This Podcast Will Kill You - Ep 82 Anthrax: The Hardcore Spore

Episode Date: September 21, 2021

Twenty years ago this month, letters containing Bacillus anthracis spores were mailed to various politicians and news media offices in the US, resulting in illness, death, and a widespread fear that transformed anthrax from an agricultural disease or occupational hazard into a potential weapon of bioterrorism. In this episode, we explore the many dimensions of anthrax, from the different ways B. anthracis can cause disease to the incredibly long and varied history of the pathogen, a history of which bioterrorism is only a very recent part. Adding to anthrax’s multifaceted nature is the fact that B. anthracis is an environmental pathogen, one that can greatly impact livestock and wild animals, which requires collaboration across fields to effectively identify and control anthrax outbreaks. To help us explore this pathogen from a One Health perspective, we were so thrilled to chat with Dr. Johanna Salzer, Veterinary Medical Officer in the Bacterial Special Pathogens Branch at the US Centers for Disease Control and Prevention, who filled us in on the veterinary side of anthrax, and Morgan Walker, spatial epidemiologist at the University of Florida, who talked us through the environmental factors that affect B. anthracis distribution and emergence. Tune in for a much more than surface-level look at this spore-forming pathogen. See omnystudio.com/listener for privacy information.

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my life. During that time, I was the victim of terrorism when I opened a letter containing a lethal amount of anthrax. Around September 18, 2001, I headed to work as a desk assistant at NBC Nightly News. One of my jobs was opening Mr. Brocault's mail. There was one letter that looked as if it were written by a child. Something seemed unusual. I had never seen a letter containing a granular substance. I mentioned the strange letter to my friends. Nothing happened for about 10 days. Then one Friday night, my throat began to swell up. A cold, I thought, but it worsened over the weekend. My glands were soon enormous. Monday morning came and my face was barely recognizable. I went to the doctor who said it was a reaction to my acutane medication and I should rest in bed. A few days later, I went back to work, but I still felt a bit off. A week or so after I was sick, Mr. Brokaw's assistant became sick. Both of our symptoms were unusual. authorities became involved. When Bob Stevens died at the American Media Building in Florida at the end of September, the pieces slowly began to come together. I soon learned why I had been sick, anthrax poisoning.

Like Mr. Broca's assistant, I had contracted cutaneous anthrax. The events over the next few months changed my life. I had carried anthrax back on my clothes and had contaminated my home. I chose to have all of my things destroyed. I lost my most personal. belongings, all my precious pictures and mementos. I worried I might die. I'll have to see doctors the rest of my life. I'll never have an overall sense of security again. That's what I lost. But what I gained was the deep, true appreciation for my family, friends, and coworkers whose support was incredible. Yeah. So that was an account of Casey Chamberlain, written in 2006, and I will post the link to the full account on our website.

And it was in regards to the 2001 anthrax letters. I remember that. Oh, yeah. I remember that too. Hi, I'm Aaron Welsh. And I'm Aaron Alman Updike. And this is, this podcast will kill you. Obviously, today we're talking about anthrax.

Obviously, yes, yes we are. This is such first season type of material, Aaron. It's big. It's a big one. It's a big one. And it makes me kind of happy that we've already done some of the enormous ones. Because I think now at this point I would be so perfectionistic and so like, oh, gosh, I didn't get this. And oh, I should talk about this too.

And the episodes would be like eight hours long. I mean, is that not what we're about to get into? Okay, yeah, it's going to be pretty long. But it's going to be fun. It's going to be really interesting. The scope of this is huge. Massive. And we've got some very exciting guests to bring on.

We really do. We really do. But first. But first, it is quarantine time. You know I always check my imaginary watch when I say that? I like it. And does that mean it's always quarantini time on your imaginary watch? Yes, it is.

So what are we drinking this real quarantini time, non-imaginary quarantini time? We're drinking Spore Me Another. Get it? What is in Spore Me Another? Well, it's basically a stout float. Yeah. And you can kind of go wild with it. Like, you know, coffee stout.

Coffee stout. Stout. Chocolate stout. Chocolate spicy chili stout. Whatever. Whatever. And whatever ice cream you want. I have chocolate chip cookie dough currently, so that's what I'm doing. Yum. Yeah.

We will post the full recipe for the quarantini and the non-alcoholic placebo rita on our website. This podcast We'll Kill You.com as well as all of our social media channels. So make sure you follow us to get to make yourself a spore me another. Yeah, exactly.

What other business do we have today, Aaron? Well, we can just go through the usual suspects. Check out our website. This podcast Will Kill You.com. You can find things like all of our sources for each episode there, as well as transcripts, alcohol-free episodes, links to our goodread list, bookshop. org affiliate account, music by Bloodmobile, our awesome, cool merch. There's Patreon links. There's honestly so much more.

go check it out. And you can also listen to this episode and all of our past and future episodes on Amazon Music, Apple, Stitcher, or wherever you get your podcasts. All right. Should we dive in? Let's do it. Right after this break. 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. Just spread the pre-chopped ingredients on a sheet pan, put it in the oven, and that's it. And if there's truly no time to cook, dish by Blue Apron meals are fully prepared. Just heat them in the oven or microwave, and dinner

is ready. And here's the exciting news. Blue Apron no longer requires a subscription. You can order meals when you want them and skip when you don't without adding another recurring charge. Order now at blue apron.com. Get 50% off your first two orders plus free shipping with code this podcast 50. Terms and conditions apply. Visit blue apron.com slash terms for more information. Anyone who works long hours knows the routine. Wash, sanitize, repeat. By the end of the day, your hands feel like they've been through something. That's why O'Keefe's working hands hand cream is such a relief. It's a concentrated hand cream that is specifically designed to relieve extremely dry, cracked hands caused by constant hand washing and harsh conditions. Working hands creates a protective

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Which probably just honestly angered people. They were like, what? That's all? Well, and that's why we're doing it right now. Exactly. So that you get the full picture. Yeah. So anthrax really is the name of the disease that is caused by this particular bacterium. But I just want to say up front that there's a really good chance that I'll probably just say anthrax at some point when I'm referring to the bacteria. So just bear with me. Oh, I'm going to do that. Okay. A lot. Good. Probably. So we'll both just do that and make someone angry.

Yeah. But anyways, the... The bacterium which causes anthrax is known as bacillus antherasis. This is a gram-positive spore-forming rod-shaped little bacterium. And we'll talk a lot more about the importance of those spores as we go through this episode. They're like, they're the most important thing. And this bacterium is related to. a pretty large group of other bacterium in the group known as bacillus cirrus, C-E-U-S. But for the most part, what I think is so interesting is that bacillus anthracis is one of the most

genetically monomorphic, meaning there is not a lot of genetic variation in this species across the entire globe. It's kind of bananas. It really is. Like, this is a bacterium that is very ubiquitous. It's found across the whole globe. And yet, if you grab one anthrax bacterium from, like, Siberia and another from North America, they're going to be so similar. Mm-hmm.

It's fascinating. And for the most part, this is the only species in the large B-serious group that usually causes serious disease in humans. But there is a serivar of B-serious that can cause a disease very similar to anthrax. And we'll probably touch on that a little bit more later in this episode. But where I want to start is with the life cycle of this pathogen, because by going over its life cycle, we'll learn who tends to get infected or affected by anthrax and we'll learn how it's transmitted and then we can get into how it actually causes all of the damage and then what those symptoms look like in humans. Okay? Sounds good. So bacillus anthracis spores are where we're going to start.

These spores exist in the soil and on vegetation. Like I said, pretty much worldwide. They can persist in a huge range of environmental conditions across the globe for years, or in some cases, decades, or maybe centuries. These spores don't really replicate, probably, asterisk. They just mostly hang out in the environment, and then at some point, they're ingested, most commonly by herbivorous mammals, especially large ungulates, like say cattle or zebras, or hippos, or antelope, or goats, whatever. And then, because these herbivores often eat things like spiky grasses, for example,

they might have small abrasions throughout their gastrointestinal tract. And these spores can then enter into the animal. 's bloodstream through these little openings, these little like cuts in their mucosal lining. Once those spores are introduced into the bloodstream, they're promptly engulfed by macrophages, which are white blood cells. And that is where the trouble starts. The spores inside these macrophages are activated back into full-fledged bacteria, and they begin to replicate. Often in the lymph nodes, which is where these white blood cells are traveling to. And then these bacteria that are replicating burst out of macrophages.

They travel throughout the bloodstream. They replicate and replicate and cause overwhelming infection that almost inevitably leads to the death of the host. It's sad. It's absolutely devastating. And in many species of animal, this generally happens so, so suddenly that very often the first symptom of infection in a herd is just the sudden death of one animal followed by many more. And it happens so quickly. Incubation period is often as short as 36 to

72 hours. How? So fast. So fast. And what's important is that when the host dies, in so doing, they release billions, billions of vegetative bacteria. So the anthrax bacteria, upon contact with the air in the environment, these bacteria sporyulate. They form those spores again. They are released into the environment and thus complete their life cycle. It's just like botulism, where we were like, why does it kill you? It's because it needs to kill you in order to be transmitted. Exactly. Exactly. Fascinating. Okay, so obviously my favorite question to try and answer is like, how? How? How can this kill so quickly? Yeah, Aaron, how? Okay, let me tell you. So, basically, Cillus anthracus, anthrax, has a couple of different virulence factors, which are the things that bacteria have that make us sick or animals sick and, like, allow them to be pathogenic. They have one virulence factor that makes a capsule. So it's like a little capsule that surrounds the bacterium that makes it really hard for immune cells to actually engulf and get rid of those bacteria via phagocytosis.

Oh, okay. So that's one, but it's not the most important. Well, it is like essential, but the other ones are more exciting. The other virulence factor they have encodes two different exotoxins. We've talked about toxins a fair amount on this podcast, but it's been, I think, kind of a little while. So as a refresher, toxins are generally, usually proteins that bacteria or other organisms can make that cause, us harm in some way. In the case of bacillus anthracis, there's two different exotoxins, which are called edema toxin and lethal toxin. Ooh, let me guess what the second one does. Yeah, yeah, you're right.

And so each of these two different toxins is made up of two proteins. They're each made up of one part, a protein called protective antigen, PA, and then lethal toxin is made up of PA plus lethal factor, which is another protein, and then edema toxin is made up of the PA plus edema factor, which is another toxin. And they do like what you said, like what it sounds like they do. The protective antigen part of each of these toxin protects the toxin itself and make sure that the toxin can make its way into our cells. And then you have edema factor, which causes a lot of inflammation and swelling, and lethal factor, which causes mostly cell death, especially of white blood cells. What's the mechanism of cell death? Like, I knew that you were going to ask, so let me scroll

to my specific questions. Aaron is going to ask me section. It's via a Caspace 1 dependent cell death program known as pyroptosis. I almost wish I didn't ask. I know. I know. So the specific mechanisms of action of both lethal toxin and ademotoxin are absolutely fascinating and they've been studied in great detail. I have a ton of papers that people can read if they want to know this specific like cell like receptor by receptor detail of how these work. But essentially to go over just the broad strokes of it for the sake of this podcast. The toxins both together have actions both in the early phase of infection, where these toxins serve to downregulate and suppress our immune response. This is what allows for bacillus anthracis to persist and replicate within our bodies.

So that you have a huge number of bacteria in the blood. And then later in the course of infection, these two toxins together create the edema, so the swelling, vascular collapse, and eventually shock that does lead to death, which like you said, Aaron, is pretty much an essential part of the natural history of this pathogen. And it's also like for at least in the 20th century, there was the prevailing thought that, oh, pathogens will evolve to be more mild. That's just the way evolution works. And this is case and point that does not happen. Not necessarily. Not for a pathogen like this, right?

For something where the host has to survive in order to transmit, yes. But this is not a directly transmitted pathogen. This is essentially an environmentally transmitted disease. It's fascinating. This is why mode of transmission and virulence, I think, are just still two. of like the most fascinating topic or one of the most fascinating topics. Oh, I agree. Absolutely amazing. Last point I want to make about these virulence factors. And this gets back to what we were talking about with these, this new syrivar of bacillus serious that we've seen. Both of these

virulence factors, so the capsule and the two toxins, both of them are required in order for anthrax to be pathogenic, like to cause anthrax. But both of these virulence factors are encoded on plasmids, which are circular little pieces of DNA that are not part of the main genome, which means they can be passed back and forth from bacterium to bacterium. But how often does that happen the passing back and forth? It's a really good question, especially in a bacterium like bacillus anthracis, which, for the most part we think doesn't replicate well in the environment. How often is it going to be

even coming in contact with other bacteria to be transmitting and passing plasmids? I don't know the answer to that. It's a really interesting question, though. So I know that, like, there has been some evidence that they form biofilms, but I don't know if that's just from, like, one individual bacterial cell. Yeah, from, and from what I understand, while bacillus antheris can infreis, can in theory replicate in the soil. Like they don't need to be inside of a host to replicate necessarily. They're really bad competitors. Right.

So in the most part in the environment, even if they could try and replicate, they're just not good at it. And so they get out competed. Okay. Cool. Yeah. Fun question, Aaron. Okay.

So now, what does this actually look like in humans? Yeah. That's what we usually talk about on this podcast. and how do humans get exposed? There are a few different ways that humans can become infected. There's three main routes that you can get infected. Cutaneous anthrax when spores enter through breaks in your skin. You can get gastrointestinal anthrax if you ingest the spores,

very similar to how most animals become infected. Or you can inhale the spores, which results in inhalational anthrax. So let's go through each of these one by one. The cutaneous form worldwide by far is the most common in humans. Something like 90 to 95% of cases worldwide are cutaneous anthrax. So this is when spores enter through like a cut in your skin. Just like in animals, like I described for the main transmission cycle or main life cycle of this pathogen, the replication still happens in macrophages.

but in the case of cutaneous, it tends to be those macrophages that stay locally in the skin surrounding where the spores were introduced or in nearby lymph nodes. So let's say you get a cut on your arm, then maybe you'll get swelling in the lymph nodes under your armpit. Okay. The first symptom that you usually see is just a little bump. That's it, just a little bump. It's generally painless, but it's often quite itchy. And this happens anywhere from one to 12 days after exposure. But usually that little bump starts to get swollen, like all around it.

There starts to be some swelling more than you would expect from something like a regular bug bite. And then this bump gets surrounded either by small little vesicles, little fluid-filled blisters all around the bump. or like one large, like one or two centimeter blister that kind of encompasses that initial bump. Anyone right now who has a bug bite is staring at it. I know. It's going to get worse. I keep going. Hopefully your bug bite won't.

And this blister, it's filled with clear fluid. So it looks at first, especially a lot like the kind of blister that you might get on the back of your heat. heel after you walk all day in new shoes. You know those really like taut, fluid-filled blisters? Oh, I'm familiar. Uh-huh. But unlike those blisters on your heel, it is surrounded in a wide margin by what they call gelatinous edema.

Oh, boy. So swelling that makes your skin feel like there's like jello underneath it. That is disturbing. Mm-hmm. often, people might also have some like low-grade fever, maybe they're feeling kind of crappy. And then this vesicle, this blister enlarges, and eventually it pops just like the blister on your heel, except that this blister leaves an ulcer, a pretty sizable one potentially. And this ulcer progresses into a black esh-car.

which is kind of like a really, really gnarly looking scab. Okay. That's the best way I can describe it. It's like completely black. It's basically entirely dead necrotic tissue that's pretty characteristic of cutaneous anthrax. How deep is that? Good question. Not necessarily that deep, but they can be quite large, like encompass a pretty large area.

They don't tend to scar. Oh, interesting. Okay. Yeah. But what's much worse even is the edema. So the swelling is still present and often it continues to grow. And especially if the lesion instead of on your arm was near your face or your neck, the swelling can get so intense that it can block your airway.

Oh my God. And it's still gelatinous? Yeah. It's like a gelatinous. Your face. I'm just imagining pressing down on my skin and just feeling like jello underneath it. That would be very alarming, to say the least. That's very alarming is a good description.

And while cutaneous anthrax is the least lethal of the three forms, and in many cases, these Esh-Kars heal over the course of two to three to six weeks, especially if this edema is near the face or neck, it can be fatal because of just how much swelling you get, or if this extends beyond just a local infection and does cause a more systemic infection. So if cutaneous anthrax is untreated, mortality ranges from 5 to 20%, although I have seen estimates as high as like 30 or more percent. With antibiotics, though, mortality is less than 1%. So that's good. Excellent. Which antibiotics, by the way? I can't remember.

A whole range of antibiotics. You can use penicillin. You can use clindomycin. You can use doxycycline. All kinds. Yeah. Resistance? Very little.

Great. Yes. Figured. So moving on to the next most deadly form. And that would be gastrointestinal anthrax. In a lot of ways, you can actually think of gastrointestinal anthrax as cutaneous anthrax, but in your guts. So, jello guts.

Jello, yeah, guts, not exactly, but kind of. Let me go into detail. Okay. So gastrointestinal anthrax is really how anthrax is spread in its enzoatic cycle, right? Erbivores are most often infected while grazing on grass or ingesting soil that's contaminated with anthrax spores. So while humans could be infected that way, most commonly humans get infected with gastrointestinal anthrax by ingesting meat that is contaminated with the spores. And there are two different forms of gastrointestinal anthrax depending on where the spores

enter your body and break through your mucosa. Either oropharyngeal, so in the back of your throat, or truly intestinal in your intestines. but pathologically both essentially result in ulcer formation, not dissimilar to the ulcers that you see on the skin, but as you can imagine, ulcers in your throat or your intestine are a much bigger problem than on your skin because they can lead to perforation, your face. Sorry, it just sounds really painful. It's not, the ulcer is not painful, right? That's what they say. I don't know. They look awful.

Gosh. Supposedly, they're just itchy. It just still seems highly uncomfortable. I'm going to get more uncomfortable. Wonderful. Okay. That's what this podcast is about. So remember when I said that often the bacteria travel to your lymph nodes and you get a lot of swelling in your lymph nodes.

If this happens in your guts, you get swelling or lymphadenopathy in the lymph nodes in your throat, potentially, if we're talking oral-ferengal infection, or in the mezzantery, which is the connective tissue that holds your guts in place. We have a ton of lymph nodes in there. And if those become severely inflamed and very swollen, that can lead to potentially intestinal obstruction. It can also lead to assyides, which we've talked about a fair number of times on this podcast, but that's basically the buildup of fluid in your abdomen because the blood vessels and the lymph nodes, the whole lymph system that should drain fluid gets congested because of all this swelling. You can, through these ulcers or through just ischemia because of all this swelling, you can get perforation of the

bowels, which is a pretty serious emergency. And because we're talking about becoming infected through the mucosa, so through a cut in your gastrointestinal tract, rather than through your skin, which is quite thick, this disease is far more systemic than cutaneous anthrax. So it makes its way to your bloodstream much more easily than from our skin. And for that reason, the mortality rate is much higher. It's usually 25 to 60% if untreated. I have a question. Yes, Erin.

So you mentioned that bacillus anthracis is not a good competitor. Mm-hmm. Does any of that potentially have anything to do with the gut microbiome and not being able to establish there? Or is it not really that because it's perforations in your gut? Yeah, so that's a really interesting question. I haven't read anything on this. I don't know that there's been studies on it, so I can't answer it like with data. but I can tell you based on what I know of the life cycle,

it enters our gut as spores. It's not establishing an infection in our gut. Okay. So it's not going to be competing with anything, any other bacteria that live in our gut that are commensals. And what's really interesting about this pathogen is that even though it's not intracellular, so it doesn't live its life inside of ourselves, it does necessarily have to enter macrophyser.

We think in order for the spores to reactivate and become, you know, replicating bacteria again. Okay. So it's able to sort of like sneak in under the guise of macrophages and then get to high enough volume or whatever. Exactly. Interesting. Yeah. And it does. And I do also think it's interesting that for the most part it does need, we think, at least, it needs a break in the mucosia.

lining. It can't just, like other bacteria that we've talked about on this podcast do, it can't burrow its way through our mucosa on its own. It has to enter through a wound of some kind that's already there. And so I wonder if that plays a lot into why different animals are different different, differentially susceptible based on what they're eating and how likely they are to have some kind of how much roughage is in their diet. How much Captain Crunch they ate. because it like leaves abrasions everywhere. That's so true. Oh, that's really, really interesting.

Okay, anyways, that's gastrointestinal anthrax. Do you have any more questions about that one? I don't think so. Symptoms, you have, you know, abdominal pain, nausea, vomiting, fever, diarrhea, and then you pretty much die very rapidly. And you die because of all the same things, like, or your body, is it diarrhea? Yeah, we're going to talk a little bit more about the mechanisms when we get to the next form, which is the deadliest form, which is inhalational anthrax. The most terrifying, yes.

The most, absolutely most terrifying. And the reason that most people who have heard of anthrax are probably most terrified of it because they think of anthrax and they think of bioterrorism and that that means. that they're thinking of inhalational anthrax, whether they know it or not. So the inhalational form, in this form, you have a biphasic illness. So you have two different parts to this infection.

The first part happens about one to six days after exposure. It starts pretty nonspecificly. Fever, I feel cruddy, my muscles ache, maybe I have a cough since I inhaled something into my lungs, maybe some chest pain. And then within two to three or four days, your fever will increase, but you'll become short of breath. You won't be able to breathe. You can't get in enough air. You might get cyanosis because you, cyanosis is when your skin turns blue because you literally don't have enough oxygen.

Often your lymph nodes and your neck will get so swollen that those will further obstruct your windpipe. So then when you breathe in, it might sound like, which is called strider. And about half of people will progress to complications like meningitis because these bacteria have crossed the blood-brain barrier. If you get meningitis, it's essentially a hundred percent chance that you're going to die, even with treatment. But even if not, as this bacteria replicates throughout your body,

because of those toxins, what happens is that, you very rapidly progress to shock. So shock, we've talked about a lot, but it's essentially, there's a lot of ways that it can happen, but what it means is that you're not getting blood and oxygen perfusing your tissues. So in this case, it can happen kind of in a lot of different ways. You're losing a lot of fluid because of these toxins and their actions both on your blood vessels and also on your lymph system, essentially just causing a lot of swelling and in some cases actual bleeding and bleeding out of places that you're not supposed to bleed. So in general, with inhalational anthrax, whether because of the meningitis or whether because of the shock,

death usually happens within 24 to 36 hours of that second stage of the illness. Okay. That's terrifying, horrifying. It's very horrifying. And what happens in inhalational anthrax and the difference between inhalational anthrax and cutaneous and gastrointestinal anthrax is that in the case of inhalational, when these spores are inhaled, they're engulfed by macrophages that live in the bottoms of our lungs, the little alveoli, which are where gas exchange. change happens. And these macrophages take those spores to a set of lymph nodes that are right along the center of our chest called the Mediastinum. And that is where they germinate and begin to replicate. And from there, they very rapidly produce a huge, huge amount of bacteremia. So tons of bacteria that are able to go throughout your whole bloodstream, a huge amount of toxin, and then the shock and the death. So this is an inhaled spore. So it's a, quote, lung thing. But it's not really a lung disease. Right. It's just the avenue of entry. Exactly. Right. So in general,

mortality rate, in some outbreaks, has been as low as 46%. That's with really good treatment. As low as 46%. Yeah. That was the U.S. in 2001. Right. The death rate was 46%. But it's usually as high as 85 to 95%. And like I said, if it progresses to meningitis, it's nearly 100%. It's treatable, especially early on in the infection, but often, especially if it progresses to meningitis, antibiotics alone often aren't enough because of the high level of toxemia.

Mm-hmm. Because of the toxins themselves. So, yeah, really briefly, there's also actually a fourth root that has been documented. Pretty rarely, but that is injectional anthrax. And this has been documented in several places throughout Europe because of contaminated heroin, which is very scary. And the reason that this is different than just cutaneous anthrax, even though it's a needle going through the skin, is that, it ends up producing a deeper soft tissue infection, which is more likely to result in systemic infection and therefore has a higher mortality rate because it's introduced much deeper than just

a superficial skin infection would be. Gotcha. So it's not the needle, it's the heroin itself. Right, yeah. It's been from contaminated heroin, not from like needles that were dropped in soil or something like that. Right, right. Yeah. Wow. Yeah. It is treatable in animals and in humans, so that's exciting. And there is a vaccine technically. Yes, yes. That's true. That's true.

And for humans. But it's not a great vaccine for animals or for humans. Yeah, low protection or? Yeah. For reasons that we don't fully understand, it doesn't produce super long-lasting immunity. So even for animals, they have to get boosters like every year. For humans, the vaccines that we have, at least the one that we have in the states, you have to get a dose at time zero and then again at two weeks and four weeks and then six months,

and then 12 months, and then 18 months, and then every year after that. That's a lot of, yeah, compliance must be challenging to achieve on that. Yeah, it definitely can be. So speaking of the anthrax vaccine and animals, we wanted to bring on a very special guest to help us explore a huge area of this disease and this microbe that we've really just barely touched on so far. And that is the impact of anthrax on domestic and wild animals. You know, Aaron, so that we don't have to just speculate about how much Captain Crunch a cow versus a deer is eating. So we consulted an expert. We were so thrilled to get to chat with

Dr. Johanna Salzer, veterinary medical officer at the CDC. So we'll let her introduce herself. So I'm Johanna Salzer. I'm a veterinary medical officer in Bacterial Special Pathogens Branch at the U.S. Centers for Disease Control and Prevention. I serve as both a veterinarian and an epidemiologist. Yay. We're so thrilled to get to talk to you today. So we wanted to ask you, you know, about because you are both a veterinarian and, you know, infectious disease epidemiologist researcher, we wanted to ask you about anthrax in animals. So could you tell us a little bit about what the course kind of in general of anthrax as a disease looks like in animals other than humans? Sure. So anthrax affects different animal species differently. So there are some animals that are

more affected and have more severe disease than others. So usually when we think about anthrax and animals, we think about herbivores, so cattle, sheep, goats, and wild herbivores such as zebras and buffalo and other antelope. And in these animals, when they either ingest or inhale the bacilicinthracis spore, they have a pretty rapid onset of disease and pretty severe. And so usually the first sign of disease in these animals is actually a sudden death. And so usually the first sign of them that you have an outbreak of anthrax in a herd is when animals are found dead. And the carcasses present with, you know, lack of rigor mortis or reduced rigor mortis and dark blood that can be oozing from the mouth or nostrils or anus, a marked bloating. and often this rapid decomposition of the carcass.

Interesting. That's awful. Yeah. So looking now more specifically, are there any big differences in how this disease happens among different animal species? Like are some animals more susceptible or seem to be more susceptible, or is it just a difference in exposure risk? Yeah, so some animals are considered more resistant.

So species like pigs, dogs, cats, carnivores, some of your scavengers. So actually, some of the animals that would maybe feed on a carcass are the animals that, you know, if they are infected, they have less severe disease and it's more rarely fatal. Interesting. That's fascinating. So, I mean, because this is a disease that can cause, you know, these really massive outbreaks. And like you were saying, just really rapid death and decomposition of the carcasses leading to further outbreaks, What do control efforts kind of look like and entail once an outbreak has been identified? And how does that control differ for an outbreak maybe in livestock versus wildlife?

Yeah. So the two primary tools that we have for controlling anthrax are livestock vaccination and vaccination programs for anthrax, especially in areas that are known to be endemic. So vaccination, it has been done in wildlife, but it is pretty challenging. because most of the time it would involve darting of an animal. And then proper carcass disposal when you do have an animal that's suspected or confirmed to have died of anthrax. The carcass disposal, so the recommendations are either to incinerate or burn a carcass. And if that's not possible, then to bury.

And even with livestock, this can be a challenge. There are places where anthrax is endemic that there's just not much top soil. you're not able to actually physically bury an animal or perhaps there's a burn ban or other reasons you wouldn't burn a carcass. With wildlife, it's even a bigger challenge because you have to find the carcass fairly quickly before scavengers do. And that's often nearly impossible with wildlife. And wildlife, they're also larger carcasses, right? You're talking about elephants or hippos, buffalo. One of the outbreaks that we recently consulted on in Amivia, some of the recommendations were just to bury the carcasses when possible and to just minimally move them to try to prevent further environmental contamination.

In places where there's like mixed cattle and wildlife grazing, I know that that's been happening a lot like integrated farms, would that practice increase the risk to domestic animals or decrease the risk? risk almost to the wildlife because maybe an anthrax outbreak could be identified more quickly, even if there are more like susceptible individuals. I was just thinking about how that practice might affect either the risk or like control measures for anthrax in those in those animal populations. Yeah. I mean, that is a perfect example of where vaccination and good vaccination programs, like our strongest weapon against anthrax, you're asking Aaron, like identifying a wildlife case early than could trigger vaccination and livestock. Yeah. And I think that actually is the case in Texas, where you do have a lot of wildlife mingling with livestock. From a veterinary perspective,

like one of the things I most love about working on anthrax is because it is one of those diseases, much like rabies, that if you can protect the animal and prevent the disease in animal, you protect people. And anthrax, working on anthrax and livestock, specifically in protecting livestock, you know, also in turn can not only protect people, but also wildlife, which is one of the things that, you know, I find so fascinating by anthrax. Like it really much like rabies has this, the connectivity is so tight between human and animal health. And with anthrax, you also have this environmental piece where you have to have all these, the right environmental conditions for the sport to survive too. So it's kind of the

poster child for one health and approaching, you know, using a one health approach to disease control. Thank you so much, Dr. Salzer, for taking the time to chat with us. It was so fantastic and we really appreciate it. Yeah, we do. It was absolutely thrilling. So, Erin, after all that, what can you tell me about the history of anthrax? Like, where did this come from and how did we get here? I can't wait, but let's take a quick break first. Anyone who works long hours knows the routine. Wash, sanitize, repeat. By the end of the day, your hands feel like they've been through something.

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Hello, hello. I'm Malcolm Gladwell, host of the podcast Smart Talks with IBM. I recently sat down with IBM's chairman and CEO, Arvin Krishna. And I asked him, how can companies use AI to its fullest potential to create smarter business? My one advice to them, pick areas you can scale. Don't pick the shiny little toys on the side. For example. If anybody has more than 10% of what they had for customer service 10 years ago, they're already five years behind it.

If anybody is not using AI to make their developers who write software 30% more productive today with the goal of being. 70% more productive. Yeah. Wow. So we are not asking our clients to be the first experiment on it. We say, you can leverage what we did. We're happy to bring out all our learnings, including what needs to change in the process, because the biggest change is not technology.

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0% APR financing for 60 months equals 1667 per month per 1,000 financed for well-qualified buyers through Stalantis financial services regardless of down payment. Not all customers will qualify. Contact dealer for details. Offer ends 3-2. For many of us, especially those that remember watching the news coverage in 2001 on the anthrax letters, more on that later. Anthrax holds a very specific meaning, that of a bioterrorism agent. And that reputation or perception of anthrax hasn't diminished over the years, despite the fact that anthrax poses a much more real threat as a disease of livestock and wildlife than it has as a bioweapon so far. And the bioweapon angle itself, that's relatively new.

Throughout its very long history, anthrax has been many things, a punishment from the heavens, an agricultural disease, an occupational hazard, and now a potential weapon of bioterrorism. So my goal for the history section is to take us through these different faces of anthrax. And let's begin at the beginning, the evolution. originary origins. Yes. So as you mentioned, Erin, bacillus anthracis, it's kind of a funky little pathogen. It's not super diverse. It reproduces clonally, primarily. And actually, this incredible lack of diversity meant that it was only in the past few decades or so, past two decades or so, with the development of next generation sequencing technology, that researchers were able to

get a full picture of its evolutionary history and relationships among different strains or clades. Before it was too difficult. Yeah, because they were just too similar across. Exactly. Yeah. Fascinating. So what did they find? Well, first of all, they found that bacillus antherasis likely evolved several tens of thousands of years ago. I couldn't actually find like a very good estimate of when it first emerged or diverged. But in any case, several researchers believe that it evolved from an insect pathogen or insect commensal. Oh. Mm-hmm.

Like some of the closely related. Exactly. Bacillus thuringensis. I don't know what that one was. Thuringensis. Thuringensis. Thank you. Mm-hmm.

So, yeah, it evolved from this insect pathogen or commensal, and it diverged from Bacillusirius after acquiring those virulence plasmids. It's thought that bacillus anthracus emerged in sub-Saharan Africa, but the location of where it's spread from and then this burst of diversification is likely to have happened somewhere in the fertile crescent, which is where the domestication of livestock primarily happened. That makes sense. Makes sense. Yeah.

And it's unclear exactly how this bacterium got to the American. but there are a couple of hypotheses, which are not mutually exclusive. So one introduction could have come during the Holocene by ungulates traveling over the Bering Land Bridge and then, you know, down into the Americas. And another source of introduction is thought to be European trappers who brought it into the eastern U.S. But overall, like you said, anthrax is a very slow-moving creature evolutionarily, accumulating mutation slowly. And this quality of anthrax has made it a lot easier to trace not only its history, but it also has great forensic value in tracing the source of an anthrax bio weapon,

such as in the case of the 2001 anthrax letters. So like pinpointing exactly where this particular strain came from. Oh. It's just pretty interesting. But anyway, I'm getting ahead of myself a little bit. And so now that we've got the evolutionary history out of the way, let's check in with ancient history in anthrax. This really is like a first season. It super is.

I'm overwhelmed. Anthrax seems like it was definitely known in ancient times. The fifth and maybe six biblical plagues, the plague of livestock and the plague of boils, respectively. which always makes me think of Brooklyn 9-9, the plague of boils, anyway. Anyway, those have often been held to be anthrax, as well as Rinderpest. Like I know that I mentioned these biblical plagues in the Rinderpest episode. Yeah. And in ancient writings in India from 500 BCE or so, describing the diseases of animals,

anthrax seems to be one of those diseases described. It was also known in ancient Greece and in ancient Rome, the poet Virgil wrote about animal plagues, one of which sounds an awful lot like anthrax. Here's a quote for you. A terrible plague once sprang up there and raged on through the warmer part of autumn, not only destroying one flock of sheep after another, but killing animals of all kinds. Nor did the victims die in easy and uncomplicated death. After a burning fever had raged through an animal's veins and shriveled its flesh,

the fluids again became abundant and virtually dissolved the bones. Ooh, yeah. Sounds rough, no matter what it is. And right. Could have been that cracks. And one of these plagues, one of Virgil's plague, supposedly wiped out almost half of both the human and animal populations of Rome, and the disease continued to be a major problem in the area for centuries, popping up over and over again. This tendency of anthrax, which is like to haunt certain farms or regions, gave rise to almost like a mythology around the disease.

And it meant that generational knowledge was required. So families or villages had to remember like where the bodies were buried, so to speak. And pass that information down so that future generations could avoid grazing livestock in those areas. Not even so to speak, but like literally. Literally. Yeah, not even so to speak. Yeah. Actually, side note, I saw a really cool paper about how the spots where carcasses are actually end up being an attractant to animals because like if an animal dies of anthrax, that nutrient influx into the soil will actually help plants grow like better and faster, thus attracting other animals, thus influencing the transmission chain. At what time frame, though? Because I was reading about how for the first year they tend to... The second year.

The second year. The first year, it's avoidant. The second, it's attractant. The third year, the preference goes away. Fascinating. I know. Because it seems like after two years is when infectivity goes down. So that second year is when...

It's crucial. Trick. Isn't that so... It's just... Evolution. Ecology. It's just magical. But this tendency to like, you know, haunt certain areas led to, for instance, in France,

some of these areas being referred to as the cursed fields, the cursed fields. So widespread trade of animals and animal products ensured that these cursed fields could spring up anywhere. And by around 1,000 CE, anthrax was really well established throughout the old world. Germany and the British Isles experienced major outbreaks of anthrax in the 10th, 13th, and 14th centuries. And these epiziotics resulted not only in the deaths of livestock, but also in the humans and dogs and birds and other animals that fed on the cattle carcasses, or they ended up starving due to food shortages or nutritional deficiencies. So does that mean that anthrax moved around the world? from livestock trading. Exactly. Yeah, well, livestock trading and fur trading and like wool and so on. So it is, this is what's so interesting to me is that, you know, for a lot of diseases that are human specific,

they moved around the world due to human travel, but it was also, it was almost an inevitability. But like with anthrax, I feel like we really lent a helping hand. Right. Like, it's oh what this is blowing my mind right now actually yeah i mean it turns out this is one of like the big ones like capital b capital oh it's it has been i mean and it has really had like a huge impact on history and ecology and it's just really fascinating to me let me give you an example Oh, please. In 1613, in Southern Europe, a massive outbreak of anthrax is estimated to have killed around 60,000 people and untold numbers of livestock. What?

Uh-huh. Over the next 100 years, so like between the 1600s and 1700s, anthrax outbreak seemed to grow stronger and deadlier in some ways, which probably, definitely, had something to do with. this increased movement and trade. And one of these places of trade was the New World. Even if anthrax had been brought over across the Bering Land Bridge around 10,000 years ago, it greatly spread in prevalence and outbreak intensity following European colonization. It seems that anthrax began to be perceived as a problem in the New World by the 1500s, but the biggest and most devastating outbreak of what was likely anthrax didn't occur until the 1770s in what is now Haiti. In this outbreak, an estimated 15,000 people died of anthrax, and untold thousands of cattle

and other livestock also perished. And a major component of this anthrax outbreak that contributed to its deadliness was the fact that an earthquake occurred in the middle of the outbreak, making food even more scarce than it was before. And so out of desperation, people began to eat the livestock that had died of anthrax, which of course led to even more cases. Yeah, I feel like it's important to also point out that cooking the meat doesn't kill the spores. Oh, no, these spores are like... They're like preons, practically.

I know. Nevertheless, they persisted. Yeah. A hardcore spore. Oh my gosh. Okay. So although this 1770 outbreak of anthrax may have been the most devastating, it certainly wouldn't be the last. But before I go into more of those, let's talk names real quick. Okay. I'm not going to go through all the different names because there are very many, but I will go over some of the patterns that we have seen in these names. And so one is that they

often called out that grazing animals were most commonly infected. So like cow sickness, goat sickness, et cetera. And another is that the skin condition caused by anthrax, which is like the most common manifestation, as you pointed out, also made an appearance in many of the names. And the word anthrax itself comes from the Greek anthracos, meaning coal or carbuncle. And many other names call out the black color that can often result from the anthrax skin condition. Right. Yeah. It's a very characteristic lesion. And the Latin word anthrax also means carbuncles or malignant boils. The French word for the disease was Charbon. Like carbon? Like coal or charcoal. And the whole body forms of anthrax, though, were of course called by many different names because no one yet knew that the disease.

diseases were linked. Right. That's what's so interesting about these ones that have such varied manifestations. Yeah. Who connected cutaneous anthrax to inhalational anthrax? Uh-huh. Oh, well, I'm going to tell you that. Oh, good. I could tell you his name. I can tell you how he did it. And another characteristic or another parallel was that many of these names included a reference to the spleen in the disease's name. So like in South Africa, the disease was referred to as spleen illness. And in German, spleen fire or inflammatory death of the spleen. Does the spleen, I mean, is that where a lot of macadamacetism?

It's a giant lymphoid organ. There we go. As I've talked about before, the names that people use for a disease can tell us about the importance of the disease to humans or what they saw as its defining characteristics. And maybe it was because of the economic importance of livestock, the fact that humans could also become ill, or the terrifyingly random and rapid way it killed. It's pretty clear that anthrax in all of its various forms was not an overlooked disease. By the 1700s, widespread global trade and population growth had led to, among other things, increasing urbanization and industrial specialization. And that also included textile production.

So rather than wool or leather products being processed at the same place where the farms were, they were sent to textile mills where many people worked the animal products. Wool, hides, skins, etc. began to be transported long distances. And Aaron, can you guess who hitched a ride? Anthrax spores. Exactly. At some of these busy textile mills in France, a physician named, and I'm going to need your help with this pronunciation, Aaron. Okay.

Nicholas. Okay. Nicholas. And then Fournier, F-O-U-R and I-E-R. Yeah, that was great. Perfect. Fornier started to notice that some of the workers began to show signs of illness similar to those experienced by the animals where the materials came from. and the rate of these conditions was substantially higher than it was in the general population,

and it wasn't just inflamed skin that these workers were experiencing, but also the GI symptoms or the full body manifestations of anthrax. Fornier, inspired in part by his older colleague, began to question whether these diseases with different names, thought at the same time to all be distinct diseases, were really all the same thing. He noticed a common thread binding the affected people together. They all had some connection to animal hair or animal parts, either eating or working or cleaning, whatever. Some sort of connection. And he published his findings and his description of anthrax in a booklet that may not have been very popular at the time of publication,

but it would go on to greatly influence other researchers and physicians and veterinarians that, that came after him. And it would also mark him, at least in my eyes, as pretty dang ahead of his time, because all of these observations and hypotheses that he was making were taking place in the mid-1700s. Wow. The birth of germ theory was still about 100 years away. That is truly remarkable. Yes. It reminds me a lot, again, of the botulism dude. I can't remember his name. He, like, made all of these amazing achievements. Yeah, he's the one who did, like, all of the things. Like, discovered the pathogen, did the test, did the thing, found a treatment, found a

use, blah, blah, blah. Everything. Yeah. Yeah, he was cool. If only I can remember his name. Like I said, limited space here. Okay. Okay.

But speaking of germ theory, shall we jump 100 years into the future? I just want to give Fornier, like, a second. credit because I am still blown away. Okay. A moment of appreciation for Fornier. Nice job, dude. Okay. There's no way we were going to get away with not laughing about that one.

Okay. Anthrax actually played a pretty huge role in the development of germ theory. What? Yes. This is again where I was like, what? This bacteria has so much beneath the surface. Okay, keep going. Okay.

Bacillus anthracus was one of the first bacterial species, actually, that was really intensively studied. It was used as one of the first case studies to develop Koch's postulates. What? To understand the ecology of the disease and the role that the environment played. What? And to develop a vaccine. Like... Why don't I know any?

of this, Erin. It feels like I should know this. I think it was all overshadowed by 2001. Yeah. But yeah, I think also there's a question in that as to why, not just why don't you know all this, but why anthrax? Why was it so heavily studied? I mean, because it was killing people and their cows? Those are a couple of the reasons. So definitely, yeah, caused these huge epizotics that led to loss of life, loss of, like, wealth, et cetera. It was terrifying, you know, just a very threatening disease in terms of the symptoms and the mortality rate and also how it seemed to appear randomly. So like untangling that mystery seemed to have, you know, would have placed it at high priority. Another reason, though, is that anthrax cases continued to rise in people who worked with

animals or animal products, not just livestock farmers, but tanners and butchers and bullsorters as well. Yeah, definitely. And number four, this is a very practical reason, but the anthrax bacillus is actually like quite large. Yeah, it's big. So, yeah, so it was large enough to be easily seen under a mid-1800s microscope. And it also turns out it's pretty easily stained as well.

So. But still, the discovery of the. Anthrax bacillus begins probably earlier than you might expect in the 1850s. What? This is like before germ theory, really. It's like the very, very beginning of germ theory. In that time, so like 1849, 1850, a French and a German researcher both observed the bacteria independently at like nearly the same time.

And no one knows, like priority doesn't really matter. But it's still led to this huge controversy in both France and Germany, trying to lay claim to who first discovered the anthrax bacillus. And I think it's interesting because this controversy between France and Germany was just a preview of the contentious rivalry that would emerge between the French Louis Pasteur and the German Robert Koch when it came to anthrax and all other things microbiology. Okay, so observing the rods in the blood of infected humans or animals was pretty, easy, like those two earlier microbiologists did, but isolating those rods and growing them in a lab

is a whole other story. Yeah. Yeah. And so by recognizing that the anthrax bacillus and other microbes were living things, early microbiologists were faced with the enormous hurdle of figuring out how to feed and shelter them, how to keep them happy enough to grow in an artificial setting outside of an animal. Yeah. And anthrax, because it has this like pretty unusual life cycle, proved to be quite technically challenging. Yeah. That's why it's surprising that it was so one of the first. Yeah. It's surprising that it was one of the first, but I also think that the way that it was studied was rather ingenious. Oh, okay. So Robert Koch, like, I'm not going to go into too many details, but what he did was he developed a culture slide.

It was like a little, had a little dip in it, that not only allowed the bacillus to live, but it also allowed an observer to closely watch its every move. And this slide is how he was able to observe that the rods at the edge of the liquid suspension, those that were like more exposed to air, they were undergoing shape changes. Stop it.

Yes. They were turning into long filling. and they started to look granular. Stop it. In other words, they were transitioning into perfectly formed spores. He was. Oh, I am losing it right now. Okay, but this is the 1800s, and we're talking about looking through a microscope and watching a bacterium sporulate.

Yeah. What? the heck 1876 i'm dead now i know because the implications for that discovery were enormous so like not only did this answer a whole host of questions why did the bacillus seem to disappear in blood and tissue samples after the animal died because it did turn into a spore oh oh why grazing animals seem to be the most affected. Because they eat so much of it in the soil. And how on earth this bacterium survived in the soil and was able to cause seemingly random outbreaks. Oh, my gracious. It's, I mean, it's amazing. So, you know, another reason why anthrax became a

model organism is because Koch published his super detailed protocol for cultivating these anthrax bacilli. And so for that reason, everyone was able to go out because, like you said, it's globally distributed or find a farm that had an anthrax outbreak, get some blood, and then, you know, work with it in a lab. So, I mean, it's really weird to think about now because A, anthrax is so deadly, and B, we're like, that should be under high, you know, it's like a highly controlled substance. three or four, like you can't just do that. You can't just do that, but they just did that.

And so anthrax was used not only to develop coaxe postulates, but also the principles that researchers would use to ensure that the bacterial species they were working on was indeed the species they thought it was. So things like morphology, lab requirements, staining principles, life. cycle illustrations. Like it was used as a model for all of those things. Wow. And Koch's anthrax research also caught the eye of none other than Louis Pasteur. Among his many achievements, Pesture is often credited with developing the first anthrax vaccine. But in doing the research for this episode, I learned that he actually was not the first.

The first was a veterinarian named Jean-Joseph-Anri Toussaint. who used heat and chemicals to develop a strain of anthrax that would produce an immune response in an animal without killing it. Heat and chemicals. Like, again, ahead of its time, 1800s, late 1800s, he successfully tested his vaccine on 20 sheep and published his findings. And Pasteur came across Toussaint's vaccine work and decided to test it out. So in a public and highly publicized demonstration, he injected anthrax into two groups of sheep, one that had been vaccinated and the other not. I mean, newspapers were like came from all over. It's been now made into a movie. Like, this was a huge demonstration. And thank goodness it worked. All of the sheep who had not been vaccinated

died and those that had lived. Wow. And this public demonstration was not only a very exciting demonstration of germ theory in action and the life-saving power of vaccines, but it also firmly placed Pesture as the creator of the anthrax vaccine. Because he was like, I'm going to do it loudest. Well, not only did he do it loudest, but he also was like, oh, no, my vaccine is way better. I used a much better like thing. You know, Toussaint's method is unreliable and unscientific and blah, blah, and poor Toussaint, who was both less well-known and less powerful than Pasteur, was also suffering from a neurodegenerative disease that would go on to kill him at the age of 41. And so he didn't have the ability to really assert his claim to fame.

That's very sad, Aaron's. Very sad. Pesture did not create the first anthrax vaccine. Maybe that's the take-home. No, it's not really. There's lots of other takehomes, but let that be one of it. So anyway, vaccine credit aside, the important thing was that there was now an anthrax vaccine. And the administration of this vaccine to livestock all over the globe did a great deal to reduce the incidence of the disease.

But it did still happen. And here is where I want to revisit anthrax as an occupational disease. At this point, in anthrax's history, history, it was still viewed primarily as a rural agricultural disease despite Fornier's work in the French textile mills of the 1700s because people just ignored that work straight up. Okay. But this characterization of anthrax as just agricultural, that was about to change. Okay. By the late 1800s, the textile industry in Europe had become very centralized,

even more so than 100 years prior, with large factories where, different types of wool and hair and skins would be imported from all over the world. In these factories, a disease started to show up with increasing prevalence in the workers who would sort the wool. Wool Sorter's disease, as it was called. Uh-huh. Uh-huh. One day, you felt fine. The next, you got a fever and pneumonia-like symptoms, and then you collapsed and died. And during these outbreaks, no one yet knew that Wool Sorter's disease was actually a type of anthrax. And that's because anthrax at the time, like I said, was still thought of just as a

disease of agriculture. And at the same time, most anthrax cases tended to be cutaneous rather than inhalational. And woolsorters disease is inhalational. Remember how scrapy, like, which is the preon disease of sheep, increased in prevalence and geographical distribution because of the wool trade? Yeah. Yeah. Anthrax. also. And there was like, so around this time, which is like also similarly when wool demand grew so much and scrape who became a huge problem and also more widely distributed, that high demand for exotic furs and wools grew so much that some farmers became more reluctant to lose out on a profitable fleece from a goat or sheep that died prematurely.

Oh, no. Perhaps from anthrax. Oh, dear. Yep. And so they would shear the animal anyway and send off the hair, which often still had bits of blood or skin attached. Yeah. The wool sorter would then comb the wool using newly developed machinery, which would often result in the dirt and dust and blood and skin particles turning a bit aerosolized. Oh, God. Yeah, just like a haze of anthrax. Oh, God. And like I think to us now, wool sorter's disease may seem like an isolated problem, limited to a very small part of the population.

But that wasn't the case at all. Wool sorders made up a huge part of the occupational, like, community. And to give you some sense of how much of an impact occupational anthrax had during this time, consider these stats from Italy. Between 1890 and 1904, 36,4, 436,436 cases of anthrax were registered among tanners, brushmakers, and woolworkers, with 7,308 deaths. Whoa. That's a lot. That's a lot. And so it makes sense, then, that there would be many epidemiologists hard at work on this problem.

But among all of these epidemiologists, John Henry Bell may have been the most influential in getting Wolfsorder's disease to be widely recognized as a form of anthrax. He was also one of the first to push for workers' rights, or at least call out the responsibility of the employer in providing a safe work environment and minimizing the risk of disease. Oh, get it. Uh-huh. As a physician, Bell would often be called upon to perform. form autopsies on those who died of Woolsorder's disease. And he became increasingly frustrated with what seemed to him to be careless employers who refused to acknowledge their own responsibility in the disease. And so under cause of death, he started to put things like

employers neglect and not properly washing or disinfecting imported mohair. Whoa. Get it. And so, you know, not employers don't want to be blamed for the death of their employees or you know and also I think that his voice was loud enough and he was prominent enough in the community to really like raise the alarm on this. Wow. And so in effect he started this activist movement among the woolsorders to protest these working conditions and to fight for protections from anthrax. And this also marked one of the first occasions of an infectious disease being recognized as an occupational hazard. So interesting. So many people. So many people. to this anthrax puzzle, Erin.

I know. Oh, my gosh. Practices like vaccination or increased sanitation of wool reduce the incidence of anthrax among these workers, but it did still pop up and not just in the wool sorters. For instance, early shaving brushes were made of like animal hair, and some of these carried anthrax spores on them. And so when somebody would use a brush on their face,

and they had tiny little cuts from shepherds. shaving? Yeah, the spores would get in there and cause cutaneous anthrax. No, thank you. And horsehair was often used as an ingredient in plaster and often, or at least occasionally, contain anthrax spores. By the early 1900s, the perception of anthrax had evolved into one of both agricultural and industrial importance and several tools had been developed to combat the disease. vaccines, which I'm not going to go into the history of, except to say that new and improved ones had been developed, better sanitation practices and serum were all variously used and seemed to make a pretty substantial dent in slowing transmission.

Anthrax seemed to be turning into a disease of the past. Not quite. The world wars of the 20th century really showcased how inventive and cruel and brutal and relentless humanity could be when it comes to killing other humans. And one of these methods of murder happened to be bioweapons. Long before the 2001 anthrax attacks in the U.S., there had been previous attempts to develop anthrax into a bioweapon by nearly every country involved in these global conflicts. Anthrax has always been near the top of the list of potential bioweapon agents

because of its high mortality rate, its relatively easy manipulation in the lab, thanks to its model organism status, its durability, its ability to survive an explosion, and the existence of a vaccine, which could protect those who were administering the bioweapon. That is a gross part that I did not realize

was a criteria for what makes a good bio weapon. Mm-hmm. Mm-hmm. Yeah. That's so gross. Yeah, gross is, yep, it's the right word. Research was carried out in many countries to work on how best to use anthrax as a weapon, maybe in warfare with shrapnel bombs, or as a massive civilian attack using high-altitude bombs or atomizers,

or maybe, you know, lace some anthrax in linseed cakes and then drop those into German fields where they would be eaten by the cattle, killing cattle, and then humans that ate the cattle. It's a very specific example that I'm giving because that was an actual British operation called Operation Vegetarian during World War II. I know. Like I wrote this and I'm like, am I reading this right? Yeah. Yeah. Scientists dealt with things like the logistics of how high a bomb should be deployed to impact the widest area, which way the wind was going, or which form of the of the bacillus.

Should we do like a liquid suspension or a spore form? That would be most likely to cause death or be the most stable or how to protect those deploying the weapon. So we know that people worked on anthrax as a bioweapon during these wars and researched it as a possibility, but did anyone ever try it out? Well, the first instance of anthrax being used as a bioweapon is often cited as a part of a World War I German sabotage program in which anthrax was. supposed to be administered to allied draft animals like horses, mules, reindeer, etc. In 1917, German spy Baron von Rosen was captured in Norway and accused of smuggling a bioweapon, anthrax-filled glass capillaries, concealed in sugar lumps. So these anthrax sugar cubes, in 1998, they were analyzed and anthrax genetic material was found.

so like maybe there was something to it. However, in 2017, a paper came out that suggests that those anthrax colonies were actually just lab contamination. So we'll never really know if the Shrker Cubs held anthrax or not. But we do have solid evidence of weaponized anthrax being tested on humans from Unit 731. And so this is the infamous unit of the Japanese army that in World War II carried out bio-weapons testing on human and animal subjects, and also where no one was ever punished because the U.S. made an immunity deal to get access to all their research in exchange for immunity. Cool. Which is the episode where you talk a lot about that one?

Hauntavirus. Hontovirus, I believe. Mm-hmm. Anyway, thousands of people primarily in the historical region, Manchuria, were intentionally dosed with anthrax to observe how quickly it killed or the dose necessary. medicalized torture that mostly resulted in death. There were anthrax shrapnel bombs that were blasted at people tied to stakes nearby, with different body parts exposed to test dose and site of entry.

What the actual? I know. Mm-hmm. And many, many other countries, including France and England and Germany and Germany and Canada and the U.S., performed similar horrifying experiments on weaponized anthrax on animal subjects throughout World War II. As you can expect, as we all expect, research into anthrax as a bioweapon did not cease with the end of World War II. Nor did it end in 1972 when nearly every country around the globe signed the Biological Weapons Convention, which banned research, development, possession, and deployment of biological weapons.

In 1979, in Svredlovsk, Russia, approximately 100 people, maybe more, fell ill and died within a few days of anthrax. Most of the people were workers at a ceramic plant located across the street from a biological research facility whose main project was, you guessed it, erasolized anthrax. Yeah, okay. Yeah, well, bioweapons with aerosolized anthrax is a lot. the main. And the Soviet government claimed at the time, oh, that's ingestinal anthrax. They just got it from eating tainted meat. And then they also happened to destroy all of the victim's medical records. And then later investigations, though, like they invited American researchers to come in and investigate the source of this outbreak. And that revealed that a filter

that was preventing the fine anthrax powder from escaping the building had been removed. And no one had noticed. And so the drying machines with this mound of like anthrax were turned on, basically blowing these anthrax spores into the outside air. Oh, no. Yeah. Downwind was, as you can guess, the ceramic plant. There's a whole book on this written by one of the American research. researchers who helped to uncover the truth about this incident. It's called anthrax, the investigation of a deadly outbreak. Looks fascinating. I didn't read it, but I'll post it.

Anyway, around the same time as the Sferdlovsk incident, an enormous outbreak of anthrax was taking place in what was then, Rhodesia, now Zimbabwe, the largest epidemic of the last 200 years. Oh, my God. Between 1978 and 1984, 101,9199,000. cattle and 17,199 people were stricken with anthrax and nearly 200 people died. Whoa. This outbreak, which was obviously economically devastating, took place at a time of great civil unrest in the country. And there has been a lot of speculation that the surge in anthrax cases was due to the

intentional release of anthrax as a bioweapon. And while there's not a whole lot of physical evidence that that's the case, there is a good deal of circumstantial evidence, and I'll post a great review that goes over this outbreak and all the different sort of hypotheses. Okay, this is a long episode, just a couple more bioterrorism incidents, and then I'll throw it back to you. Okay. In 1993 in Japan, a liquid culture of anthrax was sprayed from the rooftops by a religious cult, but no one got sick, because it turns out it was the strain of anthrax used to vaccinate animals and was therefore harmless. Yay.

Great news. And then finally, the 2001 anthrax letters. And I'm just going to go over the basics here, like some very surface-level stuff, because A, this episode is very long, as is. And B, there might be a time in the future where I give this topic the time. the time that it truly deserves, which is my way of throwing in like a very vague potential teaser. Stay tuned. Yes, definitely stay tuned for more updates on that.

But okay, the anthrax letters. The first victim of the anthrax letters was Bob Stevens, editor for tabloid publisher American Media in Boca Raton, Florida. On October 4th, 2001, a couple of days after opening a lot of the last, a letter that contained a threatening note, he checked himself into a hospital due to trouble breathing. The next day, he died. A few days after his death, one of his coworkers developed cutaneous anthrax. Then cases of anthrax started popping up in New York City news outlets, studios for NBC News,

and headquarters of the National Enquirer, all from letters containing anthrax spores. anthrax letters arrived at U.S. Senators Tom Dashill and Patrick Leahy's offices, and then postal workers in New Jersey and Washington, D.C. became sick with inhalational anthrax. In total, 22 people became sick due to these anthrax letters, 11 with cutaneous anthrax, and 11 with inhalational anthrax. And five of those with the inhalational form died. Pretty quickly, it seemed likely that the person responsible. had access to a highly secure scientific facility where the deadly so-called aim strain was kept, and genetic testing also supported this, which created this very strange situation, right,

where like everyone who worked at USAMRID, which is United States Army Medical Research Institute of Infectious Diseases, much easier to say USAMRID. Yeah, the longest acronym of all time. Yep. But everyone who was working there, you know, they were treated as both suspect and they were also these essential assistance to the case because they would be the ones performing the genetic tests and the analyses that would reveal where the anthrax from the letters came from. It's like a really strange thing to think about. Yeah, that's bizarre. Yeah. And the investigation itself into who was responsible for the anthrax letters, it has so. many twists and turns and, you know, at least a couple of dead ends. But years after the letters were mailed, super sensitive genetic tests were developed that allowed investigators to identify

not only the strain of anthrax used in the letters, but the specific flask where those spores had come from. That is amazing. I know. It's just such an interesting, like, course of investigation. Yeah. The more technology you have. and then, I don't know, and also the characteristics of anthrax itself, like, or the bacillus anthracist, right? The fact that it's so clonal, the fact that it doesn't really, like, evolve very much or is, like, so consistent. It's, yeah, that you can, like, identify it down to the flask. That's incredible.

Yeah, exactly. And it turns out that these anthrax spores had come from a flask at Usamrid that was under the care of researcher Bruce Ivans. And Ivan's motive was thought to be that he wanted to save the anthrax vaccine program, which was in danger of being shut down. And so, you know, if there were suddenly a bunch of deadly anthrax cases, then the need for the program would, you know, become clear or something. And throughout the investigation, Ivan's never confessed. I believe that there was no physical evidence found connecting Ivan's like home or car to the anthrax envelopes. And Ivan's himself died of an acetaminophen overdose in 2008. But the circumstantial evidence does seem pretty strong.

And like I said, there's a lot more to this story that I didn't do it justice. And even if we never have a conclusive answer as to who sent those letters, one thing is for sure. The 2001 anthrax letters forever seared anthrax as a dangerous bio weapon in the minds of the public. Yeah. So what started out as an agricultural disease transformed into that of an occupational hazard and now a bio weapon. Since 2001, we've learned so much more about the ecology of this bacillus, how it infects wildlife, how it interacts with plants and may not be as dormant in the soil as we previously thought, how anthrax may not just be a disease caused by bacillus anthracus, the role that necrophage is formed. flies may play in transmission, the risk that a warming climate plays in expanding the geographical distribution of this pathogen. Oh my goodness. And so on and so forth. Clearly, despite being one of the longest studied bacterial species, there are still many, many mysteries to uncover.

So, Aaron, where do we stand with anthrax today? Oh, my goodness. I will try to bring us up to speed right after this break. Wow. Okay. Those were a lot of questions that you left open for me, Erin. So let me just say off the bat,

I'm not going to be able to answer those, but we're going to call in some backup. So historical analysis reveals, and I think this is really interesting, for every 10 anthrax cases in animals that leave anthrax carcasses, essentially. That tends to result in one human cutaneous anthrax case.

Hmm. There is one case of human gastrointestinal anthrax for every 3,000, just over 3,000 anthrax infected animals that are eaten. Wow. Wait, for every 3,000 anthrax infected animals that are eaten? So we didn't get into this in the biology, Aaron, but while we don't fully know exactly the infectious dose, it's estimated to be quite high, especially for gastrointestinal and inhalational anthrax. Humans are actually probably pretty resistant to anthrax infection. That is very interesting. I know. Okay. And we also know from historical data that in humans, there are about 100,000 cutaneous cases for every enteric or gastrointestinal case that occurs worldwide.

Wow. And inhalational anthrax today is extremely uncommon. Mm-hmm. Okay. So that's what we do know. globally overall we have a fairly poor understanding of global risk and incidents of anthrax. But we do know, like I said, that human infection largely results from interactions with animals or animal products. And so outbreaks in humans tend to occur both temporally and spatially in association with outbreaks in animals.

And we also have a lot of good data that shows that in most parts of the world, widespread distribution of vaccines for domestic animals and livestock is really effective at reducing infection in animals and in humans. But like we've talked about in pretty much every episode of this podcast, our estimates of incidents and prevalence are only as good as the surveillance that we do. And in the case of anthrax, even though in almost every country, it's a global presence and it's a notifiable disease, we still just don't have excellent data in a lot of cases. And I think this is probably at least in part because it's not specifically a human disease and it can often infect wildlife. It's really hard to get a handle on something as big as that. understanding everything from the course of the disease to the ecological characteristics in so many

different ecosystems, it's a massive challenge. Oh yeah. So anthrax is really, I think probably especially fun for us, Aaron, because it's an environmental pathogen that really requires a large-scale interdisciplinary approach to understanding and control. And because, because, Because of that, we wanted to talk to someone who is an expert in this type of interdisciplinary research when it comes to anthrax, understanding the disease dynamics in wildlife, evaluating the climate and environmental patterns in the distribution of anthrax, identifying the challenges in predicting outbreaks, and most of all, working across fields to most effectively control the incidence of this devastating disease.

We were so lucky to get to chat with spatial epidemiologists, Morgan Walker, and we'll let her introduce herself right now. My name is Morgan Walker. I am a spatial epidemiologist at the University of Florida. I work in Dr. Jason Blackburn's lab, and we are housed jointly in the Department of Geography and the Emerging Pathogens Institute at UF. And my research focuses on the spatiotemporal patterns of diseases and disease spread, especially of bacterial zoonoses, which are bacterial diseases that can affect both animals and humans, one of which is anthrax. Awesome.

Excellent. Thank you so much for joining us. We're so excited to talk with you. Thank you so much for having me. So we want to just start off by asking, you know, a very basic general question. What is the current worldwide distribution of be anthracis? Like, I know it's a big one. And so because there are presumably patterns in the distribution of this pathogen,

We also wanted to ask you, you know, what are some of the environmental or climatic determinants of its distribution? What are some of the patterns that we see? Yeah, so it is definitely a big one. It's distributed pretty much globally. Some of the areas where it is endemic or where we typically see cases are areas like Central Asia, the Midwest of the United States extending up into the Northwest Territories of Canada, sub-Saharan Africa, southern and eastern Europe, and south. Eastern Australia. And part of the reason why it has such a wide range is because it can form

a protective spore around it, which makes it really hardy and really resistant to a variety of environmental and climatic conditions. But it survives best in soils with slightly alkaline pHs, and soils where there's high calcium concentrations, and in soils where there's lots of organic matter present, so fertile soils. Excellent. So then what types of, kind of environmental or ecological patterns do we know of that are tied to an increased risk of anthrax outbreaks, either among animals or even humans? That's a great question. It's something that we're definitely still researching and trying to figure out because if we have a better idea of why an outbreak happens, we can do better

predicting when they're going to occur and how intense they're going to be. There's not a clear consensus at this point. What the mechanism is that leads to an outbreak. because outbreaks have happened in such a variety of geographies and a variety of ecological conditions and to such a wide variety of animal species. But what we can't say at this point is it seems to be that in the mid to high latitudes of the world, the pattern that precedes an outbreak is that there will be a wet spring followed by a hot dry period. And then there will be a rainfall event.

So basically just it will rain really hard. And then a few days after that rain event, there will suddenly be cases popping up. And we are still researching why exactly that pattern leads to outbreaks. But in areas like West Texas, we see both on the ground and anecdotally when talking to land managers, that those conditions seem to allow the populations of biting fly populations to explode. So we think that biting flies are mechanical vectors of the disease, which essentially means that when a biting fly bites an animal that is actively fighting an infection and has the solariscus circulating through its bloodstream, it can get the bacteria on its mouth

parts and then fly to another animal, bite it, and infect it. That's like such an interesting mechanism of dispersal, because it's like, a vector, but not a vector. But not a vector. Yeah. In the way that we like traditionally think of vectors. Yeah. So, you know, and I know that you said that we're still sort of working out the exact

risk factors for an anthrax outbreak, but how do we monitor how risk of exposure to anthrax changes over time? And then also how does that risk in general differ between, you know, let's say some groups of wildlife or some groups of domestic animals and humans as well. Like how does the risk change for those different groups? Yes. So globally, the use of active surveillance or continually monitoring risk in a population for anthrax is really limited, especially because areas can go long time periods without seeing an outbreak. So people will get into a habit of not really worrying about it. And so they're not actively monitoring. It's much more common.

to do sort of passive surveillance, which means that on the animal side of things, if a land manager sees an animal that is exhibiting clinical signs of anthrax, they might have that animal tested or they might have that animal carcass tested if the animal actually succumbs to disease. And then on the human side of things, passive surveillance pretty much looks like waiting for humans that get infected to come into a clinical setting because they need to be treated. And then that's how cases get reported.

So almost all mammals are susceptible. However, the animals that we typically see dying of anthrax are herbivores. So that's why it's a big problem in livestock amongst like cattle, goats, and sheep. Whereas carnivores actually very rarely succumb to anthrax. So it does differ amongst animal groups. And then for humans, risk is definitely sort of dependent on occupation and behavior. So obviously if you're a land manager that's trying to handle an outbreak and dispose of the carcasses, that's something that will put you at risk.

But also it's not uncommon in certain areas of the world for people who are raising livestock. If they see an animal that's sick, they might go ahead and slaughter that animal just so that they can try to recover some of the financial investment that they've spent. And then once they are slaughtering the animal, handling an infected animal meat, that puts you at risk for cutaneous anthrax. And then if you go on to sell that meat and people eat it and it might be undercooked, they can also become infected that way. Got it. So as a pathogen that spends part, if not the majority of its life cycle,

in the external environment, like not being pathogenic necessarily, It seems like, very likely, that global climate change is going to, or maybe already has begun to, impact the distribution of bacillus antherisis in some way. So could you talk a little bit about what some of the models are predicting in regards to the impact of a warming climate on either a shift or expansion in the range of this pathogen? And what might that mean for the kind of shifting landscape of risk? Yes. So at this moment of time, there's a lot of uncertainty. in the face of climate change when thinking about the psilocyllus and the races. Because there could absolutely be range expansion where we see that new areas are now suitable

for the bacteria to survive, but at the same time, some models predicted there will be range contraction. Additionally, some people hypothesize that outbreaks could become more intense because those weather patterns that I talked about earlier where there's a really wet spring and then a hot dry period, that could happen more frequently or it could be on larger scales. but at this point it's really difficult to know exactly what's going to occur. We don't really have enough data. And because anthrax, there's a lot of stigma around it. So it's actually underreported globally.

So we're still kind of working on getting highly accurate maps of just where cases are occurring today. So projecting that into the future is something that's pretty difficult at this point to do. Gotcha. Gotcha. Yeah. Fortunately, for bacillus anthracis, we do have various methods of control or prevention, sometimes treatments. So we have like a vaccine. We have antibiotics. And we have also just improved sanitation and monitoring measures.

And so we wanted to ask sort of how do the use of these different control measures differ between wildlife and domestic animals, for instance, or just between animals in general and humans. So like for instance, let's say that there's an outbreak in wildlife. How might different control strategies be used in that outbreak compared to one in livestock, for instance? Yes. So that is the good news. There are different control strategies. And for livestock, there is a vaccine that's very effective and it's been in use for decades. And it's easy to administer. But the downside of that is that the vaccine is most effective 21 days after vaccination. So it might not be most effective to administer in the middle of an outbreak. And then additionally, the vaccine has to be readministered

annually. So that is time-consuming. It can sometimes be difficult. In terms of wildlife, the vaccine is safe for wildlife. That is an off-label use, meaning that there haven't been that many clinical trials done to confirm the safety and efficacy of vaccine and wildlife, but it has been used for a variety of species and seems to be effective. The problem with that is that the vaccine is an injectable vaccine. So if you can't get close to the wildlife in question, that makes it very difficult. You can dart. So if you have a dart and you put the vaccine in it and then you can shoot the animal, that is a way to administer it. And that's sometimes used for wildlife that are like on some of these closed ranches that have like exotic wildlife species that are expensive animals.

Sometimes people try to do that, but they also have to weigh the risk of then you can potentially injure the animal with a dart versus administering the vaccine. Right. Interesting. Yeah. So, you know, with these different control strategies, does their effectiveness vary regionally? Yes. Vaccine use is a strategy that varies regionally. and by country and sometimes even within countries. In the former Soviet Union, for example, they have a legacy of really high vaccination of livestock. So that's still in place in many countries in Central Asia and Eastern Europe,

whereas a lot of areas in, for example, sub-Saharan Africa and South and East Asia, the amount of vaccinations going out to livestock are really low, sometimes around like zero to five percent. So one of the methods of control during an outbreak is proper carcass disposal. So it's very important to try to dispose of the carcass in a way that will minimize the amount of bacteria that gets leached out into the environment.

How we recommend that people do that, the best method is through burning. And if you can't burn the animal thoroughly, we recommend that people bury it. If you can't bury it, we recommend decontamination with a bleach spray. But regionally, especially in areas if they're experiencing, an outbreak in the hot, dry season, it might be too dangerous to try to burn the animal carcass because of the danger of wildfires. So with anthrax, it's one of these examples of a system that there are so many different angles where not only can you study it, but you kind of have to because you have animal hosts, you have a human disease, you have the genetics or the microbiology

of the pathogen itself, but then you have the environmental aspects, you have all these different regional aspects of different cultural practices. It's so much. And then there's like public health, big scale on top of all of that. So could you talk a little bit about how interdisciplinary research is just so crucial for a disease like anthrax and kind of what interdisciplinary research looks like in practice? Yeah. So interdisciplinarity is really important for anthrax because as you know this, there are many different agencies and research groups and stakeholders all involved. And our lab aims to be a part of that in practice by being involved in so many different pieces of the puzzle. So we do things from working outbreaks on the ground with land managers to then taking those

samples that we collect back to the lab and doing diagnostics to hold genome sequences. to then mapping the outbreak and trying to analyze it, to then also working with partners internationally to try to mutually educate ourselves about the disease and also to help inform them with prevention of the disease. So there's definitely a lot of components to go into it, and it's difficult to coordinate. And it's, as many public health issues are,

there's so a lot of progress to be made. As I mentioned, there's a lot of stigma around anthrax. So it goes underreported globally. And it's also really difficult to determine the exact distribution of vaccination and how many vaccines are going out to animals. So to more accurately understand where cases are occurring, as well as vaccination, we really need more accurate reporting, which takes interdisciplinarity and the cooperation between many different groups and agencies. That was so awesome. Thank you so much, Morgan. Thank you to Dr. Salzer as well. That was just so great. I loved it. We're so lucky to get to have both of you on. Thank you.

Yeah. All right. This was a really, like, fun episode to do. It was super interesting. So many different angles. I feel like I learned a lot. Yeah. Absolutely. Speaking of learning a lot and learning a lot more, should we do sources? Let's do sources. Okay. So for this episode, I have a lot of sources. And I will list all of them on our website, but I do want to shout out a book that I used called Death in a Small Package, a short history of anthrax by Susan Jones. Yeah, I also had quite a number of sources, Aaron. A couple that I wanted to give a special shout out to. There was a paper. It's a little old now from 1998 by the World. health organization that is guidelines for the surveillance and control of anthrax in humans and animals. It's just a really nice kind of overview of just how broad anthrax is. And then a couple of

really great papers by Dr. Colin Carlson really focusing on how important interdisciplinary research is for anthrax. So there's a paper from 2018 called spores and soil from six sides, interdisciplinarity and the environmental biology of anthrax. And Morgan Walker wrote an awesome paper that came out in 2020 called Ungulate Use of Locally Infectious Zones in a re-emerging anthrax risk area. You'll find the list of all of our sources from this episode and every one of our episodes on our website, this podcast will kill you.com. Yes, you will.

Thanks again so much to our absolutely wonderful guests. It was such a joy to chat with you. It really was. Thank you also to Bloodmobile, who provides the music for this episode and all of our episodes. And thank you to the Exactly Right Network, of whom we are a very proud member. And thank you to you, listeners. You make this podcast worth making, honestly. Seriously, absolutely, 100% true.

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