Hey, everyone, We're including a content morning for the first hand account that we're about to read, which includes a description of the death of an infant. To skip this jump ahead about three minutes.
Missus Cyril Orchard Street, aged twenty four, was delivered of her third child on Friday morning, September tewond eighteen fifty nine. It was a male child, fine and apparently healthy in every respect. From Friday till Wednesday, all was well. The cord separated on Tuesday, the fifth day. On Wednesday, the child was restless, cried and kicked. On Thursday, the mother reported that he cried all day, could not open his mouth, could not suck, and frequently stretched, and was stiff. The
next day, Friday, I saw him every few minutes. He appeared as if struck by an electric shock. Every muscle
was thrown into distorted action. Will not attempt to describe this drawing tells the wrinkled forehead, the elevated brow, the closed eye, the dilated nostril, the rigid massiter, the fixed jaw, the closed mouth, the corrugated lips, the bubbling saliva, the retracted head, the shortened neck, the starting cervical muscles, the turgid veins, the arched spine, the raised chest, the troubled breathing, the catching diaphragm, the heaving abdomen, the separated arm, the
squared elbow, the bent wrist, the clenched fingers, the incurved thumb, the extended and separated legs, the bent down toes, the livid surface, the whole figure rigid as wood. A pitiful sight, the paroxysm was renewed by a slight noise, the gentlest touch, A placid interval of a few minutes succeeded, and then another fit followed. On examining the child, the umbilicus was seen prominent, at least half an inch long, red and
showing an unhealthy separating surface. The umbilicus continued to discharge emaciation rapidly advanced. The skin assumed a brownish hue and hung in shriveled folds of a leathery texture. Peace and Pang pursued their sickening interchange. The child gradually became more feeble, and on the tenth day of the disease and the fifteenth of his existence, he sank by degrees.
Exhausted, it was really difficult to read, absolutely horrible.
Yeah, and thank goodness, there's a vaccine.
Yeah.
That was from an eighteen sixty case description of tetanus in Phantom a ka neonatal tetanus or tet Yep.
Hi, I'm Aaron.
Welsh and I'm Aaron Almon Updike.
And this is this podcast will kill You.
And I'm sure you all know by now the subject of today's episode.
Yeah, tetanus. It's a vaccine preventable disease that we haven't covered yet, which is exciting, yep.
And it's obviously going to be difficult at times because it's a really truly horrible disease.
I mean, absolutely horrific, devastating, awful.
Yeah.
Yeah, But there's going to be a lot of very interesting biology. I know, there's going to be some fascinating history that I can't wait.
To learn about.
And I have some thrilling things to talk about in the current events section, Like I am really excited.
Yeah, ooh, I'm so intrigued.
So shall we, you know, get started on the important things?
Of course of course we should. What time is it?
Quarantiny time it is?
And this week we are drinking the Rusty Nail, which just so happens to be an actual cocktail.
It's a real drink.
It is. It has Scotch and RAMBOUI and I think that's it.
And we're gonna find a way to make the non alcoholic version our Plasi Brita.
Yeah, it's gonna be an interesting one to make a placy berita for. But you know, I think that it might not bear too much resemblance to a Scotch and a Scotch based liqueur. But I think that's okay as long as it's delicious, right, I trust in you erin okay, thank you, And we'll post the full recipe for this quarantiny and non alcoholic plasy burrita on our website This podcast will kill You dot com.
On our website This podcast will kill You dot Com, you can find all of the things. You can find our merch which is incredible. You can find a link to Bloodmobile, who does all of the music for this podcast. You can find transcripts of all of our episodes and the sources that we use for every single episode.
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Our bookshop dot org affiliate account, and our Goodreads list. You can find our Patreon. You can find really there's just so much there.
Yeah, you did a great job. There's a lot there. Go check it out. Can we dive.
Into us Yes, I think that we ought to right after this break. So today we're talking about another clusterdium species, Clusterdium tetani. We've covered this genus before, of course in our botulism episode, and then I mentioned it again in our sea Diiff episode, although Seaediff was reclassified as clusterritioides. But anyways, today it's clus Tritium. Clusterridium tetani is an
incredibly widespread and hardy little bacterium. It's a rod shaped gram positive spore forming bacterium that when it's making its little spores, if you look at it under a microscope, looks like a little match stick or like a tennis racket.
It's kind of cute, oh.
Because it makes it a little spore at the end. It's like real pos interesting uh huh. And like its cousin, Clusterridium botulinum, this is an anaerobic bacterium, which means it likes to grow without any oxygen. But because it's a spore former, these spores are incredibly hardy. They're very resistant to heat, to to antiseptics to oxygen, and so this is a bacterium that persists in the environment across the globe.
It makes its home in the soil, but Clusterridium tetni can also thrive in the intestines of various animals, including humans.
I found that so interesting. And what is it doing there? Like, is it just a part of your gut microbiota, Are there any sort of negative effects or is it just really hanging out?
As far as I know, at least they just hang out. I'll be honest. I didn't do a lot of digging into what they're doing in our guts. Okay, yeah, But as this is a soil bacterium, and as this is this podcast will kill you, and we're talking about the disease caused by Clusterdium tetne. People are exposed through the
soil kind of in general. Usually exposure to this bacterium tends to be from wounds, especially deep wounds or puncture wounds that come into contact with anything contaminated with this bacterium,
which again can live almost anywhere. So this can be anything from rusty nails to fence posts, thorns from a tree, even potentially bites if they are contaminated really any kind of deep wound, because those kind of wounds have pretty limited exposure to air, which means limited exposure to oxygen, and so as tissue death occurs deep within that wound, the environment can become very anoxic, which can allow for tetni spores that are present in the soil that contaminate
that wound to germinate and grow.
Interesting. Yeah, I have a really dumb question, okay. Anaerobic environment meaning there's no oxygen, there's oxygen carried by your blood if you're bleeding, is that an anaerobic environment.
It's a great question.
So no, if you have active blood flow to an area, then that tissue is not going to become very anoxic. What can happen in deep puncture wounds is that the tissue can die like deep within, and so once you have dead tissue, that tissue is not being supplied by your blood supply very well. So that is why it can become anoxic.
But that's a really good question. It's not a dumb question at all.
That is okay, Yeah, I'm fascinated.
Yeah, that's why it's in theory. Any wound can become contaminated with Clostridium tetani but not every wound is going to be as susceptible to actually harboring a active tetanus generating infection, if that makes sense. Now, I'll talk a lot in this episode about neonatal tetanus, and the first hand account that you heard was a description of neonatal tetanus.
This is a it's the same as regular tetanus in kind of what it does to the body, but neonatal tetanus is often classified as specific because it happens with contamination of the umbilical stump, so the umbilical.
Cord that's left when a baby is born.
That's just kind of an open area that can very easily become contaminated, and the base of that is dead and dying tissue, because that's what's normally supposed to happen with an umbilical cord, and so that's why it's a place that's very easily and then of course babies have almost no immune systems, so that.
Helps as well, right, right, So that's kind of.
How we get exposed.
And just like with Cloustridium botulinum and Clausterdioides, diffcill the story here is not the bacterium itself. It's also not the spores of this bacterium. The story of tetanus is the story of the toxins that this newly germinated bacterium can release within our body.
So let's talk about them.
Yeah, these toxins are Can I read a quote real quick? Actually? Can I inse? Okay? Please do? I was hoping I was going to be able to use it somewhere. Quote. An amount of tetanus batchulinus or dysentery toxin, weighing no more than the ink in the period at the end of the sentence, presumably times New Roman twelve, would be enough to kill thirty grown people. An ounce could kill thirty million tons of living matter. Half a pound would be more than enough to destroy the entire human population
of the world. I'm not sure when this was written, but I think it probably would still be sufficient.
I love Okay, I feel like I remember you reading that quote in our botulism episode.
I feel like I did too. Whoopsie, I'm pretty sure you did.
No, it's not a whoopsie.
I'm really glad that you said that again, because I was trying to classify, like how much, because the numbers that we're going to talk about are so small, and I was really worried that you were going to ask me to be able to and I'm really glad you.
Just did it for me.
Why how about that?
All right?
So let's talk about those incredibly terrifying potent toxins, shall we.
Let's do it.
So. Exotoxins are proteins that bacteria make that can disperse throughout our body and cause an effect. We've talked about them a lot on this podcast. The toxin in Cloustridium tetani is the causative agent of tetanus, not the bacteria themselves. This toxin, the tetanus toxin tetni. As a side note, it actually produces two different toxins. One is called tetno
lysin and the other tetno spasmin. Huh, techno lisin we don't really understand, at least from what I read, like maybe it helps establish an infection or something like that. But tetnospasmin is tetanus toxin.
So that's what we're going to talk about today.
So, this tetanus toxin is a neurotoxin just like bochulinum produced from Clostridium boculinum, and so it specifically binds to our nerves and affects our nervous system. Let's recap what we learned in our botulism episode, shall we. Then we can do some compare contrast my favorite.
I was so looking forward to this.
I know, I actually just took some notes, like I copypasted some notes from my any grade. It's a recap. Botulinum toxin blocks the release of acetylcholine at our peripheral nerve sine, if that sounds familiar. So what that results in is a flaccid paralysis, meaning a limp paralysis, because the signals from our brain don't ever actually make it all the way to our muscles, so your muscles are paralyzed in this flaccid limp state rather than a contracted state.
That happens when this botulinum toxin binds to our nerve cells at the neuromuscular junction, which is the junction between our nerves and the muscles that they innervate, and then blocks the release of the transmitters at that junction. Okay, Tetanus toxin does the exact same thing. It blocks the release of neurotransmitters in a synapse in a junction, but it does it in the inhibitory interneurons within our spinal cold word I'll explain, But the bottom line is that
tetanus toxin has the exact opposite clinical effect. It causes a spastic paralysis or muscles that are paralyzed in a rigid or contracted state. So let's go through the steps, shall we. Yeah, what happens in the case of tetanus toxin is it binds actually to our nerve cells in the same exact place as botulinum toxin. It binds to our nerve cells at the neuromuscular junction the NMJ, and it is internalized in those cells at the same place
as boculinum. But while boculinum toxin acts, it exerts its effects right there at the neuromuscular junction, blocking the release of acetylcholine. What tetanus toxin does instead of acting right where it enters our cells, is it actually travels retrograde along our nerve acxi allah like rabies virus.
Oh yeah, okay, that sounds familiar.
It travels all the way up our nerve axons like from the muscle in your jaw, for example, all the way up the nerve into our central nervous system where the nerve came from, and then it enters the space in between. It travels through that intersynaptic space inside our central nervous system and enters another set of neurons in our spinal cord, and there it blocks the release of
neurotransmitters the same way that bachulinum does. But it just so happens that the neurons that it enters in our spinal cord are the inhibitory neurons that primarily release neurotransmitters, whose primary job is to inhibit or block the firing of our motor neurons.
Okay, and so if they can't do their job, then all those motor neurons are going shoo shoo, shoo shoo, and then they're that's where you get the rigidity and spasms.
Exactly.
You just read my next line.
It's perfect. So exactly, if.
You can't inhibit the inhibitors, then your motor neurons are getting signals from your brain like rapid fire, which leads to this intense muscle rigidity, this spasm.
Okay, I have a question about wound location and course of disease and stuff like that. So, Yeah, the classic picture that I have of someone with tetanus, and I'll talk about this actual picture later on, is like someone who is completely Every single muscle is rigid.
Yeah.
Does that happen all the time? Does it happen in stages? For instance, if you have a wound on your hand, does that mean that the hand will become rigid? First?
Such a good question. In general, the course.
Of tetanus is the same always, and in general, the course is that the muscles that tend to be affected first are the facial nerves, so the muscles that are in your face, like your jaw and your neck and your head, and then it tends to travel kind of downward and then affect your trunk and.
Your limbs, et cetera.
Why is that?
That's a great question. I don't know, and I don't think that we fully know. So the nerve pathways to our facial muscles are a lot shorter, like the distance from the central nervous system to those muscles.
It is a lot shorter.
But it doesn't matter where you get exposed, if that makes sense, Say you get a wound on your foot. That tetanus toxin makes it in makes it to your central nervous system, and it seems to be that it's still the head and neck first and then the rest of the body after that. It is really interesting. I don't fully know why, so bizarre, I know it is.
It is really really interesting.
Huh.
Yeah.
And the same was true for botulism, where it often went from.
The head down right. Yeah.
Yeah, So that is kind of how this toxin works in general. The incubation period, the time from when you are first exposed to when these symptoms start, it's quite variable. Most sources on average say like three to fourteen days, some say seven to ten. It really can just depend on where you get exposed, whether you're talking about an infant versus an adult, things like that. And like I said,
the symptoms do tend to follow this general progression. So they often start with this neck stiffness, difficulty opening the mouth, and then that progresses to the classic name for tetanus, which is lockjaw, and that is from the spasm of the muscles of chewing, the muscles of the jaw that
spasm shut and then that continues to progress. There is a kind of characteristic facial posture called rhesus sardonicus, and it's this really awful facial expression that's a very pronounced closed mouth, teeth bared grimace because all of the muscles of your face are just rigidly contracted. At this point, the muscles of swallowing are very likely affected, so there's going to be some degree of dysphagia or difficulty swallowing.
And as it continues to progress, the muscles of the trunk can become affected, and this can lead to a rigid posturing that's known as episthotonis, which is again really really awful if you see pictures of it, but it's this very rigid arched back with head jutted back because all the muscles of your spine, like along your spine become contracted.
At this point.
Because of all of this contraction.
Of all of these muscles, the chest wall is.
Not very compliant. So that means that you can't breathe very well because the muscles between your ribs and your back they're kind of in spasm, so it can be really difficult to take in air.
Oh my goodness.
Yeah, there can also be kind of convulsions that happen similar to seizures that can happen on top of this generalized increase in muscle tone. So these spasms can look a lot like seizures. But if these spasms affect muscles like the LAYNX of the throat, then they can lead to airway obstruction, which can be life threatening. And one of the papers I wanted to read a quote from because I think it kind of sums up just how awful.
This really is. They said, after this.
Description of all of these symptoms, quote, consciousness is preserved, making tetanus a truly dreadful disease. Oh no, yeah, yeah, so it's a really horrible disease. Yeah, to say the least, to say the least, And you can imagine there are a lot of different ways that people can end up dying from tetanus. And just like with botulinum, while there is treatment for the effects of tetanus toxin, we have
tetanus IgG like antibody treatment. The treatment the main function is to bind and neutralize any of this toxin that hasn't yet bound into the central nervous system. But this can only do so much because once tetanus toxin is bound and internalized into our nerve cells. There's nothing that we can do about it. It's permanent until our nerves
essentially regenerate, which is what has to happen. Those nerve terminals have to actually, you know, remake themselves to be able to then re send the signals that they need to send to inhibit muscle contraction.
So if you don't get that early enough, it's.
Right, Yeah, Yeah, tetnus toxin doesn't kill any of the nerve cells, which I think is really important, but the neurons still do have to kind of remake those synapses in order to be able to work again properly. So you're not having to make entirely new nerves or anything like that, but you can't stop the effects of the toxin that have already been integrated into our cells.
Right.
So, on top of using treatments like the tetanus antibodies, you also have to treat the source of infection, so antibiotics or wound to breedment if there is some kind
of active wound that's still making more tetanus toxin. But really the most important thing in terms of treatment is supportive care and sedation, and one thing that's really interesting, although incredibly depressing still is that after the advent of mechanical ventilation, so like being able to intubate someone and breathe for them while this process is taking place in their body. This obviously helps keep people alive because they
usually would die from respiratory failure with tetanus. But since we have invented that, we have found that tetanus reaks
even more havoc on the body than we realized. While botch a lignum really only affects the motor nerves, because tetanus goes into our central nervous system, it causes a lot of autonomic instability as well that we didn't realize until we had mechanical ventilation to keep people alive long enough to see that process, if that makes sense, And so it can cause a lot of you know, blood pressure variation, It can cause heart rates to go really really high and then drop really really low because it
basically is blocking your autonomic nervous system from being able to send signals appropriately. So it's a very difficult disease to treat with supportive treatment. Though it's not impossible, it's absolutely possible, it's just really complicated. Jeez, and so because of that, mortality rates for people who are unvaccinated, who
have never been vaccinated can still vary really widely. One source that I read estimated anywhere from ten to sixty percent mortality for neonatal tetanus, and of course neonatal tetanus happens when babies are too young to be vaccinated, so in adults, the mortality rate can vary from eight to fifty percent I read, and it increases with age. So it's a very complicated disease to treat, but it is entirely preventable, which is amazing.
Yeah, truly, it really is.
We have an incredibly effective vaccine that has very long lasting immunity, and it is I think the cheapest vaccine to ever have been produced.
Is one thing that I read, which is, oh yeah, I love that.
And it's been around for a really long time. So that's the good news that we'll get to end this episode later with at least some happy news because of the vaccine. So that's the biology of Tetnus aarin.
It is just as maybe more horrifying than I anticipated it would be.
Yeah, I know it really, it really is. Yeah.
Yeah, I have a question for you erin, how on earth did this process evolve?
Oh?
Because okay, here's the thing, Arin, Yeah, yeah, you mentioned up at the top, just how potent this toxin is, right right, It is so potent. I didn't even know
this until researching. But getting infected with tetanus, getting infected with Clustridium tetani and then surviving an infection does not provide you with immunity because the tetanus toxin is so potent that just the tiniest amount of it causes incredible symptoms, but not enough to produce antibodies that we actually make enough of to then produce immunity, whereas we know that we produce immunity because we have a great vaccine.
And I mean, that's incredible.
And one source that I read said that the toxin may constitute five percent of the weight of this organism, so they're making a ton of this toxin.
It is so bizarre, and I'm not certain that I have a satisfying answer, but I want to like get into it. Okay, so let's take a quick break and then I'll get started.
I can't wait.
I found the history of tetanus to be so interesting for a number of reasons. First, it checks a lot of the boxes for a classic TPWKY episode. Tetanus is an infamous disease, there are plenty of ancient descriptions. Of course, war plays a role, gets a mention, and also we get to talk about the golden age of germ theory. Yeah, all that good stuff. Second, we've covered a couple of related pathogens before, as you mentioned, and so it was kind of fun to compare the evolutionary histories or human
histories of the especially with Claustridi and bochelinum. Yeah. And Third, there are parts of the history of tetanus that I feel provided an opportunity to think about how perceptions of a disease, especially who is most likely to get that disease, can really find their way into how these diseases are written about historically. And I think that's good to keep in mind as we try to read between the lines and understand how people were observing disease and why. So let's get started.
I love it.
Where did tetanus come from? Great question? I wish I had an answer. I can tell you where the word tetanus came from. Which is the Greek verb tanno, meaning to stretch. But from what I can tell, we don't really know where this pathogen originated in the world and when it's spread around the world, because it is like globally distributed. Did its global distribution predate wide scale travel by humans?
Maybe? Maybe?
Maybe it's a mysterious little little pathogen. We do know though, that humans have been exposed to tetanus for at least most, if not all, of written history, and probably have been for all of you know, all of our prehistory as well. But we'll get to that in a second, because first I want to talk about some aspects of tetanus ecology and evolution. So, like I said, we don't know where geographically tetanus emerged, but we do know that it doesn't
really seem to change all that much. Its genome is highly conserved, which is actually, I think something that we've seen for a few other spore formers, which I think is cool.
Yeah.
Anthrax, right, Anthrax especially, Yeah, bacheline Clustridium botulinum is less stable, but anyway, the plasmid carrying the tetanus toxin gene is more variable, but the gene itself is not is very stable. Yeah, Yeah, it doesn't make sense.
That's so interesting though, because like with botulism, there's more than a few different types of the toxin, but with tetanus, it's really just tetnus toxin.
Yeah, And with the botulinum toxin, it's found in many different strains of Clostridium, whereas, yeah, the tetanus neurotoxin only in clusterdim tetani.
Yeah.
And like you said, these two neurotoxins are structurally and functionally similar, but they seem to have followed different evolutionary pathways. And I think it's really cool to look at the ecology of these bacteria to see like maybe why that might be, or why these different characteristics of these two bacterial species, why they contribute to the patterns that we
see in disease and outbreaks and sporadic cases stuff like that. So, both Claustridium tetani and Clustridium bochulinum are anaerobic soil dwelling and they produce this deadly and potent neurotoxin. But why why do they do this? Why are you the way you are with the title of our bochulism episode, because we were like why why why? And we talked about how Claustridium botulinum will be picked up by a dabbling duck or something, and then the toxin will kill the bird.
That carcass becomes a great anaerobic replicating ground for the bacteria and also a great source of environmental contamination as other animals either nibble on the corpse or around the corpse or in like you know, the more dabbling ducks than the soil whatever, right, I remember that a lot. Yeah, it was a very cool thing to visual like, oh, that's why this exists. And so having this deadly neurotoxin
is key to the life cycle of Claustridium boculinum. By killing its host, it can now contaminate a big chunk of the environment and spread to other hosts. And the tetanus toxin isn't too much different. Really, it's a potent neurotoxin that can kill its host. But one key difference is that the boculinum neurotoxin can survive ingestion, and that's like how it creates disease, while the tetanus neurotoxin cannot.
And this difference is why we see outbreaks in botulism in nature and in food poisoning outbreaks, whereas we mostly see isolated, sporadic cases in Tetanus.
Whoa, uh huh, so it makes even less sense.
It makes even less sense, but it also does it does make sense to a degree, right, So this is likely a costly toxin to.
Make, uh huh.
It has to help the bacteria. It has to help Clusterium tetani to survive, to be transmitted, to help it complete its life cycle in some way. I mean, these are soil dwelling microbes, so they don't necessarily need hosts to live to proliferate. But it would be great if a host came along with a little cut on their foot and picked up some Tetanus spores tetani spores, and then that host, after it died, became another great breeding
ground for more contamination. So it might be a combination of the fact that like this is a very useful tool for the bacteria, and also they're spore formers. Yeah, so I don't know.
The whole gut thing. That's just so interesting. I feel like that was such a big part of the bochu Linum story, where you know, then you eat it and then you continue it, et cetera.
And so to know that that's not part.
Of the story here is really interesting.
Yeah. I mean I feel like the story makes sense still, like the toxin plays an important role, but it isn't as satisfying. Yeah, nearly as satisfying, right, And maybe that's the lesson is that, like evolution doesn't always tell us satisfying, it doesn't always make sense. Yeah, it doesn't always make sense. It doesn't follow logic, it's just just is what it is. Sometimes.
That being said, if anyone listening is like, wait, no, I know why this happens, or you have a paper where you can show me exactly, because I spent hours and hours on Google scholar trying to find out the elutionary ecology of this neurotoxin, please shoot us an email. Yeah, I would love to read it.
We have so many more questions.
Yeah. But the good thing about this relatively non exciting or maybe not satisfying evolutionary history and the super stable genome of cluster name tetane is that this means that the vaccine is very widely and highly effective and we don't have to worry about the emergence of strains that the vaccine doesn't protect you against, which is good because
this disease is horrible, absolutely horrible. Tetanus causes this dramatic, visually dramatic and deadly infection, and so it should come as no surprise that it has been mentioned in so many ancient texts.
Like all of them, all of them.
It's really back to back classic TPWKY with trachoma and chlamydia, last episode and now this. So we're going to run through these ancient medical texts again protet us. So we've got the edwins Smith Surgical Papyrus written around fifteen hundred BCE that mentions it. The ancient Indian physician Sushruda from around six hundred BCE made a possible reference to it.
Early Chinese medical texts from around four hundred to two hundred BCE described it, and of course we've got the Hippocratic texts from around the four hundreds BCE yep, yep. Hippocrates and other contributors to the text. Because it wasn't just Hipocrates actually wrote quite extensively about tetanus, both the local and systemic forms, and included some very colorful descriptions
of the disease. Quote a man who was struck from behind, by a sharp dart a little below the neck had a wound which did not look serious because it did not go deep. But sometime later, when the point had been extracted, the patient was seized with backward bending convulsions like those of Opisthetonis. His jaws were locked, and any liquid that he attempted to swallow was returned through his nostril. He died on the second day.
Oh goodness, h h.
And if you're looking for treatments, the Hippocratic texts have got you covered. Fatbird soup, vapor baths, cold water baths, pepper, hell bore and of course you have to throw in some blood letting, of course, of course. And over the next hundreds of years nothing really changed for tetanus. Seven hundred years after the Hippocratic texts, Aretaeus of Cappadocia added his thoughts on the disease. And you can really tell how badly he felt as a physician, completely unable to
help his patients. Quote and inhuman calamity, an incredible sight, a spectacle, painful even to the beholder, an incurable malady. He listed tree after treatment, frankincense, the hair of a polly, fleabane, turpentine, et cetera. And this variety just kind of goes to show again that nothing seemed to help. Classic tetanus like what you would see in an adult human wasn't the
only thing that these ancient physicians noticed. There was also mentions of equine tetanus and neonatal tetanus which was sometimes called trismus and not necessarily recognized to be the same thing as tetanus for hundreds of years. Interesting from these ancient texts, I'm gonna skip way ahead until the eighteen hundreds, kind of like I did also for chlamydia slash trachoma, because not very much happened in terms of tetanus until
that time. I mean, yeah, sure, there were additional descriptions of it and case reports and shifting hypotheses as to what caused the disease, but overall, the way that it was characterized in the Hippocratic texts didn't change much. A tiny injury, like one instance I read from the bite of a tame sparrow in the seventeen hundreds. WHOA, I know, there's a lot to take in in that sense, Yeah.
There really is.
But this tiny injury could lead to a horrifically painful infection that was ultimately fatal a lot of the time, with no reliable, effective treatments. Even in eighteen ninety two, when doctors had slightly better tools to help with feeding and muscle relaxation, the mortality rate was eighty percent after four days.
Yeah.
For much of human history, tetanus remained a sporadic disease except in a few instances or populations, and one of these was, of course, soldiers or during times of war, for all the usual reasons of basically not having access to sanitation, an increase in both small and large wounds, etc. There's a famous painting this is the picture of Tetanus I met that you've probably seen, depicting a soldier in
a violent, rigid spasm from tetanus infection. And I'm gonna post this probably for like the announcement release post for this episode on our social media. That was painted in eighteen o nine by surgeon and artist Sir Charles Bell. It's titled Tetanus following Gunshot Wounds and guess where the soldier got those gunshot wounds during the Napoleonic Wars. I mean again, Napoleon. It's just so many parallels. Yeah, specifically
if you're interested in the Battle of Karuna. I distinctly remember seeing that painting for the first time in my high school biology textbook or something, and being so fascinated but also terrified by it. Yeah, Like I couldn't believe it was a real thing.
Yeah.
Yeah. And soldiers, of course, weren't the only ones that were disproportionately affected by this pathogen. In the mid eighteen hundreds, several doctors in the American South became interested in what they called trismus nessentium, which would later be called neonatal tetanus, and they remarked that it was quote no uncommon disease among infants born to enslaved people in the South. I want to take a minute to talk about neonatal tetanus in the American South before the Civil War because I
think it's important for several reasons. First, it gives us an opportunity to see how much the established knowledge about a disease is so dependent on who's looking and especially whom they're looking at. Second, neonatal tetanus is I think a really clear example of how differently medicine was practiced, how medical stats were collected and whom those stats represent
between the American North and the Confederate South. And third, I think it highlights the beginning of a shift in medicine overall, from heroic medicine, so called heroic medicine, to preventive care.
I love it, okay.
So, neonatal tetanus, as you described, Aaron, and as our first hand account so vividly and horribly described, is when the umbilical stump gets infected with the tetanus pathogen. It's tightly linked to access to sanitation and hygiene practices following delivery, and it is like adult tetanus, incredibly horrific and deadly. Those are not even adequate adjectives and inhuman calamity. Yeah,
maybe we could borrow that phrase from airtase. Before the US Civil War, enslavers would frequently employ doctors to monitor the health of enslaved people, not out of the goodness of their hearts, of course, but to protect their financial interests. These Southern doctors began to notice high rates of neonatal tetanus in the infants born to enslaved people. And when
I say high rates, I mean very high. Some doctors estimated that up to two thirds of the deaths among these infants were due to neonatal tetanus.
Oh Man.
Yeah. Because of this, neonatal tetanus was labeled by many doctors, especially those in the North, as a disease of the South, or more specifically, a disease of enslaved black people. But was it especially so, We don't really have any good way of knowing, considering that statistics weren't widely used at the time, but it almost certainly wasn't. There may have been a few things that contributed to the high rates
observed by southern doctors. For instance, there were some post natal practices, such as using cow dung or charcoal to wrap the cut of the biblical cord, that could have increased exposure, and some of those practices are still used today in various places, and they are associated with higher rates of neonatal tetanus. But it was also probably a
matter of visibility. Neonatal tetanus was certainly present in the North, but northern doctors probably didn't see it as much because, unlike the Southern doctors who wrote about neonatal tetanus, Northern doctors didn't treat nearly as many people living in conditions that put them at risk for the infection. Mostly they would work at hospitals, and so if someone came into
the hospital maybe then they would see them. But they didn't travel as widely and to his varied urban and more rural centers the way that Southern doctors could do people who were living with a lack of access to sanitation, people living in poverty, et cetera. Northern doctors weren't getting
paid to treat these people, unlike Southern doctors. In addition, Southern doctors, especially those that were employed by enslavers, were much more likely to encounter cases of neonatal tetanus than their northern counterparts, since it was midwives that mostly attended
the birthing and postnatal care in the North. And another big difference was that the Southern doctors tended to keep more detailed records of the people they treated, not because they were inherently more meticulous, but again because it was more a matter of business and economics, and slavers wanted to know which diseases were contributing to the most death and disability or in their eyes, lost profit, and this informed to some degree, which diseases were given priority for study.
Neonatal tetanus garnered a substantial amount of interest in the mid eighteen hundreds in the southern US because it contributed so highly to infant mortality among babies born to enslaved people, and several doctors started to try to understand why that was doctor Mary and Simms, infamous so called father of modern gynecology. I can't resist like an opportunity to diss Mary and Sims, or at least call him out for being someone who absolutely tortured so many an untold number
of enslaved black women. Yeah. Mary and Simms was one of the doctors who tried to say, oh, I know the cause of neonatal tetanus, and he thought it had to do with the formation of the skull. He said, you should put the baby. People were obsessed with skull shape for decades too long. He said, you know, if you put the baby in a crib, you should make sure there are lots of pillows around the baby in position the baby very carefully so that the skull could grow properly.
Oh dear, oh no.
And one of his horrifying treatments involved drilling a hole in the baby's skull in all no, yeah, and there was no evidence, of course, to support his hypotheses, and a couple of other doctors fortunately were around to pick apart his arguments. William Baldwin, a physician who graduated med school Transylvania University in Lexington, Kentucky, at age nineteen.
Wow.
Yeah, I mean it was the eighteen fifties, eighteen forties. He wrote that Simms was wrong and that the disease was more common among enslaved people, not because of how they laid an infant in a crib, but because of
living conditions and lack of access to sanitation. He didn't agree with Sims's and others claims that there was a racial disposition to disease, but instead thought it was living in an environment that led to greater exposure, which is pretty like incredible to hear, or like more forward thinking than I anticipated, considering this was the eighteen fifties.
But I feel like that was we you know, malaria, et cetera. Like, yeah, people knew of this environmental yeah, miasma.
Yeah exactly. Yeah, So I think that was definitely part of it. But I also think he might have been ahead of his time with this next quote because he suggested that it was quote a grain of dust or sand, or other particle of foreign substance, however small may be lodged in the delicate granulations of the umbilicus just after the detachment of the cord.
There you go.
So there it's I mean, that's not that's not wrong.
Really, no, that's exactly exactly what it is.
Is.
I found that fascinating, and Baldwin wasn't alone. Another physician named John M. Watson from Tennessee took up the charge and further dismissed Sims in eighteen fifty nine, like kind
of harshly and directly. I appreciated it. He too, believed that it was irritation of the wound and suggested that instead of Sims's barbaric sculdrilling practice, people should try for simply cleaning the wound, having a more sanitary environment overall, basically practicing preventative medicine, which was not in fashion at the time. Instead, doctors tended to practice heroic medicine, which I talked a bit about in the antibiotics episode. Essentially,
it was a way of practicing medicine through intervention. Only your patient came in sick and you thought, Okay, how can I stop this? You made your patient sweat, purge, bleed, get a fever, be freezing cold, whatever to shock their body back into balance. Medicine was about activity and treatment rather than prevention. The concept of cleanliness and sanitation as a method of disease prevention was a fairly new one
in some degree. Yes, there was a miasma theory, but in terms of like Semulweis and Lister, you know, like all of those sanitation right, it was starting to come around. But most doctors thought that cleaning a wound that doesn't make you a doctor. Sawing off a gangrenus limb in
five seconds that Shir did. But the tide was turning from heroic medicine to preventive medicine, partially because of germ theory, and also partially because of people like Lister and Semblevice, and also partially because the emerging field of epidemiology allowed people to see wide scale patterns of disease and how interventions such as hand washing or ventilation affected the spread of disease. But the origin story of epidemiology is more complex than the classic story of John Snow and his
collar maps. One of my favorite things about this podcast is that we are wrong sometimes and we read more like we get to learn new stuff all of the time, every day, every day, and that makes us I think, both look back and go, oh, my goodness, I didn't know that I said that wrong. I didn't understand the context for this, And part of me is like, oh, I wish I could go back in time, But another part really likes to observe the fact that we are
learning and growing. Yeah, and this is one of those instances. Epidemiology didn't come about because of John Snow and his cholera maps. Of course they played a role, but it's more complicated story than that. So we've talked about how tropical medicine as a field was largely created during the huge period of colonialism in the late eighteen hundreds right
to help the imperialist to quote conquer an area. In a similar way, epidemiology developed out of colonialism, out of slavery, out of war, when doctors were incentivized to study and treat populations rather than individuals that they may not have otherwise.
These circumstances provided doctors the opportunity to see disease on a scale that they hadn't before moving through army hospitals, prison camps, ships, etc. You and I learned the story of epidemiology, and we've told the story of epidemiology as one of the early epidemiologists of John Snow and the
Broad Street Pump. But you and I, as well as the Royal we those who are also in the field of public health, we haven't fully or ever acknowledged the people who made up those maps, who are mentioned in those early studies of the spread of the disease simply as cases. And many of these people were disenfranchised. They
had no consent or knowledge of their involvement. And this theme, this new exploration of the origins of epidemiology, is the subject of next week's Bonus episode, as well as the topic of a new book by doctor Jim downs who is my expert guest for next week.
I cannot wait.
I am thrilled to be chatting with doctor Downes, who was a professor of history at Gettysburg College, about his latest book called Maladies of Empire, How colonialism, slavery and war transformed medicine. I am super excited for this conversation, So mark your calendars.
Oh, I can't wait.
Okay, But for now, let's get back to the history of tetanus. Moving into the second half of the eighteen hundreds, tetanus was still very much present, but it would soon meet its match, first in the form of antitoxin and
then in the form of a vaccine. In eighteen eighty four, Carlo and Ratone took puss from the skin lesion of an infected human's face who later died of tetanus, and injected it into a rabbit, which began showing signs of tetanus, confirming the presence of the pathogen in that lesion, and so like the story of the microbiology of tetanus began. Later that same year, a guy named Arthur Nikolaier injected
soil samples into animals who also developed tetanus symptoms. He isolated a rod shaped bacillus from these animals and hypothesized that the bacteria produced a toxin resembling strychnine in its action, which we should add to our future topics.
It's on our list.
Okay, good, But he didn't isolate the organism in pure culture. That would be done by shibasaburo quitisato in eighteen eighty nine from a fatal case of a soldier in Berlin. Does his names sound familiar to you a little bit? Yeah, diphtheria episode theory makes sense. So Key Desado and Emil von Behring worked closely together on a dipia anti toxin. Von Behring got the first Nobel Prize in Medicine in nineteen oh one for the work that they did, and
Key Desato did not. Anyway. With this pure culture of Clastridium tetani, Key Desato was able to see that it was indeed a toxin produced by the bacteria that caused some of the symptoms, which spurred him on to look for other toxin producing bacteria, including the one that causes diphtheria. Key Desato and von Bhing's work on producing anti tooxin for tetanus and diphtheria is I mean essentially that started the field of serum therapy. Wow, and this was great.
Having an anti tooxin was revolutionary in a number of ways, but it wasn't perfect.
Right.
You have to administer it early on for it to be effective, and in the case of tetanus, you had to keep the wound clean. When both of those things were pretty difficult. If you were like a soldier at high exposure risk and we have some numbers to back that up too. Dear, it's not that bad. I mean, it's bad to begin with, and then it gets better.
Okay.
In eighteen oh eight, so pre germ theory, pre tetanus, antiitoxin, pre vaccine, the rate of tetanus was twelve point five per one thousand in soldiers and the author of this didn't say which soldiers and where, But in the first months of World War One that dropped to eight per
one thousand wounded. Still high, yeah, and then as wound care and anti tooxin delivery improved, it dropped further to one point five per one thousand, and by the time the US entered the war it was down two point sixteen per one thousand.
Wow. Okay, great, that's pretty cool.
Yeah. Interestingly, tidbit here, where you were fighting like physically played a role in your tetanus risk. Fields that had been fertilized with manure over long periods of time had more tetanis and led to the misconception that horses were the reservoirs for the bacteria. Interesting, but really it can be carried, like you said, in all kinds of animals and humans like rats, chickens, cows, horses, I'm sure many
many other animals. Yeah, but further declines in tetanis were in the future, and not just for soldiers but for everyone. The tetanus vaccine was developed in nineteen twenty four by Gaston Ramon, and widespread vaccination meant a drastic drop in tetanus wherever the vaccine was available. Soldiers in World War I TiO you experienced tetanus at a rate of point zero four per one thousand.
Wow.
Yeah, and I think there was I saw a stat that like, no one who was vaccinated got tetanus.
Wow.
And neonatal tetanus rates also dropped as researchers realized that vaccination during pregnancy offered some protection to the newborn.
That's the most amazing and my favorite thing.
Yes, it's so important, It is so important. And these drops in tetanus continued throughout the twentieth century and into the twenty first, but not I'm guessing as much as they should have. So yeah, this is kind of just like a quick little scoot through the twentieth century on my end, But I'm curious to know erin where we stand today when it comes to tetanus.
I can't wait to tell you right after this break. So in the US, we'll start here. From two thousand and nine to twenty seventeen, only two hundred and sixty four cases and nineteen deaths were.
Reported from Tennis.
Wow, I know that's pretty major.
Yeah, across the globe.
While the decrease in cases overall is still very impressive, unsurprisingly, we still do have a ways to go. The World Health Organization estimated in twenty eighteen, which is the latest data that they have as of today, that in twenty eighteen, twenty five thousand newborns died from neonatal tetanus twenty five
thousand worldwide. What and as depressing as that number is, that is an eighty eight percent reduction from cases in the year two thousand and a ninety six percent reduction from cases in the nineteen eighties.
Oh my goodness, I know I had no idea just how widespread tetanus was even as recently as the nineteen nineties.
For example, a paper from two thousand and one estimated eight hundred thousand to one million deaths worldwide from tetanus every year, including over half a million from neonatal tetnis. That's two thousand and one paper estimated, and another paper from two thousand and seven, which was talking about data from the nineties, estimated that up to five percent of maternal mortality was due to tetanus and fourteen percent of neonatal mortality was due to tetanus. The scale of this disease.
I had no idea.
I cannot I mean, I can't even formulate I know a sentence.
I know.
I feel very much the same.
So we have come an incredibly long way. The World Health Organization, who tracks data on vaccinations as well as cases, estimated that worldwide in twenty nineteen, eighty six percent of children were covered by DTP three, which is the three doses of vaccine in the first year of life. Okay, so eighty six percent of children. And I want to take a minute to emphasize here just how preventable this
disease really is. Vaccination generally starts at two months old, and it's a series of three shots initially, and then a booster around kindergarten, and then boosters every ten years or so to maintain immunity. But like you mentioned Aaron, vaccination during pregnancy also confers protection against neonatal tetanus, and it's been estimated vaccination during pregnancy to reduce mortality from neonatal tetanus by ninety four percent.
That's incredible, it's amazing.
So we have the capacity to protect people from this disease. But a really important thing is that this is a continual struggle, or at least it's a continual process, because this is not a human specific disease that, for example, like smallpox, if you can interrupt the chain of transmission between humans for long enough, you can eliminate the disease. You can't do that with this because it's environmental pathogen that has always, like you said, Aaron, and likely always
will be in our environment. So it is a process of continual protection through these incredibly efficacious, incredibly safe vaccines. And as we have seen, for example in the COVID pandemic, things that drastically alter the global landscape pose really big challenges to vaccination. So you know how I said, in twenty nineteen, eighty six percent of children were covered by DPT three, while in twenty twenty that number had gone
down to eighty three percent. So an estimated twenty three million children under the age of one did not receive their basic vaccines in twenty twenty, and the number of completely unvaccinated children GLOW increased by nearly three point four million in that year alone.
So we're not done yet.
No, we're never done.
We're never But I want to end this episode on some really high notes and also just like keep ragging about the tetnus vaccine. It's fantastic, yeah, and really the tetanus toxoid. So the tetanus vaccine is a toxoid vaccine. A toxoid is just an inactivated toxin, right, and the toxin is a protein, so it's easy, it's cheap to produce.
And this tetanus toxoid that is easy to produce, that is cheap, that is very immunogenic to our immune system, is used to make a whole bunch of other vaccines, like our new Macocco vaccine, our Meninjocco vaccine hib All of these vaccines are made by conjugating or combining things like sugars, polysaccharides to the tetanus toxoid protein to induce a better protective immunity against these other diseases as well.
That is just so cool, isn't it beautiful?
And on top of that, the other reason that tetnus toxoid makes for such a good vaccine is that it's really shelf stable. It doesn't have to be frozen or refrigerated. It's stable at room temperature for months. So it's really transportable, even to remote areas that don't have access to refrigeration.
That's fantastic.
There's more. Aaron.
Literally, not ten minutes before we were going to record, I was eating dinner and I was googling because I remember a very long time ago you were like, hey, did you see this news article about something that we were going to record? And never had it crossed my mind to google news articles about whatever we're talking about.
And ever since then, and that was a long time ago. Now, I always like, the last thing that I do before I wrap up my research is I google tetanus and I press the news button on Google.
Oh, I love it.
So I did that while I was eating dinner, right before we recorded, and lo and behold, this paper was published one week ago. A group out of Albert Einstein College of Medicine published a study in Science Translational Medicine that used a combination of Listeria monocytogenies, which is a bacteria that we'll cover eventually, we haven't, right, No, okay, So a combination of this bacteria and tetanus toxoid to treat pancreatic cancer.
Incredible, I know.
Essentially, briefly, they injected mice that had pancreatic cancer that had also been vaccinated for tetanus like before they got cancer with a listeria that had been engineered to have the tetanus toxoid protein. And for whatever fascinating reason has to do with listeria, it preferentially congregates in these cancer cells, I think because the immune system wipes it out in
other places. And then the mouse's immune system has a bunch of antibodies that recognize the tetanus toxoid because they were vaccinated, and so boom they end up attacking the cancer that has these bacteria that have this toxoid protein.
What That's amazing And also, first of all, that's fantastic news for pancreatic cancer, I know, but secondly, I feel like that could be a model for many other types of cancer treating exactly. Yeah, Oh so cool.
I know, these mice had their pancreatic tumors decrease in size by eighty percent and metastases decreased by eighty seven percent, and they lived forty percent longer than untreated mice.
But it's a mice, but like, this is a big deal.
It's a big deal.
So that's a high note to end on and I will absolutely link that paper.
Cool.
Yeah, so tetanus is a horrible disease, but we have a vaccine and it is awesome.
I love that.
Yeah, yeah, any sources, sources.
I have a large number of sources for this episode. I'm going to shout out three right now and put the rest on our website. One is called No Uncommon Disease by Sally McMillan. Another is called an Essay on the History of Lockjaw by William Shalian, and the last one i'll shout out is called the population structure sure of Claustridium tetani deduced from its pan genome, and that is by Chapaton Montes at All from twenty nineteen.
I had just a few papers for this episode. I really enjoyed. Actually, a nineteen ninety four paper called the
Mechanism of Action of Tetanus and Botulinum neurotoxins. It was pretty thorough, and then a twenty nineteen Botulinum and Tetanus Neurotoxins kind of an update, a few other papers on the epidemiology as well as links to the World Health Organization and the CDC surveillance, and then that awesome paper that just came out in March of twenty twenty two was titled Listeria delivers tetanus toxoid protein to pancreatic tumors and induces cancer cell death in mice. So it really
tells you the whole study. And we'll post the list of these sources and every source from every one of our episodes on our website, This podcast will kill You dot com.
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