WEBVTT - Ep 138 Fever: Take it to the limit 0:00:00.680 --> 0:00:07.040 Experiment one. A large vessel containing one hundred and seventy 0:00:07.080 --> 0:00:10.480 gallons of salt water was placed in the open air. 0:00:11.039 --> 0:00:15.200 The atmosphere was damp and raw. The thermometer, both in 0:00:15.280 --> 0:00:18.079 the air and in the water, stood at forty four 0:00:18.120 --> 0:00:22.600 degrees fahrenheit. The subject of the experiment was Richard Edwards, 0:00:22.760 --> 0:00:25.840 a healthy man twenty eight years of age, with black 0:00:25.880 --> 0:00:29.479 hair and a ruddy complexion. The hour chosen for his 0:00:29.600 --> 0:00:33.040 immersion was four in the afternoon, about two hours after 0:00:33.080 --> 0:00:36.920 his dinner, a time doctor Curry tells us appointed rather 0:00:37.000 --> 0:00:40.720 for his own convenience than as being most proper for 0:00:40.760 --> 0:00:43.960 the purpose. The heat of the person who was the 0:00:44.000 --> 0:00:47.640 subject of the experiment was ninety eight degrees before undressing, 0:00:47.960 --> 0:00:51.599 his pulse one hundred in the minute. He was undressed 0:00:51.600 --> 0:00:54.520 in a room where the mercury was at fifty six degrees, 0:00:54.640 --> 0:00:58.360 and afterwards stood naked before the fire till his heat 0:00:58.400 --> 0:01:03.080 and pulse were examined again and found as before. He 0:01:03.160 --> 0:01:06.480 then walked pretty briskly into an open court, where the 0:01:06.480 --> 0:01:10.160 northeast wind blew sharply upon him. He was exposed to 0:01:10.200 --> 0:01:13.319 it for a minute, and then plunged suddenly into the 0:01:13.360 --> 0:01:16.920 water up to the shoulders. The thermometer, which had been 0:01:17.000 --> 0:01:19.360 kept in a jug of warm water at the heat 0:01:19.400 --> 0:01:23.319 of one hundred degrees, was introduced into his mouth with 0:01:23.440 --> 0:01:27.000 the bulb under his tongue. As soon as the convulsive 0:01:27.080 --> 0:01:32.120 sobbings occasioned by the shock were over, the mercury fell rapidly, 0:01:32.440 --> 0:01:35.240 and a minute and a half after immersion it stood 0:01:35.360 --> 0:01:40.640 at eighty seven degrees. He remained motionless in the water, 0:01:41.000 --> 0:01:44.319 and the mercury rose gradually. At the end of twelve 0:01:44.319 --> 0:01:47.240 minutes it stood at ninety three and a half degrees. 0:01:47.680 --> 0:01:50.960 Doctor Curry expected to see the mercury rise on changing 0:01:51.000 --> 0:01:54.000 the medium of water for air, and therefore he kept 0:01:54.080 --> 0:01:58.080 him exposed naked to the wind two minutes after taking 0:01:58.120 --> 0:02:01.720 him out of the bath. To his surprise, although the 0:02:01.760 --> 0:02:04.919 attendants were rubbing him dry with towels during this time, 0:02:05.320 --> 0:02:09.440 the mercury fell rapidly. He was put into a warm bed, 0:02:09.600 --> 0:02:12.480 and his heat, when examined under the tongue, was eighty 0:02:12.520 --> 0:02:17.520 seven degrees. Frictions were used and brandy mixed with water administered. 0:02:18.360 --> 0:02:23.280 Three hours afterwards, however, he had not entirely recovered his 0:02:23.480 --> 0:02:26.960 former heat, but by eight at night he was in 0:02:27.080 --> 0:02:28.720 all respects. 0:02:28.280 --> 0:02:29.280 As usual. 0:03:24.320 --> 0:03:31.080 Convulsive sobbings. As soon as I read that, I was like, 0:03:32.240 --> 0:03:32.919 that's the one. 0:03:33.760 --> 0:03:39.520 Oh yeah, they kept him cold for so long. 0:03:40.560 --> 0:03:45.480 So keep in mind that was experiment one, Experiment one. 0:03:45.960 --> 0:03:52.520 In subsequent experiments, doctor Curry seemed only encouraged to try harder. 0:03:53.000 --> 0:03:54.320 Okay, So like. 0:03:54.600 --> 0:03:57.680 The experiment seven, at which I almost included, and I 0:03:57.720 --> 0:04:01.800 was like, no, no, that's that's enough. I'll just reach 0:04:01.840 --> 0:04:04.040 you a little bit. It's supposed to be tried on 0:04:04.160 --> 0:04:09.320 Richard Sutton, aged nineteen, of a pale complexion and feebler frame. Okay, 0:04:09.640 --> 0:04:12.600 And then it said so he was in the water, 0:04:13.120 --> 0:04:15.840 intended to be in the water for forty five minutes, 0:04:16.320 --> 0:04:19.080 but only made it to like thirty five. And then 0:04:19.080 --> 0:04:22.280 when they put the thermometer in, the doctor was like, well, 0:04:22.320 --> 0:04:27.240 it's reading eighty three degrees. But it must be that 0:04:27.400 --> 0:04:30.159 his teeth are chattering so much, and so it's just 0:04:30.200 --> 0:04:36.320 the cold air causing the temperature drop. Oh god, So 0:04:36.880 --> 0:04:41.719 that was from an experiment I don't know. A paper 0:04:42.279 --> 0:04:46.280 by James Curry titled an Account of the Remarkable Effects 0:04:46.279 --> 0:04:49.880 of a Shipwreck on the Mariners, with Experiments and Observations 0:04:49.920 --> 0:04:52.520 on the influence of immersion in fresh and salt water, 0:04:52.640 --> 0:04:55.240 hot and cold on the Powers of the Living Body 0:04:55.440 --> 0:04:59.359 from the same work from seventeen ninety four, which explains 0:04:59.400 --> 0:05:05.520 like the most long detailed title and also like everything. 0:05:05.200 --> 0:05:06.000 They did in the paper. 0:05:06.520 --> 0:05:12.279 Yeah, yoh wow, well that's a lot. 0:05:13.680 --> 0:05:18.279 Yeah. Hi, I'm Aaron Welsh. 0:05:17.680 --> 0:05:19.719 And I'm Erin Olman Updyke. 0:05:19.800 --> 0:05:22.680 And this is this podcast will kill you. I like 0:05:22.839 --> 0:05:25.160 forgot that I had to do that part. 0:05:25.320 --> 0:05:27.800 Well, I mean we did have the episode, it seems. 0:05:27.600 --> 0:05:29.960 It really does seem like that. Yeah, it was a 0:05:30.000 --> 0:05:31.400 long one, oh. 0:05:31.200 --> 0:05:32.000 But really good. 0:05:32.120 --> 0:05:35.239 Really really sets us up well, I think for today's topic, 0:05:35.400 --> 0:05:40.760 which I am thrilled about. Mm hm, we are veering 0:05:41.360 --> 0:05:44.760 just slightly off course of typical. Really not that far 0:05:44.800 --> 0:05:45.359 off course. 0:05:45.200 --> 0:05:45.920 Let's be honest. 0:05:46.320 --> 0:05:52.360 Yeah, we are talking today about a medical invention called 0:05:52.360 --> 0:05:53.000 the thermometer. 0:05:53.800 --> 0:05:58.560 The thermometer, the thermometer, so I will say this is 0:05:58.600 --> 0:06:05.560 my little kind of caveat. Okay, the focus, I would 0:06:05.560 --> 0:06:11.400 say about half of my part is on the thermometer. Okay, yeah, 0:06:12.279 --> 0:06:14.400 I'll explain later. Okay, I can't wait. 0:06:14.600 --> 0:06:17.240 I'm going to talk about fevers because like, what do 0:06:17.279 --> 0:06:19.719 we use a thermometer for checking if you have a fever. 0:06:20.480 --> 0:06:23.839 That's mostly what I'm going to be talking about. Too. Great, 0:06:24.360 --> 0:06:24.880 it'll be good. 0:06:24.880 --> 0:06:27.000 I can't wait, be really fun. 0:06:27.320 --> 0:06:29.560 Yeah, but we have a few things to get out 0:06:29.560 --> 0:06:31.880 of the way before we get into like the content. 0:06:32.160 --> 0:06:34.560 So of course we do. Yeah, it's quarantine, ay time. 0:06:34.920 --> 0:06:39.799 It is, and we're drinking this week. Give Me Fever, Give. 0:06:39.640 --> 0:06:45.120 Me Fever like that that's the song, right, that's the song. 0:06:45.200 --> 0:06:48.159 Yeah, In Give Me Fever, we figured we would have 0:06:48.200 --> 0:06:53.479 to do like some sort of hot cocktail, something spicy hot. Yeah, 0:06:53.520 --> 0:06:56.279 hot isn't spicy. And so we're doing and I don't 0:06:56.279 --> 0:06:58.200 know if we've done this before, but we're doing a 0:06:58.360 --> 0:07:06.280 pineapple margarita mm hmm with hellipens, caw and mescal. Don't 0:07:06.279 --> 0:07:09.400 know if we've done this exact variation, hope not, but 0:07:09.520 --> 0:07:13.440 it's it's delicious and we will post the full recipe 0:07:13.520 --> 0:07:16.920 for the quarantini and the non alcoholic La Si rita 0:07:17.400 --> 0:07:19.679 on our website This podcast will Kill You dot Com 0:07:19.720 --> 0:07:22.160 as well as on all of our social media channels. 0:07:22.600 --> 0:07:26.280 We sure will yes on our website This podcast will 0:07:26.360 --> 0:07:27.000 kill You dot Com. 0:07:27.040 --> 0:07:29.080 There's just so many things that you can find there. 0:07:29.120 --> 0:07:31.400 You can find transcripts from all of our episodes. You 0:07:31.400 --> 0:07:33.760 can find sources that we use for every episode. You 0:07:33.760 --> 0:07:36.120 can find our bookshop dot org affiliate account, and our 0:07:36.120 --> 0:07:39.920 Goodreads list, and our merch and our Patreon and bloodmobile 0:07:39.920 --> 0:07:43.480 who does our music, and of contact us form and 0:07:43.520 --> 0:07:47.080 a first hand accounts form. It just keeps going on 0:07:47.160 --> 0:07:47.720 and on. 0:07:48.200 --> 0:07:50.240 It's the website that keeps on giving. 0:07:51.840 --> 0:07:56.400 So check it out and what else business. If you 0:07:56.480 --> 0:07:59.800 haven't already, please rate, review, and subscribe. It helps us 0:08:00.320 --> 0:08:03.440 so that other people can listen to this podcast as well. 0:08:03.960 --> 0:08:08.760 Yeah, send us episode suggestions, you know. Yeah, weekly episodes. 0:08:08.800 --> 0:08:11.520 We need some ideas. You have lots of them, and 0:08:11.640 --> 0:08:15.520 they have so manyone who has sent incredible suggestions. We 0:08:15.600 --> 0:08:17.880 are taking you up on some of those this season. 0:08:18.200 --> 0:08:19.320 It's going to be a great season. 0:08:19.880 --> 0:08:25.440 Well, should we get into fever? Yeah, I think we should. 0:08:25.520 --> 0:08:27.800 Let's take a quick break and then jump in. 0:08:54.480 --> 0:08:56.559 I'm going to try and start at the beginning here ready. 0:08:57.800 --> 0:09:02.960 Pretty much all animals seek to exist at a particular 0:09:03.280 --> 0:09:07.440 temperature set point that we have to do that, and 0:09:07.480 --> 0:09:10.800 this particular temperature that our body likes to exist at 0:09:10.920 --> 0:09:13.440 varies animal to animal. I'm not going to get into 0:09:13.440 --> 0:09:18.880 the details of it. Endotherms like mammals like us, maintain 0:09:19.040 --> 0:09:25.200 our temperature by physiologic mechanisms like energy production and then 0:09:25.520 --> 0:09:29.520 vasodilation or sweating to cool ourselves off. If we get 0:09:29.559 --> 0:09:34.480 too hot and produce too much heat or vasoconstriction or 0:09:34.679 --> 0:09:39.240 shivering or non shivering thermogenesis. If we get too cold, 0:09:40.160 --> 0:09:44.600 as endotherms, we generate our own heat via our metabolism 0:09:44.800 --> 0:09:50.480 in our body and our brain. Specifically, our hypothalamus has 0:09:50.520 --> 0:09:55.360 an internal thermometer that keeps really tight control over our temperature. 0:09:55.920 --> 0:09:59.600 Humans have to stay at around thirty seven degrees celsius 0:10:00.120 --> 0:10:04.200 ninety eight point six fahrenheit plus or minus like one degree, 0:10:04.800 --> 0:10:08.200 and our body and our brain does a really really 0:10:08.240 --> 0:10:11.320 good job of keeping us there. Despite the fact that 0:10:11.360 --> 0:10:14.280 as humans we live at all of these extremes of temperature, 0:10:15.040 --> 0:10:18.480 and despite the fact that we have massive fluctuations in 0:10:18.520 --> 0:10:21.560 our energy expenditure and our energy intake in all of 0:10:21.640 --> 0:10:23.000 these things. 0:10:23.920 --> 0:10:30.120 Why I have questions, I'm interrupting you. Why ninety eight 0:10:30.160 --> 0:10:32.120 point six or thereabouts? 0:10:32.400 --> 0:10:33.480 I have no idea. 0:10:33.559 --> 0:10:36.040 That's a really fun and interesting question because it totally 0:10:36.160 --> 0:10:38.679 varies mammal to mammal. I mean, dogs and cats run 0:10:38.760 --> 0:10:41.720 a lot warmer birds are. 0:10:41.600 --> 0:10:45.240 Super warm, and then you have things like apossums, which 0:10:45.280 --> 0:10:47.480 are like ninety four degrees. 0:10:47.280 --> 0:10:49.119 Right, well, and bears. 0:10:49.760 --> 0:10:51.559 I did a little bit of a deep dive on bears, 0:10:52.440 --> 0:10:54.640 and like animals who hibernate in the. 0:10:54.600 --> 0:10:59.400 Winter, scot we love some hibernation, I know, but I 0:10:59.400 --> 0:10:59.680 don't know. 0:10:59.720 --> 0:11:02.880 I don't know why, like why each animal has evolved 0:11:02.960 --> 0:11:06.240 their particular temperature. It might just assuman has something to 0:11:06.240 --> 0:11:08.320 do with the rate of metabolism. 0:11:08.080 --> 0:11:10.480 Or right, so there's like body size in terms of 0:11:10.840 --> 0:11:14.839 metabolism and stuff like that, and like heart rate. But right, 0:11:15.000 --> 0:11:17.640 it could also just be like drift to a certain extent, 0:11:17.679 --> 0:11:20.360 like there might not be a like a driver of 0:11:20.400 --> 0:11:21.000 it exactly. 0:11:21.120 --> 0:11:23.079 Oh, I have a lot of feelings about drivers in general. 0:11:23.120 --> 0:11:25.920 And we'll keep talking about like, okay, okay, certain things. 0:11:26.000 --> 0:11:27.440 I'll let you keep going. 0:11:27.520 --> 0:11:28.760 Okay. It's a great question, though. 0:11:30.080 --> 0:11:34.839 So extremes of temperature can and do, as we heard 0:11:34.920 --> 0:11:38.959 in our first hand account, result in things like hypothermia 0:11:39.600 --> 0:11:42.920 eighty six degrees is not okay for a human body 0:11:42.920 --> 0:11:46.600 to exist at, or heat stroke on the other end, 0:11:46.760 --> 0:11:50.760 which kills lots of people every year. But here's where 0:11:50.880 --> 0:11:55.880 things get really interesting in hypothermia or in hyperthermia. So 0:11:56.040 --> 0:12:00.280 when we are exposed to extremes of environmental temperatures, our 0:12:00.320 --> 0:12:05.560 brain would still be doing its darndest to keep our 0:12:05.679 --> 0:12:11.120 bodies at a balmy thirty seven celsius. Our temperature set 0:12:11.120 --> 0:12:16.640 point would remain the same. A fever is what happens 0:12:16.720 --> 0:12:21.439 when our temperature set point gets moved. When our body, 0:12:21.520 --> 0:12:25.760 our brain, our hypothalamus that's controlling our temperature set point 0:12:26.200 --> 0:12:30.960 decides and we'll talk about why and how decides. We 0:12:31.040 --> 0:12:33.400 got to heat things up a little bit, and so 0:12:33.440 --> 0:12:36.720 it moves that temperature set point, and then our body 0:12:37.000 --> 0:12:40.079 actively seeks to raise its temperature. 0:12:41.400 --> 0:12:42.280 And that's a fever. 0:12:43.640 --> 0:12:46.599 Okay, when can I start asking more questions? Should I 0:12:46.679 --> 0:12:49.439 just let you keep going and assume that you'll explain 0:12:49.520 --> 0:12:49.840 it all? 0:12:50.040 --> 0:12:53.040 I mean, I'll probably answer them, but like I guess 0:12:53.080 --> 0:12:54.240 what order you want things? 0:12:54.240 --> 0:12:56.000 And you can hit me with questions. 0:12:55.600 --> 0:12:58.560 Now, no, just go, just go, just go, okay, Okay. 0:13:00.160 --> 0:13:01.880 If I don't answer them, then it'll be really fun 0:13:01.920 --> 0:13:05.280 to try and figure out how to answer them. The 0:13:05.360 --> 0:13:08.200 first question that I assumed that you would ask is 0:13:08.240 --> 0:13:09.360 how high is a fever? 0:13:11.000 --> 0:13:13.200 But maybe that's too easy of a question. 0:13:14.559 --> 0:13:16.560 But it turns out, actually when I was reading this 0:13:16.640 --> 0:13:19.840 that like different places actually do define it differently. So 0:13:19.880 --> 0:13:21.360 it made me feel like I need to get off 0:13:21.360 --> 0:13:22.960 of my high horse a little bit. 0:13:24.360 --> 0:13:26.760 Because I do exist on a high horse when it 0:13:26.800 --> 0:13:27.520 comes to fever. 0:13:29.640 --> 0:13:32.400 Wait, wait, what do you mean by you exist on 0:13:32.440 --> 0:13:34.200 a high horse when it comes to fever? 0:13:34.640 --> 0:13:37.480 Well, okay, I have always, one hundred percent of the 0:13:37.480 --> 0:13:41.360 time learned that a fever is anything above thirty eight celsius, 0:13:41.360 --> 0:13:43.000 which is one hundred point four fahrenheit. 0:13:43.120 --> 0:13:45.559 So, like, there are a lot of times. 0:13:45.280 --> 0:13:47.400 When people will say, oh, I have a small fever 0:13:47.559 --> 0:13:50.080 like ninety nine point nine. That is not a fever. 0:13:51.559 --> 0:13:53.959 That is my high horse. That's me on my high horse. 0:13:54.200 --> 0:14:00.240 Ye you correcting someone. Thank god they didn't also say 0:14:00.240 --> 0:14:05.920 a spider is a bug. They would be dead to you. 0:14:06.920 --> 0:14:13.640 It would be the end of a friendship for sure. Anyways. 0:14:13.840 --> 0:14:17.280 Yeah, so is there a difference between low grade fever? Okay? 0:14:17.360 --> 0:14:20.040 Is this so they you ask that question? I hate 0:14:20.040 --> 0:14:24.560 the term low grade fever. It's another high horse. But 0:14:24.680 --> 0:14:27.760 that's just me that like lots of people use that term. 0:14:27.840 --> 0:14:31.680 So when I then was digging into this some organizations 0:14:31.680 --> 0:14:35.240 like the Infectious Disease Society of America and the American 0:14:35.640 --> 0:14:39.680 College of oh I forget the actual acronym, but it's 0:14:39.760 --> 0:14:44.760 the intensive care like academy in the US. They actually 0:14:44.760 --> 0:14:47.560 said that they kind of consider it more like thirty 0:14:47.640 --> 0:14:51.320 eight points three celsius or one on one fahrenheit, which 0:14:51.360 --> 0:14:52.680 is even higher. 0:14:53.120 --> 0:14:55.640 Wow. And so you could have been even higher on 0:14:55.680 --> 0:14:56.480 your horse. 0:14:56.560 --> 0:14:59.360 Exactly, I could have like ninety nine to nine is 0:14:59.480 --> 0:15:06.840 definitely not a fever. But it's really if you think 0:15:06.880 --> 0:15:10.880 about it, if you think of thirty seven as the 0:15:11.600 --> 0:15:15.560 kind of human typical temperature set point, it's plus or 0:15:15.640 --> 0:15:19.000 minus one degree is normal, and our temperature is going 0:15:19.040 --> 0:15:22.960 to vary throughout the day, So one degree off is 0:15:23.040 --> 0:15:25.480 really not that abnormal. And so I think that that's 0:15:25.560 --> 0:15:28.720 kind of like the main point is that, and we'll 0:15:28.800 --> 0:15:31.160 really get into like what happens when we have a fever, 0:15:31.280 --> 0:15:31.880 and like is it. 0:15:31.840 --> 0:15:32.680 Bad, is it good? 0:15:32.800 --> 0:15:32.840 What? 0:15:34.720 --> 0:15:37.000 And so I think that's why in a kind of 0:15:37.200 --> 0:15:40.200 critical care scenario, you might end up tolerating a little 0:15:40.200 --> 0:15:42.560 bit higher before you need to say this is a 0:15:42.600 --> 0:15:43.880 fever that we need. 0:15:43.800 --> 0:15:48.120 To do something about. If that makes sense, okay, And. 0:15:48.120 --> 0:15:52.840 When it comes to a fever, our body also generally 0:15:52.880 --> 0:15:55.960 has a lot of mechanisms in place that keep this 0:15:56.000 --> 0:16:01.160 from getting too high. Usually it stops around forty one 0:16:01.280 --> 0:16:04.200 celsius or one oh five point eight fahrenheit, although some 0:16:04.240 --> 0:16:07.360 papers that I read said that pre antibiotics, we saw 0:16:07.520 --> 0:16:10.600 more like forty two degrees celsius or one oh seven 0:16:10.600 --> 0:16:11.240 point six. 0:16:11.480 --> 0:16:13.520 So it's not that it's impossible to go higher. 0:16:13.960 --> 0:16:17.720 But usually if it's a fever and not heat stroke 0:16:17.800 --> 0:16:23.240 or heat exhaustion that's happening from external factors entirely, but 0:16:23.320 --> 0:16:26.240 a fever caused by this shift in your internal set point, 0:16:26.560 --> 0:16:29.520 then there's also these mechanisms in place that will stop 0:16:29.560 --> 0:16:35.040 it from getting too high. So then what is causing this? 0:16:35.200 --> 0:16:37.600 Like why does our brain decide all of a sudden 0:16:37.640 --> 0:16:41.200 to change our temperature set point and thereby cause a fever. 0:16:42.240 --> 0:16:44.880 Most of the time, it takes two different things to 0:16:45.040 --> 0:16:49.720 start a fever. It takes some exogenous substance, something from 0:16:49.760 --> 0:16:52.600 outside of us that we do not produce, like for example, 0:16:52.680 --> 0:16:56.600 a bacterial endotoxin, or like viral proteins, something that our 0:16:56.640 --> 0:17:01.920 body recognizes as foreign as not self, that interacts with 0:17:02.040 --> 0:17:06.000 our immune system and then it takes substances that we 0:17:06.200 --> 0:17:09.920 do produce, and these are called pyrogens. Really, they're both 0:17:09.960 --> 0:17:15.800 called pyrigens, exogenous and endogenous pyrogens. Our endogenous ones are 0:17:15.960 --> 0:17:19.320 things like inter lukens and TNF alpha. And I'm not 0:17:19.400 --> 0:17:21.479 going to get into the nitty gritty because it's not 0:17:21.720 --> 0:17:26.639 that important. The point is that these things together act 0:17:26.840 --> 0:17:30.720 on our hypothalamus where that temperature set point is, and 0:17:30.760 --> 0:17:34.240 our hypothalamus then produces something that we've talked about on 0:17:34.280 --> 0:17:39.320 this podcast before, which is prostaglandin E two, which acts 0:17:39.400 --> 0:17:42.359 on yet another part of our hypothalamus to kind of 0:17:42.720 --> 0:17:48.280 slow down how much our warm sensitive neurons fire, and 0:17:48.400 --> 0:17:52.280 that's what then results in the increase in our body temperature. Now, 0:17:52.320 --> 0:17:55.600 the deep deep details of like what's hitting what and 0:17:55.640 --> 0:18:00.560 why is it doing xyz we don't fully understand, but 0:18:00.720 --> 0:18:03.840 that is the basic picture of it. It's stuff in 0:18:03.880 --> 0:18:09.159 our body that our immune system recognizes, usually bacteria or 0:18:09.280 --> 0:18:15.200 viral infections that then trigger our brain to say, hey, 0:18:15.800 --> 0:18:19.560 we need to raise the temperature. So that really raises 0:18:19.600 --> 0:18:24.159 this question of is a fever this adaptive mechanism to 0:18:24.359 --> 0:18:27.880 fight off infections? Because the vast majority of the time 0:18:28.000 --> 0:18:30.080 or maybe not the vast majority, but like a lot 0:18:30.119 --> 0:18:33.280 of the time a fever is associated with an infection. 0:18:34.720 --> 0:18:38.639 So there is a lot of literature about this hypothesis 0:18:38.680 --> 0:18:43.000 that because fever is this response to infection, that it 0:18:43.119 --> 0:18:50.080 has adaptive significance specific to reducing pathogen survival. And we 0:18:50.160 --> 0:18:53.879 talked about this kind of in our blastomecosis episode, just 0:18:54.000 --> 0:18:57.719 in like, yeah, how the evolution of endothermy and like 0:18:57.800 --> 0:19:00.760 having a higher body temperature at base line might have 0:19:00.840 --> 0:19:06.000 been adaptive against fungal pathogens like blastomycosis. So then if 0:19:06.000 --> 0:19:08.919 you take that one step further, then perhaps having a 0:19:08.960 --> 0:19:13.640 fever intermittently raising our temperature even higher protects us against 0:19:13.640 --> 0:19:17.879 other pathogens as well. And we do have some support 0:19:18.080 --> 0:19:23.880 for this idea, both directly and indirectly. So indirectly, there's 0:19:23.920 --> 0:19:27.360 a lot of evidence that ectotherms like lizards will lay 0:19:27.359 --> 0:19:30.280 out in the sun to induce a fever, they will 0:19:30.359 --> 0:19:32.720 raise their own body temperature in order to fight off 0:19:32.760 --> 0:19:36.480 pathogens when they're infected, or fish, some fish will swim 0:19:36.520 --> 0:19:39.840 to warmer water if they're infected, which I find so cool, 0:19:40.520 --> 0:19:44.560 really cool. Now, in humans, the studies are a little 0:19:44.560 --> 0:19:48.000 bit maybe more indirect. I guess I don't know, but 0:19:48.160 --> 0:19:52.680 in some studies, for example in the ICU, people who 0:19:52.760 --> 0:19:57.840 have sepsis and have a fever that's not too high, 0:19:58.119 --> 0:20:04.120 so usually not above like forty one or forty even celsius. 0:20:04.680 --> 0:20:06.439 People who have a fever have. 0:20:06.520 --> 0:20:09.639 Lower mortality rates than people who do not have a fever. 0:20:10.320 --> 0:20:12.719 But if that fever gets too high, then it's no 0:20:12.800 --> 0:20:17.040 longer true. And then there's also like in vitro studies 0:20:17.080 --> 0:20:20.639 that show that various organisms that tend to cause infections 0:20:20.640 --> 0:20:26.359 in humans do poorly at higher temperatures, and that fever. 0:20:26.800 --> 0:20:30.439 One like hypothesis as to the mechanism of why is 0:20:30.480 --> 0:20:35.399 that increased temperatures increase the iron requirements of bacteria and 0:20:35.440 --> 0:20:37.000 then reduces their survival. 0:20:38.320 --> 0:20:40.040 I also found this really fun. 0:20:39.840 --> 0:20:43.040 Paper that tried to like dig deep onto like different 0:20:43.160 --> 0:20:46.320 hypotheses of like how you can inhibit pathogen growth. It's 0:20:46.520 --> 0:20:49.000 too much detail, but I'll post it because it's really fun. 0:20:49.320 --> 0:20:53.679 But the idea is just that we have pathogens that 0:20:53.720 --> 0:20:57.679 are less well adapted to survive at higher temperatures, so 0:20:57.840 --> 0:21:00.920 raising our body temperature helps us to fight off those 0:21:00.920 --> 0:21:02.600 infections I mean. 0:21:03.560 --> 0:21:08.040 And also the fact that fever is highly conserved across mammals, 0:21:08.480 --> 0:21:13.760 like mammals in general have fevers, so like and whether 0:21:13.800 --> 0:21:18.320 it's adaptive across the board, I don't think I actually, 0:21:18.359 --> 0:21:21.159 I don't think anyone has has really like tried to 0:21:21.240 --> 0:21:24.080 argue that point specifically, Like, I think it's always been. 0:21:24.440 --> 0:21:28.360 There's nuance to it, because back even in the nineteen 0:21:28.680 --> 0:21:32.960 twenties or even before then, people were seeing fever as 0:21:33.000 --> 0:21:38.200 being adaptive, but also realizing that some pathogens cause fever 0:21:38.680 --> 0:21:42.520 on their own and actually replicate better, i e. Malaria 0:21:42.920 --> 0:21:49.400 parasites replicate better at higher temperatures. So it depends. 0:21:49.560 --> 0:21:55.840 I guess it depends aarin, and fever is not a 0:21:55.880 --> 0:22:00.879 response that's specific to pathogens, right either, So we also 0:22:00.960 --> 0:22:06.560 can see fever in malignancies. We see fever in autoimmune conditions. Now, 0:22:06.640 --> 0:22:12.879 in those cases, it's very likely that the fever mechanism, 0:22:12.920 --> 0:22:15.520 like the generation of that fever, is due to the 0:22:15.560 --> 0:22:19.960 same underlying inflammatory mechanisms, right, It's still like our immune 0:22:20.000 --> 0:22:26.080 system activating the same pathways, just without the presence of 0:22:26.119 --> 0:22:28.119 a bacterial endotoxin to start. 0:22:27.880 --> 0:22:29.000 It off, if that makes sense. 0:22:30.080 --> 0:22:33.760 But then we also see fever in people with traumatic 0:22:33.800 --> 0:22:39.919 brain injury. We see fever from endocrine disruptions like hyperthyroidism, 0:22:40.119 --> 0:22:43.520 and then there's also like drug induced hyperthermia where you 0:22:43.560 --> 0:22:46.800 can get incredibly high body temperatures as a result of 0:22:47.000 --> 0:22:50.560 drug interactions, which is kind of separate, like a separate 0:22:50.600 --> 0:22:58.280 mechanism entirely. So then the question is like, can fever 0:22:59.040 --> 0:23:03.399 be bad? And like the short answer is yes, definitely, yeah, right, 0:23:04.800 --> 0:23:08.320 And part of it is that fever is not an 0:23:08.520 --> 0:23:10.040 isolated phenomenon. 0:23:11.480 --> 0:23:17.760 Yeah, so your face is like, Okay, are there people 0:23:18.600 --> 0:23:23.280 who do not get fevers or cannot change that set point? 0:23:23.760 --> 0:23:29.160 That's an excellent question, definitely, and I think that's part 0:23:29.160 --> 0:23:31.919 of why. So in some of those studies where they 0:23:31.920 --> 0:23:36.919 have looked at patients in ICUs who have sepsis, people 0:23:36.920 --> 0:23:39.440 who don't have a fever at all, who are either 0:23:39.520 --> 0:23:46.200 normalthermic or even hypothermic have less good outcomes like higher 0:23:46.240 --> 0:23:49.399 mortality and things like that. So not being able to 0:23:49.520 --> 0:23:52.719 mount a fever response is usually a sign that your 0:23:52.760 --> 0:23:57.199 immune system is not activating enough. So in terms of 0:23:57.200 --> 0:23:59.200 what the specific cause of that could be, I don't 0:23:59.200 --> 0:24:01.520 have like a list of things for you, but definitely 0:24:01.560 --> 0:24:03.879 there are instances where you could have an immune system 0:24:03.920 --> 0:24:06.520 that's not able to mount a febrile response. 0:24:07.280 --> 0:24:10.640 But I mean, like just people like that is you 0:24:10.640 --> 0:24:15.760 you can never not just situationally, but like can have 0:24:15.920 --> 0:24:18.280 never been able to have a fever. 0:24:18.440 --> 0:24:19.120 I don't. 0:24:19.119 --> 0:24:22.119 I don't know if there's like a documented human who's 0:24:22.160 --> 0:24:23.120 never fevered. 0:24:23.880 --> 0:24:24.879 Well, I'm just it. 0:24:25.200 --> 0:24:27.320 It makes me think a lot about like why is 0:24:27.359 --> 0:24:30.239 it in this part of the brain hypothalamus? When did 0:24:30.280 --> 0:24:32.560 we talk about prostaglandins on this Oh. 0:24:33.119 --> 0:24:35.840 When we talked about thailan all and when we talked about. 0:24:35.760 --> 0:24:42.000 Oh that makes sense, yeah aspirin. Yeah, okay, yeah, anyway, interesting, 0:24:42.080 --> 0:24:45.800 I'm like I now I'm sort of even struggling to 0:24:45.840 --> 0:24:49.080 think about like body heat period. Oh my gosh, what 0:24:49.359 --> 0:24:49.880 what is it? 0:24:49.960 --> 0:24:51.000 I have deep? 0:24:51.359 --> 0:24:54.840 I've got like four more pages from a paper that 0:24:54.920 --> 0:24:59.919 goes deep into like the generation of heat in mammals 0:25:00.080 --> 0:25:03.240 and different mammals and like heat generation and heat loss 0:25:03.240 --> 0:25:06.560 and all of these like thermo dynamics stuff. 0:25:06.800 --> 0:25:07.840 Because there's a lot there. 0:25:08.560 --> 0:25:11.199 I can't wrap my head around it. So I'm sorry 0:25:11.200 --> 0:25:13.320 to have interrupted. Let's just keep going. 0:25:13.520 --> 0:25:33.080 Okay, it's okay, it is really fascinating. But when we 0:25:33.119 --> 0:25:37.720 look at fever specifically, it's not an isolated phenomenon. Your 0:25:37.760 --> 0:25:40.840 brain is not causing a fever, and that's the only 0:25:40.880 --> 0:25:43.240 thing that's happening in your body, whether it's during an 0:25:43.280 --> 0:25:45.880 infection or during malignancy or whatever. 0:25:45.520 --> 0:25:46.360 The cause is. 0:25:47.400 --> 0:25:51.399