, I hope that answers your question! And dear audience, if you have any burning medical questions you want answered, please tweet them to me at AdamRodmanMD.

 

So that’s really it for the show. This was a challenging episode for me to work on. As I’m sure you can tell, it’s the unholy merger of two different projects — one on Lind, the other on the humors. I’ve been mulling over a draft on the humors for months now, and I still have a lot more material that I will likely use at some point, especially about the influence of the humors on modern  psychology. Then again, my Google drive is full of half-imagined episodes, so take anything I promise with a grain of salt. Anyway, let me know what you think! The other reason this was a challenging episode was because I the research, writing, and recording happened in the middle of my transition to being a homeowner. In fact, I’m recording this in what might eventually become a recording studio but is now a completely empty room.  Which is exciting, I suppose, but also a bit overwhelming. So bear with me these next few months.

 

Do you want more Bedside Rounds? You can listen to all my episodes on the website at www.bedside-rounds.org, or on Apple Podcasts, Stitcher, or the podcast retrieval method of your choice. I’m on facebook at /BedsideRounds, or on Twitter @AdamRodmanMD. I love to hear from listeners, and I’ve learned a lot from you guys — so come and say hi!

 

All 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.