Ep 48 Botulism: Why are you the way you are?

You don’t look surprised to see this in your podcast feed - or is that just the botox? This week we’re taking a tour of the wonderful world of Clostridium botulinum and the toxin it produces, at once both poison and prescription. First, we delve into how botulinum toxin acts to paralyze your muscles and under what circumstances you might encounter it. Then we iron out the wrinkles of the why of botulinum toxin, an answer that involves migratory birds, maggots, and marshes. The story continues with blood sausages, an unfortunate funeral party, and a massive shift from toxin to treatment as the therapeutic potential of botulinum toxin is explored. And the best part of this episode? Georgia. Hardstark. You’ve heard the always amazing, ever hilarious, and one of our personal heroes Georgia Hardstark on My Favorite Murder, but now listen to her share her firsthand experience with getting botox facial injections. This episode ranks among our top favorites we've ever recorded, and we hope you love it as much as we do!

See omnystudio.com/listener for privacy information.

Episode Transcript

Speaker 1 (00:01):
Hi, I'm Georgia Hardstark and I co host the podcast
My Favorite Murder.

Speaker 2 (00:06):
And uh, of course I had heard about botox for years.

Speaker 1 (00:09):
I think everyone you know knew about it, knew what
it was, and it didn't even cross my mind until
I had a friend who got it done and she
was you know, we were both in our mid thirties,
so you're thinking like, well, I don't need it yet,
and then I saw her face and it looked it's
just you know, she didn't She looked awake. I guess

(00:31):
was the thing that really hit struck me. And then
I was in this really cool, like secret Los Angeles
Ladies Facebook group and they all got it done, and
so I kept like it normalized it for me and
we were all you know, they were there from their
mid twenties to thirties to forties. It was all ages,

(00:51):
so it didn't suddenly feel like this thing that only
you know, you had to get when you were older
and already you know, having issues.

Speaker 2 (00:59):
The way I read it about it was that it
was preventative, which I found really interesting.

Speaker 1 (01:03):
Because you know, the less you're making the furrowing your
brows and making those creases, the less the lines are
going to stick around.

Speaker 2 (01:12):
And I was really.

Speaker 1 (01:13):
Nervous because it's you know, I had to get past
feeling vain about it, which I think is a normal thought.

Speaker 2 (01:22):
And then I, you know, I just.

Speaker 1 (01:24):
Realized there were these little things about my you know,
wrinkles that were bothering me.

Speaker 2 (01:29):
And I think that's the main thing, is like it's.

Speaker 1 (01:31):
Not for everyone, and everyone and wrinkles are beautiful and
not everyone you know, is going to want to do it,
and I think that's totally fair. But I think if
it's for me, it's like a simple fix that will
make me just feel a little more confident, you know,
which is a big, huge plus for me. So you know,
it's not going to change your face, not going to

(01:52):
change your life, but you know, yeah, So so I went.
It was and I got it the first time right
before mine, Evince's wedding, so it was like thirty five
or thirty six, and I was super nervous. I was
gonna I was scared I was going to completely change
my face. You know, it's a little needle, so of

(02:13):
course it's not going to feel good. And then you know,
they poke it in and so do you want to
do a lot of little spots. You don't just do
it in one spot. And I get it done in
my forehead and between my eyebrows and on my smile lines,
and so you get it's a couple different pokes, like

(02:33):
maybe I think mine are like twelve pokes total, and
you can kind of it's really gross. You can kind
of hear when they're injecting it. It's like a sqush
in like your inner ear. You can hear it. That's
the only horrible part. Yeah, it doesn't it hurts because
it's a needle, But I feel like with that and

(02:55):
like tattoos, when you're excited about what you're doing, it
doesn't hurt as bad. And they give you a you know,
a stress ball to squeeze, and it's over so quickly,
and you know, it's just part of it. If you
if you're totally afraid of needles, obviously you're not gonna
want to do it. But and it takes like two
weeks to start showing up, so it's kind of good

(03:16):
that it's.

Speaker 2 (03:17):
Slow and subtle.

Speaker 1 (03:18):
It's not this like right away change. And so when
I finally, you know, no one knew that I had
gotten it done. None of my even my closest friends
hadn't known. So when I finally told, like my best friend,
she was shocked and she was like, now that you're
saying it, I see it. And I was like, I

(03:38):
look like I'm thirty again, and she's she blurted, you
look better than that, and I was like, Okay, I
like this.

Speaker 3 (04:33):
Well, that was one of the most exciting things to
ever happen. Absolutely thrilling. Thank you so much, Georgia for
being a part of this and sharing your story and
wealth of knowledge. Yes, thank you, thank you. That was thrilling.

Speaker 4 (04:48):
Oh my gosh, uh huh, and much more uplifting than
other first hand accounts of the subject of today's episode, which.

Speaker 3 (05:00):
Which is botchelism bochelism, well like batchulinum toxin sure, Clasterdium botulinum.
How about that ye have about?

Speaker 4 (05:10):
Hi? I'm Aaron Welsh and I'm Erin Alman Updike and this.

Speaker 3 (05:14):
Is this podcast will kill you today.

Speaker 4 (05:16):
We're talking you know what we're talking boche line.

Speaker 3 (05:25):
Well, we have a couple of pieces of business to
get into before we start this episode, which I know
we say this all the time, but I am so
excited for this. It got to the point where I
was telling, because I know I didn't want to tell
you the things I was learning yet. But I was
like texting everyone else like, oh my gosh.

Speaker 4 (05:47):
No, yeah, I do the same thing. Ye yesterday, I
was like Brett, did you know? And I just like
started shouting botox facts at him.

Speaker 3 (05:55):
Yeah. Well, I'm glad that we finally get to lit
it all off our chests. Me too.

Speaker 4 (06:00):
It's going to be It's gonna be a good one.

Speaker 3 (06:02):
I think.

Speaker 1 (06:03):
So.

Speaker 3 (06:04):
Okay, So, like I said, though, some business Number one
is that we are going to keep doing these regularly
scheduled episodes or whatever, and we are going to keep
them COVID free.

Speaker 4 (06:20):
We are COVID. This is a COVID free zone right now.

Speaker 3 (06:23):
Yeah, so we promise we won't even say it after
too many more times and so and so what we're
doing is is, as you may have seen in your feed,
we're going to keep dropping those COVID nineteen episodes every
so often, just on a We don't really have a
particular schedule for.

Speaker 4 (06:41):
That's just whenever they happen. Happen, but in order.

Speaker 3 (06:44):
But we also recognize that people may not want to
hear about what's going on or it might be too
stressful or whatever, and we totally get that, and so
all of these normal episodes will just be normal normal episodes.

Speaker 4 (06:59):
Jinks.

Speaker 3 (07:00):
So okay, all.

Speaker 4 (07:02):
Right, all right.

Speaker 3 (07:03):
Number two, we have now joined the affiliate program of
this organization called bookshop dot org. And so what this
is is it's a website that it's an online bookstore
website that works with independent bookstores. And so as an affiliate,
we have a page where you can see our lists

(07:24):
that we have curated for what books, you know, nonfiction books,
fiction books, memoirs about disease and about health and stuff
like that. And so if you are so interested, you
could go on our website under the books tab and
you'll find a link to bookshop dot org. And also
we have links in each of our uh so, in

(07:44):
each of our episodes where we list our sources, we
will provide links to those books on bookshop if they
exist there.

Speaker 4 (07:54):
Cool.

Speaker 3 (07:55):
Cool.

Speaker 4 (07:56):
One other piece of business, if you are not aware yet,
we have now alcohol free episodes available on our website
if you'd like to use those for whatever reason, if
you don't want to hear us talk about quarantinies, you
can find those on our website yep.

Speaker 5 (08:11):
Cool.

Speaker 3 (08:11):
Speaking of quarantinies.

Speaker 4 (08:13):
It's quarantiny time, it is.

Speaker 3 (08:17):
What are we drinking this week?

Speaker 4 (08:19):
This week we're drinking can of Germs.

Speaker 3 (08:26):
And we have a big thank you to Bloodmobile for
providing that's the quarantine.

Speaker 4 (08:31):
Name for this episode and all of our episode. Just
kidding a lot of our episodes though, Ah, thank.

Speaker 3 (08:38):
You Bloodmobile slash Daniel my brother.

Speaker 4 (08:42):
Really that's a phenomenal drink name. Can of Germs from watchlism.
Oh my god, what is in can of germs? It
is rum canned pineapple of course, honey. Also, of course
we'll talk about it and lime juice.

Speaker 3 (09:04):
Yeah, it's pretty good.

Speaker 4 (09:06):
It's pretty good. Actually, yeah, it's not bad.

Speaker 3 (09:10):
So awesome?

Speaker 4 (09:11):
All right, then anything else or can we just get
into this episode, Erin.

Speaker 3 (09:16):
Let's get into the episode please?

Speaker 4 (09:19):
Awesome right after this break. So when we talk about botchelism,

(09:53):
when we talk about bocheln, botox, whatever, we're talking about
a specific pathogen that I'm very excited, Erin, for you
to tell me about where this pathogen came from, because
you specifically told me not to look that up.

Speaker 3 (10:08):
Oh, I was very adamant, like, don't read about this.
I didn't read them at all all caps text. You're
not gonna talk about this, are you.

Speaker 4 (10:17):
Nope, I am not. But we will talk a little
bit about the bacterium itself. So this bacterium is called
Clostridium botulinum. You may have heard the term clustridium if
you've ever heard of, for example, Claustridium difficile see diff Yeah,
a lot of people probably have. This is another Claustridium

(10:38):
species that causes disease in humans. It causes massive, very
serious diarrhea. It's a pathogen of pretty big concern, especially
in hospitals. So Claustridium botulinum is another bacterium in the
same genus. These Claustridium species are gram positive, which means

(10:59):
they stay purple when you look at them under a microscope.
That's what we always say on this podcast. It means
that they have a thick cell wall. Okay. Clusterdium species
are rod shaped, so they look like little tic TACs. Okay,
and very importantly, they are what we call spore forming anaerobes.

(11:24):
It's a lot of technical terms. Let's talk about what
they mean. So anaerobe means that this is a bacteria
that grows and lives without any oxygen. Okay, that's really important.
So it can't just grow like on your table out
in the open, or on your fingernail or in your
nose or something like that. Okay, I don't know why

(11:47):
I said fingernail.

Speaker 3 (11:48):
The fingernail is my favorite frame of reference. I want
to swab my fingernail now and see what's.

Speaker 2 (11:55):
I mean growing there.

Speaker 4 (11:56):
Probably find some weird stuff, but not clusterdium species.

Speaker 3 (12:00):
Okay.

Speaker 4 (12:02):
Our atmosphere, of course, is twenty one percent oxygen. So
how can this bacteria survive if it's like surrounded by
oxygen all the time?

Speaker 3 (12:15):
Quick question? Did you know that off just like the
back of your hand that it was?

Speaker 4 (12:22):
Yes? I did? Did you not? Oh? Well, now you
know listeners, did you know? Huh, it's yeah, that's I
did know. That's a that's a trivia fact. I did know.
And it's important because we talk about it in medicine,
because you know, when you put someone on oxygen, you
have to think about how much oxygen they're getting and
what that is compared to what is what they're normally

(12:44):
breathing in at room air. So if they're on twenty
one percent oxygen that's actually like room air.

Speaker 3 (12:49):
Oh so awesome.

Speaker 4 (12:51):
Yeah, oh how fun. Look medicine teaches you things who knew? Okay, so,
how did does this bacterium survive if it's surrounded by
oxygen and it needs to live and grow in an
environment without oxygen. The answer is that it's a spore former.

(13:12):
I can't remember if we've talked on this podcast before
about spore forming bacteria, So let's talk about what spores are.
So bacteria that are spore formers here, we're talking about
specifically what are called endospores. So these are things, for

(13:32):
lack of a better word, that bacteria produce that are
super environmentally stable. They're basically a stripped down structure that
contains the DNA of the bacteria but can persist in
the environment for a really, really long time. So these
are not reproductive structures. When you hear the word spore,

(13:53):
you might think of like a fern spore or a
mushroom spore. Those are like reproductive things. So endospores, bacterial
endospores are not reproductive structures. They're basically just a form
that the bacteria can produce in order to resist bad
environmental conditions.

Speaker 3 (14:15):
Yeah, just kind of like a wait and see a
little blueprint for the future.

Speaker 4 (14:19):
Exactly right. And so when a bacteria senses that environmental
conditions might be deteriorating to the point where they're not
going to be able to survive and continue to reproduce,
they begin to form this endospore. And then if those
environmental conditions deteriorate and the bacteria around that endospore dies
and deteriorates, the endospor stays alive. Essentially, it doesn't do anything.

(14:43):
It just exists until conditions are right, and then it
can reactivate okay, yeah, and go on to form another living,
reproducing bacteria. So these endospores are really important because they're
resistant to things like UV. They're in the case of anaerobes,
they're resistant to oxygen, which could kill reproducing Clostridium botulinum.

(15:08):
They're resistant to alcohol, to soaps too hot, too cold,
to certain levels of radiation. They're really really hardy little
packets of DNA, which can make them especially dangerous in
a hospital setting if things aren't sterilized properly. And so
that's part of the reason why sea diff Claustridium difficile
is really scary in hospital settings. Because like just using

(15:30):
alcohol based hand sanitizer doesn't kill the spores of these.

Speaker 3 (15:33):
Bacteria, right, And we'll do a whole episode on sea
diff in the future at some point because it's definitely
worthy of its own massive episode, absolutely, And we're also
going to do another episode at some point on another
Clostridium species, tetanus.

Speaker 4 (15:51):
Oh yeah, Oh my gosh. I forgot that tetanus was
another another tops I think that's why. Yeah, I I
went back and watched the sketchy micro videos for this,
and like, tetanus and and botulism are kind of opposite
ends of the spectrum, which is really interesting, and so
I remember like comparing the two between them. So maybe

(16:13):
I thought that we had done tetanus already. I don't know.

Speaker 3 (16:17):
The only other spore former I can think of off
the top of my head is anthrax, and.

Speaker 4 (16:21):
I, yeah, antax, we haven't done that. Yeah, we'll do
that eventually too. Anyways, there's more, but those are the
big ones. Yeah, Okay, but the spore isn't actually the
story here, Okay, of course not, of course not. It's
part of the story, but it's not the story that
we're focusing on on this podcast. Will kill you. What

(16:42):
we want to talk about, of course, is the part
of this bacteria that makes you sick. So we're here
today to talk about botulism. It turns out that botulism
is caused not by the bacterium itself, not by the
spore itself, but by the toxin that that bacterium produces. Okay,

(17:06):
oh yeah, this is called botulinum toxin. So what I
want to do first is we'll talk about that toxin itself,
the mechanism of action of that toxin, which will pretty
clearly tell you what the symptoms that you're going to
see are of this like of poisoning from botulinum toxin.

(17:26):
And then we'll talk about the ways that you can
get exposed to this toxin, because there's a few different,
very distinct ways that you can be exposed to this toxin. Okay,
all right, so first of all, what is boculinum toxin.
We've definitely talked about toxins a lot on this podcast
because lots of bacteria produce different kinds of toxins. It's
basically just usually proteins that a bacteria produces that have

(17:50):
an effect that do something for that bacterium. Okay, so
like cholera toxin exactly. Cholera toxin we talked about staff
or produces a lot of different toxins that have different effects, right,
So in the case of botulinum toxin, this is a
neurotoxic protein that the bacteria produces, so it has effects

(18:17):
specifically on our peripheral nervous system and largely on our
somatic nervous system. So if you remember in our episode
on Belladonna way back when cast my mind back so
way back when we talked about there's a lot of
different ways that you can divide up the nervous system. Right,

(18:39):
we have our central nervous system, which is like your
brain and your spinal cord. You have your peripheral nervous system,
which is everything outside your brain and your spinal cord
that like where your nerves go to your muscles and
your organs. You can also divide it into your somatic
and your autonomic nervous system. So your somatic meaning like
your sury and muscles nervous system, and then your autonomic

(19:04):
nervous system, which is like your parasympathetic and sympathetic rest
and digest versus fire or flight. Remember that kind of Okay.
So in this case, the effects of boculinum toxin, they
act on a couple of different places. They act both
on the parasympathetic nervous system, but largely on the somatic

(19:25):
peripheral nervous system. So let's first talk about what that
nervous system is and how it works, so that we
understand how botulinum toxin interferes with that process. Excellent, Okay,
So you're I'm also not a neurologist or a neuroscientist,

(19:45):
so this is real basic okay. So your brain, of course,
is what controls all of the movements of your body.
So how does your brain do that. You have nerves.
Your brain is connected to your spinal cord, which is
connected to nerve that innervate your muscles, okay, or your organs.

(20:06):
So the way that this kind of happens is that
electrical signals in your brain are transmitted along those nerves,
along what are called axons of those nerves, and then
when they get to the end of the nerve, which
is called a synapse, there's a gap between that nerve
and for example, your muscle, and so in order for

(20:29):
that electrical signal in the nerve to transmit across that
gap and have an effect on the muscle. That electrical
signal has to be translated into a chemical signal, and
then the chemicals can travel across that gap, that synapse
between the nerve and the muscle, and they can propagate

(20:52):
that signal into the muscle. Does that make sense? Yeah, yeah, cool,
that's the first time I've ever explained that. So that
was fun. Okay, So when you're looking at the synapse,
the gap between the end of your nerve and the
start of your muscle, there's the presynaptic end that's basically
the nerve that came like from your spinal cord, and

(21:14):
then the post synaptic end. You can think of that
as your muscle. It turns out that the for your muscles,
especially like your skeletal muscles, the transmitter, the chemical signal
that is used to transmit that signal is called acetylcholine. Okay.

(21:34):
Acetyl Coline is released at the pre synaptics, So from
the nerve ending, acetyl coline is released, it travels across
that gap and binds to a receptor on your muscle end,
and then that is what actually causes your muscle to go, hey,
I'm gonna contract and boom contracts.

Speaker 3 (21:53):
Gotcha.

Speaker 4 (21:55):
So acetyl colin is really important in that. So how
does botulism work. So it turns out that botulinum toxin
blocks the release of acetylcholine from that presynaptic nerve ending. Gotcha.
So you have an electrical signal that's transmitted from your brain,

(22:17):
it gets to the end and boculinum toxin is there
and says, Nope, you can't release acetylcholine. So then your
muscle goes it's got nothing.

Speaker 3 (22:28):
Are there toxins or venoms or something that block from
the other end from the muscle binding site.

Speaker 4 (22:38):
We already talked about one and that was oh yeah,
So belladonna and belladonna tends to act only on the
parasympathetic receptors because there are two different types of acetylcholine receptors,
there's muscarinic and nicotinic, and so botulinum acts on the
presynaptic end, so it blocks all acetylcholine release.

Speaker 3 (23:00):
Oh my god.

Speaker 4 (23:00):
Atropine binds to the receptor, but only the muscarinic receptor,
so not the ones in your skeletal muscle. Oh my gosh,
this is so thrilling, I know, right, I'm so glad
you find it thrilling.

Speaker 3 (23:12):
Yes, I do too, This is so exciting.

Speaker 5 (23:14):
Yeah.

Speaker 4 (23:15):
Oh wow. So yes, there absolutely are things that bind
that you know do and there's other toxins as well too.
There's other there's other venoms, there's other toxins that interfere
with this acetylcholine and whether they do it, and and
so that question is really important because in the case
of botulinum, by blocking the release of acetylcholine, you leave
those acetylcholine receptors on the muscle empty, which means the

(23:40):
muscle is not getting a signal to contract, which means
the muscle is relaxed. So the symptoms that we see
of botulinum poisoning are a flaccid paralysis rather than a
contract did paralysis, which we see in other toxins that

(24:04):
have different mechanisms of action.

Speaker 3 (24:06):
Like tetanus. Like tetanus. Yeah, that's really cool.

Speaker 4 (24:11):
I know, Okay, it's very cool. I love it. I
mean I don't love it. It's horrible. Okay. So, now
that we know the action of botulinum toxin, it's acting
at the neuromuscular junction, the synapse between nerve and muscle
and it's blocking the release of acetylcholine, which means your
muscles are getting no signal, which means they are relaxed

(24:34):
and flaccid. So we pretty much know what the symptoms
of botulism are, right, They're a flacid paralysis. These symptoms
are the same no matter how you get exposed to
botulinum toxin, right, because this is a toxin, it's traveling
throughout your bloodstream once it gets into you, no matter

(24:55):
how it gets in, it's going to travel through your bloodstream,
and it's going to act on any nerve ending that
it comes in contact with. Okay, is the.

Speaker 3 (25:06):
Flaccid paralysis just sort of generally distributed throughout your body
or is it concentrated depending on your root of exposure?

Speaker 4 (25:13):
Great question, Arin, So what's very interesting about botulism specifically
is that it causes a descending paralysis. Okay, So the
paralysis starts in your face and your head. It starts
with your cranial nerves. It causes a bilateral so both

(25:34):
sides symmetric cranial nerve palsies that then eventually travels down
and will cause flaccid paralysis throughout no matter the root
of entry and we'll talk about the specific different roots
of entry. This is botulism. Yeah, so you're exposed to
enough toxin that it is distributed throughout your body and

(25:55):
causing botulism. If you are exposed, for example, like in
our first hand account, to a very small amount of
very very dilute toxin in a very specific place, there's
not enough of that toxin to travel throughout your body
and cause systemic effects. Right, it's a doge thing exactly. Yeah,

(26:17):
and so all of the symptoms that we see with botulism,
even with botulism, are dose dependent, right of course. Yeah,
why does it start in your head? It's such a
good question, and I don't I don't know. I couldn't
figure out the exact answer to this. And what's interesting though,
is that it does distinguish. So if you clinically see

(26:38):
someone with paralysis, a flaccid paralysis, you know you have,
as a clinician in your head a list of what
you call differential diagnoses. What could be causing this? What
are all the different things that could be causing the
symptoms that I'm seeing? Right, And there's a few different
things that you have to think about, things like gion
beret for example. But gion beret causes an ascent paralysis.

(27:01):
So knowing the timeline of symptoms, like where they began
and how they've changed over time, is really important in
trying to diagnose spotulism. And I think that this is
also partly why for a long time it was thought
that this was a central nervous system toxin, because your
cranial nerves are closest to your brain, right. Yeah, they're

(27:21):
coming out like directly from your brain stem, right, But
it's actually a peripherally acting toxin. It's acting at the
neuromuscular junction. So it's very interesting that your cranial nerves
are still the first ones affected.

Speaker 3 (27:33):
This is fascinating, I know.

Speaker 4 (27:35):
Okay, so here are the symptoms, right, So the first
signs and symptoms are things like blurred vision. As the
muscles that innervate your eyes become affected, then you'll get toosis,
which is a great word that means your eyelids are droopy, okay,
because your eyelid muscles are not working right. Then you'll
get slurred speech. As the muscles of your mouth and
face get affected, then the paralysis will continue moving down

(27:58):
your body. You can get mouth and throat because again
that parasympathetic nervous system is also affected. So that's actually
similar symptoms as to what we saw in Belladonna poisoning,
dry mouth, dry as a cracker or whatever, I don't
remember what that one was. Dry as a bone, mad

(28:19):
as a hatter, a chicken, mad as a hatter, dry
as a bone.

Speaker 3 (28:22):
Dry as a bone, etc.

Speaker 4 (28:25):
And then your voluntary muscles will start to become paralyzed,
so first your neck, your shoulders, your upper arms, lower arms,
upper legs, lower legs. Eventually everyone would end up with
constipation as the muscles that innervate your gut are paralyzed,
because gut in order to have poop at all, your
gut has to be able to contract. Cause of death

(28:48):
is usually respiratory arrest, and there's two different ways that
this sort of ends up happening. The muscles that control
your breathing, your diaphragm and your innercostal muscles of your ribs,
those become paralyzed just like everything, and you can also
get airway obstruction as the muscles of your pharynx are paralyzed,
your airway can kind of collapse inward and you can't,

(29:10):
so it's kind of a combination of those two that
ends up causing death in the case of botulism.

Speaker 3 (29:15):
Oh cool, cool, cool, cool. That's horrifying.

Speaker 4 (29:18):
It's horrifying the rate that this progresses. So how long
this all takes and how far it actually progresses, So
whether it makes it all the way to your respiratory
muscles or whether you just have like only facial palsy
depends largely, like I said, on the dose of toxin exposure. Right. However,

(29:43):
and this part's really important. Botulinum toxin binds irreversibly, so
you cannot undo any damage that has already been done.
But your body does eventually regenerate those acetylcholine channels on
the terminal. It's just a slow process. So it's not

(30:03):
like if you have facial palsy, you're not going to
have a paralyzed face forever, but you can't undo that paralysis.
You just have to wait for it to resolve.

Speaker 3 (30:14):
So how long are we talking?

Speaker 4 (30:18):
Generally weeks? Possibly months?

Speaker 3 (30:20):
Okay, A couple questions. The first is something that I've
read somewhere about maintaining consciousness.

Speaker 4 (30:28):
Aaron, this is what I have next. Okay, for you,
this is just for you. Aarin. Okay, your sensory system
is generally unaffected and your intellectual function is unaffected. So yes, aarin,
it's your greatest fear. It can leave you essentially locked.

Speaker 3 (30:45):
In Cool cool, right, awesome, because why can we keep
doing these?

Speaker 4 (30:52):
Yeah? Because you're paralyzed. And here's what's really scary is
that because the muscles, like the voluntary muscles of your
face and your throat and things, are paralyzed, as you
begin to have respiratory distress, you don't show any of
the outward signs or symptoms of respiratory distress. There's no agitation,

(31:13):
there's no restlessness. You're not gasping or thrashing or flailing
because you're paralyzed. Great, So the way that you know
that someone is in respiratory distress is because their oxygen
saturation is dropping on a monitor. So if you're at home,
then you wouldn't.

Speaker 3 (31:31):
At that point what can be done?

Speaker 4 (31:34):
So that is jumping the gun. But let's talk about treatment.
The good news is there is treatment for this. It's
absolutely can be fatal, but it is also treatable. We
have an anti toxin. This anti toxin neutralizes circulating toxin
and prevents it from binding to the nerve terminal, so

(31:57):
it doesn't do anything for the toxin that's already bound. Right,
we can't unbind that toxin, but it can neutralize any
additional toxin that's circulating. So it's really important if these
signs and symptoms start to appear that you get to
a hospital for treatment, because then they can continue supportive

(32:18):
care even if it gets to the point where you
have like respiratory distress and things like that.

Speaker 3 (32:23):
To get the anti toxin early is yes, clutch, The
earlier the better, is clutch, is right?

Speaker 4 (32:31):
Okay, So that's like what botulism looks like clinically, what
the picture looks like. So how do you get it?
How do we avoid it? Right? Yea? How do we
not get it? Is what we want to know. There's
three main ways and then a couple of ancillary ways
as well. The first, most famous, I think, is food poisoning. Right,

(32:54):
So if food is contaminated with Claustritium botulinum bacteria, and
then those bacteria live in an environment that allows for
them to grow, so no oxygen, not too low of
pH so not too acidic, and just basically like a
good environment for them to start growing and reproducing, they

(33:15):
will then produce that toxin. You get botulism when you
ingest that toxin, not by ingesting the bacteria themselves, gotcha. Yeah,
So this is the same way that you might remember
when we talked about in our staff Oreus episode, our
Mersa episode, you get food poisoning from staff oureus from

(33:39):
the toxin. Right, This is the same thing you get
infected with the toxin. So if you have, for example,
like canned tomatoes are a really good example because they're
actually not that acidic. So if tomatoes are canned improperly
and you have a bunch of Clustriti and boculinum growing
in there and then producing to even if you reheat

(34:02):
those tomatoes, you might kill the bacteria, but that toxin
is still going to be there, so you can still
get sick from.

Speaker 3 (34:08):
It, Okay, but you can neutralize the toxin.

Speaker 4 (34:12):
You can absolutely, Yeah, if you like, boil it for
I don't remember how long exactly, Yeah, you can definitely yeah, yeah, okay.
But that's why it's that's why it's like so common
in foods. The bacteria can die, you know, after a
certain period of time, but that toxin can still be
in those cans of food, right, So that's one way.
That's the most common way food poisoning botulism. Okay, yep.

(34:36):
Now you can get infected with the bacteria themselves or
the spores which you're more likely to come in contact
with in the environment, right, in a couple of different ways.
The least common but less depressing is wound botulism. Oh yeah, okay,

(34:57):
So if you have a wound that gets can tam
ned either with Clustridium botulinu bacteria or they're spores, which
are very common in the environment. If that wound festers,
it can become anoxic. In that environment, the bacteria or
those spores can reactivate and begin to reproduce and produce toxin.
So then you the bacteria are making toxin in your

(35:21):
own body. The effects are the same as if you
got botulism from food poisoning. Okay, they're the same because
this is a toxin that has neuromuscular effects, so it's
the overall it's the same right now. The most common,
and I think the most depressing form of botulism, of course,

(35:42):
is infant botulism. It's always depressing when it's babies, so
and this is different. Even though this happens when an
infant ingests like so it's technically a food poisoning, it
is not the same as when an adult it's botulism.
And that's because infant botulism happens when infants ingest the

(36:07):
spores of Clustridium botulinum, So unlike adults, infants, especially of
a certain age so it's usually greater than like three
weeks but less than one year old, they have a
very naive and naked gut flora, so their guts are
not able to inactivate or prevent those botulinum spores from

(36:29):
becoming activated and colonizing their guts. Gotcha, So then the
bacteria in the infant gut reproduce and produce toxin inside
of the baby, rather than the baby eating toxin directly.

Speaker 3 (36:43):
Yeah, that's horrible.

Speaker 4 (36:44):
And infant botulism is often called floppy baby syndrome. Okay,
that makes sense with the Flacci paralysis exactly right. It
is possible. However, it's extremely extremely rare for an adult
to become colonized with clustering boculinum and then have that
same syndrome as infant botulism. It's called adult intestinal toxemia.

(37:06):
It's just very rare because we have other microflora that
are much better at competing and outcompete those clusterdium species.
It's similar with Clusterdium difficill Like, that's an opportunistic infection, right,
it's not good at taking over our gut flora.

Speaker 3 (37:23):
Right, So it's usually it's like following a huge rounds
of antibiotics and stuff like that, right.

Speaker 4 (37:28):
Yeah. One question is where do infants get exposed to? Yeah, honey,
So that's like and it's just because honey is a
it just has a ton of spores like it. There
are a lot of Clushodium boculinum spores very commonly found
in honey, and because an infant gut can't neutralize those spores,

(37:52):
they can get infected with botulism or with clus shooting
boculinum and developed botchulism from honey. It's not the only
thing in the world, but it's sort of the most
one of the most common roots of exposure. So that's
why infants under twelve months can't have honey. Yep, shouldn't
have honey.

Speaker 5 (38:09):
Yeah.

Speaker 4 (38:10):
It's also possible to be infected through aerosolized toxin, so
you could in theory inhale this. I don't know that
it's ever been recorded. It would have to be intentional.
Oh a little bit about that, can't just a little
And then of course you could get it through injection
as well. So if you injected a large amount of
this toxin into your veins or muscles, then it could

(38:32):
spread through your body and cause botulism that way as well.

Speaker 3 (38:36):
Cool.

Speaker 4 (38:36):
But now, so botulinum toxin is considered the most potent
toxin that we know of. Are you going to talk
more about that?

Speaker 3 (38:47):
Aaron, Well, I can drop the knowledge right here if
you want me to.

Speaker 4 (38:51):
Let's because I'm I I want to know about it.

Speaker 3 (38:53):
Okay, Well, all I know about in terms of that
is I read somewhere in one of these papers that
because the amount of botch linem toxin that it takes
to kill an average human is xinec whatever amount.

Speaker 4 (39:07):
Yeah, if you some very small amount, some.

Speaker 3 (39:09):
Tiny, tiny, minuscule, unfathomably small amount, if you multiplied that
by the number of people on Earth, estimates are that
it takes approximately forty grams of botchulinum toxin to wipe
out humanity.

Speaker 4 (39:23):
That's why you wanted me to weigh out forty grams
of something?

Speaker 3 (39:26):
Yeah, I texted. I texted you, and I was like, so,
can you just put like, how many slices of bread
is forty grams? Because I visualize this, So how many
slices of bread is forty grams?

Speaker 4 (39:37):
Okay, the sour dough bread that I have right now,
one slice of it weighs forty five grams. Okay. For
another visual a half a cup of coffee beans is
forty grams.

Speaker 3 (39:49):
There you go.

Speaker 4 (39:50):
So that's how much botchulinum toxin it would take to
kill all of the humans on the planet right now.
That's what I Yeah, I have, and I have the paper.

Speaker 3 (39:58):
All cite the paper on our web site so you
can go and read it for yourself. But yeah, like
thirty nine point four grams or something. Whoa that wild?

Speaker 4 (40:08):
Yeah man, that's whoa. Well, that's botulism. That was it.
That's all I got. We already talked about how you
treat it. So oh that's it's a little terrifying. But
we'll talk later about how how innovative people have gotten

(40:30):
with something that is so terrifying.

Speaker 3 (40:34):
Yeah, I'll talk about it it's super it's really fascinating.
This is I think one of my favorite episodes so far.
I don't know why tell.

Speaker 4 (40:42):
Me about it, Aaron. How did we get here? Where
did this thing come from? How did it evolve? Why
does it have a toxin that can kill all of humanity? Like?
What's up with that?

Speaker 3 (40:49):
I'm so glad you asked. I will answer as well
as I can after this break. Okay, doesn't this remind

(41:30):
you of an episode of one of our crossover episodes
with Matt.

Speaker 4 (41:34):
One hundred percent? Yes? Yeah, that's why I kept talking
about atropine and stuff exactly.

Speaker 3 (41:39):
Matt. We miss you.

Speaker 4 (41:40):
Yeah, we'll do another crossover soon.

Speaker 3 (41:42):
Yeah, we will. He doesn't know it, but he doesn't
know it. We want to do another crossover soon, Matt. Okay, So,
just like you asked, uh, why does this toxin exist?
Why does this bacterium produce this toxin? And so that's
what I want to start off by trying to answer, basically,

(42:03):
why are you the way you are?

Speaker 5 (42:05):
So?

Speaker 3 (42:06):
In our normal episodes, this type of question is generally
pretty easy to answer, right because it mostly has to
do with the pathogen increasing its chances of transmission or
something like that that's generally the pattern that we see.
Like for example, as we mentioned earlier, the toxin that
the color of bacterium produces makes you poop out a

(42:28):
ton of Bibrio cholera cells, so it can spread to
other people.

Speaker 4 (42:33):
I'm so excited about this, I can't wait, Like, yeah,
why then?

Speaker 3 (42:39):
But with batulism, humans seem more like unfortunate bystanders than
the stars of the show, right, right, So it's not
spread from person to person. Really, so what purpose does
this paralytic or fatal toxin serve? How does it actually
help the bacterium? Does it even help the bacterium? To

(42:59):
answer that question, I got to talk a little bit
about the ecology of claustride and bochulinum.

Speaker 4 (43:07):
Your favorite, my favorite.

Speaker 3 (43:09):
A lot of the research on botulism focuses on humans,
like outbreaks at potlux, the toxins use in therapeutics, the
physiological mechanism of the toxin itself, et cetera. But to
these bacteria, humans play a very small role, right, Aaron,
this is jumping the gun. But around how many cases

(43:29):
of botulism do we see a year in the US.

Speaker 4 (43:33):
Like one hundred and eighty two in twenty seventeen.

Speaker 3 (43:35):
Yeah, like very low. Yeah, but it's a whole other
story for some other animals, especially migratory birds. Really really
botulism is one of the biggest, if not the biggest
disease of migratory birds, especially those that like water, like

(43:58):
shore birds and waterfowl swamp birds.

Speaker 4 (44:02):
This is literally blowing my mind.

Speaker 3 (44:05):
I'm so excited that it is a typical outbreak of
avian bochulism. So they happen pretty much every year. It
seems like they're pretty common. Might claim the lives of
fifty thousand birds or more, but there have been outbreaks
with over a million birds dying.

Speaker 4 (44:23):
What on Earth?

Speaker 3 (44:26):
Yeah, and most of these outbreaks and you didn't really
talk about types, but just fyi, it's like types of toxins,
because it's a whole nother canama terms. Oh that's good,
but these are just for reference type C.

Speaker 4 (44:42):
Bochulinum toxic. Okay, yeah, okay.

Speaker 3 (44:45):
So the reason that we see these outbreaks occurring among
these water loving birds is that the environments where they
like to hang out they can be full of decaying
organic matter, which can make for a perfect setting for
the growth of these anaerobic bacteria. And these anaerobic bacteria
can then be easily ingested by like a dabbling duck

(45:08):
or a filter feeding shoveler. Dabbling duck, that's like an
actual term. Oh really, it's just a cute little It's like,
you know when they like kind of like across the
surface and they duck their their heads in and they
like the little butt stick out. That's like a dabble dabbling.

Speaker 4 (45:26):
You're making me like birds.

Speaker 3 (45:28):
Also, apologies to any bird people who are like, wow,
you're getting all of this wrong.

Speaker 4 (45:33):
So get an email from like Fred and Nick.

Speaker 3 (45:38):
And Maria and if we have a lot of bird friends,
I know. Sorry. Okay, So let's say that one of
these birds, one of these dabbling ducks ingest some swamp
stuff containing Clustridi and bachulinum. The bacteria may colonize that
birds and testines or liver without any apparent effects. Maybe okay, yeah,

(46:00):
And then let's say the bird dies for whatever reason.
Maybe it's because of the toxin. Maybe it's because it
hit a power line, maybe it's because it ate some whatever,
Maybe it just dies. Right, that decomposing bird is a
great environment for Clustridium bochulinum. It's warm, it's anaerobic, it's
everything you could ask for. Okay, if you're a clusterridian botchulinum, Yeah,

(46:24):
soon that carcass is teeming with C. Bochulinum and it's toxin,
and it's also hosting a ton of other decomposers, for instance,
some invertebrate decomposers like blowfly larvae. Yeah yeah, And so
normally waterfowl won't directly munch on vertebrate carcasses. But do

(46:45):
you know what they will munch on?

Speaker 4 (46:47):
Blowflies maggots.

Speaker 3 (46:48):
Yes, yeah, So the larvae that these blowflies laid in
the carcass become loaded with botulinum toxin, and invertebrates are
not affected by the toxin, and so other words, eat
these maggots die from the excessive amounts of toxin, and
that leads to more toxic maggots and so on. Whoa,
And so that's how these AVI and Bochulnum outbreaks can

(47:11):
be absolutely explosive. It's called like the carcass hold on,
let me find it's like the carcass maggot cycle.

Speaker 4 (47:20):
What how have I never heard of this? Erin?

Speaker 3 (47:25):
I know? It blew my mind?

Speaker 4 (47:29):
Oh my, Because they don't affect invertebrates. Uh huh, oh
my gracious.

Speaker 3 (47:37):
And then of course other vertebrates might directly feed on
the contaminated carcass and then die, which would then create
another amazing anaerobic environment for the bacterium to replicate, and
then that would spread the bacterium of the environment and
provide more anaerobic grin it just sort of the cycle continues.

Speaker 4 (47:56):
Oh wow, I'm getting chilled.

Speaker 3 (48:00):
Well, this is why I was so excited for this episode. Okay,
So I went into all of this to show like
a natural cycle of Cbochulinum and its ecological role. And
I did this to get at the question earlier, why
are you the way you are? Yeah, it could be accidental,

(48:20):
but most researchers believe that by killing a vertebrate host,
or even increasing the probability of a host dying, it
carves out a space for itself to replicate and produce
more toxin totally, and so the mechanism of that, like
the paralysis and blurred vision and so on, those are

(48:41):
things that even if the toxin doesn't necessarily kill you outright,
it will in the wild greatly increase your chances of
becoming a carcass.

Speaker 4 (48:51):
Absolutely of becoming a carcass. Also, I think that that's
our title, Aaron is why are you the way you are?

Speaker 3 (48:58):
Why are you are? Okay?

Speaker 4 (49:02):
I love it, It's fantastic. See it should just be see
bochul line. No, it has to be botulism, but botulism,
Why are you the way? So good?

Speaker 3 (49:12):
Are so good? I also liked no wrinkles in time,
which was tender for us.

Speaker 4 (49:17):
That's funny, but this is better.

Speaker 3 (49:23):
But yeah, so and so, if you think about it,
we've done so much laboratory research, not we, but the
world has done so much laboratory research on botchuline of toxin.
But those are under laboratory settings. And so the amount
that is that it takes to kill an animal in
a lab setting is much much, much greater than what
it takes to lead to death, right lead to natural setting.

Speaker 4 (49:45):
Yeah yeah, yeah, yeah yeah, Oh that makes so much sense.

Speaker 3 (49:48):
Yeah. So that I think is why this toxin exists.

Speaker 1 (49:53):
That is.

Speaker 4 (49:56):
Episode over. That's all I need to know. It's so cool.

Speaker 3 (49:58):
I know, I honestly was had the time of my life.

Speaker 4 (50:02):
What a fun fact, you know, I know, I don't know. Yeah,
what a clever little bacterium though.

Speaker 3 (50:11):
I know, I know, yeah, I think the whole like clever,
but you know, comparative evolution, and there's so there's so
much more that goes into this, like ecology, like why
are there multiple toxins? Why is there variation among their
toxicity or potency or whatever? Why, you know, why do
we see these different seasonalities, what triggers these avian bachulism outbreaks?

Speaker 4 (50:35):
Why quite so potent? You know what I mean, Like,
why couldn't you be like, you know, the amount it's.

Speaker 3 (50:42):
Yeah, yes, it's I mean, yeah, we could spend all
day talking about just this part of it, but but
that's not this podcast. Let's go back to the human
side of things. I guess. Okay, So see Bachulinum, as
you know, an environmental bacteria is probably super old, you know,

(51:04):
and it doesn't really seem though, to have a long
evolutionary history with humans because of this more incidental nature
of infection or impact. But at the same time, it
has not been a stranger to humans throughout history, like
probably all of human history. That makes sense, Yeah, I mean, essentially,
as soon as humans started to try to preserve or

(51:26):
store food, there were cases or outbreaks of botulism, right,
and probably honey. Honey's one of the oldest foods in
the world. Yeah, so infant botulism boom. And so while
in ancient times people may not have recognized exactly what
was causing food related paralysis or death that they may
have seen, it does seem like they took note of

(51:48):
the foods where it seemed more likely to happen, like
blood sausages or cured ham or fermented fish.

Speaker 4 (51:56):
Interesting.

Speaker 3 (51:57):
Yeah, let me give you a couple of examples. The
powder of blood sausage dried under anaerobic conditions appears as
an ingredient and at least one recipe for a deadly potion. Ooh,
and Emperor Leo the sixth of Byzantium, who ruled in
the late ninth and early tenth centuries, just go with it.

(52:18):
He outlawed blood sausages, like the production of them and
then whatever.

Speaker 4 (52:24):
And where you get your facts. I just love it.

Speaker 3 (52:29):
But some researchers think that him outlying blood sausages is
tied to blood sausages being a more common source of botulism. Okay,
And some descriptions of poisoning with atropine aka belladonna may
have actually been botulism instead, because they describe a different
They describe like the consciousness and then like the.

Speaker 4 (52:52):
Full the paralysis. Yeah right, yeah, because you don't get
that with atropine because it doesn't affect your skeleton muscles,
right yeah, oh yeah.

Speaker 3 (53:01):
But Si Bachelinum really began to get the widespread recognition
it deserved. Starting in the late seventeen hundreds, Napoleon had
been waging his wars all throughout Europe and kind of
devastating the land. Like these wars devastated the land, there
was tons of poverty. Hygiene went way down, and particularly

(53:22):
in Central Europe, and one of the victims of this
was apparently safety standards in food production. I don't know
exactly what safety standards were like for food productions downhill, yeah,
but whatever they were, it just went down from there.
And so the number of fatal food poisoning cases jumped

(53:43):
in a region in the southwest of Germany called Apologies
for the pronunciation Wurtemberg whatever, and in one outbreak in
seventeen ninety three, thirteen people became sick and six died.

Speaker 4 (53:57):
Wow, And the cases.

Speaker 3 (53:59):
Had won thing in common blood sausages, a blood sausage
can be many things, but it's generally a pig's stomach
stuffed with meat, grease, blood, herbs, bread, cereals. Sometimes the
pigs inerts and it smoked and then boiled and then eaten.
If you don't boil it long enough, guess what can happen.

(54:21):
Over the next couple of decades, these reports of fatal
food poisoning continued to pour in, and the term sausage
poisoning became the in vogue term to describe them. Okay,
in a small town in this Wurtemberg region, a twenty
nine year old medical officer by the name of Justinis Eustinus.

(54:42):
I'm not sure Kerner had become very interested in this
sausage poisoning situation. He and he would end up making
enormous strides in research on sibachulinum even before germ theory
had been developed. Cool. This is very cool, all right,
So let's go through his is various discoveries. Number one,

(55:04):
He began doing his own groundwork on sausage poison in cases,
and in eighteen twenty he published case reports of seventy
six patients and the first clinical description of botulism that
tracks very closely with how it's described today.

Speaker 4 (55:19):
Wow.

Speaker 3 (55:19):
So I'm going to read this and I want you
to just like, this is eighteen twenty and just say, wow, eron,
just react for me.

Speaker 4 (55:27):
That's my job during this section anyway, okay.

Speaker 3 (55:31):
Quote, the tear fluid disappears, the gullet becomes a dead
and motionless tube. In all mucous cavities of the human machine,
the secretion of the normal mucus stands still from the
biggest the stomach toward the tier canal and the excratory
ducts of the lingual glands. No saliva is secreted, No
drop of wetness is felt in the mouth, No tear

(55:51):
is secreted anymore, No ear wax appears in the auditory canal. Also,
signs of drying out of the Eustachian tube become apparent.
No mucus is secreted in the nose, No more sperma
is secreted. The testicles decrease. Urination can only be performed
by standing and with difficulty. Extreme drying out of the palms,
the souls, and the eyelids occurs.

Speaker 4 (56:13):
That is a great description.

Speaker 3 (56:15):
Yeah, it seems funny.

Speaker 4 (56:17):
I especially loved that he said the human machine machine.
That is my new favorite term. Oh yeah, no, yeah,
that's now. I will say that that description could also
have been Beladona because he didn't really talk about the
paralysis aspect of the skeleton.

Speaker 3 (56:38):
Muscles he does in others. So that was like an
excerpt from this yeah. Yeah, and as we'll see, yeah
he did. He did tons and tons of work, so
he did like expound more upon the paralysis aspects of it.

Speaker 4 (56:51):
It's a good like you should we should use that
in school to talk about the effects of the parasympathetic
nervous system because he did a really good job of
going through them all.

Speaker 3 (56:59):
Yeah. Nice, yeah, good job Curner. Okay, number two, that's
only number one. Okay, wow, number two. He didn't stop
with just describing sausage poisoning. He wanted to understand what
exactly was causing these symptoms and how so he collected
the sausages that he suspected were involved in the poisonings
and he compared their ingredients and the only two commonalities

(57:23):
he found were salt, which he believed to be innocent,
and fat. So he came to the conclusion that fat,
what he called fatty acid, was the cause of this
sausage poisoning, okay, And so he attempted to isolate this
fatty acid or sausage poison from these poison sausages and

(57:44):
conduct some experiments to see if he could recreate the symptoms.
And so he fed this fatty acid to birds, cats, rabbits, frogs, flies, locusts, snails,
and so on, and some of these experiences. Yeah, and
some of these experiments worked like they developed paralysis. And

(58:04):
he also experimented on himself a few times and described
what happened there, and then his professor was like, dude,
what are you doing. Stop doing that. You're going to die.

Speaker 4 (58:14):
Dude, stop doing that.

Speaker 3 (58:16):
Stop doing that.

Speaker 4 (58:18):
Oh my god.

Speaker 3 (58:19):
Yeah, all right, so number three, through these experiments, he
was able to closely examine the stages of paralysis and
even develop some hypotheses as to just how the toxin
causes these symptoms, basically deducing that it was through an
interruption of the peripheral and autonomic nervous signal transmission. What

(58:42):
isn't that amazing?

Speaker 4 (58:43):
Wow? That is incredible.

Speaker 3 (58:44):
This is what he wrote. Quote, the nerve conduction is
brought by the toxin into a condition in which its
influence on the chemical process of life is interrupted. The
capacity of nerve conduction is interrupted by the toxin in
the same way as an electrical conductor by rust.

Speaker 4 (59:02):
One hundred percent in eighteen twenty. Like, this is incredible,
That is phenomenal.

Speaker 3 (59:09):
You're about to be even more blown away because number four.
He went on to suggest possible ways to prevent sausage
poisoning through longer boiling times, through storing the sausage in
dry in aerobic conditions, and he also suggested a way
to treat it. He invented an elastic tube that some
people view as the first gastric tube to make sure

(59:32):
that his patients got enough nutrition and didn't choke to
death or didn't aspire it. Yeah. Wow, okay, number five,
this is the last one. He went on to propose
that this toxin could be used therapeutically to calm over
excited nervous systems. He suggested it could be used to
cure Saint Vitus's dance remember from Dancing plague episodes. Yeah,

(59:57):
and also some other things which are a little less
grounded in mechanism, excess sweat, rabies, plague, yellow fever. Again,
it was pre germ theory days, so you know, we
can give him a break on that, but it's amazing
that he would recommend therapeutic applications like one hundred and

(01:00:19):
fifty years before they were put into practice.

Speaker 4 (01:00:22):
Phenomenal amazing.

Speaker 3 (01:00:24):
Okay, So to recap real quick, Number one, the first
clinical description, Number two, isolation of the toxin. Number three
explanation of the mechanism of the toxin. I mean, and
also number two it's a little handwavy, but he was
able to actually he tried, he tried. Number three, explanation
of the mechanism of the toxin. Number four prevention and
treatment methods, and number five suggestions for therapeutic use.

Speaker 4 (01:00:51):
Incredible human ingenuity, right there.

Speaker 3 (01:00:54):
Human ingenuity.

Speaker 4 (01:00:55):
That is the kind of human that doctor who is
like all about yeah, yeah, yeah, no exactly anyways, Wow,
yep wow.

Speaker 3 (01:01:06):
His work on sausage poisoning earned him a bit of
notoriety as the leading expert, and he was known as
vers Kerner sausage Kerner. Also, he was apparently a very
accomplished poet, especially in his later years. You can read
his poetry online.

Speaker 4 (01:01:24):
Very cute.

Speaker 3 (01:01:25):
Okay, so I've gotten this far in the history of
Bochulinum toxin se bochulinum, botulism, whatever, And I have yet
to talk about etymology, Oh, Aaron, uh huh. Bochelism like
the term bochelism, that it got its official name in
eighteen seventy and its scientific name for sea Bochelnum in

(01:01:48):
eighteen ninety seven, And I'll tell that story in a
second about that, But first claustride and Bochulinum. Originally it
was called Bacillis botchulinum basills just basically as you said,
meaning rod shaped, but it was later renamed Claustridium from
the Greek cluster meaning spindle because the colonies of bacteria
in this genus apparently resemble spindles, and Bochulinum from the

(01:02:12):
Latin word botulis, meaning sausage.

Speaker 4 (01:02:17):
Stop it.

Speaker 3 (01:02:19):
Sausage, sausage.

Speaker 4 (01:02:21):
Not what I was expecting. But after that story, not surprise,
sindal sausage, spindle sauce.

Speaker 3 (01:02:28):
Isn't that incredible?

Speaker 4 (01:02:29):
That is hilarious sausage. Yeah.

Speaker 3 (01:02:35):
So, by the late eighteen hundreds, botulism and its association
with sausages was well known throughout Europe. But it would
take a funeral with pickled Ham nearly three dozen people
falling ill and three dead for it to be recognized
as being caused by bacteria. Ooh. In December of eighteen

(01:02:55):
ninety five, in a small town in Belgium, around thirty
four musicians in the local brass band gathered to play
at the funeral of eighty seven year old Antoine Creture,
a town elder. After the funeral was over, they were
given dinner at the local inn, and this dinner consisted of,

(01:03:15):
among other things, smoked or pickled ham. Unfortunately, it hadn't
been preserved or cured properly, and within a few days
the entire band began showing signs of botulism. The entire band,
all thirty four members, all thirty four, three ended up dying.

Speaker 4 (01:03:35):
Oh dear.

Speaker 3 (01:03:36):
A microbiologist named Emil Pierre van Ermingham jem Ermine gem
erminghem I don't know anyway. He was professor at the
University of Ghent at the time, but he had previously
worked with Robert Coch and he had caught wind of
the outbreak. He examined the ham and tissues from those

(01:03:59):
who had died and went about looking for microbes, and
he found them and called them Basillis botulinum. It would
take nearly another thirty years for the toxin itself to
be discovered and isolated, but during that time people grew
to realize that this was certainly not just a disease
of sausages or ham or fish. It could also come

(01:04:22):
from white beans in one of the first canning outbreaks, olives,
or basically anything. Cases of botulism continued to rise as
the technology to can or preserve food continued to develop
into the twentieth century, and both commercial and home canning
or food preservation carried risks of botulism, and it took many,

(01:04:44):
many outbreaks, both from mass produced cans and home canned
foods for people to gain an understanding of the techniques
you had to use to properly prevent bosulism from happening
or the toxin from developing. Right, and because treatment for
a good portion of this history was not an option,

(01:05:04):
like we didn't have the anti toxin until relatively recently,
I think the past few decades.

Speaker 4 (01:05:09):
Would just be supportive care in that case, then yeah,
m hm, okay.

Speaker 3 (01:05:14):
So in eighteen twenty at the University of California, a
researcher named doctor Hermann Summer was finally able to isolate
a bochelnem toxin type A if you're interested, makes sense
that it was a So it was the first one.
An additional research showed it to be the most toxic
substance known to humans, as we discussed earlier. So why

(01:05:36):
do you think this research was being conducted. Why were
people interested in bachelism?

Speaker 4 (01:05:41):
Oh, I don't know, maybe like biowarfare or something like that.

Speaker 1 (01:05:44):
There you go.

Speaker 3 (01:05:47):
Yeah, so it was probably a good thing that it
was isolated, that the toxin was isolated a couple of
years after World War One ended. Oh dear, But guess
what was just around the corner World War two? Not
that World War Two was exactly looming on the horizon
in nineteen twenty, but you know it kind of whatever,

(01:06:09):
there was always, you know, a reason to be able
to produce a bio weapon, right, So the US Army
Biological Warfare Laboratories at Fort Dietrich in Maryland had a
special interest in developing bochelism or bochulnum tocsin as a
weapon to use in the war during World War II,
and supposedly, supposedly they had even developed a plan to

(01:06:31):
try that out that involved having people assassinate high ranking
officers in the Japanese Army by dropping a gelatin capsule
containing bachulinum toxin into their food or drink. WHOA. The
plan was abandoned when the capsules were tried out on
donkeys and had no effect.

Speaker 4 (01:06:53):
They didn't make a good enough capsule or something.

Speaker 3 (01:06:56):
I well, So one of the hypotheses is that donkeys
are in immune to botch lineum toxin, but that seems
to be really debated, and so it just seems unclear
what interesting. Yeah, In any case, botch lineum toxin was
abandoned as a bioweapon for a lot of the same
reasons that ricin was abandoned. If you remember in that episode,
it doesn't spread person a person, the dosage is hard

(01:07:19):
to control, it's easily inactivated, and it now can be treated.
So you know, in terms of a bioweapon, it's not great.

Speaker 4 (01:07:27):
It also like it it's not super fast acting. I
don't know if that's a good thing or a bad
thing in terms of bioweapons. I've never I don't know
what the objective is, like to terrorize people. Then you know,
then it's not that great.

Speaker 3 (01:07:39):
Yeah, And now you know Fort Dietrich is now all
about biodefense rather than offense. So anyway, it was abandoned. Okay,
So in keeping with the theme of poisons that we
usually use for these types of for those crossover episodes
that we take, I think it's time to chat about
the other side of the coin.

Speaker 4 (01:08:00):
Yes, the other side of the can, the other side
of the can. Okay, they tell me about it, okay.
Bochulenum toxin in therapeutics, so Kerner suggested it in eighteen twenty,
way ahead of the game, way ahead of the game.

Speaker 3 (01:08:16):
But it wasn't until the nineteen sixties or nineteen seventies
that it was developed for treatment purposes.

Speaker 4 (01:08:23):
Cool.

Speaker 3 (01:08:24):
The first pilot study of type A botchelinum toxin to
treat strabismus in humans basically cross eyedness, right.

Speaker 4 (01:08:32):
Yeah, misalignment of your eyes.

Speaker 3 (01:08:33):
Here we go. This first study was done in nineteen
seventy eight and was shown to be effective. The FDA
approved its use a year later. Cool, and that really
opened the door for doctors to use it to treat
all kinds of involuntary muscle contractions. Yeah, and Aaron, I'm
sure you're going to talk more about what those treatments are.

(01:08:55):
Absolutely in the next section. But before we get to that,
we have one more little piece of business to cover,
the botox business. To be precise, how did this begin?
So let's head to nineteen eighty seven. Okay, Botulinum toxin
had been used for these various things about ten years
at that point, and an ophtalmologist named doctor Gene Carruthers

(01:09:18):
had been shooting bochulinum toxin into her patients to treat
abnormal involuntary blinking. Do you know what the technical terms
for that?

Speaker 4 (01:09:26):
God, I feel like I should so to the b
ends in spasm, oh, blarfospasm or something.

Speaker 3 (01:09:34):
Yeah, blufferospasm. It's a very awkward sounding word.

Speaker 4 (01:09:38):
It really is. Yeah.

Speaker 3 (01:09:41):
So she noticed that when she did this, when she
injected this botulinum toxin into her patients near their eyes,
their frown lines disappeared, some of the wrinkles around their
eyes disappeared. So she went home and mentioned it to
her husband, who happened to be a dermatologist. Oh, and
they were like, holy cow, we just stumbled upon what

(01:10:03):
might be the most revolutionary cosmetic procedure yet.

Speaker 4 (01:10:08):
Yep.

Speaker 3 (01:10:09):
And they worked on it for about ten years before
publishing their first report in nineteen ninety six, and since
then it has become, perhaps and you'll maybe talk more
about this, perhaps the most widespread and profitable cosmetic treatment
by far.

Speaker 4 (01:10:27):
So absolutely, that's kind.

Speaker 3 (01:10:28):
Of where my story ends from sausage poisoning to wrinkle
reducing the glorious story of Clastidium bachelino.

Speaker 4 (01:10:38):
Wow, that is so fun. Isn't that fun?

Speaker 3 (01:10:42):
Migratory birds, blood sausages?

Speaker 4 (01:10:45):
What a like? What an interesting story?

Speaker 3 (01:10:50):
Do you see it? Where I was like, so, it's
like one of my favorites. It just feels, you know,
I don't know, it's very satisfying.

Speaker 4 (01:10:56):
The whole satisfying. It is so fun.

Speaker 3 (01:10:59):
And there's a lot too, Like, you know, I didn't
mention sort of the food outbreaks that have happened throughout
the twentieth century, because there have been a lot, but
I didn't go into detail on those, but I will
say there have been many.

Speaker 4 (01:11:13):
Yeah, So let's talk about where we stand with botulism
and clusterating bochulatum today.

Speaker 5 (01:11:21):
Let's take a quick break.

Speaker 4 (01:11:56):
So let's talk first just about kind of the depressing
botulism part of it and get that out of the
way so we can end on happy notes. Okay, yeah, Okay,
So in twenty seventeen in the United States, like I
mentioned already when you asked, there were one hundred and
eighty two laboratory confirmed cases of botulism reported to the CDC.

(01:12:21):
Botulism is a reportable illness because it is very rare
and serious. Most of those the vast majority, and this
has been true, like at least since the eighties, the
vast majority of botulism cases are infant botulism. So like
seventy to eighty percent of all cases of botulism in
the US are infant botulism, about ten percent are food born,

(01:12:45):
or at least in twenty seventeen they were, and about
ten percent were wound botulism. Okay, there were at least
in twenty seventeen three classified as other. So two of
them were iatrogenic, so they somehow got infected through like
hospital procedures or something like that, and then one was

(01:13:07):
suspected adult intestinal colonization, which I mentioned can happen but
is of course exceedingly rare. Cool, yes, and so I
don't really have a lot of details on like these
are the foods that are most common to cause botulism,
because I just don't really find it that interesting. Like,
in theory, almost any canned food, if it doesn't have

(01:13:29):
enough acid in it can be a medium for Claustridium
bochulinum to grow, right, therefore, could put you at risk.

Speaker 3 (01:13:35):
It's like, there's like a decent temperature range and a
decent pH range where this bacterium can reproduce under anaerobic conditions,
and so.

Speaker 4 (01:13:44):
You can google that and then if you're gonna can food,
just do it properly. That's fine, no big deal. But anyways,
it's you know, it is still possible. It absolutely still happens,
but the vast majority of cases are infant botulism, and
most of those are from honey. So uh yeah, Okay,
So let's talk about the more interesting and kind of

(01:14:06):
fun cool aspects of botulinum toxin, and that is all
the different ways that we use it currently. Okay. Botulinum
toxin is used medically to treat a lot of different dystonias,
which is what you mentioned aaron A. Dystonia is inappropriate
muscle contractions, and these can be really really painful. So

(01:14:28):
one of the most common uses for botulism is to
treat cervical dystonia, which is a contraction of your neck
muscles that can be really, really painful. It's also used
to treat laryngial dystonia, so contraction of your larynx that's inappropriate.
It has been used to treat tremors, certain types of tremors.

(01:14:50):
It's often used in the treatment of cerebral palsy, which
is you have a lot of inappropriate contraction in cerebral palsy. Interestingly,
it's more recently been used to treat headaches, both migraine
headaches and chronic like contraction like muscle type headaches. I

(01:15:11):
saw that how how does that work? It's such a
good question. We don't really know because from what I
understand the there have been a number of studies, although
not a ton, but a number of studies, like placebo
controlled studies that show that injection of botox like in
your like pair of vertebrals, like a near your cervical vertebrae,

(01:15:33):
is more effective than place ebo in treating chronic headaches.
But when they have tested like whether you're muscles like
whether you can still have pain conduction that is intact
and it's the same as placebo, so they don't actually
understand what the mechanism is that is relieving these headaches.

(01:15:58):
But we also don't really understand what causes a lot
of headaches.

Speaker 3 (01:16:00):
That's what I was going to say. We don't really
know about headaches and migraines. That's very especially migraines. Yeah,
it's very interesting. And they just discovered this by accident.

Speaker 4 (01:16:12):
No, I think it was because a lot of the
a lot of treatments for migraines have to do with
like vascular dilation and things like that, so like and
a lot of you can achieve that type of dilation
by relaxing the muscles around the blood vessels as well.
So I don't know if they if that was the
thought process behind it. But also not just it's not

(01:16:34):
just migraine headaches, it's other tension headaches as well, which
is not Maybe that has to do with you know,
muscle tension right right.

Speaker 3 (01:16:41):
Right, that's so interesting.

Speaker 4 (01:16:44):
Also going still in your head and neck area, TMJ
has been treated with botox, I know. I was like,
can I get some of that? Anyways, you mentioned the
that it was suggested to be treated for a sessive
sweating that is actually a use of botox today. Yeah,

(01:17:05):
so hyperhedrosis, which is excessive sweat, you can treat that
with botox.

Speaker 3 (01:17:12):
Kurder got one thing right, he sure did.

Speaker 4 (01:17:15):
I have to tell you this is really fun. I
have injected botox into someone ooh me personally. I have
injected botox into the detruser muscle of the bladder during
my obie gine rotation.

Speaker 3 (01:17:29):
That's exciting.

Speaker 4 (01:17:30):
So this is a treatment for overactive bladder.

Speaker 3 (01:17:34):
Oh that makes sense.

Speaker 4 (01:17:36):
Uh huh, yeah, you relax that muscle. I want to
say that the physician that was doing the surgery actually
stuck the needle in and was guiding the camera. I
literally just pushed the plunger. So I was very well
supervised in doing this. So yeah, there are a lot

(01:17:56):
of different ways that botox is one of the uh
like trade names I guess.

Speaker 3 (01:18:04):
For registered or copyrighted or trademarked or whatever.

Speaker 4 (01:18:07):
Yeah, there's a whole bunch of different forms of it.
There's so in addition to botox, which was the first one,
there's one called die Sport that's actually a type B
toxin where botox is type A. There's myoblock, there's neuroblock.
There's a brand in China called Hengley. There's a lot
of different types, but botox was like the first that

(01:18:31):
was commercially available bochulinum toxin. Right, Okay, so then let's
talk about botox because when you hear botox, you think of.

Speaker 3 (01:18:43):
Face injections for wrinkle reducing.

Speaker 4 (01:18:45):
Yes, you think of face injections wrinkle reducing botox. And
this is absolutely, without a doubt, not only the most
common use of botox but also or of bochulinum toxin,
but also the most common cosmetic procedure by far. So

(01:19:10):
according to the twenty eighteen Plastic Surgery Statistics Report put
out by the American Society of Plastic Surgeons, there were
in twenty eighteen over seven million botox procedures. Wow, isn't
that amazing?

Speaker 3 (01:19:28):
Yeah, that's a lot.

Speaker 2 (01:19:29):
That's a lot.

Speaker 3 (01:19:30):
That's a lot of procedures.

Speaker 4 (01:19:31):
It is by far the most common minimally invasive cosmetic procedure.
And this has grown a ton. So it was licensed
by the FDA for cosmetic use in two thousand and two,
and it's increased in like popularity and demand like over
seven hundred and fifty percent in like twenty years. Yeah,

(01:19:55):
so it's just on the rise because At first, when
I was looking up statistics on how man any people
get botox or how many botox procedures, this is not
people who get botox. This is botox procedures. In twenty fourteen,
it was like six million that they estimated, So now
we can see in twenty eighteen it was over seven million,
close to eight million. Actually, gotcha, gotcha, seven and a

(01:20:17):
half million. So yeah, it just it it's really really increasing,
which is it's fascinating. So I want to talk about
a few things having to do with botox. Okay, So
the reason that botox works to reduce your wrinkles is
because you inject a very small, very very small, very

(01:20:42):
dilute amount directly into the muscles, and that toxin is
going to affect the neuromuscular junction. It's going to block
the release of acetylcholine, and it's going to cause those
muscles that are innervated by those nerves to relax. Ok
And if you have relaxed muscles, then you're not going

(01:21:03):
to have the appearance of wrinkles because those are caused
by muscles contracting in different ways. Okay, However, even though
botulinum toxin binds irreversibly to those nerve terminals. Eventually your
body regenerates the ability to release the seedle colin. So

(01:21:25):
eventually you're going to have movement of those muscles again
when your body is able to kind of work around
the fact that those have been blocked by botulinum toxin.
Does that make sense, Yeah, So the effects of botox
or botulinum toxin don't last forever, which is why you
have to re up your botox every however many months,

(01:21:47):
and it depends you know, how much you inject and
also just person to person variation how often that is
going to be. The other thing I want to say
is that because so this is a but obviously a
very very very potent toxin. This is a drug that
is highly regulated. I found at least one paper that

(01:22:11):
I don't think was legit that was like someone collapsed
and died in a beauty salon after botox injection. And
I just want to say that, like, even if someone
were to die from getting too much botox, because in
theory that is of course possible, because it's a very
deadly toxic.

Speaker 3 (01:22:31):
Getting too much botox is in too much botulinum toxin, right,
not the treatment.

Speaker 4 (01:22:35):
Yeah, yeah, yeah, exactly too, like inappropriate use of botulinum
toxin rejection, not just like you know, Huan a little
heavy or whatever. Uh, you wouldn't die right away, right,
That's not how botulinum toxin works. You wouldn't just collapse
and die.

Speaker 3 (01:22:52):
Yeah.

Speaker 4 (01:22:52):
Even the effects of botox take time to work. That
it's not something that happens automatically. This isn't a toxin
that just like blocks all of your nerve signals and
kills you right away or anything like that. That's not
the mechanism of how you would die from bachulanum toxin
to begin with. So if you ever see something like that,

(01:23:12):
that's not real. That's not how it works. And I
found it on a cursory search, So I feel like
I need to put that out there. But it's very
it's very interesting. I think it's it's very fascinating that
we have so many uses for something that is so deadly.

(01:23:33):
It's so cool.

Speaker 3 (01:23:34):
It's so cool. I think it's amazing. I mean, it's
just more of those like I don't know, being very
innovative with h and open minded in terms of like
what can we do and then and also testing it
out in like very regulated ways and sort of letting
it build upon what we see.

Speaker 4 (01:23:52):
Yeah.

Speaker 3 (01:23:52):
Absolutely amazing. Yeah, I feel like this is such a
big like, this topic is so much bigger than I
thought it was going to be starting out.

Speaker 4 (01:24:02):
Yeah, and it's so much more fun. Like, I mean,
bochelism poisoning is really depressing, but of course, but the
overall story of Clostridium bochulinum and of bochulinum toxin is
fascinating and fun.

Speaker 3 (01:24:15):
It's so interesting. It's just so interesting.

Speaker 4 (01:24:19):
Yeah, I love it.

Speaker 2 (01:24:21):
Cool.

Speaker 3 (01:24:21):
Okay, Well, sources sources, I have a bunch, but I
want to highlight a few that I really enjoyed or
relied heavily on. The first is a chapter called avian
botchulism in a book titled Infectious Diseases of wild Birds,
and the other one someone named HERB. Guth Okay wrote many,

(01:24:46):
many papers on the history of bochulism, and so there
are several of those. One that I'll call it in
particular was from two thousand and eight. And then another
paper about sort of the why of bochulism is by
Mansfield and Doxy from twenty eighteen. It's titled Genomic Insights
into the evolution and ecology of Botchulinum neurotoxins. And then

(01:25:09):
finally Montecuco and Risotto from twenty fifteen titled on Botchulinum
neurotoxin Variability awesome.

Speaker 4 (01:25:21):
I have a couple really in depth papers on the
toxin of clushrity and botchulinum, especially if you want to
know more about all the different types because there are
a lot of different types of this toxin. Those are
old papers, but they're still valid. There's a nice clinical
infectious diseases paper just titled botulism that I used if

(01:25:42):
you want to know kind of about the disease syndrome
of botulism. And then a few other papers that I'll
put up about kind of Boulis botchulinum toxin use in
clinical scenarios. So yeah, all right.

Speaker 3 (01:26:02):
As that it. I think that's.

Speaker 4 (01:26:05):
It, so wow cool. Thank you to Bloodmobile for providing
our quarantine title and the music for this episode in
all of our episodes.

Speaker 3 (01:26:15):
And thank you to you listeners for listening. And also
we want to especially thank everyone who keeps jumping on
the quarantiny posts and stuff and saying tpwkhy did it first?

Speaker 4 (01:26:28):
We love you, We really do. I get a warm
feeling in my heart every time I see.

Speaker 3 (01:26:34):
Those me too. Also, it came to our attention that
apparently we didn't really do it first, that it was
on an episode of Scrubs. But I genuinely like, I
haven't watched that show, and so.

Speaker 4 (01:26:46):
And you like, definitely, I we thought that you came
up with it, so like in our hearts, we yeah, we.

Speaker 3 (01:26:53):
Tried, so, you know, I mean, I think that just
goes to show that there's nothing new, ever invented ever
so ever, that's fine by us.

Speaker 4 (01:27:00):
Except photox that first time. Except verst Contra did it first.

Speaker 3 (01:27:08):
What was his name vers versed Kerner.

Speaker 4 (01:27:12):
Verse Curner, He did it first.

Speaker 3 (01:27:15):
The sausage King s.

Speaker 4 (01:27:19):
Okay, well, good lord, with that, wash your hands, you
filthy animals.

Speaker 2 (01:27:28):
Mm hmmm