Athena:	00:00:04	Have you been zombified by microbes and the microbiome. Welcome to the Zombified Podcast, your source for fresh brains. Zombified is a production of ASU and the Zombie Apocalypse Medicine Alliance. I'm your host, Athena Aktipis, psychology professor at ASU and chair of the Zombie Apocalypse Medicine Alliance.
Dave:	00:00:27	And I'm your co-host Dave Lundberg-Kenrick, media outreach program manager at ASU and brain enthusiast.
Athena:	00:00:33	Brainz. Its all about brains
Dave:	00:00:35	Yup. And microbes, right?
Athena:	00:00:38	Yeah. We'll and microbes and brains together.
Dave:	00:00:40	So they're microbes in our brains.
Athena:	00:00:44	Actually there probably are. Um, for a long time people thought that our brains were sterile, but it does not actually look like that's the case anymore.
Dave:	00:00:51	But are we talking about the microbes in where, what sort of microbes are we talking about?
Athena:	00:00:54	Well, it depends what you mean by brains, also. Because we have so many nerves in our guts that microbes can actually interact with. They can like send signals that get picked up by all of these nerves that, um, like enervate all of our guts.
Dave:	00:01:12	Interesting. So, so tell me about who were hearing from today.
Athena:	00:01:15	Well, we're talking to Joe Alcock who has been thinking about microbes and behavior and to what extent do microbes manipulate us? For a long time actually. And uh, we, Joe and I work together on this, this question about to what extent might microbes be manipulating our behavior and in particular making us eat things that feed them.
Dave:	00:01:40	Oh. Interesting.
Athena:	00:01:42	Yes. So we have a fun conversation about that. And he also just know so much about all these different strategies that microbes can use to manipulate their hosts in order to help the microbes propagate themselves.
Dave:	00:01:58	Cool.
Dave:	00:01:59	Some really creepy things.
Dave:	00:02:00	So, is this good for us or bad for us?
Athena:	00:02:02	You'll have to listen and see.
Dave:	00:02:04	All right, sounds good.
Athena:	00:02:06	Let's hear from Joe.
Intro:	00:02:08	[Psychological by Lemi]
Joe:	00:02:44	Welcome to the apocalypse. [laughter]
Athena:	00:02:46	Welcome, Joe Alcock to the apocalypse.
Joe:	00:02:51	Thank you, Athena. I'm glad to be here in the apocalypse.
Athena:	00:02:53	It's amazing to have you joining me for today's apocalypse. Um, Joe, can you start by telling us a little bit about yourself, who you are, maybe why you're here. Like in general,
Joe:	00:03:08	In the apocalypse or here, pre apocalypse or post?
Athena:	00:03:12	Why you exist and what you do that kind of thing.
Joe:	00:03:17	What do I do.
Athena:	00:03:17	Yeah.
Joe:	00:03:17	You know of who I am.
Athena:	00:03:19	I know, I know, but but not everybody who's listening knows you as well as I do.
Joe:	00:03:26	Okay. We're going to edit that part out. [laughter]
Athena:	00:03:31	Maybe [laughter] So, Joe, you study a lot of things.
Joe:	00:03:38	I do.
Athena:	00:03:38	And you also help people because you're a real doctor, not like us kind of PhDs.
Joe:	00:03:44	So, my background is in emergency medicine. I am a clinician. A couple of days ago, I worked a busy shift in the hospital at the University of New Mexico, which is a tertiary care hospital, urban, busy E.R. Where we get patients flown in from all over the state with all manner of problems including gunshot wounds and trauma and all sorts of nonsense that we do. That's the only part of my life.
Athena:	00:04:11	That's the apocalypse part.
Joe:	00:04:13	That's the apocalypse part. Exactly. Before I went to medical school, I was gonna to become a behavioral ecologist. I was super interested in evolutionary biology and I had no plan really to go to medical school. But when I was in graduate school at Cornell, um, studying to become a PhD behavioral ecologist. I heard a talk about microbes and evolution, and this is a talk by Paul Ewald and that kind of convinced me to switch gears and go into medicine. But I've carried that with me.
Athena:	00:04:47	So what was that talk about exactly?
Joe:	00:04:49	The talk was about diarrhea. [laughter]
Athena:	00:04:52	Gross! [laughter]
Joe:	00:04:52	It was, it was the time that changed my whole life-course. Amazing, huh? But looking back on it, it was about gut microbes and that's, that's what I remain interested in now. But yeah, so Paul Ewald said in effect that he was talking about cholera and dysentery and why it is that microbes evolved to be as virulent and harmful to you as they do. They don't always evolve to be, you know, helpful little cooperative mutualists, which was the, one of the prevailing ideas before that. And he laid it out all in what I thought was a really clever way. There was, there's a lot to it, but the bottom line was applying evolutionary and ecological precepts to infectious disease and things like diarrhea and human illness and health was a really fantastic approach. So one that I wanted to do,
Athena:	00:05:47	So what was the, um, like in a nutshell, what he was saying about when they evolved to be virulent versus when they evolve to be not virulent.
Joe:	00:05:56	So he apparently, he was, he was telling us about an anecdote of travel in South America someplace where he was just on the toilet all day.
Athena:	00:06:05	Oh, no.
Joe:	00:06:06	Yeah. So he had like, yeah, it Salmonella or some kind of, some kind of dysentery. And it occurred to him that it wasn't possible that pathogens would always evolve towards a benign and helpful state. Um, that they could, you know, that's really, pathogens have, have in their best interests, uh, in making you very, very, very sick. But, but really the, the predominant idea before that, the idea was that, pathogens over evolutionary time would evolve to become mutualists. That cooperation was the natural order of things. And that over time, uh, a, any kind of a dyad, dyadic relationship between the host and the pathogen would evolve towards commensalism, but it's not the case.
Athena:	00:06:48	So when, when does it evolve to be symbiotic and commensal and helpful? And when does it evolve to be exploitative?
Joe:	00:07:00	So, we can talk first about when it evolves to be exploitative. Um, so one of the ecological ideas that Paul Ewald talked about was that if you are a pathogen that's transmitted by a vector. So for instance, like malaria being transmitted by a parasite, that's a great example of when, uh, pathogens don't have your best interests at heart. Um, and, and you could be totally debilitated, laid up with malaria, unable to move. And in fact, that benefits the malaria parasite. Falcip- falciparum malaria gets taken up by mosquitoes way better when you're unable to swap the mosquitoes away. When you're just lying in bed. Other diseases require face to face contact. So things like upper respiratory tract infections or influenza, they require you to be awake, up at em, interacting with other people, kind of maintaining your social calendar at least to some extent. And that is how they get transmitted.
Athena:	00:08:04	Hmm. So the microbes that don't really care if we're, or in fact would rather sort of have us be laid up and get transmitted by vectors are gonna evolve to be more virulent, virulent, while the ones that need us to be moving around and interacting with other people to get transmitted are, all else equal going to evolve to be less virulent.
Joe:	00:08:30	Ah, that's right. Or at least that would help shape the direction of the virulence in that direction. So that's part of it but, getting back to the diarrhea thing, the idea is that some pathogens don't require you to be alive at all. They can survive just fine in the environment and then infect somebody else and you can be long dead. So cholera is a good example of this. So the cholera, you know, vibrio cholerae, the responsible agent of the disease, cholera, you when you poop and it causes voluminous, massive, massive diarrhea. It's called rice water diarrhea that can make you become so dehydrated that you die. In fact, that's how a lot of people do die of cholera. But a lot of that poop ends up in waterways and in places that don't have enough sanitation, those spores can live in water that is then consumed by people and animals weeks to months later. The spores are really hardy, and they do, they do great. So in other words, the cholera organism doesn't require you to be alive, to be tran transmitted, unlike influenza, where you have to be at least alive and coughing on somebody. Right?
Athena:	00:09:33	So this is kind of a zombie thing actually, right? It's like if the parasite kills you, but then, they were like, they've managed to hijack and capitalize on your bodily fluids enough that they can then use them to continue to infect after you died. There's does some sort of weird un-dead something.
Joe:	00:09:58	Cholera is definitely an un-dead actually, or dead apocalyptic sort of disease. [Joe and Athena both agree]. And it relies on the breakdown of society and the fact that it can sort of lay and, wait and then attack you and infect you weeks later. That's kind of a scary thing.
Athena:	00:10:16	Yeah. So this whole idea of like that, that people might be dead, but they could still be vectors for transmitting disease. I mean, maybe some of the whole, zombie idea, right? That you're like dead, but you're un-dead and you're still a vector. Maybe that somehow comes from this notion that sometimes people who are dead are still vectors of disease. I don't know. I'm totally wildly speculating now, but
Joe:	00:10:46	Yeah, no, I like the idea. Definitely has some zombie implications.
Athena:	00:10:51	Yeah. Yeah. Okay. So you were talking about how you got to studying medicine and I kind of derailed you with the Paul Ewald thing to explain the, the basics. But uh, do you wanna take us a little further into your journey?
Joe:	00:11:05	So, so but, that was the moment. That was the moment where I thought, I mean, I had a couple of ideas that were, that were just wrong. One is that I thought that in evolutionary biology, most of the major questions had been answered. And so I really thought that this application of evolution to humans was novel and new and cool and exciting. I still think that's true. But of course my original thought that all the big ideas that have been answered in evolutionary biology that I, that was totally off base.
Athena:	00:11:32	So, why did, why did you think that? That all the big questions had been answered?
Joe:	00:11:38	That's a good question. But I was looking back on some of the major advances in the field and a lot really evolution laid, evolution and the idea that evolution explains behavior, the groundwork was put in place by people in the fifties sixties and seventies
Athena:	00:11:56	Like your dad, Sorry.
Joe:	00:11:58	Like my dad and others. And maybe I was thinking that a lot of the big stuff had really been fleshed out and we understood a lot of what explained animal behavior, human behavior and that sort of thing. But again, this was the naivety of a 20-year-old. I had no idea.
Dave:	00:12:16	You didn't realize that your dad didn't answer all of the questions.
Joe:	00:12:19	Well, yeah, or even scratched the surface. But anytime anybody, in any scientific field thinks that the big questions have been answered, they're almost always wrong. [Athena and Joe both agree] So I, you know in the benefit of hindsight, I know that I was wrong, but at the time I thought I need to kind of focus my attention on this new shiny object, which is evolutionary medicine. So I decided to go to med school, I went to UCLA, I did some work with Jared Diamond, who has, absolutely has an evolutionary point of view. And interestingly, again, in retrospect, he was interested in gut kinds of behaviors and gut transporters. But I thought that that was too esoteric and not evolutionary enough for me. And so I've kind of put that aside and I focused my efforts on different stuff in medical school. But I wrapped up med school at UCLA, went to UNM for, for residency, and then afterwards started all the things you have to do to be a functional emergency physician, which takes a lot of work and get board certified and, and that kind of thing. And it was a few years later before I kind of circled back to evolutionary medicine.
Athena:	00:13:27	And, and now you teach evolutionary medicine?
Joe:	00:13:29	Yeah. So, I've taught evolutionary medicine for over a decade to undergraduates, grad students, medical students. I started a rotation in evolutionary medicine at the University of New Mexico. And I like teaching at other places too. So this week, for instance I'm teaching Mayo medical students in combination with Arizona State University's Center for evolution in medicine.
Athena:	00:13:52	Awesome.
Dave:	00:13:52	Yeah. Fun stuff.
Athena:	00:13:53	Yeah. So, now you're a, ER physician and you teach evolutionary medicine and you do research on microbiome and other issues and
Joe:	00:14:07	So this is typical, I think, for a lot of academic clinicians. That there's a clinical part of my job, there's an education part of my job and there's a research part of my job. So the research part is I'm super interested in the microbiome and I'm also, the thing that really motivates me is I want to know how the microbiome plays a role in disease and how it [stutters and gets caught on words]. I want to know how in particular microbes can hijack our bodies, our physiology, and make us sick, make us do things we don't want to do and possibly affect our behaviors.
Athena:	00:14:43	Yeah, the zombie apocalypse. [Joe and Athena agree] Awesome. So, can we talk about microbes and behavior little bit? And what microbes can do and can't do? So,
Joe:	00:14:55	So there's echoes of Paul Ewald here. [Athena agrees] Back in the day he was reacting to a conventional wisdom that pathogens would evolve towards becoming mutualists. And the same is true for the microbiome. That there's lots and lots of really high profile researchers out there and they think that the microbiome basically behaves as a mutualistic organ and is as integral to your body and your body functioning as other organs in your body, like your heart, your brain, your liver, you know, whatever. But of course the microbiome doesn't behave that way. So we, the two of us we've written with Carlo Maley about how there are genetic conflicts of interest within the microbiome and there's all these competing genomes in our microbiome and that is what we'd expect as an outcome of evolution. And in fact, that's what we really observe when we look carefully. The microbiome is not a mutualistic organ. It does all sorts of things and it can, it can go wrong. It can go badly off the rails and actually hurt you in really important ways,
Athena:	00:16:05	Right. So it sometimes has aligned interests with us as an organism. Sometimes it doesn't, right. Sometimes its a, it's more of a zero sum game over the resources and other times it's a non zero sum game. And
Joe:	00:16:22	S,o just because we are a habitat for our microbiomes doesn't mean that our microbiomes are dependent on us for their fitness, if that makes sense. They can sometimes profit when we get sick and even if we die. And that's the same, the same is true for cholera. So cholera can be busy infecting other people long after we're dead. And our microbiome has many opportunities for horizontal transmission, which we haven't talked about much, but transmission to other people, even if we're sick, even if they're hurting us.
Athena:	00:16:51	Yeah. Yeah. So, uh, part of the backstory on all of this is that you and I started talking about these things a long time ago.
Joe:	00:17:03	Yeah. We were at a conference over, sitting on the deck, discussing some of these ideas and you asked me something about, "Hey, do you think it's possible that microbes might hijack our brains? And make us eat things that we don't want to eat." I said, "Of course they do that."
Athena:	00:17:23	And then we're like, "let's work on this paper together." And I mean really it's that conversation that was the nidus for the Zombie Apocalypse Medicine Meeting that we put together last fall, which was the reason that this podcast even exists. So Joe, this podcast wouldn't exist without you really. This would not have happened. So it's really awesome to have you here.
Joe:	00:17:56	Head exploding. [laughter]
Athena:	00:17:56	So we can talk about all this. Um, but yeah, and so we have been chatting about this for a long time.
Joe:	00:18:02	I wish that, I wish I could take as much credit as you're uh, suggesting, but of course that's not true. Now the paper did have a zombie element to it. Definitely. The one that we wrote, the paper that we're talking about is, Is eating behavior manipulated by the gastrointestinal microbiota?
Athena:	00:18:20	I think that's what it's called in Bio Essays.
Joe:	00:18:21	In Bio Essays.
Athena:	00:18:22	Yeah. Look it up.
Joe:	00:18:24	Right. So neuronal and brain hijacking by, by microbes. So we went deep into this idea of the gut-brain access. A concept that gut microbes influence our nervous systems.
Athena:	00:18:37	Right, and the idea is kind of simple, right? If you just take the basic premise that microbes need to consume resources and they, the microbes that live in our GI tract rely on us to provide them with those resources. Then if they can do anything to make us eat those things that preferentially feed them rather than their competitors, then they're going to have higher fitness than the ones that don't do that. Right?
Joe:	00:19:10	Right. Yeah. The basic argument was that microbes in our guts, they're competing not just with us for food and energy, they're competing with each other and certain microbes do better if they get certain nutrients and certain foods. Some are better at digesting proteins via proteo, pro -teo -lytic
Athena:	00:19:34	Proteolytic metabolism? Something like that. [laughter]
Joe:	00:19:34	Some microbes are better at digesting proteins via proteolytic pathways. Other microbes are better at digesting complex carbohydrates like in in fiber, and so it makes sense that if you're going to give benefits to some populations of microbes that are in your guts, that you can do that by what you eat.
Athena:	00:19:54	I think we should come up with some sort of a tongue twister involving populations of protein eating proteolytic, probiotic something
Joe:	00:20:05	Proteolytic. Something like that.
Athena:	00:20:05	But we should, we should come up with some tongue twisters. [Joe and Athena Agree]
Joe:	00:20:11	So we hypothesized, moving right along, that if a microbe could influence satiety or hunger or even make you crave certain foods or your idea was they could make you unhappy or undergo visceral pain.
Athena:	00:20:29	Yeah, well, isn't it much easier to make an organism unhappy, then make them happy? Like in general, the, the mechanisms for making you feel uncomfortable or feel pain or feel bad, like, much easier.
Joe:	00:20:45	Are you speaking from personal experience? [laughter] Yeah So, the idea is that from a gut microbes perspective, if they could make you hangry, angry, and hungry, that, that would prompt you perhaps to eat certain things
Athena:	00:20:57	Or they just release some virulence factors and you don't feel so good, right? That's, I mean, they've got the genes for that already.
Joe:	00:21:04	So here's the amazing thing, people. So we wrote this paper a few years ago and still the jury's out on part of this. We don't know, we don't know the whole story yet. And we don't know if certain microbes actually make us crave certain foods. But a lot of the story has been flushed out. Absolutely- microbes make appetite hormones. Absolutely - they produce substances that regulate our satiety and hunger. They do this and this is really well described and there's a whole bunch of behaviors now where the microbes are deeply involved.
Athena:	00:21:34	Yeah. And they also tap into our reward systems, right? They're producing Dopamine and Serotonin analogs and stuff. So,
Dave:	00:21:41	They do all these things.
Athena:	00:21:42	Yeah. Yeah. And then their signaling the Vagas Nerve right directly to the brain. So,
Joe:	00:21:46	So we have this nerve super highway between our guts and our brains. And that's called the Vagas Nerve. So, if we want to understand why it is that a transmitter that's made by a microbe in the gut, how it might possibly affect the brain, the Vagas Nerve is part of the answer to that. But this, this pain idea, this, this hangry kind of idea about how gut microbes might make us feel bad and thereby could make us do things that they want us to do. Again, we're speaking in shorthand here.
Athena:	00:22:14	Right. The 'as if intentionality' that uh, we often used as evolutionary biologists to just speak about how something's going to evolve to look like it's intentional. [Joe and Athena both agree]
Joe:	00:22:27	We know, we know now that like with no susception that, pain sensations in pain processing, the Gut Microbiota is actually super deeply involved in that. So you can take away the Gut Microbiota. You can do this in germ free mice, in germ free mice feel a whole lot less pain just in general. So even the capacity to feel pain seems like it's dependent on having a gut microbiota. One of the examples we used in our paper that I think we cut from the final version, um, had to do with opioid production. And we use the example of the worm Dracunculus. Dracunculus is the worm that is, uh, emerges from someone's foot. And this happens in Equatorial Africa, in places where, where people take up the parasite by drinking infected water that has this copepod in it.
Athena:	00:23:21	Yeah. Parasites are gross. That's just a fact.
Joe:	00:23:22	Yeah. And the parasites, the rosens, it ends up in the lymphatics of the leg. What's amazing about this super long worm, and it can be like a couple feet long, is it lives in your body and it secretes morphine or something that looks like morphine. It activates opioid receptors in your body it manipulates you so you can't feel this worm in your, in your leg until it wants you to feel pain.
Athena:	00:23:44	This sounds like a really bad marriage. [laughter]
Joe:	00:23:48	So the next thing you know, your foot's on fire and the little worm is burrowing its way through your skin. So it stops producing the morphine and it produces, other substances that cause absolutely ridiculous amounts of pain and your foot's on fire. And so what do you do when your foot's on fire?
Athena:	00:24:06	You put in it water.
Joe:	00:24:06	You plunge in under water, right? And that's exactly what, what the worm- again, we're speaking of shorthand here- wants you to do. It's evolved to manipulate the behavior of its host in a way that promotes its reproduction and fitness. So the infected person puts their foot in the water, the worm burrows out, lays a bunch of eggs, and then goes up, goes around its merry way. So as an aside, the Dracunculus worm is the one that is, we think responsible for that snake on a staff symbol, which is the universal medical symbol.
Athena:	00:24:40	Really?
Joe:	00:24:41	That's one of the ideas behind it. Who knows if that's true or not, but physicians or healthcare workers, or healers in some of these communities would very carefully try to wind up this parasite onto a stick and it would be this weeks- long process to, to pull it all the way out of the body.
Athena:	00:24:59	What?
Joe:	00:25:00	If you mess up and you break the worm, then it causes massive inflammation and infection and you can lose your leg.
Athena:	00:25:06	Wow.
Joe:	00:25:07	Yeah.
Athena:	00:25:09	Wow. So it's kind of like a, not quite a bomb, but sort of like, if you don't like, if you set it off, then
Joe:	00:25:19	Yeah, you have to do it just right. And that takes some skill.
Athena:	00:25:23	Wow.
Joe:	00:25:23	And patience. And it's miserable for the people undergoing this. What's remarkable is that this bug, this parasite, this worm is likely to go extinct. There's some pretty effective and easy public health measures being put in place in some of these countries. All you have to do to avoid getting infected is you have to avoid drinking the copepod, which is like this little tiny miniature crustacean in freshwater sources. So yeah drink filtered water and they give people a little straw with a filter on it. So they're very close to making this organism extinct. It only infects people. It's a parasite, which has evolved just to parasitize human beings. Which is also kind of amazing. [Athena agrees] It has no other natural vector or reservoir in other organisms.
Athena:	00:26:12	Are there a lot of parasites that just affect one species or is that a really unusual thing in general?
Joe:	00:26:19	Well, I think this particular one is unusual. I'm not aware of other worms, but they must exist. There must be some relatives that of, of this, that infect other organisms.But this one's super specialized to deal with people.
Athena:	00:26:30	Right. Yeah, I mean sometimes, don't you have parasites where there'll be sort of subspecies that then specialize on you know, certain other species? But,
Joe:	00:26:42	Well, Influenza is kind of the poster child for an infection that's really good at switching hosts. That's why we have Swine flu and Avian flu and we worry about, you know, ducks and geese flying in with Influenza. It can really do a good job of infecting different kinds of organisms. But on the other hand, there's a reason why you're not going to get Kennel cough from your dog and your dog is probably not going to get your cold. Um, a lot of other kinds of infections that are much more specialized on their host.
Athena:	00:27:14	So for us as humans, these parasites and microbes that can effect our behavior, what are your feelings or thoughts about, is this a problem for us? Like in terms of our autonomy? Like are they, you know, is there a philosophical problem here?
Joe:	00:27:36	Of course there is and people, even without considering microbes that are hijacking your brain, people argue about whether we have free will and some people, some, some good people think that in fact that we don't really have free will. That if you can go, if we could actually get an accurate picture of your internal mental state that we could predict with some certainty of what you're about to do in the future and that we're really just a automa automatons. I'm not sure if I believe that. I like to think, as most people do, that we have some agency in the world and we know what we're doing, at least some of the time. But this, these data kind of challenge that. And we know that when we look at germ-free animals versus not, and we extrapolate from some of these results and other organisms, it looks like your internal mental state, your mood, your, some of your behaviors, whether you're eating or not, whether you're hungry, whether you're sleepy, whether you're, who knows what
Athena:	00:28:38	anxious,
Joe:	00:28:39	anxious,
Athena:	00:28:40	feeling social,
Joe:	00:28:41	feeling social, all these things, everything that that Athena just mentioned, we know are affected by microbes. So to look at the data briefly, you make germ free animals and they become relatively antisocial or a-social. They don't like to hang around with their litter mates and or socialize with other conspecifics other mice. Germ-free mice also exhibit, they can exhibit some anxiety behaviors. And it turns out that if you transplant microbes from an anxious mouse into a germ free mouse, you can make the mouse even more depressed and anxious. And if you transplant microbes from a confident, robust non-depressed mouse, you can make the mouse confident and brave. All these things have been shown. So if that's true, if our internal state is really dependent on microbes that we're interacting with, maybe we don't have free will.
Athena:	00:29:34	Hmm. Okay. So if we can wildly speculate for a minute here,
Joe:	00:29:40	No way. We never do that.
Athena:	00:29:41	We never do that. Um, if microbes are indeed having these substantial effects on our mood, our feelings of well-being our, um, anxiety, depression, sociality, etcetera. And we know in animal models that you can transfer microbes and then that actually changes the behavior or the outcome in the expected way.
Joe:	00:30:12	We're no longer in control people. [laughter]
Athena:	00:30:15	Well, and what is happening with human social contact? Are we transmitting microbes that could be then effecting the mood or well-being of the people who we're coming in contact with? Like when I shake your hands? Is there any substantial transmission when we eat together?
Joe:	00:30:40	Well, I think I maybe told you about this study, but at least in other cultures it's very common for people after making physical contact with another person that they smell their hand. Didn't I tell you this?
Athena:	00:30:53	Oh yeah, I saw something about that.
Joe:	00:30:53	Yeah, so the idea is that, there is transmission of microbes and that we have actually evolved ways of detecting some of those microbial cues and that they might be important. So the other thing that you're talking about is the idea that, this is true, that we have this little miasma of microbes that are inhabiting us at a very low concentration that are floating around us all the time. All the time. This is true. We know this is true.
Athena:	00:31:20	It's like that character in Charlie Brown. What was his name?
Joe:	00:31:23	Pig-Pen.
Athena:	00:31:23	Yes! He has that little
Joe:	00:31:24	It's Pig Pen. So yeah, so we are, yeah, he's a visualization of the microbial miasma. Yeah, I love it.
Athena:	00:31:30	Yeah. Charlie Brown, like knew it back in. When was that?
Joe:	00:31:34	Yeah, so the speculation is, does that miasma, does that effect other people? I think it probably does. I mean, it'd be a bit distressing to think about, what happens when the, miasma is really bad if sick people, right? Cause we're dealing with, in the ER where I work, there's lots of disturbed microbiomes, lots of them. And there's people that have behavioral disturbances. And we're at, you know, the hospital is one of these workplaces where we're really close proximity to people in ways that we're really not in any other setting, as far as I know. Even most, most industrialized workplaces like factories these days, there's very few people in them and people aren't interacting or their. It's a, it really is truly a sterile environment, but the hospital is not. The hospital, despite the fact that we like to think of it as being sterile, is hugely non-sterile.
Athena:	00:32:27	It's about as sterile as a Starbucks.
Joe:	00:32:29	Exactly. It's pretty scary. [laughter]
Joe:	00:32:33	Yeah. So we're being exposed to this little orbit of microbes around every person that we're interacting with.
Athena:	00:32:41	Sort of like the baristas.
Joe:	00:32:43	What's the baristas? [laughter]
Athena:	00:32:44	Just, you know, they're handing the cups and taking the orders, but for you it's even more, right, cause you're, you touch people, you talk to them more extended.
Joe:	00:32:54	Now, we do wash our hands. We do wear masks when we think about it. But still, we're being exposed to all kinds of badness. Can't all be good.
Athena:	00:33:03	Right, right. Okay. So we're, as we move through life, we have this microbial cloud that moves along with us and, and we don't really know what, if anything, that's doing in our social interactions.
Joe:	00:33:22	So this is really the story of the microbiome. I mean, that encapsulates it in a nutshell. Is that right? That's maybe a mixed metaphor. [laughter] But the idea that there's something that we haven't paid attention to, but it's hugely important in modulating some of our social interactions and other things that are important to our health and our lives.
Athena:	00:33:47	Yeah. So we have lots of chemoreceptors, right? Like the, they're called what? MAMPs and PAMPs and molecular, what are they?
Joe:	00:33:58	No, you're right. Our immune system in our bodies are built in such a way that a lot of our body's systems are pay an inordinate amount of attention to microbial cues. There really, we're really plugged into this microbial world, whether we're aware of it or not, and so yeah, MAMPs, that's microbial associated molecular patterns. We have all kinds of receptors that, that whose job it is to pay attention to those things.
Athena:	00:34:25	That's like little pieces of microbes, basically. [Joe confirms]
Joe:	00:34:25	We have receptors for the things that microbes make or the little, little chunks of microbes that are, we're being exposed to all the time. Of course, our bodies are full of microbes. We have 20 trillion microbes that live in our guts. It's a lot. So they're shedding little parts of themselves. They're metabolizing things. All those signals are being integrated by our immune system and are being taken up, at some small level, into your bloodstream and affecting gene expression and the functioning of your entire body.
Athena:	00:34:58	So maybe we should think of this system as the sixth sense of sorts?
Joe:	00:35:05	That's great. I like it.
Athena:	00:35:06	Could be your gut feeling? [Joe agrees]Yeah. Maybe those are, maybe that's an additional one on top of it, because maybe the Vagas Nerve is part of that too.
Joe:	00:35:15	I like the sixth sense analogy. You know, like the ghost analogy. Right? If you take away the human, you're left with the little, the little shell of microbes within us and on us. Like a ghost.
Athena:	00:35:26	Right. And then the MAMPs are the ways that our physical bodies communicate with the, you know, ethereal of the microbiome or something.
Joe:	00:35:38	The undead.
Athena:	00:35:39	Oh yeah, the undead.
Joe:	00:35:39	Let's talk a little bit about that.One of the things that made me start thinking about how the microbiome is not always your friend- I mean like we've said it can be your friend, but it's often not- is what happens when you're about the time to die. And in fact there is this thing called the Mutiny Hypothesis. I thought this was my idea back, back in the day and I presented this topic, but someone actually went to the trouble of writing it up. And there is truly a mutiny hypothesis and the idea is this; which is that, when you get sick and when you're about to die, all of a sudden all the little microbes in your body that had been happily living in you ingesting nutrients that you eat and doing various things that don't hurt you. And not making you sick.
Athena:	00:36:21	Their interests are aligned with yours.
Joe:	00:36:22	Yeah. All of a sudden their interests are not aligned and when you get sick, they can turn on you and make you sicker. So if they can sense that you're stressed, having some life threatening problem, maybe about to die, then they start burrowing out of your guts going into your bloodstream, trans-locating to different organs. And what's remarkable is when you do die, when you longer have an immune system that can keep them in check. They rapidly transmit themselves to what we think of as being sterile tissues. Gut microbes can be founded to your heart within minutes. They can be found on your brain within a short amount of time. They're there ready to rock and roll and actually start consuming, eating you alive.
Athena:	00:37:03	Wait, so there is microbes in all of us right now that are literally just waiting for us to die or seem like we're about to die and they're just going to have a party?
Joe:	00:37:13	Right. So they can, they can hasten your death.
Athena:	00:37:16	They can hasten your death.
Joe:	00:37:18	Yeah.
Athena:	00:37:19	we're sure about that?
Joe:	00:37:21	Well, that's the Mutiny Hypothesis. There's another hypothesis out there called the Trojan Horse Hypothesis.
Athena:	00:37:27	Okay. What's the Trojan Horse Hypothesis?
Joe:	00:37:29	This is kind of the idea that, again, we have these supposedly friendly little creatures that are living in us, but in fact they are ninja warriors ready to erupt at anytime. I didn't come up with this.
Athena:	00:37:43	Those sound like they're kind of similar.
Joe:	00:37:45	They're kind of similar, but the Trojan Horse Hypothesis doesn't rely on you being about to die. It basically says that, you have within you microbes that can turn on you at any time and make you sick. So commensals that aren't making you sick can find their way into other tissues of your body and then they can make you really sick.
Athena:	00:38:07	Right, and that we do know.
Joe:	00:38:08	Now we know that that's true. That's for sure. No doubt about it.
Athena:	00:38:12	What parts of this are not for sure?
Joe:	00:38:13	Well we don't know, well, I'll put it this way. There is a guy by the name of Stephan Schuster who presented the house fly. Actually it was carrion fly. These are blow flies. He looked at the microbiome of blow flies and he argued that the fly and the microbes are in cahoots, kind of. They have a, a bit of a biological conspiracy to infect organisms and then kill them so that, that will increase the number of carrion flies and microbes. So the question really is, are the microbes really, do they really have it in for you? And do they, do they, is it really in their best interest to kill you off?
Athena:	00:39:00	But we're kinda talking as if microbes are some unitary thing, but they're not. I mean, there's so many different species and some presumably have generally more aligned interest with us and some have less.
Joe:	00:39:13	Yeah. We're going to have hundreds, hundreds or thousands of different, different varieties of microbes at any given body site.
Athena:	00:39:20	Yeah. And of those microbes, some of them are going to do better when we're healthier and some might benefit more from making us sick than others. Right? So,
Joe:	00:39:35	But the, the key thing to keep in mind is that microbes can change their strategies. Some are are obligate pathogens that are gonna make you sick almost no matter what. But the more we look, the more we're finding that a lot of pathogens and potential pathogens can change their state. They can go from being this little benign, not going to hurt anybody kind of a critter to something which is super dangerous, lethal.
Athena:	00:40:04	And they do this by changing their gene expression, presumably. [Joe and Athena agree]
Joe:	00:40:08	So I mentioned that microbes can sense your stress state and they do this, they have, there are adrenal receptors, that are receptors for stress hormones on a whole bunch of pathogenic microbes and that can regulate their virulence and their, uh, growth. Microbes also have receptors, getting back to the opioids, they have receptors for opioids, pathogens. This is something that I was just looking into today.
Athena:	00:40:34	What do they have those for?
Joe:	00:40:38	I don't know, but they seem to mess with us. So, a paper that was brought to my attention today by one of the medical students that we're teaching. He shared with me this paper, and I somehow have missed this. But it turns out that microbes can adjust our sensitivity to opioids.
Athena:	00:40:58	What?
Joe:	00:40:59	Yeah. So not only can, can microbes effect pain sensation, but they can also effect how we respond to opioids. So that's kind of cool. So the reason why this is important is that opioids tend to favor the growth of gut microbes and especially pathogenic ones. So people that are heroin addicts, people that we're giving lots of opioids to people that are dependent on opioids for chronic pain, they have bad things happening in their guts. And if fact overall they have a higher risk of gut infections, surgical complications, and higher mortality, overall. So you might imagine that microbes might benefit from having a sort of a high opioid environment, if that's true. But this sort of amazing paper looked at the phenomena that's called Tachyphylaxis. And, Tachyphylaxis is where, say, drug addicts, if they want to get a certain amount of high, they have to inject more and more and more of the drug to get the equivalent amount of high cause you develop a certain, a sort of dependence and a sort of tolerance to the, to the drug in question. So here we're talking about opioids. So of course that causes people to overdose when say a drug addict gets incarcerated, goes to jail for a few days, gets out, they actually recover, some of the tolerance goes away, they inject the same amount of drug that made them high before but now it kills them. But the underlying problem there was that, is this ramping up of, of dose. We see this in people who are addicts and we see it in patients in the hospital. Tachyphylaxis, this whole phenomenon of tolerance it doesn't happen if you're germ-free.
Athena:	00:42:38	What?
Joe:	00:42:38	Yeah. If you're a mouse and you're made germ-free, right? Germ free mice don't undergo this, this phenomenon.
Athena:	00:42:46	So microbes may be playing a huge role in addiction that we just haven't yet figured out?
Joe:	00:42:53	Well there's that and microbes might just be playing us, period. [laughter] You know? They might be, they might be messing with our pain systems, our opioid systems. Because if we, of course we produce endogenous opioids, that's why we have receptors for opioids. We didn't evolve, you know, these receptors in anticipation of there being heroin or refining poppies for these purposes. We have these things in our bodies. But the microbes are paying attention too and they're interfering in some ways with some of these systems. Is that was that a absolute? No. Kind of like the microbes effecting our eating behaviors. It's, it's a little speculative. But, wow they're doing some cool stuff.
Athena:	00:43:35	Yeah. Well you have to ask, you know, if we, you know, and we do know that microbes have the ability to interact with all of these systems in our bodies than if you're taking an evolutionary perspective, you have to ask you know well, is it just like noise? Is it a byproduct or is it an adaptation? Right? And so,
Joe:	00:43:59	So, we're going to be careful about these things.
Athena:	00:44:01	So if it's noise right, then it's just like, oh, it's totally random. It doesn't have any function for either us as humans or the microbes. Um, if on the other extreme, if it's an adaptation, then it's like both or one of the parties evolved to do it because it benefited them. In this case, presumably then, microbes evolved to mess with us but we also evolved to have these systems to be functional.
Joe:	00:44:30	So I am weird and I actually think about these things a lot. And I really wonder about it. So, any given interaction, there is a bunch of different possibilities, just like you said. It can benefit us and not benefit the microbe. It can benefit both partners, which is, seems to be the default position of many theorists in the field right now. Or it could be, could benefit neither party and just be sort of a neutral thing. We don't know exactly what's going on here, but it's awesome. It's kind of amazing. Can't believe this stuff.
Athena:	00:44:56	Yeah. Well and I mean sometimes right, like if you have a situation where two parties can manipulate each other, then it can escalate into a situation that's really bad for both. Even though, like, it wouldn't have to be that way. Right? Like anytime you have an arms race, both parties can end up investing a huge amount in the arms race when they would've just both been better off not engaging with each other in the first place. Like my kids when they start to like fight with each other, and it just
Joe:	00:45:29	Come on, your kids kids are angels. They would never do that.
Athena:	00:45:31	Oh yeah totally. They would never do that.
Joe:	00:45:32	I don't believe it.[laughter]
Athena:	00:45:32	But, but yeah, I wonder about that issue of like how much, um, of disease is actually a sort of escalation between parties. So you know, the microbes are say, um, you know, producing factors whether they're virulence factors that make us not feel as good or if they're, you know, factors that are trying to manipulate our physiology in other ways. And then maybe our immune system has some counter response to that. And then perhaps the microbes have another counter response and then we have a counter response and, and you know, maybe that's one of the sort of feedback loops that contributes to disease.
Joe:	00:46:22	I think you're right, those things have to play out, at least to some degree. I think we'd be naive to think that they don't work in that way sometimes. But the great thing is, if you didn't think about stuff like this in evolutionary perspective, you wouldn't look for these kinds of things. And you have to be, you have to think about it, to look for it. And the more we look in the microbiome, the more we find some of these unexpected, crazy sorts of phenomena.
Athena:	00:46:51	Yeah. Yeah, so we've kinda been sort of taking this angle of like, you know how are microbes manipulating us, right? Are microbes zombifying us, but let's turn it on its head for a minute. Are, are we zombifying the microbes inside of us?
Joe:	00:47:10	I think people have thought about domesticating microbes?
Athena:	00:47:14	What's the relationship between zombification and domestication?
Joe:	00:47:19	Well, when you look at a domesticated animal, let's imagine a cow for instance, or even a dog or a cat, and you compare it to it's wild cousin, What's the major feature that's, uh, that's missing?
Athena:	00:47:33	Aggression, right?
Joe:	00:47:33	No. They're missing their brains, anyhow. [laughter]
Athena:	00:47:34	Braiiinnnsss.
Joe:	00:47:35	Yeah, their brains. They have much smaller brains.
Athena:	00:47:35	We ate their brains.
Joe:	00:47:35	Domesticated animals don't need brains. Brains are gone. They're not totally gone.
Athena:	00:47:45	I mean, figuratively, ate their brains. Made them disappear.
Joe:	00:47:47	Did you know that human cranial capacity has also diminished in the last 10,000 years?
Athena:	00:47:53	I just learned that recently.
Joe:	00:47:54	I was really surprised by that. But people have said that we humans are self-domesticated because of agriculture and other reasons, so we don't need to have as much, you know, stuff going on upstairs. We're becoming dumber over time.
Athena:	00:48:12	Which is, so not what most people think.
Joe:	00:48:15	Right. I was surprised by this, but then I looked it up. [laughter]
Athena:	00:48:20	And it's true?
Joe:	00:48:20	It's true. [sounds of intense thought] Yeah. So domestication involves sort of the loss of one's brain, then you could imagine that in some ways were domesticating on microbes too. Maybe.
Athena:	00:48:34	But, if we, well, let's just talk about the relationship between domestication and zombification for a minute. Because if domestication involves brains getting smaller than presumably that involves being more pliable, being more malleable, being more manipulable.
Joe:	00:48:55	Absolutely. Yes. Some other thing, in the case of us and our pets, we're taking care of their dietary needs and we're making sure that they have enough resources to get by with. And so they don't need to have a big brain. And that that absolutely requires them to be somewhat malleable and pliable. A hundred percent.
Athena:	00:49:18	So, uh, on one hand, domestication and taking care of the needs of something seems like a really good thing. It's a positive thing. It's helpful, it's kind, it's giving, but on the other hand, it's creating an entity that is more dependent and hijack-able for your own ends.
Joe:	00:49:43	That's scary. But yeah, I think that's the, that's the way to look at it.
Athena:	00:49:47	Hmm. Um, before we go too much off in this direction, which I'm enjoying, but I want to make sure we have a chance to talk about the heat-stroke idea that you talked about at the Zombie Apocalypse Medicine Meeting. Do you want to talk about that briefly? Not so much?
Joe:	00:50:08	I want to talk about it for 4 hours. I'm just kidding.
Athena:	00:50:10	[laughter] Bonus episode!
Joe:	00:50:11	We can see if we can do it briefly.
Athena:	00:50:16	Because I mean it relates a lot to, the idea you were talking about earlier of like, you know when your microbes mutiny.
Joe:	00:50:22	Yeah. So let's get into that for a second. Before I do though, I want to talk about the one example of a microbe that does seem to influence its hosts eating behavior in a way that benefits the microbe, that Salmonella Enterica. So, it causes dysentery in people and similarly like dysentery in mice. And typically when we get sick with a GI infection, we lose our appetite and we exhibit sickness behavior, right? We, you know, want to lie in bed, we're going to call in sick, we're going to just not do the normal same things that we do. We're not going to be super social. And that is thought to be adaptive and beneficial and good for us. Well, Salmonella Enterica, at least in mice, turns off sickness behavior. So here you have this little diarrhea mouse and it's wandering around, interacting normally with, with it's, uh, with other mice and it's eating the normal amount so that they don't lose their appetite, they continue to eat. So that makes more Salmonella Enterica and it gives them more opportunities to transmit itself. So this is the best animal example of that hijacking of brain and behavior that we see. In a way which really seems like it benefits the microbe perhaps at the expense of the host, although that's debatable.
Athena:	00:51:37	That's interesting. Is there any other, are there any other examples of like when hosts get infected?
Joe:	00:51:45	There's Rabies. So, I think that the zombie idea has to take in large measure, inspiration from the example of rabies. Rabies victims are nuts. They want to bite you. They're frothing at the mouth and they lose their mind. It is literally an encephalopathy. Right there their brains are becoming liquified with virus.
Athena:	00:52:10	Are they really?
Joe:	00:52:11	Maybe not. That could be some artistic license. [laughter]
Athena:	00:52:15	That's permitted. [laughter]
Joe:	00:52:17	But their brains are super inflamed when they have this massive inflammatory response. And the behaviors just so happen to benefit the virus. Uh, hydrophobia which is then thought, is actually an inability to swallow. So it's, there's a buildup of saliva in the mouth and animals lose that coordinated swallow reflex and the aggression and the animals change their circadian patterns. So, a nocturnal raccoon will then become diurnal and be wandering right in the middle of the street and people will sit, go down to pet it and off, off they go to the races with rabies. Crazy stuff. Okay. But heat stroke. Heat stroke is kind of like the mutiny idea that heat, in heat stroke where we're exposed to high temperatures, the lining of the gut becomes unable to contain microbes and their products. And so, bits of microbes then leak into the bloodstream, cause massive amounts of inflammation and heat stroke looks just like overwhelming sepsis. So heat stroke is an example where, like the trojan horse or like the mutiny idea, our, our commensal microbes turn on us and they elicit this massive inflammation that is deadly. It kills a lot of people, has a huge mortality and that's why heat waves are so deadly.
Athena:	00:53:39	So the physiological mechanisms underlying heatstroke are basically the same as the physiological mechanisms that underlie sepsis?
Joe:	00:53:49	They look very similar and in fact, even clinically, they look similar. The temperature's elevated, blood pressure can be low, heart rate is super fast, and there's a lot of similarities. Um, if you look even biochemically, we'll find an elevated lactate in sepsis, we'll find activation of the coagulation cascade, massive activation of inflammatory markers and inflammatory cells. It looks just like sepsis. So some, again, people have argued that the microbiome is there to buffer us from environmental extremes. It compliments our genomes and it provides us these evolutionary advantages, these fitness advantages that allow us to cope with differences in environment so we can exploit these different environments. So here's a different environment, you just crank up the heat a little bit and instead of buffering us or making us better able to deal with it, the microbiome turns on us, actually makes us sick. So, I'm fascinated by this.
Athena:	00:54:47	Uh, I'm going to play devil's advocate for a moment here. Just cause you know, I'm, I'm always the optimist about there being some cooperation somewhere.
Joe:	00:54:56	That's true. There is cooperation.
Athena:	00:54:59	Yeah. So, could it be that some species of microbes, if you have them in your system, you're going to be more protected than if you have other species of microbes. So you have, you know, species that are less likely to um, you know, be ready to jump ship and mutiny because they, you know, are either better kept under control by our bodies or intrinsically have more aligned interests with us or something?
Joe:	00:55:28	So at the symposium that you held at Saguaro Lake, somebody said "you can't have cooperation without conflict. It's really a Yin and a Yang." Do you think that's true?
Athena:	00:55:43	I think that conflict is one of the big forces that can encourage cooperation. Right, cause if there's like some outside conflict, then, it's easier for people to team up. But I think you can also just have sort of inherently harsh environments and get cooperation without necessarily having to have direct conflict.
Joe:	00:56:10	So that can happen sometimes. But my view on this is that of course, I don't think that everything is conflict. I don't think that everything is manipulation. I don't think that we're being hijacked all the time. And in fact, we do have some pretty good examples of things that look like mutualism in our guts. But it makes sense to me that there's always this potential for conflict, competition and harm from the microbiome. So the immune system, the job of our immune system really is to encourage alliances between our bodies and the potentially protective ones. And of course there's going to be a gradation of harmful to less harmful ones or microbes that have our fitness interests more in alignment with theirs. So our immune system tries to encourage the growth of those microbes and may in fact produce increasing cooperation in the way, which is the inverse of what you were talking about earlier with increasing conflict that happens. But really it's, it's two sides of the same coin.
Athena:	00:57:07	I mean, presumably our bodies can exert selective pressure on the populations of microbes within us, right? Depending on what the factors our body is producing, depending on whether we're feeding sugars to the microbes in the lining of the gut or not, there's a lot of things our bodies can do.
Joe:	00:57:28	Yeah. So evolutionary theorists have proposed that you can't really get widespread cooperation in the microbiome without selection and the selection that's happening is being, happening because of the immune system
Athena:	00:57:44	Yeah. But if you know our bodies are constantly doing that selection, then that's going to be influencing, you know, who the players are that are in the gut. Right? [Joe agrees] And, and also you mentioned earlier how some microbes have really conditional behavior, right. They'll be beneficial sometimes and yeah, virulent other times, depending on their gene expression and our bodies can potentially reinforce the behavior that we want.
Joe:	00:58:18	Yeah. So when you have, when we, when we, when we subject this, this, this complicated system to something like a game theoretical approach, we can acknowledge that both sides have conditional strategies. You can up-regulate your immune system or down-regulate the immune system depending on conditions. And the microbes can do the very same thing. And it's gonna be in both parties interests sometimes to kind of lay off each other. [Athena agrees] Down-regulate virulence and immunity.
Athena:	00:58:50	Yeah. Otherwise you can potentially get stuck in this ever escalating situation where... Okay. Again, speculating here that, that kind of escalation could be responsible for a lot of the,
Joe:	00:59:06	Well, we should look for it. We should look for both of those things. And maybe sepsis and heatstroke, like we talked about, are examples of sort of a, a forward positive feedback loop in which things have gotten out of control.
Athena:	00:59:18	Feedback loop. Interesting. Well that actually leads us to the question that we always have to ask in this podcast. Which is,
Joe:	00:59:30	Are you a Zombie?
Athena:	00:59:32	Well that too. I do want to know. Um, but are, the question is what is the Zombie Apocalypse of microbes manipulating human behavior? Like, what's the extreme, you know, if you, if you sort of take what we know about how microbes effect behavior. An, and then you extrapolate that into a Zombie Apocalypse, what does that apocalypse look like?
Joe:	01:00:05	I think it's full of poop. [laughter] From the microbes perspective, the human is just a way to make more microbes.
Athena:	01:00:12	This is the shittiest Apocalypse! [laughter]
Joe:	01:00:12	That's right. So, the apocalypse is just mountains of poo everywhere.
Athena:	01:00:19	The poopocalypse. [laughter]
Joe:	01:00:19	Right?
Athena:	01:00:22	Yeah. I guess. Or, what if it's,
Joe:	01:00:28	And actually, we humans are doing a pretty good job of that on our own.
Athena:	01:00:31	A lot of shit. We're generating a lot of shit.
Joe:	01:00:32	Well yeah. We're contaminating our environment.
Athena:	01:00:35	Yeah. Yeah. Well, how about if there's some microbes that are just really good at transmitting without killing us?And they're manipulating us to make us extra social? Or maybe want to help people? Or become a physician or something like that?
Joe:	01:01:04	There are some physician sociopath's. [laughter] It's not all good. I guess I'm going to bring it back the other way. Which is, thinking realistically about what can we do to protect ourselves from the, from the microbiome? So whether or not we're being zombified, whether or not we're being hijacked and whether or not we're being manipulated, we do know for sure, the microbiome has the capacity to one, make us feel bad and to make us sick and to kill us. All of those, they're very, very real things. They're not up for debate. That stuff is known. So how do we protect ourselves from this and given that microbes do have these conditional strategies, we want to put all the incentives in the way, away from them being virulent and manipulative and harmful to us. And this kind of gets back to the domestication idea. We want to corral those microbes and make them do our bidding. We want to, we want to keep them in place. We don't want a microbe with agency. If you think about it, Ecoli, with its little flagellum is, when they become motile and they start moving around, that's when they're dangerous. They, that's when they have escaped the control of the immune system. That's when they find their way into your body tissues and make you sick. It's your job to say, you know what? That's a bad idea. Don't. You just stay put, stay where you're at. Don't grow a flagellum. Don't activate those virulence factors. We're going to give you a couple of things to pay you off and keep you cool, but just don't do it. So that's really, really our agenda. Okay? So our immune system does this, but we can have dietary choices, lifestyle things that we can do and a bunch of stuff. Even maybe some social interactions that we can do that to try keep our microbiomes as healthy for us as possible, as domesticated as possible.
Athena:	01:02:52	So you're saying zombify your microbiome, so it doesn't zombify you.
Joe:	01:02:56	Exactly. You got it. [laughter] Sounds like a winner to me.
Athena:	01:03:02	All right. Well, Joe, thank you so much for joining us today. It was truly amazing having you.
Joe:	01:03:10	Yeah, we have a lot to think about and thank you Athena.
Outro:	01:03:12	[Psychological by Temi]
Athena:	01:04:29	All right, it is time for my shout-outs. Thank you to the Department of Psychology at ASU and to ASU in general for helping to support Zombified. Specially thanks to The Strategic Initiative from the president's office, the Interdisciplinary Cooperation Initiative that helps to support this podcast and the Lincoln Center for Applied Ethics. Also, thanks to my lab, the Aktipis Lab for all of your help and support and of course the Zombie Apocalypse Medicine Alliance. We are on Twitter and Instagram zombifiedpod on Patreon as zombified and our website is zombified.org if you love Zombified, think about supporting us. We're an educational podcast. We have no ads. If you can even contribute just $1 a month to us that will help us make more awesome episodes. And finally, thanks to all of the brains that helped make this podcast. Thanks to Tal Rom who does our amazing sound to Neil Smith who does all of our illustrations. And thank you also to Lemi, who is the artist behind our theme song, Psychological. If you're interested in listening to that, you can hear the whole thing on our website or on Spotify or wherever you listen to music.
Athena:	01:05:53	And finally, I'm going to share some of my brains, like I do. At the end of any episode, I give some sort of a story or some connection to my work or a wild speculation of some sorts. So I'm going to offer today maybe the craziest thing that I have ever done in a semi academic situation. Which is, I wrote a one act play with um, my husband and colleague Carlo Maley to explore a hypothesis. Um, so we wrote the play and then we actually also performed it at the Zombie Apocalypse Medicine Meeting. The name of the play is The First Church of the Microbiome. And we wrote this play to explore the hypothesis that microbes might be responsible for religiosity and spirituality.
Athena:	01:06:50	So, the idea is that we know that microbes can influence our emotions, our physiological states, and there is sort of this possibility that they may potentially, possibly be responsible for things that we think of as spiritual feelings or religious feelings. Um, so in this sort of hypothesis framework-slash play, the spirit is the microbiome and you know, it enters through our breath like through the air that we breathe and, um, interacts with our nervous systems and physiology that way. And so, one of the fun things about this wild hypothesis is that, if it is true, then you can actually think of all of us as, um, sort of spiritual slash microbial kin by virtue of sharing microbes. And if we, you know, come together and, um, you know, sing together or dance together or eat together, that we actually can become more genetically related in terms of the microbes that we have.
Athena:	01:08:06	So yes, lots of interesting ideas kind of swarm around this notion and they're all wild and speculative, speculative. And that's why we wrote a play instead of writing a paper and trying to get it published. So, one last bit, which is I realized that if this is the case, that we can kind of, you know, become more microbially related through doing things together like this, then maybe, maybe that makes it easier for us to share our brains if we're more microbially related. Well, with all that, I want to thank you for listening to Zombified, your source for fresh brains.
Outro:	01:09:00	[Psychological for Temi]