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#144 Classic episode – Athena Aktipis on why cancer is a fundamental universal phenomena
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- [00:00]
A
Hey everyone. Welcome back to our next holiday classic episode from back in 2023. I often cite this episode as maybe among our most unappreciated of all time, because I think many people, they read the title of it and they mistakenly thought of it as an episode about cancer biology. And if they're not that into science episodes, then maybe they didn't really give it a chance. But this is actually an exploration of the fundamental forces of order and cooperation that arise at many different scales of organization throughout the universe. And how their success then creates the slack for defectors to flourish internally inside that order and undermine the corporation. But then how even within that disorder, even within cancers, the cheaters often start cooperating themselves through specialization and division of labor, which then creates the opportunity for hypercheaters to exploit that cooperation inside the cancer, making it a sort of defection all the way down or a cooperation all the way up, depending on whether you want to see the glasses half full. While we're talking about cancer though, have you ever wondered why it is that elephants with literally 100 times, I think more than 100 times more cells than human being don't get cancer far more often? You'd kind of expect that because elephants in a sense have 100 times as many shots on goal, 100 times as many opportunities for a single cell to start to want to proliferate uncontrollably. And if elephants figured out a way to drive per cell cancer rates to less than a hundredth the rate that human beings get, why evolution couldn't be bothered to deliver the same benefit to human beings. But we don't only talk about the kind of corporation defection dynamic. Athuna and I also discuss multi level selection, intergenerment conflict and parent off conflict theory. All of the juiciest stuff that I really enjoyed in my genetics undergrad degree. The fact that paternal and maternal genes in a child in a fetus are engaged in a kind of eternal arms race over resource extraction from the mother, one that can actually escalate into preeclampsia. Threatening completely the interests of both parties is among the more genuinely dark things I think I ever learned at university. So I couldn't be more excited to be re releasing this episode to you today. Keep in mind if you're watching rather than listening, that this was an episode from three years ago. So it's a video episode from long before we were typically doing video. And so it's not quite as beautiful, not quite the quality standards that you might be used to if you've been regularly watching us on YouTube this year. But with that small caveat out of the way, I'm so happy to bring you Athena Aktippus. Why Cancer is one of the Fundamental Forces in the Universe. Today I'm speaking with Athena Aktippus. Athena is an associate professor in the Department of Psychology at Arizona State University, where she's the director of the Cooperation and Conflict Lab and the Human Generosity Project. Her research interests lie at the intersection of cooperation, theory, evolutionary biology, evolutionary psychology, and cancer biology. She also started the Zombified podcast, where she and a co host explore various ways that organisms, including people, can be tricked into ceasing to pursue the actual goals that they have or ought to have. In 2020, she wrote the Cheating How Evolution Helps Us Understand and Treat Cancer, which is going to be the starting point for today's conversation and was a book that I really loved. Thanks for coming on the podcast, Athena.
- [03:03]
B
Thank you so much for having me here. I am really excited to talk to you about all the things.
- [03:09]
A
Yeah, I think some of my friends have been a little. It's been just cancer, cancer, cancer for me this week, for my housemates and colleagues. I'm going to be able to get all of the cancer stuff out of my system and then stop hassling them about it. I can hassle all of this is all at.
- [03:24]
B
Yeah.
- [03:24]
A
So I hope we're going to get to talk about what cancer really is at a theoretical level and what we might possibly be able to learn about societal cooperation from intercellular cooperation. But first, as always, what are you working on at the moment and why do you think it's important?
- [03:39]
B
Oh, what am I working on at the moment? I am so deep right now in trying to finish my next book, which is called Everything is Fine how to Thrive in the Apocalypse. So, yeah, it's like a playful take on existential risk and how we can deal with it as the social beings that we are.
- [04:02]
A
Yeah. How did you end up writing that book?
- [04:07]
B
Gosh, I ended up writing this book because I just could not stop thinking about and talking about these issues, you know, when even before COVID you know, I was sort of already like, using the apocalypse as a. As a. As a. Like a way of thinking about and talking about existential risk that I thought was maybe like a little bit more playful and fun and. And appealing than. Than just, you know, the sort of more straight approach to it. And then the pandemic happened, and then that kind of just like accelerated like, you know, very quickly. Like people were just talking about the apocalypse like, yep, we're in the apocalypse. And I think, like, that actually provided some, you know, levity almost to just be like, yeah, it's the apocalypse. And so. So I just kind of, like, leaned into that and, you know, started doing more, like live streaming. We started Channel Z, which is, you know, television and the zombie apocalypse, which is basically, like, just an excuse to make a bunch of TV shows that address issues like, you know, what are the risks that we're facing? How can we work together in community to deal with it? How can we prepare as individuals and, you know, and how can we just understand our world using evolutionary biology, using a really interdisciplinary approach that includes both science and humanities and sort of considering policy and ethics, like, bring all of those things together, bring all those people together to start thinking and talking about those issues. So that really kind of like, got me going in that direction. And then at some point I was just like, yeah, I want to. I want to write a book to get these ideas across, like, with a playful tone, with illustrations. And, yeah, it ended up being something that Workman was really interested in. And so, you know, then just kind of got set on that. That pathway. And it's been really fun, I have to say.
- [06:13]
A
Nice. All right, well, we'll come back to the apocalypse, I think, later in the interview, but I suppose for now we're going to do cancer. So I said, yeah, you know, it's.
- [06:22]
B
Like, what are we going to talk about? How about some really morbid topics like cancer and the apocalypse? You know, just choose which one.
- [06:31]
A
Well, I suppose a more positive framing on it is corporation. So I guess I said in the intro that you're a corporation theorist, because what is cooperation at kind of the highest level of abstraction? Because I guess your whole thing is thinking about cooperation at a high level. And then you can use that to analyze all kinds of different ways that different organisms or I mean, even like, subatomic, sorry, molecules that even interact with one another.
- [06:56]
B
Yeah, yeah. I mean, my whole thing is like looking at the world through the lens of cooperation and conflict, too, sort of as these organizing principles. And, you know, just like with, you know, with physics, the rules of physics, the laws of physics apply at all scales right now. Some laws of physics apply maybe more at some scales and others just because of the way, you know, the universe is set up. I think it's really similar with the law's kind of underlying cooperation. There are many things that apply across systems and scales, but then there's some things that apply more to some systems than others. So you know, for example, you can look at things like, you know, division of labor. Like, that's a basis of cooperation across pretty much all systems that have cooperation, that you can have division of labor or, you know, in many systems, that's something that you can have economies of scale. Right. That's another one where it's like, as you scale up, some things become more efficient. Maybe you reach a point where that stops and then it becomes less efficient. Right. So, so there, there are principles that apply. Another one is, you know, that the larger and more complex a group is, all else being equal, the easier it will be for cheating to arise and go undetected and potentially undermine the system unless you have other mechanisms there that can sort of, you know, protect, monitor, or respond. And so, you know, that last, that last idea, that last sort of, you know, thread is really what the big picture inspiration was for the book the Cheating Cell. Right. So thinking about our bodies as this cooperative system and as cancer, you know, as, as a breakdown of that, that cellular cooperation. But yeah, you know, big picture is we can look at cooperation at all these different levels and using different methods. Right. And so that's another thing that, like, has been really important to me in my career is not just having one methodological approach or one disciplinary approach. So, you know, bringing anthropological fieldwork together, psychology experiments together with computational modeling, and, you know, doing all of that also in the context of considering policy implications, ethical implications, and having that be part of the same conversation, the same research project, you know, not splitting those things out and then, you know, having like one, one, you know, place where you're like, oh, let's try to bring it all together. No, it's like part of the process is having all those things happening at the same time. Getting that cross fertilization and being able to, you know, be truly interdisciplinary as a result. So, so that's what I love. And that's, you know, a lot of what. What I've been doing in my career up until this point and hope to continue to do.
- [09:52]
A
Nice. Okay, so the structure of the conversation that we're going to have here is we're going to work through some of the key insights about cancer biology that, that, that you put in the, in the Cheating Cell. Then we're going to zoom out and consider analogies to cooperation at the human level, and then maybe even the, the species level or the planetary level. And then we might, may and instead talk about a cooperation within cells rather than between them. Now, I guess before I saw this book, I thought of cancer Kind of just as a disease that arises somewhat at random because of chance mutations in genes that happen to go wrong. And I guess there's a sense in which that is true, but it's not the whole story. And I guess the cheating cells made me see the tension between cancer and non cancer very differently and kind of as a far more fundamental phenomenon that comes along with. With life in all its forms and probably and potentially could forever. Yes. First up, what is the opposite of cancer?
- [10:47]
B
The opposite of cancer, I would say, is multicellular cooperation. You know, so basically the opposite of cancer is us. It's having a functional multicellular body that is cooperating effectively in order to make that multicellular body function.
- [11:05]
A
Yeah. And then, so what is cancer, basically? What traits does cancer have? And how is that relevant to the lack of cooperation?
- [11:13]
B
Sure. So we can look at multicellularity as arising as a result of five foundations of multicellular cooperation that made it possible. Inhibition of proliferation, the control of cell death, mechanisms for resource transfer. Right. Because as you get bigger, you can't just rely on diffusion for resources. You have to somehow get resources into, you know, the middle basically of a, of a clump of cells. And you also have division of labor, right? So having multiple cell types can do multiple jobs, different expression states, you know, things like that. And then you have the creation and maintenance of the extracellular environment. Right. So this is all of the things that are on the outside of the cell that make it make the organism more viable. You know, proteins that are produced, the, you know, matrix in which, you know, all the cells are embedded. And that's an environment that can be, you know, really healthy, or it can be quite literally polluted by, you know, acids and things like that. If cells are, you know, being wasteful and messy, which they can be, right. So they can sort of be, you know, cheaters in that sense of polluting their environment. So, so you have these five foundations of multicellular cooperation. And what we see with cancer is a breakdown in each of those. Right? So cells will proliferate when they shouldn't, they won't die when they should. They avoid apoptosis. They won't engage in the kind of division of labor that they should. Right. They will not sort of do the jobs that they're supposed to do. They'll monopolize resources and they will trash the environment. And so you can get a breakdown in all these foundations of multicellular cooperation. And in fact, when you, when you look at, you sort of, you know, take the sort of like, grounded in theories of evolution, of multicellularity approach with these, you know, foundations of multicellularity. And you that on to, you know, how have cancer biologists looked at the phenotypes of cancer? So there's this framework called the hallmarks of cancer that's sort of classic work. The breakdown in those foundations of multicellularity map very well onto the hallmarks of cancer. And, you know, we don't have to get into the details of this, but there's a couple places where it doesn't match up 100%, which are actually like, really interesting and useful then to sort of take these frameworks from thinking of the evolution of multicellularity and ask are we missing something in how we're defining cancer? Like, division of labor originally is not really part of the hallmarks framework. And, you know, we've suggested that, you know, a breakdown in differentiation should be considered a hallmark of cancer. And now things are kind of coming around to that. That actually being, you know, part of how people are looking at, you know, the sort of next generation now of the hallmarks of cancer. It's a good example of where, you know, that sort of cross fertilization between the fields and. And being able to have, you know, collaborators and expertise and, you know, reading in both fields and really trying to bring things together can lead to new insights. So, yeah, so I'll just put a pin in that one of like, okay, you know, like this can. It can do things that you can't do if you just stay in one discipline.
- [14:24]
A
Yeah. Part of the change in framework that I've had in my mind thinking about cancer is so when we imagine bacteria in the environment or bacteria living inside ourselves, we understand that they are facing evolutionary pressures to figure out how they can replicate more, how they can get resources, how potentially, if they're bad bacteria that our immune system doesn't like, that they are going to learn to evade the immune system and avoid our antibiotics and things like that. We don't normally think about ourselves in that way because we don't normally think of each individual cell in us as having its own kind of interests, its own pursuits and its side project and its desire to. To replicate.
- [15:01]
B
It's got a little side hustle going on, you know.
- [15:04]
A
Yeah, no, I'm just a liver during the day, you know, really what I want to be is a metastasis. But within our bodies during our lifetimes, Our cells are facing the same kinds of evolutionary pressure that a bacteria within us would. And because they like well, so the cells within us, they replicate much faster than we do we only replicate ourselves every 20, 30, 40 years or so? But the cells are turning over incredibly quickly, so their generation time is much faster. So they're evolving way more quickly than we do as an organism. And that gives them evolutionary time potentially to become more like bacteria that might be parasites on us. And that's kind of what's going on here. Yeah. Is there anything you'd add to that?
- [15:46]
B
Yeah, absolutely. I mean, it is a big shift of perspective to, especially as somebody who's trained in evolutionary biology, and the default is to think about evolution as this really, really, really slow thing. Right. But if you, if you think about like, what do the parameters of evolution look like within the body for cells that are evolving, you know, or potentially evolving inside the body? You have super short generation times. You have just completely mind blowing population sizes, right? And once you start getting, you know, mutations existing, which like, you know, you called a mutator phenotype, where then, you know, mutations just are sort of like going crazy. You know, it's just there's so much variation. So if you have, you know, those kinds of parameters, then evolution by natural selection and also, you know, drift too. But, you know, evolution by natural selection can go really, really fast. And you can get, you know, the opportunity for, you know, evolution by natural selection to operate, you know, just over the course of like, cancer progression is much vaster than all of the evolutionary time that we have had, you know, as humans since, you know, Homo sapiens came about. Right. So it's, it's a lot. It's, you know, orders of magnitude more. And so we just have to like, shift to a different scale. Like, I almost think of it in like, the body is a world with all these different, like, ecosystems in it. And the cells, you know, like, they're existing on a timescale that like, you know, if we're gonna map it on to anything, like what we experience, like a day is at least, you know, 10 years for them. Right? So it's like, it's a very, very different way of thinking. And then once you kind of shift to that, you're like, oh, wow, there's so much that could be happening in terms of adaptation inside the body. You know, how cells are actually evolving inside the body over the course of our lifetimes. And, and that, that shift just opens up, you know, all this potential for using evolutionary approaches and adaptationist thinking to, to, you know, generate hypotheses that then you can test. So I don't know how much you guys talk about adaptationism on the Podcast, but, like, the, you know, basic idea. Should I say, what's the basic idea of it?
- [18:16]
A
It might be the first time we've said that word on the show. It's possible. Wow.
- [18:19]
B
Amazing.
- [18:20]
A
Okay. Okay.
- [18:21]
B
Yeah. So adaptationism is idea that you can look at sort of the. The world through this lens of what's the function of things. Of, you know, like, if an organism has some physical or behavioral, you know, characteristics, what's. What is the. The function of that? And it's a way of kind of, you know, bringing in an evolutionary perspective where. Where you're kind of thinking of things as, like, you know, as if there's a purpose. So you actually kind of use some of this language earlier of like, you know, bacteria are trying to survive. Well, you know, they're not like, oh, how do I do this inside the body? Right. But. Yeah, but they, like, behave as if they are. Right. And so, you know, one of the ways that you can kind of think of adaptationism is this, like, you know, you're looking at what's happening as if it is with the purpose of surviving or reproducing. And so when you take that lens, thinking about cells in the body, you know, that come from the lineage that, you know, originated with the Conceptus that was us. Right. It really starts to. To change. Change things and opens up all these possibilities for evolutionary and ecological processes that could be going on inside the body over the course of our lifetimes.
- [19:47]
A
Yeah. I think one thing that makes it less natural to think about cancer this way is that, of course we know that the endpoint of canc death of the organism that hosts it and the death of the cancer itself. But, of course, evolution has no foresight. This is the thing you've always got to remember that there's nothing that stops evolution from driving an organism to extinction as long as at every step, the changes are good for the individuals that host them. Maybe that's a little bit extreme. And in fact, maybe that leads very nicely to the next question, which is, so go back half a billion years or so, give or take. Until then, it's all been kind of individual cells. But these cells are maybe trying, or there's evolutionary pressure for them to get the benefits of being larger and having multiple cells and specialization if they can make it work. But how on earth do they make it work? Because once you have multicellular organisms, then they're always at risk of being undermined from within by any individual cell that defects from the interests of the organism as a whole. Even just in the short Run and then brings the whole project crashing down by becoming cancerous, basically. I remember when I was studying evolution at university, there was this discussion of group selection among humans. So you could have a question of is it possible for humans to evolve altruism and cooperativeness because, say, groups of humans in the past that were more cooperative tended to thrive more and reproduce more. And so the individuals who had that attitude would then become more numerous. I think in general, evolutionary theorists, at least back when I was at university, didn't really like this idea because it suffers from this problem that any group of operators can then be really easily undermined by a cheat who is able to fool everyone else and take advantage of the group and then bring the whole cooperative system of the group, undermine it and then make it not work. So I'm kind of wondering, why doesn't multicellular life suffer from that same fatal issue?
- [21:46]
B
I have so much to say about this. So first pass is multicellular life does suffer from this very issue. Cancer is a problem for all multicellular life. You know, somewhere between 30 and 50% of people, you know, get cancer by the end of their lives. So it is a problem now. I think thinking has shifted a little bit in the last few decades around, you know, these ideas of group selection. And I have always kind of been like a, an advocate for using like multi level selection as the language because I think that the idea of, of group selection or the, the phrasing of group selection has been kind of like almost a political issue within, you know, within like evolutionary biology with people being like, oh, I'm a group selectionist or I'm not, right? So it's been sort of like a, almost like a marker of coalitional identity more than anything else. And the fact is you can always get natural selection to act in situations that meet the criteria for natural selection. And there are situations where groups can, those can meet those criteria. And so if you're in a situation where those criteria are met, then you should say, yes, group selection can happen when, you know, you have heritability and you have, you know, differential fitness. And you, you know, when, when, when you have situations where those criteria that you should just say, yeah, we'll, we'll have, you know, you can have selection acting on that level. One way of looking at, you know, what happened in the transition to multicellularity is that you basically shifted, you know, from situations where you had, you know, individual cells getting selected to having groups of cells getting selected. So, so you could say, you know, that actually was, you know, group selection or is continuing to be group selection and that we're made of 30 trillion cells that are cooperating and coordinating to make us viable. I think that, you know, the way that a lot of people have sort of framed this in order to kind of stick with the sort of like individual level kind of analysis and individual level mathematical analysis is to say, you know, there's, well, there's a transition in individuality where you go from, you know, it being individual cells to now being organisms that are getting selected in their own right. And, and that's absolutely a legitimate way to look at it as well. But all of this is really a matter of what assumptions you're making about, you know, what constitutes a group versus what constitutes an individual. You know, when, when you want to make that, you know, mental or mathematical leap from what you're saying is a unit. So, you know, I'm, I'm pretty pluralistic about this, I think, you know, just like sort of open, you know, talking about how like all the laws of physics apply, like at all scales, but in some, you know, some apply more than others just because you're dealing with different kinds of entities. I think that's the case with a lot of the, you know, mathematical and conceptual models around the evolution of cooperation that, you know, some apply more at some level than, than others and that it's useful to have many of these tools kind of in your toolkit to be able to use in the, you know, in the right context. And, and multi level selection, I think is one of the ones that's like a little bit more general because you can, you know, be like, oh, this is a situation where the selection pressures are greater between groups because you have more variation between groups than within them, for example. Right. So I think that it's a more broadly useful framework.
- [25:43]
A
Yeah, I guess we could see from the result that body stellar life exists that basically evolutionary. This challenge was overcome and it was overcome by the creation of the immune system, basically by all of these sentinels or all of these processes going on within a multicellular organism that are constantly monitoring each cell, or like most is most cells, to see whether they're acting suspicious and then to try to put a stop to it if they seem like they're not coordinating properly with the group. And it's by investing lots of effort in that that multicellular life has become viable, basically. Is that right?
- [26:23]
B
Yeah. I would just add it's not just the sort of immune system. We have really three different levels on which you have monitoring and responses to cellular cheating. So A first one, I would, you know, start with the cellular intrinsic mechanisms, I. E. What the cell is doing on the inside to monitor what genes are being expressed, what, you know, what proteins are being produced, what the cell is doing in terms of its physiology. You know, genes like TP53, they're basically like listening in on like all the stuff that the cell is doing from the inside. And if it seems like the cell is maybe, you know, doing things it shouldn't be doing, then it, you know, raises an alarm. And you know, initially, like that alarm halts the cell cycle, you know, starts engaging the DNA repair process. And if that doesn't work, then it's like, you know, what, we're just gonna. So that we don't mess things up for everybody else. So it's kind of like the cellular conscience. Like you could think of it that way if we're gonna, you know, like that's one set of mechanisms. And you know, TP53 is not the only one. There's many, many, you know, genetically based systems inside the cell that are monitoring the behavior of that cell and changing the state of that cell. Right. To do DNA repair, halting cell cycle, engaging, you know, cellular death. All of those things are, are options, you know, to, to keep the cells from making a problem for the rest of the body. So, so you have that level and then you have the neighborhood level. So cells are constantly monitoring each other and constantly sending signals to each other. They're sending survival signals and anti apoptosis signals. Right. So basically cell suicide. Yeah, yeah, so, and sending growth, growth signals as well. So basically, you know, the survival signals, the, you know, those anti apoptosis survival signals are basically saying, cell, you're good, you know, hang in there with us. And then the growth signals are saying, you know, yeah, you can keep dividing, you know, everything's all good in my opinion. With you. Right. So that again, anthropomorphizing. But it's useful, I think, because, you know, these same kinds of processes, you know, there's elements of that that happens, you know, across all systems if you.
- [28:48]
A
Don'T use this language of intent and purpose. I feel like the sentences just become so absurdly convoluted. It's such a, such a slicker way of thinking about it. Although I guess you have to have all these red flags go off when, when you're doing it wrong or doing it in a way that's. Yeah. Where the evolution wouldn't actually cause it, but. Sorry, sorry, go on.
- [29:04]
B
Yeah, yeah, yeah. So, so, so, so You've got those two levels, and then you have also the systemic level, which you were referring to earlier, where, you know, you have of this sort of broader system that's monitoring the body for, like, regions where maybe something isn't right. And that's a. It's a really good, you know, backup system for, you know, those other systems that. That we already talked about. And it also, you know, plays. Plays a broader role in just, you know, sort of like looking at if there's bacteria or viruses that shouldn't be there. But even like the cell intrinsic system, then the neighborhood systems, they're. They're not just monitoring sort of for these sort of internal things in the cell. They're also sort of monitoring for viruses and stuff like that, too. So there's overlap in terms of some of these. These mechanisms that are, you know, they're just to sort of protect us from things that might be trying to hijack us or undermine the, you know, broader evolutionary interests of the whole organism.
- [30:05]
A
So. Yeah, so an interesting thing that I hadn't really. I guess I'd heard of contagious cancer before, but I'd never really thought about it before this book. But if you think about it in the abstract, it is kind of weird that cancer can't be contagious because in as much as one person has these cells that are refusing to get shut down and are just proliferating as much as possible, if they got into someone else's body, then, or another body of the same species, or possibly even a different species, then why wouldn't they proliferate as well? And basically the answer is the same as the reason why it's difficult for pathogenic bacteria or viruses to do it, that we have all of these systems in order to make sure that that can't happen. But in the very early days of multicellular life, this was a massive challenge. Before organisms, I guess, had figured out how to prevent contagious cancer so effectively. But the funny thing is that it seems like with viruses and bacteria, we're constantly in this difficult arms race. It feels like it's a bit of an even fight between us and these various other pathogens, between our immune system evolving and. And them trying to work to get around it. But with contagious cancer, with most organisms, it feels like the immune system has just done such a good job that we very rarely see contagious cancer. We only see it in unusual cases like Tasmanian devils, where they have very low genetic diversity. And they also spread the cancer by literally biting wounds into. I Know other. Other individuals. And then as we discussed later, healing, wound healing releases growth hormones that then are conducive to cancer production aside, I.
- [31:39]
B
Just have point out, like, if there is a species in which, like a zombie apocalypse is going on, right. It's the Tasmanian devils are biting each other's faces and spreading contagious cancer. I mean, does.
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A
Does the cancer make them more vicious and cause them to bite more?
- [31:53]
B
There, There is a hypothesis that, you know, that the cancer actually is affecting aspects of. Of their behavior, including also their reproductive behavior. So I. I don't know this literature that well, but there's a. There's definitely some interest in it. And I have a grad student intrigued by this as well. So maybe we'll.
- [32:14]
A
Nice. Yeah. That seems like a full. That seems like a full zombie apocalypse.
- [32:18]
B
Yeah, exactly. Right. Yeah.
- [32:19]
A
Sorry. It's terrible. It's tragic, but it is.
- [32:22]
B
Anyway, we have to. I mean, but that's the thing. It's like we have to, like, approach all these terrible things with a little bit of humor. Otherwise, how are we gonna, you know, keep working on them, so.
- [32:32]
A
Very true.
- [32:33]
B
Yeah.
- [32:34]
A
Yeah. Why do you think that we've mostly successfully beaten contagious cancer, but not so much bacteria and viruses and sometimes fungus. Fungus guy.
- [32:43]
B
So I think that one of the things that's actually missing from the way that a lot of people think about cancer, especially in, you know, sort of oncology and cancer biology, is this window of, like, what was going on very early in multicellularity, which, you know, you made a reference to. But, you know, if you consider, you know, like the early. The early stages where you've got like, some, you know, groups of cells and they're. They're growing and they're, you know, produc public goods, you know, that like, are good for all of the cells in there. If you get like a cell, you know, coming from this other group and popping in there, it can, you know, get the benefits of what, you know, that other group has created. It's just, you know, it's a free rider problem of common pool resource problem. It's like, you know, the sort of classic kind of, kind of issue. And I think, you know, the very evolution of multicellularity is not just about regulating the cooperation within an entity that is, you know, beginning and might evolve, you know, that cheating. But the. The early evolution of multicellularity was the evolution of prevention of contagious cancer. I think, I think we should be thinking about that as one of the fundamental things that was going on in the early Stages of multicellularity. And so a lot of these systems that we have that, you know, are part of our immune system have their, you know, many of their origins in that original selection pressure in one way or another. Or at least that's where we need to kind of start when we think about what kinds of mechanisms might have evolved that adaptive problem of, you know, cells just, you know, popping in and trying to get the benefits of that. That entity. So many of our cancer suppression systems could potentially originally have been in place for prevention of contagious cancer, Right? Yeah. It's an open question, you know, like, what of our cancer, you know, prevention mechanisms have to do with that versus having to do with the, you know, maybe the more modern problem. Problem of, you know, preventing cancer from the inside as opposed to that thing from the outside.
- [35:09]
A
I'm seeing some academic politics going on there. How can. How can that be an open question? Surely we can just theorize about this and kind of tell that it sort of has to be true. Unless all of the mechanisms that we originally designed 500 million years ago to prevent cheating cancer have subsequently all disappeared and being replaced by something else.
- [35:27]
B
Well, so, you know, Rob, when you, like, are working in, like, an area where you're, like, applying theoretical, New theoretical frameworks, you're bringing things together, There are many places where, like, you start to question the assumptions that are out there about how things work. And, you know, sometimes there are a lot of really good reasons for those assumptions. Other times they're not. I, you know, I think we're kind of on the same page of like, you know, I like to be like, okay, first principles. This is. This is what we should assume. Like, it's almost like a bayesian kind of thing, like, coming from first principles. Here's what I think a reasonable assumption is. But I think that, you know, it's important. It's hard to prove. Yes. Yeah. So it's important to acknowledge, right, that there's, like, a community of researchers who, you know, have been working with a particular frame, have made progress on problems with a particular frame. And so I think that it's. It's a. It's a good thing to. To frame it as, like, you know, this is a. This is a hypothesis that, you know, comes from these first principles. It, you know, makes some predictions that could be tested and, you know, encouraging people to.
- [36:43]
A
People to. To do that.
- [36:45]
B
Yeah. Yeah, because I can't. I can't do this. That's the other thing is, like, I can't test all of the hypotheses myself that come from this. And so it makes much more sense to. It's like an opportunity for us to consider alternative hypothesis based on evolutionary first principles.
- [37:01]
A
Totally. Okay. Sorry, yeah, I interrupted you there. I think we're heading towards. Why is the anti cancer. Why are our anti contagious cancer mechanisms so successful maybe relative to our ability to stop other pathogens.
- [37:15]
B
Yeah, right. So a lot of that I think is because the very evolution of multicellularity required that, you know, that that occur. And you know, also the kinds of threats that you could have from, you know, a human cell that is trying to, you know, hijack a human body are specific in a way that you could get, you know, specific anti cancer mechanisms evolving for. Versus if we're thinking about, you know, pathogens, we're thinking about, about viruses and you know, bacteria and you know, fungi. Right. You have so many different species, so many different mechanisms of action. And so you can't just have, I mean, you had. You have to get evolution on every one of those specific kinds of potential, potential risks or, or some, you know, general purpose systems which we have as well. But yeah, I think, you know, that it's worth that perspective. It's not just like, oh, you know, human cells versus pathogens. It's like human cells as one kind of thing that could be an infection.
- [38:32]
A
Yeah. Yeah. Okay. So yeah, one way I might rephrase that is kind of every contagious cancer has to start from its starting point is a healthy human cell. And then it's got to modify from there. And that's like a very limited design choice. Whereas if you're looking at viruses and bacteria, they've got a very blank canvas on which they can write any possible infectious behavior or life cycle or so on. And I guess maybe also, I mean, human cancer cells, they reproduce unusually fast relative to our normal cells because they try to evade the limits on reproduction. But they're not replicating and evolving quite as fast as viruses and bacteria potentially can because I guess they're even smaller and they just have a faster life cycle. Is that generally right?
- [39:16]
B
Yeah, there, I mean, there's certainly, I mean, viruses, right. Like if they're inside a cell, they can replicate like crazy cancer cells. I think, you know, the current thinking is that they, you know, can reproduce as quickly as, you know, 24 hours or a little less. So they, they can get pretty, pretty fast. But, but you're absolutely right that there's. There's just a much broader canvas on which to paint if you consider all of the potential Pathogens that are out there in the world. And so. But also, I mean, we need to recognize that, like, there's a pretty big repertoire that cancer cells can access as well. Because our, our genomes have a lot of things that can be messed with to, you know, make these cells that do things that are, yeah. Evolutionarily unprecedented, at least for like, whatever a cell in a multicellular body should do.
- [40:14]
A
Yeah. So by having a much larger genome than a bacteria can potentially have much more complicated capacities. And also it's like, of course, a human cell is kind of ideally already situated to live in a human body in a way that a bacteria might not be. So it does have that sort of leg up. But I guess, evidently it's turned out to just balance out into being. Usually it's easier to prevent contagious cancer than contagious bacteria. Yeah. Do. Do plants and fungi get cancer as well as animals?
- [40:42]
B
It all comes down to how you're defining cancer. So there's like, you know, or sort of like there's some, like, politics about that. Right. Like, you know, academic politics. Right. So some people are like, oh, you can't call that cancer. But if you're asking, you know, do you get disruptions in cell proliferation and apoptosis and differentiation of cells. Right. The division of labor, like, all those things, the answer is yes. You, you know, essentially any multicellular lineage that you look at, you see examples of at least, you know, what we could call cancer like, phenomena where, you know, cells are proliferating when they shouldn't, you know, for the sort of, you know, survival or reproduction of the organism and where, you know, disrupt, you can have disruption of the, the division of labor of the, you know, differentiation of the cells.
- [41:36]
A
So, you know, I've known people who've said, oh, unfortunately, you know, my pet has cancer, it's going to die. I've never known anyone who said my houseplant has cancer. And unfortunately, it's dying. Yeah. In what ways is plant or fungi cancer different than that in animals? And it seems like, on balance, it's a bit less visible or like less of a big deal.
- [41:54]
B
Yeah. So there's actually one of, one of the things that happened, like, early on in my, like, interest in cancer was that I actually came here to Arizona before I lived here and saw a crested saguaro cactus. Now, this is a pretty, pretty awesome thing there. There's a decent number of them around here where rather than, you know, having like a, you know, the sort of classic shape, Right. Where they have like, you know, Know, one or a few, right, you know, kind of trunks coming out. You get this, like, crown kind of on the top. It just like, fans out. It's beautiful. And. And I was like, wow, that is, you know, that really is like a plant cancer. You have this disruption in the growth. And when I, when I looked into the physiology of it, you basically have a situation where, you know, the growth tip, like, you know, on the tip of any, any plant that's growing, it's usually a few cells that are, you know, they're called meristem cells or basically like the plant equivalent of stem cells. And they, as they proliferate, they create like, you know, sort of linear thing. But you can get a disruption where rather than like just a few cells in a little clump, you have some cells in a line. And then what ends up happening is as those cells are all proliferating, they start to kind of like, you know, fan out and you get like, you know, all these almost like brain like patterns or crown like patterns. And. And so in a way, with faciation, it's called faciation, it's almost more visible. You can see it. You can envision a little bit more like, well, what is going on with cell proliferation when you have these disruptions? Just because the physiology of plants, you know, you don't have stem cells just stuck inside all of the tissues at the ends. Right. So I think it's a really cool lens to think about, you know, like, what happens with cancer. And they're also, because they're like, they're structurally beautiful, really. It's a way that I think we can engage with cancer that is emotionally more accessible and just has a framing that I think for a lot of people feels more inviting than other ways of thinking about cancer. And we actually created a garden here with crusted cacti to kind of teach about how cancer is this phenomenon that exists across life and so kind of cultivating it as a space for people to go to, to remember people who've been affected by cancer and, you know, using it as a way of thinking about how can we live with cancer as opposed to just like, fighting it. So, yeah, so I love, I love, you know, plant cancers and, you know, the. What they. What they do for us on so many levels in terms of thinking about, like, what cancer is, how it manifests. And, and with plants, a lot of times they can survive with these faciations. They're more vulnerable often than plants that don't have faciations. But if they're taken care of, they can thrive. And so, you know, there's just a lot of like nice metaphors there. Right. For thinking about how we can deal with cancer differently.
- [45:21]
A
Yeah, because I used to say this. Very stupid. This now sounds incredibly stupid to me. But I used to say that kind of plants don't get cancer because plants are cancer. And I think what I meant by that is that plants have a very flexible body structure which allows them to absorb, I guess, tumors or cancerous behavior in a more elegant way where it's less fatal to them. Or like more often you just. That they could just grow off in some direction and that doesn't necessarily kill the entire organism. And a plant can just like let go of part of its body, potentially kill off a particular trunk and then carry on if it's not working out. Is that kind of the reason why it seems like plants die less often of cancer? I mean, you were saying 30 to 50% of people will have cancer by the time they die. It doesn't seem like 30 to 50% of wheat stalks have cancer problems by the time we're harvesting them. I suppose maybe with plants that are that short lived, it's just like they haven't been around for long enough. But what about old trees? We don't see old trees dying this way. And I imagine it's something to do with the fact that, that cells move around less within plants. They don't have as much of an aggressive circulatory system and maybe also just that they can absorb the damage more flexibly.
- [46:30]
B
Yeah. So plants, totally awesome. Right. Like, they're just so cool. And we, you know, I think a lot of times we sort of are, you know, not just anthropocentric in terms of thinking about like how the rest of life works, but like mammalian centric and you know, a lot of plants, plants, there's a huge amount of genetic diversity that exists, like within them. Right. Like, different branches will be like really genetically different. You can have fruits that are genetically different from each other and you, you can get, you know, this process of natural selection really happening even like within a plant, you know, with different branches thriving versus others and. Yeah. And then like dropping branches and sometimes those can actually grow into new trees. I mean, the myology is just really different and yeah, it's just, it's so different from what, you know, what our sort of assumptions are as these, you know, like honestly, not very resilient organisms that we are, we think we're so awesome. But like, you know, I mean, with the exception of like Some, you know, fanciful Marvel movies, like we can't even regenerate a limb. You know, like, it's, we're, we're kind of pathetic. Yeah. It's embarrassing. Yeah.
- [47:41]
A
So.
- [47:43]
B
But yeah, I think, you know, that, that broader frame of, you know, just thinking about, well, how does life, you know, solve these various problems? How does life, you know, adapt, you know, during, like, how do some organisms adapt during their lifetimes? Like actually genetically adapt, not just behaviorally adapt. I think that, that expanding that frame is not just like, really important for how we look at and think about biology, but it's also really fun to like, know these things. Right? To like, be like, oh, wow. Yeah. That, you know, that plant is got, you know, all of these unique, you know, mutations in, you know, different branches potentially that could lead to differential survival and reproduction. It blows my mind. And of course, many, like, it's not like all plants are the same. Like, there's all sorts of different ways that different plants work and different ways that their, you know, reproductive systems work. So, yeah, there are, there's, there is so much. And I'm no plant expert, I'm just a, I'm just a fan. So.
- [48:51]
A
So, yeah, another fascinating thing in the book. Elephants have way more cells than humans and no surprise there, I think it's like 100 times as much or something. And yet they get deadly cancers less often than we do. And then that's super counterintuitive on its face because you'd think that the probability of you developing a seriously, a seriously dangerous cancerous tumor would be roughly proportional to just the total number of cells you have because each one of them has an opportunity to itself become cancerous. Yeah. Why is it that elephants don't get cancer much more than humans?
- [49:21]
B
That's a great question. And you know, again, we have to think about definitions here. Right. So because a lot of, a lot of elephants actually have growth, have tumors, are just not, you know, metastatic and cancerous and they don't, you know, threaten their, their lives so much. But to kind of get back to your, your main question about, you know, why. Why is, you know, an elephant less likely to die of cancer than we are or than a mouse is? Right. That's, I mean, that's a big contrast. And that, you know, to think about sort of, you know, those, those big picture issues, we have to consider that there's different selection pressures on organisms that are long lived and large versus short lived and small and, you know, long lived large organisms. They have to invest a lot more in what we call somatic maintenance, which is just like a fancy way of saying like fixing your body and making sure that like the body maintains itself well. So in order to have a chance at reproduction, a large long lived organism needs to, to be doing a lot more, you know, cellular things to take care of the body, including DNA repair, you know, monitoring for cellular cheating and all of that. So organisms that are larger and longer lived more robust cancer suppression mechanisms than organisms that are smaller and shorter lived. And, and you know, this ties in with an idea in evolutionary biology called life history theory. Whereas basically.
- [50:59]
A
Yeah, yeah. Can you explain that for a bit?
- [51:00]
B
Yeah, yeah, sure. So you've probably heard the phrase like live fast, die young, right? Like it's, you know, it's something, it's kind of part of our collective consciousness. Right. There's this idea that you can kind of like have a strategy of, you know, like living for a long time and living slower or you could like live fast and you know, potentially burn.
- [51:20]
A
Out, plan for the long term.
- [51:21]
B
Yeah, that's right. And so there's a sort of version of this that just applies to like all life that evolves, which is the organisms, you know, in general have trade off, trade offs between surviving and you know, taking care of their bodies, maintaining their bodies and reproducing. And so depending on whether an organism is prioritizing survival or reproduction, that's, that's going to change how um, their you know, physiology and behavior, um, manifest and it, and it can have a lot of knock on effect effects then that are self reinforcing. Right. So, so, so basically, you know, a mouse is a fast life history strategist. We would say it's you know, invests in, you know, becoming reproductive quickly, having lots of offspring and doesn't invest a lot in its soma, in its body and you know, things like cancer suppression. An elephant on the other hand, you know, grows big, grows relatively slowly, has fewer offspring, but invests a lot more in each of them and does a lot more somatic maintenance. There's a lot more taking care of the, the body itself, which is, is necessary if you're going to be able to stick around long enough to successfully reproduce. If you're a slow life history organism.
- [52:48]
A
Yeah, I kind of like to picture life history imagining evolution kind of embodied in these engineers or something who are standing around kind of chatting about the animals. They're going, and one of them's like, I got this great idea. It's going to be called an elephant. It's going to be massive it's going to be this huge organism. It's going to have no predators because nothing's going to be able to eat it or beat it. And it's going to be able to reach up really high in the trees, get all this energy. Imagine another engineer being like, that's never going to work. It's going to have way too many cells. It's going to have cancers all the time. What are you thinking? You're an idiot. And the other engineer says, no, I've thought about this. What we're going to do is we're going to invest a ton of. Okay, yeah, all right. It's got all these benefits, and all we're going to get is we're going to invest a ton of energy and molecules in making sure it doesn't get cancer. So we're going to have real, like, trip wires everywhere. So any cell that seems to be acting out, we're gonna. We're gonna shut it down right away. And, okay, this is gonna. This is gonna slow down the growth. We're gonna have to. It's gonna have an overhead, all right. But at the end of the day, we're gonna have this massive elephant. It's gonna live for ages. It'll be able to have lots of. Lots of babies because it will live long enough. You can imagine. Yeah. And then you could do the opposite with a mouse, basically, where you're like, okay, forget it. We're not going to worry about the body. It's just going to replicate like crazy. Is this basically the idea?
- [54:03]
B
I love this. And I mean, you're just like, being like, the adaptationist engineer right now. You're like, all right, how are we going to design this thing for this function or that function? And, yeah, I think it's a great cognitive tool to use to just, like, wrap our minds around. Like, how are things going to evolve given constraints and, you know, what kinds of adaptations would we expect, given that you want an organism to be able to do this thing or that thing. Right. So. So, yeah, I think, you know, the engineering metaphors are right on for thinking about, you know, how do organisms evolve to, you know, maximize that combination of survival and reproduction that, you know, that whatever the. That combination is that they're sort of, you know, aiming for or choosing. Again, I'm using scare quotes just because, you know, we're using this, like, as if intentionality as a shortcut for thinking and talking about something that is a long, complicated process of natural selection acting on all these, you know, mechanisms. But. But we can Use this cognitive shortcut as long as we, we acknowledge it's a cognitive shortcut.
- [55:09]
A
So, yeah, I just remembered in, in our annual feedback for the show, there's one person who wrote in their feedback everything Rob says about evolution wrong. Unfortunately, I didn't elaborate on that. So I don't know. I can only imagine this. This poor soul is just hating this episode. If you actually, if you manage to stick with it long enough, please, please email me and tell me what I've been saying wrong about evolution on the show. I would, I was, I was, I was very curious anyway, continuing with maybe wrong things. What is the.
- [55:38]
B
I think we're pretty good. You know, we just need like the right caveats in there, you know, so I think, I think we're good.
- [55:48]
A
I guess I slightly went over quickly what the downside is of having this slow life history strategy and these and like a very large scale. But I guess so. One thing is if you're going to lower massively the probability that each cell becomes cancerous or dangerous tumor, which you have to do, if you're going to have lots of cells, then you literally just have to invest in a lot more proteins to do the monitoring. You have to do a lot more double checking every time you duplicate replicate the genome to make sure that even fewer errors are getting through. Are there other downsides like that that people should be aware of.
- [56:22]
B
Other than the sort of cellular bureaucracy that you have to deal with? Like if you're in elephant, it's like, oh, can I do this Byzantine?
- [56:30]
A
Yeah, it's like this Byzantine thing that you have to go through to get permission to do anything.
- [56:33]
B
Yeah, I submitted the request three weeks ago. What's going on? You know, can I please divide now? Yeah, I mean, there are all sorts of trade offs. I mean, like the, you know, basic principles of sort of like, you know, thinking in evolutionary terms is that, you know, there, there are going to be trade offs. If you want to, you know, divide quickly, then, you know, you have to deal with the potential of having more mutations. Right. And so then if you don't want to have that trade off, like if you, you can be stuck up against the fact that, well, there's actually physical constraints to, you know, if you're going to divide and check the DNA, that takes actual time. Right? Yeah, so, so, so, yes, you know, you can make more, you know, proteins that monitor things. You can, you know, even try to get as much friction out of the system as possible. But eventually, you know, there are some trade offs that you just can't escape once you, you know, get to a certain point when a lot of things have already sort of been optimized in terms of, of getting those systems functioning efficiently.
- [57:48]
A
So one time that you need to have cells divide quickly is when you sustain an injury, say a skin injury, and you need to grow that back. Or I suppose our intestines are constantly sustaining a bit of damage and they have to really have pretty rapid cell turnover in order to fix that because they're just exposed to a lot of tough situations. Is it because elephants, if they sustain a couple cut, the cut doesn't grow back so quickly? Or maybe their, their cell turnover within their stomachs and intestines isn't, isn't as good as it is for, for humans.
- [58:18]
B
Yeah. So, you know, I, I actually, I'm not sure how systematically that has been measured in elephants, but, but there is a, a general set of trade offs with, for example, wound healing and cell turnover and, and cancer susceptibility. So you know, anytime you have of a cellular system that, I mean, so if we think of an organism that can heal a wound quickly, right? What's going on there? Well, the process of wound healing requires cells to be proliferating quickly and to be moving to close that wound. And it's good to be able to do those things quickly. Right. Because if you don't, you're more likely to get an infection. You're more likely to, you know, have your, your ability to do things impacted. Right. If you, if you heal less quickly. So there's a lot of benefits to, to being able to close a wound more, you know, rapidly than, than not. But if you do that, you also have cells that are, you know, more likely to be on a hair trigger for increasing their proliferation and moving if the environment is like, you know, suggest that there's a wound. And so, you know, one of the things that, that you actually sometimes see in tumors is that the physiology inside the tumor kind of looks like a wound that doesn't heal. You know, we have like a set of buttons, the levers, right, that can kind of get pushed and that leaves us susceptible to cancer. And so, you know, the, the more rapidly your wounds can heal, potentially the more susceptible, you know, those organisms to cancer because the cells are sort of erring on the side of being able to heal wounds quickly so that they are less likely to die of infection, less likely to have functionality impacted for as long.
- [60:22]
A
Yeah, one thing we maybe skipped over a little bit quickly is with, so with a mouse, say it could invest more effort in ensuring that there's no mutations in its genome when its cells replicate. And that would have a long term benefit where potentially for then as long as the organism lives, it has avoided those mutations. The problem is as a mouse, your odds of being predated, your odds of being killed in the environment are really high. So why would you want to be planning for years ahead when you're unlikely to survive that long anyway? Or at least the odds are far lower for a mouse than an animal elephant and that fact that you might well die of other reasons anyway. So let's not think about the long term. That then greatly reduces the evolutionary pressure in favor of maintaining, building, ramping up these anti cancer measures because they just don't carry as much importance because you'll probably be dead before too long regardless.
- [61:17]
B
Yeah, absolutely. That's a really important part of life history theory, which is what are the selection pressures that make it more likely that an organism is going to evolve to be a fast life history strategist versus a slow life history strategist and having what's called, you know, high extrinsic mortality. Right. Like having the chance that you will die from something random in the environment. If that's high, then the, the organisms will evolve to invest less in somatic maintenance because could just be gone like, like that. So you know, versus situations where resources are a little bit more stable and you get selection for slow life history strategies.
- [62:00]
A
Yeah. So yeah, I think we've now had enough background to ask this question. There's a whole lot of people who are working on trying to extend human life and slow down aging. And I guess as part of that they're going to want to ramp up these mechanisms, these anti cancer mechanisms that we have in order to prevent us from developing these cheating cells that create problems. And potentially I think there are avenues to do that. There are people that thinking about other drugs that we can do to basically ramp up these, to give greater intensity to these existing processes that we have to try to prevent cancer. But it sounds like in so doing we would produce some problems. For example, if we did manage to try to reduce aging and extend human lifespan this way, would our injuries heal less quick? Would we have to be more careful about, you know, anything that went wrong in our intestines? Because there's the cell turnover wouldn't, wouldn't be what it was.
- [62:54]
B
Yeah, there's potentially a lot of, you know, inadvertent trade offs that, you know, could arise. There's also, you know, a sort of tough bind of like you Know, if you want to extend life by reducing the risk of cancer and you interfere with things like cell proliferation and you know, the sort of rejuvenation of tissues that stem cells help us do. Right. It's like, well, how do you have your evolutionary cake and eat it too? You know, how do you both, like, you know, make sure that the organism is, you know, renewing itself properly while at the same time not allowing that renewal capacity to get hijacked by, you know, agents that could. Yeah, yeah. So, you know, and, and this is part of why, you know, cancer is such a tricky problem is because you run up against all of these trade offs and you know, if you, you know, you think you've got it like cornered over here, but then, you know, you've got like all these things happening over here, so you're like, oh wait, no, I got to get over here. So it's, it is a, is a slippery thing to think of, you know. Okay, well, you know, how would we, we, how would we eliminate cancer? And what would we lose if we try to eliminate cancer? Right. So it, it's, there are a lot of trade offs and, and we're not going to get around that because cancer is a susceptibility that is just built in to being a multicellular organism. You know, we can, we can evolve a lot of mechanisms to detect it, to respond to it. And those, you know, systems can evolve to be pretty good in terms of, of, you know, the efficiency and, you know, reducing side effects and trade offs and things like that. But there are fundamental trade offs that we can't escape.
- [64:44]
A
Yeah, yeah. I mean, I don't want to suggest that there's no way that humans could be better from our well being point of view. Because I mean, to start with, elephants exist. They have a much lower rate of cancer per cell than we do, at least dangerous cancer per cell than we do. And they are a functional organism. So there are directions that you can go here that aren't an engineering dead end. I suppose it's just that we probably would face some other trade offs and we might have to try to compensate for the problems that we might be creating elsewhere. I suppose if you were trying to do this from birth, then one issue that we haven't talked about is that you might grow a whole lot slower because a baby growing is closer. Its cells are behaving more closely to cancer than an adult's cells when they're just in maintenance because of course they're proliferating all the time. The message is get Bigger. Get bigger.
- [65:28]
B
Yeah, yeah. I mean, the better a job that you want to do at sort of avoiding these trade offs, also the more complex all the system to be, which then in itself creates vulnerabilities for the system to be more hijackable. So, you know, like, there is a lot that, that, you know, can potentially be done, but, you know, like, how, how good are we going to be at anticipating what the, you know, side effects are going to be and, you know, making sure that those are trade offs that we want to make for ourselves or for, you know, the next generation? I think, you know, there's. There are a lot of, of issues that we definitely should be thinking about and grappling with. You know, when, when, when we think about, like, you know, when we think about cancer and the future of cancer, because it's not as simple as just, you know, oh, what's the magic bullet to make cancer go away?
- [66:18]
A
Cancer signal, right?
- [66:20]
B
Yeah. Yeah.
- [66:22]
A
So a new thing. Because cancer, cancer cells, they're cheats by nature. They're cheating on the cells around them in the organism that they're a part of. But that presents them with a problem that how do they coordinate among themselves? Is it possible to maintain honor among thieves, so to speak? To what extent do cancer cells figure out a way to cooperate among themselves or are they all kind of stabbing one another in the back as well?
- [66:44]
B
Well, you know, anytime you have the conditions that will select for cooperation, like, you can get the evolution of cooperation. And so, yeah, on a first pass, we can think of cancer cells as cellular cheaters. But if they're in a situation where, where, you know, they can produce growth factors not just for themselves but for their neighbors, then, you know, especially if you have, you know, clones, right, you have the same genetic lineage, very easy to evolve, you know, this sort of cooperative trait of producing growth factors that, you know, promote the growth of the cells around as well. You can also get, you know, division of labor, right? Like some cells specializing in. In producing growth factors, other cells specializing in evading the immune system, even other cells specializing in reproduction, right? So there's, you know, there's certain kinds of cancer cells. We call them cancer stem cells because they, you know, they're the ones that replicate. And there's a lot of cancer cells that don't. And, you know, one potential explanation for why that is the case is because you have a sort of proto multicellularity almost going on where, you know, some cells, cells can be specializing in the reproduction side of things, and other cells can be specializing in you know, doing all of the things to help that little, you know, cluster of proto. Multicellular cancer, cancer protoplasm, like, you know.
- [68:08]
A
Yeah.
- [68:09]
B
Get around and, and replicate. So it's, I think once you have.
- [68:14]
A
A cancer, though, that has developed this level of cooperation, because. So cancer cells are kind of always one step away from, from wanting to defect on the cells around them because kind of their nature. What does it look like when cancer gets cancer and like, does, does that happen very much?
- [68:30]
B
Yeah, well, so this is sort of the, you know, idea that like you can have like a hyper cancer or like a meta metacancer. Right. And I think, you know, in, in practice. Yeah. Anytime that you have cooperation, so you have a cluster of cells that are all, you know, know, producing growth factors. You know, if you get a mutant that stops producing that growth factor, they can potentially gain an advantage as long as they're in an environment where growth factors are being produced. Right. So. So whether or not you get the evolution of cheating or the, you know, extended evolution of cheating is going to be dependent on, you know, being able to sort of maintain a population of entities that you can keep exploiting. Um, so there's, you know, I think there, there are some barriers to like, you know, cancer cells even kind of getting, getting to the point where, where you would have the evolution of sort of like hypertumors or hyper cancers just because constantly, sort of at every stage, you know, you have cheaters that like, you know, emerge and are sort of getting purged because of the population structure or, you know, other factors. Yeah, because I mean, the thing is like, yes, within any group, right. The cheaters are going to do better than the others in the group. But once you expand your frame and you realize, oh, there are multiple groups, this is like a meta population. Some groups are more stable than others. Right. And the groups that are more stable than others tend to be the ones that are more cooperative. Then, you know, that actually really changes the dynamics a lot and makes it so that cooperation can be favored. You know, so, so on this model.
- [70:12]
A
You'D expect like a lot of. You'd expect, you know, a tumor to grow and then kind of collapse as it's undermined from within, but then another tumor to grow because they figured out that they're still cooperating for now, and so they take over and it will be like quite a dynamic situation. Is that accurate?
- [70:26]
B
So you can get dynamics like that happening with the blood supply to tumors. So, you know, basically, you know, the cells can be signaling, you know, for more, more resources Sort of opening up the taps right from the, from the circulatory system. Yeah, Know, and as that happens, actually, you know, it's very similar to what, you know, like a irrigation system where the upstream individuals, if they open up the taps all the way, you know, they're depriving the downstream individuals. And you know, actually you can also get the collapse of the sort of infrastructure because if all the taps are opened up, then you don't have enough pressure inside the vessels to maintain the flow. So, you know, you, you can get this sort of like, you know, collapse. It's like civilizational collapse. Right. Because of basically exploiting of the, the commons. You know, there's like not, not a good resource regulation set of mechanisms there. So that kind of dynamic does happen. And, but, you know, there are a lot of other places where you can, you know, get the evolution of, of cooperation and cheating. And you know, honestly, to me, the scariest thing about cancer is the cooperation side. And I think that, you know, we've talked a little bit about this, you know, kind of like working from first principles to, you know, make some predictions. And I think if, you know, if we look at this from a first principles kind of perspective, it's quite likely that early on in the dissemination of cancer, so you have a primary tumor, but then you can get metastasis, which is the real problem in cancer. Usually it's the systemic dissemination of these cells. I think it's quite likely that by the time you have a metastasis that is visible in any sort of screening, that very often that might have really come from a long lineage of clusters of cancer cells that were sort of selected on the basis of being already able to cooperate effectively in order to extract resources, reproduce and, and move. So yeah, my colleagues and I have written about this some, and I, you know, I wrote some about this in, in my book, but I think it's, it's one of the sort of most neglected but most important evolutionary dynamics and evolutionary processes that you know, is going on in cancer. Potentially going on in cancer. So, you know, when we look at, when we look at metastasis, we might be looking at something that is actually the result of, you know, many, many, many generations of selection on group level phenotypes of cancer cells already. So, so, so that's something that.
- [73:30]
A
I think it's a very evolved beast.
- [73:32]
B
Yeah. So I think that requires a lot more attention. Um, that possibility requires a lot more attention than it has had up until this point because it has, you know, very different implications for how we might be treating metastasis. Right. If it is the result of many generations of selection on a collective phenotype or set of collective phenotypes.
- [74:00]
A
Yeah. One really mind blowing thing in the book is I remember I was on the tube when I was listening to this and I thought I knew the answer to it and then I was completely wrong. So basically you set up in the book that we have this gene and this I guess, set of processes that will occur, I guess the TP53 gene, which collects a lot of information about what's going on in the cell and in the local environment in order to decide whether the system cell should commit suicide. And so it's trying to look for funny business and see if A is wrong and B is triggered and there's also X, then okay, then we're going to shut down this cell. We got to shut this down because it's too high a risk that I've become cancerous now. Now the interesting thing is that because so much work is being done by this1tp53 gene protein and general system system that creates a single point of failure where if you have a really destructive mutation in the TP53 gene such that it cannot function anymore, then your chances of that cell becoming cancerous go way up. And so you might think, why wouldn't you have a more robust system where rather than put so many of your eggs in one basket, why not have lots of different processes going on at the same time, all independently deciding whether something has gone wrong and the cell should commit suicide slash apoptose. Now think, think, think about audience like why, why do you think it is that the cell puts so many eggs in one basket?
- [75:30]
B
So two things. So one thing is there are a lot of, there are many different processes that are all sort of going on. It's not just TP53, but it is the case that, you know, like you said, all of this information is kind of flowing through, you know, TP53. And that's the case for many of these other systems where, where, you know, there is sort of one, one point where if you break that point then the whole system can, can get messed up. And yeah, so then the question is why, you know, why have that sort of, why have everything flowing in to one spot and then flowing out? And one, one potential explanation for why this is the case is that, you know, in order for a cell to really sort of figure out, out if there's a problem or not with the cellular behavior, it needs to integrate information from many, many different sources. So, you know, for example, earlier we were talking about, you know, wound healing, right? So, you know, it would be important to know, right, if the reason that the cell is proliferating and moving has to do with being in an environment where that's actually what is beneficial for the organism. Right. Is this a wound healing situation or is it not? And in order to be able to integrate information from all those different sources, at some point it all has to come together. And so you can potentially have, you know, these sort of points of vulnerability because you need to integrate information across a lot of different domains, I guess you could say, in order to actually sort of make a smart decision, you know, in, in, in scare quotes, right. So for the. Because it, it has a very different meaning, right? You could say for a cell to be proliferating and moving if it's in a wound healing environment versus if it's in a normal tissue environment. So the downstream consequence of what should happen is going to be different in those two cases. Cases.
- [77:37]
A
Yeah. Maybe an analogy would be if you had a really big company and the CEO, say at the end of the year, has to decide, should this company expand or should we make layoffs, should we be growing or shrinking? You might think, well, that creates a single point of failure where if the CEO has bad judgment, then this is going to really mess things up. Why don't we have two different people who each only look at half of the information from the organization and then if either one of them thinks we should expand, then we'll expand. You can immediately see the problem there, that if they're doing this stuff independently and they're relying on different information rather than just duplicating it, then they're blind to half of what's going on. And that's going to potentially make their decision making a lot faultier. But elephants have lots of redundant copies of this TP53 gene or something like that, right?
- [78:22]
B
Yeah, some of them are not functional, but yeah. So you, you can get, you know, genomes with multiple CEOs, I guess you could say. And, you know, but then the question is, you know, what happens with those over evolutionary time? Do they continue to process the same information? Do they differentiate into, you know, processing sort of different streams of information? And, you know, and I mean, I like thinking about it in these sort of information processing terms more generally because, you know, I think that we, we tend to sort of look at the cells in our body as like, you know, oh, they're just like, you know, blobs of biological stuff, but actually they're computational systems that are taking in, you know, huge amounts of complex information, processing it and then changing, you know, gene expression as a result. And every one of our 30 trillion cells is doing it every millisecond. Right. So it's, it's mind blowing. And I think it, you know, it forces us to consider possibilities for the kinds of things that might be going on in our bodies that we might otherwise think of as, like, impossible or, you know, anthropomorphic. But no, because there's actually a lot of information constantly being processed by every single cell.
- [79:44]
A
It is quite funny that I feel like I couldn't consciously do the mental work that even a single cell in my body is doing. Absolutely.
- [79:51]
B
Yeah.
- [79:51]
A
There's so much information processing going on that. Yeah, it's, It'll. But it all has to be this automatic mechanical thing rather than something that's conscious.
- [79:58]
B
Yeah, yeah.
- [79:58]
A
You think that it might be the case that the human body sometimes opts to produce not very dangerous tumors in order to kind of crowd out the appearance of more dangerous tumors. Yeah. Can you explain that?
- [80:08]
B
Yeah, yeah. So, I mean, whether you want to call it like a tumor or not depends on, like, how scared you are of the word tumor. Right. But I do think that there are situations where if there's a mutation or there's sort of a disruption in the sort of local environment in a particular spot in the body, that it, it can actually, you know, there's a situation where it can make sense to have a clone proliferate that doesn't have a high chance of going on to be cancerous so that it can take up that ecological space. So, you know, wound healing would be one situation where, you know, perhaps it's. It makes sense in some contexts for cells to take over those sort of, you know, open ecological spaces that are good at replicating quickly, perhaps because they have some mutations that might, you know, in some cases be associated with cancer, but are. Are less likely to actually create more vulnerability in the medium term or, or long term. And so, yeah, this is, you know, it's a. Yeah, I think it's, it's a counterintuitive idea. But there's, you know, there's some evidence that, you know, you do have these sort of, you know, hotspots for mutation where, you know, if, if you do get a situation like a, a wound, it might be more likely that you get a mutant arise that sort of allows for, for that quick proliferation, but doesn't create other vulnerabilities that you might get if it was just sort of any random mutation that could confer some selective advantage for the cells.
- [82:01]
A
Yeah. One question I'm going to skip over, but I'll tempt people to buy the book by teasing them with the idea. So think, if you can, of what would be the benefit of treating a cancer patient with a chemical that has a similar structure to chemotherapy but isn't toxic at all, how that might help. And if you want to know the answer, you could go buy the Cheating Cell. Go buy the Cheating Cell in all good bookstores. In the book, you suggest that cancerous tumors are more likely to evolve, to spread, to metastasize to the rest of the body when their local tissue environment seems like it's running out of resources or its access to energy and resources is very volatile. But I would have thought naively that these mutations that foster travel to the rest of the body would arise kind of just randomly in proportion, basically just to the number of cells that are present in the tumor. Am I missing something about the evolutionary process here?
- [82:59]
B
Well, I mean, you're absolutely right that the population size is critical for sort of what's the likelihood that you'll get the emergence of a mutation that might affect any aspect of physiolog. Um, so if there's smaller population sizes in, you know, regions where there's lower resources, that, that's gonna certainly affect the likelihood that a mutation would. Would arise. But then the question is if you have a mutation that affects movement and, and that could be a mutation that actually just affects even the threshold for movement that the cells have. So they can be, you know, more or less likely to move given, you know, a certain level of resource sources. So once you have any mutation that affects movement or the likelihood of movement, then it's more likely to get selected because of the fact that only the individuals who are leaving that depleted environment. Yeah. And getting to a new place, even if it's nearby. Right. That they're going to have a selective advantage. And so, you know, so it really, it's not so much about overall the environment being depleted. It's more sort of about the patchiness of the resources that, like, you know, if there are situations where, you know, it could be really bad, you know, in one little area and then very close by it's good. Then, then you can start getting the evolution of these motile phenotypes, which then once you have them, has implications for sort of, you know, what, what's going to happen in the, you know, greater system of the body. And over the longer term. So, so, so, yeah. So the idea, you know, in this model that I made with some of my colleagues to explore this, you know, our conclusion is basically that you can get, you know, the evolution of dispersal. Right. Based on having sort of patchy resources and you know, locally, you know, at least in a small environment, lower resources, sources, and that this suggests that you almost kind of might have like the pre. Evolution of these cellular abilities, these adaptations for, for movement and for conditional movement that, you know, appear in a. In a sort of different way later with metastasis, you know, but that there's. There may be a sort of continuity there in terms of, you know, having how those abilities sort of start to evolve just in a local tumor environment before you see invasion, before you see things like metastasis.
- [85:47]
A
Yeah. Well, let's talk now about some potentially surprising or counterintuitive approaches to managing cancer that maybe jump out of this more evolutionary understanding of what cancer is and why it exists and why it gets worse over time. Time. I guess one thing they talk about in the book is the possibility of not trying to kill a tumor, but instead taking an approach like a more subtle soft approach where you just try to manage its behavior. Can you explain that whole approach?
- [86:17]
B
Yeah, well, so the approach I think you're referring to is adaptive therapy, which was really kind of proposed and brought to the fore by Bob Gatenby from Moffitt Cancer center in, in Florida. And the main idea of this is that if you try to treat a cancer with high dose therapy with the approach of trying to eradicate it, you can inadvertently select for the cells that are most resistant to the therapy. So this is akin to, you know, what happens with the evolution of resistance to like pest control and you know, antibiotics. Yeah, yeah. So, you know, if you high doses and you know, for a long time, you're actually applying the strongest possible selection pressure to favor the cells that are resistant. Right.
- [87:16]
A
And because all of the other cells will be dead.
- [87:19]
B
Exactly. Yeah. So the only cells that survive are the ones. Ones that can survive in the presence of the drug that you're trying to use to get rid of the tumor. And so then the question becomes, well, you know, well, what's the alternative then? You know, like, you know, and, and if you accept that for certain kinds of tumors, at least, especially if they're advanced. Right. And are likely genetically diverse, they probably already have resistance mutations, um, then you kind of have to, for a certain class, I'm not going to say for all tumors because there's some where yes, you can get rid of them with standard chemotherapy, but there are certain classes of tumors for which, you know, the sort of logical approach is to look at it and say, okay, it's unlikely that this could be eradicated with high dose therapy. So we have to sort of take as, given that this tumor is going to stick around, around. So what kind of tumor do we want to cultivate? Right? And you know, well, what you want is a tumor that's going to respond when you treat it, right, that's going to be controllable, that's going to not become invasive and metastatic. One that's, you know, not going to disrupt the life of the, you know, person who harbors it as much. Right. So, you know, you can, you can then approach it from this perspective of like, well, okay, given that it's going to stick around, what are the priorities? And so the approach of adaptive therapy is really that, you know, you, you start by giving a dose of the drug to kind of get the tumor to a smaller size so that it's, you know, like a little bit more manageable. And then you only treat it when it's growing, growing, and when it's not growing, you let it be. And the idea here is that, you know, there is, there's usually a cost to resistance to drugs because it, you know, there's, it takes energy for cells to pump up, pump out drugs from the cell or you know, do other things that, you know, can confer resistance. So that means that when you're not applying the drug, the cells that are sensitive to the treatment, treatment are going to be more likely. Yeah, they're going, they're going to have an advantage over the cells that are resistant. And so, you know, you, you, you kind of manage the drug or manage the tumor by treating it when it's growing too much and then you back off. So then, you know, you can get more of the sensitive cells there. And, and you know, patients are able to live for much longer than expected with these, these kinds of treatments. When, you know, in the clinical trials that have been done, there's, it's, it's, there's ongoing work. You know, there's a lot more work to be done. But the clinical trials that have been done are really promising. You know, even with late stage cancer.
- [90:24]
A
Yeah, it's one thing that happens. So if the, so you use, use some chemo, you get the tumor to shrink somewhat and then you wait until it starts growing again and then I guess you've got the evolution of some more grow Some more pro growth cells inside it and then you treat it again. And I suppose the cells that are growing proliferating more quickly, they're probably more vulnerable to the chemo because they're kind of there, they're at their like, metabolic limits trying to, trying to grow. And so they get disproportionately killed. And so what you're left with again is the less grow, less, less pro growth cells in the tumor. And then you hope that that will. Then they're just going to lie low for a little bit while you don't use the chemo.
- [91:00]
B
Yeah, that's, that's another one of the, you know, hypotheses that I have about what, what's going on with adaptive therapy that you know, it might not just be. Be about, you know, allowing sensitive cells to, you know, grow back, but also that, you know, every time you treat a tumor, conditional on it growing, you're going to be, you know, essentially able to target those cells that grow more because not only will there be, be, you know, more of them, but they're going to be more vulnerable because they're, you know, in, in that state of. Yeah, dividing and you know, doing. Doing that, that life history trade off of investing in the, you know, reproduction over the survival. So, so yeah, it's there. There are a lot of potential mechanisms that, that could be underlying that is.
- [91:55]
A
Adaptive therapy getting applied in more, more places now like try it on a larger scale, I suppose. And I imagine it was initially trying to trialed in cancer situations were that were most promising for it where the existing more aggressive treatment wasn't working very well. And so people are looking for alternatives. I wonder. Yeah. Are people trying it in a wider range of situations now as well?
- [92:17]
B
Yeah, I mean there, there are a lot of efforts now to, you know, start clinical trials with adaptive therapy. A lot of that has happened at the Moffitt Cancer center, you know, where Bob Gatenby is and you know, he's developed a lot of collaborations there. There's, we have some efforts going on here as well to test adaptive therapy in some mouse models, but also, you know, trying to actually, you know, start some clinical trials with breast cancer patients. But there's unfortunately there, there aren't a lot of like economic interests in the private sector that are aligned with adaptive therapy because, you know, there's patent.
- [93:01]
A
The idea of giving someone less medicine.
- [93:03]
B
Yeah. And it's, you know, it's an algorithm. Right. For treatment. It can be used with any drug or approach really. I mean, you have to sort of figure out how to, how to use it. But the, it's an idea, you know, it's a, that can be computationally instantiated and might be a little different, you know, in different systems. So you know, it really relies on having funding from know, agencies. Yeah. NIH and well actually NCI National Cancer Institute, which is, you know, within there. But you know, there's a, and there, I mean there is funding that is happening. There are, you know, clinical trials going on. But it's, there need to be more, you know, and there we need to think about, you know, how can we facilitate, you know, these, these kinds of approaches that frankly are, are, they're cheaper, they're easier on patients and they're probably, I mean not probably. They're definitely a lot more exportable to countries where really expensive chemo, you know, with intense monitoring and testing and all of that isn't as much of an option. So I think there's a real, real opportunity to, you know, to think about how we can take these sorts of approaches to bring at least, you know, some, some management of cancer to places where expensive methods and drugs are just not an option.
- [94:35]
A
Yeah. Some other evolution inspired treatment ideas that you talk about in the book. One is to give kind of a local tumor a constant supply of food and resources with the kind of aforementioned logic that if the tumor is, if the cells that are just doing best are the ones that stay put in a particular given location, then you're not selecting for ones that are, that are likely to move. That one says a little bit crazy to me because it also feels like you're still feeding the tumor, you're still feeding the cancer. It seems like it's going to be a double edged sword.
- [95:06]
B
Yeah, yeah, yeah. I mean I think it's, it's obviously something that, you know, like there are caveats there. Right. Like maybe you would want to be feeding it and then treating it with adaptive therapy, for example. Right. But if you're, if you're feeding it, then you're reducing the selection pressures on the cells to disperse. Which if you're trying to prevent the evolution of invasion and metastasis could be a good strategy. So yeah, you know, if you start applying these ideas from ecology like dispersal theory and you know, theories like life history theory and you know, thinking about, well, you know, how do we affect the parameters of natural selection? You know, you think of all of these things, it opens up, up this, this creative space for thinking about new strategies for controlling cancer and then, you know, potentially combining them in ways that you Know, allow you to, you know, prevent the things that you don't want and cultivate the things that you do want. I mean. Yeah, so, but. But it is really. It really is. It's a mental shift to thinking, okay, well, how do we live with cancer? You know, and I think a cross species perspective is useful not just because we can learn things from other species about how, you know, they suppress cancer or, you know, deal with it, but also because it, I think, forces us to just think more broadly about the fact that living with cancer is the norm for multicellular life. And so, you know, if we can be more deliberate, it about using, you know, our, our technology and our abilities to, you know, gather information, process it ourselves, right Then that opens up a whole new space for, you know, treating and preventing cancer differently. That, that leverages, you know, the, the brains that we have here and the network brains that we all have, you know, and, and all of the, like, real, really rich theory that's been developed in evolutionary biology and ecology, you know, over, you know, the decades, centuries. Yeah, yeah.
- [97:23]
A
Another one you mentioned is using kind of chemicals that might disrupt the signaling and the ability of these cancer cells to cooperate and collaborate with, with one another, which, which makes intuitive sense. Another one that I was amazed by is obviously would be helpful if we could reduce the rate of evolution among, among the cancer cells. And one way to do that would be to reduce the rate of mutation, the ongoing rate of mutation within these cells so they can't change as quickly. I think you were suggesting that was it aspirin or NSAIDs, you know, Panadol, paracetamol, acetaminophen, that they could really reduce the rate of genetic mutations within cancer cells. I remember the amount. It seemed like it had a large effect and like a crazily large effect.
- [98:02]
B
Yeah. So I think there's been some newer studies on this too that I think maybe challenge that effect was. But the, the original studies that were done, yeah, they, you know, it basically looked like, you know, people who were taking these NSAIDs had lower likelihood of progressing from this early cancer like state called Barrett's esophagus, where, you know, you have sort of what's called dysplasia, where, you know, cells are in the wrong places and growing, you know, in ways that they shouldn't in the esophagus, lower likelihood of progress to cancer. And that seemed to be related to a, you know, decrease in mutation rate that was associated with a nsaid. So, you know, it may be that, you know, because of sort of evolutionary Mismatch. We have just higher inflammation than, you know, is. Is ideal because of, you know, toxins or, you know, exposures to more pathogens, you know, things like that, that, that could be kind of kicking our body into a, you know, a state of inflammation because, you know, inflammation is another situation where, you know, there's trade offs. Right. It's like inflammation. Yeah. Maybe it's less likely that you'll have, you know, acute problem with the pathogen, but you're creating an environment that's, you know, potentially more pro cancer because it's basically being more permissive signals.
- [99:25]
A
Right?
- [99:25]
B
Yeah. Cells doing things that. Yeah, could.
- [99:29]
A
It wouldn't do in maintenance.
- [99:30]
B
Yeah, yeah, yeah.
- [99:34]
A
Cool. Okay. Let's. Let's push on from cancer a little bit and think about other, other levels of cooperation. So on this show, because we're not a medical show, but we're probably closer to being a social sciences show where maybe more interested usually in cooperation between people and cooperation between countries and societies and so on. So, yeah, I'm kind of curious to explore whether we can use any of the ideas and frameworks that we've been using to discuss cancer to think about cooperation between people. This could be a slightly futile effort. I haven't writing these questions. I wasn't always fully on board with the ideas that I was putting down. But I'm curious to see your take on them. One thing I should say up front is that here we are going to be drawing analogies between behavior of people, cheating behavior of people and cheating behavior of cells, which in this case means cancer. So we will in some sense be drawing an analogy between the behavior of people and cancer, which is slightly, I don't know, it seems like a little bit offensive. I think if you ever caught some individual cancerous, that might be a little bit offensive. But we're here at the ideas level. We're looking at level of abstraction, of cheating and cooperation and so on. So hopefully, hopefully listeners will let us get away with that. Yeah. What are some ways in which humans defecting against organizations or groups of friends or their societies can be structurally similar to cells in the body forming cancer and not cooperating with one another?
- [100:51]
B
Yeah, I mean, there are some parallels and there's also some, you know, places where the analogy, you could say breaks down. So, so I like to kind of think about it in terms of what are the components of multicellular cooperation that break down in cancer? And then we can ask, are there parallels to that in what happens in human societies? And so if we take the regulation of cell Proliferation. There are, you know, human societies in which people do regulate how many offspring other people can have. Right. So we see that. Now, do we think that that's a good thing or bad thing? That's an ethical question, you know, whether that's, you know, cooperation and, you know, it's also, you know, on some level, I guess it can be interpreted that way. It could also be interpreted as, like, you know, authoritarian control. That's not cool. Right. So, like, there's, you know, like, already we're kind of in, like, oh, the body is like a fascist state. Right. Like, if you start, like, making, you know, these. These analogies are like, okay, we're on.
- [102:02]
A
Yeah, we're on touchy ground already here.
- [102:04]
B
Exactly.
- [102:05]
A
But I suppose you're right. I mean, the body is a very authoritarian place. Cells that step out of line get shot.
- [102:11]
B
That's right. Yeah. Yep. No questions asked, you know, I mean, yes and no. Right. I mean, there's like, there is some. There is some cost, right, to, like, you know, just killing a cell like that. So. So, you know, you do have mechanisms to, you know, try to do the DNA repair and, you know, you know, make sure that, like, if it's easy to solve the problem, you know, the cell doesn't get, you know, completely destroyed. But cells don't have a lot of autonomy and, you know, that's a good thing for the function of us as a, you know, unit. But, you know, if you take really.
- [102:48]
A
Seriously for every cell.
- [102:49]
B
Yeah. If you take seriously the perspective of the cell and it's, you know, it's a different story, if you'll permit me a slight digression. Sure. So I worked on a song, a rap with Baba Brinkman early. Early on when I was just starting to, you know, really kind of bring these ideas together about cooperation theory and cancer where, you know, basically, you know, the idea was like, how can we, like, write a rap about cancer from an evolutionary perspective and, you know, the cooperation theory perspective. And what he ended up doing was taking the perspective of a cancer cell that is not happy with being stuck in this body and having to do all of the things that are, you know, required. And it was. It was a really great way, you know, for me to. To. To really shift my perspective. And it's also just really fun. So, you know, it's called Revenge of the Somatic. If you, you know, want to look it up, it, like, starts, you know, my forefathers were free but I was born a slave I keep the memory of freedom in my DNA. Right. So it's like, okay, like we're setting up a, you know, totally, totally different frame for, for thinking about it, but it, it really does draw that parallel between, you know, what's going on in the cellular SoC and some of these things that, you know, we think about on a, on a social level. So. Yeah, so anyway, so that's my, like, big digression. But, but, you know, but we can bring it back to like these, you know, foundations of multicellularity we can think about. Okay, you know, is there an analogy for, you know, cellular suicide and, you know, for, for cell death? And it's like, well, you know, you know, there's analogies, but like, that's not something that happens a lot, I think, in modern soc. So, you know, there's some situations where, like, if people are being forced to do something that they think is going to damage their, you know, their families, their countries, right. That, you know, they will swallow the pill to get themselves out of the system so that they don't end up doing something damaging. Right. So I think at the very extreme case, you can maybe see some examples of this, but mostly that, you know, those kinds of processes aren't really going on, I think in human societies. Um, but division of labor, we see a lot of that, you know, resource distribution, you know, reallocation of resources moving things around so they can get from one place to another. We see that. We see also, you know, maintenance of the shared environment. Right. Like that's, you know, we have, you know, in our cities, we have our trash collection, we have, you know, you know, the lots of efforts that people do to take care of the environment that we share. So I think that there are, there are a lot of parallels and then there's some interesting, you know, discontinuities that I, you know, I think it can be informative to think about those and talk about those in terms of, well, you know, why do they not happen in exactly the same way? How much of that has to do with levels of selection? Right. Like our bodies have been selected on this level of all the 30 trillion self cells, like doing a thing together to help us survive and reproduce. While, you know, in humans, arguably there's been a lot less selection on collective phenotypes. So I think, yeah, there's. Yeah. And then there's also, you know, in humans there's a whole other set of processes that have to do with culture and institutions. And you know, yes, we have set those up, are, you know, they've come from us in a way to like, then Allow us to regulate ourselves in collectives. But they're, you know, they're not necessarily going to have, have the same, you know, structures and, and functions exactly as the, you know, systems that have evolved through natural selection to regulate a multicellular body. So, so, yeah, so there's a, there's a lot more that we, I mean, we could probably talk about just this for an hour, but absolutely.
- [107:06]
A
Yeah, yeah, yeah, I guess. I mean, so one of the, one of the differences that has become immediately apparent is that we can care about the interests and well, being of individual people in a way where we don't normally care about the interests of individual cells because I guess we don't think that they're moral patients. And so that makes the issue potentially very different. But I guess, yeah, there is, I suppose you had this analogy of the rubbish housemate who's kind of like a cancer cell. So they come in and then they eat all of your food and they don't buy any groceries and then they just leave their trash lying about everywhere. They're not taking care of the extracellular environment. And then I suppose in the Gatsu analogy what happens is that they then immediately have children. So the next day you've got two rubbish housemates and then you've got four of them and then eight of them and 16 of them. That doesn't really happen with people on the same scale. You don't get replication in the same way. I suppose you could think about maybe like bad ideas or bad behaviors spreading through people through ideas. Um, so maybe that would, that would be more of a, an analogy where maybe you could have a society undermined by the spreading of the idea that we shouldn't pay taxes or shouldn't cooperate or shouldn't contribute to society.
- [108:15]
B
Oh, that could never happen. We could never, we could never have like society break down because of bad information.
- [108:22]
A
Fortunately, yeah, we're completely robust against that, I suppose. I mean, other differences are that people learn through reasoning and can anticipate ahead the effects of their, their actions in a way where evolution doesn't plan ahead and cells can't process information in the same way. So maybe that does make it really quite different.
- [108:42]
B
Yeah, I mean there are certainly the ability to think ahead and plan ahead changes the sort of decision making process. But also if you have evolution happening over and over again, or you have evolution happening in multiple clusters of, you know, cancer, you know, cells that are, you know, little collectives and you know, it's happening 25 times, you know, in parallel, like. Right. So you can get Variation and selection acting in ways that can look kind of like things like, you know, learning and anticipation, even though that's not actually what's going on. So yeah, you can have different mechanisms leading to sometimes, you know, the, the same, same kinds of structures and behaviors.
- [109:31]
A
Which is also interesting analogy I was curious to explorers. So we had this very fundamental constant tension between the need to crack down on protocancers and also the need that sometimes you do need cells to move and grow and so on. And I guess you can imagine that within society there's also this tension always existing between needing to be open to new practices and new ideas and deviation from existing rules with at the same time not wanting the existing order to break down in ways that when it actually is valuable and the rules are good ones. I think we see this in, I guess this is the idea of closed versus open societies where some societies just allow individuals to do what they want to a greater degree, getting some of the benefits from that. I guess they're living in a fast life history style. And then there's other societies that are much more conservative where they really don't like deviation from existing practices and they're much more conservative about that because they're worried about where that might lead. Does that analogy pour over in your mind?
- [110:33]
B
Yeah, I mean, I think that there's definitely some, some parallels there. And if we kind of go back to this idea that, you know, the body really is a sort of, you know, fascist state that doesn't let cells like do anything, I mean, to me that would be like a personal hell because like, I love, you know, thinking about things differently, being of, you know, asking like, well, why do we have this rule? Like, I mean, to me that is, that's really important. And you know, and sometimes it's actually important for cooperation in human societies to be willing to challenge the systems, to be willing to break rules that, you know, might be things that people you know, are accepting that might not be ethical, that might not be the right way of organizing things for the well being of society. So I think, you know, it isn't the case that cheating is always bad. If we define cheating as, you know, breaking shared rules that you know, that have, you know, some, some fitness consequences for the individuals within them. I mean, if, you know, if, if cheating is always about like, you know, you have a group that's like really agreed, hey, we're gonna go in on this together and follow these rules and you have, have you know, breaking of those rules and then yeah, you can say there's like cheating, exploitation going on. But, you know, sometimes people are born into systems that they never agreed to the rules of or sometimes, you know, rules are put in place to exploit people. Right. So I think that, you know, it's, it gets interesting, you know, when we start really interrogating these ideas of like, you know, what does it mean, mean to cheat, to be a cheater. And you know, and sometimes, you know, we do need to challenge the systems that we're in and, and push them a little bit or even straight up cheat in the rules so that we don't have, you know, people getting exploited. So I think it's, it's important, it's important to, you know, to not just be like, oh yeah, we should just not have any rule breaking. And, you know, the world would be so much better if everybody always just, you know, did the thing that is expected.
- [112:46]
A
Yeah, yeah. I suppose the interesting thing is that so every time you have a new generation of a new human, then they're born with a slightly rejigged genome that now has a new agreement between the cells, a new set of rules that they might follow that might allow, you know, some cells to grow a little bit more and like change the body shape in this way or that might be a bit more permissive to some types of cells in some situation, situations and not others. The thing is, but there's like billions of humans and I guess in the past there was millions of humans, so there was a lot of innovation constantly with that. Thing is that we don't have so many societies. Especially now. The number of group societies with different cultures and different rules has now shrunk massively because we're all in such great communication with one another. So I guess we have to allow them to change quite a bit, otherwise we really would be incredibly stagnant because there's not room for experimentation among small groups, groups anymore. Does that make any sense?
- [113:41]
B
Yeah, I mean, I think like, there's, there's different ways to sort of think about the units here. Right. So you could think about, you know, societies as, you know, sort of, okay, you have everyone who, you know, feels like they're part of the same culture. They feel, you know, they shared norms and, you know, ideas and approaches. But, but you could also think, you know, a little bit more, maybe look loosely about what constitutes, you know, a group where you could have creativity. Right. So you could have companies or even teams within companies or, you know, groups at universities that are, you know, looking at certain questions in certain ways. So I think you Know, the, the, the unit of analysis is maybe a little bit flexible in a way that, you know, hopefully allows for, you know, the kinds of, you know, good innovation and good, you know, challenging to norms that, you know, does need to happen, especially when you're, when you're in a system that, you know, might not itself be, you know, generating that innovation. Right. Like if you're in a bureaucracy, it's like, how do you, how do you do things in a new way? Well, maybe you could do things in a new way by suggesting more bureaucracy, but other than that. Right. Like.
- [115:02]
A
Maybe the analogy between, yeah. You know, the innovation that you get from sexual reproduction where the genome is substantially changed each generation might be that we start new firms, we start new companies, charities, you know, social groups, and they can each have somewhat different social norms, somewhat different rules for what is cheating and not cheating than what came before and then the ones that flourish and achieve people's goals and those, those practices might spread. So that's kind of a cultural evolution analogy.
- [115:28]
B
Yeah.
- [115:29]
A
Is there an interpersonal analogy to the strategy of not treating cancer so aggressively so that you can try to create a more boring static tumor? Is there any way that we could apply that to fighting crime or antisocial behavior or marriages? I don't know. Yeah.
- [115:50]
B
I mean, yes, we can certainly apply these analogies, right. To thinking about like, you know, how do you, instead of sort of approaching things that we see as problematic as like, oh, the thing to do is eradicate them. Instead, we could ask, well, you know, how do we live with something that maybe isn't ideal and accept that, you know, you know, maybe it won't be perfect. Maybe, you know, there'll be some exploitation going on, but it won't be to the point that it's devastating, you know, or how can you cultivate, you know, relationship to the point where, you know, you, you're able to, to live with each other and, you know, at least, you know, maybe they're not always doing the dishes, but at least they're, you know, not exploiting you on a, on a large scale or something. Right. So it's like, what can you live with and what can you not, I think, you know, in of terms, terms of crime, that there are, there's a lot of really important work going on right now in terms of looking at restorative justice as a strategy for, you know, dealing with situations where people are, you know, imposing costs on one another or, you know, violating rules and, you know, rather than focusing on sort of punishment or, you know, putting Somebody away, you know, forever, or, you know, even death penalty. Right. Like, instead of those catastrophic kinds of, you know, ways of dealing with it, which actually can undermine a lot of the connections in a society. You know, restorative justice is really about, well, okay, how do you right the wrongs to the extent that you can, and how do you keep that individual, you know, as a part of the society and, you know, do the damage control to the extent that you can, but then, you know, try to actually cultivate some, something out of that that's, that's positive. So I think, you know, when, when we talk about human societies, there's, you know, there's analogies, but it can go even further than just, you know, analogies, because I think there are, you know, if we look at small scale societies, there are a lot of situations where, you know, restorative justice does work to actually reintegrate people, you know, and rebuild social relationships in situations where, you know, if you were just using punishment, that wouldn't happen.
- [118:17]
A
Yeah, yeah. Another analogy that just occurred to me is, so I've heard this story from kind of theory of fighting crime. I think when you get to a point where gangs are at a particular level of power, especially if they have massive funding, often through the, through the drug trade, it becomes impractical for the police to like, even hope or dream of eradicating the organizations. They simply are not going to be resourced at all to do that. And often what they do in that case is reach an agreement with the gangs where they're like, okay, these are the, these are the things that you can do that we can tolerate. Like, we can, we can live with the drug trade and we can live with you running underground casinos or something. But if you kill one another, if you start like creating violent problems on the streets, then that is what we'll crack down on. And so any gang that just does these other peaceful things, we will largely leave you alone. But anyone that falls out of line and breaks these other rules, then those are the rules that we're going to actually try to defend, because that's what we care about much more. And so they reach this kind of compromise that actually does seem structurally quite similar to the chemotherapy case.
- [119:20]
B
Yeah, that's interesting.
- [119:22]
A
Potentially, I guess you could even shift the culture within the gang over time towards the people who will flourish are the ones who are able to live within those more narrow rules. What about with memes? Can you have cancerous cheating memes, like ideas spreading between people? Does that make any sense?
- [119:38]
B
So there's one level on which it makes sense and another level, I think, on which it doesn't quite. So the idea that, you know, memes could be like exploiting our, our brains and our information systems to spread themselves. Because the ones that, you know, are good at spreading spread like a hundred percent. Right. Like there's certainly exploitation going on. Um, but to call them cheating, like there has to be some entity that they're cheating on and, you know. Yeah. Like what are the rules that they're breaking of what collective system that they're a part of? So I would say that, you know. Yeah, they can exploit us, but maybe they're more like, you know, viruses or pathogens where they're, they're not necessarily breaking a set of pre existing rules, you know, that come from inside, you know, the system that they're within, but rather they're, you know, just little sneaky things that can find the, you know, vulnerabilities and exploit them. Of course, I'm, I'm anthropomorphizing here, right. They're not like actually sneaky and looking, but they act as if they are because the ones that do it are the ones that proliferate.
- [120:41]
A
So they're around. Yeah. So I guess if you had an idea that wasn't helpful to the person who hears it say it's either false or just useless, but it's the kind of idea that people really love to repeat a lot to other people and so they spread it. I guess that is kind of. Well, it's like a virus of a, of a, of an idea.
- [120:58]
B
Yeah, yeah, it's like a virus of an idea. Right. And I wonder what that would look like.
- [121:03]
A
We might have like unpleasant urban legends or like fake facts. I don't know.
- [121:08]
B
Yeah, I, I mean, you know, there, there are a lot of ideas that, you know, aren't necessarily good for the survival or the reproduction of the individual who, you know, possesses them. Like there, there are cults, right. That, you know, advocate for things like, you know, suicide, that advocate for, you know, not having children. Right. Like things that are at odds with the survival and reproduction of the, the organism that, you know, harbors them. But in certain kinds of conditions, those memes can, you know, take hold and also spread within a population.
- [121:52]
A
Yeah, makes sense. Okay, let's turn that to cooperation on different scales again, I guess. Zooming out further. If humans as a species were kind of damaging the natural environment in a way that made it harder for humanity to survive in future, would that kind of be like a cancerous Behavior in a sense because we're destroying the extracellular matrix where we're making it hard for us to survive. And you might think, well, it's like it's a behavior that's going to undermine this, like, meta. Organism of the entire species.
- [122:25]
B
Yeah. I mean, if you want to kind of like look at our, you know, whole species as an entity or, you know, kind of go. Go a little Gaia and be like, hey, you know, Earth, right. It's like we're, we're all like one, one big system or we're, you know, a unit on some level. Like, if you do zoom out, right, and if you accept that it's reasonably likely that there may be other life out there there in the universe that is, you know, also existing on planets where there are resources and using them, then, you know, there is a certain level on which, you know. Yeah, you can think of all of us as part of, you know, a, a unit that, you know, is probably the, the, the right level of analysis is the, you know, planet is, you know, Gaia. Even though, like, I know, like, there's there's sort of been a lot of. Of pooh, poohing of the idea of Gaia and evolutionary biology. But, but there's a certain level on which it does make sense if you zoom out far enough. And also if you think about sort of the interdependence of, of systems on Earth, you know, that, that. Yes. That there, there is some level, I think, on which it's at least a reasonable tool to use to think about some of these things. And yeah, I mean, there, I think there are absolutely ways that we could think about, you know, our behavior vis a vis the limited, you know, resources that are on our planet as having some analogies with some of the processes that, that go on with, with cancer and, you know, efforts to try to, you know, increase sustainability and, you know, make sure that we're, we're living in a way that will, you know, be. Will make it more likely that future generations will, you know, have, have a, have a decent chance of a good life. I think, you know, all of those are. Are questions that have some analogies with, you know, sort of shortsightedness that can happen with cancer inside the body.
- [124:24]
A
Yeah. That idea of us like humans engaging in this cancerous behavior sounds, sounds a little bit cuckoo if you think that humans are the only living thing in the universe. I think, however, if the universe were teeming with life such that there was life originating on many different planets and from some planets, it Spread because the organisms there cooperated together in order to make a flourishing place. And in other places life went extinct because the societies went to war and they couldn't collaborate and they died out. And then of course, the cooperative ones spread to other planets and they end up taking over the galaxy. Then I think the analogy would hold very clearly. But the idea of this then corporation uncorporation, the uncooperative thing dies out or in the long term kills off the organism that it's a part of or the entity in which the cooperativeness is represented. And then it's a bit funny that, that we think it's crazy that for us to think about Earth this way, just because there aren't, there doesn't happen to be that much life out in, on other planets, as far as we can tell.
- [125:19]
B
Yeah. Well, I'm smiling for a few reasons. One is because, like, I love talking and thinking about like, extraterrestrial life and you know, the like, possibility that, you know, the things that are going on elsewhere in the universe, you know, like, like they can provide a frame for thinking about what's going on here that's just so different. So I'm smiling because I love that and also because, you know, another way of thinking about like, you know, space faring, you know, intelligent life is that, you know, maybe there's a certain way in which it's more like a transmissible cancer that's like, you know, really good at like, cooperating to like extract the resources and then go find far even, you know, beyond the body or the, the planet and, and you know, find another extant, you know, life form to, to colonize.
- [126:13]
A
So, okay, so do you think that of humanity would then be a kind of transmissible cancer that started on this planet and then is going to spread to other planets and use up the resources there?
- [126:23]
B
I mean, you know, we're kind of off the deep end, but it's fine.
- [126:25]
A
No, I love it. I love it. Yeah.
- [126:29]
B
Yeah. But in all seriousness though, right, like, the ability to, you know, be an intelligent life form that can, you know, get into, into space, it's going to require some level of cooperation. So you do have, you know, sort of a filter there. And you know, I know in like the sort of great filter hypothesis idea, there actually isn't very much about cooperation. And I think, you know, like, like it's not just being technological, but, you know, having the ability to, to cooperate is, is key to avoid destroying ourselves. Yeah, yeah, to the point of, you know, yeah, we could destroy ourselves, you know, and humans Also oftentimes use cooperation for, like, really sinister ends. Right? So, like, cooperation isn't in itself good. It's all a question of, you know, what is that cooperation used for? And, you know, know that. So. So it's all to say, I'm not. I'm not saying that, like, it's inherently bad to go into space because we can make, like, a transmissible cancer analogy. But I think we, you know, we do have to ask, well, you know, what is the, you know, what are the goals? What, you know, and, you know, if. If we do figure out how to be, you know, an interplanetary species, like, you know, is. Is that. Is that the, you know, the direction that is going to help life thrive the most, you know, our life. Life in the universe, you know, Anyway, so many open questions. I feel like this is a whole lot. This is a whole different episode that we're having right now.
- [128:06]
A
We're just for listeners who annoyed. I'll try to. I'll try to ground this a little. So I think, yeah, the analogy to cancer, I'm not sure is how helpful it is. But I think what we do see in the universe repeated at different scales is cooperation between different elements to achieve common goals. And they coordinate and follow a set of rules that creates a surplus that allows them to succeed. That surplus can then potentially be grabbed by subcomponents that decide to deviate from the rules that created that surplus. And I think you just see this kind of recapitulated in different ways. And it makes sense, theoretically. It makes sense structurally. Yeah, I like that. Does that sound right?
- [128:45]
B
Yeah, it's a very succinct explanation. Explanation of a very complicated process.
- [128:51]
A
All right. Well, I guess on that topic of kind of many different. Well, of different ways that uncooperativeness can arise in structures at different kind of scales. Because one thing that could potentially change that in future is the ability for intelligent beings to prevent themselves from drifting and changing over time in a way that kind of creates the variance that might permit, I guess, deviation between the interests of different components of this system. To be more specific, I'm thinking if you had artificial intelligence systems that were as capable as humans are, say, or substantially more capable, and they could copy themselves perfectly. And like with. When you copy files on a computer, the computer can just check that it's all been copied identically and that there's no mutations, certainly no changes anywhere near it. There's rate that you get genetic changes as humans reproduce. In that case, could this kind of flawless error detection be the first sort of self replicating life that potentially avoids the phenomenon of being undermined by uncooperative subcomponents that deviate in their interests from the interests of the original agent.
- [130:03]
B
So sort of kind of doing a thought experiment here that like, if you could have totally permanently perfect replication, never have errors, then could you sort of get systems that would evolve to like be able to maintain cooperation forever? And I'm going to answer maybe because even without mutation there could still be, you know, other factors that could move. So I'm thinking of this on like the cellular level, right? Like you can have epigenetic changes, right? So if you go into an expression state or like, if you're thinking about artificial life, if you go into, you know, some sort of aspect of like the, you know, running of the processes that maybe isn't exactly appropriate for the context because maybe the inputs got mixed up or maybe it went into an environment that was weird, then it could actually be, you know, in an expression state that's not appropriate, appropriate for what would be most beneficial for the organism or the higher level entity. And, and also, you know, in order to even kind of know what is going to be the best thing at the organism level, there has to be a history of selection for those things that allow the, the entity to optimize for that organism level. And if you have a rapidly changing environment, then it actually, actually, you know, it's not possible to anticipate every, you know, situation and what would be optimal for the higher level entity in that case. So, you know, yeah, if we could completely eliminate errors of copying, that would reduce the sort of, you know, problem that comes from mutations or alterations to the sort of underlying code code that leads, you know, cheating to arise. But there's still other ways in to, you know, get things that aren't actually functional at the organism level. And you know, and if they're benefiting the entity itself that's like in the weird expression state or whatever, then you can get the propagation of, you know, those, those things that are not ideal for the higher level.
- [132:26]
A
Yeah, I guess. Is that another way of saying that? I suppose if you have an AI system that keeps kind of duplicating or keeps copying its original version in order to go and complete other tasks elsewhere. Presumably those new agents are going to encounter new situations and they're going to try to learn and be altered by the environment as they're going about their work. And then even if kind of the original code or the original goals haven't changed, at least not apparently the brain is going to change. The neural network is going to adapt to the environment and be shifting. And that could cause at least some slippage in goals because you just, I guess at least with current AI technology, we wouldn't really know how to ensure that the goals are preserved because it's just this incredibly complicated mess, a little bit like the brain. So you start learning one thing and then you don't know necessarily what consequences are most might have elsewhere.
- [133:18]
B
Yeah, that's one way to, to think about it. And I would just add to that that, you know, information has to be processed at so many levels for anything to be able to happen. And, and you know, thinking about this at the cellular level, like, to me it really, it makes it much easier to, in a way easier, but harder to like, wrap my head around, like, how much information processing needs to happen. And, and so even just the idea that, you know, we can say, okay, we're giving this AI, you know, a goal to, you know, do a specific thing. Like in order for that AI to accomplish that goal, it needs to be able to, you know, process and respond to really complex environment. Right. Like you, you could say, oh, a cell, like, it has the goal of maximizing the survival and reproduction of the organism that it's a part of and the inclusive fitness and interdependence of whatever. Right. Like you could say, okay, that, like, that's the goal that each cell in our body has on some level. But you can't just expect the cell to know how to do that. Right. It has all of these rules encoded into its genome and then it's interacting with all these other stuff, cells in ways that lead to sort of the emergence of the pursuit of those goals at the higher level. But yeah, it's, I mean, it's a lot harder to be goal directed than we think because that's so easy for us. Like, we're, we're so used to operating that way and projecting goals onto other entities in order to kind of make sense of their behavior. Because it's a really good heuristic. But that's what it is. It's a heuristic for what is underlying. You know, the underlying mechanisms are so complex that we can't even wrap our brains around them.
- [135:17]
A
Yeah. Speaking of cells, I guess we've mostly been talking about cheating and defection between cells, but we should talk for a minute about, yeah. Ways that you can get cheating within cells, which sounds a little bit crazy because it's already like a single cell or such. A, such a Small scale. How can you have subcomponents of a cell fighting against one another? But it turns out that you totally can. Yeah. Can you explain how it is that you can get kind of genes cheating against other genes that are on the same strand of DNA that are on the same chromosome?
- [135:46]
B
To me, this is all kind of an extension of our earlier conversation about the evolution of life and multicellularity. And it's just kind of taking it back a few steps. So you know, like very, very early on in the evolution, evolution of life there, you know, there wasn't anything like a genome like a bunch of, you know, DNA that is, you know, teaming up to replicate itself together with all the machinery to replicate and all of that. You had, you know, probably something that was much more RNA like so you know, you had basically just these, you know, molecules that were able to replicate, replicate themselves in one way or another. And once you start sort of having situations where these entities that are replicating can, can do so more effectively in a cluster, then they, you know, they will stick together and then maybe, you know, machinery then evolves that allows them to replicate together. Now you can imagine though, early on in the evolution of that if you had a chance cheater, right, that was actually replicating itself more than the others, that that cheater could then, you know, be overrepresented in the next generation. And this is, you know, very, very likely what was going on in the evolution of, you know, proto life I guess we could call it, or maybe it's life if you think, you know, self replicating entities are life. So the very design of like how, how our DNA works, how it replicates is there's actually like all of these cheater suppression mechanisms already built in. And that's the only reason that it works is because there is a suppression of all of these sort of, you know, gene level cheaters. So, so when we see, you know, fragments of DNA that over replicate or jump into new chromosomes and you know, replicate themselves in there. Rather than seeing something like weird and really unusual, we're just seeing the like uncovering of the like, you know, fundamental.
- [137:58]
A
That were already there.
- [137:58]
B
Yeah, yeah, that, that were sort of overcome in you know, what, what's called like the, these are called like the major transitions in, in evolution. These like times when previously independent entities kind of came together to form higher level entities which then allowed for, you know, more complexity and then yet higher level entities so sort of coming together, regulating genes into a genome, having some teeter detection, suppression response mechanisms at that level really is. Yeah, it's one of the steps in kind of getting, you know, complex multicellular life, at least on this planet.
- [138:39]
A
Yeah, so. So there's a stylized illustration of what might have been going on is you've got lots and lots of different strands of DNA, lots of different genes in this kind of soupy mixture. And they're like, we could do better if we all stick together, if we all get on one very long strand of DNA so that we're all there and we're always available to use these genes if that's going to be useful for replicating ourselves. But every time the organism wants to replicate, each of the genes is like, no, copy me a little bit more. Why not make more copies of me?
- [139:08]
B
Yeah, something like that.
- [139:09]
A
I'd rather become more. And I would rather become a bit, little larger and larger fraction of the genome, I guess, at least until the point where that causes the thing to become completely non functional and then the cell is dying completely. That would set some limits pretty quickly. That would set some limits, yeah.
- [139:23]
B
And that's where we get into multi level selection again too. Right. Because you had presumably little clusters all over the place doing this over long periods of time. And those that were best at, you know, forming together, at replicating together, at suppressing cheating, were the ones that were more likely to create copies of themselves at that higher level. And so, yeah, so multi level selection is absolutely key for kind of understanding these major transitions in cooperation where you go from, you know, these lower level entities that are competing or just sort of facultatively cooperating, like in the right circumstances, circumstances, to kind of being locked in that they can only replicate as a unit together.
- [140:11]
A
Yeah. What are the mechanisms that stop cheating by individual genes that we're dealing? I suppose it's something like, it's a system that would detect whether something has been copied too many times, whether the same kind of DNA is repeating too many times and then it might snip it out in one of the cases.
- [140:25]
B
Yeah. You know, I'm not a geneticist and expert in this, but I know that there are a lot of mechanisms by which you can get, you know, replication, you know, of, of these, of these genes in the same place. You can get them sort of jumping from genome to genome and that, you know, part of our sort of overall kind of monitoring of the genome that's happening right by like the genome itself is monitoring itself, that it's not just, you know, sort of errors in terms of like point mutations, but places where there's, you know, too many replicates Right. And because, because it's double stranded when the DNA is, you know, lining back up, there would be like chunks that are weird if things, you know, have gotten replicated too much. Or there might be other, other mechanisms that allow for the sort of, you know, compilers and detectors of the genome to, to get in there and, and sort of figure out what's going on again. Figure out and then, you know, clip things out if necessary or you know, get rid of cells that might actually have, you know, so much. Yeah. Jumping DNA in there that it's like, oh, maybe we just lose this one. So.
- [141:43]
A
Yeah. Okay. So I guess cells in the body do sometimes die because of these phenomena. I guess that's the last line of defense is that if a cell has been a victim of cheating genes and it's like, and the damage is too severe, then it just needs to kill itself in order to avoid damaging the organism more broadly.
- [141:59]
B
Yeah, that's right.
- [142:01]
A
Does this have anything to do with the kind of repetitive junk DNA? I guess, I know it's not very politically correct to call it junk DNA. We're meant to realize that it's very important and sophisticated and we just don't understand what it is. But I'm not sure what it's called these days. But the kind of repetitive non gene DNA is that maybe a result of genes copying themselves all the time and creating these stretches?
- [142:21]
B
Yeah, yeah. It's likely that some of those mechanisms are at work now, whether that is, you know, providing any specific benefits for those genes other than just, you know, they're, they're replicating themselves and so they replicate more. Right. It's sort of this just, you know, default of, you know, the things that are good at replicating end up replicating more. Yeah, but yeah, I think that there's, you know, there are a lot of open questions still about what exactly, exactly is going on with a lot of the, the DNA that is, you know, are these many copies. Right. Because sometimes you can actually have sort of differentiation of function that begins because you've had, you know, you have like two copies of a, of a gene and then you can actually have one do one thing and one specialize on the other. So there's, you know, potential functionalities that can come from that in the medium term. But, but you know, they're also, I mean, we just, the fact is we don't understand still a lot about how we go from genotype to phenotype, especially with sort of all of the dynamism that comes from, you know, epigenetics how we're affected by our environment, how cells affect, are affected by the cells around them. It's really, really hard to drill down to the time frame and the spatial scale that we would need to be looking at to like really, really understand what's going on. Right. We, we just don't have great tools yet for like getting so minuscule into, you know, what the function is or even just what they're, what they're doing, even if it's not like functional from an evolutionary perspective. So lots of open questions there that are, that are cool.
- [144:07]
A
So, so we've gone from cells cheating against the organisms that they're a part of, to genes cheating against the genomes that they're a part of, or the cells that they're a of part. They're a part of. Can we go any smaller or have we hit kind of rock bottom here? Can we talk about individual base pairs on a gene defecting against the gene that they're a part of? Or maybe, or maybe does it just not become practical for that to happen?
- [144:30]
B
Well, I mean, I think we can probably go all the way back to the origins of life and replication in general, but we don't know exactly what the, those entities looked like. But you know, once, once you start having anything that is a replicator, right, it's going to be, it's going to have some level of complexity, right. Even if you just think of like a replicator is something that when, you know, it's out in the environment, maybe it attracts things that are similar to it, right? So you could have like a very, very simple molecule that's just like good, good at, you know, maybe it has three parts and each of those three parts can attract a thing that is the same as it and then it has some mechanism for like, you know, letting that other thing go and then that, you know, like a sort of self catalyzing process. So at that level even you could imagine that there could be variation among entities that are, you know, replicating or, or you know, some are just not able to do that at all. So there could be very, very sort of mechanistic kind of cooperation that's just, oh, well, how do these things, you know, attach together in what configuration? And then how do the forces, you know, at the level of the, you know, physics like work at that level? Like, so there could be, you know, selection that's going on, on things that we think about as like the sort of chemistry and physics that, that are, that are, you know, leading to maybe selection for Cooperation, but also the possibility that like, you know, cheating is undermining it. But it would be cheating in a very primordial kind of sense.
- [146:17]
A
So yeah, okay, yeah, we're about to leave biology and all this kind of genetic stuff. But before we do that, it would be really cool if you could explain this I guess, quite dark aspect of how, how I guess like sexual organisms work at least, which is that. Yeah. Can you explain how it is that the genes that come from the father tend to encourage offspring to grab a lot of resources from the mother and the genes that come from the mother encourage the opposite. They encourage the baby, like the offspring to consume as few resources as possible. Why is that?
- [146:52]
B
Oh yeah. So genetic conflict. This is one of my favorite topics because it's just so weird, right? When it starts to make manifest. So yes, it all kind of starts with the idea that, you know, we as sexually reproducing organisms are, we're not genetically identical to our parents or our offspring. Right. If you're, you know, typically you're 50% related. Right. To parents and offspring. So if you have, you know, your mom and your dad, they each contributed 50% to who you are in terms of the, the genes. And that means that you don't have 100 aligned interests with your kin. Now evolutionary thinkers often sort of focus on like this idea of, you know, kin selection, kin based altruism, like parental investment. Right. So altruism, easy, easy to get altruism among kin. And yes, but yeah, yeah, you don't actually have 100% aligned interests. And from the perspective of the genes that you inherit from your father, the mother's body and the mother's future capacity for reproduction is, is not really relevant unless they're, you know, they're a partnership for life and there's no other possibilities of, you know, the, the, the female having offspring with, with other males. So you have, you have a situation where it's in the best interests, evolutionarily speaking, of the genes from the father, to extract more resources from the mother's body than what would be optimal for the mother, who is presumably probably you know, trying in evolutionary terms to more like equalize investment over present and potential future offspring. Maybe not 100 equal, but you know, having a, a distribution that is closer to equal. And so this, you know, kind of makes sense on theoretical level. But the, the absolutely crazy thing is that this male manifests in the way that genes are tagged. So the epigenetic tags that are on genes, depending on whether they come from the maternal side or the paternal side and the genes that come from the paternal side, they tend to be expressing genes that increase the resource delivery to the fetus while the mother is pregnant. And the genes that are coming from the mother's side, they're. They're basically tagged in a way that makes them interfere with the transfer of resources that the paternal genes have kind of turned up. And similar things are going on with, you know, growth factors and, you know, other processes that have to do with the transfer of resources, resources from the mother's body to the fetus. Now, all that being said, there is a huge range of sort of shared interests where it's like, yes, it's in the maternal interest to transfer these resources, and it's in the fetus's overall interest and paternal interest to, you know, get those resources. So there doesn't have to be serious conflict. But things can escalate into situations where there's serious conflict. And in fact, preeclampsia is a result of the escalation of genetic conflict where essentially the, you know, mother system is shutting down the resource transfer in terms of the structure of the blood vessels. And the fetal system is then upregulating signaling that increases the blood pressure. And then the mother system responds and the fetus responds. Bonds. All completely unconscious, but it can push the maternal body actually into a state where both the mother and the fetus are at risk in terms of their viability. So it. It's interesting and scary and weird and cool that, you know, you can have these systems where underlying it, there's a lot of overlap, trapping interests. But if you start this sort of, you know, move and counter move and counter move and counter move and counter move, you can. Yeah, exactly. It's an arms race. Yeah. And then everybody can end up dead, which sucks. Right? So, yeah, yeah.
- [151:42]
A
So I guess, yeah, going. Going back to the. To. To the beginning of sexual reproduction. At that point you have this slight misalignment between the interests of the male, which I guess in this case is defined as the sex that provides less resources to the offspring or has less obligate parental investment is the term. So it can get away with contributing less to the creation of offspring, and then the female who contributes more. And there's this slippage between their interests because the male will care as much about the female's future reproduction as the female does if there's permanent monogamy between them. But inasmuch as there's not permanent mandatory monogamy between them, then the female cares 100% about her future and the male cares less than 100%. And so the male wants to ramp up relative to the female, how many resources the offspring extract from the female, like sacrificing her future potential reproduction. And basically this just escalates over time. So the male bids some more and then the female offsets it by changing, changing their genes. And then the male bids higher to offset that and then the female bids higher to offset that. Until you've got radically different requests, radically requests a different procurement of resources from the child, depending on whether we're talking about the male coded or female coded contribution to the genome. And then if you only have one of them, then the system is just completely broken and then it's just completely out of whack. And in no one's interests, you'd either have a massive baby that kills the mother or a completely malnourished baby that could, couldn't survive.
- [153:15]
B
Yeah. Sometimes I use the analogy of a tug of war. Right. And so what you have is a situation where, you know, the maternal interests are pulling on one end and the paternal interests are pulling on the other end. And every time, you know, one side tugs harder, the other side has to tug harder again in order to just keep things in the same place. And then, you know, if you end up with a mutation that interferes with one of the genes that regulates how much is being put pulled, then you can actually end up in a, in a situation that is, you know, suboptimal for both parties. It's outside of that range of. Yeah. What would, what would make sense? You know, so it's like. Yeah, it's like you've got like, you know, the balance in the middle and the, you know. Yeah, the paternal interest would like it a little bit this way and the maternal would like it a little bit this way, but none of them want the rope to go slack and just, you know, have nothing in that range at all.
- [154:13]
A
Yeah, well, what is the limiting factor on this? Because I suppose it escalates to an explosive and dangerous situation where you really have to hope that everything is perfectly balanced, otherwise it breaks. But it seems like something must stop this at some point, or maybe not. We just have. All of the male's genes are coded to go really hard to extract as many resources as they can. The female is the opposite and that's where. That's where it stops.
- [154:38]
B
Yeah, well, I mean, there are, I think, a few kind of constraints on the evolution of this. I mean, one is obviously that if there's too much of attention and you have Mutations often enough that lead to, you know, a total totally suboptimal situation, then those, the sort of more intensely competitive genes on the whole, are going to be less favored because you can have these catastrophic outcomes. And, and there's also, you know, you also have this sort of evolution of these regulatory pathways as well. And so when you, if you have a situation where, you know, what's being encoded is this sort of escalation and counter escalation, like on the timescale of the organism's lifetime or, you know, on the timescale of a pregnancy, if those genes that code for that escalation are more likely to lead to, you know, a catastrophic situation where, you know, nobody's evolutionary interests are being served, then there's also going to be, you know, less selection on that. I actually have a game that I designed for like teaching about this in the classroom. Like one individual plays like the parent, and then you have three that are like the, the, the, the, the, the baby bird. So it's like a mother bird and baby bird just like so, you know, takes a little bit out of the realm of like, you know, being human. And then the parent is like rolling a die every, every time period and has to choose how many points to give to each of the three offspring. And the offspring then can decide to either kind of accept what the parent gives or the. They can use one unit of energy to compel the parent to give them two units of energy. And then the parent can either comply or use one unit of energy to shut down the request. So you have a situation where you can have dead loss, right? If, you know, I request or make a demand, right, I use one unit of energy to say, hey, give me two. And then you say no. Then we have both just lost a unit of energy. And if I succeed, then, you know, I've gained one, but at a greater expense to you, right? You've lost two. So it, it's a very sort of simple way of getting this, this tension across. And you know, and then I play it with my class where there are, you know, a dozen or so of these groups of four. And, and then we talk about it afterwards, right? And you see like, oh yeah, where like everyone was like signaling and shutting down. Like they, in the end, you know, didn't have as, as high success as the groups that were actually, you know, being more cooperative and not protesting. And, and it's also, it can be very funny sometimes, right, because you'll have, have like one of the, you know, one of the baby birds is like a total pain in the ass. And all the other siblings are like, oh, come on, you're, you know, making it bad for all of us. So it's a, it's a, It's a really fun, fun way for the, the students to kind of learn about these ideas of genetic conflict and in particular, parent offspring conflict.
- [158:08]
A
So. Yeah, yeah, yeah. I deliberately wasn't using human specific language. I mean, markers are just distasteful to think about this.
- [158:15]
B
It is, yeah, I might among humans.
- [158:17]
A
But also it would, this would be, this would be less pronounced among humans relative to most species because humans often reproduce together repeatedly, whereas in many species, male and female go their separate ways and don't, don't reproduce like a year after year, in which case the male has almost no interest in the future reproduction of the, of the female beyond that point. And this is going to be even more extreme, more awful.
- [158:41]
B
Yeah. And when we play it, you know, it's just like a parent and then offspring because it, you know, it's really the same, the same dynamics. If you just have one individual that's basically like the individual who has access to the resources and is trying to distribute them. That's really the key piece of this. It's not, it doesn't have anything to do with, you know, what we associate with being male or female in any broader sense. It's just, you know, who's, who's. Who's distributing the resources.
- [159:10]
A
So. Yeah, I don't know why I included this. I guess it's just the moral of the story to me is that game theory and evolution and genetic conflict are really, really screwed up. It's a dark, dark vision of the world. And I'm glad, and I'm glad that people on a conscious level don't operate this way, at least like, only, only 10%.
- [159:27]
B
I'm, I'm so glad to. But. And you know what, though? I will add though, that, like, it can be really funny. And like, from, you know, teaching in my class and using these games, the students have a lot of fun and end up making lots of jokes that I think, like, there's, I think anytime you have tension, you have conflict. We like humans, we like to learn about that and engage about that because it's, it's really important for us to understand how those things work with life. Yeah. And so I think it can, like, I think there's this sort of sense in which maybe, you know, it's inherently rewarding to think and talk about it in, in terms that are humorous because it does allow us to, like, wrap our heads around around it, but without taking it so seriously that it has to make us depressed.
- [160:14]
A
All right, we've done cancer and cooperation to death, so let's push on to something more cheerful. As you said in the intro, your next book, Everything is How to Thrive in the Apocalypse, is about how we think about civilizational disaster scenarios and the effect that thinking about that has on us. This is super relevant, this audience, because a lot of listeners study nuclear war, bioterrorism, worst case, climate change, artificial intelligence gone wrong, and naturally, that can be pretty psychologically taxing. And it's also worth thinking about how you're thinking about it and what potential biases you might be bringing. Yeah. What's the problem? The practical problem that you were hoping to solve with this one?
- [160:54]
B
Yes. So the book, it's called Everything Is Fine, how to Thrive in the Epoxy.
- [161:01]
A
And.
- [161:01]
B
And it's meant to be both sort of serious and ironic, like, yes, everything is fine on some level, but really we are also in denial about everything being fine. We have to kind of deal with that. But really the only way that things ultimately will be fine and are fine is if we are able to figure out how to network our brains together in an effective way to leverage all the information that we have about how our systems work and not just the sort of technicalities of our, you know, global systems and, you know, ecological systems and economic systems, but also the social systems that we as humans have that have helped us deal with risk for as long as we have been around. And so it's kind of a, you know, half like, humorous field guide to living in our apocalyptic times. And half a call for, you know, bringing out our heads together to do a much better job of sharing information and managing risk collectively and being able to sort of build that up from simpler components. And so, yeah, so for me, the whole point of the book is to, number one, make the crazy times that we're living in now now not feel quite so scary by bringing some humor, some playfulness, some cool illustrations from Neil Smith in To Make It Fun and then kind of creating a space that I hope people will see as sort of an invitation for us to. To all work together more effectively and, you know, and leverage our ability to cooperate and share information in a way that will help us do a better job job of dealing with all of the challenges we're facing now and will absolutely continue to face as the future unfolds.
- [163:04]
A
You mentioned early on in the book that it seems like human beings have Found it extremely gripping to talk about massive disasters and ways that things could go really wrong for as long as we have records from people. Yeah, tell us about that.
- [163:18]
B
Yeah, I mean, if we look at small scale societies, if we look at any societies around the world, really ideas about that there are threats out there in the world, some of which might sort of end civilization as we know it. Or simply the idea that there are sort of cycles where sometimes things are good and then sometimes things are worse and that we have to have sort of mechanisms for being able to deal with those times when things are worse. Those are all very, very common, you know, probably universal across all societ. You know, storytelling is I think, an important piece also of, you know, especially in small scale societies, how people kind of retain that memory, you know, when things are good that yeah, sometimes things aren't so good. And so, you know, we need to be thinking about how to manage risk, you know, at all times. What, you know, even if it's just like on a yearly basis, like if you, you know, deal with really severe words, winter storms, like Mongolian herders do, right. They're managing risk all year. They're not just waiting until the winter storm hits. They're fixing, you know, their shelters for themselves and their livestock. They're, you know, collecting hay and you know, other feed so that they can keep their livestock alive through the winter. And you know, you can kind of think of that on then larger scales where we, we want to be managing risk proactively, not just waiting for a crisis and then dealing with it in that moment.
- [165:00]
A
Yeah, I suppose it makes sense that humans would have a big attraction towards thinking about ways that things could go wrong. I suppose it's another expression of how, I mean, people just tend to worry a lot. Like our default way of when we're just sitting alone by ourselves, we tend to think about there are ways that things could go wrong in future, future. A lot or at least many people have that predilection. And I guess it makes sense for societies as a whole to also think about ways that things could go wrong for society so that you can plan ahead and think about ways that you might solve. It seems like humans are also interested in even more extreme disaster scenarios than that. It makes sense that we'd be worried about the winter and the weather and some flooding, drought. But there's something that's also very attractive about just thinking about the end times. Yeah. Have you thought, thought about that at all?
- [165:47]
B
Yeah. Well, I mean, you know, when you say end times, right. And you Think about like really like big disasters. I think one of the things about that that's compelling is, and scary, of course, is the idea that the, a lot of the structures that we, you know, know, the norms of society, the just the ways that we do things, those can and often do change in those times. I mean, even, you know, with the COVID pandemic, which, you know, on a sort of long time frame is not a particularly horrible pandemic. I mean, obviously it was very, very bad. But just compared to, you know, others that we know could have been much worse, has been much worse. It changed so many things about how society was structured. And you know, people talked about it as an apocalypse. And I mean, I, I think like, you know, Covid also kind of brought the idea of like the apocalypse as like a household word kind of, you know, like people just started using it and you know, I started talking about the before times, like right away when Covid happened, because I was like, all right, now we can, you know, kind of use the apocalypse playfully, but, but you know, it's, it's serious, it's, it's hard, it. But there's also a sort of interesting open endedness and potential for creativity, potential for re envisioning things that comes when systems get disrupted. And so I think that there's, you know, both opportunity to think about how we might do things differently when a lot of change is already being forced. But it is also, you know, it's also scary and can potentially be very problematic to have, you know, institutions disrupted that might actually be playing a very important role already in regulating cooperation or, you know, keeping society functioning in a way that, you know, doesn't disadvantage some people. But there also might be things about the way society is working that can definitely be improved. Right. And when a lot of things change, that I think opens up some opportunities to, to think differently about how we're doing things.
- [168:07]
A
Are there any particular classes of disasters that trouble you in particular? I suppose earlier this year I was pretty worried about the risk of nuclear war due to Russia's invasion of Ukraine. It felt all too real. Sometimes. I guess really rapid advances in AI this year also kind of had me a bit on edge. You don't know what AI is going to be capable of next. It seems like the future's coming up at us pretty fast. Yeah. Are there any things that trouble you?
- [168:35]
B
Yeah, well, off the top of my head I've got, I've got three. So certainly nuclear events very of the moment now and I think also will not go away. As a threat because, you know, we just, we have the technological capacity to do, do this. And I don't think that we're going to be able to get to a point point where every, you know, entity who could make a nuclear weapon would refrain from, from doing that. So I think it's, it's something that is likely to be there for the long term future. Pandemics. Absolutely. I think, you know, we saw with COVID you know, just how vulnerable our systems were and unfortunately, we haven't done a huge amount to try to fix the, the weaknesses and vulnerabilities in the systems that we have for, you know, early response to emerging pandemics. So I worry about that. And you know, my, my AI worry is less sort of, you know, like what happens with AI on its own. And it's, my worry is much more sort of what happens with AI in combination with humans that have goals that are nefarious. And I think that there's a, there's a sort of leveraging that you can get when you bring together human minds and the, you know, artificial minds that, that allows for a level of, you know, exploitation and undermining of, you know, systems that you, you just can't get with one or the other separately. And, you know, and, and I'm, I'm, I'm very aware of the, the weaknesses that AIs have in terms of some of the sort of like, you know, big picture assessments of, you know, like, what actually is a path that makes sense to go given a lot of, you know, uncertain variables and, you know, potential pitfalls, that it might be hard to sort of represent all of those if you don't already understand them well enough yourself to articulate them in computational terms. But I think, you know, I, I think there are humans who have sort of instincts about how to navigate very complex strategic situations that when you pair that with the computational power, the raw power that, you know, artificial minds have and their ability to integrate, you know, massive amounts of data. To me, that's, that's the scary thing. And I think to some extent, extent, we're kind of already there in that human AI interface apocalypse.
- [171:46]
A
Yeah. With the chatbots improving as quickly as they are. Even if you don't have any alignment issues between humans and machine learning models. I don't know what we do in a world where someone with a few thousand dollars worth of computer hardware can affect, effectively produce the language output of 10,000 people having conversations or 1,000 people having conversations, or they can just output all of this text as if they're simulating all kinds of realistic human interaction, sending emails, posting stuff online, I mean you can even simulate video extremely realistically. Now, I don't know what that world looks like. It's coming down the barrel awfully fast.
- [172:26]
B
It is.
- [172:27]
A
We're going to need to adapt all of these protective mechanisms in order to, to prevent like fake people basically.
- [172:32]
B
I mean we have it already, right? I mean it's, I mean I, I don't know what the data is about, what's actually going on on Twitter in terms of this, but from the friends I have who are, you know, on Twitter in spaces where there's a lot of, there used to be a lot of valuable dialogue going on, they're becoming dominated by what, you know, sounds to me from their description descriptions like a bunch of nasty chat bots that are just, you know, trying to interfere with what otherwise would be real conversation. So, so yeah, I mean, yeah, I.
- [173:08]
A
Guess I've definitely seen that on Twitter. That has been the case for a while that you've got this problem with really stupid bots that just, well, that just interject nonsense and shut down useful conversation. The crazy thing is now it's going to be potentially very cheap to have 100,000 bots arguing extremely, un articulately, extremely persuasively as well as any human could in favor of whatever chosen thing and having real conversations back and forth based on what people are saying. I'm not sure whether you've tried ChatGPT. It's really impressive. At least we've gotten to the level of being able to reproduce arguments at the level of a smart 15 year old. But at some point they're just going to be able to articulate arguments in these chats as better than humans might be able to honestly in other cases. And it's a very similar strange future.
- [173:49]
B
Yeah, yeah. I think there's a lot of really interesting things to explore about this sort of issue of, you know, human AI interactions. And you know, you mentioned the alignment issue and you know, I think we tend to think about that as a large scale, right, like alignment with human interests and human well being. But you know, the fact is humans have their own strategic goals and interests, you know, that are many, many of them are at the individual level or at the, you know, level level of groups or at the level of, you know, nation states and things like that. And so to the extent that AI can be leveraged for particular interests, I think that that is, you know, and that that process of really, you know, what's Ultimately, cooperation between humans and AI to accomplish certain goals, even if those goals are at the expense of the rest of humanity. To me, that. That is one of the most important issues for us to grapple with at this moment, with what's happening with AI Right now.
- [174:54]
A
Yeah. Setting aside AI in the first chapter of the book, which you kindly sent me, you seem kind of very negative about the current moment that we're in or the kind of crises that we're facing or like how apocalyptic our current moment is. But I guess, yeah, when I looked it up on Artworld Index, it seems like globally, deaths from natural disasters are going way down. So deaths from famine, from drought, from flooding, from earthquakes and all of that sort of thing. Do you think that we really do in some ways live in an era of very like. Of unusual risk, or is it maybe just that we have heightened perception of risk?
- [175:29]
B
So I think there are a lot of things going on. I think we have many systems that have done a decent job of helping us to make. Manage risk using financial instruments and things, but I think that there. That we have a lot of vulnerabilities that are sort of just inherent in living in a. In a world that is. Is changing rapidly right now on so many levels. And so there's, you know, simultaneously, you know, we can sort of look at the. At some of the data, like on our world and data and see, you know, there are a lot of ways that things have. Have been improving. But I think that the key piece is really that we have vulnerabilities that exist and I think are growing that we would do well to try to get ahead of in terms of managing them. And I think that also just on a sort of human scale, that people. People's anxiety about what's happening in the world is going up. Right. Like, it's just there. There's this sense of, like, change is happening so fast. There are, you know, all of these risks. I mean, the, you know, example you brought up of sort of, you know, the. The possibility of nuclear events. Right. I mean, the Doomsday clock is, you know, pretty damn close to midnight and has been for a while. So, you know, if we think of, like, the things that could kind of end the world like that, you know, that's. That's certainly, I think, a real and present risk. And there's also, you know, there's. There's. There are a lot of natural disasters that I think have been striking closer to home for people in terms of wildfires, in terms of terms of, you know, droughts. Especially, you know, in the US like, there's just, you know, serious issues with water, you know, use and availability in the medium term. And, you know, people see, you know, like, out their, you know, backyards or on their drives to work that, like, things aren't the same with water or you can't actually take your boat out. Right. So. So I think that there's a. It's something that's present for people in. In their lives and not just because of the pandemic, kind of making, like, apocalyptic, you know, ideas a little more. Yeah, so. So I think that, you know, there's. There's certainly. We're at it. We're sort of at an apocalyptic kind of moment just in terms of, like, I think people's receptors captivity to the idea that maybe we should be managing risk more proactively. And. Yeah, and. And a lot of the sort of, you know, setup for the book with the first chapter is. Is kind of meant to, like, put a, like a playful tone on the fact that things are fucked up in a lot of ways right now. So it's. It's not meant to be, like, pessimistic, really. It's just like, hey, there's a lot of stuff going on.
- [178:48]
A
Risk that we face.
- [178:49]
B
Yeah, yeah.
- [178:52]
A
Yeah. So what kind of advice do you have about how people should think about the apocalypse in order to, I guess, yeah. Be happier while they're doing it and maybe think about it in a more productive way?
- [179:03]
B
Yeah. So I think one of the easiest things that we can do is just think about risk management in a fun way. Right. So. So there are a lot of things that we can do at the household level to manage risk better. And then we can also sort of build communities that do a better job of managing risk. And then you can take that up to the highest scales as well and things like making sure that you're ready for an emergency. Right. So there's this idea of all hazards preparation, which is basically just, you know, emergency preparation, but you can make it a little bit more fun by being like, hey, are you ready for the zombie apocalypse? You know, do you have, like 72 hours worth of stuff so you could just shelter in place? So, you know, things like some basic emergency preparedness that actually, you know, helps to make our. Our overall systems more robust too. Because if there is a natural disaster and all households are able to. To shelter in place, say, for 72 hours, then whatever, you know, institutional level, you know, support is available to, to deal with the problem can be focused on the acute problem. As opposed to having to split effort between the problem and the humanitarian crisis that can emerge in, in, in those situations. So, and that's not to put it all on like individual households to do this because you know, really we should all be thinking about how can we help everyone in our communities be able to, you know, weather a storm, you know, supporting, supporting all households in, you know, being able to have what they, what they need to, for example, shelter in place. Just, just to take one example of, you know, the kinds of things that we can do. So that's one and then the other one is kind of building these networks where we can get help in times of need, ask for help. Those often spontaneously emerge in disasters. But having some networks already set up ahead of time before things get really bad, it's an easy way to make, manage risk by sort of doing what people call limited risk pooling, where it's like, yeah, if you're in need and I'm available, you know, I have enough to help, then I'll just help you without expecting to get paid back.
- [181:39]
A
That's interesting. I haven't really heard that idea before. What sort of agreements would you, or like what sort of relationships might you want to build ahead of time? I suppose here we're kind of thinking of disasters like. Well, I suppose in an extreme place, nuclear war possibly you manage to survive it. I guess also earthquakes would be another classic or massive wildfires in some places.
- [181:57]
B
Yep. Flooding, you know, massive power outages in the winter or the summer. Right. Like there's, there are a lot of.
- [182:07]
A
I suppose now we have to worry about cyber attacks that could shut down the electricity grid. Something kind of unprecedented.
- [182:11]
B
Absolutely. Yeah. This kind of then opens up like this whole other, whole other area of my work which is really about, about looking at cooperation in human society. So we have this project called the Human Generosity Project where we've looked at almost a dozen small scale societies around the world now and how they help each other, how people within those societies help each other in times of need. And we have found that, you know, if you kind of look at the risk management strategies that people are using, using that need based transfers, this like, you know, hey, if I'm in need, I will only ask for help if I'm genuinely in need. And then if you receive a request, you will help if you're able to without going below what you need. So we see this in, in pretty much every society, the, the one society where they don't use it as much as this society I was telling you about in Mongolia, where they have these, you know, winters that are just horrible. So they have to help each other kind of ahead of time. They have to manage the risk proactively rather than, you know, because they can't like go to each other's houses when there's like, you know, six feet of snow outside. Yeah.
- [183:24]
A
So what do they do?
- [183:25]
B
So they, they will help each other build shelters and make sure that everybody has the, you know, the, the resources that they need. Yeah. So it's basically sheltering in place for the winter. They're helping, helping each other, you know, be able to do that for their families and their livestock.
- [183:43]
A
But, but anyway, I would immigrate. This sounds awful.
- [183:46]
B
Yeah, but, but the, the bottom line here is that people, you know, around, you know, around the world in small scale societies do this and also like in rural societies here in the US So we've studied ranchers in the southwest in, here in Arizona and New Mexico, near the border with Mexico. And they have a system they call neighboring which is largely a need based transfer system where they help each other in times of need and they don't expect to get paid back for those things that like arise unpredictably. So, so these are things that already, you know, exist and you know, they're, they're really good at handling the kinds of things that, you know, typically we want insurance for. Right. Those things that we can't predict and can't control. And if you take them to, if you take it to the extreme, there's certain things that market based insurance actually cannot insure against because there's no way to.
- [184:53]
A
Everyone gets hit at once.
- [184:54]
B
Yeah, so that's one possibility, everyone gets hit at once. But another is just that it hasn't happened yet. And there's no way to really calculate what the probability is of the event or how severe it was would be. And in the absence of any of that information, you know, you can't, you, you can't calculate what an insurance premium could be. It's an actuarial problem. Right. It's like you need the data in order to price the insurance. But with these need based transfer networks, you know, they like, you can at least have them in place for any kinds of needs that arise unpredictably. Now whether the system will be able to effectively handle that, those is another question. But you, you at least are able to set up systems that can deal with things that are, that have never happened before, that we can't even understand what the risks are like.
- [185:49]
A
So, so I live in a city, London what should I try to coordinate with my, with my neighbors around? I suppose a big issue is people don't have very large places, so you can't really stock. Oh, it's like difficult to stockpile enough water or food or anything, anything like that. And I guess in a, well, in a, in a worse scenario, London's a very juicy target. So I think things could get pretty, pretty grim.
- [186:12]
B
Yeah, I mean, I think no matter where you live, having, you know, 72 hours of supplies is, is wise and, and you can actually do this in a way that makes sense for having a very busy lifestyle, which is something that I love. So, you know, if you serve prep on the go. Exactly. And it's like, you know, apocalypse casual lifestyle. Like, how do you do this? Well, like, for example, you know, if you like couscous. Couscous is a great food to have around. Not only can you prepare it very quickly on a weeknight if you need something to eat, but it stores well and you actually don't even need hot water, water to prepare it. You just, you can just add water to it and let it sit for like a half an hour and then you could eat it. So if, you know, if couscous is something that like you're fine with, then you can just make sure to buy enough couscous at the store that you could, you know, at least have it be part of what you would be eating for those 72 hours. And whenever you buy a new one, you put it at the back, you just have like some extras. And then, you know, like, it also makes it easier when you're super busy and you don't, you don't have time to go to the store. You're like, oh, I got my 72 hours of preps. I mean, obviously next time you go to the store, you want to like, but you know, sort of thinking about being prepared, not as like, oh, I have to go and like figure out how to buy like really long shelf life food on Amazon. And then, you know what, who's a reliable source for this? No, you just look at the kinds of things that you like to eat that are shelf life stable and just have more of those on hand because that will make your day to day life easier and also will put you in a better position if something totally unexpected happens and you have to shelter in place.
- [188:07]
A
Yeah, I mean, the UK has a pretty precarious food situation actually because it relies on constant stream of imports. It just, I mean, it just doesn't produce anywhere near enough food for the, for the population that it has. So I would suggest having. Having enough food for weeks, conceivably months, would be not. Not outrageous if you were able to do that here. I guess the storage issues. I did at one point store a whole bunch of rice, but I didn't store it well enough, and mice got into it. And that was very embarrassing. I was a very amateurish prepper. But yes, no, we have some rice and pasta in a thick Tupperware.
- [188:43]
B
Yeah. Yeah. And. And I mean, I think, like, that another thing is just not being. Not feeling intimidated by, like, oh, I have to do all of these things. It's like, no, just start with, like, having enough water around and, you know, having some extra dry food that is stuff that you eat anyway. And then, you know, you can. You can work from there. It's not like you have to do all of the things all at once or anticipate, you know, every possibility because it's. Because you just can't, you know, know, and, you know, and having conversations with people about, like, you know, what they're doing, do they have their preps? Like, it can be fun. And, you know, I mean, if you get into, like, a, you know, little social competition about it, I could be like, playful, fun, like, all right, let's. You know, I have this idea for like a, like a new kind of dinner party. I haven't tried it yet, but I absolutely want to, which is like, you. You like, roll the dice to, like, figure out whose house you're going to go to, and then you show up at that house, and then you have to figure out how to, like, make a really nice dinner with just the shelf, stable prep food that's there. And so then you kind of practice, like, making fun, fun meals and, you know, surviving. And you're like, you know, mini apocalypse dinner party. So, yeah, stuff like that. I think, you know, we could make it fun. And then it just kind of puts our attention on, like, yeah, maybe we should just be, you know, ready for the unexpected so that at least we have some more time to plan, you know, and that's the thing. It's like, you might not be able to, like, you know, have enough food around to actually manage the risk of something, you know, catastrophic that would happen. But you can have enough food around so that you have a few days to figure out what your next steps are if something, you know, really catastrophic happens.
- [190:26]
A
Yeah. Makes. Makes a lot of sense. Those. Yeah. When you start talking about. Yeah. Stockpiling food to protect yourself against disasters. I think some people's eyes kind of roll and Yeah, a bit crazy to start associating you with, with preppers who get, who get really into it. Maybe a little bit, a little bit too into it. It is. Earlier this year my partner and I did spend a bunch of time thinking about, you know, what would we do if there's a nuclear war and we survive? What would that look like? I mean it was, it was a very, it was very long odds, but maybe it was getting probable enough that it was worth having a conversation about it. Yeah, it is, it is really fun on some level.
- [191:01]
B
Exactly. That's the thing.
- [191:02]
A
I mean maybe not everyone enjoys this so it's easier for them to kind of have disdain for survivalists, but there is something just. Yeah. Very entertaining I guess. You know, our lives can be a little bit boring on a day to day level. Imagining, you know, what would we do if just everything was destroyed? How would, how would we cope?
- [191:18]
B
Yeah, yeah. I mean there's like people have called it survival porn. Right. There's something like, just like appealing about like imagining yourself like out there or inside trying to survive, you know, in challenging odds. Um, it's, yeah, it's like a little like a story that we like tell ourselves. Right. That makes us have fun and style.
- [191:40]
A
When we're little kids we play make believe all the time and it's really fun but as grown ups we don't get to do that very much. Yeah, but this gives us an excuse to imagine a really different reality.
- [191:48]
B
Exactly. Yeah. And I think that's, you know, that really puts a really, you know, nice like pin on what I'm trying to do with this book which is like, it's an invitation to play a little bit of make believe about all of the, the things that could go wrong, things that are already going wrong place. I mean there's places in the world that are just straight up apocalyptic right now. Right. But we, but if we go into that place of like having fun imagining the zombie apocalypse or how we would survive in a, you know, nuclear war where there were you know, giant huge spiders outside. Right. Like you like add something fun and silly and then, and then it like, it makes it not as real which makes it easier for us to engage without that fear response kind of dominating. Right. And so I think like, you know, we can learn a lot from looking at you know like horror and looking at like apocalyptic fiction. And like, you know, people like to engage with these things if there's enough of an element of play to it. And so I think if we can Keep that play playfulness, cultivate that playfulness and make it social as well. You know, that, that, that's really, that's what's going to help us to manage our risk as individuals and ultimately, you know, collectively manage our societal risk more effectively.
- [193:12]
A
Yeah. What's something that people worry about in the apocalypse or in a catastrophe that maybe they shouldn't worry about quite as much as they do?
- [193:21]
B
Yeah, well, the big one for me is this like this idea that as soon as something starts going wrong that the, you know, fabric of society is going to fall apart and that everyone will just be like every person for themselves. Because if, if we look at, you know, what actually happens during times of disaster, people jump into action to help each other in this sort of need based way. Even, you know, helping strangers, even, you know, going to extract extreme risks yourself to like rescue people. Like people just do this spontaneously when the hits the fan and you know. Yes. If, you know, disasters go on for a really long time, if you have, you know, slurp, slow burn situations where people are, you know, starving and that lasts for, you know, months or years. Right? Yeah. Then, you know, when people are in a state where they just like literally don't have enough food or water or whatever, like our physiology starts to not function normally and you know, things can break down once you get into that like, famine territory. But you know, if we're just talking about sort of acute disasters and if we're talking about situations where, you know, ultimately people are able to, you know, jump in and help each other and, you know, and deal with like, you know, fixing some of the problems that have arisen together. You see that, you know, in the first few weeks, especially after a disaster, before everyone kind of like, oh, now we're going to kind of go back to normal. So. So yeah, so I think that, that people having the wrong assumptions about what happens in those moments, you know, not only is that not supported by what we see in times of disaster, I think it can also be really problematic.
- [195:24]
A
Destructive attitude.
- [195:25]
B
Yes. Yeah. And, and it doesn't necessarily put us in a good place to be proactively managing risk together either. Right. If you're like, oh, you know, everybody's going to turn on everyone, everyone for themselves.
- [195:37]
A
I got to get my knife.
- [195:38]
B
Yeah, yeah. This sort of like, you know, know, survivor mentality. Right. You know, that like show. Right. Like in the end it's like everybody's pitted against everyone else even if they cooperate a little bit. You know, like that's not often, that's not how it works. Usually that's not how it works. You know, we humans survive because we, you know, cooperate and work together. And that is how we have survived forever. Yeah, yeah. You know, hunter gatherers, like, you don't just have one, like, hunter, gathering, gatherer, like, foraging and hunting. Like, they live in a group and like, they share, you know, at a central place, usually around a fire. Right. Like, with, you know, whoever's gotten what. Like, that's just. That's how we.
- [196:19]
A
How our organism operates, basically.
- [196:20]
B
Yeah, yeah. And we like it. Like, we like to eat.
- [196:23]
A
A single hunter gatherer is a dead hunter gatherer.
- [196:25]
B
Yeah, yeah, yeah. And. And I, you know, I think, like, a lot of. A lot of that's reflected in just how we set up psychologically and emotionally. Right. We. We like eating with people. You know, like a dinner party is super fun, or like, preparing food with people or, you know, just spending time with others, creating things together or, you know, like, we really thrive on being. Being social and taking care of others to a certain extent too. Right. That's something that a lot of people intrinsically enjoy. And so I think, you know, really, really delving into that side of, you know, our human nature that desires to be interdependent and embedded and generous and helping others and, you know, part of systems that are functioning well where, you know, we're there to back each other up and manage risk together. I think, you know, we like that stuff. And the better we can understand the sort of, you know, evolutionary mechanisms and, you know, cognitive and emotional mechanisms that underlie that, the better a job we will be able to do to manage the risk of the multitude of apocalypses that we're likely to be facing in.
- [197:37]
A
This can go wrong. Yeah. Yeah. It's been interesting watching the conventional wisdom on this shift over the last few years. I think back in 2019, the conventional wisdom, or like, people's intuitions are really that even quite modest disasters would lead to the breakdown of law and order. Yeah, everyone's just like, stealing from one another just because it's a relatively mild problem. And then I remember early on in COVID 19, some people were predicting, oh, there's going to be, like, blood on the streets. It's going to be chaos. Everyone is just going to look out for themselves. There'll be a crime wave. The exact reverse was the truth. Crime went way down. Violence went way down. I mean, to start with, if people are staying home, it's much harder to get into fights. It's much harder to burglarize their house. When there's people in there. I think actually the US Is almost the only country in the world where crime didn't go down all that much. I think there was some kind of unique US Specific factors there. Although I think it did go down in the short term. But yeah, now there's been quite a big correction. And I keep hearing this point that people make that it's remarkable how extraordinarily cooperative humans are when things go wrong. Like when everyone's part of the same struggle, the same, they're fighting against adversity together, then actually we're way more cooperative in that situation than we are just on a typical day when we run our commute to work normally. Is it possible that we've overcorrected in some way? Is there anything to be said for the idea that people can be uncooperative or is there any way to tend to that?
- [199:02]
B
I mean, absolutely. It's a matter of sort of understanding in what ranges of parameters you get what behavior. Right. So in situations where things, you know, are bad for a long time and people are starving, then you can get, you know, what we would consider the breakdown of like society and families and all of that because, you know, people are literally just, you know, on the brink of dying.
- [199:28]
A
It's quite zero sum.
- [199:30]
B
Yeah. And, and also, you know, I think there's, we don't really know, like when you get to the point of people being in that sort of starvation state where they're, they're very likely to die. Like what of the behavior that you see would we call adaptive from an evolutionary perspective? I. E. Was selected because it provided an advantage versus a byproduct. So it's just like, you know, this is very, you know, unusual state for the organism to be in. And there are things that are happening that are just the result of molecular pathways. Yeah. So, so we don't know and you know, it's not something that we can really study, obviously. So I think, but, but practically what we see is in those situations that you, you do get a, a breakdown and you know, the other situation where you, you know, definitely can have, you know, favoring of cheating is in, you know, groups where, you know, there's a bunch of anonymity, they're large people don't necessarily feel like they have a, a stake in the well being of the group that they're a part of.
- [200:49]
A
It's not kind of peer monitoring or perhaps, you know, justice done when injustices are committed.
- [200:55]
B
Yeah, yeah. And so in, know, in those kinds of situations. Yeah. Individuals that are exploiting are going to, you know, do better. And if people see that, you know, exploitation and, you know, cheating is happening, then that can very quickly unravel, you know, if the sort of norms start changing about that. So I think we, you know, we absolutely need to consider both sides of the coin here. You know, what are the situations where cooperation is, you know, not just, not just makes evolutionary sense, but also is like, you know, how people behave in practice? And then where are the situations where, you know, exploitation and cheating really, you know, are problems both from an evolutionary perspective and a practical perspective? Again, yeah.
- [201:48]
A
Cool. Well, I'm sure there's tons more that there will be tons more in the, in the book on it when it comes out. One of the fun things about imagining these scenarios is that they're so diverse that you can, you can just keep on going. There's so many different considerations. There's a lot of, a lot of things that you can think through. When is the book coming out?
- [202:04]
B
It will be coming out in the spring of 2024, so still, still a little ways away.
- [202:11]
A
But yeah, well, hopefully we're all still around in spring of 2024 so that people, people could buy the book and get the extra advice.
- [202:20]
B
And I, and I am going to be, be posting lots of tips and things in the lead up. So I'm on Twitter and on Instagram and posting about this stuff all the time. So you can find me there if you, if you want to learn more or ask questions about it, I'm always happy to share.
- [202:35]
A
Yeah, well, you've been very generous with your time, but we should, we should finally, finally set you free again to continue with your normal life. But I guess a final question is I saw on your website that you're involved in some like, zombie apocalypse medicine preparation thing. I don't really understand the nature of this, but, but what was it? And I guess what's something useful you learned about surviving the zombie apocalypse?
- [202:57]
B
Yeah, well, so I, I started and I'm the executive producer for this, like, whole group of, you know, really fun and interesting scholars. We were called Zombified Media. And we have, you know, the Zombified podcast that I co host with, with my friend and colleague Dave Lundberg, Henrik. We have this live stream channel called Channel Zed where we have all sorts of shows that are, you know, based around the idea that the zombie apocalypse is going on now. And here's like, you know, how you, like, get your pantry set up. Here's how you, you know, set up Your go bag. Here's how you, you know, deal with the. The zombies outside in a way that, you know, makes sense, given cooperation theory. Right. So. So we like, kind of use the zombie apocalypse for there as like, a fun way to. To engage people. And it all actually started with the zombie apocalypse medicine meeting. So we just had the third one of those. We do those every two years. And it's basically a academic conference framed around this idea that the zombie apocalypse is going on. And we have to try to understand, you know, zombie behavior. We have to, you know, look at, like, what's actually, what are the threats that we're facing in the world now? What are the threats we're facing in the future? And so it's. It's a really.
- [204:15]
A
Did your head of department sign off on this? Who. Who approved this?
- [204:18]
B
Oh, so. Because we. So Zombified Media is a educational, nonprofit media company, I have to acknowledge we have a lot of support from ASU and, you know, financially, but also, you know, there are a bunch of amazing people who are professors at asu, part of the Lincoln center for Applied Ethics in the Psychology department, in the center for the Future of Innovation Society, the Center for Science and the Imagination, lots of places that have supported us and, you know, people who've come on and talked with us. So we, you know, we have a special relationship.
- [204:54]
A
It's great to see all these bodies finally supporting an interdisciplinary research project. Exactly. So. So rarely interdisciplinary. Get the support that it deserves. Here it is. Yeah, sorry, I interrupted. Carry on.
- [205:07]
B
No, you're absolutely right. And I mean, part of why we all love it is because it is a space that is fundamentally interdisciplinary. And by setting up this frame that it's the zombie apocalypse and we're trying to figure out what to do, it automatically takes all of the sort of, like, jargon and like, status positioning and like all of these things that are really obnoxious at academic meetings. It's just off the table. And the people who are into that stuff, they don't come to the meetings. Right. So it's like, you know, it's like all these people who are like, yeah, like, let's play. Let's talk about, like, you know, zombie, you know, food choice as a way to, like, you know, understand like, what's actually going in in terms of. On in terms of how people perceive food and their disgust. Right. So. So people, you know, come to it with this creativity. People even will design studies specifically in order to be able to talk about them at this meeting as a fun way of framing a research project. So it's a really generative, fun space. And now as we're moving forward with zombified media, we are starting to integrate ASU students in helping to produce shows, coming up with content, and, um, you know, sort of doing all levels of things. So we're, we're trying to make it this very, you know, interdisciplinary space that also bridges across, you know, the different levels of, of learners. Because ultimately we're all trying to figure out what's going on in this crazy world. Right? And I think young people have a lot to bring to the table that, you know, those of us who've been around for a few extra decades, like maybe, maybe we, you know, have some blinders on and we need to have, you know, fresh brains with us so that we're not just, you know, eating old brains that are, like, filled with prions. Right?
- [207:00]
A
So, yeah, yeah, think of that. Maybe in a real, in a real zombie apocalypse, most of our effort would be going towards getting the CDC to finally, finally acknowledge, stop dragging its heels on the fact that zombification is spread through biting and that washing your hands is just never going to be sufficient. Sick CDC burn there. My original question was, yeah, what is an unusual. What's an unusual tip that you've learned for how to survive a zombie apocalypse? I mean, I guess there's a wide range of different possible apocalypses of the zombie kind, so maybe you need to be more specific about the exact scenario you find yourself in. But, yeah, any advice for listeners?
- [207:37]
B
So, absolutely, I've got one big tip, and it applies to all apocalypses, which is to build your Z team. So this is. Who are the people who you would want by your side in the zombie apocalypse or really in any, any hazard? And that doesn't necessarily mean that somebody, you know would have to be like, literally by your side, but somebody who you would want to be sharing information with that you would want to, you know, be there to back each other up if something went really wrong. And, you know, so that's, I think, you know, and that's basically risk transfer. That's the risk pooling, limited risk pooling. You know, start setting up those relationships. You probably have a bunch of people in your life already. You just don't even think about them in those terms. Terms. But, you know, have a conversation with them about, you know, like, hey, like, if, you know, the zombie apocalypse happened, like, what. What would we do? Or if, you know, a nuclear event happened. If you want to be more serious, right? So you can, you can start to have those conversations and, you know, just think about how, you know, you can proactively manage. Manage your risk. And, you know, cultivating that Z team is a super fun way to do it. And, you know, hopefully, hopefully your Z team members, you know, they're like, hey, do you have your 72 hours? Because, like, you know, that's like, you.
- [209:00]
A
Know, it's a bare minimum to get in the team.
- [209:03]
B
And if not, you know, let me help you. Right? So we, I think we can approach it, you know, from this, from this perspective of how do we kind of bring. Bring. Bring more people in to this idea of, you know, making managing risk fun and, and, and also, you know, we should absolutely not neglect the neighborhoods and communities that we live in, because in the event of an emergency, it's likely that, you know, there'll be some interdependence with the people who, who live near us. And, and then, you know, we can all can also think about scaling, scaling that up. Right? So there's like, you know, these sister cities programs that really, they arose for, like the, for cultural exchange and educational exchange, but now, you know, when there are disasters in cities that are sister cities, oftentimes there's just this spontaneous, like, outpouring of help. They. They're kind of like, you know, Z team members to each other. So I think we can kind of generalize this, like, Z team idea, this risk transfer idea to a lot of different levels, try to grow those systems that, you know, increase our resilience at the individual level, household level, neighborhood, community, national, international levels, and yeah, risk management for the win is what I. Is how I like to look at it.
- [210:21]
A
My guest today has been Athena Actifas. Thanks so much for coming on the 80,000 Hours podcast, Athena.
- [210:26]
B
My pleasure. Thank you so much for having me.