SIO404: Are We Attracted To Our Mate's Immune System?

Transcript

This transcript was generated automatically and may contain errors — the audio is the record.

0:00:16 Thomas: Hello and welcome to Serious Inquiries Only. This is episode 4. I'm Thomas Smith and I'm so excited for today's show. I know I always say that but this one was truly a lot of fun. Magic school bus -esque, I would go ahead and say if I may be so bold. Now today's guest is Dr. Rick Sullivan and more immune system stuff but a little bit different did you know that one factor in being attracted to your partner might be their immune system because it turns out that if uh you know you do some science and sciencey science. Looks like we're maybe slightly more attracted to people with kind of a different immune system in a way that kind of promotes diversity of immune responses in a way that is, it's so cool.

Sullivan's going to tell us all about that, plus so much more. He gives us a really fun lesson on on the immune system. I know we've talked about, food you allergies, but this is a totally different thing. This is like viruses and all that kind of thing. And it's on a more mechanical level. And, just fascinating. I, I cannot believe that this is how our body works all the time. S crazy. Excited to get to that.

But first, as I always say, if you'd like to avoid the auto ad that is just about to happen, plus the other ones in the show, go to patreon.com/seriouspod. Enjoy the bonuses. Ooh, we're recording Seriously Awful Movies tomorrow. I'm really excited about it. It is so bad. Oh, oh, it's bad. Can't wait. That'll be up soon for patrons, of course. And there's the hangout on the 30th. Hope you're going to join us. Check Patreon for for all that.

You got to be in the top two tiers of Patreon. So, forward to some code names and so much more over on patreon.com/seriouspod. So hope to see you over there. And if not, here's an auto ad for you probably selling some horrible conservative crap, but it's actually really, you know, kind of better if they waste their money on you guys, cause there's no way you're spending any money on them. So that's a service you're performing for the world. All Rick Sullivan, how are you doing today?

0:02:19 Rick: Doing great, Thomas. Thanks for having me.

0:02:21 Thomas: My pleasure. Thanks for coming on. I'm really excited to learn some cool stuff about the immune system today. I love to do though is do you mind giving a little personal background, how you got into this subject area and this expertise, all that stuff?

0:02:35 Rick: Absolutely. Well, I got my PhD in immunology from the University of Colorado and went on to do a postdoc in immunology at UCSF, looking at malaria and host pathogen interactions. But that's sort of my professional life. I would say the other big part that describes me is I'm diehard romantic, and I have an incredible partner. And we met in high school and fell in love and Went our separate ways for 10 years, and then our paths crossed again. Michigan, and actually, while I was getting my PhD. So we spent two years long distance. So that love story for me is just so incredible. And so one of the big hooks when I got into immunology was when I heard how much love actually shapes, or our immune system shapes, who we fall in love with.

0:03:00 Thomas: Oh, wow.

0:03:20 Thomas: Shoot, I should have held this one for Valentine's Day, but that's okay. Maybe we can do a follow-up around that. No, that's super cool. But it sounds like you always kind of going down the immunology route and didn't really look back. I know a lot of people kind of change their minds or don't know. So what fascinated you about immunology specifically from get -go?

0:03:24 Rick: Sure, absolutely.

0:03:39 Rick: You know, it took me quite a while. Actually, I for a long time I was going to have a life in music and art and whatnot, but then went back to school and

0:03:45 Thomas: There you go. Yeah, same. I guess I better go study immunology. Okay, I get it.

0:03:50 Rick: That's how it goes. That's, you know, one thing leads to another and you're an immunologist. Think it was just how complicated and how layered the immune system was. And it is this sense of how can immune system, how can you body with a finite set of DNA may be prepared to deal with anything that's coming at you, in the world, you know, and there's that perpetual arms race, and we evolve more slowly than a bacteria that has a life cycle of 20 minutes, you know, uh, And so how do deal with that, and then you look around at the world and you're like, man, all this was possible because we were able to fight off you infections and you get cut and heal and repair and move forward with life.

0:04:02 Thomas: Yeah, yeah, right. Yeah, right, and like it's also, you probably have a lot of work since COVID, or has that just changed how you work or, you you know, what you've studied or anything like that.

0:04:41 Rick: Know, actually, I'm no longer doing immunology work in my day job. I work at a biotech company that we're really advancing. Guess since COVID, a lot of people have heard, you know, there's a lot buzz around RNA and mRNA vaccines, well, attacking RNA as a therapeutic level, uh, cure genetic diseases, and we like to say we're on that cutting edge of RNA meets AI, there you go.

0:04:46 Thomas: Oh, okay. Yeah. There you go. Well, that's so cool. I I'm think a big reason the immune system is able to do what it does is because it really from, from a previous episode, I think it really just like has one approach, which is just swells up if you get anything around you at all. So far, that's what we've learned on this show, but I imagine you're going to tell us more detail than that today. So I'm exciting to get into it.

0:05:06 Rick: Yeah. Yeah, Absolutely, I think, uh, uh, was, was Dr. Proper, right? I sorry. I think he did a wonderful job really setting this up today. So yeah, we can dive into it that, know, you inflammation, the whole idea of that word is quite a huge orchestration of multiple pieces of your immune system coming together.

0:05:27 Thomas: Appropriate. Yeah, Yeah. Yeah. So, kind of in a little bit of the pitch was were talking about the fact that we seem to attract mates who have like, what, different immune systems or complementary or something. And I was really curious about that question in particular. And also, how do we know that and how do do we really like kind of measure that kind of thing?

0:05:49 Rick: Yes. Yeah. I mean, I a recent bout recently with a virus that kind of took you down in it.

0:06:04 Thomas: Yeah. Okay. I was going to say, yeah, the way Lydia and I do it is I'm always sick and she's never sick. So it's very complimentary. You know, it's like she has like a perfect system and I have a zero apparently. So that's do it.

0:06:06 Rick: Yeah, right. Exactly. I feel the same way. I think it out that way at my house as well. Guess not universally, but I think a lot of us have experienced where, you have know, our partner comes down with a cold and we're kind of bracing for it to just tear through the entire house. And maybe it makes its way through a little bit of the house, but a lot of times couples don't get sick at the same time with the same thing.

I think a lot people sort of anecdotally notice that, but the big reason for that is one of the biggest drivers of genetic diversity in our genome at all has to do with these little molecules on our cells, especially, well, they're on all of our cells that kind of are ID tag. And we call call these molecules the MHC class one or class two molecules. And that MHC stands for major histocompatibility complex.

So this, and that term came about because that's where doctors were looking and understanding that you could implant something from one person to another, or it'd be rejected. And if your MHC was incompatible, then you can't be a donor for somebody. Well, it turns out that you know that's how we named it, but diversity of within the human species of those MHC molecules, we actually call them now HLA alleles or an HLA antigen, those vary widely throughout the human species. In fact, there's... There's looked up a paper in preparation for this, and it came out in 2013, and they had reported like 9,000 plus variants of this gene in the human, in the the human population.

So having a lot of diversity there is really important. And it's really important because when we get new antigens that jump out on the scene and could be really nasty, we don't have time to, you know, really evolve defenses against it. We need something thing to go right away.

0:07:18 Thomas: Right, right.

0:08:08 Thomas: Yeah. We're not like, oh, hold on. I'm going to evolve real quick. I've got to get sick. Burst of vein in our forehead, you know, coming out. I done it. I've evolved. Okay.

0:08:12 Rick: Exactly. So it's kind of immunity on that population level in which you're hoping that as something new tears through the population, there's going to be some people that are just naturally resistant to that pathogen, or they get a really mild form of it for some reason, where other people, it's Really deadly. And a lot of that comes down to this little interface of this molecule and how important it is to talk to our adaptive immune system. And that's like the T cells and the B cells that make antibodies.

0:08:36 Thomas: Yeah.

0:08:49 Thomas: But you know, that's also a really weird thing. Cause I, you know I imagine it's a long topic to get into, but something like that, where the, these population level things, when you talk about evolution, I'm always really curious How that works. Cause it's like for any individual, it's weird to be like, well, yeah, this person will survive better, but it's like, no, we need a diversity of it. So how that actually evolves is super fascinating to me, to where it's like, yeah, somehow the whole group is better off. So maybe is it, is it among like small populations that broke off and then like one survived and one did? I don't know, it's just interesting, right?

0:09:00 Rick: Right.

0:09:24 Rick: Remember, a classic example for evolution was in the Pacific Northwest, where there was the Mount St. Helens eruption. And there was, you know, prior to the eruption, you would have these really dark, uh, moths that would be everywhere, and they'd be perfectly blended in with the trees, and There'd be a very low level, uh, just random mutation that would occur to have a gray moth, and those weren't as well camouflaged, so they, they were, were sort of negatively selected against until the eruption happened, and everything was covered in ash, and now all of a sudden being gray, even though that was just a random fluke, was heavily selected for. And so it kind of works like that with pathogens as well. You can imagine, you know, something comes online, you know. Malaria, I think, is a great example. I studied that quite a lot in my postdoc work. Incredibly deadly to a lot of people, but having folks that are going to be a little bit more naturally resistant to it, it ensures that whole population survives, even if it wipes out 90% of us.

0:09:42 Thomas: Yeah.

0:10:28 Thomas: But how, so that's the weird thing though, is like, so how did we get to that diversity in the first place? Is kind puzzles me because it's it doesn't necessarily make any one person, or is it just, yeah, maybe just coming across different pathogens and different times and places. Yeah, it's really cool that we all benefit from that diversity, even if no like individual person necessarily will benefit from it at a given time. It's just fascinating.

0:10:36 Rick: Right, Right, right, right. As I, you know, I found it so interesting to just kind of feel that, you like my, who I choose as a partner is being, you know, in some way sort of moving, the biology moving Through me to some degree, and that I'm less conscious of why, you, wife and I fell in love so well, and and each other was the one, uh, there were so many other unseen forces, and you haven't tested our immune systems or our HLA, uh, types, to know that they're different. So, you know, because again, this functions at a population level, so any individual couple could could have a total difference but You can can imagine the evolutionary benefits to this, especially, you know, I'm talking at a population level where you might wipe out huge parts of the population, but you think at a family level, you know? And the phenomenon that we describe where you see your partner's

0:11:03 Thomas: Yeah. Right. Sure. Yeah? Mm hmm. Right? Yeah. That's

0:11:41 Rick: Doing fine, even though you feel like you're on your deathbed. Well, if you really are on your deadbed, you know, it's better to have one partner that survives to keep those kids going and to get them to the next going. So, there is a huge selective advantage to having that diversity, so you our genetic, our genome is constantly introducing mutations accidentally, but if you do it in the wrong place, it's negatively selected against and and, you know, kills you off, but this is an area where there's a lot of tolerance for change.

0:11:41 Thomas: A good point. Right, yeah, true. Sure? Yeah?

0:12:13 Thomas: Yeah, so how do do we know about the part where it's kind of like couples might be pairing off with that in mind? I mean, can you talk about any of that evidence or

0:12:22 Rick: Absolutely. So there have been a number of studies done, many of of them were done in the like late 80s and into the 90s, in which they would uh look at, well, there was a famous uh done where uh a group had uh men wear the same shirt for a few nights in a row and so smell like them, and thenthey would have

0:12:41 Thomas: Were like, yeah, I will definitely change my behavior in order to do that, sure.

0:12:41 Rick: Oh, isn't that normal, yeah. So they, they wore their shirts to extra long to get them nice and smelly. And then they had women smell these shirts and rate sort of how attracted they were to that smell or what it reminded them of. And it turned out, when they looked at the different HLA alleles from these people that were involved in the study, that the more diverse or distant those alleles were from one another correlated with how much she enjoyed smelling that sweaty, smelly shirt. Yeah.

0:12:44 Thomas: Yeah Yeah.

0:12:56 Thomas: Man.

0:13:18 Thomas: Yeah, that's, it is crazy to think about how much of that, you, it feels like we're now conscious of that, much, you know. But then think about it for a second and it's like, yeah, I mean, it does feel like there's people where you're just like not compatible in some way. You can't put your finger on it, but you're like, yeah, it just doesn't, you know, like it just doesn't seem right. I wonder if it's if it can be that kind of thing where it's Like, they don't smell correct. I don't know. They don't. There's something about it. Yeah. Yeah.

0:13:35 Rick: Yeah, yeah. This is the friend zone. You

0:13:45 Thomas: Yeah. You smell like a friend.

0:13:45 Rick: Smell like the friend zone, yeah, yeah exactly. I that's what I found so cool with this topic, and something that just kind of really moved me, and something that, early you on when I took my first immunology class, I was like, Like, how in the world? Why? And then to think, you know, and being that that diehard romantic, I wanted to know more and more about that. And it has been long sort of a pet project of mine to keep up and and look through the different publications and the way that they figured this out. And, you wasn't just one study, youknow, was just how people smell and their sweat. But, you know, there have been other studies, and they've looked at, you know, long-term successful couples and tested their alleles, and they seem to be very different. There's one study, which I think is, you controversial in some of their methods, but they reported seeing, you know, differences in fidelity or things like that when you had couples with more of too similar of alleles that there was reported Less Happiness.

0:13:53 Thomas: Yeah.

0:14:44 Thomas: Interesting. Thing. Look.

0:14:45 Rick: In their relationships to some Again.

0:14:47 Thomas: I'm Sorry, evolution told me to Do it, I, if we, you smelled different, it wouldn't have happened. Sorry, yeah.

0:14:50 Rick: Yeah. Exactly. Yeah, that'll be the new defense, right? Uh, yeah, I think there's the, you know, again, disclaimer that that these are true at a population level, anybody at an individual level, results this, may vary, but there've been other studies like that. There've been more recent studies, you called into question the idea that I keep saying at a population level this is true, that, it's not recommended that you, should start a dating service that's based off of your genetics, you know, I can go.

0:14:56 Thomas: Yeah.

0:15:16 Thomas: Well, I know. You have a lot of those, uh, don't know what the word form is, but I guess idiot men online, the dating, pickup artisty type people, who are like, "You want to smell like shit because of this thing because then they're pheromones." It's like a lot of that stuff. I don't know how much that is being applied properly, but, you know, it sounds like there's something to the whole smelly thing, I guess. But then again, wouldn't maybe you want to like a completely neutral smell so that you can't be disqualified by your, immune you system incompatibilities sneak in.

0:15:20 Rick: Yeah. Exactly. Yeah. Yeah. Yeah, I mean, if all other things are, are going well, you'd hate for the, uh, the your smell to get in the way at a deeper level, uh, see this, uh, going, going on. And why it's hooked me as I've gone deeper and deeper into immunology is just understanding that it really is this fundamental trait, is the crux of the junction between what we call our innate immune system and our adaptive immune system. And our innate immune system, we call it the innate immune systems because it's kind of already there, ready to go. It's not going to make any quick changes, so you're usually not vaccinating somebody to get their innate immune system going, you, you're vaccinating them to get the adaptive immune system going.

0:16:30 Thomas: Right. What kinds of things does the innate system do? And is the innate systems? Then I take it it's like pretty consistent among different humans, it's more the the other one that's different, or is that not true? Sure.

0:16:45 Rick: Well, Know, it is, everything's different at a population level, right? So, you on how far down the the rabbit hole you want to go, uh, is going to have variations in their innate immune, but a lot of the native immune system was like what was previously talked about with allergies. So a lot of, you know, things, know, like eosinophils and mast cells and neutrophils are part of the innate immune system, and they're macrophages, dendritic cells, monocytes, they're all very similar to each other. They are in the sort of bulk receptors that we call them PAMPs, or pattern recognition receptors, that look at sort of both things. So those come preloaded to identify antigens,

0:16:48 Thomas: Yeah. What?

0:17:30 Thomas: Was that PAMP?

0:17:30 Rick: Like say PAMPS, P -A -M -P -S. Yeah. Or okay.

0:17:31 Thomas: Pants? What? Okay. Okay. Because Lydia, where's the PAMPs in this relationship? She's got the actual immunity going, that's can keep that one for you, you know, for your, yeah.

0:17:42 Rick: Okay. That's my million dollar idea. My new unicorn.

0:17:47 Thomas: Who wears the pants in this relationship? It's Lydia, she's immune to everything, and I'm not.

0:17:53 Rick: So these are the things that are going to be there that, you evolved to kind of look at general things that we're going to see whole classes of things. So they're going to say, oh, bacteria, that's a bacteria, oh virus, but your adaptive immune system is there to say oh that's flu strain H1N1, I need to attack it real hard.

0:18:03 Thomas: Yeah. Right.

0:18:13 Rick: And so that's a very different level of complexity, but everything has to go through the innate immune system. So a lot of our allergies, you know, are caused by the innate immune system, but also when you have a lot inflammation, it's a lot, lot of those innate cells that are going in there to kind of see what's going on. You get that leakiness out of the blood vessels that you guys discussed on the allergy episode. And that's, those immune cells will infiltrate into that local area.

And some of the time, they really don't know the difference from a cut from a sterile scalpel and being with something, know, something covered in tetanus, right? Those immune systems are going in there to assess what's going on, see, is it just damaged and they need to repair and clean up and fix the tissue, or is there some new invader that's coming from the outside?

And a silly analogy for this is, uh, thinking about like you think of all the different monster movies you've seen, and then you say, okay, uh, there have been a lot of different ways to depict a vampire, but there's some universal things too. Like they're probably going to have fangs. They're

0:19:23 Thomas: Sure.

0:19:23 Rick: Probably gonna want to suck blood, right? In most of the vampire movies I've seen, that's true. And so that innate immune system is going to be keyed in to try to find those really common things like fangs, this say silly analogy. And that is where these pattern recognition receptors are going to come in and recognize recognize bulk things that say this is a bacteria. But when they do that, that activates a bunch of things inside of those cells. And it causes some of them like the macrophages, well, more of the dendritic cells and monocytes, but a of these innate immune cells to really activate. So they get triggered when they get tickled through these receptors. And then they're going to eat some of that antigen or that bacteria, and they're gonna digest it. And when they digest it, they're They're going to start saying, here's all the new weird pieces that we don't recognize, and we're going to put those like a hot dog in a hotdog bun.

0:19:37 Thomas: So It's like tasting the vampire being Okay. It's doing a little wine tasting there, it's like, you know, this is from the old world.

0:20:21 Rick: Yeah, right. This is an Anne Rice.

0:20:26 Thomas: Yeah. Yeah, and

0:20:26 Rick: This is an Ann Rice vampire, I think.

0:20:28 Thomas: It's got notes of Bram Stoker, but not, you know, it's like more than the finish. Yeah, okay.

0:20:29 Rick: Yeah. Exactly, Exactly. So we need to take this over to the adaptive immune system and let them really figure out the true, you know, vintage for that, for that vampire. And they do this by chopping up, uh, proteins that come off of whatever it is that they took up, and they take these little proteins and these turn them into peptides, these, these of amino acids. And I, I mentioned that the classic, classic description of this is a the hot dog in a hot dog bun. So that HLA, or that MHC, that complex that we discussed earlier, is the hot dog bun. The antigen that you want to go take to your adaptive immune system is the hot dog that goes in it. And then they put that on the exterior of the cell.

0:21:17 Thomas: Yeah, I'm still on vampires. What's the hot dog part? How did we get to the hotdog part?

0:21:19 Rick: Okay, So you now seen a vampire and you said I see fangs.

0:21:24 Thomas: Okay, saw a vampire. Sure.

0:21:27 Rick: And I'm a big blob. Yeah, Yeah. And I'm really hungry.

0:21:28 Thomas: I'm really hungry. I need some energy fight this vampire. Oh, let me make a hot dog. Okay. Okay. Can it be a vegetarian?

0:21:35 Rick: Exactly. So I'm going to turn it into a vampire hot dog. In fact, a vampire vegan

0:21:38 Thomas: Yeah. I need a vegan hot dog if you can.

0:21:40 Rick: Hot dog Yes, absolutely. It's a plant-based vampire. Plant. So you consume the plant-based vampire and you chop up the plant-based empire into a number of different pieces and you turn those into hot dogs, vegan hot dogs. And Now you're going to put that hot dog into the bun and go offer it to the adaptive immune system to see who wants to eat it, because it's kind of weird And gross, right? You don't want to eat it. You want to, you want to take it to adaptive immune systems and say, hey T cell, which one of you guys is willing to eat this? And the T cell comes over and it has a complementary receptor on its surface and it's gonna dock to that MHC that's loaded with That peptide

0:21:42 Thomas: Okay. Hmm. Okay, so you're making vampire dogs to get rid of the vampire. Okay, you're like, who's got the correct bun for this vampire dog?

0:22:26 Rick: Mm -hmm You're right and Some people are Gonna Be

0:22:31 Thomas: Right? Okay. You're like a serial killer. You're Like Dexter. You're like, okay, we're going to chop this vampire pyre up and dispose of the body. This is a, wow, the immune system is a lot darker than I thought it would be. I mean,

0:22:35 Rick: Exactly I didn't know it was gonna go quite this dark Today But

0:22:47 Thomas: I guess It Is a cold-blooded killer. I mean, that's what its job is, right? It's like the defense force of your body. So yeah,

0:22:53 Rick: Exactly, it's it's pretty lethal and and we one even have cells called the natural killer cells, so it does continue to get darker.

0:23:00 Thomas: It's us or Them, so

0:23:01 Rick: Yeah But Anyway, yes, the immune system, a very dark Place, yeah, you Can imagine a situation where that hot dog bun is where we have all that diversity. So you have a million different types of hot dog buns, yeah.

0:23:02 Thomas: Yeah, yeah Yeah Yeah And sometimes it's like it's toddler and you're like, you love this, I swear you love this hot dog, they're I know you Love this hot, you have eaten it. No, I don't want it. I don't don't like hot dogs anymore. And you're like, shit, are we going to get, yep.

0:23:19 Rick: Yeah Yeah And Every Time you put the hot dog in the bun, they just dump It right back out again, yeah

0:23:30 Thomas: How are we gonna get rid of this? How are you going to serial kill this vampire kids? If you don't eat your fucking dinner, God damn it. And that's

0:23:36 Rick: Exactly Yeah But You've Never, you've ever seen that vampire and you've never tried to make that kind of hotdog before, so How did You know That You Needed that bun, yeah Yeah It's Really dad It's Your Fault again That's

0:23:43 Thomas: True. Yeah. It's really, it's really on me. Yeah, that's fair. The kids are just like, no, man, I don't want that. And I'm like, yeah, all right. We have vampire at home.

0:23:52 Rick: The way it goes, yeah, yeah That's where we have that diversity of saying, well, you all of those, those have very different properties to them because we, we chop them up. They're about, you know, between seven to ten amino acids long, and each amino acid has a different charge, it has a different shape to it, has different, like, chemical processes that mean it's gonna, going to like to stick to one type of hot dog bun in this scenario, or the MHC, better than others. And so you need to have diversity. So within each of us, we have a number of different HLA alleles or these MHC molecules that, yeah, different hot dog buns within each us. But then when you and Lydia or two parents come together and they make a child, they're going to have a blend of those hot dog buns.

0:24:23 Thomas: Crazy. Different hot dog buns. Okay. Okay, let's make some. Let's make some dough, baby. That's what I call it. Let'S bake some buns.

0:24:44 Rick: Exactly. Some buns for some vampire hot dogs. Yeah. Some vampire dogs.

0:24:51 Thomas: Yeah. She was confused at the the time, but now I think she gets it, it's, it was a long, it was a long time pickup line, yeah, the long but con, she gets it now, yeah,

0:24:58 Rick: This is the long play. Are the best cons though, So really, yeah. So you need a lot of diversity there. And then the adaptive immune system does a whole other trick that I think is really amazing. So their sort complementary molecule for T cells, we call it the T cell receptor, the TCR. THC, are. Anyway, something where, you adaptive immune cells, your T cells, your B cells, outside of reproductive cells, are, I guess, red blood cells, are the only cells in our body that actually don't have a complete set of DNA. Cells have engineered a trick, and this is how you have a finite amount of DNA, but an almost endless world world of possibilities in what you could make into a hot dog bun and

0:25:03 Thomas: I was I think what we need right here is the Ratatouille scene where he's like talking about different flavors, he's endless possibilities to be discovered, you know, he's going through all the different flavors, oh.

0:25:56 Rick: Exactly, exactly, I I actually saw that relatively recently, I wish I I had that that those quotes, like, right, so absolutely, it now has this like recipe book in front of it, and what it has is is ingredients that kind of fall into different categories, to it off of this ingredients idea. So you're going to have different areas. So in B cells, when you're making an antibody that can be virtually endless in what it's specific to, or T cells in their T cell receptor, virtually endless what it could be specific to, you're doing is you have different short short pieces, we call these VDJ regions, you would have a bunch of V choices, a bunch of D choices, and a bunch J choices that are all different. And you can think about these as you have a bunch of spices, you have different proteins, and you have different vegetables, and you're going to put them together, but you really only want one spice, you're not going to put in all the spices, that'd be crazy. But

0:26:00 Thomas: It's the best I love that movie, oh.

0:26:53 Rick: Only want one form of protein and you only want one form of vegetable, but you can imagine that there's a lot of choices within each of those. And yeah.

0:27:00 Thomas: You need your, what is it, salt, acid, fat, heat, or fat, something that thing, okay.

0:27:05 Rick: Well, in this scenario, you only get three choices, up to three choices. But

0:27:08 Thomas: So whatever, take one of those away, no salt. I guess, yeah.

0:27:11 Rick: And Exactly, low sodium. This, you now have an endless array of possibilities by just picking one thing from each of these three different categories, now you have an almost endless supply of meals that you can make, and things that you could be reactive to, and what, how they actually make that work is they cut out the intervening pieces of DNA, so take whatever that spice is, and in that one cell, let's say it's garlic, they're going to throw away everything else and get rid of the rest of that DNA, and then they're going to attach it to tofurkey. And then we're going to have okra to go with that. It's a weird meal, but it's going to be tasty, right?

0:27:42 Thomas: Hmm, interesting, yeah.

0:27:56 Thomas: Well sometimes you come across that particular vampire and you have to do that, hmm.

0:27:59 Rick: And you basically throw everything else in the kitchen away. That would be all the intervening pieces of ingredients or DNA. And now you only only have those things, so now that cell is just going to make that recipe over and over, but it doesn't know, yeah.

0:28:15 Thomas: Do do you ever just go like how the fuck is all this, you know, let's just nuts

0:28:16 Rick: Yeah oh yeah that's why I'm still here, that's what I'm interested, you know, two decades in, you know, this is, it's still fascinating that this all actually works enough to make the world around us as crazy as it is, yeah.

0:28:21 Thomas: Yeah crazy yeah and little hot dog bun factory is the reason we can kind of immunize to different stuff, but happen happening when we catch COVID, let's say, since that's just an example that we're all going to be familiar with lately. We catch COVID.

0:28:35 Rick: Yep uh -huh, is this just before the 5G or after the 5G?

0:28:47 Thomas: Yeah. Yeah. We cast COVID and it's, we aren't good at it. Obviously we're, we're not doing very well, but, then we eventually get the vaccine going. And now like, what is the change to the hotdog bun factory there? Cause the way you're describing it, it sounds like, okay, if that hotdog fun factory just finds COVID, Then it should be able to make those those hot dog buns. Why is it that we need the whole, you to like supercharge that or to make that work better or what?

0:28:52 Rick: Uh huh. Right.

0:29:14 Rick: So there are, there are two reasons for that. Um, of it is just that kind of practicality of, let's say you told, told you, every T cell or B cell, when it goes through its maturation process, it's gonna, it's gonna choose what recipe, the one recipe it can make, it will, more diversity that gets introduced in there as well, that's like the mutations that are also entered into the DNA that make random changes when you're combining these recipes as well, I don't know how that works, as far as like a random spice fairy flies in and just dollops something random in there, some chaos in there, um, yeah, experimental cooking, right?

But that, that cell now will only make that one recipe, can think of that as like that chef, right, that chef can only make that one recipe, so now, you know, it's okay to have a dozen or two dozen chefs in a restaurant to one recipe each, but eventually, you can't have, you and billions and trillions of T cells that all are specific to something different and yeah, you don't have enough counter space, your kitchen isn't big enough, your lymph nodes aren't big, you know, you get sick, your lymph nodes swell, the reason they swell is because you're going through this process where you're rapidly figuring out which T cell likes that hot dog bun, and that hot dog, and is happy

0:29:44 Thomas: Hmm. Yeah, you're experimenting. OK. Okay.

0:30:09 Thomas: Yeah. Not enough counter space.

0:30:30 Rick: To eat it yeah, that's where all the chefs are, is in your lymph nodes.

0:30:30 Thomas: Is that where all the chefs are? Oh,

0:30:34 Rick: And they're waiting, and yeah

0:30:34 Thomas: Wow. Okay. Know, I'm not, that's, comforting that'S actually. Cause those fucking things get really swollen on me and I don't like it, but now it's, it's a little comforting to know that it's like, no, they got to do it. That's, That's fair.

0:30:40 Rick: Yeah. But actually, it's a bunch of chefs having a free-for-all fight for who gets to eat that hot dog, I'm not kidding, they

0:30:48 Thomas: Yeah, they're having Oh okay. Okay, but and it's also like a great British bake -off to see who's actually making the best hot dog bun, right?

0:30:54 Rick: Well yeah, I would say this is a darker world, we already established, so it's A little more cutthroat.

0:31:01 Thomas: Oh, okay, so the guys already have, no, I have one bun, that's it. We're just trying to get in there and some eat vampire.

0:31:07 Rick: Yeah. And if that chef is making the recipe for that bun, then it it lights up. It but what usually ends up happening, and this is where we get into how we even evolve from year to year, so you have a vaccine from last year and then a different flu vaccine this year, but you're going to evolve your immunity from one to the other if they're pretty closely related. You've already established your immunity from being vaccinated the last year, but you're now going to evolve to meet the new needs with the new vaccine. And what happens there is you actually have a whole bunch of chefs making a very similar recipe. And this is now where you're at the like great British bake -off or America's test kitchen, where they're going to basically say, these are all basically the same recipe, but with very slight variations to one another. Other. You must compete for who can get to that hot dog better and faster. And the ones that don't die, the ones that do now replicate rapidly.

0:31:14 Thomas: It's Lights Out. Oh, wow.

0:31:34 Thomas: Yeah, that'S a different show. That's one that I don't think they're allowed to make, but yeah.

0:32:07 Rick: Yeah, I wouldn't recommend it. I wouldn'T go on that show.

0:32:11 Thomas: Yeah. That's the one from the Chris Farley sketch back in SNL, if anyone remembers that. But okay, that's fascinating. All right. I've wondered, so you really can only carry, there is kind of a limitation to you can learn, your immune system can learn then.

0:32:18 Rick: Yeah.

0:32:28 Rick: Well, and it expands, it uses a ton of resources. I mean, it's insane how many new cells are made in such a short order of time, but that's that's why your lymph nodes get so swollen, is because they're fighting over who gets the hot dog, and who wins now makes a heck of a lot more of themselves. And that's where you get that swelling. And then it's going to leave, and then it's going to go out, and it's not going to be looking for fangs. It's going to be looking for that anirisian with a hint of Bram Stoker vampire specifically, and

0:32:56 Thomas: And are you saying it just kind of goes all over your body at that point? Like, you had your trial run in the lymph nodes. We liked what you did. We're drafting you into the league. Going, okay,

0:32:59 Rick: Yep. Yep. Right. Right. Right. And we talked about inflammation earlier, so there's probably a site where that that pathogen, where that vampire made its way into the body, and when it did that, it caused a bunch of cells to get, you know, injured and hurt, or or these, those pattern recognition receptors get activated, and those local innate immune cells, they're going to release a lot of chemicals called chemokines and and cytokines. And these chemokites act like a gradient, and your immune cells, like your T cells, basically are sniffing out that gradient, they want to go to where it's the strongest.

0:33:38 Thomas: Hmm.

0:33:38 Rick: So that's where they home from their local lymph node, where they just got out of this, what we call a germinal center, that's where the swollen part happens.

0:33:46 Thomas: Okay. So this is the cartoon where there's a pie on the windowsill and then the cartoon character sniffs it and does the like, yeah, floating.

0:33:47 Rick: Yeah. Yeah. Through, yeah. Yeah.

0:33:56 Thomas: Yeah. So that's what the Iron Chef is doing now, right? What

0:33:57 Rick: All Right, yeah, so that that is now floating over the fence, it was in the bloodstream, but it smelled it over the fence, and so it it found a hole in the fence, uh, you know the leaky blood vessels, uh, that are caused by that smell, and it's going to passage. And then once it gets there, it's going to start checking the IDs of every everybody around. And when it's checking the ID is it's that HLA. So it's, so there's that hot dog bun with the hot dog from the guy that ate the vampire. Right. Right. Okay. So

0:34:27 Thomas: Okay, this is really, we're going to get, we can incorporate all the elements. Here we go. Ah,

0:34:34 Rick: That we would call an antigen presenting cell. And so it uses call an MHC type two or class two molecule on its surface. So it can only go talk to one type of T cell. And that T cell is like the grand general. It's a, we call them a a CD4 T cell. They what everything else happens.

So that cartoon that just wafted over to go smell that pie is actually a different type of T cell, it's a CD8 cell, but it got marching orders to go kill that vampire. But this vampire is a very tricky vampire, it can invade normal people, or it could be outside of it.

So, that CD8 T cell that has been given its orders, and and it smelled that pie, and it's floated out of the bloodstream and into the local tissue, is now going to start going to all the cells around it and start checking everybody's ID and everybody's idea. And the reason that we reject organ donation is because of this little surface marker called MHC class one. And every cell in our body has an MHC plus one molecule.

And we're constantly putting our own hot dogs made from our own proteins on the surface. And those T-cells hate those self hot dogs, they can't stand them, at least in a good environment. When you have autoimmunity, it's because you've made a T-cel that now likes to eat yourself, eat yourself hot dogs.

0:35:58 Thomas: Shit.

0:35:59 Rick: Yeah. So

0:35:59 Thomas: Okay? Okay, you have become the hot dog that, yeah, this

0:36:03 Rick: Exactly, exactly, so, uh, kind of it's like, you know, the police, the the like really not cool policeman that's going around checking everybody's id and just kind of being a jerk, at you know, a kager, right, until it finds somebody that has the vampire id, and it goes, aha, and then it's going to kill that vampire even if it looks like a normal cell, even if its invaded a normal cell and is hiding inside that normal cell, it's gonna kill that cell as well as the pathogen. Inside Of it.

0:36:31 Thomas: Is fucking impossible. Actually, I'm, I hate to undermine your entire profession and everything you do, but this is, I, I'm gonna say no, this doesn't exist. Because that's not possible. Go

0:36:35 Rick: Yeah. Yeah. Right. It's crazy, and things things have evolved over such a long time.

0:36:45 Thomas: Tell all your friends To re-check this, can't redo, although this can't be right, whatever you did to find this, is, there's no way this is possible, so no.

0:36:56 Rick: Mean, This is where some of the most remarkable things. So the first job in biotech I had was at a CAR T-cell company. And that's a type therapy where they take your T-cells and they actually put in a new receptor that now lets it see cancer. And then puts your own T-cells back in your body, and it goes and kills certain types of blood cancers.

0:36:56 Thomas: Yeah.

0:37:15 Thomas: Is that the headlines you see every single week, that's like they can do this now, cancer is a thing of the past, and it's like no, still there's somehow there's always still cancer but there's, we're always doing that, still, I don't know.

0:37:20 Rick: Yeah. Yeah. Not quite yet, yeah there's still a lot of it, yeah right Well, it's because cancer is not one disease, it's a thousand different diseases, right. Yeah, these T-cells, uh, of then go around checking stuff, and then, oh, we we talked about that lymph node that was swollen, so you have two different types of T-cells that are in that swollen area talking to each other, giving each other orders, and then going out into the environment and looking, uh, find that that vampire in our analogy here, but you also have, um, cells that are there, and those B cells are also getting orders from that general, they're talking to that T cell, and and have these these, you, antibodies basically that are stuck to their surface. And when they grab an antigen, they take it up, and they chop it up. And they've also put it in that MHC molecule and show it to the T cell. And if that T cell likes that hot dog, it now tells that B cell, yeah, go make antibody. This is good. And

0:37:30 Thomas: Yeah. Yeah. Is

0:38:19 Rick: So now instead of being kind of a hot dog bund, man, where are we going to go with this? So an antibody, it's like a corn dog. I don't know. Yeah, I don't know. It's a, yeah, something like that, right? So it's different a hot dog bun. It doesn' t work in that classical sense. But it basically recognized something from that, yeah.

0:38:29 Thomas: It getting drilled down even more Oh corn dog bite, okay in the classical hot dog sense All

0:38:43 Rick: In the classical hot dog sense, this falls apart.

0:38:44 Thomas: Right I'll need to get out of the classical hot dog paradigm that I, that I'm in. Forget everything you learned in hot dog school. Okay. All right.

0:38:49 Rick: Yeah, this is going off the rails fast. Sorry, Thomas. Yeah. Did I mention it was actually the Hormel School of Immunology I graduated from? Anyway, yeah.

0:39:03 Thomas: It's not like the real thing will be easier for me to understand. So this is good. No, it's just, yeah.

0:39:08 Rick: All right. I want to make it accessible because I find it so fascinating that, again, how does this all work in conjunction? And how do we not kill ourselves all the time?

0:39:11 Thomas: Yeah, totally. Yeah. So, Yeah. Okay. To try to understand what's happening, so we had the T cells, we had a hot dog, this thing. Is this different cell thing doing this, beef cell, that's broken it down to something different than a hotdog. Sure.

0:39:22 Rick: This So we know about antibodies, right? Right. A lot of people have heard about antibodies. They're in our bloodstream. That's usually what we're going for when we're getting a vaccine. So you asked about the COVID vaccine earlier. What from a vaccine is we want to trigger this immune response, those germinal centers in your lymph nodes to get the T cells and the B cells to come together. And the B cell cells need to get orders from the T cell cells to go forth and actually make these antibodies, but

0:39:37 Thomas: Right oh okay, I think I thought that that we were already at the antibody phase so we're not even, we haven't been there yet.

0:40:00 Rick: So just like those T cells have one recipe that they can make because they've thrown away all the other, uh, a B cell does that same thing but for a totally different molecule and the way that they worked as they also put it on their surface just like a T cell does, but instead of talking to that, that antigen presenting the hot dog, the hotdog bun, that whole thing. They actually don't care. They just want, they'll like have an antibody that's for the arm of the vampire. Like it doesn't need to be digested and cut up into hotdog form. It will just be a big, larger thing. They didn't intend to, like the B cell wasn't programmed to recognize vampire arm. It was just random. It was a random set of things that came together, and then once it bound it and it grabbed onto something, it always takes it up and brings it inside and chops it up to make a hot dog out of it.

0:40:06 Thomas: Oh oh well oh so these are, are like the find me more, there's like the henchmen of the T cells are they're like find me more vampires to make into hot dogs, kind of, okay oh interesting, okay

0:40:58 Rick: Of yeah yeah and make them easier to see, right? So then once you, you realize that you have this great thing that can find the arm of vampires really easily, it's now, instead of being on the surface of those B cells, they clip off the, that holds it to the surface when they make that protein now. So they just spit it out into your bloodstream. And then it flies around in your blood stream, these, and when it comes across a arm, it's now going to stick to it and it's going to act like a homing beacon. It's going cause even more chemokines and cytokines to be activated and released. You know, is going to go be even stronger and boosted.

0:41:40 Thomas: Fill your bloodstream with pies, love it

0:41:46 Rick: With pie smell. Yeah. But the added benefit, in the case of a virus and something like COVID, is that those antibodies can now actually block the ability for that virus to get into a new cell. When it coats a virus, it now makes it inert, right?

0:41:47 Thomas: Oh okay, okay, so it's not just about destroying stuff necessarily, it's like, like, OK, it and yeah, gotcha.

0:42:10 Rick: Making it inert. It's kind of of like, it's like hog tying the vampire and saying you can't bite anybody if you've been hog tied, and waiting for the cops to come

0:42:19 Thomas: Right. So it's is like it a question of, you fixing what's infected, but also preventing new infected cells? Is that kind of what it is? Or so like the T cells are the ones that are maybe more in the fixing the infected stuff by by killing stuff. Is that right?

0:42:27 Rick: So at the CD8 cells, those are the, and the natural killer T cells, uh, that I mentioned earlier those, uh, it's all in the name, right, they around killing cells that are infected with with viruses, so that's kind of a tale of the body snatchers type of monster, we'd leave the world of vampires and, you snatchers now are more like viruses, so our immune system has had to evolve very differently in order to deal with different types of pathogens, so viruses need a very different response than bacteria, uh

0:42:35 Thomas: OK. Hmm. Yeah. Yeah, OK.

0:43:03 Thomas: Oh, Oh, could you I mean, I don't know if we have time, but broad strokes, could you explain that difference at all or no? It's too complicated, we're late in the recording. It's we

0:43:11 Rick: Yeah immune system has evolved to deal with different pathogens very differently. So if you get infected with a virus, once it's gone into a host cell and invaded it, because that's what they have to do, they have to replicate, then it's game over for that cell, cell, most of the time. Once it's in, that's it.

0:43:30 Thomas: Oh. Oh. It's so oh wait, now I got it, that's the like you're in the zombie movie or the vampire movie and you're like they bit me you gotta, you promise you gotta shoot me, okay, gotcha oh

0:43:37 Rick: Yes. There we go. Yep. Yep, exactly. So now you're in that scenario where the only way out is to kill that cell and prevent the virus from reproducing inside.

0:43:50 Thomas: He's fucking hardcore, man, what a what a barren wasteland it is in there, do any of these cells have friends, like, do they, are they socialize yeah it's dark, okay it's real game of thrones in there you know, there's not, it's there's There's not, it's yeah.

0:43:52 Rick: Right? Tell you, Osmosis Jones had a much brighter take on all this. But it's it's that that's how you it's dark, right but that's that's the world it really is dog

0:44:11 Thomas: Dog eat dog. Okay.

0:44:13 Rick: Eat dog, so within the world of viruses, that's only way out is just eradicate every host, and and then use the antibodies to make it inert when it's outside of the host so it can't spread. Where bacteria, on the other hand, doesn't necessarily, it depends on the type of bacteria, doesn't need to get into a cell in order to replicate. It just wants to harvest all the nutrients from the local environment.

0:44:16 Thomas: Yeah. Oh, so it can kind of just like chill in your body in some way that's not particularly that way.

0:44:43 Rick: Right. And so like if you're septic or something in your bloodstream, that means you have a bunch of bacteria hanging on your blood stream. And serum and your plasma and all that is, blood is a great feeding material for them. They'd love it. We don't. And of response you have to have. So that's where things like your neutrophils come in that I mentioned earlier from the innate immune system. They do something really crazy. They will come across bacteria and they will recognize that they've hit paydirt on a bacteria cluster.

0:44:43 Thomas: Hmm. Yeah, okay.

0:45:11 Thomas: Are it, are they, they asking for ID in the same way? Papers, please, in the samem? Or is it markers different for that?

0:45:16 Rick: Yeah, they're not asking for papers. Yeah. They're using different markers and they They just come along and they, yeah, basically, yeah. But in this case, they actually then detonate themselves and they use their chromosomes and their DNA as what we call nets, and it like spits out their DNA to coat the bacteria into a cluster, cluster, and and hold it together. Uh, naked DNA in your bloodstream or anywhere else in your body is a huge inflammation activator because, you know, DNA goes on the inside, not the outside of

0:45:18 Thomas: Oh, okay. They're racial profiling. Oh, geez. Okay. Oh,

0:45:53 Rick: Itself, right. So are really highly immunogenic, or or inflammatory, and they're going to cause a lot more these neutrophils and other things to come in and then actually eat the bacteria and degrade them. Yeah.

0:45:53 Thomas: I see. Yeah.

0:46:05 Thomas: Is crazy.

0:46:06 Rick: And can be involved in that. Typically you don't have T cells involved, and outside of just giving orders to the B cells to make antibodies to help the neutrophils or other things deal with bacteria. So, like, you know, when we have hay fever and we're sneezing like crazy, a lot of that is actually a probably anti-parasite response that that we just don't have parasites anymore, and

0:46:25 Thomas: Really? Because a lot of, because it feels like, is it true that, you know, a lot of getting sick is more about your immune response than it is about the thing you're sick with? Like it's more, those are more the symptoms? Okay.

0:46:37 Rick: Yeah, well, and it can go other way, I mean, that's a whole other wonderful discussion that I've used in teaching immunology before of, you

0:46:43 Thomas: Sure. Oh, maybe, maybe that'll be our next episode. Maybe we'll tease that one or something.

0:46:49 Rick: Absolutely. It's kind of, what is the symptom, and who does it benefit, the host or the pathogen? Because even sometimes the same symptoms can actually change who it benefits depending on the illness if That's a good tease for that, um,

0:46:53 Thomas: Yeah. Yeah. Oh, interesting. Yeah. Well, shoot. I can't believe we've already gone the allotted time. Is there anything from this of the partner pairing off stuff, you know, that angle that that you want to make sure we covered that we didn't get to? Or what do you think?

0:47:16 Rick: Not. I, I think we've covered just about everything. I would say one of the, one of these great examples for why this population level is so important, uh, a theory, we, we've seen different bottlenecks in human history, uh, you know, pre-history, especially, you know, 50 to 100,000 years ago, it's thought that we collapsed Down To, yeah.

0:47:34 Thomas: Are Yeah. We're down To, like, yeah. I've, I've read This, yeah, what is the number, isn't like fucking thousand, few Thousand Crazy.

0:47:40 Rick: Right. Yeah. Three To three to ten thousand individuals. Yeah.

0:47:46 Thomas: Absolutely. Crazy.

0:47:47 Rick: Crazy, within The last Hundred Thousand Years.

0:47:47 Thomas: I For One Would Be so anxious, I'd be like, there's not enough There's, this is, oh, I don't want to move, I don't want to step on anything, I don't want to, like Just, no. Cuts. No, you know, no Everybody Stay very still, we Can't lose many more of us.

0:47:51 Rick: Right. Yeah. Yeah. Nobody Move, yeah, yeah. Yeah. Yeah, yeah, exactly. And there are a lot of theories on why that is, and it kind of depends on What bottleneck And, and, and it's hard to really figure out what's causing what, but there is a theory I heard about, I don't know, 10 years ago, that was really interesting, and as I said, I studied a lot of malaria, so I know lot of malaria stuff, and malaria is just a prolific, prolific parasite that was a scourge on human evolution, and it's

0:48:09 Thomas: Yeah. Oh.

0:48:29 Thomas: It's A parasite I'm an idiot, I thought that Was just Like A virus, like A, what's The

0:48:31 Rick: Actually a parasite. I know, right? But it invades your red blood cells, so a, it's a weird thing. It's a single cell being parasite, but can have a whole thing on malaria because of the staggering statistics that I believe is true, although I'm not going to stake anything on it, is that half of all people that have ever lived have thought to have died of malaria.

0:48:40 Thomas: Hell, okay, yeah. This Is fascinating, what Oh, I don't know about that. Maybe It's half Of all people That have died Yeah, I donno, that's, yeah, we'll look that up, yeah.

0:48:56 Rick: Yeah. Right. It sounds impossible. All There was a, there's a researcher who had a theory that one of the drivers of this bottleneck might have been when malaria first burst out onto the scene and That it actually wiped out a huge amount of humans, except for a small genetic minority. So think about that moth with Mount St. Helens, all of a sudden the gray moths were selected for, and that that might have caused one of these genetic bottlenecks. And that we've bottlenecking of malaria as well that corresponds to roughly those same time periods as well. So it also probably evolved as we did. Yeah, yeah.

0:49:10 Thomas: Yeah. Yeah. Oh. Right. Cause They're Doing the Same thing. Yeah. Bastards.

0:49:38 Rick: Yeah. So it's not conclusive. It's definitely a theory. But I think that that just shows at a population level where you could have 90% constriction, but that diversity might have saved the human race in that scenario. Area.

0:49:50 Thomas: Right. Yeah, yeah. Super fascinating. OK, well, we definitely have to do some follow ups. This was a lot of fun. I'm going to go eat some hot dogs, but I need some veggie dogs and I'm gonna try to make sure my kids eat them, too. And then we'll reconvene at a later date. But no, this was amazing. Rick Sullivan, is anywhere you'd like to appoint people. I always give everyone the opportunity to plug anything they want to.

0:49:51 Rick: Yeah. Yeah, yeah.

0:50:14 Rick: Well, first of all, Thomas, thank you so much. I really appreciate this. This is a been a longtime listener. So it's such a such a treat to get to to be on one of your shows. And I really appreciate what you do in the world.

0:50:20 Thomas: Oh, cool. Oh, thank you so much.

0:50:27 Rick: Yeah, absolutely. I'm not a big kind of social media person. I work at a company called Shape Therapeutics, which I think is doing wonderful things, and maybe sometime we'll get to talk about some of that. I'd love to come back and talk about other immune stuff

0:50:38 Thomas: Hey, you've earned it. Do a fucking infomercial for your company next time. That's fine. That is really, as long as there's hot hot and more hot dog talk.

0:50:40 Rick: Sure Yeah, exactly. Uh, and then beyond that, my other big passion in life is music, uh, like you so I play in the Old Man Dad band now it's not dad Bantha

0:50:50 Thomas: Nice. Ooh, old man, dad, man. Sure. Plug your old man. Dad, man, I

0:50:55 Rick: Yeah. Uh so we're the the Cali Mocho Boys Boys, K-A-L-I-M-O-C-H-O, Boys, B-O-'Y-S, .com or YouTube, all those things. And we like to play some rock and roll and keep going.

0:51:05 Thomas: Love it. That was fantastic. So cool. Uh, this was a pleasure. I'm excited to, uh, speak to you again that Thanks so much.

0:51:09 Rick: Yeah. Yeah. Yeah, absolutely. I loved it. Thank you so much, Thomas.