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https://youtube.com/watch?v=7D-gxaie6UI.
Tuberculosis is often thought of as an old-timey disease, but in reality, it continues to kill over a million and a half people per year, despite its known cure. How did we get here, to a world where decades of work toward a cure stalled in its dissemination around the globe? And how can understanding the history of TB point us toward a different future? If you’ve been following author and TB-hater John Green in any way for the last year or so, this video is the deep dive you’ve been waiting for…

TB Fighters: You can learn more about the TB Fighters Community at https://tbfighters.org

This lecture was produced thanks to the generosity of the Crash Course audience, including those who fund us on Patreon, who’ve purchased Crash Course coins, and who share Crash Course with others. Your support lets us experiment with new formats, cover lesser-known topics, and go deeper than we ever have before. Thank you!

Sources: https://docs.google.com/document/d/1C8jRj6cE50pnoDyLQVGYhCWyazHz4vC-TC_KXC6tnak/edit#heading=h.4kgrhaj5zoui

Chapters:
The Deadliest Infectious Disease of All Time 00:00
Tuberculosis is Weird 3:36
"Man Got to Tell Himself He Understand" 7:05
The Allure of Consumption 14:46
The White Man's Plague 21:07
Treatments and the Cure 27:29
Where the Drugs Are Not 34:06
A Fundamental Mistrust 36:48
The World We Choose 45:34


The surprising history - and current dilemma - of TB


***
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This is the story of the deadliest infectious disease of all time.

It's been with us for 3 million years, since before humans were homo sapiens. We have evidence of it in the mummies of ancient Egypt, and it's mentioned in the Hebrew Bible.

We’ve made extraordinary medical advances. Vaccines, antibiotics, and clean water have saved millions of lives. And yet despite that, in 2022, this disease killed more people than malaria, typhoid, cholera, homicide, and war…combined.

It has gone by many names. In ancient China, it was known as huaifu, meaning “destroyed palace.” In ancient Hebrew, “schachepheth,” meaning wasting away. The 19th-century term: "consumption," for the way it seemed to consume the body.

Today, we call it tuberculosis. But tuberculosis is more than just a disease— it reveals fundamental truths about who we are as human beings, and how we have changed, or failed to change, throughout history. We are powerful enough to light the world at night, to artificially refrigerate food, to reshape the balance of gases in the atmosphere.

And we’ve even identified the cure to TB. So, why are so many people still dying of it? I’ve always found it strange that in studying history we tend to focus so little on disease.

Something like 90% of people die of disease, a phenomenon so entrenched in human life that we describe many such deaths as “natural causes,” and yet if you attend a college survey on the history of humans, you will learn more of wars and empires and trade routes than of microbes. As Virginia Woolf wrote in On Being Ill, it is “strange indeed that illness has not taken its place with love, battle, and jealousy among the prime themes of literature.” Or put another way: Hamlet never gets a headache, but the rest of us do. I suspect that we want to imagine that we choose our fate, that human history is largely the story of human choice.

Like, perhaps that's why rumors swirled that Alexander the Great died of poisoning even though he almost certainly died of typhoid or malaria. We simply don’t want a world where even the world’s most successful emperor can be felled by mere infection. And yet that is the world we live in– a world where disease shapes history in profound ways.

But also a world where history shapes disease. Like, anyone can get tuberculosis, but not everyone has an equal chance of getting it. And certainly not everyone has an equal chance of dying from it.

And to understand why, I had to go back–way back–to discover how our earliest understandings of TB evolved, alongside culture, into the problem we’re now facing. First, let me give you a very basic overview of our current understanding of the disease, which can be summarized as: Tuberculosis is weird. It’s an infectious disease, meaning it’s caused by germs.

Like COVID-19, it’s spread through the air we breathe. And you might be surprised to learn that around a quarter of all humans are currently infected with mycobacterium tuberculosis. But, only 5 to 10% of them will ever progress to what is called “active disease,” which is when the infection makes you chronically sick.

If an infection does proceed to active disease, it usually happens within two years of the initial infection, but TB also may lie dormant for decades before suddenly exploding. What causes this progression to active disease? Well, again, it’s complicated.

We don’t fully know, but risk factors include malnutrition, lack of access to medical care, crowded housing conditions, and a severely compromised immune system, especially from insufficiently treated HIV infection. But even once the disease becomes active, its course is extremely unpredictable — it may kill its victims within a few weeks, or over many years. It usually attacks the lungs, but can also invade other organs — like the brain, or pancreas, or spinal column.

For reasons we don’t fully understand, some patients will recover without treatment, but most, if left untreated, will eventually die of tuberculosis. Much of this strangeness is related to the bacterium itself. Mycobacterium tuberculosis has an unusually fatty, thick cell wall, which makes it difficult for infection-fighting cells to destroy the bacteria.

So instead, the bacteria is surrounded, first by one white blood cell, and then by many, which creates this ball of calcifying tissue called a tubercle. As long as these vaguely spherical tubercles hold the bacteria within them, active disease never develops, but if the bacteria escapes and the immune system isn’t strong enough to surround all the new bacteria with tubercles, the body can slowly be overwhelmed by infection, eventually leading to death. Now because it takes so long to build the complicated fortress of its cell wall, mycobacterium tuberculosis has an incredibly slow growth rate compared to other bacteria.

Like in laboratory environments, E. coli divides and doubles about once every 20 minutes; Mycobacterium tuberculosis divides about once per day. And so infections simply take longer to make a person sick. In short, TB is not like a plague that sweeps through a community, where one member of a household gets sick and everyone else in the household is sick three days later.

It’s not like a cancer or heart disease that affects one person in a home but rarely spreads to others. And it’s not like an E. coli infection where you get violently sick all at once. And being so fundamentally different from other infections is precisely why the classical understandings of tuberculosis varied so widely, and why even today, the stories we tell ourselves about the disease reveal at least as much about humans as they do about tuberculosis.

So it wouldn’t be accurate to say that we thought of tuberculosis one way or another in antiquity — we thought of it many different ways. [inquisitive string music] Some communities believed the disease was genetic; others thought it was contagious. Some thought it was caused by foul air; others by a disharmony of fluids within the body. Some even approached a germ theory of disease.

Like, hundreds of years before humans invented the microscope, the great Persian scholar and poet ibn Sina wrote that diseases such as TB were caused by “tainted foreign organisms that are not visible by naked eye.” Which, very impressive, but no way to confirm it pre-microscopy. I want to pause here to note a defining feature of humans, which is that we like to know why things happen, especially why really bad things happen. And if a reason is not immediately apparent, we will find one.

I'm reminded of a short poem by Kurt Vonnegut: “Tiger got to hunt, bird got to fly; Man got to sit and wonder ‘why, why, why? Tiger got to sleep, bird got to land; Man got to tell himself he understand.” And this brings us to an important facet of understanding human responses to illness: stigma. As part of our desire to answer the question “why why why” by telling ourselves we understand, humans commonly construct moral and ethical narratives around illness.

Like, my dad had cancer twice when I was a kid, and I saw some of this firsthand. People kept their distance from us. Some said he got cancer because his parents smoked, or because he didn’t exercise enough, or because he didn’t eat broccoli, or whatever. [contemplative music swells] And it’s true that second-hand smoke and poor diet are risk factors for cancer, but it’s also true that the vast majority of people whose parents smoked do not get cancer when they are a 32-year-old father of two young kids.

We do not want to reckon with a world that is merely unfair, where some people get sick not because they did something wrong, but because the world is unjust— and insofar as it is just, it’s random. And so we tell ourselves we understand, which too often means creating explanations that blame the sufferer. Stigma is a way of saying, “You deserved this to happen,” but implied within the stigma is also, “And I don’t deserve it, and so I don’t need to worry about it happening to me.” Stigma can become a kind of double burden for the sick– in addition to living with the physical and psychological challenges of illness, there’s the additional challenge of having their humanity discounted.

Think of the word, universally used in English, to describe tuberculosis patients in the 18th and 19th centuries: They were called invalids. They were, literally, invalid. People living with TB today have told me that fighting the disease was hard, but fighting the stigma of their communities was even harder.

Now stigma is very complex, of course, but researchers have identified certain hallmarks of highly stigmatized illnesses. Chronic illnesses are more likely to be stigmatized than acute ones, for instance, as are illnesses with high levels of perceived peril. And critically for understanding tuberculosis, stigma can be compounded if a disease is understood to be infectious.

Finally, the origin–or perceived origin– of a disease also matters. If an illness is seen to be a result of choice, it is much more likely to be stigmatized. So for instance, people with major depression are often told to just choose to be happier, just as those with substance abuse disorders are told to just choose to quit drinking.

And some cancers and heart diseases are stigmatized for resulting from purported choice as well. Of course, this is not how biology works– illness has no moral compass. It does not punish the evil and reward the good.

It doesn’t know about evil and good. But we want life to be a story that makes sense– which is why, for example, it was commonly believed up until the middle of the 20th century that cancer was caused by things like social isolation. Parents were actually told their kids got leukemia because they hadn’t been adequately loved as infants.

If a clear cause and effect isn’t present, we will invent one, even if it’s cruel– because tigers gotta sleep, and birds gotta land, and man gotta tell himself he understand. TB occupies an interesting place in this conversation: It’s a chronic disease with high levels of perceived peril, but it wasn’t always understood to be infectious and, in much of the world, it wasn’t seen as a choice. And yet, TB was a highly stigmatized disease– it was often associated with demon possession or excessive alcohol consumption or moral frailty.

But in Northern Europe, beginning in the mid-18th century, it became untenable to understand the disease then known as consumption through only a stigmatic lens. [music intensifies] The disease had exploded — especially in Britain’s cities and North American colonies. Stigmatizing away an illness becomes harder when everyone seems to be getting it, not just the poor or the vulnerable but even the rich. I mean, the richest individual of the 19th century died of TB at the age of 56.

It killed presidents and kings and poets and actresses. And so suddenly, consumption became a romanticized disease–a disease of beauty, and refinement, and intellectual sophistication. “Death and decay are often beautiful,” Henry David Thoreau wrote, “like the pearly tear of the shellfish or the hectic glow of consumption.” [contemplative piano] So it may be tempting to think that romanticizing a disease would be better than stigmatizing it. But, as somebody who suffers from mental illness, I understand firsthand that the two aren’t entirely separable.

Like, both strategies ultimately other the sufferer, imagining them as somehow removed from the social order. Mental illness is often romanticized as unwellness that brings on creative genius or other superpowers. [Scientist laughs maniacally] But of course, mental illness is also heavily stigmatized in our culture. And so romanticization and stigmatization are essentially, like, complementary strategies for casting people out of society and finding a story that makes sense for why “those people” ended up sick.

In the case of consumption, this romanticization goes deep...and wide. Like, once you start noticing the impacts of this story on contemporary culture, you start to wonder if there’s anything in our lives today that’s not connected to TB. So classically, consumption was viewed as a disease of the air.

It was an illness of the breath, of the place where the body interacts with the atmosphere. Consider many of our words for the human soul: The Hebrew ruach, the Chinese chi, the English spirit, and the Inuit sila all derive from words meaning breath or breathing. Breath is life– to be inspired is literally to breathe in; to be expired is literally to breathe all the way out.

And so it was easy to make this disease of breath into a disease of the spirit, the chi, the sila, and the ruach. So much so that at times consumptives were seen as paragons of brilliance and beauty. In men, consumption was believed to bring creative powers to new levels.

Scholars pointed to the fact that everyone from Stephen Crane to Frederic Chopin to the sculptor of the Statue of Liberty died of consumption. (Less attention was paid to the fact that, in a world where roughly 30% of all northern Europeans were dying of a disease, it shouldn’t be particularly surprising that many northern European artists and writers were dying of it.) But like one magazine at the time linked TB to authors in particular, writing that an author’s “waywardness, peevishness, irascibility, misanthropy, [and] murky passions … are referable to their constitutional peculiarities and condition" In simple words, that their mental eccentricities result from the derangement of bodily health. And that's precisely what I mean when I say that romanticization is not a kind or generous way of treating the ill. I am an author, and I for one am deeply offended by the notion that my waywardness, peevishness, irascibility, misanthropy, and murky passions are caused by a derangement of bodily health, even as I am impressed by a 19th-century magazine’s ability to absolutely nail my personality.

It’s hard to overstate how profound the link between consumption and male creative genius was believed to be. It is said that Victor Hugo’s friends, for instance, joked with him that he could’ve been a truly great novelist, if only he’d contracted consumption. Lord Byron wrote, “I should like, I think, to die of consumption … because then the women would all say, ‘ See that poor Byron – how interesting he looks in dying!” And if men in northern Europe were seen to achieve via consumption greater artistic and creative heights, then women were believed to become more beautiful, and ethereal, and wondrously pure.

As Charlotte Bronte put it two years after the publication of her novel Jane Eyre, “Consumption, I am aware, is a flattering malady.” That flattering malady, incidentally, would kill Charlotte also and all three of her sisters. Patients with active TB typically become pale and thin with rosy cheeks and wide sunken eyes due to the low blood oxygenation and fevers that accompany the disease. Like the English actor Eliza Poe, whose beauty was widely admired, looked stereotypically tubercular– her rosy cheeks, alabaster skin, wide eyes, and tiny body were all the result of consumption, which killed her in 1811, when she was 23 or 24 and her son, Edgar, was two.

Edgar Allen Poe would go on to describe many of the women in his stories and poems as similarly wispy, pale, and large-eyed. By the time of Eliza’s death, so-called “consumptive chic” had taken over European beauty standards. American and European magazines encouraged women to apply the poison belladonna to their eyelids to dilate their pupils so they could have that wide-eyed consumptive look— —and offered instructions for how to apply red paint to the lips and cheeks to capture the hectic glow of consumptive fevers.

I probably do not need to point out that from runway shows to fashion magazines, these standards of beauty are still molding what is considered to be feminine beauty. But TB shaped not only the makeup and beauty standards of the era but also fashion, which, for women, sought to emphasize the visible symptoms of illness. The most glaring such clothing was the pointed corset, which emphasized the narrowness of women’s waists (the similarity by the way between “waste” and “waist” is an etymological coincidence in English, but a telling one).

These corsets were so restrictive that women were limited in the kinds of physical activities they could accomplish, and struggled to get full breaths of air, both of which mirrored the experience of actual consumption. And so consumption had become fully glamorous, and idealized. [pensive music plays] “There is a dread disease,” Charles Dickens wrote in Nicholas Nickleby, “… in which the struggle between soul and body is so gradual, quiet, and solemn… that the spirit grows light and sanguine with its lightening load.” Dickens did not name the disease– nor did his readers need him to. Everyone knew of the disease that shrank the body and enlarged the soul.

But of course, this belied the true violence of consumption. Perhaps the most famous 19th-century victim of tuberculosis was the English poet John Keats. When Keats’ body was autopsied a couple days after his death at the age of 25, the doctor wrote, “The lungs were completely gone.” This was–and is–the truth of death by tuberculosis.

The afflicted often drown as blood and pus fill their lungs. They die starved of oxygen, in agony. Here is where the romanticization of tuberculosis becomes–believe it or not–even more insidious.

Because underlying all these shifts was a feeling that consumption was, as some 18th-century observers put it, a disease of civilization. People at the time knew that city-dwellers were far more likely to develop consumption than those in rural communities, and this concept of consumption as a civilized disease also meant that it could not be a disease of uncivilized people, which led to a racialization of the illness. In Europe and the U.

S., most white doctors believed that TB could only infect white people, and it was sometimes known as “The White Man’s Plague.” One American doctor, for instance, called it, “a disease of the master race not of the slave race.” As Frank Snowden writes, “In the United States, the prevailing wisdom was that African Americans contracted a different disease. This phenomenon also extended to other colonial empires. Many European colonialists believed that TB was either rare or nonexistent among people of color.

In reality, there was extensive illness and death from consumption in colonial South Asia and Africa, and many local healthcare providers sought to bring attention to the crisis. But it went undetected and uncounted by colonial authorities because the entire premise of colonialism relied on white supremacy, and the genetic understanding of consumption relied upon the idea that only supreme people could contract it. Acknowledging that consumption was common among enslaved, colonized, and marginalized people would’ve undermined not just the theory of consumption, but the project of colonialism itself.

Toward the end of the 19th century, the romanticization of consumption began to decline as it became increasingly obvious that the illness was not exclusively or even primarily a disease of the rich and brilliant. Scholars had begun to turn their eyes “away from the languorous, fainting young women and their romantic lovers,” write René and Jean Dubos. “They noticed instead the miserable humanity living in the dreary tenements born of the Industrial Revolution. In the ‘tentacular cities’ they saw hosts of men, women and children, pale too, often cold and starving, working long hours in dark and crowded shops, breathing smoke and coal dust.

Tuberculosis was there, breeding suffering and misery without romance.” Still, arguments raged over what caused the disease until 1882, when a “vexatious little organism” called m. tuberculosis, was first identified by the physician Robert Koch. Over the next few years, the replication and acceptance of Koch’s research meant that the era of consumption– as an inherited condition that grew the soul by shrinking the body –slowly faded away. No longer could consumption be understood as an inherited condition shaped by sad passions and wondrously translucent skin.

Now, it was a germ disease– an illness of filth and overcrowding and poverty. The era of tuberculosis had begun. [old-timey orchestral music swells] [NEWS ANCHOR] From your local tuberculosis association... [orchestral music swells] Today, we understand the explosion of TB in the 19th century to have been primarily a result of the Industrial Revolution, which led to cramped living conditions in cities where workers could easily spread TB to one another, and where widespread malnutrition– an important risk factor for developing active disease– made people especially vulnerable. And so, just as Britain was Ground Zero for the Industrial Revolution, it was Ground Zero for the rise of tuberculosis.

And we’ve seen TB grow with industrialization in other communities as well, from India to Nigeria. “TB’s parallel journey with capital,” as Vidya Krishnan puts it, has been seen in outbreak after outbreak. But at the time, industrialization was not seen as the culprit. Instead, as understandings of TB shifted to being about poverty rather than romance, racialized stigma did a 180.

Where before Black and brown people were seen as incapable of getting such a beautiful disease; now, they were blamed for it. “The negro race suffers from tuberculosis, tainting the country,” one American official wrote. Racialized medicine no longer maintained that high rates of consumption among white people was a sign of white superiority; instead, racialized medicine now maintained that high rates of consumption among Black people was a sign of white superiority. But of course, none of that was true.

Black people were not more susceptible to TB because of factors inherent to race; they were more susceptible to tuberculosis because of racism. TB especially preys on those who are marginalized not because of their choices or habits, but because they are marginalized. It’s important to note that all this racialized medicine was challenged– it was obvious hogwash from the beginning, and there was loud rejection– especially from Black healthcare workers.

After a white doctor claimed “the negro is to blame for his own susceptibility to tuberculosis,” a Black physician wrote a response arguing that this kind of racialized medicine “smacked more of the cheap politician seeking notoriety and office by playing to passion and prejudice than a doctor discussing, philosophically, a scientific subject for the diffusion of knowledge.” Which is the doctor version of an extraordinarily sick burn. And in fact, this bias against marginalized people and the healthcare workers serving them has proven to be one of the great facilitators of tuberculosis over the last century. Even after establishing that tuberculosis was an infectious disease caused by a bacterium, nobody was quite sure how this disease spread.

But man got to tell himself he understand, and so attention came to focus on the kinds of places and environments that seemed to foster outbreaks of tuberculosis –crowded housing tenements and dirty factories. Some public health efforts did made a significant impact: Covering one’s cough or sneeze with a handkerchief which really did lessen the risk of spreading TB, as did discouraging spitting in public places like trolley cars and sidewalks, which was common in the U. S. at the time.

People were also told not to kiss babies. Or… kiss at all. Another obsession was with dirt and dust.

Which again changed fashion, grooming, and social habits. “There is no way of computing the number of bacteria and noxious germs that may lurk in the Amazonian jungles of a well-whiskered face, but their numbers must be legion,” argued Dr. Edwin Bowers in 1916. Fear of TB germs getting caught in beards led to what Harper’s Weekly called “the revolt against the whisker,” ushering in an era of clean shaves.

For women, hemlines grew shorter as anxiety rose that floor-length dresses might pick up TB germs off dirty floors. Vidya Krishnan points out that “as women’s hemlines rose a few inches at the beginning of the 1900s, shoes became an important feature of women’s fashion.” By the early 20th century, entire industries had grown up in the U. S. to try to treat tuberculosis. [MALE VOCALIST sings "You Can Lick TB"] I got the blues, the TB blues I got the heeby-jeeby TB blues... [Blues music continues] [JOHN] Dry air, sunshine, and rest were believed to be the best available treatments, and so sanitariums where consumptives could rest and breathe fresh air popped up around the world. [MALE VOCALIST] ...when the doc can say "Be on your way"...

Southern California came to be known as “the land of new lungs.” In a mass migration that rivaled the Gold Rush, consumptive patients traveled west, and–if they survived–began families, reshaping the landscape of the United States. By 1920, around 10% of all people living in New Mexico were TB patients living in sanitariums, where the dry air and open spaces were said to heal the lungs. [MALE SINGER] Blue and low down, way, way, way down, low down Aimin' for that doc at showdown. Buildin' to that special day When the doc can say "Be on your way"... [JOHN] Life in these sanitariums could be excruciatingly dull for the sufferer.

The job of the so-called “invalid,” was to improve their health by lying very still. Like, one sanitarium patient, Elizabeth Mooney, wrote "I do nothing all day except lie here staring at the mountains. I wish they would rearrange them a bit." Family members were discouraged from visiting the sick, not only because visits risked spreading infection but also because visits were seen as detrimental to health.

People might get excited and you couldn’t be excited because you had to rest. Often you were discouraged even from reading books and there was no YouTube. Many patients did recover in sanitariums– rest and adequate nutrition are much better for the body than malnourishment and stress– but recovery rates don’t seem to have been much higher for those taking the so-called “traveling cure” than for those who lived at home as invalids.

Nonetheless, separating millions of the ill from their homes did decrease the spread of the disease within families, and combined with better overall nutrition, safer housing, and lower rates of poverty, tuberculosis declined around the world. Between 1882 and 1930, overall mortality from the disease in the U. S. fell by around 80%.

But those improvements were not evenly distributed in the American population– the declines for African Americans and Chinese Americans were much lower, and for Indigenous people, there was very little decline at all. Even as we developed better tools to diagnose and treat tuberculosis– including the stethoscope, the X-ray machine, and chest drains– the illness was still fundamentally incurable. But then between 1940 and 1965, eight different classes of drugs that kill m. tuberculosis were discovered and synthesized.

But there was, however, of course, a catch. Because the tuberculosis bacteria with its waxy coating is uncommonly hard to kill, each of these drugs needed to be administered long-term in order to be effective. And that meant the bacteria had more time to develop resistance to drugs.

On top of that, no single drug was capable of treating TB on its own. So, it wasn’t until the mid-1950s that a combination treatment involving three different drugs was tested and approved, and for the first time in human history, tuberculosis became curable. As treatment, case-finding, and contact-tracing improved, new cases of TB were able to be identified and treated.

But in impoverished communities, which had for so long been believed by the rich world to be immune to TB, the illness continued to kill millions every year. Attempts to get combination therapy to colonized regions were haphazard and inconsistent, forcing many people in poor communities to find whatever antibiotics they could, regardless of their effectiveness against TB. In 2000, the Ugandan physician Dr.

Peter Mugyenyi gave a speech about the global failure to get HIV drugs into impoverished communities. “Where are the drugs?” he asked. “The drugs are where the disease is not. And where is the disease? The disease is where the drugs are not.” So, too, was the case with tuberculosis.

By the mid-1960s, curative therapy for TB was available everywhere– except for where it was most needed. I mentioned earlier that in the 25 years between 1940 and 1965, eight different classes of drugs were developed to treat tuberculosis. And then in the 47 years between 1965 and 2012, no new drugs were synthesized to treat tuberculosis.

The reason for this is straightforward– as TB declined in rich countries, the profit incentive for researching new drugs went away, and as a result, funding dried up. When TB ceased to be a problem of rich people, it not only ceased to be romanticized; it also ceased to exist in the minds of many. But a system of pharmaceutical research driven exclusively by profit incentive is of course not the only way to develop drugs.

As Dr. Carole Mitnick has told me, the failure to develop drugs for illnesses that are not seen as profitable is “a human-manufactured problem that needs a human solution. … If medications were a public good, the burden of disease would drive the priorities of the industry and TB treatment would be varied and plentiful.” In short, there is nothing inevitable about living in a world where developing drugs that lengthen eyelashes is more highly rewarded than developing drugs that treat tuberculosis. So all of this combined to keep the rates of TB death steady in much of the developing world even as it declined precipitously in rich nations. [foreboding music plays] And then, beginning in the early 1980s, physicians and activists in the Global South began to sound the alarm about an explosion in uncommonly swift and severe tuberculosis deaths that seemed to be associated with a new pandemic, that of HIV/AIDS.

Because untreated HIV lowers resistance to infection, TB infections are far more likely to progress to active disease as the immune system weakens. And although many were pointing out this connection in the mid-1980s, far too little was done to expand access to either TB or HIV medications. This inaction contributed to tens of millions of deaths from the intertwining pandemics of HIV and TB.

In fact, between 1982, when the term AIDS was first used, and 2005, when HIV deaths in poor countries finally started to decline thanks to increased access to treatment, roughly as many people died of tuberculosis as died in World War I and World War II combined. At a TB conference not long ago, I met a young South African woman named Phumeza Tisile, who was diagnosed with TB as a teenager. She had just received a full scholarship to university, but from the start of her freshman year, something felt off.

She had lost weight and was experiencing shortness of breath, eventually struggling just to walk up stairs. “So I went to the clinic and coughed into a cup,” she explained to me. Although we now have extremely accurate molecular tests for TB, they remain unnecessarily expensive, and so TB is still most commonly diagnosed via a person looking at a sputum sample through a microscope and trying to identify TB bacteria in that sample, which is exactly how Robert Koch diagnosed TB in 1882. Unfortunately, microscopy misses about 50% of positive cases, and Phumeza was told–catastrophically– that she was negative for TB.

But she kept getting sicker. She had to drop out of school. Her weight dropped to 70 pounds. “I was really struggling to breathe,” she remembered, and then finally, she received a chest X-Ray, whereupon it was obvious that tuberculosis was everywhere in her lungs.

She started on a standard TB treatment immediately. Now I have to take a little detour here to explain a protocol that’s been around since the late 70s, called Directly Observed Therapy (short course). The thing to understand about DOTs is that it really only exists because of a lack of trust that certain patients will take their medications consistently.

You might recall that TB is particularly susceptible to developing antibiotic resistance, which is worsened by haphazard treatment. So, the idea behind DOTs is to have a healthcare professional directly observe patients taking their medicine every day. And in the beginning, this protocol did help because any regular access to adequate supplies of appropriate antibiotics was good news.

But requiring patients to find their way to a clinic or doctor every day for months, or else live in inpatient facilities to receive their daily medications, creates extreme challenges for many with TB. As Dr. Jennifer Furin put it to me, tuberculosis “is the only disease I know where the core of therapy is based on fundamental mistrust.” Now it has long been argued that antibiotic resistance is driven by so-called “patient noncompliance,” which is to say, patients failing to take their medication.

And it is true that many TB patients fail to complete their full regimen. But the concept of “compliance” turns out to be really complicated when you zoom into the level of individual patient experience. [contemplative piano music] By the time she was finally diagnosed, Phumeza could not walk to the clinic by herself. She was simply too sick.

And public transport was expensive, not to mention the potential to spread the illness. Did her inability to access daily treatment make her non-compliant? Fortunately, Phumeza was able to avoid DOTs because South Africa had recently begun allowing seriously ill people to take home two weeks of treatment.

But after two weeks, she had to return to the hospital for more medicine, and it was clear she was getting no better. Eventually, Phumeza was hospitalized and after months of treatment, it was discovered that the drugs were failing because Phumeza had multi-drug resistant tuberculosis, also called MDR-TB. When she learned of her diagnosis, she told me, “I was searching stuff online, and it was really really scary to see because on Google so many of the people on images were already dead.

Their ribs were exposed and I thought I was gonna be like that, too. I thought I was likely going to die.” At this point, the only treatment regimen available to Phumeza involved painful injections and dozens of pills taken each day– and the injections came with a very high risk of permanent hearing loss. One day, as Phumeza put it, “I just woke up and everything was quiet.” [sharp humming sound] As it turned out, Phumeza didn’t have MDR-TB; her particular strain of tuberculosis was resistant to even more drugs, making it pre-XDR TB or pre-extensively drug resistant tuberculosis.

The painful injection she received that caused permanent and total hearing loss for four years until she received a cochlear implant? That drug didn’t help her at all. If Phumeza had been able to access molecular testing, or if her TB had been correctly identified from the beginning, she could’ve been saved her hearing and so much suffering.

Instead, she was in treatment for tuberculosis for three years and eight months– during which time she took between 20- and 30,000 pills before finally being cured. For many patients, this is still the reality in 2024, even though we now have treatment protocols that can cure patients with drug-resistant TB within just six to nine months, with five to seven pills per day. These drugs and protocols are only beginning to reach those who need them most.

But each year more people are accessing these better treatments, albeit belatedly– and this is due, in no small part, to Phumeza herself. [inspiring marimba music] Today, she’s a college graduate, a sociologist, and a leading voice in the fight against tuberculosis, whose efforts have helped increase access to life-saving drugs. [PHUMEZA] But I ask you to act now. I ask you for change. Thank you. [JOHN] Bedaquiline, first released in rich countries in 2013, is a critical medication for treating drug-resistant tuberculosis, but for years the price had been artificially high due to a lack of competition.

With support from the organization Doctors without Borders, Phumeza and her friend Nandita Venkatesan filed a lawsuit in India to prevent the pharmaceutical company Johnson & Johnson from extending its patent on the drug past its initial 2023 expiration date. Phumeza and Nandita succeeded in convincing Indian courts that J&J shouldn’t have a forever patent on this critical drug, which eventually allowed for generic competition and far less expensive bedaquiline. Experts estimate that over 50,000 people with MDR-TB will receive treatment every year who otherwise would have had little if any chance of being cured.

Many people with TB have survived because of Phumeza’s work expanding access to diagnosis and treatment. And at the same time, she herself only survived because of activism and innovation that preceded her. Until quite recently, the World Health Organization’s recommendations for people like Phumeza with drug resistant TB was “supportive care,” which Dr.

Carole Mitnick summarized to me as “put people in a hut by the side of the road and wait for them to die.” But in the late 1990s, Partners in Health, known as Socios en Salud in Peru, proved via a study that similar cure rates for MDR-TB could be achieved in poor communities as were achieved at the world’s finest hospitals. Still, many of the drugs that effectively treat highly resistant tuberculosis remain very expensive, not because they are made of gold or platinum, or because we have to fly to the moon to find them. They are expensive because 1) prices are kept artificially high by pharmaceutical companies, and 2) We are afraid that making these drugs less rare will lead to further antibiotic resistance.

And listen, I understand the fear of antibiotic resistance. This isn’t just about

TB: the idea of a world where we cannot treat bacterial infections is indeed terrifying. But that should never mean that we reserve the most powerful and efficacious drugs for the rich. I would not accept my child being denied the best available treatment for TB. How can I ask Phumeza’s family to accept such a world?

I asked a tuberculosis doctor, KJ Seung, recently: Of the 1.5 million people who will die of TB this year, how many would survive if they had access to the kind of healthcare afforded to the wealthy in the UK, or Japan, or the U. S.? After all, while TB is often curable now, it remains a very difficult disease to treat, especially in cases of extensive drug resistance. “How many would die if everyone could access good healthcare?” He asked me, as if confused by my question. "Yeah," I said. “None.

Zero. Zero people should die of TB.” We could choose to live in a world where no one dies of TB. That choice would require sacrifices, as most choices do– it would involve long-term, large-scale investments by rich countries to strengthen the healthcare systems of impoverished countries.

And it would require the training and employment of far more healthcare workers, and likely investments in new treatments. But we could choose that world. And instead, we choose this world.

And this is why I would submit that TB in the 21st century is not really caused by a bacteria that we know how to kill. As Dr. A Wilberforce Williams correctly noted over a century ago, the real causes of TB are “poverty, bad housing, bad sanitation, bad working conditions, long hours, high rent, [and] poor food.” To put it another way, in the 21st century, the real cause of contemporary tuberculosis is, for lack of a better term, us.

And that’s bad news. But it is also good news. In 1800, there was nothing anyone could do to stop people dying of TB.

But we no longer live in that world, thanks to the accumulation and dissemination of knowledge about the illness and how to treat it. [uplifting music begins] If we are the cause of TB, we can also be the solution to TB. And that’s the challenge I want to leave you with: In 2000, around 2.3 million people died of tuberculosis. In 2021, 1.5 million did.

In 2032, that number could decline by half, or even more. Millions of lives can be saved in the next decade if we pressure our governments and other institutions to invest more in research and the global effort to provide curative therapy. We’ve done this successfully before– thanks to the hard work of activists, researchers, and healthcare workers, access to HIV treatment has dramatically expanded in the last two decades.

Malaria deaths have dropped precipitously. And I know treating TB is complex– it has always been a strange disease– but it is curable. We can live in a world where no one dies of tuberculosis.

We are the cause. But we can also be the cure. [uplifting music fades] Thanks for watching our very first Crash Course Lecture Series! Do you want to see Crash Course do more videos like this?

What other topics would you like for us to cover? Let us know in the comments below. If you’re interested in the ongoing fight to end TB, I’d encourage you to check out the TB fighters community at tbfighters.org, where lots of people have worked together to achieve astonishing success in lowering the cost of treatment and diagnostics.

Also, your attention matters. We tend to address the problems we pay attention to, and so we need more people like you who make it all the way to the end of very long videos about tuberculosis. [Crash Course Theme Music] This video was filmed here at the Indiana Medical History Museum and was made with the help of all these nice people. If you want to help keep Crash Course free for everyone, forever, you can join our community on Patreon.