WEBVTT - Listener Questions #10 0:00:05.400 --> 0:00:10.039 How do prions infect healthy proteins? Someone please ask about 0:00:10.080 --> 0:00:11.800 Aunt Lion Queen's. 0:00:11.560 --> 0:00:14.520 What does a concert sound like near a black hole? 0:00:14.880 --> 0:00:17.720 Can medical maggots help make a wound hole? 0:00:18.000 --> 0:00:24.880 Biology, physics, archaeology, forestry. We like medicine, so thank you chemistry. 0:00:25.600 --> 0:00:28.800 Do you have questions about particles or cats? We'll find 0:00:28.840 --> 0:00:30.040 answers to all of that. 0:00:30.320 --> 0:00:33.240 Whatever questions keep you up at night. Daniel and Kelly's 0:00:33.280 --> 0:00:34.599 answer will make it right. 0:00:34.840 --> 0:00:38.320 Welcome to another Listener Questions episode on Daniel and Kelly's 0:00:38.440 --> 0:00:56.120 Extraordinary Universe. Him Daniel, I'm a particle physicist with a 0:00:56.200 --> 0:01:01.000 growing interest in biology, and I love here feedback from 0:01:01.120 --> 0:01:03.120 listeners about the new podcast format. 0:01:03.760 --> 0:01:07.080 Hello, I'm Kelly Wiener Smith. I study space and parasites. 0:01:07.120 --> 0:01:09.800 I also love hearing from the listeners, and I'm excited 0:01:09.800 --> 0:01:12.319 about the kind of creepy crawley stuff we're talking about today. 0:01:13.640 --> 0:01:16.080 I am too. There's so much about our natural world 0:01:16.160 --> 0:01:19.119 which is amazing. Even if we don't understand quantum gravity 0:01:19.160 --> 0:01:21.640 and how all the particle bits come together to make 0:01:21.680 --> 0:01:24.760 this bizarre world, it's still totally worth studying. With so 0:01:24.840 --> 0:01:27.640 many incredible, gooey mysteries and the. 0:01:27.640 --> 0:01:30.400 Non gooey mysteries are good too. I'm also becoming a 0:01:30.480 --> 0:01:33.360 budding physics enthusiast. You gave me the other day a 0:01:33.400 --> 0:01:35.680 pod in physics, and I'll take it. 0:01:37.240 --> 0:01:39.480 Yeah. It turns out people can be interested in physics 0:01:39.520 --> 0:01:42.279 and in biology and and all sorts of crazy things 0:01:42.440 --> 0:01:45.959 about our extraordinary universe. And I just wanted to read 0:01:45.959 --> 0:01:47.880 a snippet from a listener who wrote to me and 0:01:48.040 --> 0:01:50.640 encourage anybody out there to write to us questions at 0:01:50.720 --> 0:01:52.920 Daniel and Kelly dot org. Send us your questions, send 0:01:52.960 --> 0:01:55.120 us your feedback, send us your ideas, send us your 0:01:55.120 --> 0:01:57.920 hopes and dreams, send us your love letters from fifth grade, whatever, 0:01:58.000 --> 0:02:00.880 and we'd love hearing from you. Particular listener has a 0:02:00.880 --> 0:02:04.600 long history with me and wrote that he originally quote 0:02:04.840 --> 0:02:06.920 had the idea that I wouldn't be as interested in 0:02:06.960 --> 0:02:10.280 a podcast that wasn't focused entirely on physics. How wrong 0:02:10.360 --> 0:02:14.080 I was. I have found myself fascinated by the biology episodes, 0:02:14.160 --> 0:02:17.840 especially the recent episodes on insulin and gender, and I 0:02:17.840 --> 0:02:20.200 have to feel like I'm going along for the ride. Also, 0:02:20.280 --> 0:02:22.880 like I didn't know how fascinating biology was, and so 0:02:22.919 --> 0:02:25.800 I'm really grateful to get to explore all these topics. 0:02:25.960 --> 0:02:29.120 And I'm so grateful for everyone who's given the biology 0:02:29.120 --> 0:02:31.440 a chance, everyone who sort of came for the physics 0:02:31.440 --> 0:02:34.040 but is staying for the biology and hopefully is enjoying 0:02:34.040 --> 0:02:38.440 it as well. And the listener mentioned the insulin episode. 0:02:38.480 --> 0:02:41.680 We are super lucky to have Katrina Whitson coming for 0:02:41.720 --> 0:02:45.000 a little guest appearance on the show again today. But yes, 0:02:45.040 --> 0:02:47.640 I read that email too, and it absolutely made my month. 0:02:48.080 --> 0:02:49.360 I love when we get emails like that. 0:02:49.760 --> 0:02:52.800 Me too. And also, you can't mention Katrino without referring 0:02:52.880 --> 0:02:55.120 to all of her accolades. I know if you're aware 0:02:55.160 --> 0:02:57.360 she's the Whites And Endowed Chair at the Whites And Institute. 0:02:57.400 --> 0:03:01.880 Oh my gosh, wow incredible. I have been dying to 0:03:01.919 --> 0:03:05.160 get an adjunct position at the Whites And Research Institute. 0:03:05.800 --> 0:03:08.720 The review process is really strict. Yeah, a bunch of 0:03:08.760 --> 0:03:09.600 snobs over there. 0:03:12.320 --> 0:03:14.480 I've met Katrina. I'm not sure about that. She seems 0:03:14.560 --> 0:03:15.160 very nice. 0:03:15.400 --> 0:03:18.639 No, of course, we'd love to have you anyway. Today 0:03:18.680 --> 0:03:22.520 we are talking about your questions about this extraordinary universe, 0:03:22.760 --> 0:03:27.120 physics questions, black hole questions, weird protein questions. We'd love 0:03:27.160 --> 0:03:30.560 to answer your question on the podcast. Please do right 0:03:30.639 --> 0:03:34.000 to us questions at Danielankelly dot org. Again, if you 0:03:34.080 --> 0:03:36.480 write to dot com, you'll be sending your message to 0:03:36.560 --> 0:03:38.960 a very lovely couple who just got married, but that's 0:03:38.960 --> 0:03:39.320 not us. 0:03:39.440 --> 0:03:44.040 Congratulations Daniel and Kelly. We wish you a beautiful forever together. 0:03:45.080 --> 0:03:47.560 And Daniel and Kelly dot com. If you guys have questions, 0:03:47.640 --> 0:03:49.440 send them to us. We'd love to have you guys 0:03:49.560 --> 0:03:50.240 on the podcast. 0:03:50.320 --> 0:03:52.440 Hey, Daniels and Kelly's. 0:03:53.320 --> 0:03:53.520 Well. 0:03:53.560 --> 0:03:57.040 Our first question today is an amazing question by Niall 0:03:57.240 --> 0:04:00.320 about pry on or pre on. I don't know I'm 0:04:00.320 --> 0:04:02.320 going to say it, however, you know it comes out 0:04:02.320 --> 0:04:03.800 of my mouth at the time, but let's go ahead 0:04:03.800 --> 0:04:04.440 and hear the question. 0:04:05.120 --> 0:04:08.480 Hi, Kelly and Daniel, my name is Nile, and I 0:04:08.480 --> 0:04:13.160 have a question regarding preons and preon diseases. I understand 0:04:13.200 --> 0:04:17.040 that preons are misfolded proteins that are capable of causing 0:04:17.120 --> 0:04:20.839 significant damage to our nervous systems if we are exposed 0:04:20.880 --> 0:04:26.240 to them. However, I am particularly interested in understanding why 0:04:26.360 --> 0:04:32.880 preon diseases are infectious slash contagious. Specifically, I'm wondering what 0:04:32.920 --> 0:04:38.080 causes our normal properly folded proteins to adopt the misfolded 0:04:38.200 --> 0:04:42.680 preon structure when exposed to them, rather than just defaulting 0:04:42.720 --> 0:04:47.280 to their correct structure. I would greatly appreciate any insight 0:04:47.400 --> 0:04:50.200 you can provide on this topic. Thank you so much, 0:04:50.240 --> 0:04:51.000 And I love the show. 0:04:51.560 --> 0:04:54.279 This is a fantastic question that I did not know 0:04:54.360 --> 0:04:57.360 the answer to, and you'll see that by the end, 0:04:57.400 --> 0:04:59.839 I spent five hours slamming my head against the lit 0:05:00.440 --> 0:05:04.520 and eventually we called in someone smarter than either of us, 0:05:05.000 --> 0:05:07.159 and that's where Katrina comes in. But let's back up 0:05:07.200 --> 0:05:10.240 a little bit, all right, So how do diseases usually 0:05:10.640 --> 0:05:15.039 replicate and transmit? So, if you have a bacterial infection, 0:05:15.240 --> 0:05:17.800 like you've got a cold, the bacteria get into your 0:05:17.839 --> 0:05:20.440 body and then those bacteria start making more and more 0:05:20.480 --> 0:05:23.080 of themselves and they, you know, spread throughout your body. 0:05:23.120 --> 0:05:25.919 That's kind of creepy, right, You're being like colonized by 0:05:26.240 --> 0:05:27.359 some malevolent force. 0:05:27.560 --> 0:05:30.840 It is pretty creepy. Yeah. And then if you get parasites, 0:05:31.080 --> 0:05:33.120 like you know, the parasites that I love to talk 0:05:33.160 --> 0:05:36.880 about so much, something like tapeworms or nematodes, what usually 0:05:36.960 --> 0:05:40.560 happens there is every single infection you get is because 0:05:40.600 --> 0:05:44.000 you have accidentally, for example, consumed an egg that was 0:05:44.000 --> 0:05:46.240 in the environment. And so the way you get more 0:05:46.240 --> 0:05:49.840 of those infections is you accidentally encounter and consume more 0:05:49.839 --> 0:05:53.320 of those eggs. For viral infections, the way you get 0:05:53.360 --> 0:05:56.120 more of those is that the virus injects some of 0:05:56.120 --> 0:05:57.320 its genetic material. 0:05:57.880 --> 0:05:59.400 So gross, so gross. 0:05:59.480 --> 0:06:03.080 Yes, yeah, I know I hate viruses and bacteria, but 0:06:03.120 --> 0:06:04.800 none of them are as bad as ticks. Ticks are 0:06:04.800 --> 0:06:08.440 the worst. Yes, So they inject genetic material into your 0:06:08.480 --> 0:06:12.920 own cells, hijack your cell's machinery, and your cell essentially 0:06:12.960 --> 0:06:15.000 makes more viruses for the virus. 0:06:15.320 --> 0:06:18.240 All of these things have nucleic material, right, this DNA 0:06:18.360 --> 0:06:21.000 or RNA or something, and all these things. People argue 0:06:21.000 --> 0:06:23.799 about whether viruses are alive or not, but like they 0:06:23.839 --> 0:06:26.240 have this code inside of them. That's what they all 0:06:26.240 --> 0:06:26.839 have in common. 0:06:26.920 --> 0:06:30.400 Right, Yeah, that's right. And so when the first person 0:06:30.520 --> 0:06:34.080 suggested that what's happening with what ended up being called 0:06:34.080 --> 0:06:37.839 prion diseases is that it's actually a protein that is 0:06:37.920 --> 0:06:41.279 essentially replicating, not by sort of copying itself using genetic 0:06:41.360 --> 0:06:45.560 material like you would expect, but is essentially touching other 0:06:45.640 --> 0:06:51.000 proteins and making those other proteins infectious. That was a 0:06:51.000 --> 0:06:53.560 bit controversial for a while because that's not how we 0:06:53.680 --> 0:06:56.600 usually see infections transmitting in any of the ways that 0:06:56.640 --> 0:06:57.640 we sort of understand this. 0:06:57.920 --> 0:07:00.479 Are you underplaying it a little bit, a bit controvert, Like, 0:07:00.600 --> 0:07:02.680 wasn't that sort of laughed out of the room for 0:07:02.720 --> 0:07:04.520 a while, People are like, that's impossible. 0:07:04.760 --> 0:07:07.520 Yes, yes, no, we were all very skeptical. It took 0:07:07.520 --> 0:07:09.720 a while for that to be widely accepted. 0:07:10.560 --> 0:07:13.040 And for those of us who are not biologists or biochemist, 0:07:13.400 --> 0:07:15.920 remind us what you mean when you say protein. You're 0:07:15.960 --> 0:07:18.880 using in a technical sense, not like chicken breasts or 0:07:18.920 --> 0:07:21.600 tofu on top of your salad. When your server asks 0:07:21.640 --> 0:07:24.080 if you'd like to add protein? You mean something about 0:07:24.120 --> 0:07:25.360 the chemical structure, right. 0:07:25.320 --> 0:07:28.080 Yeah, so I mean chicken breast is made of proteins. 0:07:28.280 --> 0:07:31.559 So your genetic code contains the information that your body 0:07:31.600 --> 0:07:34.800 needs to make proteins. And proteins are strings of amino acids, 0:07:35.120 --> 0:07:38.280 and they essentially make up all of your body, and 0:07:38.320 --> 0:07:43.560 they help your chemical reactions happen, and they are ubiquitous, and. 0:07:43.480 --> 0:07:47.440 They're incredible little molecular machines. Right, they do stuff. They 0:07:47.480 --> 0:07:49.720 come from the DNA and then they fold into these shapes. 0:07:49.760 --> 0:07:53.440 They're like little robots, right, They're amazing. The engineering here 0:07:53.560 --> 0:07:53.920 is just. 0:07:53.880 --> 0:07:57.360 Astounding, delicious in your salad and fantastic in your body. 0:07:59.120 --> 0:08:01.840 So the listener to know about prions. So these are 0:08:02.040 --> 0:08:05.600 protinaceous infectious particles, is the fancy way of sort of 0:08:05.640 --> 0:08:08.840 saying it. And there's a couple different ways that proteins 0:08:08.880 --> 0:08:11.360 can transmit disease. So one of them is that they're 0:08:11.440 --> 0:08:14.200 sort of infectious in the way you might usually think 0:08:14.240 --> 0:08:17.160 of infectious material. So, for example, if you eat meat 0:08:17.760 --> 0:08:22.320 that has the mad cow prion in it, and you 0:08:22.440 --> 0:08:25.440 consume that meat, that prion can then move around your 0:08:25.440 --> 0:08:29.160 body and cause your proteins to become abnormal. So that's 0:08:29.720 --> 0:08:31.640 infectious in a way that we sort of are used 0:08:31.640 --> 0:08:33.160 to thinking about infectious material. 0:08:33.520 --> 0:08:35.200 And just to make sure I'm following, when you say 0:08:35.320 --> 0:08:39.400 prion is a protinaceous infectious particle, it's still just a protein. 0:08:39.520 --> 0:08:42.320 Is just like a weird protein in a particular shape, right, 0:08:42.600 --> 0:08:44.880 It's not like it's turned into a particle the way 0:08:44.920 --> 0:08:45.679 we talk about it. 0:08:45.880 --> 0:08:48.760 Oh yeah, no, forget the physics, man, forget the physics. 0:08:48.760 --> 0:08:49.760 We're in bio world. 0:08:49.840 --> 0:08:53.000 Right now, I'm listening to biologists talk about particles, but 0:08:53.040 --> 0:08:54.959 it has nothing to do with particles. That's great. 0:08:55.240 --> 0:08:58.200 I don't know whether particles in biology are more confusing 0:08:58.240 --> 0:09:01.480 than particles in physics, but either we're gonna buddle through. 0:09:01.920 --> 0:09:04.720 All right. So you can get these in your body 0:09:04.760 --> 0:09:07.280 and they can turn some of your proteins into preon's. 0:09:07.320 --> 0:09:09.000 What's another way that you can get one of these 0:09:09.000 --> 0:09:09.960 horrible diseases. 0:09:10.080 --> 0:09:12.800 Another way you can get one of these horrible diseases, unfortunately, 0:09:12.880 --> 0:09:15.000 is if you end up with a mutation in your 0:09:15.040 --> 0:09:19.160 own genes, and then your genetic code now produces a 0:09:19.240 --> 0:09:22.480 protein that folds in a way it's not supposed to fold. 0:09:22.920 --> 0:09:27.000 And usually when you get this heritable gene that has 0:09:27.040 --> 0:09:29.840 this bad mutation, you don't start making these weird proteins 0:09:29.880 --> 0:09:32.600 until you're a little bit older, like sixties or more. 0:09:33.080 --> 0:09:34.640 Funny story, I was talking to a neighbor the other 0:09:34.720 --> 0:09:36.320 day who said something to the effect of, oh, well, 0:09:36.320 --> 0:09:38.440 when I'm talking to young people, they're not so interested 0:09:38.480 --> 0:09:40.520 in this, And I was like, oh, I'm interested. And 0:09:40.559 --> 0:09:44.120 then I realized that he didn't mean me exactly. He 0:09:44.160 --> 0:09:46.120 could tell I was interested because I was one of 0:09:46.120 --> 0:09:49.319 the old people, and he was talking about other people. Anyway. 0:09:49.480 --> 0:09:50.880 Did I ever tell you about the time I was 0:09:50.960 --> 0:09:53.880 accidentally c seed on an email where they were looking 0:09:53.880 --> 0:09:56.680 for a young ish professor to take on some roll 0:09:57.000 --> 0:09:59.600 and somebody said whites and is he youngish anymore? I'm 0:09:59.600 --> 0:09:59.960 not sure? 0:10:00.280 --> 0:10:03.760 And I was like, oh, nice. Oh I thought I 0:10:03.800 --> 0:10:05.440 just had a little gray in my hair. And someone 0:10:05.480 --> 0:10:07.440 told me I was rocking the salt and pepper look, 0:10:07.520 --> 0:10:09.160 which was very nice. But that was the first time 0:10:09.200 --> 0:10:11.960 I realized that I had transitioned to salt and pepper. Anyway, 0:10:12.400 --> 0:10:14.800 you and I are aging, but hopefully we don't have 0:10:14.840 --> 0:10:15.760 this mutation. 0:10:15.559 --> 0:10:18.280 All right, So this mutation just means that you produce 0:10:18.400 --> 0:10:22.120 a protein through the normal mechanism of like DNA RNA protein, 0:10:22.400 --> 0:10:24.840 But it's one of these bad proteins. Yes, you said 0:10:24.840 --> 0:10:27.320 that it doesn't fold the way it's supposed to. Is 0:10:27.320 --> 0:10:29.160 it that it doesn't fold the way the DNA tells 0:10:29.160 --> 0:10:31.600 it to, or that it folds in a way that's damaging. 0:10:31.760 --> 0:10:33.920 It folds in a way that's damaging if you have 0:10:34.000 --> 0:10:38.680 this mutation. Mutations often result in changes in an amino 0:10:38.720 --> 0:10:41.120 acid in the sequence that makes up a protein, and 0:10:41.120 --> 0:10:43.160 when you have a change in that amino acid, it 0:10:43.200 --> 0:10:46.760 can change the shape of the protein. So the protein 0:10:46.840 --> 0:10:49.280 might be doing what the genetic code told it to do, 0:10:49.760 --> 0:10:52.120 but now it's folding up in a configuration that's bad 0:10:52.160 --> 0:10:54.480 for you and can go and cause other proteins to 0:10:54.520 --> 0:10:54.920 do it too. 0:10:55.080 --> 0:10:57.080 All right, So you can either get through from outside 0:10:57.080 --> 0:10:59.840 the body or you can just have your genetic code 0:11:00.080 --> 0:11:02.920 do these terrible things. Is that it or is there 0:11:02.960 --> 0:11:04.240 another thing we have to worry about. 0:11:04.480 --> 0:11:07.600 The third way is what they call spontaneous. So you've 0:11:07.640 --> 0:11:10.680 got proteins, and actually, something that I learned while doing 0:11:10.720 --> 0:11:14.680 this research is that sometimes your proteins will change shape 0:11:15.000 --> 0:11:17.680 and then go back to their normal shape. Wow, while 0:11:17.679 --> 0:11:20.160 they're in your body, and it doesn't seem efficient, just 0:11:20.320 --> 0:11:23.920 like be consistent, man, But so I guess sometimes they 0:11:23.920 --> 0:11:26.040 will sort of get out of their configuration and when 0:11:26.040 --> 0:11:29.000 they go back into their configuration, they don't go back correctly, 0:11:29.559 --> 0:11:32.959 and so now they've got this bad shape. And once 0:11:33.000 --> 0:11:37.040 you've got either the heritable or the spontaneous version of 0:11:37.080 --> 0:11:40.800 these prions, they start to act infectious. So they go 0:11:40.880 --> 0:11:44.280 around and they make other prions abnormally shaped as well. 0:11:44.800 --> 0:11:48.240 Weird. That's incredible that one protein can turn another protein bad. 0:11:48.679 --> 0:11:50.319 It's like the bad influence protein. 0:11:50.720 --> 0:11:54.000 This spontaneous prion thing. This is like stay up at 0:11:54.080 --> 0:11:57.360 night worrying about what all your proteins are doing. I'm 0:11:57.360 --> 0:11:59.520 not worrying about my kids anymore. I'm worried about whether 0:11:59.600 --> 0:12:02.559 or not my proteins are behaving. But I'm sure it's fine. 0:12:02.640 --> 0:12:05.720 This is a whole fascinating area though. Protein folding. We 0:12:05.800 --> 0:12:08.520 describe it as if it's like DNA RNA protein, but 0:12:08.559 --> 0:12:09.559 it's very complicated. 0:12:09.600 --> 0:12:09.720 Right. 0:12:09.760 --> 0:12:12.400 You build this sequence of amino acids and when they fold, 0:12:12.440 --> 0:12:15.640 they're like settling into a lower energy state. They're like 0:12:15.679 --> 0:12:18.679 relaxing into it. And it's really hard to know what 0:12:18.720 --> 0:12:20.600 that state is. You can look at the DNA code. 0:12:20.760 --> 0:12:24.280 It's not easy to predict the configurations of proteins that 0:12:24.320 --> 0:12:26.559 come out of that sequence. There was a huge result 0:12:26.600 --> 0:12:29.520 recently alpha fold where people were able to predict these 0:12:29.559 --> 0:12:32.920 things very well using AI. Really an incredible breakthrough. People 0:12:32.920 --> 0:12:34.160 have been working on that for decades. 0:12:34.360 --> 0:12:38.120 Yeah, that is fantastic. Let's go into one real example. 0:12:38.760 --> 0:12:45.160 Fritz Feld Jacob disease. So sorry about my pronunciation, apologize 0:12:45.160 --> 0:12:45.760 ahead of time. 0:12:46.280 --> 0:12:48.040 I'm not even going to correct you because I enjoy 0:12:48.080 --> 0:12:49.640 listening to your mispronunciations. 0:12:49.760 --> 0:12:51.800 Okay, do you know how to pronounce it correctly? 0:12:52.440 --> 0:12:54.720 I'm pretty sure it's quartz failed yakup disease, but I 0:12:54.800 --> 0:12:55.640 like the way you said it. 0:12:55.760 --> 0:12:57.480 Oh okay, well thanks, I appreciate that. 0:12:57.360 --> 0:12:59.280 Especially like the way you like tiptoe through it in 0:12:59.320 --> 0:13:00.280 a terrified. 0:13:02.040 --> 0:13:03.520 But from now on, it's CJD. 0:13:03.960 --> 0:13:04.320 Okay. 0:13:04.720 --> 0:13:07.520 So for CJD, what happens is that in older people 0:13:07.640 --> 0:13:11.080 sometimes you sporadically get a protein that folds up incorrectly. 0:13:11.120 --> 0:13:13.559 Now you've got this abnormal form. And I read a 0:13:13.559 --> 0:13:16.960 bunch of papers that suggested that as various vertebrates age, 0:13:17.160 --> 0:13:20.840 our proteins are sort of more likely to fold the 0:13:20.880 --> 0:13:23.120 wrong way because aging is a real pain in the 0:13:23.160 --> 0:13:25.600 rear end. And then in ten to fifteen percent of 0:13:25.640 --> 0:13:28.120 the cases, this has to do with a genetic mutation 0:13:28.240 --> 0:13:32.560 that's giving the protein essentially bad instructions, and every once 0:13:32.600 --> 0:13:34.600 in a while, in a rare case, you can get 0:13:34.600 --> 0:13:37.520 it transmitted. So, for example, if you get a cornea 0:13:37.559 --> 0:13:41.840 transplant from somebody who has CJD, then you can get CJD. 0:13:41.920 --> 0:13:43.800 So it's important to screen for this kind of stuff, 0:13:44.040 --> 0:13:46.120 and so unfortunately, once you get it, we don't have 0:13:46.120 --> 0:13:50.480 any treatment, and usually the symptoms get worse quite quickly 0:13:50.520 --> 0:13:54.040 by the time the symptoms are identifiable, and according to 0:13:54.080 --> 0:13:57.079 the CDC website, it causes a person's brain to break 0:13:57.120 --> 0:13:59.600 down or stop working normally, which I'm sure we can 0:13:59.640 --> 0:14:01.640 all is not a way we would like our brains 0:14:01.679 --> 0:14:02.320 to be described. 0:14:02.440 --> 0:14:04.120 No, I do not want my brain to turn into 0:14:04.120 --> 0:14:04.720 a smoothie. 0:14:04.800 --> 0:14:08.840 No, no me either. I think most people initially started 0:14:08.840 --> 0:14:12.240 hearing about prions when they learned about bovine sponge of 0:14:12.320 --> 0:14:18.520 worn and cephalopathy BS bad cow disease, and this showed 0:14:18.600 --> 0:14:20.440 up in cows. Turns out cows were getting it from 0:14:20.480 --> 0:14:24.120 one another because we were feeding cows cow parts. And yeah, 0:14:24.240 --> 0:14:24.800 bad idea. 0:14:24.920 --> 0:14:26.840 Cannible cows annible cows, right. 0:14:26.720 --> 0:14:28.680 And you might remember from when we were feeding pigs 0:14:28.720 --> 0:14:31.720 pig parts that that was bad for the transmission of 0:14:31.880 --> 0:14:33.800 trick and ella. So in general, it seems like it's 0:14:33.800 --> 0:14:36.320 a bad idea to feed animals animal parts, although I 0:14:36.400 --> 0:14:40.520 do feed my chickens chickens sometimes. Oh I know, maybe 0:14:40.560 --> 0:14:41.400 I'm asking for it. 0:14:41.720 --> 0:14:44.960 That's horrible. Yeah, there's something really creepy about that. I 0:14:44.960 --> 0:14:47.520 don't know why I like chickens eating pork whatever, chickens 0:14:47.520 --> 0:14:49.080 eating chickensoh. 0:14:49.200 --> 0:14:52.040 They don't seem to mind. They love the nuggies. They 0:14:52.080 --> 0:14:54.120 love the chicken nuggies. All right? 0:14:55.280 --> 0:14:56.920 What kind of sauces do they like to like? The 0:14:57.080 --> 0:14:58.960 dip it? Are they into the barbecue? 0:14:59.520 --> 0:15:01.320 No, they don't. We have the dexterity for that. I 0:15:01.360 --> 0:15:03.600 don't know. If you've seen chicken claws, they're not real good. 0:15:03.640 --> 0:15:05.000 They can scratch and that's about it. 0:15:05.160 --> 0:15:07.560 All right. So we know that getting these preons is bad. 0:15:07.640 --> 0:15:10.640 You get these terrible diseases and they spread from body 0:15:10.680 --> 0:15:13.680 to body, and even if you eat like meat that's 0:15:13.720 --> 0:15:16.240 been cooked. We're used to like cooking something to kill it. 0:15:16.640 --> 0:15:19.360 But if you cook a preon, is it then better? 0:15:19.560 --> 0:15:21.640 Is it like denatured or can you still get it 0:15:21.680 --> 0:15:22.800 from cooked meat? You know? 0:15:22.840 --> 0:15:24.600 As far as I can tell. One of the things 0:15:24.600 --> 0:15:27.600 about these preons that is incredible is that they're really 0:15:27.720 --> 0:15:31.240 resistant to things like cooking, and so you can cook 0:15:31.280 --> 0:15:34.720 your burger and if it had bs, there's still some 0:15:34.880 --> 0:15:35.880 chance that you could get it. 0:15:36.000 --> 0:15:37.960 I heard that even if you irradiate these things, like 0:15:38.080 --> 0:15:41.400 zap them with radiation, they're super dup or robust, which 0:15:41.440 --> 0:15:43.440 is one reason that they're able to spread from one 0:15:43.480 --> 0:15:46.360 to the other. And so it's like really hard to 0:15:46.440 --> 0:15:49.200 kill a preon. Like when they do brain surgery in hospitals, 0:15:49.200 --> 0:15:52.240 they just throw away everything that touched the brain because 0:15:52.280 --> 0:15:54.080 it might have a preon in it, and you do 0:15:54.160 --> 0:15:55.520 not want that stuff to spread. 0:15:55.760 --> 0:15:59.080 We are so stink and lucky that preon diseases are 0:15:59.080 --> 0:16:02.680 not more common. Thank your lucky stars everybody. 0:16:02.880 --> 0:16:05.000 So then let's get to the heart of the listener's question, 0:16:05.120 --> 0:16:07.840 right he's asking about the fundamental mechanism, like how does 0:16:07.880 --> 0:16:10.480 this happen? You were talking about one preon turning ou 0:16:10.520 --> 0:16:13.360 a normal protein into another preon. Do we know how 0:16:13.360 --> 0:16:13.960 that happens? 0:16:14.200 --> 0:16:17.640 If by we you mean Katrina, the answer is yes. 0:16:17.840 --> 0:16:20.800 Let me quickly summarize the three problems that you need 0:16:20.840 --> 0:16:24.800 to understand to understand prions. So, one, an abnormal protein 0:16:24.880 --> 0:16:26.600 is made. This is pretty much what we've been talking about, 0:16:26.640 --> 0:16:29.320 the various ways that you start getting these abnormal proteins. 0:16:29.800 --> 0:16:34.000 Problem too, is that the prion starts causing more prion 0:16:34.040 --> 0:16:36.360 proteins to be made, so it interacts with the healthy 0:16:36.360 --> 0:16:39.400 proteins in the area and starts turning them into bad proteins. 0:16:39.720 --> 0:16:43.640 And then problem three is that these proteins start clumping together, 0:16:43.800 --> 0:16:46.560 and it's these clumps that start causing problems. So the 0:16:46.640 --> 0:16:49.680 brain has trouble clearing these clumps out. So the listener 0:16:49.720 --> 0:16:52.800 wanted to know the details for problem too. How does 0:16:53.000 --> 0:16:57.880 one prion cause another protein to start misfolding and becoming 0:16:57.920 --> 0:17:01.120 another one of these sort of infectious prions. And I 0:17:01.200 --> 0:17:03.640 was so annoyed because I found so many papers, and 0:17:03.800 --> 0:17:06.600 every paper was like, Okay, here's how we're gonna illustrate 0:17:06.600 --> 0:17:09.280 how it works. And they were like, the normal protein 0:17:09.400 --> 0:17:12.120 is a circle and the abnormal protein is a square, 0:17:12.600 --> 0:17:15.040 and the circle becomes a square, and then the square 0:17:15.119 --> 0:17:17.359 interacts with other circles and turns them into squares. And 0:17:17.400 --> 0:17:19.920 I was like, that doesn't really explain what's happening. 0:17:20.359 --> 0:17:21.240 That's just a cartoon. 0:17:21.359 --> 0:17:23.960 It's just a cartoon. How does the circle turn the 0:17:24.000 --> 0:17:27.920 squares in? Anyway? Eventually I threw my hands up and 0:17:27.960 --> 0:17:31.600 we were so happy that we know a biochemist. And 0:17:31.680 --> 0:17:36.080 so Daniel, go ahead and introduce your amazing wife. 0:17:36.240 --> 0:17:39.920 That's right, Katrina actually has a PhD in biochemistry protein 0:17:40.080 --> 0:17:42.639 folding DNA all this kind of interaction. She did her 0:17:42.720 --> 0:17:45.719 PhD on like how proteins cut DNA and interact with it. 0:17:45.920 --> 0:17:48.080 So she like has her head around all of this stuff. 0:17:48.280 --> 0:17:50.479 So I asked her, Hey, can you explain to us 0:17:50.520 --> 0:17:53.879 how this actually happens? How two proteins come together and 0:17:53.960 --> 0:17:56.439 both end up bad? Like why don't they both end 0:17:56.480 --> 0:17:59.280 up good? You know, all these arguments are like template this, 0:17:59.359 --> 0:18:02.240 template that, Like why did they both end up bad? 0:18:02.560 --> 0:18:04.359 So I asked her on the cash last night, and 0:18:04.440 --> 0:18:07.399 here's what she had to say. Hey, Katrina, so how 0:18:07.400 --> 0:18:10.320 does a prion turn another protein into a preon? 0:18:10.600 --> 0:18:14.159 So proteins are just these chains of amino acids, and 0:18:14.320 --> 0:18:18.439 each block has different likeness for water, like some of 0:18:18.480 --> 0:18:21.080 them like to be near water, some of them hate water. 0:18:22.160 --> 0:18:25.520 The balance of those things forces the protein into a 0:18:25.520 --> 0:18:30.760 certain shape, so each protein makes a really unique shape. However, 0:18:31.160 --> 0:18:35.359 some proteins have more than one stable state, so they 0:18:35.440 --> 0:18:39.600 might be happy in a slightly different shape. And what 0:18:39.680 --> 0:18:44.400 preons do is they force the protein into an alternative shape. 0:18:44.520 --> 0:18:46.280 I think that's the bit we want to dig into. 0:18:46.440 --> 0:18:49.439 When two proteins come near each other, why does the 0:18:49.480 --> 0:18:52.440 preon force the good one into a preon shape rather 0:18:52.480 --> 0:18:55.560 than the good one, forcing the preon into a good shape, 0:18:55.600 --> 0:18:56.840 why does the preon win? 0:18:57.080 --> 0:18:59.280 And that shape is usually one that's a little hard 0:18:59.280 --> 0:19:01.560 to get itself out of, so they get stuck in 0:19:01.600 --> 0:19:07.200 that direction. So basically, if a protein forms the preon shape, 0:19:07.200 --> 0:19:09.679 which it usually does at a lower rate than the 0:19:10.000 --> 0:19:13.639 healthy correct shape, but if that happens, then when another 0:19:13.680 --> 0:19:18.480 healthy protein gets near it, it gets peer pressured essentially 0:19:18.600 --> 0:19:23.680 into forming that alternative but like disastrous and like disease 0:19:23.800 --> 0:19:29.920 forming alternative shape. This happens for certain sequences of proteins, 0:19:30.520 --> 0:19:36.320 and they often have repeat zones in them that are 0:19:36.440 --> 0:19:40.359 like making it easier for them to collapse into this 0:19:40.480 --> 0:19:43.800 unhealthy state. And so I can think of a couple 0:19:43.920 --> 0:19:46.800