Episode 39: The White Plague

 in Podcasts  tagged evolution / history / koch / Laennec / plague / public health / sanatorium / sanitarium / social determinants of health / tuberculosis by

Tuberculosis has been humanity’s oldest and greatest killer. Starting at the turn of the nineteenth century, the White Plague was decimating entire generations in the crowded and unclean cities of Europe, North America, and across the globe. But as medical science learned more about the disease, doctors and reformers developed new ways to combat it, most notably specialized tuberculosis hospitals that sought to heal their patients with fresh air, rest, and a nutritious diet. This episode discusses the sanatorium movement and the gradual conquest of tuberculosis, long before effective antibiotic therapy existed. Along the way we’re going to talk about the King’s Evil, the dangers of rebreathed air, the healing powers of mountains, and the social determinants of health. Plus, a brand new #AdamAnswers about maternal placentophagy. All this and more on Episode 39 of Bedside Rounds, monthly podcast on the weird, wonderful, and intensely human stories that have shaped modern medicine, brought to you in partnership with the American College of Physicians. To claim CME and MOC credit, please go to www.acponline.org/BedsideRounds.

 

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  • CDC: World TB Day 2018, retrieved from: https://www.cdc.gov/tb/worldtbday/history.htm
  • Cox GL. Sanatorium treatment contrasted with home treatment. After-histories of 4,067 cases. Br J Tuberc 1923; 17:27–30.
  • Coyle CW et al, Placentophagy: Therapeutic Miracle or Myth? Arch Womens Ment Health. 2015 Oct; 18(5): 673–680.
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  • Daniel VS and Daniel TM,, Old Testament Biblical References to Tuberculosis, linical Infectious Diseases, Volume 29, Issue 6, 1 December 1999, Pages 1557–1558.
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  • Dormandy T, The White: A History of Tuberculosis, 1999.
  • Farr et al, “Human Placentophagy: A review,” AJOG, April 2018.
  • Frith J, History of Tuberculosis. Part 1 – Phthisis, consumption and the White Plague. J Mil Vet Health, 22,2.
  • Gaensler EA. The surgery for pulmonary tuberculosis. Am Rev Respir Dis 1982;125:73–84.
  • Grigg RN. (1958), The arcana of tuberculosis. Am Rev Tuberc Resp Dis; 78:151-172.
  • Hayman J, “Mycobacterium Ulcerans: An infection from Jurassic Time?” The Lancet, Nov 3, 1984.
  • Holloway-Kew KL et al, Lessons from history of socioeconomic improvements: A new approach to treating multi-drug-resistant tuberculosis, Journal of Biosocial Science 46(5):1-21, October 2013.
  • Jacobaeus HC. The Cauterization of Adhesions in Artificial Pneumothorax Treatment of Pulmonary Tuberculosis under Thoracoscopic Control. Proc R Soc Med 1923;16:45-62
  • Morse D, Brothwell DR, Ucko PJ. Tuberculosis in ancient Egypt. Am Rev Respir Dis. 1964;90:524–541.
  • Murray JF. Bill Dock and the location of pulmonary tuberculosis: how bed rest might have helped consumption. Am J Respir Crit Care Med 2003;168:1029–1033.
  • Murray JF. Mycobacterium tuberculosis and the cause of consumption: from discovery to fact. Am J Respir Crit Care Med 2004;169: 1086–1088.
  • Murray JF, Sanatoriums and climate, The Lancet Infectious Disease, Vol 16, Issue 7, P786, July 01, 2016.
  • Murray JF. The white plague: down and out, or up and coming? J. Burns Amberson Lecture. Am Rev Respir Dis 1989;140:1788–1795.
  • Murray JF et al, “Treatment of Tuberculosis. A Historical Perspective,” Annals of the American Thoracic Society. Vol. 12, No. 12 , Dec 01, 2015.
  • Pomerantz M. Surgery for the management of mycobacterium tuberculosis and nontuberculous mycobacterial infections of the lung. In: Shields TW, Lo Cicero J, Ponn RB, et al. eds. General Thoracic Surgery, 6th ed. Lippincott Williams & Wilkins: Philadelphia, PA; 2005:1251-61.
  • Tuberculosis Chemotherapy Centre, A concurrent comparison of home and sanatorium treatment of pulmonary tuberculosis in South India, Bull World Health Organ. 1959; 21(1): 51–144.
  • Warren P, The evolution of the sanatorium: the first half-century, 1854-1904, Can Bull Med Hist. 2006;23(2):457-76.

Transcript

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, brought to you in partnership with the American College of Physicians. If you are a member of the ACP, you can get CME/MOC points for listening to this episode by going to www.acponline.org/BedsideRounds. This episode is called “The White Plague,” and it’s about one of the most dramatic phenomena in the history of medicine — the onslaught of tuberculosis in the nineteenth century, the advent of specialized tuberculosis hospitals and treatment centers called sanatoria, and the gradual conquest of the disease, long before effective antibiotics existed. Along the way we’re going to talk about  the King’s Evil, the dangers of “rebreathed air,” the healing powers of mountains, and the social determinants of health. So let’s get started!

 

The story of mycobacterium tuberculosis — a slow-growing, rod-shaped bacteria, named after fungus for its waxy, modly surface on growth plates — is the story of humanity itself, our oldest companion and our oldest killer. TB has likely killed more humans than any other microbe. But the murky beginnings of the mycobacterium species start considerably older. Scientists really hadn’t had a good grasp on just how ancient the mycobacterium species was until major flooding struck the Bairnsdale district, near Melbourne in Australia in the 1930s.  Numerous children presented with large swollen ulcers on their extremities. From these ulcers, a new species of mycobacterium was identified, which researchers realized was closely related to tuberculosis. They called it mycobacterium ulcerans. Rapidly, M. ulcerans was identified all over the world — Uganda, Nigeria, Ghana, Cameroon, Malaysia, New Guinea, Mexico, and Australia. In 1984, an Australian pathologist John Hayman noticed that when known reservoirs of M. ulcerans were mapped out, they formed a curious pattern — they were located in now disparate locations that about 150 million years earlier had former the southern supercontinent Gondwanaland. Split apart by the vagaries of tectonic movement to be scattered across the globe, the ulcerans distribution now suggested that the mycobacterium species was far older than anyone had previously suspected.

 

Modern DNA evidence suggests that mTB likely evolved about three million years ago in the Horn of Africa, infecting our hominid ancestors. The bacteria then apparently co-evolved with humanity, with modern strains emerging between 20 and 15 thousand years ago, and traveling with homo sapiens as we set out across the globe. TB enters the historical record shortly after historical records start to be collected. Murals from Egypt appear to show people suffering from Pott’s disease, TB of the spine which would cause a characteristic hunchback as it destroyed the lower vertebrae. Mummies als o show characteristic pathologic and soft tissue changes in their preserved tissue — and with modern techniques, DNA from the organism has actually been isolated from these. That being said, there’s no evidence of the disease in any Egyptian medical papyri. The first possible reference to tuberculosis the disease in the written record actually comes from the Old Testament, from Leviticus 26:16, when God threatens — and I’m quoting the New International Version here — “I will bring on you sudden terror, wasting diseases and fever that will destroy your sight and sap your strength.” The Hebrew word is schachepeth, which is the etymology of the modern Hebrew word for tuberculosis, schachefet. Now comes my standard disclaimer on nosology. Ancient doctors would not have seen tuberculosis as a disease of a specific organ, and they likely would have had difficulty separating it from other wasting diseases, especially cancer. However, scholars have argued — and reasonably so — that given the fact that the Israelites lived in Egypt around the time Leviticus was composed, and that the best evidence we have suggests that TB was endemic during this time, schachepeth likely refers to TB. Unlike Old World diseases like smallpox, TB crossed between the Old World and New with humanity; just as in Egypt, Pott’s has been identified in mummies from Peru, and TB DNA amplified from their tissues. 

 

Tuberculosis most likely has a showing in the Huángdì Nèijīng, the foundational Chinese medical text, theoretically a discussion between the semi-mythical Yellow Emperor and his physician. The traditional Western conception of the disease comes from the Greeks, and it is from them we get the modern name — phthisis, translated to consumption in English. 

By the time of Galen, an association with lung disease — especially coughing up blood — had been made explicit with the disease. All of this is to say — there is ample evidence, hidden in the DNA of the bacteria, in human remains, and in the historical and medical record, that tuberculosis has been with us pretty much since the beginning.

 

Unfortunately, prior to the beginning of the nineteenth century, we don’t have a good sense of how prevalent tuberculosis really was. But there’s some fascinating evidence to suggest it was pretty common, and that’s records kept from the French and English tradition of the Royal Touch. So first, let’s talk about the disease call the “King’s Evil” — scrofula. Scrofula literally means “little sows” in Latin, either from the belief that it primarily affected pigs, or because its lesions were thought to look like the animals. We know it today as a tuberculosis infection of the lymph nodes of the neck, but prior to the nineteenth century, it was thought to be a separate disease; no one had linked it yet to consumption. Scrofula starts as a swollen, slowly growing mass in the neck — but unlike other swellings of the body, it is cool and non-tender.. Eventually, this mass would open into a pus-filled ulcer, and could form non-healing sinus tracts. Just like syphilis, which also caused very public and disfiguring lesions, scrofula became linked with sin, gluttony in particular. And it was apparently quite common. There was essentially no medical record-keeping, but when traditional healing methods failed, stricken patients would get a chance for a second opinion — the Royal Touch. The touch of a reigning monarch was thought to have been able to cure the disease, and starting with Robert the Pious in the 10th century CE in France, kings in both France and England would host massive ceremonies where they would touch the scrofula. During Charles II’s reign in England in the 17th century, over 100,000 people received the Royal Touch. The Royal Touch was seen as an explicit extension of the Divine Right of Kings, which probably explains why it lasted until 1825, with Charles X, a restored Bourbon after the French Revolution. It still hadn’t been linked to tuberculosis at that point, but persistent republicanism likely did the tradition in.

 

So yeah, it’s an active area of debate just how prevalent tuberculosis was prior to the 18th century, but one thing we know for sure — it was pretty terrible after. Some statistics: analysis of London’s Bills of Mortality suggests that in the 18th century, anywhere between 15-30% of deaths were due to the disease. Things were similar in the countryside; English parish records suggest that 1 in 4 deaths were from TB, with similar numbers in parish records from New England. The death rate was estimated at 1000/100,000 inhabitants. As early as the Hippocratics in the fifth CE, doctors had noted that TB had a predilection for the young, and things were no different now. Tuberculosis primarily killed the young, with a particular passion for children and people of childbearing age. With death rates this high, entire generations were decimated. Society, in turn, normalized infection with tuberculosis — and even romanticized it. Consumptives were seen as melancholic, even romantic, and were lionized in novels and poetry. Lord Byron — who did not have tuberculosis — once remarked, “I should like to die of a consumption.” When his friend asked him why, he retorted, “Because the ladies would all say, ‘Look at that poor Byron, how interesting he looks in dying!” It is from this romanticization we get another famous name for the disease — “the white plague” or “the white death,” named for its parallel to the bubonic plague centuries earlier, and the seemingly attractive pallor of its sufferers.

 

By the time Charles X touched his last scrofula, the scientific understanding of tuberculosis had begun to change. The patron saint of TB is probably my most-talked about physician of all time on Bedside Rounds — Rene Laennec, inventor of the stethoscope. If you will recall, much of this early work on pulmonary auscultation was done on patients with pulmonary tuberculosis. Laennec’s careful autopsies showed that lesions in multiple parts of the body — tubercles, lymph nodes like the scrofula, the GI tract, the bone — were in fact manifestations of the same disease. Laennec, of course, would himself die at the age of 45 from tuberculosis, likely caused from his dedicated care of his patients. He retired to his home in Brittany, hoping that fresh air would cure him. Too weak to write, he continued to dictate a chapter for the new edition of his book on pulmonary auscultation until the day he died.

 

Laennec still called the disease phthisis; in 1839, Shonlein argued that the lung tubercle was the fundamental lesion, giving the disease the name we know today. By the middle of the nineteenth century, the disease had largely been described the way that we know it now — pulmonary, miliary, Pott’s disease of the spine, scrofula, TB enteritis, TB of the adrenals — no matter the cause, it was a disease that truly had systemic effects on humans. But just what was the cause? This was up for a fierce debate. There was a huge divide in Europe; in Spain and Italy, it was generally understood that TB was a contagious disease — that is, it could be spread from one person to another. But in Germany and England, doctors pointed to demographic data that suggested that TB clusterted in families. Didn’t it make more sense, they argued, that TB was hereditary?

 

Now, I should mention that to early nineteenth century physicians, “contagious” had somewhat of a different meaning than we have today. Contagion is the theory promoted originally by Fracostoro that epidemic disease is spread through “germs,” which he envisioned not as living creatures but as a chemical substance. Arguments between contagion and miasma were common and fierce in the nineteenth century, especially around cholera — and I should also point out that miasma largely won out. The miasmatic cause of tuberculous was largely thought to be rebreathed air. Florence Nightingale asserted she saw this caring for wounded soldiers: “After the Crimean war, it was found that the death rate among soldiers from consumption alone and its cognate diseases (the monstrous products of breathing foul air) exceeded the death rate from all causes among the civil population.” Even those who argued against heredity agreed that individual factors could make a patient more susceptible diseases; women were thought to get it more often because of the constriction of their corsetry, or pregnancy itself. 

 

But even among the more fringe belief of contagion was the idea of “contagium vivum” — living contagion, what we would now call infectious disease. The first to promote this was an English physician of whom we know quite little, named Benjamin Martin. In 1720 , inspired by Leuwenhoek’s discovery of little creatures living in water, he speculated that consumption was due to “some certain species of animalcula.” There is no evidence that this idea was influential at the time.

 

Independently, in 1865, a French military doctor named Jean-Antoine Villemin noticed that farcy, the inflammatory form of the horse disease glanders, appeared to be contagious; we know today it is caused by the bacteria burkholderia mallei. The ulcerations, inflammatory lesions of farcy were similar to that of scrofula in humans, and Villemin decided to run an experiment.

 

He acquired “a small amount of purulent liquid from a tuberculous cavity of a consumptive who had been dead twenty-three hours,” and injected it into the ear of two rabbits. After three months, the rabbits seemed as health as ever, but on necropsy, the body was filled with TB cavities. We know now that rabbits are actually quite resistant to tuberculosis infection, but Villemin repeated his experiments with a variety of other animals, all showing the fundamental transmissibility of the disease. In 1867, he presented his findings to the French Academy of Medicine, but he received largely a cool reception. Villemin’s experiment was certainly well known, and taken as additional evidence in Southern Europe, but the majority of doctors still remained unconvinced. 

 

That is, until the evening of March 24, 1882, in a lecture hall at the Physiological Society of Berlin, where Robert Koch gave one of the most famous medical lectures of all time. I talked more about how Koch proved germ theory in Episode 36, but a brief refresher — Koch was a young health officer in the rural Wollstein district, and between his time taking care of his patients he ran a brilliant series of experiments that proved that anthrax was caused by an infectious organism, and developed a method, which we now call “Koch’s Postulates,” to prove that a microorganism caused disease. That was in 1872. In the interim, he had found considerable fame, and had been appointed to the Imperial Department of Health in Berlin. In Wollstein, he built a makeshift lab behind his house, using a microscope that had been a gift from his wife, no more advanced than Leuwenhoek’s 150 years before. But now, he had the latest equipment, all the lab animals he could want, and laboratory assistants who could go on to make history themselves. And he put all of his energy into proving that tuberculosis, like anthrax before, was an infectious disease.

 

Koch was apparently not a dynamic speaker. But his address that night was uncharacteristically short and elegant. There were no questions or interruptions. Everyone in the room understood the gravity of what had just happened as Koch presented his findings of the tuberculous bacillus. Within days, it was front page news in pretty much every major world newspaper; I can’t think of a similar scientific parallel in my lifetime. 

 

This new understanding called for a new type of treatment. Traditional therapies for phthisis should be familiar to anyone who listens to Bedside Rounds. The patients on Laennec’s wards were treated with a combination of a bland diet, mild purgatives, and bloodletting. More extreme bloodletting became increasingly popular with “Broussais-mania”, not only in France, but also in England and the United States, like I talked about in the two-parter on bloodletting and the birth of population medicine. But as doctors slowly learned more about the disease, more and more fanciful cures were concocted. Lugol’s solution, an iodine solution that was used to treat thyrotoxic goiter prior to surgery well into the twentieth century, was first used for consumption, though iodine toxicity was common. Tuberculosis was thought to deplete the blood of essential fats and oils — to replace them, cod-liver oil became a standard treatment, again, well into the 20th century.  It apparently tasted vile, but at least was relatively harmless. More destructively, as consumption was gradually understood to be a primary lung problem, doctors started to experiment with inhalations. Coal gas was pumped into patients’ lungs, and once the age of antisepsis dawned, carbolic acid was favored. As the gasses became more complex, they were pumped directly into the rectum; once mycobacterium tuberculosis was identified, and experiments showed that it was incredibly heat sensitive, superheated air — to 150 degrees fahrenheit — was used as well.

 

But by the end of the nineteenth century, a remarkable new phenomenon in tuberculosis treatment had emerged — the sanatorium movement. “Sanatorium” takes its name from Latin, to cure. They were also known by the name sanitarium, more commonly in the United States, which comes from “sanitas” — health, downplaying the active role of the physician. In any event, sanatoriums were specialized tuberculosis hospitals, focused on gradual exercise, fresh air, and the healing of of tuberculosis. At their height, there were 839 of them in the United States, capable of taking care of 136,000 patients at any time. Your city probably had one — and most likely the building is still there. I actually drove out to the old Boston Sanatorium, the Boston Consumptives Hospital, located in the neighborhood of Mattapan, which at the time was at the rural suburbs of Boston. It’s a beautiful brick building, on a sprawling campus nestled on the banks of the Neponset River. Now it serves as housing for older adults, and even though the location is now nestled in the suburbs of Boston, I still felt the healing atmosphere of the place. They seem so old-fashioned now, romantic like the White Plague itself, and so out of place with a more scientific age. But in many ways, the sanatorium movement was the beginning of scientific treatment for tuberculosis.

 

There was nothing inevitable about their advent. In 184 0, an English physician named George Bodington noticed that cold air seemed to help his patients, and advocated not treating phthisics with dangerous medicines but with cold air, a nutritious diet, and exercise. He was not heeded; the Lancet was dismissive, writing that they wanted to avoid  “expending any portion of our critical wrath on his crude ideas and unsupported assertion.” 

 

The movement started with the same amount of scientific rigor as superheated rectal air. The first sanatorium was started by Hermann Brehmer, a young German doctor. He wrote his medical thesis on tuberculosis in 1853, and became convinced that tuberculosis was a curable disease. On autopsy of his patients, he noted the presence of healed tubercles in the lungs, as well as an atrophic heart. He also pointed out the observation — which we now know to be untrue — that tuberculosis is absent from people who live at high elevations. Brehmer, a good German, felt that tuberculosis was fundamentally a heritable disease. But a weak heart caused those who were susceptible to fall ill. Perhaps a mountain climate could help strengthen their hearts?

 

He chose the tiny mountain village of Gorbersdorf in Silesia, where he built a few rustic chalets and began accepting patients in 1859. He would lead his patients on daily outdoor walks through the woods, and prescribe a healthy diet and local springwater. He soon realized that the intense exercise was too much for many of his patients, and installed permanent benches along his walking routes for patients to sit and rest. These benches would be copied in pretty much every sanatorium to come, and would eventually be adopted by landscape designers looking for a new type of park. If you’ve ever walked along a park trail and found a pleasant little place to sit and take a rest, you can thank Hermann Brehmer and his concern for consumptives.

 

Brehmer’s sanatorium never got any support from the government — he was a democrat in a Prussia that was shaken by the revolutions of 1848. And if it were not for one of his patients, the whole scheme might have died right there. Peter Dettweiler was a military surgeon who contracted tuberculosis while in the military fighting against France, and came to Gorbersdorf to recover. He later relapsed, and came again for a cure. A convert, he became Brehmer’s assistant, and later started his own sanatorium in Falkenstein, close to Frankfurt. Unlike Brehmer, he published his work widely in medical journals, and traveled around the world — especially in the English speaking world — promoting the idea of sanatoriums. While many of the statistics from these early sanatoriums should be viewed with considerable skepticism, Dettweiler claimed a cure rate of 53% among patients who stayed for longer than a month. Rapidly sanatoria spread across the world — the most notable were Nordrach in Germany, Davos in Switzerland, and for the purpose of this story Lake Saranac in New York. 

 

Across the Atlantic, Edward Trudeau was a young doctor living in New York City, with a wife and a young daughter, when he came down with a scrofula. He ignored the symptoms for two years, until he started to have daily fevers and a cough. He went to a friend, who diagnosed tuberculosis. He had seen his younger brother die of the disease, and he later recalled his emotions as he stepped outside the clinic:

 

“It seemed to me that the world had suddenly grown dark. Had I not seen all the horrors of consumptions in my brother’s case? It meant death and I had never thought of my death before. Was I ready to die? How could I tell my wife whom I had just left in unconscious happiness with the baby in our new house? All lay shattered now, and in their place only exile and the inevitable end remained.”

 

Trudeau’s vision came to past, and he slowly wasted away, trying traditional treatments to no avail. Finally, realizing he was soon to die, he traveled to the Adirondack Mountains in upstate New York, where he had spent his childhood, hoping to spend his last days hunting and fishing. He tried to get as deep into the wilderness as possible, and he ended up at Paul Smith’s Inn on Saranac Lake. But he didn’t die — spending his days in the outdoors, fishing and hunting, he slowly gained his strength back and gained 15 pounds. After a few months, he returned triumphantly to New York — only to fall sick with consumption again. Realizing what he had to do, he moved his growing family permanently to Lake Saranac. It was there he read both of Brehmer and Dettweiler’s sanatoria, and of Koch’s discovery of the tuberculus bacillus. He decided to meld the two — the romantic sanatoriums with the science of germ theory — at Saranac Lake. He set about teaching himself to stain the tuberculous bacillus from sputum, and at the same time ran experiments on rabbits. Channeling Villemin, he infected two groups of rabbits with tuberculosis; another served as a control. Four of the five confined to a dark and damp space died; only one of the five allowed to run free did. And unlike the sanatorium movement in the Old World, which often catered to the wealthy, Trudeau decided that his sanitarium would be open to all. He set about raising funds for a new type of hospital, and in 1885 opened his “Little Red Cottage” on the shores of Lake Saranac. To say that it was a success was an understatement — Lake Saranac exploded, and soon sanatoria were opening all over the country, especially in the mountainous West. 

 

By the early 20th century, the form of sanatoria ranged dramatically — from luxurious and alcohol-fueled parties for the fabulously wealthy in Davos, to hospitals for the destitute in New York City. But the regimen for patients was largely similar. Finsen and Ransome had shown that sunlight — especially ultraviolet light — could kill the bacillus, and that an ultraviolet bulb could actually heal tuberculosis skin lesions. Therefore, patients were kept in both fresh air and sunlight as much as possible. Covered balconies served to keep them safe from the elements. Cod-liver oil was a constant, and a fatty diet was prescribed, with up to seven meals a day. In the early sanatoriums, there was an uneasy mix between rest and exercise. Brehmer led strenuous walks, and in England, the poor in sanatoria were often put to manual labor. But Dettweiler and Trudeau favored rest, especially for active tuberculosis. Eventually, a regimen was settled on of graduated exercise — initially rest, lying down at an incline, then gentle exercise, eventually becoming more and more vigorous as the patient improved. Sanitation and infection control were essential; spitting was forbidden, and the new innovation of linoleum was put into place to prevent places for the bacillus to hide. Sanatoria began to lose the ornamental features that hospitals were associated with in the nineteenth century, all in the name of cleanliness. And finally, life was incredibly regimented, and “against medical advice” discharges were common. William Osler would write, “A rigid regime, a life of rules and regulations, a dominant will on the part of the doctor, willing obedience on the part of the patient and friends—these are necessary in the successful treatment of tuberculosis.”

 

For the most part, medication was discouraged in sanatoriums on the basis it was a hindrance more than a help, other than laudanum and morphine for the seriously ill. But in the beginning of the 20th century, increasingly sophisticated microbiological, surgical, and radiological techniques started to be used. Trudeau had championed staining sputum to look for “acid fast bacilli,” to track response to therapy, and soon this  was practiced worldwide. What’s crazy — when I worked in Botswana, treating many tuberculosis patients on my TB ward, I used the exact same method! New surgical techniques were developed to collapse tubercles and convert sputum to negative — artificial pneumothorax, artificial pneumoperitoneum, thoracoplasty, plomage, phrenic nerve crushing, and even lung resection in extreme cases. These sound rather horrific — but there’s evidence that they actually worked. A retrospective review in the British Journal of Tuberculosis in 1939 looked at who had confirmed sputum positive TB, who were treated with artificial pneumothorax — allowing air into the pleura to partially collapse the lung. By the end of the six year follow up period, 56% were sputum negative. A similar study in Cleveland used a control arm, looking at patients who agreed to receive thoracoplasty — the resection of ribs to allow the pleura to obliterate the tubercle — and comparing them with those who rather reasonably declined this procedure. Sixty-six percent of the thoracoplasty group converted to negative sputum, and only 17% of those who didn’t get it. And finally, by the early 1920s, chest x-rays had improved to the point that they were used, along with sputum, to track the success of therapy.

 

So here’s the million-dollar question — over a period of 100 years, sanatoria became widespread across the globe, and both in form and function dramatically influenced medicine. So did they work? 

 

Knopf published a systematic review of mortality statistics from 15 different institutions in Les Sanatoria in 1895 which suggested that the European sanatoria were actually doing what they claimed. Mortality rates were between four and 14 percent, with cure rates anywhere between 13 and 44%. Mean length of stay was three months. That being said, this data is spotty at best, with no standardized case definitions for what constituted a cure, and no follow up over a longer period.

 

In 1923, Cox decided to perform a more detailed analysis, which he published in the British Journal of Tuberculosis. Realizing he didn’t have the resources for an actual clinical trial, he decided to use retrospective data from the Lancashire County Council. At this point, every citizen in the county who was diagnosed with TB was required to register the the Council. These TB registries not only included objective case definitions, as defined by a county physician, but also sputum studies, and data about treatment. He decided to analyze all patients over a five year period from 1914-1918. 2310 patients completed a sanatorium course, and 1757 opted to be treated at home. Fourteen percent of the sanatorium cases had died by 1921, compared with 38 percent of non-sanatorium cases. Of the sputum positive, 61% had died, compared with 81% of non-sanatorium. From this he concluded that sanatorium treatment was in fact quite useful, especially for early, sputum-negative cases.

 

Ultimately, it’s impossible to know now whether or not sanatoriums really worked. Certainly, their founding principles were based on unfounded science on the heredity of tuberculosis and weakness of the heart. But what little data we have suggests there was some sort of positive effect on patients there. Confounding all this, as I alluded to in the beginning, is that during the nineteenth century, humanity seemed to gain the upper hand over the White Plague. After death rates peaked around 1800, they began a slow decline. I’ve posted a remarkable graph to my twitter feed (https://www.researchgate.net/figure/Tuberculosis-mortality-rate-per-100-000-population-for-England-and-Wales-between-1838-and_fig2_257533173) of mortality statistics in England, showing a death rate per 100,000 of almost 400 in the early 1830s, declining to about 130 by the turn of the twentieth century, to finally only about 50 by 1946, when streptomycin was introduced. Could the sanatorium movement have caused this dramatic decrease in death?

 

Probably not on its own. During the nineteenth century, there were two converging societal changes that fundamentally changed our relationship with disease. The first is the advent of public health — the idea that infectious disease can be fought by population-level interventions. If you look at that graph, you can see some of those interventions — mandatory reporting of TB cases, screening for tuberculosis, isolation of infectious individuals, and education about ways to decrease transmission. In this telling, sanatoria likel y played an important part in isolating individuals when they were the most infective, and encouraging sanitary practices like reducing spitting.

 

The second large-scale societal change in improvements in what we now call the “social determinants of health” — the idea that disease is intimately tied to the economic and social status of populations. This would include improving nutritional status, building sanitation systems, increasing wages, increasing human rights, and increasing education. For example, Holloway-Kew and her colleagues analyzed a variety of statistical data and determined that improved public health measures and the social determinants of health alone lead to an 88% decrease in mortality prior to introduction of effective medication. Again, sanatoria, with their focus of proper nutrition and exercise, likely played a part in this change.

 

This has become the dominant view in explaining the victory over the White Plague. But I’d be remiss if I didn’t discuss an intriguing alternative hypothesis advanced by Davies and his colleagues. They analyzed mortality data from England and Wales from the beginning of modern record-keeping in 1850, comparing tuberculosis mortality with mortality from both dysentery and cholera. Their hypothesis was that if public health interventions and improvements in the social determinants of health alone were responsible for the decrease in mortality from tuberculosis, all would be expected to go down in lockstep. But in fact, while mortality from tuberculosis did in fact go down and real earnings did go up, cholera and dysentery mortality remained unchanged. The authors conclude that some other factor must be responsible for TB’s decline, and advance the theory that since TB causes the most mortality among young adults of child bearing age, perhaps it provided some selective pressure on humanity — maybe humanity evolved to be more resistant to our greatest foe?

 

Regardless of the reasons, tuberculosis mortality continued to decrease throughout the 20th century, with brief upticks during each world war, until 1946, when the first randomized controlled trial in history was run on streptomycin for treatment of pulmonary TB. Shortly thereafter, combination antibiotic therapy was introduced, and TB mortality essentially dropped to zero in high-income countries. The sanatorium movement wouldn’t last much longer. In 1959, a randomized controlled trial was performed in India that showed sanatorium care with antibiotic therapy was noninferior to home care with antibiotic therapy. Almost overnight, sanatoria were shuttered all over the world, within a decade ending a movement that had lasted a century and reshaped medicine. And as for TB? The medical community congratulated itself on almost eliminating a disease that had been a scourge on our species since the beginnings of humanity itself — until it roared back with a vengeance in the 1980s with the onset of the HIV/AIDS crisis. Today, in 2018, TB remains one of the top 10 causes of death worldwide, and the number one killer of patients with HIV. In 2017, 1.6 million humans still died of the disease. The White Plague stalks us still. 

 

Okay, that’s it for the show!

 

But wait — it’s time for a #AdamAnswers. #AdamAnswers is the segment on the show where I answer whatever questions you have about the practice of medicine, no matter what they are.

 

This week’s come from Stephanie Eck via twitter, who asks, “What is with the increase in women consuming their placenta after giving birth? Is there really any benefit to it or are they falling victim to a kind of placebo effect? The idea of people doing this is just…well…hard to swallow.”

 

Well, Stephanie, that is a Grade A pun, and this is certainly a topic that I never really thought I would be covering on Bedside  Rounds. The scientific term for consumption of the placenta is “placentophagy”. But before I get too much into that, let’s talk about the placenta itself. I was recently lucky enough to spend a week recreating classic scientific experiments at the Mount Desert Island Laboratories in Maine; that’s neither here nor there, but one of my colleagues there was a PhD researcher on the placenta. And talking with her basically blew my mind. I think as an internist I just haven’t thought much about the it — but what a fascinating organ! It’s a single organ, but composed of two different organisms — both the mother and the fetus. The immunological implications of this is crazy — it basically needs a cloaking device to protect itself and the fetus from the mother’s immune system. My favorite organ — the kidney — just seems so dull in comparison.

 

But back to the topic on hand. We’re talking about eating them. My major references here are two reviews, the first by Alex Farr and his colleagues in the April 2018 American Journal of Obstetrics and Gynecology; the second is a slightly older review by Cynthia Cove and her colleagues in the Archives of Women’s Mental Health. Basically every non-human mammal consumes their placenta after birth. There’s experimental studies showing that placentophagy is beneficial in rats, and the evolutionary thought is that consumption of the placenta helps hide evidence of birth from predators. That being said — it appears that no human societies eat the placenta. In 2010, Young and Benyshek used an anthropological database to cross-reference 179 different societies. There was no practice of maternal consumption of the placenta as part of any cultural tradition, and only three references to non-maternal placentophagy, as part of traditional medicine. The authors conclude that there’s no evidence that placenta-consumption is cross-culturally widespread. Why don’t humans consume the placenta? The “fire theory” has been expressed; essentially, that when humans began to cook meat, they had a ready source of iron, and therefore less need to consume the placenta after birth for its iron content. 

 

So — human societies don’t appear to traditionally consume the placenta, though most other mammals do. There certainly seems to be a perception that women are consuming their placenta more frequently after birth. For example, google searches for “placenta encapsulation” — the most common preparation — have steadily ticked up over the past decade. We don’t have great information of just how many women have practiced placentophagy, and how this has been increasing. The first accounts in the medical literature are from the 1970s. But all evidence seems to suggest popularity and interest are growing. Right now there are any number of websites with instructions on how to cook, dehydrate, encapsulate, or chop of the placenta such that it can be eaten raw. The movement has even spurred three U.S. states to pass explicit laws allowing release of the placenta to women. 

 

Why do mothers do it? An internet-based survey suggested the most common reasons women practice placentophagy were to prevent postnatal mood disorders (depression, baby blues, and anxiety), but also for increased energy, and improved lactation. And to the second part of your question, Stephanie, does it work? The AJOG paper performed a systematic review of studies looking at the effects of maternal placentophagy. There are two randomized controlled trials on the subject. The first, a high quality (grade A) trial found that maternal iron stores were no different in woman who consumed encapsulated placenta. The second is an RCT from 1954 with significant limitations; however, it did find that 86% of women self-reported good increase in milk production. I should point out that there are a number of self-reported surveys (many run by people who sell placentophagy products) that show considerable improvement in self-reported mood or energy.

 

So the best quality evidence we have is that there’s no effect on maternal iron stores, and maybe (with a big asterisk) improvement in milk production. Even if the mood and energy effects are placebo, that should be enough to either support (or at least not condemn) the practice, right?

 

Not so fast — because there are very real concerns of adverse effects from placentophagy. The first is the very real risk of infection. There’s reports of group B strep sepsis being transmitted, and reason to believe that viruses could be transmitted as well, including HIV, hepatitis, and Zika. There’s also of evidence of heavy metals accumulating in the placenta, and a recent study in fact found that placental pills had detectable amounts of cadmium. Farr and his colleagues conclude at the end of their paper, “There is no scientific evidence of any clinical benefit of plancentophagy, and there is evidence for an actual risk of harm.” With this, they say, doctors should not offer the procedure, and actively counsel against it. 

 

Okay, thanks so much for the question Stephanie! I’m always happy if I get to spend a little more time reading about the placenta. And, dear, listener, do you have a question about medicine that you want me to answer? Tweet at me @AdamRodmanMD! 

 

That really it for the show! I hope you enjoyed this episode — I had a ton of fun working on it. Tweetorial King and Bedside Rounds editorial board member Tony Breu initially put me up to this — and he has a pending Tweetorial on how some of the sanatoria treatment physiologically worked. But I also have a soft spot, as it were, for TB. In high income countries, we have this antiquated perception of TB — something that happened in the distant past. But as I read about doctors struggling in London, Paris, and Boston to try and treat TB during the nineteenth century, it reminds me of my time in Botswana, where TB infections, including TB sepsis, accounted for about a third of my patients. Even some of the treatments — open windows (I rounded with a coat and gloves in the winter, and my poor patients were covered in blankets), sun-filled courtyards, and essentially using the same method to quantify “acid fast bacilli” as Koch — this isn’t ancient history, this is going on in low-and-middle income countries every day. 

 

Finally, if you want to read more about humanity’s battle with the White Plague, I can’t speak highly enough of the book The White Death, by the late Thomas Dormandy. It’s an eminently readable tome through the cultural impact tuberculosis has had on our society. 

 

If you are a member of the American College of Physicians, you can get CME or MOC credit just by listening to this episode. Go to www.acponline.org/bedsiderounds and take a brief quiz for your credit. All of the episode are on the website at www.bedside-rounds.org, or on iTunes, Spotity, Stitcher, or the podcast retrieval method of your choice. You can reach out to me on facebook at /BedsideRounds, or on Twitter at AdamRodmanMD, which is pretty much my social network of choice now. I Tweet about, of course, medical history, but also evidence-based medicine.

 

All of the my 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.