Speaker 1: Hey, everyone, We're including a content morning for the first
Speaker 1: hand account that we're about to read, which includes a
Speaker 1: description of the death of an infant. To skip this
Speaker 1: jump ahead about three minutes.
Speaker 2: Missus Cyril Orchard Street, aged twenty four, was delivered of
Speaker 2: her third child on Friday morning, September tewond eighteen fifty nine.
Speaker 2: It was a male child, fine and apparently healthy in
Speaker 2: every respect. From Friday till Wednesday, all was well. The
Speaker 2: cord separated on Tuesday, the fifth day. On Wednesday, the
Speaker 2: child was restless, cried and kicked. On Thursday, the mother
Speaker 2: reported that he cried all day, could not open his mouth,
Speaker 2: could not suck, and frequently stretched, and was stiff. The
Speaker 2: next day, Friday, I saw him every few minutes. He
Speaker 2: appeared as if struck by an electric shock. Every muscle
Speaker 2: was thrown into distorted action. Will not attempt to describe
Speaker 2: this drawing tells the wrinkled forehead, the elevated brow, the
Speaker 2: closed eye, the dilated nostril, the rigid massiter, the fixed jaw,
Speaker 2: the closed mouth, the corrugated lips, the bubbling saliva, the
Speaker 2: retracted head, the shortened neck, the starting cervical muscles, the
Speaker 2: turgid veins, the arched spine, the raised chest, the troubled breathing,
Speaker 2: the catching diaphragm, the heaving abdomen, the separated arm, the
Speaker 2: squared elbow, the bent wrist, the clenched fingers, the incurved thumb,
Speaker 2: the extended and separated legs, the bent down toes, the
Speaker 2: livid surface, the whole figure rigid as wood. A pitiful sight,
Speaker 2: the paroxysm was renewed by a slight noise, the gentlest touch,
Speaker 2: A placid interval of a few minutes succeeded, and then
Speaker 2: another fit followed. On examining the child, the umbilicus was
Speaker 2: seen prominent, at least half an inch long, red and
Speaker 2: showing an unhealthy separating surface. The umbilicus continued to discharge
Speaker 2: emaciation rapidly advanced. The skin assumed a brownish hue and
Speaker 2: hung in shriveled folds of a leathery texture. Peace and
Speaker 2: Pang pursued their sickening interchange. The child gradually became more feeble,
Speaker 2: and on the tenth day of the disease and the
Speaker 2: fifteenth of his existence, he sank by degrees.
Speaker 3: Exhausted, it was really difficult to read, absolutely horrible.
Speaker 1: Yeah, and thank goodness, there's a vaccine.
Speaker 3: Yeah.
Speaker 2: That was from an eighteen sixty case description of tetanus
Speaker 2: in Phantom a ka neonatal tetanus or tet Yep.
Speaker 1: Hi, I'm Aaron.
Speaker 2: Welsh and I'm Aaron Almon Updike.
Speaker 1: And this is this podcast will kill You.
Speaker 2: And I'm sure you all know by now the subject
Speaker 2: of today's episode.
Speaker 1: Yeah, tetanus. It's a vaccine preventable disease that we haven't
Speaker 1: covered yet, which is exciting, yep.
Speaker 2: And it's obviously going to be difficult at times because
Speaker 2: it's a really truly horrible disease.
Speaker 1: I mean, absolutely horrific, devastating, awful.
Speaker 4: Yeah.
Speaker 2: Yeah, But there's going to be a lot of very
Speaker 2: interesting biology. I know, there's going to be some fascinating
Speaker 2: history that I can't wait.
Speaker 4: To learn about.
Speaker 2: And I have some thrilling things to talk about in
Speaker 2: the current events section, Like I am really excited.
Speaker 1: Yeah, ooh, I'm so intrigued.
Speaker 2: So shall we, you know, get started on the important things?
Speaker 1: Of course of course we should. What time is it?
Speaker 4: Quarantiny time it is?
Speaker 1: And this week we are drinking the Rusty Nail, which
Speaker 1: just so happens to be an actual cocktail.
Speaker 4: It's a real drink.
Speaker 1: It is. It has Scotch and RAMBOUI and I think
Speaker 1: that's it.
Speaker 2: And we're gonna find a way to make the non
Speaker 2: alcoholic version our Plasi Brita.
Speaker 1: Yeah, it's gonna be an interesting one to make a
Speaker 1: placy berita for. But you know, I think that it
Speaker 1: might not bear too much resemblance to a Scotch and
Speaker 1: a Scotch based liqueur. But I think that's okay as
Speaker 1: long as it's delicious, right, I trust in you erin okay,
Speaker 1: thank you, And we'll post the full recipe for this
Speaker 1: quarantiny and non alcoholic plasy burrita on our website This
Speaker 1: podcast will kill You dot com.
Speaker 2: On our website This podcast will kill You dot Com,
Speaker 2: you can find all of the things. You can find
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Speaker 2: You can find our Patreon. You can find really there's
Speaker 2: just so much there.
Speaker 1: Yeah, you did a great job. There's a lot there.
Speaker 1: Go check it out. Can we dive.
Speaker 2: Into us Yes, I think that we ought to right
Speaker 2: after this break. So today we're talking about another clusterdium species,
Speaker 2: Clusterdium tetani. We've covered this genus before, of course in
Speaker 2: our botulism episode, and then I mentioned it again in
Speaker 2: our sea Diiff episode, although Seaediff was reclassified as clusterritioides.
Speaker 2: But anyways, today it's clus Tritium. Clusterridium tetani is an
Speaker 2: incredibly widespread and hardy little bacterium. It's a rod shaped
Speaker 2: gram positive spore forming bacterium that when it's making its
Speaker 2: little spores, if you look at it under a microscope,
Speaker 2: looks like a little match stick or like a tennis racket.
Speaker 4: It's kind of cute, oh.
Speaker 2: Because it makes it a little spore at the end.
Speaker 2: It's like real pos interesting uh huh. And like its cousin,
Speaker 2: Clusterridium botulinum, this is an anaerobic bacterium, which means it
Speaker 2: likes to grow without any oxygen. But because it's a
Speaker 2: spore former, these spores are incredibly hardy. They're very resistant
Speaker 2: to heat, to to antiseptics to oxygen, and so this
Speaker 2: is a bacterium that persists in the environment across the globe.
Speaker 2: It makes its home in the soil, but Clusterridium tetni
Speaker 2: can also thrive in the intestines of various animals, including humans.
Speaker 1: I found that so interesting. And what is it doing there? Like,
Speaker 1: is it just a part of your gut microbiota, Are
Speaker 1: there any sort of negative effects or is it just
Speaker 1: really hanging out?
Speaker 2: As far as I know, at least they just hang out.
Speaker 2: I'll be honest. I didn't do a lot of digging
Speaker 2: into what they're doing in our guts. Okay, yeah, But
Speaker 2: as this is a soil bacterium, and as this is
Speaker 2: this podcast will kill you, and we're talking about the
Speaker 2: disease caused by Clusterdium tetne. People are exposed through the
Speaker 2: soil kind of in general. Usually exposure to this bacterium
Speaker 2: tends to be from wounds, especially deep wounds or puncture
Speaker 2: wounds that come into contact with anything contaminated with this bacterium,
Speaker 2: which again can live almost anywhere. So this can be
Speaker 2: anything from rusty nails to fence posts, thorns from a tree,
Speaker 2: even potentially bites if they are contaminated really any kind
Speaker 2: of deep wound, because those kind of wounds have pretty
Speaker 2: limited exposure to air, which means limited exposure to oxygen,
Speaker 2: and so as tissue death occurs deep within that wound,
Speaker 2: the environment can become very anoxic, which can allow for
Speaker 2: tetni spores that are present in the soil that contaminate
Speaker 2: that wound to germinate and grow.
Speaker 1: Interesting. Yeah, I have a really dumb question, okay. Anaerobic
Speaker 1: environment meaning there's no oxygen, there's oxygen carried by your
Speaker 1: blood if you're bleeding, is that an anaerobic environment.
Speaker 4: It's a great question.
Speaker 2: So no, if you have active blood flow to an area,
Speaker 2: then that tissue is not going to become very anoxic.
Speaker 2: What can happen in deep puncture wounds is that the
Speaker 2: tissue can die like deep within, and so once you
Speaker 2: have dead tissue, that tissue is not being supplied by
Speaker 2: your blood supply very well. So that is why it
Speaker 2: can become anoxic.
Speaker 4: But that's a really good question. It's not a dumb
Speaker 4: question at all.
Speaker 1: That is okay, Yeah, I'm fascinated.
Speaker 2: Yeah, that's why it's in theory. Any wound can become
Speaker 2: contaminated with Clostridium tetani but not every wound is going
Speaker 2: to be as susceptible to actually harboring a active tetanus
Speaker 2: generating infection, if that makes sense. Now, I'll talk a
Speaker 2: lot in this episode about neonatal tetanus, and the first
Speaker 2: hand account that you heard was a description of neonatal tetanus.
Speaker 2: This is a it's the same as regular tetanus in
Speaker 2: kind of what it does to the body, but neonatal
Speaker 2: tetanus is often classified as specific because it happens with
Speaker 2: contamination of the umbilical stump, so the umbilical.
Speaker 4: Cord that's left when a baby is born.
Speaker 2: That's just kind of an open area that can very
Speaker 2: easily become contaminated, and the base of that is dead
Speaker 2: and dying tissue, because that's what's normally supposed to happen
Speaker 2: with an umbilical cord, and so that's why it's a
Speaker 2: place that's very easily and then of course babies have
Speaker 2: almost no immune systems, so that.
Speaker 1: Helps as well, right, right, So that's kind of.
Speaker 4: How we get exposed.
Speaker 2: And just like with Cloustridium botulinum and Clausterdioides, diffcill the
Speaker 2: story here is not the bacterium itself. It's also not
Speaker 2: the spores of this bacterium. The story of tetanus is
Speaker 2: the story of the toxins that this newly germinated bacterium
Speaker 2: can release within our body.
Speaker 4: So let's talk about them.
Speaker 1: Yeah, these toxins are Can I read a quote real quick? Actually?
Speaker 1: Can I inse? Okay? Please do? I was hoping I
Speaker 1: was going to be able to use it somewhere. Quote.
Speaker 1: An amount of tetanus batchulinus or dysentery toxin, weighing no
Speaker 1: more than the ink in the period at the end
Speaker 1: of the sentence, presumably times New Roman twelve, would be
Speaker 1: enough to kill thirty grown people. An ounce could kill
Speaker 1: thirty million tons of living matter. Half a pound would
Speaker 1: be more than enough to destroy the entire human population
Speaker 1: of the world. I'm not sure when this was written,
Speaker 1: but I think it probably would still be sufficient.
Speaker 2: I love Okay, I feel like I remember you reading
Speaker 2: that quote in our botulism episode.
Speaker 1: I feel like I did too. Whoopsie, I'm pretty sure
Speaker 1: you did.
Speaker 4: No, it's not a whoopsie.
Speaker 2: I'm really glad that you said that again, because I
Speaker 2: was trying to classify, like how much, because the numbers
Speaker 2: that we're going to talk about are so small, and
Speaker 2: I was really worried that you were going to ask
Speaker 2: me to be able to and I'm really glad you.
Speaker 4: Just did it for me.
Speaker 1: Why how about that?
Speaker 4: All right?
Speaker 2: So let's talk about those incredibly terrifying potent toxins, shall we.
Speaker 1: Let's do it.
Speaker 2: So. Exotoxins are proteins that bacteria make that can disperse
Speaker 2: throughout our body and cause an effect. We've talked about
Speaker 2: them a lot on this podcast. The toxin in Cloustridium
Speaker 2: tetani is the causative agent of tetanus, not the bacteria themselves.
Speaker 2: This toxin, the tetanus toxin tetni. As a side note,
Speaker 2: it actually produces two different toxins. One is called tetno
Speaker 2: lysin and the other tetno spasmin. Huh, techno lisin we
Speaker 2: don't really understand, at least from what I read, like
Speaker 2: maybe it helps establish an infection or something like that.
Speaker 2: But tetnospasmin is tetanus toxin.
Speaker 4: So that's what we're going to talk about today.
Speaker 2: So, this tetanus toxin is a neurotoxin just like bochulinum
Speaker 2: produced from Clostridium boculinum, and so it specifically binds to
Speaker 2: our nerves and affects our nervous system. Let's recap what
Speaker 2: we learned in our botulism episode, shall we. Then we
Speaker 2: can do some compare contrast my favorite.
Speaker 1: I was so looking forward to this.
Speaker 2: I know, I actually just took some notes, like I
Speaker 2: copypasted some notes from my any grade. It's a recap.
Speaker 2: Botulinum toxin blocks the release of acetylcholine at our peripheral
Speaker 2: nerve sine, if that sounds familiar. So what that results
Speaker 2: in is a flaccid paralysis, meaning a limp paralysis, because
Speaker 2: the signals from our brain don't ever actually make it
Speaker 2: all the way to our muscles, so your muscles are
Speaker 2: paralyzed in this flaccid limp state rather than a contracted state.
Speaker 2: That happens when this botulinum toxin binds to our nerve
Speaker 2: cells at the neuromuscular junction, which is the junction between
Speaker 2: our nerves and the muscles that they innervate, and then
Speaker 2: blocks the release of the transmitters at that junction. Okay,
Speaker 2: Tetanus toxin does the exact same thing. It blocks the
Speaker 2: release of neurotransmitters in a synapse in a junction, but
Speaker 2: it does it in the inhibitory interneurons within our spinal
Speaker 2: cold word I'll explain, But the bottom line is that
Speaker 2: tetanus toxin has the exact opposite clinical effect. It causes
Speaker 2: a spastic paralysis or muscles that are paralyzed in a
Speaker 2: rigid or contracted state. So let's go through the steps,
Speaker 2: shall we. Yeah, what happens in the case of tetanus
Speaker 2: toxin is it binds actually to our nerve cells in
Speaker 2: the same exact place as botulinum toxin. It binds to
Speaker 2: our nerve cells at the neuromuscular junction the NMJ, and
Speaker 2: it is internalized in those cells at the same place
Speaker 2: as boculinum. But while boculinum toxin acts, it exerts its
Speaker 2: effects right there at the neuromuscular junction, blocking the release
Speaker 2: of acetylcholine. What tetanus toxin does instead of acting right
Speaker 2: where it enters our cells, is it actually travels retrograde
Speaker 2: along our nerve acxi allah like rabies virus.
Speaker 4: Oh yeah, okay, that sounds familiar.
Speaker 2: It travels all the way up our nerve axons like
Speaker 2: from the muscle in your jaw, for example, all the
Speaker 2: way up the nerve into our central nervous system where
Speaker 2: the nerve came from, and then it enters the space
Speaker 2: in between. It travels through that intersynaptic space inside our
Speaker 2: central nervous system and enters another set of neurons in
Speaker 2: our spinal cord, and there it blocks the release of
Speaker 2: neurotransmitters the same way that bachulinum does. But it just
Speaker 2: so happens that the neurons that it enters in our
Speaker 2: spinal cord are the inhibitory neurons that primarily release neurotransmitters,
Speaker 2: whose primary job is to inhibit or block the firing
Speaker 2: of our motor neurons.
Speaker 1: Okay, and so if they can't do their job, then
Speaker 1: all those motor neurons are going shoo shoo, shoo shoo,
Speaker 1: and then they're that's where you get the rigidity and spasms.
Speaker 4: Exactly.
Speaker 2: You just read my next line.
Speaker 4: It's perfect. So exactly, if.
Speaker 2: You can't inhibit the inhibitors, then your motor neurons are
Speaker 2: getting signals from your brain like rapid fire, which leads
Speaker 2: to this intense muscle rigidity, this spasm.
Speaker 1: Okay, I have a question about wound location and course
Speaker 1: of disease and stuff like that. So, Yeah, the classic
Speaker 1: picture that I have of someone with tetanus, and I'll
Speaker 1: talk about this actual picture later on, is like someone
Speaker 1: who is completely Every single muscle is rigid.
Speaker 4: Yeah.
Speaker 1: Does that happen all the time? Does it happen in stages?
Speaker 1: For instance, if you have a wound on your hand,
Speaker 1: does that mean that the hand will become rigid? First?
Speaker 4: Such a good question. In general, the course.
Speaker 2: Of tetanus is the same always, and in general, the
Speaker 2: course is that the muscles that tend to be affected
Speaker 2: first are the facial nerves, so the muscles that are
Speaker 2: in your face, like your jaw and your neck and
Speaker 2: your head, and then it tends to travel kind of
Speaker 2: downward and then affect your trunk and.
Speaker 4: Your limbs, et cetera.
Speaker 1: Why is that?
Speaker 2: That's a great question. I don't know, and I don't
Speaker 2: think that we fully know. So the nerve pathways to
Speaker 2: our facial muscles are a lot shorter, like the distance
Speaker 2: from the central nervous system to those muscles.
Speaker 4: It is a lot shorter.
Speaker 2: But it doesn't matter where you get exposed, if that
Speaker 2: makes sense, Say you get a wound on your foot.
Speaker 2: That tetanus toxin makes it in makes it to your
Speaker 2: central nervous system, and it seems to be that it's
Speaker 2: still the head and neck first and then the rest
Speaker 2: of the body after that. It is really interesting. I
Speaker 2: don't fully know why, so bizarre, I know it is.
Speaker 4: It is really really interesting.
Speaker 2: Huh.
Speaker 4: Yeah.
Speaker 2: And the same was true for botulism, where it often
Speaker 2: went from.
Speaker 4: The head down right. Yeah.
Speaker 2: Yeah, So that is kind of how this toxin works
Speaker 2: in general. The incubation period, the time from when you
Speaker 2: are first exposed to when these symptoms start, it's quite variable.
Speaker 2: Most sources on average say like three to fourteen days,
Speaker 2: some say seven to ten. It really can just depend
Speaker 2: on where you get exposed, whether you're talking about an
Speaker 2: infant versus an adult, things like that. And like I said,
Speaker 2: the symptoms do tend to follow this general progression. So
Speaker 2: they often start with this neck stiffness, difficulty opening the mouth,
Speaker 2: and then that progresses to the classic name for tetanus,
Speaker 2: which is lockjaw, and that is from the spasm of
Speaker 2: the muscles of chewing, the muscles of the jaw that
Speaker 2: spasm shut and then that continues to progress. There is
Speaker 2: a kind of characteristic facial posture called rhesus sardonicus, and
Speaker 2: it's this really awful facial expression that's a very pronounced
Speaker 2: closed mouth, teeth bared grimace because all of the muscles
Speaker 2: of your face are just rigidly contracted. At this point,
Speaker 2: the muscles of swallowing are very likely affected, so there's
Speaker 2: going to be some degree of dysphagia or difficulty swallowing.
Speaker 2: And as it continues to progress, the muscles of the
Speaker 2: trunk can become affected, and this can lead to a
Speaker 2: rigid posturing that's known as episthotonis, which is again really
Speaker 2: really awful if you see pictures of it, but it's
Speaker 2: this very rigid arched back with head jutted back because
Speaker 2: all the muscles of your spine, like along your spine
Speaker 2: become contracted.
Speaker 4: At this point.
Speaker 2: Because of all of this contraction.
Speaker 4: Of all of these muscles, the chest wall is.
Speaker 2: Not very compliant. So that means that you can't breathe
Speaker 2: very well because the muscles between your ribs and your
Speaker 2: back they're kind of in spasm, so it can be
Speaker 2: really difficult to take in air.
Speaker 1: Oh my goodness.
Speaker 2: Yeah, there can also be kind of convulsions that happen
Speaker 2: similar to seizures that can happen on top of this
Speaker 2: generalized increase in muscle tone. So these spasms can look
Speaker 2: a lot like seizures. But if these spasms affect muscles
Speaker 2: like the LAYNX of the throat, then they can lead
Speaker 2: to airway obstruction, which can be life threatening. And one
Speaker 2: of the papers I wanted to read a quote from
Speaker 2: because I think it kind of sums up just how awful.
Speaker 4: This really is. They said, after this.
Speaker 2: Description of all of these symptoms, quote, consciousness is preserved,
Speaker 2: making tetanus a truly dreadful disease. Oh no, yeah, yeah,
Speaker 2: so it's a really horrible disease. Yeah, to say the least,
Speaker 2: to say the least, And you can imagine there are
Speaker 2: a lot of different ways that people can end up
Speaker 2: dying from tetanus. And just like with botulinum, while there
Speaker 2: is treatment for the effects of tetanus toxin, we have
Speaker 2: tetanus IgG like antibody treatment. The treatment the main function
Speaker 2: is to bind and neutralize any of this toxin that
Speaker 2: hasn't yet bound into the central nervous system. But this
Speaker 2: can only do so much because once tetanus toxin is
Speaker 2: bound and internalized into our nerve cells. There's nothing that
Speaker 2: we can do about it. It's permanent until our nerves
Speaker 2: essentially regenerate, which is what has to happen. Those nerve
Speaker 2: terminals have to actually, you know, remake themselves to be
Speaker 2: able to then re send the signals that they need
Speaker 2: to send to inhibit muscle contraction.
Speaker 1: So if you don't get that early enough, it's.
Speaker 2: Right, Yeah, Yeah, tetnus toxin doesn't kill any of the
Speaker 2: nerve cells, which I think is really important, but the
Speaker 2: neurons still do have to kind of remake those synapses
Speaker 2: in order to be able to work again properly. So
Speaker 2: you're not having to make entirely new nerves or anything
Speaker 2: like that, but you can't stop the effects of the
Speaker 2: toxin that have already been integrated into our cells.
Speaker 4: Right.
Speaker 2: So, on top of using treatments like the tetanus antibodies,
Speaker 2: you also have to treat the source of infection, so
Speaker 2: antibiotics or wound to breedment if there is some kind
Speaker 2: of active wound that's still making more tetanus toxin. But
Speaker 2: really the most important thing in terms of treatment is
Speaker 2: supportive care and sedation, and one thing that's really interesting,
Speaker 2: although incredibly depressing still is that after the advent of
Speaker 2: mechanical ventilation, so like being able to intubate someone and
Speaker 2: breathe for them while this process is taking place in
Speaker 2: their body. This obviously helps keep people alive because they
Speaker 2: usually would die from respiratory failure with tetanus. But since
Speaker 2: we have invented that, we have found that tetanus reaks
Speaker 2: even more havoc on the body than we realized. While
Speaker 2: botch a lignum really only affects the motor nerves, because
Speaker 2: tetanus goes into our central nervous system, it causes a
Speaker 2: lot of autonomic instability as well that we didn't realize
Speaker 2: until we had mechanical ventilation to keep people alive long
Speaker 2: enough to see that process, if that makes sense, And
Speaker 2: so it can cause a lot of you know, blood
Speaker 2: pressure variation, It can cause heart rates to go really
Speaker 2: really high and then drop really really low because it
Speaker 2: basically is blocking your autonomic nervous system from being able
Speaker 2: to send signals appropriately. So it's a very difficult disease
Speaker 2: to treat with supportive treatment. Though it's not impossible, it's
Speaker 2: absolutely possible, it's just really complicated. Jeez, and so because
Speaker 2: of that, mortality rates for people who are unvaccinated, who
Speaker 2: have never been vaccinated can still vary really widely. One
Speaker 2: source that I read estimated anywhere from ten to sixty
Speaker 2: percent mortality for neonatal tetanus, and of course neonatal tetanus
Speaker 2: happens when babies are too young to be vaccinated, so
Speaker 2: in adults, the mortality rate can vary from eight to
Speaker 2: fifty percent I read, and it increases with age. So
Speaker 2: it's a very complicated disease to treat, but it is
Speaker 2: entirely preventable, which is amazing.
Speaker 1: Yeah, truly, it really is.
Speaker 2: We have an incredibly effective vaccine that has very long
Speaker 2: lasting immunity, and it is I think the cheapest vaccine
Speaker 2: to ever have been produced.
Speaker 4: Is one thing that I read, which is, oh yeah,
Speaker 4: I love that.
Speaker 2: And it's been around for a really long time. So
Speaker 2: that's the good news that we'll get to end this
Speaker 2: episode later with at least some happy news because of
Speaker 2: the vaccine. So that's the biology of Tetnus aarin.
Speaker 1: It is just as maybe more horrifying than I anticipated
Speaker 1: it would be.
Speaker 4: Yeah, I know it really, it really is. Yeah.
Speaker 2: Yeah, I have a question for you erin, how on
Speaker 2: earth did this process evolve?
Speaker 1: Oh?
Speaker 2: Because okay, here's the thing, Arin, Yeah, yeah, you mentioned
Speaker 2: up at the top, just how potent this toxin is,
Speaker 2: right right, It is so potent. I didn't even know
Speaker 2: this until researching. But getting infected with tetanus, getting infected
Speaker 2: with Clustridium tetani and then surviving an infection does not
Speaker 2: provide you with immunity because the tetanus toxin is so
Speaker 2: potent that just the tiniest amount of it causes incredible symptoms,
Speaker 2: but not enough to produce antibodies that we actually make
Speaker 2: enough of to then produce immunity, whereas we know that
Speaker 2: we produce immunity because we have a great vaccine.
Speaker 1: And I mean, that's incredible.
Speaker 2: And one source that I read said that the toxin
Speaker 2: may constitute five percent of the weight of this organism,
Speaker 2: so they're making a ton of this toxin.
Speaker 1: It is so bizarre, and I'm not certain that I
Speaker 1: have a satisfying answer, but I want to like get
Speaker 1: into it. Okay, so let's take a quick break and
Speaker 1: then I'll get started.
Speaker 4: I can't wait.
Speaker 1: I found the history of tetanus to be so interesting
Speaker 1: for a number of reasons. First, it checks a lot
Speaker 1: of the boxes for a classic TPWKY episode. Tetanus is
Speaker 1: an infamous disease, there are plenty of ancient descriptions. Of course,
Speaker 1: war plays a role, gets a mention, and also we
Speaker 1: get to talk about the golden age of germ theory. Yeah,
Speaker 1: all that good stuff. Second, we've covered a couple of
Speaker 1: related pathogens before, as you mentioned, and so it was
Speaker 1: kind of fun to compare the evolutionary histories or human
Speaker 1: histories of the especially with Claustridi and bochelinum. Yeah. And Third,
Speaker 1: there are parts of the history of tetanus that I
Speaker 1: feel provided an opportunity to think about how perceptions of
Speaker 1: a disease, especially who is most likely to get that disease,
Speaker 1: can really find their way into how these diseases are
Speaker 1: written about historically. And I think that's good to keep
Speaker 1: in mind as we try to read between the lines
Speaker 1: and understand how people were observing disease and why. So
Speaker 1: let's get started.
Speaker 4: I love it.
Speaker 1: Where did tetanus come from? Great question? I wish I
Speaker 1: had an answer. I can tell you where the word
Speaker 1: tetanus came from. Which is the Greek verb tanno, meaning
Speaker 1: to stretch. But from what I can tell, we don't
Speaker 1: really know where this pathogen originated in the world and
Speaker 1: when it's spread around the world, because it is like
Speaker 1: globally distributed. Did its global distribution predate wide scale travel
Speaker 1: by humans?
Speaker 4: Maybe? Maybe?
Speaker 1: Maybe it's a mysterious little little pathogen. We do know though,
Speaker 1: that humans have been exposed to tetanus for at least most,
Speaker 1: if not all, of written history, and probably have been
Speaker 1: for all of you know, all of our prehistory as well.
Speaker 1: But we'll get to that in a second, because first
Speaker 1: I want to talk about some aspects of tetanus ecology
Speaker 1: and evolution. So, like I said, we don't know where
Speaker 1: geographically tetanus emerged, but we do know that it doesn't
Speaker 1: really seem to change all that much. Its genome is
Speaker 1: highly conserved, which is actually, I think something that we've
Speaker 1: seen for a few other spore formers, which I think
Speaker 1: is cool.
Speaker 4: Yeah.
Speaker 1: Anthrax, right, Anthrax especially, Yeah, bacheline Clustridium botulinum is less stable,
Speaker 1: but anyway, the plasmid carrying the tetanus toxin gene is
Speaker 1: more variable, but the gene itself is not is very stable. Yeah, Yeah,
Speaker 1: it doesn't make sense.
Speaker 2: That's so interesting though, because like with botulism, there's more
Speaker 2: than a few different types of the toxin, but with tetanus,
Speaker 2: it's really just tetnus toxin.
Speaker 1: Yeah, And with the botulinum toxin, it's found in many
Speaker 1: different strains of Clostridium, whereas, yeah, the tetanus neurotoxin only
Speaker 1: in clusterdim tetani.
Speaker 4: Yeah.
Speaker 1: And like you said, these two neurotoxins are structurally and
Speaker 1: functionally similar, but they seem to have followed different evolutionary pathways.
Speaker 1: And I think it's really cool to look at the
Speaker 1: ecology of these bacteria to see like maybe why that
Speaker 1: might be, or why these different characteristics of these two
Speaker 1: bacterial species, why they contribute to the patterns that we
Speaker 1: see in disease and outbreaks and sporadic cases stuff like that. So,
Speaker 1: both Claustridium tetani and Clustridium bochulinum are anaerobic soil dwelling
Speaker 1: and they produce this deadly and potent neurotoxin. But why
Speaker 1: why do they do this? Why are you the way
Speaker 1: you are with the title of our bochulism episode, because
Speaker 1: we were like why why why? And we talked about
Speaker 1: how Claustridium botulinum will be picked up by a dabbling
Speaker 1: duck or something, and then the toxin will kill the bird.
Speaker 1: That carcass becomes a great anaerobic replicating ground for the
Speaker 1: bacteria and also a great source of environmental contamination as
Speaker 1: other animals either nibble on the corpse or around the
Speaker 1: corpse or in like you know, the more dabbling ducks
Speaker 1: than the soil whatever, right, I remember that a lot. Yeah,
Speaker 1: it was a very cool thing to visual like, oh,
Speaker 1: that's why this exists. And so having this deadly neurotoxin
Speaker 1: is key to the life cycle of Claustridium boculinum. By
Speaker 1: killing its host, it can now contaminate a big chunk
Speaker 1: of the environment and spread to other hosts. And the
Speaker 1: tetanus toxin isn't too much different. Really, it's a potent
Speaker 1: neurotoxin that can kill its host. But one key difference
Speaker 1: is that the boculinum neurotoxin can survive ingestion, and that's
Speaker 1: like how it creates disease, while the tetanus neurotoxin cannot.
Speaker 1: And this difference is why we see outbreaks in botulism
Speaker 1: in nature and in food poisoning outbreaks, whereas we mostly
Speaker 1: see isolated, sporadic cases in Tetanus.
Speaker 2: Whoa, uh huh, so it makes even less sense.
Speaker 1: It makes even less sense, but it also does it
Speaker 1: does make sense to a degree, right, So this is
Speaker 1: likely a costly toxin to.
Speaker 4: Make, uh huh.
Speaker 1: It has to help the bacteria. It has to help
Speaker 1: Clusterium tetani to survive, to be transmitted, to help it
Speaker 1: complete its life cycle in some way. I mean, these
Speaker 1: are soil dwelling microbes, so they don't necessarily need hosts
Speaker 1: to live to proliferate. But it would be great if
Speaker 1: a host came along with a little cut on their
Speaker 1: foot and picked up some Tetanus spores tetani spores, and
Speaker 1: then that host, after it died, became another great breeding
Speaker 1: ground for more contamination. So it might be a combination
Speaker 1: of the fact that like this is a very useful
Speaker 1: tool for the bacteria, and also they're spore formers. Yeah,
Speaker 1: so I don't know.
Speaker 2: The whole gut thing. That's just so interesting. I feel
Speaker 2: like that was such a big part of the bochu
Speaker 2: Linum story, where you know, then you eat it and
Speaker 2: then you continue it, et cetera.
Speaker 4: And so to know that that's not part.
Speaker 2: Of the story here is really interesting.
Speaker 1: Yeah. I mean I feel like the story makes sense still,
Speaker 1: like the toxin plays an important role, but it isn't
Speaker 1: as satisfying. Yeah, nearly as satisfying, right, And maybe that's
Speaker 1: the lesson is that, like evolution doesn't always tell us satisfying,
Speaker 1: it doesn't always make sense. Yeah, it doesn't always make sense.
Speaker 1: It doesn't follow logic, it's just just is what it is. Sometimes.
Speaker 1: That being said, if anyone listening is like, wait, no,
Speaker 1: I know why this happens, or you have a paper
Speaker 1: where you can show me exactly, because I spent hours
Speaker 1: and hours on Google scholar trying to find out the
Speaker 1: elutionary ecology of this neurotoxin, please shoot us an email. Yeah,
Speaker 1: I would love to read it.
Speaker 4: We have so many more questions.
Speaker 1: Yeah. But the good thing about this relatively non exciting
Speaker 1: or maybe not satisfying evolutionary history and the super stable
Speaker 1: genome of cluster name tetane is that this means that
Speaker 1: the vaccine is very widely and highly effective and we
Speaker 1: don't have to worry about the emergence of strains that
Speaker 1: the vaccine doesn't protect you against, which is good because
Speaker 1: this disease is horrible, absolutely horrible. Tetanus causes this dramatic,
Speaker 1: visually dramatic and deadly infection, and so it should come
Speaker 1: as no surprise that it has been mentioned in so
Speaker 1: many ancient texts.
Speaker 4: Like all of them, all of them.
Speaker 1: It's really back to back classic TPWKY with trachoma and chlamydia,
Speaker 1: last episode and now this. So we're going to run
Speaker 1: through these ancient medical texts again protet us. So we've
Speaker 1: got the edwins Smith Surgical Papyrus written around fifteen hundred
Speaker 1: BCE that mentions it. The ancient Indian physician Sushruda from
Speaker 1: around six hundred BCE made a possible reference to it.
Speaker 1: Early Chinese medical texts from around four hundred to two
Speaker 1: hundred BCE described it, and of course we've got the
Speaker 1: Hippocratic texts from around the four hundreds BCE yep, yep.
Speaker 1: Hippocrates and other contributors to the text. Because it wasn't
Speaker 1: just Hipocrates actually wrote quite extensively about tetanus, both the
Speaker 1: local and systemic forms, and included some very colorful descriptions
Speaker 1: of the disease. Quote a man who was struck from behind,
Speaker 1: by a sharp dart a little below the neck had
Speaker 1: a wound which did not look serious because it did
Speaker 1: not go deep. But sometime later, when the point had
Speaker 1: been extracted, the patient was seized with backward bending convulsions
Speaker 1: like those of Opisthetonis. His jaws were locked, and any
Speaker 1: liquid that he attempted to swallow was returned through his nostril.
Speaker 1: He died on the second day.
Speaker 4: Oh goodness, h h.
Speaker 1: And if you're looking for treatments, the Hippocratic texts have
Speaker 1: got you covered. Fatbird soup, vapor baths, cold water baths, pepper,
Speaker 1: hell bore and of course you have to throw in
Speaker 1: some blood letting, of course, of course. And over the
Speaker 1: next hundreds of years nothing really changed for tetanus. Seven
Speaker 1: hundred years after the Hippocratic texts, Aretaeus of Cappadocia added
Speaker 1: his thoughts on the disease. And you can really tell
Speaker 1: how badly he felt as a physician, completely unable to
Speaker 1: help his patients. Quote and inhuman calamity, an incredible sight,
Speaker 1: a spectacle, painful even to the beholder, an incurable malady.
Speaker 1: He listed tree after treatment, frankincense, the hair of a polly, fleabane, turpentine,
Speaker 1: et cetera. And this variety just kind of goes to
Speaker 1: show again that nothing seemed to help. Classic tetanus like
Speaker 1: what you would see in an adult human wasn't the
Speaker 1: only thing that these ancient physicians noticed. There was also
Speaker 1: mentions of equine tetanus and neonatal tetanus which was sometimes
Speaker 1: called trismus and not necessarily recognized to be the same
Speaker 1: thing as tetanus for hundreds of years. Interesting from these
Speaker 1: ancient texts, I'm gonna skip way ahead until the eighteen hundreds,
Speaker 1: kind of like I did also for chlamydia slash trachoma,
Speaker 1: because not very much happened in terms of tetanus until
Speaker 1: that time. I mean, yeah, sure, there were additional descriptions
Speaker 1: of it and case reports and shifting hypotheses as to
Speaker 1: what caused the disease, but overall, the way that it
Speaker 1: was characterized in the Hippocratic texts didn't change much. A
Speaker 1: tiny injury, like one instance I read from the bite
Speaker 1: of a tame sparrow in the seventeen hundreds. WHOA, I know,
Speaker 1: there's a lot to take in in that sense, Yeah.
Speaker 4: There really is.
Speaker 1: But this tiny injury could lead to a horrifically painful
Speaker 1: infection that was ultimately fatal a lot of the time,
Speaker 1: with no reliable, effective treatments. Even in eighteen ninety two,
Speaker 1: when doctors had slightly better tools to help with feeding
Speaker 1: and muscle relaxation, the mortality rate was eighty percent after
Speaker 1: four days.
Speaker 3: Yeah.
Speaker 1: For much of human history, tetanus remained a sporadic disease
Speaker 1: except in a few instances or populations, and one of
Speaker 1: these was, of course, soldiers or during times of war,
Speaker 1: for all the usual reasons of basically not having access
Speaker 1: to sanitation, an increase in both small and large wounds, etc.
Speaker 1: There's a famous painting this is the picture of Tetanus
Speaker 1: I met that you've probably seen, depicting a soldier in
Speaker 1: a violent, rigid spasm from tetanus infection. And I'm gonna
Speaker 1: post this probably for like the announcement release post for
Speaker 1: this episode on our social media. That was painted in
Speaker 1: eighteen o nine by surgeon and artist Sir Charles Bell.
Speaker 1: It's titled Tetanus following Gunshot Wounds and guess where the
Speaker 1: soldier got those gunshot wounds during the Napoleonic Wars. I
Speaker 1: mean again, Napoleon. It's just so many parallels. Yeah, specifically
Speaker 1: if you're interested in the Battle of Karuna. I distinctly
Speaker 1: remember seeing that painting for the first time in my
Speaker 1: high school biology textbook or something, and being so fascinated
Speaker 1: but also terrified by it. Yeah, Like I couldn't believe
Speaker 1: it was a real thing.
Speaker 2: Yeah.
Speaker 1: Yeah. And soldiers, of course, weren't the only ones that
Speaker 1: were disproportionately affected by this pathogen. In the mid eighteen hundreds,
Speaker 1: several doctors in the American South became interested in what
Speaker 1: they called trismus nessentium, which would later be called neonatal tetanus,
Speaker 1: and they remarked that it was quote no uncommon disease
Speaker 1: among infants born to enslaved people in the South. I
Speaker 1: want to take a minute to talk about neonatal tetanus
Speaker 1: in the American South before the Civil War because I
Speaker 1: think it's important for several reasons. First, it gives us
Speaker 1: an opportunity to see how much the established knowledge about
Speaker 1: a disease is so dependent on who's looking and especially
Speaker 1: whom they're looking at. Second, neonatal tetanus is I think
Speaker 1: a really clear example of how differently medicine was practiced,
Speaker 1: how medical stats were collected and whom those stats represent
Speaker 1: between the American North and the Confederate South. And third,
Speaker 1: I think it highlights the beginning of a shift in
Speaker 1: medicine overall, from heroic medicine, so called heroic medicine, to
Speaker 1: preventive care.
Speaker 4: I love it, okay.
Speaker 1: So, neonatal tetanus, as you described, Aaron, and as our
Speaker 1: first hand account so vividly and horribly described, is when
Speaker 1: the umbilical stump gets infected with the tetanus pathogen. It's
Speaker 1: tightly linked to access to sanitation and hygiene practices following delivery,
Speaker 1: and it is like adult tetanus, incredibly horrific and deadly.
Speaker 1: Those are not even adequate adjectives and inhuman calamity. Yeah,
Speaker 1: maybe we could borrow that phrase from airtase. Before the
Speaker 1: US Civil War, enslavers would frequently employ doctors to monitor
Speaker 1: the health of enslaved people, not out of the goodness
Speaker 1: of their hearts, of course, but to protect their financial interests.
Speaker 1: These Southern doctors began to notice high rates of neonatal
Speaker 1: tetanus in the infants born to enslaved people. And when
Speaker 1: I say high rates, I mean very high. Some doctors
Speaker 1: estimated that up to two thirds of the deaths among
Speaker 1: these infants were due to neonatal tetanus.
Speaker 4: Oh Man.
Speaker 1: Yeah. Because of this, neonatal tetanus was labeled by many doctors,
Speaker 1: especially those in the North, as a disease of the South,
Speaker 1: or more specifically, a disease of enslaved black people. But
Speaker 1: was it especially so, We don't really have any good
Speaker 1: way of knowing, considering that statistics weren't widely used at
Speaker 1: the time, but it almost certainly wasn't. There may have
Speaker 1: been a few things that contributed to the high rates
Speaker 1: observed by southern doctors. For instance, there were some post
Speaker 1: natal practices, such as using cow dung or charcoal to
Speaker 1: wrap the cut of the biblical cord, that could have
Speaker 1: increased exposure, and some of those practices are still used
Speaker 1: today in various places, and they are associated with higher
Speaker 1: rates of neonatal tetanus. But it was also probably a
Speaker 1: matter of visibility. Neonatal tetanus was certainly present in the North,
Speaker 1: but northern doctors probably didn't see it as much because,
Speaker 1: unlike the Southern doctors who wrote about neonatal tetanus, Northern
Speaker 1: doctors didn't treat nearly as many people living in conditions
Speaker 1: that put them at risk for the infection. Mostly they
Speaker 1: would work at hospitals, and so if someone came into
Speaker 1: the hospital maybe then they would see them. But they
Speaker 1: didn't travel as widely and to his varied urban and
Speaker 1: more rural centers the way that Southern doctors could do
Speaker 1: people who were living with a lack of access to sanitation,
Speaker 1: people living in poverty, et cetera. Northern doctors weren't getting
Speaker 1: paid to treat these people, unlike Southern doctors. In addition,
Speaker 1: Southern doctors, especially those that were employed by enslavers, were
Speaker 1: much more likely to encounter cases of neonatal tetanus than
Speaker 1: their northern counterparts, since it was midwives that mostly attended
Speaker 1: the birthing and postnatal care in the North. And another
Speaker 1: big difference was that the Southern doctors tended to keep
Speaker 1: more detailed records of the people they treated, not because
Speaker 1: they were inherently more meticulous, but again because it was
Speaker 1: more a matter of business and economics, and slavers wanted
Speaker 1: to know which diseases were contributing to the most death
Speaker 1: and disability or in their eyes, lost profit, and this
Speaker 1: informed to some degree, which diseases were given priority for study.
Speaker 1: Neonatal tetanus garnered a substantial amount of interest in the
Speaker 1: mid eighteen hundreds in the southern US because it contributed
Speaker 1: so highly to infant mortality among babies born to enslaved people,
Speaker 1: and several doctors started to try to understand why that
Speaker 1: was doctor Mary and Simms, infamous so called father of
Speaker 1: modern gynecology. I can't resist like an opportunity to diss
Speaker 1: Mary and Sims, or at least call him out for
Speaker 1: being someone who absolutely tortured so many an untold number
Speaker 1: of enslaved black women. Yeah. Mary and Simms was one
Speaker 1: of the doctors who tried to say, oh, I know
Speaker 1: the cause of neonatal tetanus, and he thought it had
Speaker 1: to do with the formation of the skull. He said,
Speaker 1: you should put the baby. People were obsessed with skull
Speaker 1: shape for decades too long. He said, you know, if
Speaker 1: you put the baby in a crib, you should make
Speaker 1: sure there are lots of pillows around the baby in
Speaker 1: position the baby very carefully so that the skull could
Speaker 1: grow properly.
Speaker 4: Oh dear, oh no.
Speaker 1: And one of his horrifying treatments involved drilling a hole
Speaker 1: in the baby's skull in all no, yeah, and there
Speaker 1: was no evidence, of course, to support his hypotheses, and
Speaker 1: a couple of other doctors fortunately were around to pick
Speaker 1: apart his arguments. William Baldwin, a physician who graduated med
Speaker 1: school Transylvania University in Lexington, Kentucky, at age nineteen.
Speaker 4: Wow.
Speaker 1: Yeah, I mean it was the eighteen fifties, eighteen forties.
Speaker 1: He wrote that Simms was wrong and that the disease
Speaker 1: was more common among enslaved people, not because of how
Speaker 1: they laid an infant in a crib, but because of
Speaker 1: living conditions and lack of access to sanitation. He didn't
Speaker 1: agree with Sims's and others claims that there was a
Speaker 1: racial disposition to disease, but instead thought it was living
Speaker 1: in an environment that led to greater exposure, which is
Speaker 1: pretty like incredible to hear, or like more forward thinking
Speaker 1: than I anticipated, considering this was the eighteen fifties.
Speaker 2: But I feel like that was we you know, malaria,
Speaker 2: et cetera. Like, yeah, people knew of this environmental yeah, miasma.
Speaker 1: Yeah exactly. Yeah, So I think that was definitely part
Speaker 1: of it. But I also think he might have been
Speaker 1: ahead of his time with this next quote because he
Speaker 1: suggested that it was quote a grain of dust or sand,
Speaker 1: or other particle of foreign substance, however small may be
Speaker 1: lodged in the delicate granulations of the umbilicus just after
Speaker 1: the detachment of the cord.
Speaker 4: There you go.
Speaker 1: So there it's I mean, that's not that's not wrong.
Speaker 2: Really, no, that's exactly exactly what it is.
Speaker 4: Is.
Speaker 1: I found that fascinating, and Baldwin wasn't alone. Another physician
Speaker 1: named John M. Watson from Tennessee took up the charge
Speaker 1: and further dismissed Sims in eighteen fifty nine, like kind
Speaker 1: of harshly and directly. I appreciated it. He too, believed
Speaker 1: that it was irritation of the wound and suggested that
Speaker 1: instead of Sims's barbaric sculdrilling practice, people should try for
Speaker 1: simply cleaning the wound, having a more sanitary environment overall,
Speaker 1: basically practicing preventative medicine, which was not in fashion at
Speaker 1: the time. Instead, doctors tended to practice heroic medicine, which
Speaker 1: I talked a bit about in the antibiotics episode. Essentially,
Speaker 1: it was a way of practicing medicine through intervention. Only
Speaker 1: your patient came in sick and you thought, Okay, how
Speaker 1: can I stop this? You made your patient sweat, purge, bleed,
Speaker 1: get a fever, be freezing cold, whatever to shock their
Speaker 1: body back into balance. Medicine was about activity and treatment
Speaker 1: rather than prevention. The concept of cleanliness and sanitation as
Speaker 1: a method of disease prevention was a fairly new one
Speaker 1: in some degree. Yes, there was a miasma theory, but
Speaker 1: in terms of like Semulweis and Lister, you know, like
Speaker 1: all of those sanitation right, it was starting to come around.
Speaker 1: But most doctors thought that cleaning a wound that doesn't
Speaker 1: make you a doctor. Sawing off a gangrenus limb in
Speaker 1: five seconds that Shir did. But the tide was turning
Speaker 1: from heroic medicine to preventive medicine, partially because of germ theory,
Speaker 1: and also partially because of people like Lister and Semblevice,
Speaker 1: and also partially because the emerging field of epidemiology allowed
Speaker 1: people to see wide scale patterns of disease and how
Speaker 1: interventions such as hand washing or ventilation affected the spread
Speaker 1: of disease. But the origin story of epidemiology is more
Speaker 1: complex than the classic story of John Snow and his
Speaker 1: collar maps. One of my favorite things about this podcast
Speaker 1: is that we are wrong sometimes and we read more
Speaker 1: like we get to learn new stuff all of the time,
Speaker 1: every day, every day, and that makes us I think,
Speaker 1: both look back and go, oh, my goodness, I didn't
Speaker 1: know that I said that wrong. I didn't understand the
Speaker 1: context for this, And part of me is like, oh,
Speaker 1: I wish I could go back in time, But another
Speaker 1: part really likes to observe the fact that we are
Speaker 1: learning and growing. Yeah, and this is one of those instances.
Speaker 1: Epidemiology didn't come about because of John Snow and his
Speaker 1: cholera maps. Of course they played a role, but it's
Speaker 1: more complicated story than that. So we've talked about how
Speaker 1: tropical medicine as a field was largely created during the
Speaker 1: huge period of colonialism in the late eighteen hundreds right
Speaker 1: to help the imperialist to quote conquer an area. In
Speaker 1: a similar way, epidemiology developed out of colonialism, out of slavery,
Speaker 1: out of war, when doctors were incentivized to study and
Speaker 1: treat populations rather than individuals that they may not have otherwise.
Speaker 1: These circumstances provided doctors the opportunity to see disease on
Speaker 1: a scale that they hadn't before moving through army hospitals,
Speaker 1: prison camps, ships, etc. You and I learned the story
Speaker 1: of epidemiology, and we've told the story of epidemiology as
Speaker 1: one of the early epidemiologists of John Snow and the
Speaker 1: Broad Street Pump. But you and I, as well as
Speaker 1: the Royal we those who are also in the field
Speaker 1: of public health, we haven't fully or ever acknowledged the
Speaker 1: people who made up those maps, who are mentioned in
Speaker 1: those early studies of the spread of the disease simply
Speaker 1: as cases. And many of these people were disenfranchised. They
Speaker 1: had no consent or knowledge of their involvement. And this theme,
Speaker 1: this new exploration of the origins of epidemiology, is the
Speaker 1: subject of next week's Bonus episode, as well as the
Speaker 1: topic of a new book by doctor Jim downs who
Speaker 1: is my expert guest for next week.
Speaker 4: I cannot wait.
Speaker 1: I am thrilled to be chatting with doctor Downes, who
Speaker 1: was a professor of history at Gettysburg College, about his
Speaker 1: latest book called Maladies of Empire, How colonialism, slavery and
Speaker 1: war transformed medicine. I am super excited for this conversation,
Speaker 1: So mark your calendars.
Speaker 4: Oh, I can't wait.
Speaker 1: Okay, But for now, let's get back to the history
Speaker 1: of tetanus. Moving into the second half of the eighteen hundreds,
Speaker 1: tetanus was still very much present, but it would soon
Speaker 1: meet its match, first in the form of antitoxin and
Speaker 1: then in the form of a vaccine. In eighteen eighty four,
Speaker 1: Carlo and Ratone took puss from the skin lesion of
Speaker 1: an infected human's face who later died of tetanus, and
Speaker 1: injected it into a rabbit, which began showing signs of tetanus,
Speaker 1: confirming the presence of the pathogen in that lesion, and
Speaker 1: so like the story of the microbiology of tetanus began.
Speaker 1: Later that same year, a guy named Arthur Nikolaier injected
Speaker 1: soil samples into animals who also developed tetanus symptoms. He
Speaker 1: isolated a rod shaped bacillus from these animals and hypothesized
Speaker 1: that the bacteria produced a toxin resembling strychnine in its action,
Speaker 1: which we should add to our future topics.
Speaker 4: It's on our list.
Speaker 1: Okay, good, But he didn't isolate the organism in pure culture.
Speaker 1: That would be done by shibasaburo quitisato in eighteen eighty
Speaker 1: nine from a fatal case of a soldier in Berlin.
Speaker 1: Does his names sound familiar to you a little bit? Yeah,
Speaker 1: diphtheria episode theory makes sense. So Key Desado and Emil
Speaker 1: von Behring worked closely together on a dipia anti toxin.
Speaker 1: Von Behring got the first Nobel Prize in Medicine in
Speaker 1: nineteen oh one for the work that they did, and
Speaker 1: Key Desato did not. Anyway. With this pure culture of
Speaker 1: Clastridium tetani, Key Desato was able to see that it
Speaker 1: was indeed a toxin produced by the bacteria that caused
Speaker 1: some of the symptoms, which spurred him on to look
Speaker 1: for other toxin producing bacteria, including the one that causes diphtheria.
Speaker 1: Key Desato and von Bhing's work on producing anti tooxin
Speaker 1: for tetanus and diphtheria is I mean essentially that started
Speaker 1: the field of serum therapy. Wow, and this was great.
Speaker 1: Having an anti tooxin was revolutionary in a number of ways,
Speaker 1: but it wasn't perfect.
Speaker 2: Right.
Speaker 1: You have to administer it early on for it to
Speaker 1: be effective, and in the case of tetanus, you had
Speaker 1: to keep the wound clean. When both of those things
Speaker 1: were pretty difficult. If you were like a soldier at
Speaker 1: high exposure risk and we have some numbers to back
Speaker 1: that up too. Dear, it's not that bad. I mean,
Speaker 1: it's bad to begin with, and then it gets better.
Speaker 4: Okay.
Speaker 1: In eighteen oh eight, so pre germ theory, pre tetanus, antiitoxin,
Speaker 1: pre vaccine, the rate of tetanus was twelve point five
Speaker 1: per one thousand in soldiers and the author of this
Speaker 1: didn't say which soldiers and where, But in the first
Speaker 1: months of World War One that dropped to eight per
Speaker 1: one thousand wounded. Still high, yeah, and then as wound
Speaker 1: care and anti tooxin delivery improved, it dropped further to
Speaker 1: one point five per one thousand, and by the time
Speaker 1: the US entered the war it was down two point
Speaker 1: sixteen per one thousand.
Speaker 4: Wow. Okay, great, that's pretty cool.
Speaker 1: Yeah. Interestingly, tidbit here, where you were fighting like physically
Speaker 1: played a role in your tetanus risk. Fields that had
Speaker 1: been fertilized with manure over long periods of time had
Speaker 1: more tetanis and led to the misconception that horses were
Speaker 1: the reservoirs for the bacteria. Interesting, but really it can
Speaker 1: be carried, like you said, in all kinds of animals
Speaker 1: and humans like rats, chickens, cows, horses, I'm sure many
Speaker 1: many other animals. Yeah, but further declines in tetanis were
Speaker 1: in the future, and not just for soldiers but for everyone.
Speaker 1: The tetanus vaccine was developed in nineteen twenty four by
Speaker 1: Gaston Ramon, and widespread vaccination meant a drastic drop in
Speaker 1: tetanus wherever the vaccine was available. Soldiers in World War
Speaker 1: I TiO you experienced tetanus at a rate of point
Speaker 1: zero four per one thousand.
Speaker 4: Wow.
Speaker 1: Yeah, and I think there was I saw a stat
Speaker 1: that like, no one who was vaccinated got tetanus.
Speaker 4: Wow.
Speaker 1: And neonatal tetanus rates also dropped as researchers realized that
Speaker 1: vaccination during pregnancy offered some protection to the newborn.
Speaker 2: That's the most amazing and my favorite thing.
Speaker 1: Yes, it's so important, It is so important. And these
Speaker 1: drops in tetanus continued throughout the twentieth century and into
Speaker 1: the twenty first, but not I'm guessing as much as
Speaker 1: they should have. So yeah, this is kind of just
Speaker 1: like a quick little scoot through the twentieth century on
Speaker 1: my end, But I'm curious to know erin where we
Speaker 1: stand today when it comes to tetanus.
Speaker 2: I can't wait to tell you right after this break.
Speaker 2: So in the US, we'll start here. From two thousand
Speaker 2: and nine to twenty seventeen, only two hundred and sixty
Speaker 2: four cases and nineteen deaths were.
Speaker 4: Reported from Tennis.
Speaker 2: Wow, I know that's pretty major.
Speaker 1: Yeah, across the globe.
Speaker 2: While the decrease in cases overall is still very impressive, unsurprisingly,
Speaker 2: we still do have a ways to go. The World
Speaker 2: Health Organization estimated in twenty eighteen, which is the latest
Speaker 2: data that they have as of today, that in twenty eighteen,
Speaker 2: twenty five thousand newborns died from neonatal tetanus twenty five
Speaker 2: thousand worldwide. What and as depressing as that number is,
Speaker 2: that is an eighty eight percent reduction from cases in
Speaker 2: the year two thousand and a ninety six percent reduction
Speaker 2: from cases in the nineteen eighties.
Speaker 1: Oh my goodness, I know I had no idea just
Speaker 1: how widespread tetanus was even as recently as the nineteen nineties.
Speaker 2: For example, a paper from two thousand and one estimated
Speaker 2: eight hundred thousand to one million deaths worldwide from tetanus
Speaker 2: every year, including over half a million from neonatal tetnis.
Speaker 2: That's two thousand and one paper estimated, and another paper
Speaker 2: from two thousand and seven, which was talking about data
Speaker 2: from the nineties, estimated that up to five percent of
Speaker 2: maternal mortality was due to tetanus and fourteen percent of
Speaker 2: neonatal mortality was due to tetanus. The scale of this disease.
Speaker 4: I had no idea.
Speaker 1: I cannot I mean, I can't even formulate I know
Speaker 1: a sentence.
Speaker 2: I know.
Speaker 4: I feel very much the same.
Speaker 2: So we have come an incredibly long way. The World
Speaker 2: Health Organization, who tracks data on vaccinations as well as cases,
Speaker 2: estimated that worldwide in twenty nineteen, eighty six percent of
Speaker 2: children were covered by DTP three, which is the three
Speaker 2: doses of vaccine in the first year of life. Okay,
Speaker 2: so eighty six percent of children. And I want to
Speaker 2: take a minute to emphasize here just how preventable this
Speaker 2: disease really is. Vaccination generally starts at two months old,
Speaker 2: and it's a series of three shots initially, and then
Speaker 2: a booster around kindergarten, and then boosters every ten years
Speaker 2: or so to maintain immunity. But like you mentioned Aaron,
Speaker 2: vaccination during pregnancy also confers protection against neonatal tetanus, and
Speaker 2: it's been estimated vaccination during pregnancy to reduce mortality from
Speaker 2: neonatal tetanus by ninety four percent.
Speaker 1: That's incredible, it's amazing.
Speaker 2: So we have the capacity to protect people from this disease.
Speaker 2: But a really important thing is that this is a
Speaker 2: continual struggle, or at least it's a continual process, because
Speaker 2: this is not a human specific disease that, for example,
Speaker 2: like smallpox, if you can interrupt the chain of transmission
Speaker 2: between humans for long enough, you can eliminate the disease.
Speaker 2: You can't do that with this because it's environmental pathogen
Speaker 2: that has always, like you said, Aaron, and likely always
Speaker 2: will be in our environment. So it is a process
Speaker 2: of continual protection through these incredibly efficacious, incredibly safe vaccines.
Speaker 2: And as we have seen, for example in the COVID pandemic,
Speaker 2: things that drastically alter the global landscape pose really big
Speaker 2: challenges to vaccination. So you know how I said, in
Speaker 2: twenty nineteen, eighty six percent of children were covered by
Speaker 2: DPT three, while in twenty twenty that number had gone
Speaker 2: down to eighty three percent. So an estimated twenty three
Speaker 2: million children under the age of one did not receive
Speaker 2: their basic vaccines in twenty twenty, and the number of
Speaker 2: completely unvaccinated children GLOW increased by nearly three point four
Speaker 2: million in that year alone.
Speaker 4: So we're not done yet.
Speaker 1: No, we're never done.
Speaker 2: We're never But I want to end this episode on
Speaker 2: some really high notes and also just like keep ragging
Speaker 2: about the tetnus vaccine. It's fantastic, yeah, and really the
Speaker 2: tetanus toxoid. So the tetanus vaccine is a toxoid vaccine.
Speaker 2: A toxoid is just an inactivated toxin, right, and the
Speaker 2: toxin is a protein, so it's easy, it's cheap to produce.
Speaker 2: And this tetanus toxoid that is easy to produce, that
Speaker 2: is cheap, that is very immunogenic to our immune system,
Speaker 2: is used to make a whole bunch of other vaccines,
Speaker 2: like our new Macocco vaccine, our Meninjocco vaccine hib All
Speaker 2: of these vaccines are made by conjugating or combining things
Speaker 2: like sugars, polysaccharides to the tetanus toxoid protein to induce
Speaker 2: a better protective immunity against these other diseases as well.
Speaker 1: That is just so cool, isn't it beautiful?
Speaker 2: And on top of that, the other reason that tetnus
Speaker 2: toxoid makes for such a good vaccine is that it's
Speaker 2: really shelf stable. It doesn't have to be frozen or refrigerated.
Speaker 2: It's stable at room temperature for months. So it's really transportable,
Speaker 2: even to remote areas that don't have access to refrigeration.
Speaker 1: That's fantastic.
Speaker 4: There's more. Aaron.
Speaker 2: Literally, not ten minutes before we were going to record,
Speaker 2: I was eating dinner and I was googling because I
Speaker 2: remember a very long time ago you were like, hey,
Speaker 2: did you see this news article about something that we
Speaker 2: were going to record? And never had it crossed my
Speaker 2: mind to google news articles about whatever we're talking about.
Speaker 2: And ever since then, and that was a long time ago. Now,
Speaker 2: I always like, the last thing that I do before
Speaker 2: I wrap up my research is I google tetanus and
Speaker 2: I press the news button on Google.
Speaker 1: Oh, I love it.
Speaker 2: So I did that while I was eating dinner, right
Speaker 2: before we recorded, and lo and behold, this paper was
Speaker 2: published one week ago. A group out of Albert Einstein
Speaker 2: College of Medicine published a study in Science Translational Medicine
Speaker 2: that used a combination of Listeria monocytogenies, which is a
Speaker 2: bacteria that we'll cover eventually, we haven't, right, No, okay,
Speaker 2: So a combination of this bacteria and tetanus toxoid to
Speaker 2: treat pancreatic cancer.
Speaker 1: Incredible, I know.
Speaker 2: Essentially, briefly, they injected mice that had pancreatic cancer that
Speaker 2: had also been vaccinated for tetanus like before they got
Speaker 2: cancer with a listeria that had been engineered to have
Speaker 2: the tetanus toxoid protein. And for whatever fascinating reason has
Speaker 2: to do with listeria, it preferentially congregates in these cancer cells,
Speaker 2: I think because the immune system wipes it out in
Speaker 2: other places. And then the mouse's immune system has a
Speaker 2: bunch of antibodies that recognize the tetanus toxoid because they
Speaker 2: were vaccinated, and so boom they end up attacking the
Speaker 2: cancer that has these bacteria that have this toxoid protein.
Speaker 1: What That's amazing And also, first of all, that's fantastic
Speaker 1: news for pancreatic cancer, I know, but secondly, I feel
Speaker 1: like that could be a model for many other types
Speaker 1: of cancer treating exactly. Yeah, Oh so cool.
Speaker 2: I know, these mice had their pancreatic tumors decrease in
Speaker 2: size by eighty percent and metastases decreased by eighty seven percent,
Speaker 2: and they lived forty percent longer than untreated mice.
Speaker 4: But it's a mice, but like, this is a big deal.
Speaker 1: It's a big deal.
Speaker 2: So that's a high note to end on and I
Speaker 2: will absolutely link that paper.
Speaker 1: Cool.
Speaker 2: Yeah, so tetanus is a horrible disease, but we have
Speaker 2: a vaccine and it is awesome.
Speaker 1: I love that.
Speaker 4: Yeah, yeah, any sources, sources.
Speaker 1: I have a large number of sources for this episode.
Speaker 1: I'm going to shout out three right now and put
Speaker 1: the rest on our website. One is called No Uncommon
Speaker 1: Disease by Sally McMillan. Another is called an Essay on
Speaker 1: the History of Lockjaw by William Shalian, and the last
Speaker 1: one i'll shout out is called the population structure sure
Speaker 1: of Claustridium tetani deduced from its pan genome, and that
Speaker 1: is by Chapaton Montes at All from twenty nineteen.
Speaker 2: I had just a few papers for this episode. I
Speaker 2: really enjoyed. Actually, a nineteen ninety four paper called the
Speaker 2: Mechanism of Action of Tetanus and Botulinum neurotoxins. It was
Speaker 2: pretty thorough, and then a twenty nineteen Botulinum and Tetanus
Speaker 2: Neurotoxins kind of an update, a few other papers on
Speaker 2: the epidemiology as well as links to the World Health
Speaker 2: Organization and the CDC surveillance, and then that awesome paper
Speaker 2: that just came out in March of twenty twenty two
Speaker 2: was titled Listeria delivers tetanus toxoid protein to pancreatic tumors
Speaker 2: and induces cancer cell death in mice. So it really
Speaker 2: tells you the whole study. And we'll post the list
Speaker 2: of these sources and every source from every one of
Speaker 2: our episodes on our website, This podcast will kill You
Speaker 2: dot com.
Speaker 1: Thank you Tomobile for providing the music for this episode
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Speaker 2: You filthy animals. M.