Experiment one. A large vessel containing one hundred and seventy gallons of salt water was placed in the open air. The atmosphere was damp and raw. The thermometer, both in the air and in the water, stood at forty four degrees fahrenheit. The subject of the experiment was Richard Edwards, a healthy man twenty eight years of age, with black
hair and a ruddy complexion. The hour chosen for his immersion was four in the afternoon, about two hours after his dinner, a time doctor Curry tells us appointed rather for his own convenience than as being most proper for the purpose. The heat of the person who was the subject of the experiment was ninety eight degrees before undressing,
his pulse one hundred in the minute. He was undressed in a room where the mercury was at fifty six degrees, and afterwards stood naked before the fire till his heat and pulse were examined again and found as before. He then walked pretty briskly into an open court, where the northeast wind blew sharply upon him. He was exposed to it for a minute, and then plunged suddenly into the
water up to the shoulders. The thermometer, which had been kept in a jug of warm water at the heat of one hundred degrees, was introduced into his mouth with the bulb under his tongue. As soon as the convulsive sobbings occasioned by the shock were over, the mercury fell rapidly, and a minute and a half after immersion it stood at eighty seven degrees. He remained motionless in the water, and the mercury rose gradually. At the end of twelve minutes it stood at ninety three and a half degrees.
Doctor Curry expected to see the mercury rise on changing the medium of water for air, and therefore he kept him exposed naked to the wind two minutes after taking him out of the bath. To his surprise, although the attendants were rubbing him dry with towels during this time, the mercury fell rapidly. He was put into a warm bed, and his heat, when examined under the tongue, was eighty seven degrees. Frictions were used and brandy mixed with water administered.
Three hours afterwards, however, he had not entirely recovered his former heat, but by eight at night he was in all respects.
As usual.
Convulsive sobbings. As soon as I read that, I was like, that's the one.
Oh yeah, they kept him cold for so long.
So keep in mind that was experiment one, Experiment one. In subsequent experiments, doctor Curry seemed only encouraged to try harder.
Okay, So like.
The experiment seven, at which I almost included, and I was like, no, no, that's that's enough. I'll just reach you a little bit. It's supposed to be tried on Richard Sutton, aged nineteen, of a pale complexion and feebler frame. Okay, And then it said so he was in the water, intended to be in the water for forty five minutes, but only made it to like thirty five. And then when they put the thermometer in, the doctor was like, well,
it's reading eighty three degrees. But it must be that his teeth are chattering so much, and so it's just the cold air causing the temperature drop. Oh god, So
that was from an experiment I don't know. A paper by James Curry titled an Account of the Remarkable Effects of a Shipwreck on the Mariners, with Experiments and Observations on the influence of immersion in fresh and salt water, hot and cold on the Powers of the Living Body from the same work from seventeen ninety four, which explains like the most long detailed title and also like everything.
They did in the paper.
Yeah, yoh wow, well that's a lot.
Yeah. Hi, I'm Aaron Welsh.
And I'm Erin Olman Updyke.
And this is this podcast will kill you. I like forgot that I had to do that part.
Well, I mean we did have the episode, it seems.
It really does seem like that. Yeah, it was a long one, oh.
But really good.
Really really sets us up well, I think for today's topic, which I am thrilled about. Mm hm, we are veering just slightly off course of typical. Really not that far off course.
Let's be honest.
Yeah, we are talking today about a medical invention called the thermometer.
The thermometer, the thermometer, so I will say this is my little kind of caveat. Okay, the focus, I would say about half of my part is on the thermometer. Okay, yeah, I'll explain later. Okay, I can't wait.
I'm going to talk about fevers because like, what do we use a thermometer for checking if you have a fever.
That's mostly what I'm going to be talking about. Too. Great, it'll be good.
I can't wait, be really fun.
Yeah, but we have a few things to get out of the way before we get into like the content.
So of course we do. Yeah, it's quarantine, ay time.
It is, and we're drinking this week. Give Me Fever, Give.
Me Fever like that that's the song, right, that's the song.
Yeah, In Give Me Fever, we figured we would have to do like some sort of hot cocktail, something spicy hot. Yeah, hot isn't spicy. And so we're doing and I don't know if we've done this before, but we're doing a
pineapple margarita mm hmm with hellipens, caw and mescal. Don't know if we've done this exact variation, hope not, but it's it's delicious and we will post the full recipe for the quarantini and the non alcoholic La Si rita on our website This podcast will Kill You dot Com as well as on all of our social media channels.
We sure will yes on our website This podcast will kill You dot Com.
There's just so many things that you can find there. You can find transcripts from all of our episodes. You can find sources that we use for every episode. You can find our bookshop dot org affiliate account, and our Goodreads list, and our merch and our Patreon and bloodmobile who does our music, and of contact us form and a first hand accounts form. It just keeps going on and on.
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So check it out and what else business. If you haven't already, please rate, review, and subscribe. It helps us so that other people can listen to this podcast as well.
Yeah, send us episode suggestions, you know. Yeah, weekly episodes. We need some ideas. You have lots of them, and they have so manyone who has sent incredible suggestions. We are taking you up on some of those this season.
It's going to be a great season.
Well, should we get into fever? Yeah, I think we should. Let's take a quick break and then jump in.
I'm going to try and start at the beginning here ready. Pretty much all animals seek to exist at a particular temperature set point that we have to do that, and this particular temperature that our body likes to exist at varies animal to animal. I'm not going to get into the details of it. Endotherms like mammals like us, maintain our temperature by physiologic mechanisms like energy production and then
vasodilation or sweating to cool ourselves off. If we get too hot and produce too much heat or vasoconstriction or shivering or non shivering thermogenesis. If we get too cold, as endotherms, we generate our own heat via our metabolism in our body and our brain. Specifically, our hypothalamus has an internal thermometer that keeps really tight control over our temperature.
Humans have to stay at around thirty seven degrees celsius ninety eight point six fahrenheit plus or minus like one degree, and our body and our brain does a really really good job of keeping us there. Despite the fact that as humans we live at all of these extremes of temperature, and despite the fact that we have massive fluctuations in our energy expenditure and our energy intake in all of these things.
Why I have questions, I'm interrupting you. Why ninety eight point six or thereabouts?
I have no idea.
That's a really fun and interesting question because it totally varies mammal to mammal. I mean, dogs and cats run a lot warmer birds are.
Super warm, and then you have things like apossums, which are like ninety four degrees.
Right, well, and bears.
I did a little bit of a deep dive on bears, and like animals who hibernate in the.
Winter, scot we love some hibernation, I know, but I don't know.
I don't know why, like why each animal has evolved their particular temperature. It might just assuman has something to do with the rate of metabolism.
Or right, so there's like body size in terms of metabolism and stuff like that, and like heart rate. But right, it could also just be like drift to a certain extent, like there might not be a like a driver of it exactly.
Oh, I have a lot of feelings about drivers in general. And we'll keep talking about like, okay, okay, certain things.
I'll let you keep going.
Okay. It's a great question, though.
So extremes of temperature can and do, as we heard in our first hand account, result in things like hypothermia eighty six degrees is not okay for a human body to exist at, or heat stroke on the other end, which kills lots of people every year. But here's where things get really interesting in hypothermia or in hyperthermia. So when we are exposed to extremes of environmental temperatures, our brain would still be doing its darndest to keep our
bodies at a balmy thirty seven celsius. Our temperature set point would remain the same. A fever is what happens when our temperature set point gets moved. When our body, our brain, our hypothalamus that's controlling our temperature set point decides and we'll talk about why and how decides. We got to heat things up a little bit, and so it moves that temperature set point, and then our body actively seeks to raise its temperature.
And that's a fever.
Okay, when can I start asking more questions? Should I just let you keep going and assume that you'll explain it all?
I mean, I'll probably answer them, but like I guess what order you want things?
And you can hit me with questions.
Now, no, just go, just go, just go, okay, Okay.
If I don't answer them, then it'll be really fun to try and figure out how to answer them. The first question that I assumed that you would ask is how high is a fever?
But maybe that's too easy of a question.
But it turns out, actually when I was reading this that like different places actually do define it differently. So it made me feel like I need to get off of my high horse a little bit.
Because I do exist on a high horse when it comes to fever.
Wait, wait, what do you mean by you exist on a high horse when it comes to fever?
Well, okay, I have always, one hundred percent of the time learned that a fever is anything above thirty eight celsius, which is one hundred point four fahrenheit.
So, like, there are a lot of times.
When people will say, oh, I have a small fever like ninety nine point nine. That is not a fever. That is my high horse. That's me on my high horse.
Ye you correcting someone. Thank god they didn't also say a spider is a bug. They would be dead to you.
It would be the end of a friendship for sure. Anyways.
Yeah, so is there a difference between low grade fever? Okay?
Is this so they you ask that question? I hate the term low grade fever. It's another high horse. But that's just me that like lots of people use that term. So when I then was digging into this some organizations like the Infectious Disease Society of America and the American College of oh I forget the actual acronym, but it's
the intensive care like academy in the US. They actually said that they kind of consider it more like thirty eight points three celsius or one on one fahrenheit, which is even higher.
Wow. And so you could have been even higher on your horse.
Exactly, I could have like ninety nine to nine is definitely not a fever. But it's really if you think about it, if you think of thirty seven as the kind of human typical temperature set point, it's plus or minus one degree is normal, and our temperature is going to vary throughout the day, So one degree off is really not that abnormal. And so I think that that's kind of like the main point is that, and we'll really get into like what happens when we have a fever, and like is it.
Bad, is it good?
What?
And so I think that's why in a kind of critical care scenario, you might end up tolerating a little bit higher before you need to say this is a fever that we need.
To do something about. If that makes sense, okay, And.
When it comes to a fever, our body also generally has a lot of mechanisms in place that keep this from getting too high. Usually it stops around forty one celsius or one oh five point eight fahrenheit, although some papers that I read said that pre antibiotics, we saw more like forty two degrees celsius or one oh seven point six.
So it's not that it's impossible to go higher.
But usually if it's a fever and not heat stroke or heat exhaustion that's happening from external factors entirely, but a fever caused by this shift in your internal set point, then there's also these mechanisms in place that will stop it from getting too high. So then what is causing this? Like why does our brain decide all of a sudden to change our temperature set point and thereby cause a fever. Most of the time, it takes two different things to
start a fever. It takes some exogenous substance, something from outside of us that we do not produce, like for example, a bacterial endotoxin, or like viral proteins, something that our body recognizes as foreign as not self, that interacts with our immune system and then it takes substances that we do produce, and these are called pyrogens. Really, they're both called pyrigens, exogenous and endogenous pyrogens. Our endogenous ones are
things like inter lukens and TNF alpha. And I'm not going to get into the nitty gritty because it's not that important. The point is that these things together act on our hypothalamus where that temperature set point is, and our hypothalamus then produces something that we've talked about on this podcast before, which is prostaglandin E two, which acts on yet another part of our hypothalamus to kind of slow down how much our warm sensitive neurons fire, and
that's what then results in the increase in our body temperature. Now, the deep deep details of like what's hitting what and why is it doing xyz we don't fully understand, but that is the basic picture of it. It's stuff in our body that our immune system recognizes, usually bacteria or viral infections that then trigger our brain to say, hey, we need to raise the temperature. So that really raises this question of is a fever this adaptive mechanism to
fight off infections? Because the vast majority of the time or maybe not the vast majority, but like a lot of the time a fever is associated with an infection. So there is a lot of literature about this hypothesis that because fever is this response to infection, that it
has adaptive significance specific to reducing pathogen survival. And we talked about this kind of in our blastomecosis episode, just in like, yeah, how the evolution of endothermy and like having a higher body temperature at base line might have been adaptive against fungal pathogens like blastomycosis. So then if you take that one step further, then perhaps having a fever intermittently raising our temperature even higher protects us against other pathogens as well. And we do have some support
for this idea, both directly and indirectly. So indirectly, there's a lot of evidence that ectotherms like lizards will lay out in the sun to induce a fever, they will raise their own body temperature in order to fight off pathogens when they're infected, or fish, some fish will swim to warmer water if they're infected, which I find so cool, really cool. Now, in humans, the studies are a little
bit maybe more indirect. I guess I don't know, but in some studies, for example in the ICU, people who have sepsis and have a fever that's not too high, so usually not above like forty one or forty even celsius.
People who have a fever have.
Lower mortality rates than people who do not have a fever. But if that fever gets too high, then it's no longer true. And then there's also like in vitro studies that show that various organisms that tend to cause infections in humans do poorly at higher temperatures, and that fever. One like hypothesis as to the mechanism of why is that increased temperatures increase the iron requirements of bacteria and then reduces their survival.
I also found this really fun.
Paper that tried to like dig deep onto like different hypotheses of like how you can inhibit pathogen growth. It's too much detail, but I'll post it because it's really fun. But the idea is just that we have pathogens that are less well adapted to survive at higher temperatures, so raising our body temperature helps us to fight off those infections I mean.
And also the fact that fever is highly conserved across mammals, like mammals in general have fevers, so like and whether it's adaptive across the board, I don't think I actually, I don't think anyone has has really like tried to argue that point specifically, Like, I think it's always been.
There's nuance to it, because back even in the nineteen twenties or even before then, people were seeing fever as being adaptive, but also realizing that some pathogens cause fever on their own and actually replicate better, i e. Malaria parasites replicate better at higher temperatures. So it depends.
I guess it depends aarin, and fever is not a response that's specific to pathogens, right either, So we also can see fever in malignancies. We see fever in autoimmune conditions. Now, in those cases, it's very likely that the fever mechanism, like the generation of that fever, is due to the same underlying inflammatory mechanisms, right, It's still like our immune system activating the same pathways, just without the presence of a bacterial endotoxin to start.
It off, if that makes sense.
But then we also see fever in people with traumatic brain injury. We see fever from endocrine disruptions like hyperthyroidism, and then there's also like drug induced hyperthermia where you can get incredibly high body temperatures as a result of drug interactions, which is kind of separate, like a separate mechanism entirely. So then the question is like, can fever be bad? And like the short answer is yes, definitely, yeah, right, And part of it is that fever is not an isolated phenomenon.
Yeah, so your face is like, Okay, are there people who do not get fevers or cannot change that set point?
That's an excellent question, definitely, and I think that's part of why. So in some of those studies where they have looked at patients in ICUs who have sepsis, people who don't have a fever at all, who are either normalthermic or even hypothermic have less good outcomes like higher mortality and things like that. So not being able to mount a fever response is usually a sign that your
immune system is not activating enough. So in terms of what the specific cause of that could be, I don't have like a list of things for you, but definitely there are instances where you could have an immune system that's not able to mount a febrile response.
But I mean, like just people like that is you you can never not just situationally, but like can have never been able to have a fever.
I don't.
I don't know if there's like a documented human who's never fevered.
Well, I'm just it.
It makes me think a lot about like why is it in this part of the brain hypothalamus? When did we talk about prostaglandins on this Oh.
When we talked about thailan all and when we talked about.
Oh that makes sense, yeah aspirin. Yeah, okay, yeah, anyway, interesting, I'm like I now I'm sort of even struggling to think about like body heat period. Oh my gosh, what what is it?
I have deep?
I've got like four more pages from a paper that goes deep into like the generation of heat in mammals and different mammals and like heat generation and heat loss and all of these like thermo dynamics stuff.
Because there's a lot there.
I can't wrap my head around it. So I'm sorry to have interrupted. Let's just keep going.
Okay, it's okay, it is really fascinating. But when we look at fever specifically, it's not an isolated phenomenon. Your brain is not causing a fever, and that's the only thing that's happening in your body, whether it's during an infection or during malignancy or whatever.
The cause is.
The mechanisms of that inflammatory response that are triggering fever also trigger things like an increase in your heart rate, an increase in your metabolism and oxygen requirements.
And these things.
Are not physiologically benign, right, they are costly for us. So that is one way that fever can actually cause more damage. Right, It's metabolically very costly to have a fever because of what all of the other things that come along with it. But on top of that, at a certain point, the heat alone damages ourselves. So we see both cellular and tissue level and then even like organ level damage as a result of that increase in body temperature as a result of fever.
And so it.
Makes sense then that there are usually these mechanisms in place, these kind of negative feedback loops that kick in over certain temperatures in order to keep our fevers from getting too high. But you're right, there are situations in which those fail, and there's a few ways to think about
that depending on what the cause of fever was. If it is something like accepsis or an overwhelming infection, then a fever that is getting so incredibly high that it's causing things like brain damage or other organ damage is a sign that the damage has already begun, and so your body can no longer regulate that fever cycle, if
that makes sense. And the same thing is true if it's a cause like a TBI, like a traumatic brain injury, where you've just you've disrupted the ability to do that temperature regulation period.
Why when you have a fever do you feel cold?
Oh, that's a really good that's a really good question.
From what I read, It's because your body is trying to raise its temperature, and so it's doing that by things like vasoconstriction in your extremities in order to funnel the heat into your core. So you're going to feel cold. It's also then behaviorally going to cause you to put on layers, which is going to help you raise your body temperature.
How cool is that?
Huh yeah, yeah, so it's not. I think what's interesting too is a lot of times people are like, oh, if you have a fever.
You should try and cool your body down.
You should put on cold you know, put a cold cloth on, et cetera. But that is going to fight against what your body is trying to do, so then it will actually probably cause you to shiver more, which is the way that you're trying to generate heat. Shivering is trying to generate heat. So it kind of like works against yourself to do those mechanisms. It doesn't mean they're harmful necessarily, but right, it's interesting.
But then also like, okay, maybe this is just I'm thinking of I don't know, the Secret Garden or something. Okay, is it like ice bath when the fever is out of control really high, where you can sort of like overwhelm externally your body to the point where it brings the temperature down. Sounds and it looked from the movie Secret Garden really painful.
Yeah, I don't know that in a fever situation an ice bath would be the way to lower your temperature. In a hyperthermia like situation, something like that, yes, potentially, okay, right, like it like because your body got overheated externally.
Like heat stroke type of thing.
Exactly heat stroke type of thing, but this was not that. But no, I think I.
Think we have better ways than an ice bath to right, they didn't in the Secret Garden, but we do today.
Okay, good to Yeah, don't do an ice bath. Not to tell you what to do. This is not medical advice, but yeah, that is kind of that. That is the fever. That's the fevers.
That's it.
That's what I have. Did you have more questions?
I have a lot more things I could talk about, but that was what I really wanted to get across.
Yeah, okay, so talk to me about the when fevers get out of control? Why does it cause certain types of responses like convulsions, seizures.
Like seizures, Okay, seizures we don't febrow seizures we don't fully understand. Like, okay, straight up, Febrow seizures.
Are most common in young kids.
They're not impossible to happen in older individuals as well and in adults, but they're most common in young kids. And you don't have to have a high fever to have a febrow seizure. Like, it's not necessarily a function of how high the temperature is, and it's not indicative
of damage. Really, what we think is going on is that the same cytokines that are inducing fever also can result in increases in excitatory neurotransmitters and decreases in the inhibitory neurotransmitters, increases in glutamine, decreases in GABBA, and so that those things together can result in seizures, right, Okay, So it's not necessarily a result of the temperature, it's a result of the other parts of the inflammatory response that are doing the same thing. Why is it more
common in kids? I don't fully know, But is it because like their brains and neurotransmitters are just not all online the way that adults are.
Okay, probably that question about treatment, Like, so obviously you know we've covered a couple on the podcast before. Yeah, aspirin, acetaminifin slash paracetamol. We have to do, ibiprofen we do someday someday, and probably something else. Am I forgetting something?
Those are really that I know about, which is.
Kind of interesting. I guess quinine, which we've already talked about. But this kind of goes along with the whole like evolutionary meta in type of thing which I like very briefly touch on in my section in terms of just like mentioning that there is this conversation sometimes that that springs up about when to treat a fever and are we being are we fighting against our millions of years of evolution leading to this response that is in many
ways good for us or protective potentially? Yeah, potentially, So like, yeah, is there sort of are there guidelines for this or is this not really I don't know, Yeah.
It's such a good question.
There's not guidelines for it, at least not for like normal people living their normal lives. There are you know, guidelines for like ICUs where there's you know, consensus of this is when you should investigate versus treat a new fever in the ICU type setting because that's where we have like the most data.
But really there's.
There's not a ton of clinical evidence one way or the other to say like, oh, we should be treating fevers because the fevers are detrimental on their own, or there's not data saying like we should let fevers run their course because treating a fever causes more problems than letting it run its course. We don't have the data to say that one way or the other.
And I feel like I mean, I guess you could probably design studies that would not be entirely unethical to do this, you know.
What I mean, you could.
I think that part of the problem is just that it's so the medicines that we use, like acetaminifin and yboprofen are just so common and so generally safe and well tolerated.
And fevers suck, man, they do.
They feel crappy, and so I think that that is why they're just so common to be used. But I do think that what to know that a fever has even the potential to help, like, is a sign that our body's immune system is doing what it is supposed to do and is trying to fight off this infection if it is a result from an infection, right, like assuming that it's you have a fever because you have
an infection. What I think that can provide is just like a peace of mind that like there is no data saying we have to treat a fever if you are not uncomfortable from it, or if you're sleeping through it, or like whatever the situation is, you don't have to treat it, right, And I think that that like we don't have data that says you have to treat a fever in order to prevent harm, even if it gets pretty high.
Quite honestly, is.
This is this my moment to tell you about my high fever that went untreated? Yes, Okay. So I was a freshman at the University of Kentucky in too zosand
and five. It was my first semester. I was living in Donovan Hall with my roommate Megan, and it was like really just pretty early on and I got sick, you know, like achy, I don't even know, sore throat probably, And I don't remember much of the week, and I missed class a few days in a row, and I was it was the first time living on my like living on my own quote unquote, and I just laid on my top bunk four days covered in blankets, freezing.
Couldn't even watch Gilmore Girls, which I watched religiously at the time.
I do.
I remember like vaguely seeing like the intro and then just passing back out and then on. I feel like it was Thursday or Friday. In the afternoon, my roommate came back from class and she was like, I am really worried about you. This is bad, Like you have not moved. Have you eaten anything? Have you had anything to drink? And I was just like could not take care of myself because I was used to my mom taking care of me, and I did. We didn't have a thermometer, we didn't have any sort of tile and
all I'd beprofen anything to like relieve fevers. Yeah, of course not. So then I walked like the half a block with my roommate. My roommate was like, we're going to Campus Health right now, and I remember almost passing out on the walk.
Oh my god.
And I get in. This is such a longer story than I intended it to be. Get into the doctor's office. They see me right away, and the doctor she takes my temperature with an electronic thermometer and looks at it and then leaves the room. And then she comes back again and takes my temperature again, looks at it, leaves the room and comes back with a mercury thermometer and takes my temperature. And I'm just like laying like I can't even form sentences. And she is like, Okay, uh,
we're gonna you probably have strep throat. We'll test you to make sure. But I'm going to give you antibiotics anyway, and you need to take tailan al or something. She's like, I, your fever is one hundred and five point five. I didn't believe it. This is why she took my temperature with the mercury thermometer because she's like, it must be malfunctioning.
Yeah, that's something's wrong with the electronics. Yeah.
And so then she was like sent me back to my dorm with instructions to do all that and over, and she called the ers like during the night to see if I had checked in because she.
Was like, I was really so worried.
She's like, I felt bad about sending you back. And then by the next day I was fine. It was like ninety seven point six.
Gotta love antibiotics.
Huh, antibiotics. I know. That's my fever story. It's a good fever story. Thanks. One hundred and five point five never want to one is just.
Below what I said. The physiologic set point.
Was right, listen, I push at your take to the limit one more time. Never again though.
Yeah.
Yeah, it's also I feel like that also like brings up the interesting point of like treating a fever alone versus like, if you're giving antibiotics, you're treating the fever because you're treating the infection which is causing the fever. Right, So yeah, but just like straight antipyretics are like not doing that, right, They're just bringing down the fever. So it's interesting, it is.
It's interesting. I feel like I'm going to have more questions for you as we go on.
Oh that sounds great, So Aaron, tell me how did we learn I'm not going to say, like what is temperature, but like, oh god, yeah, how did we start to measure it?
Tell me about the thermometer. I'm thrilled.
Thermommy, Okay, let's take a break and then I'll get started. Okay, well, Aaron, Aaron, the history of fever. This is not what I told you that I was going to research initially, not what we were like, Oh, we'll do this episode on thermometers and it'll be medical invention, really cool and like that is really cool and really interesting. Yeah, and I thought, okay, I started out reading and being like how did we even begin to conceptualize temperature? And then to create this
tool to measure it? We needed fixed points, like because you can't just like how do you know what ninety degrees is?
Yeah?
Right, like right exactly, So like what is this set? You know these different fixed points and then there's like the whole standardization thing all of that, So like how do you do that across the world?
I mean, we still don't, right celsia's fahrenheit kil then.
Right, but but we can we can like communicate among those like we can like what do you call it, calculranslate, translate.
Yeah that's not the right word, but yeah, what is it?
It doesn't matter. Convert, convert, thank you. I was like calculate translate somewhere in there. But yeah, I mean, like how do you standardize that those temperatures? Like and so even if you're talking about the freezing point of water or the boiling point of water, there is down the
rabbit hole. Turns out boiling is not as simple as you would think it would be because it's like there were entire decades of arguments about like, no water is boiling when it looks like this, No water is boiling when it looks like this, And then you can superheat water so that it actually is higher than one hundred degrees celsius, which is the boiling point of water, but then like, at what point does it turn into steam?
Is it still we well? And like what atmosphere are you at?
Right elevation in Denver? It boils lower, like at a lower temperature. So I quickly was like, this is not for me. I am not equipped to do this, but I do you know, I wrote this whole intro thing where I was like, it's so amazing that we have these thermometers because because like and it is really cool, Like what what was life like before we had standardized measurements? Like nowadays I can be like Aaron, what's the temperature
in San Diego? How much does your dog weigh? Can you send me that recipe for espresso fudge cheesecake so I can see if I have enough cream cheese to make it?
Sure can three bricks.
But we can understand and relate to one another and the world around us because we have those standardized units. You can say to me, oh, it takes two cups of cream cheese, which that sounds like an awful lot, but maybe that's okay. Well, instead of like I don't know, two scoopfuls of this bowl that I have in my house. How much does your dog way, I don't know, kind of heavy, but I can lift him like that. It's
like that kind of thing, right, Yeah. And so before it would be like, oh, the castle is three days by horseback, and like what kind of horse do you have?
Is it fast broken foot? Yeah?
Is it carrying something? Like? Are you dragging something?
Yeah?
Exactly exactly. And so these standardized units are really because they help us navigate the world and also really important in science of course, like we can it's so crucial for us to be able to replicate scientific studies being like zero point five mills whatever.
Yeah, but then.
You know the boiling and superheating. I was like, this is I can't. I can't do this. I'm out of my depth. So then I went back to the drawing board and I was like, okay, what about like the medical use of thermometers. When did we decide that we needed to use those? And then that kind of led me down into what are fevers and the history of fever from capital f fever to fever the symptom, and I wanted to kind of like take this approach by looking at like what did fever mean to someone in
to Hippocrates at all? What did fever mean to someone in the seventeen hundreds, What did fever mean to someone in the early nineteen hundred. It's like those things are very different. And then I want to kind of incorporate the use of the thermometer in clinical medicine. Love it, That's what I did. Okay, I love it so long intro. But if fever started out at least as far as we can tell, as a cluster of symptoms, kind of as a disease in its own right, or as a
frequently uncountered state of being like it wasn't. It wasn't something that was like super rare. And I will say that if you want like a very full, comprehensive history of fever and all of its metaphors. The book that I used for this is called More Than Hot, A Short History of Fever. It's by Christopher Hamlin. And yeah,
there's a lot more information that I ever anticipated in there. So, But in ancient Greece and Rome, fevers were, like I said, kind of this state of being broad on often by external fact, is not necessarily tied to specific disease, Like working out too hard when it's hot outside could lead to a fever. You're overheating. Your body might feel like warm to the touch, and your sweat is cooling you down. And so then if you stop working out, that could
lead to chills. Sure. Sure, And then there were fevers associated with epidemics of what we now know to be infectious diseases. Those were kind of more on the periphery of things, like they happened, but they weren't as much of an everyday part of life as something like this, you know, exerting yourself fever.
I guess interesting.
Soushruda So, the ancient Indian medical scholar from around the seven hundreds BCE, described fever as the quote unquote lord of ailment, king of all bodily distempers, inasmuch as it can affect the whole organism at one time quote and I have a lot of quotes, an indispensable condition under which a creature can come into being or depart from this life. I think that's kind of interesting. Yeah, I don't want to give the impression that fevers were not
indistinguishable in ancient times, because they were. People did recognize that certain fevers followed certain patterns, like malaria, for instance. So there were many ancient medical texts from China and India and Greece that like characterize malaria or other fevers that seem to follow this like every three days or
every you know. However, it is this pattern or those fevers that tend to appear during certain times of year, or those that appear after wounds, like putrid fevers, And the prognosis was different for each of these different kinds of fevers. But the fever was the disease, do you know what I mean? Like it was a putrid fever. It wasn't like, oh, that fever is really high because
he has a wound and that wound is clearly infected. No, it was like that he had full seed state of being capital f Yeah, and those make sense, Like I feel like those that characterization makes sense to us today. But what I think is a little bit more challenging to grapple with, at least in terms of what we know now, is something like this passage from the Hippocratic text, which kind of brings into question, like, wait, what is
favor quote? Favors? Some are pungent to the touch, some gentle, Some are not pungent but increasing, some are sharp but decreasing to the touch. Some are straightway burning hot, and some are faint throughout, some dry, some salty, some with blisters, dreadful to see, some damp to the touch, some are red, some livid, some yellow, and so on. End quote.
It's almost like they're just using the word fever to mean infection, right or am I am I missing it?
Yes? No, I think I don't think you're missing it. But I also don't know, Like I feel like what we're having a hard time doing is like putting that in our current framework of understanding of disease, and it's hard to make parallels with that, and so it is it is sort of like infection but also fevers. Like
when we think of fevers today, they're an indicator. It's like it's like a in your car and check engine like going on, Like there's something that might be a miss here, and we're not super concerned about the fevers themselves. It's more about like the overall infection, but for the most part, we have a strategy with how to handle it. And this was less so like fevers were much more a morphous I don't know. It's really hard to wrap
my head around. And I think that at least the impression that I get was that distinguishing which type of
fever that someone had. It was important in understanding like the natural history or possible treatments for a disease, but it was less important, at least in ancient Greece and China, than understanding the process of fevers, because then you have to add on this layer of like the humors and humoral theory of disease and balancing out the humors and how much moisture is in your body or whatever, because okay, you can have putrid fever or you could have bilious
fever or something like that, and those could be caused by totally different infections and they could look totally different on the surface, but you would still treat them to balance out the humors. And then the fever schedule also mattered great deal and was kept track of, like if someone felt bad on the fourth and seventh day with good days in between, they would probably die. It was almost like here's your prognosis based on when your fever peaks.
And this also lasted like well into the eighteen hundreds. It's interesting, and this was in theory supposed to help with intervention, as in like the physician would time their visits to be with the patient during those more critical periods and providing treatment or maybe a spell throwback to abercadabra and malaria. But in terms of treatment, if we're going with the humoral theory of disease, different fevers caused by different imbalances of the humors, which are blood, flem,
black bile, yellow bile. Most of the time it was excess of one humor, and so how do you get rid of a humor, Well, if you have too much blood, you bleed them. And bleeding really was like a primary treatment for fevers for hundreds of years. And this also sometimes applied to the prevention of fever, which was dependent upon the cause, which was dependent largely upon the patients themselves.
So if the cause was something like, oh, you have too much phlegm, then maybe you should hold off on eating this thing or over indulging in this way, that kind of thing, and that also in turn had very personalized to the person's like social status and class, all of that kind of thing just the normal thing that
we expect to see. But I also think it's really interesting because this framework of disease that was highly individualized in this way Oh, it's your overwork that caused this humor to increase, and this is what you need to do. All of that was challenged when epidemic fevers appeared. But then those there's always an explanation. Those could be explained away by society at large. Is bad and you're all
being punished for what you've done. Now go into your room and think about your decisions, or like the bad winds blow into town. Whatever. So the concept of fever, or the umbrella term of fever, I think, is kind of hard to get a handle on, even if you're just looking at one time period like antiquity, it was recognized to be elevated body temperature, but it was also fever with a capital F. Like a collection of symptoms. It could be brought on by everyday events or seasonal contagions.
It could be cyclical or follow a totally different schedule. It could represent a horrible, deadly disease or just be a symptom of a more mild one. It was caused by an imbalance in the humors or too little moisture in the body, or over exertion or over indulgence. Was anything everything, all of it, all of it, and Over the centuries, these different definitions of fever kind of ebbed
and flowed. Some became more popular, it fell out of favor that sort of thing, And as society and science changed, so did the meaning of fever. So we've already seen this a bit, with the onset of fever thought to be caused by like various personality types or lifestyle habits or larger societal issues. But beginning in the eighteenth century, fever in the quote unquote Western world became less about
disease and even more a state of mind. It's hard from our twenty first century vantage point, at least for me to understand like again, what this fever then shifted into. So let me give you a couple of examples and quotes of like some of the range of things that a fever could be. This is from the eighteenth century.
Oh.
The first one is about someone who isolated herself quote, resolved never to think, speak, answer, or hear. She is quite wearied with saying good night and good morning, and has almost every day a touch of fever, which a little rest always carries off end quote. So is that malaise, fatigue, elevated temperature, something else, entirely all.
Three like touch a fever.
And then there's this about somebody else's fever quote at the point of death of a violent fever he got with swallowing two glasses of brandy upon a debauch of wine end quote. So like, was he really hungover? So he was he was had a violent fever from drinking a lot of brandy and wine.
Right, I mean that would make me feel crappy?
Right?
Does that mean like body aches and vomiting. It's so interesting.
I never thought about it because, like I just always assume when I've read old timey things, if they say the word fever, they mean what we mean fever.
Yeah, nope, nope, nope. And during this period, like the seventeen hundreds the early eighteen hundreds, fevers seem strongly tied to the brain, either brought on by too much mental work or intense emotions, or directly affecting the mind, like someone's fever causing quote a lowness of spirits and falling away that alarm everyone end quote. And I think that this is also really interesting because there is a term.
I didn't really get into this too much, but like brain fever is a thing that pops up a lot in Victorian literature, I guess, like the Bronte Sisters, Charles Dickens, like Pip in Great Expectations gets brain fever at one point, Catherine from Wuthering Heights gets brain fever, dies of brain fever. Spoilers,
you're allowed to spoiler. There's statute of limitations. But there you know, Elizabeth Gaskill, there were someone who had a fever in one of her books, like there is brain fever was like a trope almost in literature from this time, where it was like this emotional shock brought on this fever that could then be very like physical manifestation of an emotional shock.
It wasn't mensis, I mean, or maybe it was like it very well could be, who knows.
Wow, Okay, I do.
Think it's really interesting to use like popular literature as a lens through which, like people every day people saw like medical understanding from that, like contemporary medical understanding. Anyway, Sorry, that's our next book club. Yes there probably is a
book like that. Yeah, okay. But also the meaning of fever had to do with your social standing, right, So those who are living in poverty fell victim to contagious fevers transmitted through unsanitary living conditions or like working too hard, the strenuous physical work, and it was seen as like a societal problem or personal shortcomings, and especially it was like clean it up so that the contagion doesn't affect the rich, and whereas the origin of the upper classes
fevers seemed to be much more refined, like too much thinking over indulgence in rich food or wine or whatever. But this brain fever, which I already mentioned, was very different than like bilius or putrid fever, or remitting fever
or Tertian fever. And so it was understood that fevers could be caused by many different things, in that there were many different types of fevers, and there began to be I think a dawning recognition that maybe fever as a symptom was at the core one mechanism, one thing with degrees of severity and a basis in the nervous system and vascular system malfunctioning. And so fever as a symptom what I mean by that is, well, it's a
little unclear, but like mostly temperature. Yeah. But the question then became, like how do you measure how severe a fever is? Like how dangerous it is and so since since ancient times, physicians had recognized that fever was associated with the body being warmer to the touch than normal, and sometimes they also observed that the pulse was elevated. One of the earliest pulse measurements was made in the third century BCE. Okay, Aaron, how do you measure a pulse?
You just count it against what the like, what is the what is the unit of pulse? Right?
Beats, beats, per minutent?
But how do you measure a minute? If you don't have a watch, then have clocks, so the whole clocks sundial. In this third century BCE, Heropholus used a water clock. I'm not sure how it worked, but it was like presumably you could measure against this, like how many drops of water? How long it took?
Yeah, like a sand timer thingy.
But yeah, yeah, I didn't think about that.
Oh, clocks are because and then you could use like pendulum clocks type of thing. But you couldn't use those on ships for navigation because there was right, it's so interesting. Yeah, anyway, I'm not even gonna get so.
Deep just to be able to measure a fever.
Uh, huh. And so in general, although these two characteristics of fever, body temperature and pulse rate had been recognized since ancient times, there wasn't a whole lot of effort made to quantify them, at least until around the seventeen hundreds. So, okay, we talked about pol right. It was in the sixteen nineties that watches with second hands were introduced.
Sixteen nineties.
Wow.
Yeah, I don't know how to feel about that. It feels very early somehow, But I guess I've never thought about when watches were invented.
I know the stuff we take for granted. I'm curiously, I'm telling.
You talking to each other on the freaking airwaves, Internet, the world Wide Web.
Worldwide Web. When has a watch invented? Wow? Sixteen ninety with second hands? Okay?
I mean so before then there were other like clocks or ways of measuring time, but they weren't widely available or or widely recognized to be useful in medicine. And so in seventeen oh seven, Sir John Floyd wrote about his observations of pulse rate measured against a watch. Quote, our life consists in the circulation of blood, and that running too fast or slow produces most of our diseases. The physician's business is to regulate the circulation and to
keep it in a moderate degree. I don't know how he expected to do that, but that was that was his job, his job. And so with the introduction of the sixty second watch, pulse rate kind of took center stage in terms of diagnosing a fever by the seventeenth century. So it was like a fever was not temperature, it was pulse rate.
Right, Okay, that's interesting, Yeah.
But pulse rate is not ideal for this. Like your pulse can rapidly change if you're active, if you get stressed, it can go up or down without a corresponding change in body temperature. So it became apparent that like pulses could not be relied upon for like every sort of diagnosis. If only there was something that could quantify something like body heat. Right, And the thing is, by the seventeen hundreds, thermometers had already been developed. So I love this. This.
This is a quote by Thomas Willis from sixteen ninety two about using pulse to diagnose fever. It's about pulse. Quote. First, we consult the pulse as a thermometer constituted by nature for measuring the heat kindled in a fever end quote.
So they had the word thermometer, and they have the thermometers, but they're like the pulse.
Thecuse the thermometer. It is a nature's thermometer. Isn't that amazing?
That is fascinating.
Yeah, So clearly people knew what thermometers were by this point. What kept them from being used in a medical set? So the broader history of thermometers, like I said, is too much for me to get into, but I do want to focus on, like when they were first used medically.
So people had been toying around with measuring temperature for centuries, but most histories put Galileo's invention of the thermoscope around fifteen ninety five as the first major advance in measuring temperature since ancient times.
Wow.
Yeah, yeah, fifteen ninety.
That is a lot earlier than I thought, Aaron, I don't know anything about history. We've done this for so long, and this blows my mind, Like, Oh, it's embarrassing.
It's not, it's like, I mean, it's really hard to put this in in context. Yeah, I don't know. Yeah, I also don't know how the thermoscope worked so and how different it was to thermometers. But but in the decades that followed, people did try to use various thermometers or thermometer like instruments to measure human body temperature, so like somebody would be holding the bulb end of a thermometer in their hands or popping it in their mouth.
But these methods and the measurements produced were pretty crude and certainly not fine enough to make any meaningful connection between fever severity or even establishing a baseline, like I feel like, especially when we're talking about fever being one hundred point no one hundred and one excuse me, one hundred point.
Four hundred point four one on one I here in the ICU.
Okay, Okay, but like that's not very far off from some of the extreme temperatures that you could measure from just like air to ground.
Totally whatever water go to Arizona, Yeah.
Exactly, And so there really needed to be a lot more work done to establish a baseline and create instruments that had more fine where you could actually like measure more finely. So in seventeen fourteen, Gabriel fahrenheit like, guess what he did one he was the one, the chosen one. He invented the mercury thermometer. I don't know anything else about him, so I don't know if he was indeed
the chosen one. But seventeen fourteen, right, mercury thermometer. And despite how revolutionary this tool could have been has been for medicine, some people did point that out, it didn't really take off very quickly. So some people, like the Austrian physician Anton de Haan, took extensive measurements of both temperature impulse of people of varying ages with varying health throughout the day. He changes in temperature or pulse after
activity or certain drugs. He was a firm believer that the physician's hand for assessing fever would no longer suffice thermometer only from here on out. But he scattered his observations that he had made these tons of observations throughout a massive treatise that he published in the second half of the seventeen hundreds, and so it was just like way too long for anyone to actually make any sense
of So what kind of just skipped? Yeah, And I think that it is still it's from this vantage point it is a little bit baffling to be like, here's this obvious tool that could be so helpful. How do you not see it? It is literally a part of every physician interaction pretty much, or like go to a doctor's office, you're going to get your temperature taken. But I think that we have to keep in mind a
few things. So it wasn't that people didn't care about quantifying previously subjective things like that was very much in style in this time. In the mid sixteen hundreds, the Royal Society stated that they want to bring quote all things as near the mathematical plainness as they can end quote butt and kind of considered was considered to be
separate from science at this point in history. From the seventeen hundreds into the eighteen hundreds, I've seen it described as science wanting to use these new measuring devices to better understand the world around them, whereas medicine was more concerned with a cure, with testing therapies on fever rather
than understanding and characterizing fever. So you have people like Benjamin Franklin, like very much like scientists observing that human body temperature stayed the same despite the weather outside, but not necessarily measuring the body temperature, you know, in someone who had a smallpox or plague or something like that yellow fever. Plus it was harder to conduct experiments on
the mechanism of fever than on possible treatments. The other major factor in this delay was in the thermometers themselves, which still had a long way to go in terms of standardization or quality control. So people would get recordings of one hundred and eighteen degrees fahrenheit like body temperature recordings of one hundred and eighteen hundred and twenty two, and the person would be like, I'm okay, Like I'm just chilling. I don't know, I don't know, I don't
know what I did. So so you can imagine being a physician looking at this reading and going this person shouldn't be alive if this thermometer is right. So like, this thing is useless. I'm not going to use it anymore. And so thermometer accuracy did get better, and in eighteen thirty five, the mean body temp of a healthy adult was established to be ninety eight point six. The last
bit of the recipe is just preconceived notions. If you think you knew how fevers worked or even what a fever was, then you're going to be less likely to investigate whether you were right, Like we just take this knowledge for granted, and we're like, yeah, of course it's that. Of course this fever is caused by X, Y and z. We don't need to measure the body temperature because it's
the pulse rate. Or we don't need to measure the body temperature because I took a full patient history and they seem to have brain fever.
Yeah.
And so it took until around the mid eighteen hundreds for enough curiosity or doubt or need or knowledge to emerge to get people to reconsider how fevers worked and conclude that body temperature is actually a much better clinical guide for fevers than pulse. And it was then quickly
integrated across medical practice. So, for instance, before the mid nineteenth century, patient records at mass General included pulse and respiratory rates, but only some of them had those, like, not all patients had these things, no other quantitative metric at all. By the eighteen eighties, though, you've got daily
pulse temperature and respiratory rate being charted. The thermometer was here to stay, and the knowledge that it generated was exponentially increased by all of the other scientific achievements or advancements happening during the eighteen hundreds, the laws of thermodynamics, discoveries of antipyretics, germ theory showing that different fevers could
be caused by different pathogens. Comparing temperature and pulse between typhus and typhoid, for instance, even before germ theory was able to distinguish between the two, just looking at temperature and pulse could say that's typhoid, that's typhus.
Because of the pulse temperature dysregulation that happened in typhoid took our episode.
Uh, it's really thrilling.
And so all of this helped to transform fever capital f the disease in to fever the symptom, from the whole diagnosis to just a data point. It was a huge shift in how diseases were perceived and managed. The individual personality or lifestyle habits like overwork or a troubled mind, particularly among the wealthy, we're no longer seen to be the leading cause of fever. I was trying to think of what the opposite of a silver lining is is just like the gray cloud across the sun. I think, So, okay,
that's what this is. Thermometers began to show that what a patient felt might not be fact. So you know how like we talked about when you're shivering and you're like, no, I'm really cold, I'm piling the blankets on, doctors could take your temperature and be like, you're not cold, you're hot. You don't understand what you're feeling. Oh dear, yeah, I mean. And so this is one of the less extreme examples.
But the author of this book, Christopher Hamlin, wrote this little quote that I really enjoyed, where he said, for a patient quote a century earlier, fever or feverishness would have referred to a state of feeling akin to a modern mood disorder. One expected a physician to assess its type and probably course, and then suggest the best response,
not sanction its existence. End quote. So all in all, obviously temperatures or thermometers were an incredibly valuable thing, and if we only had ways to objectively measure many other things, I feel like we could really advance treatment and care for people. But what we see happening with temperature and thermometer. In the twentieth century. The late the late eighteen hundreds and into the twentieth century is the trivialization and domestication
of fever. Medications became available to bring a fever down, and most households began to have a mercury thermometer at home and these medications, so if someone had a fever, you just took care of it at home, or you monitored it at home until it got worse, whereas in the past you would probably have a doctor to make a house visitor. You would take someone to a doctor. But the story of the fever isn't over. It's almost over. It.
Don't worry about it. Because once capital f fever became lowercase fever, people began to wonder why this response existed, kind of like what we talked about, and whether it
could be beneficial. And so fever as a response to infection was found to be super widespread across the animal kingdom, and so some researchers took this friend not foe idea and ran with it, maybe a little too far, developing something called fever therapy cabinets in the early twentieth century, where they would treat infections like syphilis that did not
include fevers. By locking someone's body in a cabinet with just their head poking out, and they would crank up the heat until their body temperature got to like one of six one o seven.
Which is not a fever, that's just hyperther yah.
Yeah, yeah, great idea called fever therapy. Aaron, get with the program, I am objecked. Would you like this next program? Because, oh dear, I think I've mentioned this before. In nineteen twenty seven, the Nobel Prize for Physiology or Medicine was awarded to Julius Wagner Jareg, who treated cases of neurosyphilis by infecting his patients with the malaria parasite. A malaria parasite.
You got a Nobel prize for that?
Uh huh. I should have checked to see whether it worked. I assume it did.
Yeah, I would assume you get the Nobel price for it.
Yeah. It's kind of interesting anyway. And so this debate, you know, is fever friend is it foe? Is it like the casual acquaintance that you met that one time and you don't really ever think about and it's just
kind of like there in the background. I feel like that debate is still going on, like we about but yeah, I mean I think, like I said, I think that the thermometer, it was really one of those things where I was like, if only we could measure pain in this way, because once we develop the thermometer and we're able to use it in clinical medicine, then we could much better test things like does quinine actually bring down your fever? You know, does aspirin bring down your fever?
How does it bring it down? How when should we administer it? What are the different courses of these things? Just like because I think we're always down on quantifying symptoms and being like, oh, objective symptoms are or objective signs of a disease are leaned on very heavily by modern medicine at the cost of the whole person and like the other things that they're experiencing that are harder
to describe, right, And I think that's valid. But I also think that like would be beneficial to have all of the things.
I know, Yeah, yeah, I agree.
So there's a lot more to learn about fevers, and especially by like the evolutionary side of fevers, if you want to go into that, and like evolutionary medicine. It is an interesting field. When you mentioned something about Iron yeah, Iron City shows, I was like, we're going to have to do hemochromatosis.
Oh, it's on our list.
I think it's like, like I really in the season season? Oh sweet, Yeah, it's already like on our schedule. Perfect. I should check our schedule.
And if you would like to check our sources, you can. Let's do it, Okay, I already mentioned mine. What is it? A Short History of fever more than Hot? A Short History of Fever by Christopher Hamlin. I have a bunch of other papers too that I'll post up there.
I had just a few papers that I used for this episode. Actually one if you want really fun deep dives, I have some really really fun ones. This one was
called the physiology of Mammalian temperature homeostasis. And I already have like three other pages of notes that we didn't even get into about like bears and hibernation and blubber and like we it does make you want to do a whole episode on temperature homeostasies, But tell us if that sounds too boring listeners, because like I could go off and then I.
Also have a couple on like.
There was one by Walter at All from twenty sixteen that was a pathophysiological Basis and Consequences of fever That was a really good primer on fevers and a few more.
We'll post the links for all of our sources from this episode and all of our episodes on our website, this podcast will Kill You dot com under the episodes tap.
We will thank you to Bloodmobile for providing the music for this episode and all of our episodes.
Thank you to Tom and Leanna for the wonderful audio.
Mixing, Thank you too, exactly right, and thank you to you listeners.
We had a lot of fun with this episode.
Yes, I actually really loved this me too.
It was super fun.
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I've been recording so many of these book club outros that I forget. Oh yeah, wash your hands
You feel the animals