This Podcast Will Kill You - Ep 9 Tuberculosis: A Slow Burn

Episode Date: January 2, 2018

Today, we’re taking a page straight out of Dickens and talking about tuberculosis- a disease as rich in history as it is in bloody sputum. We'll travel the path of an individual Mycobacterium tuberculosis as it makes it way down the respiratory tract of its victim and waits patiently, hidden and untouchable. We’ll learn why Nicole Kidman's skinny physique was so en vogue in Moulin Rouge, talk about ‘The Royal Touch’, which isn’t quite as creepy as it sounds, cover enough of Koch's postulates that you can give yourself an honorary microbiology degree, and oh so much more. See omnystudio.com/listener for privacy information.

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with built-in AI for real-time insights. Learn more at Intuit.com slash ERP. There is a dread disease which so prepares its victims, as it were, for death. A dread disease, in which the struggle between soul and body is so gradual, quiet, solemn, and the result's so sure that day by day and grain by grain, the mortal part wastes and withers away so that the spirit grows light, A disease in which death and life are so strangely blended that death takes the glow and hue of life, and life, the gaunt and grisly form of death.

A disease which medicine never cured, wealth warded off, or poverty could boast exemption from, which sometimes moves in giant strides, or sometimes at a tardy, sluggish pace. But slower quick, it is ever sure and certain. That was incredible. That was very dramatic. Yeah, you did a great job. Thank you. So what is that from?

That was from Charles Dickens' 1879 novel Nicholas Nickleby, in which he described tuberculosis. Is that why we're here this week? That's why we're here this week. Good. I think that set us up nicely. I think so too. Hi, everybody. Welcome.

Hi, welcome to this podcast, We'll Kill You. Episode 9. Nine? Holy cow. I know. I'm Aaron Welsh. And I'm Aaron Alman Updike. Thanks for joining us.

We're very excited. All right. Do we have any business to take care of? I don't know. Do we? Okay. I actually do. Oh.

I have a self-correction. Okay. Two weeks ago, or whenever malaria came out. I think that will be two weeks ago from when you're listening to this. Yeah. I kept using the word synchon to talk about these actually the synchona tree, which is the tree whose bark contains quinine. So I just, you know, whoops. It happens. Pronunciationations are hard. It's syncona, you know, I just needed to, I needed to say that. Yeah. And I think the other bit of

business is, you know, I hope everyone is having a great winter break. Yeah. If you're, if you're, If you have that. If you have a break? We do. Fortunately. So, yeah. And have a happy new year. Oh, it's already New Year's by now.

Yeah. This is January 2nd. Yeah. Happy New Year. Oh, my God. It's 2018. I wonder what it's like. Like, we don't know now because it's not there yet.

Yeah. I mean, maybe everything's magically better. Oh, wouldn't that be wonderful? All right. Cool. Well, on that note, let's start drinking. Let's do it. What are we drinking?

Quarantine time. We are drinking alcohol consumption. So, thus named because tuberculosis was often referred to as consumption, particularly in like the 17-18-100s. Oh, that's cool. I never knew the time period of it. I just knew like back in the day. Yeah. I mean, that's a rough estimate. I'll go with it. 17-100s. Chios. Chios. Chios, darling.

Should we try to cling? Yeah. I don't think it's going to. I don't know if that picked. It's not a good clink. They're coffee mugs. Oh, by the way, an alcohol consumption is essentially a hot toddy. And as always, we'll post the recipe on all of our social media, so check it out. It's delicious.

It is really good. It's way better than I was expecting. It's going to be my winter drink. Yeah, it's a good winter drink. So, tuberculosis. Tuberculosis. A big, nasty. It's a bigger nasty than I realized.

I'm thrilled to hear all about the biology. of it. Can't wait. Take us away. Let's do it. So tuberculosis is caused by a bacterium. It's not so very different from one that we've seen already. Do you remember which one so many weeks ago? Leprosy. Leprosy. So tuberculosis is another bacterium in the same genus, mycobacterium. This time, mycobacterium tuberculosis, so they name them so that you can remember them easily. It probably evolved from a cattle bacteria. I don't know if you're going to talk about its evolutionary history later. Very briefly. All right. So we'll very briefly cover it here too. Probably evolved from cattle bacteria. There's actually still cases of zoonotic tuberculosis that are caused by the bacterium

that normally causes bovine TV. They're very similar bacteria. Also similar to leprosy, tuberculosis is transmitted via respiratory droplets. So you cough or whatever and the spittle that you spit out is full of bacteria and when it gets into someone's face or also, and this is what's different than leprosy, TB can hang out in the actual air because they're teeny tiny little particles so you can cough. If you have TB and you cough a bunch and then another person walks into the room and breathes, they can get TB. That is a nightmare. I know. That's horror movie. It's crazy. But what's really interesting about TB is that if you get infected, you only have about a 5 to 15% chance of actually developing active TB, which is the disease TB.

So TB can get a little bit confusing. So I'm going to do something a little different today. Okay. I'm going to walk you through what happens in your body when you get exposed to tuberculosis. Oh, my gosh. I'm so excited. Oh, good. I'm excited that you're excited.

Okay, so you're a little mycobacterium. Okay? Hi. I'm going to call you Tebes. Oh, my gosh. It's cute, right? So you're just swimming along and then all of a sudden, a chew.

Uh-oh. You get sneezed out into the open air. You're free. Luckily, the person that you came from was a close talker. So you end up flying pretty much. I know, right? You end up playing pretty much directly into the face of a brand spanking new human. I hope this one is also a close talker because I want to be exposed to as many people as possible.

Oh, you will be. Okay, so now, here you are with a few of your friends that you brought with you, and you find yourself in the upper respiratory tract of a new human. It's pretty cool, right? Yeah. You get settled in, you make yourself at home, near a bunch of cells that make mucus, that are kind of trying to get rid of you. It's not exactly a warm welcome.

They're, like, beating their cilia at you. Like, who the heck are you? Get out of here. Hey, man. Yeah, right? Let me hang out here. It's no big deal. And for most people, or for most bacteria, rather, that would be enough.

They're like, man, I just can't take this. I'm out of here, and that's the end of the story. But I'm not most bacteria, am I? No, you're not, little tebbs. You're really not. Oh. All right, so you made it past the beaters and the bloodletes. up in the upper respiratory tract.

And you're finding your way down to the bottom of the lungs, the alveoli. All right. These are the pockets in your lungs where the gas exchange actually happens. And that's what I want. That's where you want to be. So you make it there. And then all of a sudden some freaking macrophages. Oh!

Right? They're basically like Pac-Men. Okay. They're giant Pac-Men and they come in and they are literally trying to eat you. Uh-uh. I'm not going to stand for that. Exactly. So at this point, your human host, he knows you're there, right? I mean.

They probably don't actually, but their immune system does. So the immune system is now basically surrounding you. You and your brothers and your friends are just, like, surrounded by the immune system. Uh-oh. So in a lot of stories, this would be the end. The human would kick the infection, but... Is this not most stories? This is not most stories.

Yes. You little teeps, you keep right on kicking. Oh, man. You just slowly multiply. Not as slow as your cousin, Mike Leprey. Remember him? Oh, yeah. Oh, Mikey.

Man, what a slow poke. Real slow. But you're, you know, you're pretty slow, too. Maybe once every 25, 32 hours you might divide. You know, that's fast for some people. It's fast. You're right, Tebes. Sure is.

So, the immune system just keeps trying to fight you off. and you just keep slowly growing. And this goes on and on for like two, maybe 12 weeks, somewhere in that range. Man, we're like at a standoff. Yes, you really are. But I'm secretly back there just like building my army. Just building, building. And eventually you end up pretty trapped in a little ball surrounded by immune cells.

The tissue around you might become necrotic. It might die a little bit. The pH might drop and the environment will be. become really acidic. They'll stop sending food to you, but you just keep living. That's not fair. It's not fair. But you don't do anything. You're not even growing much anymore. You're just still there. I can just picture myself leaning back, elbows crossed, like go on, keep coming. Exactly. Throw everything you got at me. And this, my friends, is the latent stage of tuberculosis. So your human isn't infectious at this point, but that doesn't mean you're dead.

You're just biding your time because eventually your human host, it's going to get old. Listen, patience is a virtue. Exactly. They're going to get old or they're going to get sick. And then those immune cells around you are going to have to go off and deal with the oldness and the sickness. And you, well, your time has come. Just when their backs are turned. So you'll break free with your friends and your family and you'll go forth and you'll multiply.

And that is when you get an active TB infection. Oh, yeah. Was that fun? I loved that. Good. I could see it perfectly so much better than Osmosis Jones. Right. Make that a movie.

Oh, my God. I forgot about Osmosis Jones. So I remember our eighth grade science teacher got real up in arms about it because it should be really called diffusion Jones. I remember. I remember a science teacher saying the same thing. Because osmosis is only water. Right, exactly. Oh, man, that's funny.

Anyway, that was fantastic. Oh, good, I'm glad. So that is sort of how TB initially happens. Dinner shows up every night, whether you're prepared for it or not. And with Blue Apron, you won't need to panic order takeout again. Blue Apron meals are designed by chefs and arrive with pre-portioned ingredients, so there's no meal planning and no extra grocery trip. There, assemble and bake meals take about five minutes of hands-on prep.

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designed to be your new wardrobe essential. And each piece is made with premium materials in ethical trusted factories and priced far below what other luxury brands charge. I recently got a pair of Quince's Bella stretch wide leg jeans and they are now in constant rotation. They are so comfortable. The fit is amazing and they come in a bunch of different washes so I'm about to go order some more. Refresh your wardrobe with Quince. Go to quince.com slash this podcast to get free shipping on your order and 365-day returns, now available in Canada, too. That's Q-U-I-N-C-E.com slash this podcast to get free shipping and 365-day returns, quince.com slash this podcast. So, do you want to talk about the symptoms? Yeah, so what's happening now that I'm inside somebody else? Great question. So the symptoms

associated with active TB are actually pretty non-specific, but they are really long-lasting. So often end up with progressive fatigue, malaise, general weakness, maybe some weight loss. You'll definitely get a cough, right? Because Tebes and all of your friends and family are just filling your lungs with bacteria. You'll probably have fever, night sweats. You probably don't have much of an appetite since your immune response is like on high alert. So that's why you end up losing a lot of weight. And that cough might be nondescript and unproductive at first, but it eventually will end up with what they call perulant sputum.

That does not, that does not sound good. Right? And it's often bloody. You've seen the movie, right? The movie? Moulin Rouge. Oh, yes. Yeah.

You've seen that. You've probably seen a hundred other movies where somebody dies of TB and the way that you know they're dying of TB is they're coughing up blood. And you're like, well, there you go. I just watched Bleak House, the BBC production. And, yeah. I don't know what that is. It's a Charles Dickens novel.

And not Nicholas Nickleby. Yeah. Anyway, yeah. And so one of the characters, spoilers, but the book's been out for like over 100. 40 years. Yeah. So. Dyes of TB.

It's not much of a spoiler at that point. Yeah. So the infection might be mild for like months. You literally could be coughing up, Tebes. and friends and family for months without going to the doctor because you're like, oh, I've got bronchitis or I just have a cold or whatever. So remember when we talked about R not, the number of secondary infections that you get from a single infectious person, guess what it is for TB?

Ooh. And this is under current circumstances, like in today's population level? You know, that's a good question. This number is from the World Health Organization, so I would guess that it's in current. Okay. If a person goes undetected and untreated. Okay, so I'm going to guess that are not. So the number of people that one infectious person can infect with TB,

I'm going to guess three. Wow. Keep going. Six. Keep going. Nine? Keep going. Ten to 15, literally.

You could infect 10 to 15 people with TB over the course of a year. My jaw dropped. I know. And without treatment, the mortality. rate is 45%. I did not, I really did not know that. I have so many questions, but I know that they're all going to be answered in the current events. So I'm just going to have to hold them in. Hold them in. Hold them so tight. Yeah. Wow. I know. Like I knew that back in the day everybody died. It was either syphilis or TB that everyone was dying from. But I really didn't know that the

mortality rate was that high. It also sounds like a really horrible way to die. It's also, that's the mortality rate if you're immunocompetent. People with HIV are 20 to 30 times more likely to develop active TB and it's almost 100% fatal. 20 to 30 times more likely to develop TV. Exactly. Yeah. And 100% fatal. And almost every one of them will die. Like it's, that's really awful. It's really gnarly. And so while the respiratory system is the most commonplace, that tuberculosis invades and infects because the root of transmission is respiratory, it's not the only place. You can get some weird TB, as it turns out. They call it extra pulmonary TB. This is sounding weird. Right? Keep going. It's basically just when you have

mycobacterium tuberculosis growing in literally any tissue that's not your lungs, it's considered extra pulmonary. The most serious of these, as you might guess, because it's kind of the most serious place for any creature to invade, is your central nervous system. So you can end up with meningitis. They call it tubercular meningitis. And we've talked about meningitis before. It's basically just an inflammation of the outer layer that surrounds your brain and spinal cord, your meninges. You can also end up with essentially almost tumors where you have tons of bacteria surrounded by immune cells that just take up space in your nervous system, which you can imagine is really problematic. Yeah, what happens in that case? Like, do you become paralyzed in certain areas

or just lose motor function? They're called space occupying tuberculomas. Okay. Which as far as I know, it's just a granuloma that takes up space in your central nervous system. So I would guess that you're going to have some kind of nervous involvement, but I didn't really look that much into the symptoms of it. That's okay. Sorry. Another form of extra pulmonary TB that's almost always fatal is when it invades your bloodstream. Ooh. Yeah. You can imagine that having any bacteria grow in your bloodstream is pretty much bad news.

And this, which is called disseminated TB, is particularly hard to deal with because it progresses really rapidly and it's really difficult to diagnose. So that sucks. Yeah. That sounds terrible. Yeah. Side note. Is that also, is disseminated also called milliary? Yes.

Okay. Yeah, disseminated TB is also called milliary TB. Okay, I kept seeing that pop up in different areas and I was like, and yeah, but it sounded like the same thing. And you know why they call it milliary? No, tell me. Because they look like little millet seeds, so it disperses throughout your body. That's grody. Yep.

Grody. You also can get invasion of your lymph system, which is actually the most common form of extra pulmonary TB. It can infect your bones, your joints, your GI tract, your genital tract. Ooh. Yeah, genital TB is a thing. You also can get TB in your skin. Like, it just can grow everywhere. So you just, like, throw a dart at a body, and you can have TB in any part of that?

A hundred percent. Ooh. Yep. Yikes. But it's primarily pulmonary? It is primarily pulmonary. Lungs. Lungs.

Yeah. And that's basically what I think you want to know about the biology of tuberculosis. What do you think? I think that's great. I mean, I think you did great. I think tuberculosis is terrible. It is. Yeah.

It's more terrible than I even realized. Yeah. That's true of almost, almost every disease that we've talked about. Yep. Yeah. Turns out the more you read, the more you're horrified. The more you know. The more you know, the sadder you'll be.

Want to stay home and never touch anyone. Yeah, not to mention airplanes. Oh, my God. So, you want to tell me how this all started? I absolutely do. Yes. You know that I do. I know.

Okay. Every week, I start with where the earliest evidence for infection can be found for whatever disease we're talking about. Can I guess? Can I guess? I was going to say. Yeah, please guess. Is it? Dena, nah, nah, nah.

Egypt. You got it. Ding, ding, ding. Winner, winner. Yep. Yeah, Egyptian mummies as per euse. Tuberculosis leaves traces of infection on bone, kind of like its cousin disease, leprosy.

Ah. So, researchers can actually do post-mortem diagnosis on skeletons that are thousands of years old. Which is really cool. That's amazing. Okay. So we've got skeletal evidence of tuberculosis in Egyptian mummies dating from around 3,700 BC. We've also got skeletal evidence of TB dating back a few thousand years in other old world regions, such as India and China. Wow.

But another thing we have, and this is really exciting, we have, we have skeletal evidence of tuberculosis in a mummy from Peru dating back to almost. 3,000 years ago. No. That means that tuberculosis was in the Americas long before the European invasion. What? Yeah, isn't that insane? Wait, that's really cool. I mean, that's really interesting.

Yeah, it's incredible. So from what I read, it could have either been brought over during the early migrations to North and South America, or it could have evolved to infect humans from the cattle-borne version of tuberculosis, like you mentioned, which was present in ungulates. during that time like alpaca or llamas or bison. So would that mean that there was like more than one evolution of tuberculosis? I don't know if that's the case. So the thing is, I don't know the different clinical manifestations of the cattle-borne

version of the disease and what was on the skeletal remains. Okay. But you maybe can't tell in a mummy if it was maybe from a bovine TB versus like actual mycopacterium tuberculosis. Exactly. Interesting. So I don't know. Oh, that's so cool, though.

Yeah, very cool. Wow. Ancient Greek physician described the pulmonary form of tuberculosis and called it Tysus, which is spelled horribly. All right, you ready? I'm ready. P-H-T-H-I-S-I-S. Yeah, that's a pH and a T-H at the beginning.

FISA. I had to look it up. I'm pretty sure it's Tysus. You always look up how to pronounce things and I don't, so probably people are like, oh, God, Aaron, with the pronoun of the H-N. Also, it just seemed too ridiculous to have to pronounce it, pathisis. Or pathisis.

Well, and anyway, tysis means wasting away, which is kind of the precursor of consumption. Yep. Tuberculosis and ancient Greece was devastating enough to be written about for hundreds of years, and writers often noted that children were particularly affected by the disease. Oh, yeah.

Yep, and their method for treating TB, bloodletting, of course. Of course. Ancient Greek physicians believed that disease was caused by a an imbalance in one of the four humors of the body, one of them being blood. So when someone started coughing up a bunch of blood and showing their doctor, the doctor was like, oh, you know, you've got too much blood in your body. Way too much. I can help you.

Let's get that bad blood out. Come over here. Give me your arm. No big deal. Oh, dear. Obviously, this did nothing to help the patient and probably made them sicker. but I guess you can't really fault them for trying something. I don't know.

For the next, oh, 1,600 years or so, basically until the Industrial Revolution, tuberculosis continued at a slow burn throughout much of the world, with no crazy pandemic that wiped out the majority of a population like the plague did. Okay. But that doesn't mean that it wasn't super impactful or that it wasn't noticed enough to be written about, because it was. And around 1,000 AD, the reign of the crazy Greek physicians had long since ended, and a new cure came on the scene.

And this one may have actually done some good, question mark. The poor and the sick flocked by the thousands to the castles of European royalty, where the king or queen would perform, quote, the royal touch. Oh. Sounds creepy. It sounds really creepy. And afflicted individual would kneel at the feet of a monarch. The monarch would then place their hands on the sores or affected areas of the patient.

while a priest said a prayer. Sometimes the patient would be allowed to stay for a few days or weeks in the castle area. And for many of them, the Royals Touch actually did some good, but not because the monarch had any kind of magical healing power. It's more likely that rest in an improved diet helped to bolster their immune system. They were like eating off of the king's table instead of just not eating. Oh, vegetables. Right.

This is amazing. And once they were back home working in the fields and eating what little they could afford, the TB probably came back with a vengeance. Yep. Nevertheless, the practice remained pretty popular. The last Royal Touch in Europe was done in 1886. Wow. Yeah.

Dickens was around. Yeah, he was. Good old Dickens. Wow. It's important to note that the contagious nature of tuberculosis was still unknown throughout all of this royal touching. I was going to ask, like, they were just exposing themselves like crazy. It doesn't seem like a royal thing to do.

I mean, if they knew that it was contagious, do you think that any monarch would be like, oh, yes, come here. Let me touch you. Literally no way. No, not at all. By the early 1700s, tuberculosis was fairly common and extremely widespread. Although it wasn't exclusively a disease of poverty, it did disproportionately affect those who were forced to live butt to elbows in cramped dingy houses with poor ventilation.

But to elbows. And the number of people living in these conditions took a huge upsurge following the Industrial Revolution. Before the Industrial Revolution, which happened around the mid-1700s to the mid-1800s, the norm was small-scale farming and manufacturing, with much of the population living in dispersed villages. Under these conditions, tuberculosis can still exist, but it's not going to thrive the way it would during the Industrial Revolution. Basically what happened during this time was a shift away from. from these individual hand production methods to large-scale mechanized production

of things like textiles, steel equipment, tools, et cetera. Cities became centers for production and people flocked there en masse. Soon, thousands or millions of people were living in these new metropolitan areas. To give you some idea of just how massive this influx was between 1800 and 1850 in just 50 years. Okay.

New York grew in population from 60,000, to over 500,000. What? In 50 years? Mm-hmm. That's insane. Massive. Almost 10-fold.

Yeah. Yeah. Wow. Yeah, so everyone was just like coming to cities, which were also filthy and dirty, as we've talked about before. And made more filthy and dirty by all these people coming. Mm-hmm. And then they're just breathing on each other.

Positive feedback loop. Mm-hmm. Yeah. And there was no way that housing or building construction. could keep pace with this kind of population growth, so many people were forced to live in extraordinarily crowded conditions. Houses meant to hold a single family were instead occupied by seven families. Oh, man.

In many boarding houses, people rented beds in shifts. And when your shift ended, you had to give up your bed to someone else. This way, the bed never got cold. Oh, my God. Oh, can you just sleeping in someone else his first. Filth. Can you just imagine that? I mean, I've, I've been through some pretty sketchy hostile situations. Yeah, me too, but I still feel like there's like, I don't know. I mean, you're also, you're not just sleeping in someone else's filth. You're sharing bedbugs. Yeah, you're sharing everything.

Please. Yeah. Oh. We can't stress enough how disgusting this was. We are disgusted. And although jobs were plentiful, working conditions were even more hazardous than living conditions. Wages could barely get you clothed and fed. It's no wonder, really, that under these crowded, malnutricious and poor conditions, tuberculosis flourished. It was probably really happy. Tebes was just like, this is my dream world. I mean, flourish doesn't really even begin to describe the uptick in cases during the industrial revolution. Yeah. It's estimated. Oh. Yeah, here's some numbers. Give me, give me. That by 1850, between 75 and 90% of all people on

earth had the tuberculosis bacterium in them. What? And 20% of those would go on to develop the disease. Holy, whoa. So you have 90% of people that have the bacterium and 20% of them end up getting, I mean, that's higher than we see today probably because of how horrible everyone's immune status was. I mean, because you weren't just infected with TB. No. Probably were going to be exposed to cholera to smallpox at some point. All the things we've talked about. Malaria. Civilis. I mean, the list goes on and on and on. It really does. So yeah, it, I mean, tuberculosis really had like a grip on the world. Wow. At one hospital in Paris, because you know how I love stats. I do. Yeah. At one hospital, Paris in the early 1800s, tuberculosis was identified to be the cause of death in more than

one-third of all autopsies. Whoa. At least a contributing factor, if not the cause of death in the majority, I think of all autopsies probably. Dang, dude. Mm-hmm. And it was during this period of high tuberculosis spread that tuberculosis got its reputation as a disease of creative types of those.

with low morals who indulged in too much drink and too much sex. I don't think I knew that about TV. I mean, think of Moulin Rouge. Oh, that's true. Yeah, that's definitely true. Tuberculosis or consumption, as it was known during this time, due to the way that a person wasted away while infected, was almost fashionable. Yeah.

Like if you had TV, you must be in with the in crowd? Well, kind of. It was the look. So appearing pale and gaunt became in style. and women began starving themselves, drinking only lemon water, or in one case, eating sand to achieve the chic consumptive look. I'm sorry, was it Gwyneth Paltrow? Did you? Next on Goop. The consumption look.

How to get yours. Here's a bag of sand for only 89.95, four small installments. Oh, my God. That's awful. I hate that idea. Yeah. It's really bizarre. And reading a list of famous victims of tuberculosis during the 1800s reads like a who's who of the art, music, literary world.

We've got the Bronte Sisters who wrote Jane Eyre, Weathering Heights. We got Edgar Allan Poe, The Raven, Teltail Heart, etc. Robert Louis Stevenson, Treasure Island. Ah. Henry David Thoreau, Walden, like Walden Pond. The Pond. Kafka metamorphosis. I remember that. It's one of my favorites. George Orwell.

1984. Animal Farm. Wow. And that's not including the composers, Chopin, Paganini. I mean, the list goes on and on and on. That was just a small sampling, like a tiny, teeny tiny sampling of all the celebs who died of tuberculosis. Eleanor Roosevelt, tuberculosis. Really? Why was this disease so, in a way celebrated when other slow-bernia, diseases like leprosy or syphilis elicited feelings of terror and disgust.

Well, leprosy probably was gnarlier to look at. Well, that's the thing. So at this point, people didn't know that it was contagious. Oh. And except for looking pale and emaciated, which was in vogue, there were no other superficial signs of tuberculosis. Most commonly, not many open sores, no nervous system involvement for the typical cases. Yeah, exactly. And so it was viewed as almost a romantic disease, a great plot device. I mean, we already know from the intro that Dickens loved tuberculosis. Yeah. Wow, that's so interesting. Yeah. God, I've said interesting like a hundred times already. I mean, it is interesting, though. You need to look up some synonyms in the future.

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Contact dealer for details. Offer ends 3-2. So we know now, of course, that tuberculosis is transmitted through respiratory droplets. But when and how was this discovered? Yeah, good question. Well, to answer that, I'm going to tell you a little story. Yes. A story of a bitter rivalry, of scientific revolution, and of hopes raised so high only to be dashed to the ground, resulting in ruined reputation and heartbreaking despair.

Okay, I am like really into this right now. I hope it lives up to it. The star of this story is none other than Robert Koch. Ah. If you've ever taken a microbiology course, aka the study of microorganisms like bacteria, viruses, fungi, etc., you've heard the name Koch, K-O-C-H. Probably in reference to Koch's postulates. We'll get to that. First, though, let's meet the man himself.

Yes. Robert Koch was born in Germany in 1843, and as a young man during the Franco-Prussian War, which is between France and Germany, Koch worked in field hospitals, performing hundreds of misguided amputations and generally witnessing the horror of war firsthand. Wow. This experience would stay with him for the rest of his life and provided some of the basis for his belief in germ theory and his resentment toward the leading microbiologists of the day, the Frenchman, Louis Pasteur, because it was Germany versus France. Oh, that's fun.

I was like, oh my gosh, there's a political side to this. Cook and Pasteur were rivals? I didn't know that. Huge. Oh, there is some, like, pure venom. in public letters to each other. Oh, 100%. Except they never used to be mad love. Right, they just were only bad blood.

Only. Oh my God. Yeah, okay. After getting burnt out on the fields of war, Koch returned home to a small village in Western Germany where he acted as the town doctor. On his birthday, I don't know, sometime in his 30s, I saw conflicting things.

His wife gave him a gift that would change the course of medicine and history. Way to go, wife. A microscope. Yeah. Immediately he was enamored with it and used it to examine everything he could think of. At this time, which was in the 1870s, germ theory was making major splashes but still remained a controversial topic. Right.

And as a reminder, germ theory is the idea that certain diseases are caused by microscopic organisms such as bacteria or viruses. It's like not a very shocking theory today in 2017. No, but at the time it was revolutionary. Exactly, yeah. It's so hard to imagine living in a time like that. I mean, we are, though. You know that there's bound to be something, you know, 50, 100, 200 years from now that they're going to look back and go, wow.

How did you not know? Man, I never thought about that. Wow. I mean, we even like look at practices, medical practices of the 70s and 80s and go, that's very true. Come on. What were you thinking? It's going to be antibiotics. That's going to be the thing.

Antibiotics. What are you thinking? I've heard chemotherapy is one that they're going to look back and go, that's torture. That kind of is, man. Yeah, it is. Yeah. Yeah. So, anyway, Coke, aware of germ theory, but not completely convinced, decided to examine the blood of some sheep who had recently died in an anthony

anthrax epidemic in his town. Oh. To his surprise, he saw millions of rod-shaped bacteria under the microscope. Oh, that's cool. Not wanting to jump the gun, which was unlike pretty much every other scientist during this time, he said about designing a series of experiments which would conclusively show that anthrax was caused by this bacilli that he saw. Oh, that's awesome. First, he would isolate the bacterium from a sick animal.

then he would reproduce the bacteria in culture. Then he would inoculate a healthy animal with some of this bacteria-ridden culture. Finally, he would isolate the bacterium once again from this newly sick animal. And these, dear listeners, are what is known as Cox postulates. You just took Biology 101. Yep, I mean, essentially. No, really. Isolate, reproduce, inoculate, and isolate again.

Yeah. Easy four steps. And these became standard practice for determining the infectious agent responsible for a particular disease. Because he was able to successfully do this with the anthrax bacilli, this set him apart and made his evidence for germ theory much more convincing. Louis Pasteur, a huge name in microbiology, was more than a bit salty, that it was a German man who would take credit for this discovery and that his evidence would be accepted so readily when Pasteur had fought so hard in previous. years. Yeah. He was so messy though. Like Pasteur was just all over the place. Yeah. Yeah. He was just like, blah blah blah. This was like the development of actual scientific methods. Right. Exactly. Yeah. And so Pasteur decided that he was going to develop the anthrax vaccine.

How'd that go, Pastor? Oh, it worked. Oh, cool. He did it. I mean, and it was great, but Coke was like, this is this Frenchman came in here. and he took my research and he didn't even credit me. He was so upset about it. It was, I mean, these letters are hilarious to read. Did they write to each other? Or did they write to, like, their newspapers about how angry they were? Yeah, it was, if I'm using this word correctly, sub-tweeting. They were just like, well, this guy. I'm not sure. I don't, I don't do Twitter. That was really good. Yeah. Guess which one of us manages the Twitter account?

So I didn't use it right? No, it's perfect. Okay. Blissful innocence. Yes. Blissful ignorance. Perfect. Yeah.

So nationalistic pride ran pretty deep in these two, and their feud was famous in its day, because it was not only very vicious, but, as I mentioned, very public. But very productive, so at least there's that. Yeah, yeah, for the most part. But we're not here to talk about anthrax this week. Future episode. Future. We're here to talk about tuberculosis.

Contemporary theories as to the cause of tuberculosis ran from having a weak heart to too much horse riding in youth. To a genetic predisposition or maybe playing instruments too much. Wow. But Coke had a different idea as to its origin. After the anthrax success, Coke set his sights upon tuberculosis. And with tuberculosis, he took the same tack as he did with anthrax. Isolate, reproduce, inoculate, isolate again. And he was successful.

Wow. Which was huge because it required him to develop staining methods, which were really difficult in the time. Yeah, I was going to say, I actually didn't expect him to be successful so easily because tuberculosis is notoriously difficult to culture. It takes forever to grow. He had to be patient. What a baller. Uh-huh. And then his, also, this is a side note, but his student or assistant was named Paul Ehrlich, like Ehrlich.

Ehrlich, yeah. And he also, a great microbiologist in his own right. Yeah. Actually, Ehrlich, who developed the staining method for, or improved upon the staining method for the acid-fast bacteria, like microbiacterium. Yeah. Diagnose himself with tuberculosis using this technique. Oh, my gosh. That's so sad and poetic.

Also, yeah, romantic. There you go. Yeah. Hollywood would get on it. Yeah, let's make a movie about Coke and Ehrlich. I'd watch it. I'd watch it for his wife who was like, I'm going to give you the tool that you need to be so famous. Well, sidebar, he left her for a 17-year-old art student when he was in his...

No longer on the Coke train. Like late 40s, early 50s, I think. No longer on that train. Yeah. Not into it. Oh, I mean, you would have jumped off before that happened. Ugh. Okay.

So, yeah, as I mentioned, he was successful in isolating the tuberculosis bacterium. But he still wasn't satisfied. So he repeated this experiment over and over again until he was sure. In a public presentation in an October day in 1882, Koch announced his findings to the most notable doctors and researchers of the day, who were knocked speechless. Wow. It was really one of the first. of the most momentous occasions for science ever, apparently. That's pretty cool.

According to contemporary accounts. I do want to note that Coke was not the first to suggest or even experimentally indicate that tuberculosis was infectious, but his experimental evidence backed up with microscopic demonstrations would make his voice the one that was heard. The guy who actually did it was French, and so Pester was so annoyed. Just kept building. It's for you. Poor Pest. store. I know. Unlike the ready acceptance of the anthrax bacilli, the announcement of tuberculosis

as infectious was met with resistance initially. Eventually, though, it gained traction as scientists, including Pasteur, set their sights on a cure. It was a race to the finish line who would develop the first tuberculosis vaccine. Coke determined that he would be the victor, threw himself into his work and emerged less than two years after his first announcement of tuberculosis bearing another supposedly ground-breaking discovery. He had concocted a cure for tuberculosis. This supposed cure, when injected, was supposed to reverse the damaged areas of the lungs and leave the sufferer disease free.

He called the substance tuberculin. Almost immediately, tuberculin was one of the most in-demand substances in the world, and people rejoiced for the long-awaited tuberculosis treatment that would relieve so many of their suffering. Supply was nowhere near enough to keep up with the demand, obviously, which was probably for the best. Because I'm guessing it didn't work. Did not work. Sure, it produced an immune reaction in the person who has been injected, but it does nothing to heal the patient. instead it causes fever, pain, and often death.

Oh my God. Particularly in those that were most severely afflicted with tuberculosis. Coke, so intent on beating pasture to the finish line, wasn't thorough in his testing of tuberculine and prematurely announced success. Toxic masculinity, bro. There you go. It's ego. Come on. Yeah.

And it would nearly ruin his reputation as a scientist, and he was all but chased out of Germany, at least immediately after. Wow. So tuberculin, you may have heard that word because it's what people use in skin test, TB skin test for today. Yeah, yeah. That's where it came from. That's really cool. I didn't know that's where that came from. Yeah.

That is so interesting. So there the world stood at the end of the 19th century, with the knowledge that tuberculosis was infectious, but no cure to treat the ill. Tuberculosis was no longer the romantic disease of poets and artists. It was something that would get you reported by your neighbor to the health authority, for a nice cash reward. Whoa. Yeah. Predictably, tuberculosis patients began to be ostracized, their clothing burned, and forced into treatment centers called Sanatoria.

Oh, yes. Not yes, but... You're excited to learn about sanatoria. I love this. At the time, fresh mountain air combined with a healthy diet and ample lung rest, i.e., no exercise, talking, laughing, singing, etc. was thought to be a cure for tuberculosis. All over the world, these sanatoriums started popping up.

Not many kept stats on how many people actually recovered, and in reality, your chances weren't much better in a sanatorium than in your dingy home. Yeah. But at least in a sanatorium, you had someone feeding you and you were resting, which probably provided an immune boost. Tuberculosis patients flocked to these places, most of which were, A, racially segregated,

and B, reserved spots for paying customers only. There were exceptions. For many tuberculosis sufferers, this was the only choice, and this would remain the only choice well into the 20th century. For the next 50 years after Koch's failed tuberculine experiment, there would be many attempts to come up with a cure for tuberculosis. But none were successful until a lowly grad student named Albert Schatz, studying soil microbes isolated one that, when exposed to some bacteria, killed them.

Awesome. So we tested it on a bunch of kids. of different types of bacteria, killed them all. So Shats was pretty excited about this, and he begged his reluctant advisor to let him test it on tuberculosis. He got permission. Awesome. And it worked.

Finally, there was a very promising cure for tuberculosis, and it was called streptomycin. Ah. Over the next few years, and after many animal and human trials, streptomycin was ready for distribution. The effects were astonishing. Here, finally, was the cure that humanity had been waiting on for hundreds, thousands of years. Almost overnight, tuberculosis sanatoria emptied, and many sit abandoned to this day. Yeah. There's one in Louisville, Kentucky, called Waverly Sanatorium. It's huge. Have you been in it?

I haven't, but it's been turned into a haunted house. Oh, yes. This is why, oh, I love this. Because they're always really, like, creepy places. They're always the kind of places where people are like, oh, that building is definitely haunted. Yep. Like, no question. Yeah, they're like, body shoots and stuff like that. Yes, they're so creepy. We should do a field trip. Oh, my God. We'll Google. We need to get a digital recorder so that we can record our whole trip. Yeah. And so for his amazing discovery, which completely changed the world in terms of tuberculosis, Shatz's advisor would receive the Nobel Prize. Um, zero percent surprised about that. Just a real bummer. That is typical. Selman walks.

He got the Nobel Prize. Shats, we're looking at you. Yeah, we know. Thanks, buddy. We're giving you credit. Thanks, Al. Not that it comes with much, but... For many years, streptomycin seemed like it would bring about the end of tuberculosis.

And it came kind of close, in some ways, particularly when used in combination with other antibiotics. But TB would return again with a vengeance during the AIDS epidemic of the 1980s. and this time antibiotics were no match for resistant strains. I'm going to let you pick up here. Tell me about tuberculosis in the world today. Oh, okay. I wish, actually, that I had a happier way to end this episode, but I don't. I mean...

So tuberculosis, this actually blew my mind. Tuberculosis is the ninth leading cause of death worldwide. Nine? Number nine. Isn't that, I mean, seriously? Tuberculosis. This is a bacteria that we can treat. And it is, to this day, the ninth leading cause of death worldwide. That is astonishing. I know. And for the period from 2012 to 2016, it was the number one cause of death from a single infectious agent. So because most of the other causes of death are either not infectious or they're kind of generalized, like lower respiratory infections, which is like pneumonia. It's kind of, it could be caused by a number of different things. TB was the leading cause of death by a single agent. What the F?

Whoa. Yeah. What does that put the mean annual mortality rate at? Let's talk about it. So in 2016, the incidence, so the number of cases. that were reported of tuberculosis was 10.4 million. What? 10.4 million people in the world were diagnosed with tuberculosis in the year 2016,

and the mortality was 1.7 million. Literally 1.7 million people died in 2016 because of tuberculosis. 1.3 million of those were HIV negative, so these are generally immunocompetent people. Okay. About 374,000 of them were HIV positive. Tuberculosis is a leading cause of death in HIV patients. Yeah, it's 40%. These are just so many numbers. I know. 40% of all deaths due to HIV are actually due to TB. So on the death certificate, it will say HIV. But it's, but 40% of those are because of TB. And we'll talk, so two weeks from now will be HIV and we'll talk so much more about it then. But no one really dime. eyes from HIV itself. HIV is not what kills you. HIV kills your immune system and then opportunistic bacteria and other things, but opportunistic bacteria like teens, just jump right in there

and they sit there and just wait for you to get sick. So yeah, do you want to get even sadder? I mean, 1.7 million people dying last year isn't enough. A million of the new cases that were diagnosed were children. And 250,000 of those deaths. or children. Okay, that is horrifying. Is this related to drug resistance at all or just not getting the treatment to the people that need it? So it definitely has to do with drug resistance. So the World Health Organization estimates that of the cases that are reported to them, treatment is effective if it's not resistant and about 85% of cases. So about 85% of people without the resistant form, will recover completely.

And others might sort of go back to the latent state and not die from it, but not be rid of it either. Drug-resistant TB definitely has a major effect. So in 2016, about 600,000 of those cases were resistant to at least one drug. Whoa. And about 500,000 were resistant to multiple drugs. And so the evolution of drug resistance,

I didn't really talk about it very much. And I don't know if you're going to cover it. I'd love to. You want to talk about it right now? Yeah, please. So basically, the reason that tuberculosis is so susceptible to becoming resistant is in large part because of how dang long it takes to be treated in order to cure it. So if you have a non-resistant form, a normal TB that's susceptible to antibiotics, it still takes six months of treatment.

Wow. If you have a form that's resistant to only one or two drugs, They now recommend 9 to 12 months of treatment. They used to recommend 20 months of treatment. Wow. Yeah. So let's talk really quickly about how antibiotic resistance evolves. Basically, if you're treating something like strep throat, for example, with antibiotics,

you are pummeling those bacteria, and you do it really hard and really fast because the strep bacteria are just hanging out right in your mouth, in your throat. So you pummel them with antibiotics, and they basically all die really quickly. So it's no problem. But with TB, the bacteria aren't just hanging out, remember? They're really well hidden. They're covered in sacks of your immune cells and of tissue, and they're infiltrated really deep into your lungs,

and they're slow growing, and they're hearty as hell. So you hit them with antibiotics, but you have to keep hitting them, and you have to keep hitting them, and it takes so long that, first of all, not everyone is finishing their course of antibiotics. but also the populations of bacteria in your lungs are just living under this selection pressure for a really long time. All the susceptible ones are being picked off and all the resistant ones are staying and being

allowed to reproduce. Exactly. And the chances that eventually one of these is going to reproduce with some random mutation that allows them to be super resistant is just a lot higher because of the amount of time that they're able to sit there and reproduce. So essentially, if you're under pressure from an antibiotic for this long and you happen to pick up resistance, then you're going to be the one who's able to keep reproducing. And then all of your friends are going to die off.

And eventually, all that's left are you and clones of you. And then you end up with antibiotic resistance. Yikes. So the longer you take antibiotics in a situation like this, the more likely it is that something like this can happen. That makes sense. And it's scary. It's scary. and it sucks, and it's also so much more expensive to treat drug-resistant tuberculosis

as compared to regular tuberculosis. Okay, I have a question. Okay. What are the most susceptible populations today? Today, for sure, people who are immunocompromised are by far the most susceptible. So people living with HIV, children, and anyone who has any sort of autoimmune disease or other, if you're on chemotherapy, anything that would make you more susceptible to general. Oh, prison populations.

Anywhere where you have crowding. Crowding and not great sort of sanitation and access to nutrition and things like that. So it's definitely more prevalent in developing countries, but it's also everywhere. I mean, TB is absolutely everywhere. Uh-huh. Yeah. So, okay, so the status of TB today is if I had a magic eight ball, it would be Outlook not so good. Outlook not so great.

And that the WHO apparently needs to step up its game and actually, you know, practice what they preach. I think, yeah, it's interesting because they definitely do a lot of work on TB. It's one of their major focuses. And I just really am curious to know, I don't know, does anyone work there? Like, what are the gaps that are not? I'm very curious to know really, like, what are the logistical hurdles that are not being met? What are the biggest thing standing in the way? Yeah.

I'm actually reaching these goals. And is it like, is it just money? Is it just that they don't have enough money to treat all of these and or to put the money where it needs to go. Like, I'm... Compliance with antibiotics. Compliance is a big thing. But the thing is you also see resistance developing in areas where you have really high compliance.

So... It's just the nature of TB? Exactly. TB is a gnarly one. It is, yeah. It's not a disease of the past. It's not. At all.

It's not. Okay. Well, I think on that note, we should read out our sources. Let's do it. I have a couple of books for you guys. One is called Invincible Microbe by Jim Murphy and Allison Blank. And this is more of like a, I don't know, young adult book. But I got it from the library.

And it was actually super accessible, easy to read, provided a great overview of the history and biology of tuberculosis. Another one is called The White Death by Thomas Dormandy. That is the opposite of the invisible microbe. of its accessibility. It's just, man, an author reveled in detail. But it does do a lot of in-depth history. Another one is The Remedy by Thomas Getz. And this is a really interesting book. So this is the one that explores in-depth, Koch, Pasteur, and also Sir Arthur Conan Doyle, whom I didn't talk about, but he was a physician before he was a writer. I didn't know that. And he was a science communicator. He loved to try to bring science to the public.

Wow. Hashtag Cycom. Yeah. And this is why Sherlock Holmes was such a logically minded, careful person. Oh, that's cool. Yeah. I never knew that. Very cool.

Scientific thinker. The last one is a book called The Plague and I by Betty McDonald. And this is a memoir book written by this woman, Betty McDonald, who went to a sanatorium in Washington State in the 30s, I think. It is hilarious. Oh, I was not expecting that. It is so funny. She is so clever, so witty.

It's full of great observant humor that is so ahead of her time. It reads all. It's like a little bit, got a little flavor of Gilmore girls. I really highly recommend it. It's got some great parts in it. I should check it out. And that's all I've got. I obviously cited the WHO.

WANTW. They have the Global Tuberculosis Report from 2017. so it's recent. But also, I got all the awesome, gory details on the clinical pathophysiology from this article called tuberculosis, Pathophysiology, Clinical Features, and Diagnosis, written by Nancy Kniechel.

Nettchel. Sorry, Nancy. Run with it. Published in the Critical Care Nurses Journal. So, yeah, that's all I have. Cool. Shortlist. Well, thanks so much.

much for listening. Yeah, thanks. This was maybe kind of a rough one. Yeah. Have an alcohol consumption. Yeah. We hoped you learned something. Yeah, I definitely did. Yeah, so did I. So thank you also to Bloodmobile for the music, as always. As always. Love it, love it, love it. And join us next week when we're talking about Yellow Fever. Oh, yeah. Oh, I can't wait. Make sure you rate, review, and subscribe. We really love it when you do that. It helps other people find our podcast. Follow us on social media. Yep. And

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