Ep 9 Tuberculosis: A Slow Burn

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 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.

Certain that 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 eighteen seventy nine 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, Will Kill.

You, Episode nine nine. Holy cow.

I know.

I'm Aaron Welsh and I'm Erin almon Updyke.

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, that will be two.

Weeks ago from when you're listening to this. Yeah.

I kept using the word sincone to talk about these Actually the Sincona tree, which is the tree that whose bark contains quinine. So I just you know, whoops.

It happened. Pronunciations are hard. It's sincona, 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 have that. If you have a break, we do for now. So yeah, and have a happy New Year. Oh it's already New Year's by now. Yeah, this is January tewod Yeah, happy happy. Oh my god, it's twenty eighteen. 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, wow, well, on that note, let's start drinking.

Well, let's do it. What are we drinking? Quarantiney time?

We are drinking alcohol consumption. So thus named because tuberculosis was often referred to as consumption, particularly in like the seventeen eighteen hundreds.

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. Seventeen hundreds, chios darling. Yeah, I don't think it's gonna I don't know if 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. That's gonna 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. So 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

That is a nightmare. I know, that's a horror movie.

It's crazy. But what's really interesting about TB is that if you get infected, you only have about a five to fifteen percent chance of actually developing active TV, which is the disease TB. So TB can get a little bit confusing. So I'm gonna do something a little different today. Okay, I'm gonna 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, so you're a little micobacteria. Okay, Hi, I'm going to call you teebs. Oh my gosh. Cute. Right, So you're just swimming along and then all of a sudden, cho uh oh, you get sneezed out into the open air. Luckily, the person that you came from was a close talker. So you end up flying pretty I know, right, You end up flying 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. 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, they're 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 tebes, You're really not all all right? So you made it past the beaters and the bloodgers up in the upper respiratory drag 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 pass back and they come in and they are literally trying.

To eat you. Uh huh. I'm not going to stand for that exactly.

So at this point, your human host he knows you're there, right they I mean, they probably don't actually, but their 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 tubes, you keep right on kicking. Oh man, you just slowly multiply, not as slow as your cousin mike lepre 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 twenty five thirty two hours you.

Might divide, you know, that's fast for some people.

Your right tubes. Sure, 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 twelve 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 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 everything you got at me.

And this, my friends, is the latent stage of tuberculosis. So you're here isn't infectious at this point, But that doesn't mean you're dead.

Mm mmm.

You're just biding your time because eventually, your human host it's gonna get old. Listen, Patience is a virtue. Exactly. They're gonna get old or they're gonna get sick, and then those immune cells around you are gonna 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, 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 the sides teachers 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. So do you want to talk about the symptoms?

Yeah, so am I what's happening now that I'm inside somebody else?

Great question. So the symptoms associated with active TB are actually pretty nonspecific, but they are really long lasting, so you often end up with progressive fatigue, malaise, general weakness, maybe some weight loss. You'll definitely get a cough, right because teabes 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

That does not that does not sound good.

Right, and it's often bloody. You've seen the movie, right, the movie mo On Moge. 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 one hundred.

Hundred years, forty years. Yes, dies of TV. 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 teabs and friends and family for months without going to the doctor because you're like, oh, I've got bronchitis or I just have it called or whatever. So remember when we talked about are not the number of secondary infections that you get from a single infectious person? Right? Guess what it is for TV?

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 like undetected and untreated.

Okay, So I'm gonna guess that are not so the number of people that one infectious person can infect with TV?

Yeah, I'm gonna guess three. Wow, keep going, six.

Keep going nine, keep going ten.

Ten to fifteen. Literally you could infect ten to fifteen people with TV over the course of a year. My jaw drops, I know, and without treatment, the mortality rate is forty five percent. I did not I really did not know that.

I have so many questions, but I know that the all going to be answered in the current events. So I'm just gonna 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 TV 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 your immunal competent ooh, people with HIV are twenty to thirty times more likely to develop active TB and it's almost one hundred percent fatal.

Twenty to thirty times more likely to develop exactly TB. Yeah, and one hundred percent 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 effects because the root of transmission is respiratory, it's not the only place you can get some weird TV as it turns out they call it extra pulmonary tb M.

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.

Aha.

So you can end up with meningitis. They call it tubercular meningitis. Ok 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 mining's 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 I'm as far as I know, is just a granulma 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 TV that's almost always fatal is when it invades your bloodstream. Ooh yeah. You can imagine that having having any bacteria

Side note is that also is disseminated also called milliary yes, okay.

Yeah, disseminated TV is also called milliary TV.

Okay. I kept seeing that pop up in different areas than I was like, and yeah, 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 through your body garrody, yep, garrody. You also can get invasion of your lymph system, which is actually the most common form of extra pulmonary TV. 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 everything.

You just like throw a dart at a body, and you can have TB in any part of that 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.

It turns out the more you read, the more you're horrified.

The more you know, the more you know, the satter 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 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 gonna say, yeah, please guess is it? No?

No? No, no, Egypt you got it?

Winn winner Yep, yeah, Egyptian mummies. As per usual, tuberculosis leaves traces of infection on bone, kind of like its cousin disease, leprosy. 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 thirty seven hundred BC. We've also got keletal evidence of TB dating back a few thousand years in other Old World regions such as India and China.

Wow.

But oh, another thing we have, and this is really exciting. We have skeletal evidence of tuberculosis in a mummy from Peru dating back to almost three thousand years ago. No, that means that tuberculosis was in the America's long before the European invasion.

What.

Yeah, isn't that insane?

Wait, that's really cool. I mean, it's 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 cattleborn version of tuberculosis like you mentioned, which was present in ungulates during that time, like alpaca or lamas 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 born 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 above I TV versus like actual microbactium tuberculosis exactly interesting.

So I don't know.

Oh that's so.

Cool though, Yeah, very cool. Wow. Ancient Greek physicians described the pulmonary form of tuberculosis and called it tysis, which is spelled horribly all right, you ready ready pH th I S, I S.

Yeah, that's a pH and.

The thh at the beginnings. I had to look it up. I'm pretty sure it's tysis.

You always look up how to pronounce things, and I don't, so probably people are like oh God.

Also, it just seemed too ridiculous to have to pronounce it pthysis phthysis. Well, and anyway, tysus 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 TV blood letting. Of course, of course, ancient Greek physicians believed that disease was caused by 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, Ugh, you know, you've got too much blood in your body.

Way too much.

I can't help me.

Let's get that back.

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, sixteen hundred 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 one thousand a d. 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 ooh sounds creepy.

It sounds really creepy. An 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

They were like eating off of the king's table instead of 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.

Yeap.

Nevertheless, the practice remained pretty popular. The last royal touch in Europe was done in eighteen eighty six. 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 gonna 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, there's let me touch you.

Literally, no way, no, not at all.

By the early seventeen hundreds, 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 but to elbows and cramped dingy houses with poor ventilation 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 seventeen hundreds to the mid eighteen hundreds, 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 these individual hand production methods to large scale mechanized production

What in fifty years, that's insane.

Massive, almost tenfold. 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 people.

Coming, and then they're just breathing on each other positive feedback loop. 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 bed 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's 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 bed bugs.

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 malnutritious and poor conditions, tuberculosis flourished.

It was probably really happy. Teebs was just like this is a 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 eighteen fifty, between seventy five and ninety percent of all people on Earth had the tuberculosis bacterium in them. What and twenty percent of those would go on to develop the disease.

Holy whoa. So you have ninety percent of people that have the bacterium and twenty percent 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. Probably we're going to be exposed to cholera, everything, smallpox at some point, all.

The things we've talked about, malaria.

Syphilists, I mean, the list goes on and on, and it really does. So yeah, it I mean, tuberculos has 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 in Paris. In the early eighteen hundreds, 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

I don't think I knew that about TV. I mean, think of Mulan 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 DV 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 ic consumptive look.

I'm sorry, was it Gwyneth Paltrow did she next on Goop? The consumption. Look how to get yours.

Here's a bag of sand for only eighty nine ninety five for small installments.

Oh my god, that's awful. Mm hmm, I hate that idea.

Yeah, it's really it's really bizarre. And reading a list of famous victims of tuberculosis during the eighteen hundreds 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 of Course, Telltale Heart, et cetera, Robert Lewis Stevenson, Treasure Island, Ah Henry David Thireaux, Walden like Walden, Pond, The Pond, Franz Kafka, Metamorphosis.

I remember that, it's one of my favorites.

Yeah, George Orwell nineteen eighty four, Animal Farm mm hmm.

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 burning 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, and except for looking pale and emaciated, which was in vogue, there were no other superficial signs of tuberculosis, most commonly.

Not many open swords.

There's no nervous system involvement for them 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 one hundred times already. I mean, it is interesting, though, you need to look up some synonyms in the future.

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, et cetera, you've heard the name Coke Koh, probably in reference to Coke's postulates.

I didn't know that.

Oh, there is some like pure venom oo in public letters to catch Oh, except they never used to be mad love right, they just were only bad luod only Oh my god, yeah, Okay. After getting burnt out on the fields of war, Cooke 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 thirties, 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 eighteen seventies, germ theory was making major splashes but still remained a controversial topic. 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 twenty seventeen.

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, fifty one hundred, two hundred 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 seventies and eighties, and that's very true.

Come on, what were you thinking. It's gonna be antibiotics, that's gonna be the thing.

Antibiotics I've heard chemotherapy is one that they're going to look back and go that that's a torture.

It 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 anthrax epidemic in his town. Oh. To his surprise, he saw millions of rod shape 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 set about designing a series of experiments which would conclusively show that anthrax was caused by this bacilla 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 sick and this newly sick animal. And these dear listeners are what is known as Cox postulates.

You just took biology one oh one yep.

I mean essentially, no, really, isolate, reproduce, inoculate, and isolate again. 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 that with the Anthrax bacilli. This set him apart and made his evidence for German

Yeah. Just he was so messy though, Like Pastor was just all over the place.

Yeah, yeah, he was just like this was like the development of actual scientific methods.

Right degree.

Yeah, and so Pasture decided that he was going to develop the anthrax vaccine.

How'd that go? Pastor?

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. It was if I'm using this word correctly, subtweeting. They were just like, well, this guy, I'm not sure. I don't I don't do Twitter.

I'm sorry. That was really good. Yeah, I guess which one of us manages the Twitter?

So I didn't use it, right, No, it's perfect, okay, blisful 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 Future weird 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 yeah, to a genetic predisposition or maybe playing instruments too much. Wow. But Coke had a

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. And then his.

Also, this is a side note, but his student or assistant was named Paul Erlick, like yeah, yeah, and he also he's a great microbiologist in his own right.

Yeah.

Actually, Erlik who developed the staining method for or improved upon the staining method for the acid fast bacteria like microbacteria diagnosed himself with tuberculosis using this technique.

Oh my gosh, that's so sad and poetic, also romantic. There you go.

Yeah, Hollywood, get on it.

Yeah, let's make a movie about Coke and airlick. 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 seventeen year old art student.

When he was in his No longer on the coke train, like late forties, early fifties. No longer on that train. Yeah, not into it. Oh, I mean you would have jumped off before that happened.

Okay, So yeah, As I mentioned, he was successful in isolating the to bberculosis 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 eighteen eighty two, Coke announced his findings to the most notable doctors and researchers of the day, who were knocked speechless.

Wow.

It was really one 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 Pasture was so annoyed, just kept building, Poor Pastore.

I know.

Unlike the ready acceptance of the anthex pacilla, the announcement of tuberculosis as infectious was met with resistance initially. Eventually, though, it gained traction as scientists, including Pasture, set their sights on a cure. It was a race to the finish line who would develop the first tuberculosis vaccine. Coch determined that he would be the victor, threw himself into his work and emerged less than two years after his first

Toxic masculinitybra you go every time.

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 so tuberculin escalated. You may have heard that word because it's what people use in skin test. He'd be skin tests 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's so interesting.

Oh yes, not yes.

But you're excited to learn about sanatoria.

Love this.

At the time, fresh mountain air, combined with a healthy diet and ample lung rest I eat, no exercise, talking, laughing, singing, etc. Was thought to be a cure for tuberculosis. All over the world, these.

Sanatorias 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 and immune boost. Tuberculosis patients flocked to these places, most of which were a racially

Its huge.

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. There are always the kind of places where people are like, oh, that building is definitely haunted yet 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 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 zero percent surprised about. That's just a real bummer. That is typical Selman Waksman. 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 nineteen eighties, and this time antibiotics were no match for resistance strains. I'm gonna 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 twenty twelve to twenty sixteen, 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 twenty sixteen, the incidents, so the number of cases that were reported of tuberculosis was ten point four million. What ten point four million people in the world were diagnosed with tuberculosis in the year twenty sixteen, and the mortality was one point seven million. Literally, one point seven million people died in twenty sixteen because of tuberculosis. One point three million of those were HIV negatives.

Tuberculosis is a leading cause of death and HIV patients.

Yeah, it's forty percent. These are just so many numbers. Forty percent of all deaths due to HIV are actually to TV. On the death certificate, it will say HIV, but forty 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 dies from HIV itself. HIV is not what

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 eighty five percent of cases. Okay, so about eighty five percent 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 TV definitely has

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, 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 nine

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

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

So okay, So the status of TV 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 TV. It's one of their major focuses. And I just really am curious to know. I don't know, doesn't even 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 things standing in the way and 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 or 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 TV exactly. TV 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 Alison 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 in terms

I didn't know that.

And he was a science communicator. He loved to try to bring science to the public.

Wow hashtag psicon.

Yeah, and this is why Sherlock Holmes was such a logically minded, careful person.

Cool. Yeah, I never knew that. Very cool scientific thinker.

The last one is a book called The Plague and I by Betty MacDonald and this is a memoir book written by this woman Betty MacDonald who went to a sanatorium in Washington State in the thirties. 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 Gilmour girls. I really highly recommend it. It's got some great parts in it.

I should check it out.

And that's all I got.

I obviously cited the who want wah waht. They have the Global Tuberculosis report from twenty seventeen, so it's recent. But also I got all the awesome gory details on the clinical path of physiology from this article called Tuberculosis Pathophysiology, Clinical Features and Diagnosis, written by Nancy Knietchel Netchell m just sorry nance run with it, published in the Critical Care Nurses Journal. So yeah, that's all I have. Cool shortlist.

Well, thanks so much for listening.

Yeah, thanks, this was maybe kind of a rough one. Yeah, have an alcohol consumption. Yeah we hope 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 and join us next week when we're talking about yellow fevers. 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 wash your hands, you have filthy animals.