Rob’s intro [00:00:00]
Rob Wiblin: Hi listeners, this is The 80,000 Hours Podcast, where we have unusually in-depth conversations about the world’s most pressing problems, what you can do to solve them, and what I should do when my genes pull knives on each other in a darkened alley.
I’m Rob Wiblin, Head of Research at 80,000 Hours.
Cooperation and conflict are absolutely fundamental concepts that one has to have to hand both in order to understand the world and figure out how to improve it.
Last year we did an episode on the theory around one form of conflict, #128 – Chris Blattman on the five reasons wars happen.
And today’s episode with the academic evolutionary theorist and podcaster Athena Aktipis, we cover the theory around one entirely different sort of cooperation and conflict — that between genes and cells.
As Athena explains in her book, The Cheating Cell, cellular cooperation expresses itself in the wonder of multicellular life, and when that cooperation breaks down and turns to conflict, that conflict expresses itself as cancer.
But similar forces of peace and cooperation as well as cheating and conflict arise at all levels of complex organisation across our universe, so we look at other scales these phenomena appear — within cells themselves, in human societies as they exist today, and perhaps in the future, between civilizations spread across different planets or stars.
Deeply understanding these ideas is useful in so many domains I can definitely recommend listening to this one as well as picking up The Cheating Cell if you’d like to understand them better.
Alright, without further ado, I bring you, Athena Aktipis.
The interview begins [00:01:51]
Rob Wiblin: Today I’m speaking with Athena Aktipis. Athena is an associate professor in the Department of Psychology at Arizona State University, where she’s the director of The Cooperation 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 Cell: 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.
Athena Aktipis: Thank you so much for having me here. I’m really excited to talk to you about all of the things.
Rob Wiblin: Yeah, it’s been just “cancer, cancer, cancer” for me this week for my housemates and colleagues. So I’m going to be able to get all of the cancer stuff out of my system and then stop hassling them about it. Or I can hassle all listeners all at once.
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?
Athena Aktipis: 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. It’s like a playful take on existential risk and how we can deal with it as the social beings that we are.
Rob Wiblin: How did you end up writing that book?
Athena Aktipis: Gosh, I ended up writing this book because I just could not stop thinking about and talking about these issues. Even before COVID, I was sort of already using the apocalypse as a way of thinking about and talking about existential risk that I thought was maybe a little bit more playful and fun and appealing than just the more straight approach to it.
And then the pandemic happened, and then that just accelerated very quickly. People were just talking about the apocalypse: “Yep, we’re in the apocalypse.” And I think that actually provided some levity almost, to just be like, “Yeah, it’s the apocalypse.” So I just kind of leaned into that and started doing more livestreaming.
We started Channel Zed, which is television in the zombie apocalypse. Which is basically just an excuse to make a bunch of TV shows that address issues like: 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 how can we just understand our world using evolutionary biology, using a really interdisciplinary approach that includes both science and humanities and considering policy and ethics? Bring all those things together, bring all those people together, to start thinking and talking about those issues.
So that really got me going in that direction. And then at some point I was just like, “I want to write a book to get these ideas across with a playful tone, with illustrations.” And it ended up being something that Workman Publishing was really interested in, and just got set on that pathway. And it’s been really fun, I have to say.
Rob Wiblin: 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.
Athena Aktipis: Yeah, it’s like, what are we going to talk about? How about some really morbid topics like cancer and the apocalypse? Just choose which one.
Rob Wiblin: I suppose a more positive framing on it is “cooperation.” So I said in the intro that you’re a cooperation theorist. What is cooperation at the highest level of abstraction? I guess your whole thing is thinking about cooperation at a high level, and then you can use that to analyse all kinds of different ways that different organisms, or even molecules, interact with one another?
Athena Aktipis: Yeah, yeah. I mean, my whole thing is looking at the world through the lens of cooperation, and conflict too, as these organising principles. And just like with physics, the laws of physics apply at all scales. Right now, some laws of physics apply maybe more at some scales than others, just because of the way the universe is set up. I think it’s really similar with the laws underlying cooperation.
So there are many things that apply across systems and scales, but then there’s some things that apply more to some systems than others. For example, you can look at things like division of labour. That’s a basis of cooperation across pretty much all systems that have cooperation, that you can have division of labour — or in many systems, that’s something that you can have.
Economies of scale: that’s another one where, as you scale up, some things become more efficient. Maybe you reach a point where that stops and then it becomes less efficient. So there are principles that apply.
Another one is 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 protect, monitor, or respond.
That last idea, that last thread, is really what the big-picture inspiration was for the book, The Cheating Cell. So thinking about our bodies as this cooperative system and as cancer as a breakdown of that cellular cooperation.
But big picture, we can look at cooperation at all these different levels, using different methods. That’s another thing that has been really important to me in my career: not just having one methodological approach or one disciplinary approach. So bringing anthropological fieldwork together with psychology experiments together with computational modelling — and doing all of that also in the context of considering policy implications and ethical implications, and having that be part of the same conversation, the same research project. Not splitting those things out and then having one place where you’re like, “Let’s try to bring it all together.” No, part of the process is having all those things happening at the same time, getting that cross-fertilisation, and being able to be truly interdisciplinary as a result.
So that’s what I love. And that’s a lot of what I’ve been doing in my career up until this point, and hope to continue to do.
Rob Wiblin: Nice. 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 you put 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 species level or the planetary level. And then we might maybe zoom in and instead talk about cooperation within cells rather than between them.
Now, before I saw this book, I had thought of cancer just as a disease that arises somewhat at random because of chance mutations and genes that happen to go wrong. I guess there’s a sense in which that is true, but it’s not the whole story. The Cheating Cell made me see the tension between cancer and non-cancer very differently, and as a far more fundamental phenomenon that comes along with life in all its forms — and probably potentially could forever. First off, what is the opposite of cancer?
Athena Aktipis: The opposite of cancer, I would say, is multicellular cooperation. 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.
Rob Wiblin: So what is cancer, basically? What traits does cancer have, and how is that relevant to the lack of cooperation?
Athena Aktipis: 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 — because as you get bigger, you can’t just rely on diffusion for resources; you have to somehow get resources into the middle, basically, of a clump of cells;
- division of labour — so having multiple cell types that can do multiple jobs, different expression states, things like that;
- and then the creation and maintenance of the extracellular environment — this is all of the things that are on the outside of the cell that make the organism more viable: proteins that are produced, the matrix in which all the cells are embedded. And that’s an environment that can be really healthy, or it can be quite literally polluted by acids and things like that if cells are being wasteful and messy, which they can be — so they can sort of be “cheaters” in that sense of polluting their environment.
So you have these five foundations of multicellular cooperation. And what we see with cancer is a breakdown in each of those: 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 labour that they should; they will not do the jobs that they’re supposed to do; they’ll monopolise resources; and they will trash the environment. So you can get a breakdown in all these foundations of multicellular cooperation.
And in fact, when you take the “grounded in theories of evolution of multicellularity” approach with these foundations of multicellularity, and you map that onto how cancer biologists have looked at the phenotypes of cancer — there’s this framework called the hallmarks of cancer that’s sort of classic work — the breakdown in those foundations of multicellularity mapped very well onto the hallmarks of cancer.
And 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 really interesting and useful then to take these frameworks from thinking of the evolution of multicellularity and ask: “Are we missing something in how we’re defining cancer?” For example, division of labour originally was not really part of the hallmarks framework. We suggested that a breakdown in differentiation should be considered a hallmark of cancer. And now, things are coming around to that actually being part of how people are looking at the sort of next generation of the hallmarks of cancer.
Rob Wiblin: I think part the change in framework that I’ve had in my mind, thinking about cancer, is: when we imagine bacteria in the environment or bacteria living inside our cells, we understand that they’re 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’re going to learn to evade the immune system and avoid our antibiotics and things like that. We don’t normally think about our cells 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 in its desire to replicate.
Athena Aktipis: It’s got a little side hustle going on, you know?
Rob Wiblin: Yeah. “I’m just a liver during the day. Really what I want to be is a metastasis.”
But of course, within our bodies, during our lifetimes, our cells are facing the same kinds of evolutionary pressure that a bacteria within us would. 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. Is there anything you’d add to that?
Athena Aktipis: Yeah, absolutely. I mean, it is a big shift of perspective. Especially as somebody who’s trained in evolutionary biology, and the default is to think about evolution as this really, really, really slow thing. But if you think about what the parameters of evolution look like within the body for cells that are evolving or potentially evolving inside the body, you have super short generation times. You have just completely mind-blowing population sizes. And once you start getting mutations existing, you can get what’s called a “mutator phenotype,” where mutations just are going crazy, there’s so much variation.
So if you have those kinds of parameters, then evolution by natural selection — and also drift too — but evolution by natural selection can go really, really fast. And the opportunity for evolution by natural selection to operate just over the course of cancer progression is much faster than all of the evolutionary time that we have had as humans since Homo sapiens came about. It’s a lot — it’s orders of magnitude more — so we just have to shift to a different scale.
I almost think of it in… What was that show when we were three years old, where you shrunk down and went inside the body?
Rob Wiblin: Yeah, The Magic School Bus? I think that’s an American thing?
Athena Aktipis: Yeah. So you have to go and kind of put yourself on a different spatial scale and time scale, and just shift your thinking to be like: the body is a world with all these different ecosystems in it, and the cells are existing on a time scale where, if we’re going to map it onto anything like what we experience, a day is at least 10 years for them, right?
So it’s a very, very different way of thinking. Then once you shift to that, you’re like, “Oh, wow, there’s so much that could be happening in terms of adaptation inside the body, how cells are actually evolving inside the body over the course of our lifetimes.” That shift just opens up all this potential for using evolutionary approaches in adaptationist thinking to generate hypotheses that then you can test.
So I don’t know how much you guys talk about adaptationism on the podcast. Should I say what the basic idea of it is?
Rob Wiblin: Yeah, go for it. It might be the first time we’ve said that word on the show. It’s possible.
Athena Aktipis: Oh, wow.
Rob Wiblin: Breaking new ground.
Athena Aktipis: Amazing. OK, so adaptationism is basically this idea that you can look at the world through this lens of What’s the function of things? If an organism has some physical or behavioural characteristics, what is the function of that? It’s a way of bringing in an evolutionary perspective where you’re thinking of things as if there’s a purpose. You actually used some of this language earlier, of “bacteria are trying to survive.” Well, they’re not like, “Oh, I don’t know how I do this inside the body,” but they behave as if they are, right?
So one of the ways that you can think of adaptationism is you’re looking at what’s happening as if it is with the purpose of surviving or reproducing. And when you take that lens thinking about cells in the body that come from the lineage that originated with the conceptus that was us, it really starts to 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.
Rob Wiblin: One thing that makes it less natural to think about cancer in this way is that we know that the endpoint of cancer is the death of the organism that hosts it, and the death of the cancer itself. But of course, evolution has no foresight. I think 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.
Athena Aktipis: Absolutely.
How multicellular life survives [00:18:58]
Rob Wiblin: Actually, maybe that’s a little bit extreme. And in fact, maybe that leads very nicely to the next question. Let’s wind back. Remind me, how long ago was it that multicellular life actually managed to get off the ground?
Athena Aktipis: 500 million years to a billion years. Something like that, approximately.
Rob Wiblin: Yeah. So go back half a billion years or so, give or take. Until then it’s all been kind of individual cells. But I guess these cells are trying, or there’s evolutionary pressure for them to get the benefits of being larger and having multiple cells and specialisation 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 interest 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 cooperators can then be really easily undermined by a cheat who is able to fool everyone else and take advantage of the group, bring down the whole cooperative system of the group, undermine it and make it not work.
So I’m kind of wondering, why doesn’t multicellular life suffer from that same fatal issue?
Athena Aktipis: 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. Somewhere between 30 and 50% of people 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 these ideas of group selection. I’ve always kind of been an advocate for using multilevel selection as the language, because I think that the idea of group selection, or the phrasing of group selection, has been almost a political issue within evolutionary biology — with people being like, “I’m a group selectionist,” or “I’m not” — so it’s been 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 meet those criteria. So if you’re in a situation where those criteria are met, then you should say, “Yes, group selection can happen when you have heritability and you have differential fitness.” And when you have situations where those criteria are met, you should just say, “Yeah, you can have selection acting on that level.”
One way of looking at what happened in the transition to multicellularity is that you basically shifted from situations where you had individual cells getting selected to having groups of cells getting selected. So you could say that actually was group selection, or is continuing to be group selection — in that we are made of 30 trillion cells that are cooperating and coordinating to make us viable.
Now, I think that the way that a lot of people have framed this — in order to stick with the individual-level analysis and individual-level mathematical analysis — is to say there’s a transition in individuality, where you go from it being individual cells to now being organisms that are getting selected in their own right. 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 what constitutes a group versus what constitutes an individual — when you want to make that mental or mathematical leap from what you’re saying is a unit or not.
So I’m pretty pluralistic about this. We sort of opened by talking about how all the laws of physics apply at all scales, but 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 mathematical and conceptual models around the evolution of cooperation: that some apply more at some levels than others, and that it’s useful to have many of these tools in your toolkit to be able to use in the right context.
And multilevel selection, I think, is one of the ones that’s a little bit more general, because you can be like, “This is a situation where the selection pressures are greater between groups, because you have more variation between groups than within them,” for example. So I think that it’s a more broadly useful framework.
Rob Wiblin: OK, so I guess we can see from the result that multicellular life exists that basically, evolutionarily, 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 most cells to see whether they’re acting suspicious and then trying 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?
Athena Aktipis: Yeah, I would just add that it’s not just the immune system. We have really three different levels on which you have monitoring and responses to cellular cheating.
So the first one, I would start with the cellular intrinsic mechanisms: i.e., what the cell is doing on the inside to monitor what genes are being expressed, what proteins are being produced, what the cell is doing in terms of its physiology. Genes like TP53 are basically listening in on all the stuff that the cell is doing from the inside. And if it seems like the cell is maybe doing things it shouldn’t be doing, then it raises an alarm. Initially, that alarm halts the cell cycle, it starts engaging the DNA repair process. And if that doesn’t work, then it’s like, “You know what? We’re just going to [die] so that we don’t mess things up for everybody else.” So it’s kind of like the cellular conscience. You could think of it that way.
Rob Wiblin: The cell gets ashamed.
Athena Aktipis: I have some fanciful metaphors. Yeah, yeah. It’s like, “Oh, sh—” — oh, can I swear on this podcast?
Rob Wiblin: Definitely. Yeah.
Athena Aktipis: Oh, OK. Good, good, good. So that’s one set of mechanisms. And TP53 is not the only one. There’s many, many genetically based systems inside the cell that are monitoring the behaviour of that cell and changing the state of that cell to do DNA repair, halting cell cycle, engaging cellular death. All of those things are options to keep the cells from making a problem for the rest of the body.
So you have that level, and then you have the neighbourhood level. So cells are constantly monitoring each other and constantly sending signals to each other. They’re sending survival signals and anti-apoptosis signals.
Rob Wiblin: Apoptosis is cell suicide?
Athena Aktipis: Yeah, yeah. And sending growth signals as well. So basically those anti-apoptosis survival signals are saying, “Cell, you’re good, hang in there with us.” And then the growth signals are saying, “Yeah, you can keep dividing. Everything’s all good, in my opinion, with you.” So, again, anthropomorphising, but it’s useful I think — because these same kinds of processes, there’s elements of that that happen across all systems.
Rob Wiblin: If you don’t use this language of intent and purpose, I feel like the sentences just become so absurdly convoluted. It’s such a slicker way of thinking about it. Although I guess you have to have all these red flags go off when you’re doing it wrong, or doing it in a way where evolution wouldn’t actually cause it. Sorry, go on.
Athena Aktipis: Yeah, yeah. So you’ve got those two levels, and then you have also the systemic level — which you were referring to earlier — where you have this sort of broader system that’s monitoring the body for regions where maybe something isn’t right. And that’s a really good backup system for those other systems that we already talked about. It also plays a broader role in just looking at if there’s bacteria or viruses that shouldn’t be there.
But even the cell intrinsic systems and the neighbourhood systems, they’re not just monitoring for these internal things in the cell — they’re also monitoring for viruses and stuff like that too. So there’s overlap in terms of some of these mechanisms that are there just to protect us from things that might be trying to hijack us or undermine the broader evolutionary interests of the whole organism.
Rob Wiblin: Yeah. 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 inasmuch 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 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 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 uneven fight between us and these various other pathogens, between our immune system evolving and improving 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 in Tasmanian devils, where they have very low genetic diversity and they also spread the cancer by literally biting wounds into other individuals. And then, as we’ll discuss later, wound healing releases growth hormones that then are conducive to cancer production.
Athena Aktipis: Yeah. As an aside, I just have to point out: if there is a species in which a zombie apocalypse is going on, it’s the Tasmanian devils who are biting each other’s faces and spreading contagious cancer.
Rob Wiblin: Does the cancer make them more vicious and cause them to bite more? Maybe it makes them mad.
Athena Aktipis: There is a hypothesis that the cancer actually is affecting aspects of their behaviour, including also their reproductive behaviour. So I don’t know this literature that well, but there’s definitely some interest in it. And I have a grad student who’s intrigued by this as well, so maybe she’ll be working on that.
Rob Wiblin: Seems like a full zombie apocalypse. Brilliant.
Athena Aktipis: Yeah, exactly, right?
Rob Wiblin: It’s terrible. It’s tragic.
Athena Aktipis: It is, it is. But that’s the thing. It’s like we have to approach all of these terrible things with a little bit of humour, otherwise how are we going to keep working on them?
Why our anti-contagious-cancer mechanisms are so successful [00:30:52]
Rob Wiblin: Very true. Why do you think that we’ve mostly successfully beaten contagious cancer, but not so much bacteria and viruses and sometimes fungi?
Athena Aktipis: I think that one of the things that’s actually missing from the way that a lot of people think about cancer — especially in sort of oncology and cancer biology — is this window of what was going on very early in multicellularity, which you you made a reference to.
If you consider the early stages — where you’ve got some groups of cells, and they’re growing and they’re producing public goods that are good for all of the cells in there — and if you get a cell coming from this other group and popping in there, it can get the benefits of what that other group has created. It’s a free rider problem, a common-pool resource problem. It’s the sort of classic issue.
I think the very evolution of multicellularity is not just about regulating the cooperation within an entity that is beginning and might evolve cheating, but the early evolution of multicellularity was the evolution of prevention of contagious cancer. I think we should be thinking about that as one of the fundamental things that was going on in the early stages of multicellularity. A lot of these systems that we have that are part of our immune system have many of their origins in that original selection pressure in one way or another. Or at least that’s where we need to start when we think about what kinds of mechanisms might have evolved: that adaptive problem of cells just popping in and trying to get the benefits of that entity.
Many of our cancer suppression systems could potentially originally have been in place for prevention of contagious cancer. It’s an open question of which of our cancer prevention mechanisms have to do with that, versus having to do with maybe the more modern problem of preventing cancer from the inside as opposed to hijacking from the outside.
Rob Wiblin: I’m seeing some academic politics going on there. How could that be an open question? Surely we can just theorise about this and 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 been replaced by something else.
Athena Aktipis: Well, so Rob, when you are working in an area where you’re applying new theoretical frameworks, you’re bringing things together, there are many places where you start to question the assumptions that are out there about how things work. Sometimes there are a lot of really good reasons for those assumptions. Other times, there are not. I think we’re kind of on the same page. I like to be like, “First principles, this is what we should assume.” It’s almost like a Bayesian kind of thing: “Coming from first principles, here’s what I think a reasonable assumption is.”
Rob Wiblin: It’s hard to prove.
Athena Aktipis: Yeah, so it’s important to acknowledge that there’s a community of researchers who have been working with a particular frame, and have made progress on problems with a particular frame. I think that it’s a good thing to frame it as: This is a hypothesis that comes from these first principles. It makes some predictions that could be tested. And encouraging people.
Rob Wiblin: To do that.
Athena Aktipis: Yeah. That’s the other thing. I can’t test all of the hypotheses myself that come from this, and so it’s an opportunity for us to consider an alternative hypothesis based on evolutionary first principles.
Rob Wiblin: Totally. OK, sorry, I interrupted you there. I think we were heading towards why our anti-contagious-cancer mechanisms are so successful, relative to our ability to stop other pathogens.
Athena Aktipis: Yeah, right. A lot of that I think is because the very evolution of multicellularity required that that occur. And also the kinds of threats that you could have from a human cell that is trying to hijack a human body are specific in a way that you could get specific anticancer mechanisms evolving for. Versus, if we’re thinking about pathogens, we’re thinking about viruses and bacteria and fungi: you have so many different species, so many different mechanisms of action. You have to get evolution on every one of those specific kinds of potential risks, or some general-purpose systems, which we have as well. But yeah, I think it’s worth that perspective. It’s not just like human cells versus pathogens. It’s like human cells as one kind of thing that could be an infection.
Rob Wiblin: Right. Yeah, yeah. One way I might rephrase that is: every contagious cancer’s starting point is a healthy human cell, and then it’s got to modify from there. And that’s a very limited design choice. Whereas if you’re talking about viruses and bacteria, they’ve got a very blank canvas on which they can write any possible infections or behaviour or lifecycle or so on.
I guess maybe also, human cancer cells 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 they’re even smaller and they just have a faster lifecycle. Is that generally right?
Athena Aktipis: Yeah. Viruses, if they’re inside a cell, they can replicate like crazy. Cancer cells, I think the current thinking is that they can reproduce as quickly as 24 hours or a little less. They can get pretty fast.
Rob Wiblin: Pretty swift, yeah.
Athena Aktipis: But you’re absolutely right that 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. Also, we need to recognise that there’s a pretty big repertoire that cancer cells can access as well, because our genomes have a lot of things that can be messed with to make these cells that do things that are evolutionarily unprecedented, at least for what a cell in a multicellular body should do.
Rob Wiblin: Yeah. By having a much larger genome, then a bacteria can potentially have much more complicated capacities. And also of course a human cell is ideally already situated to live in a human body in a way that a bacteria might not be. It does have that sort of leg up. But evidently it’s turned out to just balance out into usually it’s easier to prevent contagious cancer than contagious bacteria.
Do plants and fungi get cancer as well as animals?
Athena Aktipis: It all comes down to how you’re defining cancer. There’s some politics about that, academic politics. Some people are like, “You can’t call that cancer.” But if you’re asking, do you get disruptions in cell proliferation and apoptosis and differentiation of cells, the division of labour, all those things — the answer is yes. Essentially any multicellular lineage that you look at, you see examples of at least what we could call cancer-like phenomena, where cells are proliferating when they shouldn’t for the survival or reproduction of the organism. And where you can have disruption of the division of labour, of the differentiation of the cells.
Rob Wiblin: I’ve known people who have said, “Unfortunately 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.” In what ways is plant or fungi cancer different than that in animals? It seems like on balance it’s a bit less visible or less of a big deal.
Athena Aktipis: Actually one of the things that happened early on in my 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 awesome thing. There’s a decent number of them around here, where rather than having this sort of classic shape — where they have one or a few trunks coming out — you get this crown on the top, it just fans out and it’s beautiful. And I was like, “Wow, that really is a plant cancer.” You have this disruption in the growth.
And when I looked into the physiology of it, you basically have a situation where, on the tip of any plant that’s growing, there’s usually a few cells that are called meristem cells — they’re basically the plant equivalent of stem cells. And as they proliferate, they create a sort of linear thing. But you can get a disruption where rather than just a few cells in a little clump, you have some cells in a line. Then what ends up happening is as those cells are all proliferating, they start to kind of fan out. And you get all these almost like brain-like patterns or crown-like patterns.
It’s called fasciation. In a way, with fasciation, it’s almost more visible. You can see it, you can envision a little bit more what is going on with cell proliferation when you have these disruptions. Just because of the physiology of plants, you don’t have stem cells just stuck inside all of the tissues. They’re kind of at the ends, right? So I think it’s a really cool lens to think about what happens with cancer. Also because 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. We actually created a garden here with crested cacti, to teach about how cancer is this phenomenon that exists across life — cultivating it as a space for people to go to remember people who’ve been affected by cancer, and using it as a way of thinking about how can we live with cancer as opposed to just fighting it.
Yeah, I love plant cancers and what they do for us on so many levels, in terms of thinking about what cancer is, how it manifests. With plants, a lot of times they can survive with these fasciations. They’re more vulnerable often than plants that don’t have fasciations, but if they’re taken care of, they can thrive. There’s just a lot of nice metaphors there for thinking about how we can deal with cancer differently.
Rob Wiblin: This now sounds incredibly stupid to me, but I used to say that 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 tumours or cancerous behaviour in a more elegant way, where it’s less fatal to them. They could just grow off in some direction and that doesn’t necessarily kill the entire organism. And a plant can just 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 the reason why it seems like plants die less often of cancer? You were saying 30–50% of people will have cancer by the time they die. It doesn’t seem like 30–50% of wheat stalks have cancer problems by the time we’re harvesting them. I suppose with plants that are that short-lived, it’s just that they haven’t been around for long enough. But what about old trees? We don’t see old trees dying this way. I imagine it’s something to do with the fact 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.
Athena Aktipis: Yeah. Plants: totally awesome, right? They’re just so cool. I think a lot of times we are not just anthropocentric in terms of thinking about how the rest of life works, but mammalian centric. And a lot of plants, there’s a huge amount of genetic diversity that exists within them. Different branches will be really genetically different; you can have fruits that are genetically different from each other. And you can get this process of natural selection really happening even within a plant, with different branches thriving versus others, and then dropping branches — and sometimes those can actually grow into new trees.
I mean, the biology is just really different. It’s so different from what our assumptions are, as these honestly not-very-resilient organisms that we are. We think we’re so awesome, but with the exception of some fanciful Marvel movies, we can’t even regenerate a limb. We’re kind of pathetic.
Rob Wiblin: Pathetic. Embarrassing.
Athena Aktipis: It’s embarrassing, yeah. But yeah, I think that broader frame of just thinking about: How does life solve these various problems? How does life adapt? How do some organisms adapt during their lifetimes — actually genetically adapt, not just behaviourally adapt? I think that expanding that frame is not just really important for how we look at and think about biology, but it’s also really fun to know these things. To be like, “Oh, wow, that plant has got all of these unique mutations in different branches potentially that could lead to differential survival and reproduction.” It blows my mind.
And of course it’s not like all plants are the same. There’s all sorts of different ways that different plants work and different ways that their reproductive systems work. There is so much. And I’m no plant expert; I’m just a fan.
Why elephants get deadly cancers less often than humans [00:46:02]
Rob Wiblin: Another fascinating thing in the book: elephants have way more cells than humans — and no surprise there; I think it’s 100 times as much or something — and yet they get deadly cancers less often than we do. That’s super counterintuitive on its face, because you’d think that the probability of you developing a seriously dangerous cancerous tumour would be roughly proportional to the total number of cells you have, because each one of them has an opportunity to itself become cancerous. Why is it that elephants don’t get cancer much more than humans?
Athena Aktipis: That’s a great question. And again, we have to think about definitions here, because a lot of elephants actually have growths, have tumours — they are just not metastatic and cancerous, and they don’t threaten their lives so much.
But to get back to your main question about why an elephant is less likely to die of cancer than we are, or than a mouse is? That’s a big contrast. And to think about 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.
Long-lived large organisms have to invest a lot more in what we call “somatic maintenance,” which is just a fancy way of saying fixing your body and making sure that the body maintains itself well. In order to have a chance at reproduction, a large, long-lived organism needs to be doing a lot more cellular things to take care of the body — including DNA repair, monitoring for cellular cheating, and all of that. Organisms that are larger and longer-lived have more robust cancer suppression mechanisms than organisms that are smaller and shorter-lived. And this ties in with an idea in evolutionary biology called life history theory.
Rob Wiblin: Yeah. Can you explain that for a bit?
Athena Aktipis: Yeah, sure. You’ve probably heard the phrase, “Live fast, die young,” right? It’s something that’s kind of part of our collective consciousness. There’s this idea that you can have a strategy of living for a long time and living slower, or you could live fast and potentially burn out.
Rob Wiblin: Not plan for the long term, yeah.
Athena Aktipis: Yeah, that’s right. There’s a sort of version of this that applies to all life that evolves, which is that organisms in general have tradeoffs between surviving and taking care of their bodies, and maintaining their bodies and reproducing. Depending on whether an organism is prioritising survival or reproduction, that’s going to change how their physiology and behaviour manifests.
And it can have a lot of knock-on effects that are self-reinforcing, right? Basically a mouse is a fast life history strategist, we would say: it invests in becoming reproductive quickly, having lots of offspring. And doesn’t invest a lot in its soma, in its body, and in things like cancer suppression. An elephant, on the other hand, 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 body itself, which 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.
Rob Wiblin: I like to picture life history strategy by imagining the evolution kind of embodied in these engineers or something, who are standing around chatting about the animals they’re going to design. And one of them’s like, “I’ve 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 to get all this energy.”
I 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.”
The other engineer says, “No, I’ve thought about this. What we’re going to do is we’re going to invest a tonne, OK? It’s got all these benefits and we’re going to invest a tonne of energy and molecules in making sure it doesn’t get cancer. We’re going to have real tripwires everywhere. Any cell that seems to be acting out, we’re going to shut it down right away. And OK, this is going to slow down the growth; it’s going to have an overhead. But at the end of the day, we’re going to have this massive elephant. It’s going to live for ages. It’ll be able to have lots of babies because it will live long enough.”
Then you could do the opposite with a mouse, basically, where you’re like, “OK, forget it. We’re not going to worry about the body. It’s just going to replicate like crazy.”
Is this basically the idea?
Athena Aktipis: I love this, and you’re just being 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 wrap our minds around how things are going to evolve given constraints, and what kinds of adaptations we would expect, given that you want an organism to be able to do this thing or that thing.
Yeah, I think the engineering metaphors are right on for thinking about how organisms evolve to maximise that combination of survival and reproduction, whatever that combination is that they’re sort of “aiming for” or “choosing.” I’m using scare quotes just because we’re using this intentionality as a shortcut for thinking and talking about something that is a long, complicated process of natural selection acting on all of these mechanisms. But we can use this cognitive shortcut, as long as we acknowledge it’s a cognitive shortcut.
Rob Wiblin: I just remembered in our annual feedback for the show, there was one person who wrote in their feedback, “Everything Rob says about evolution on the show is wrong.” Unfortunately they didn’t elaborate on that. So I don’t know. I can only imagine this poor soul is just hating this episode. If you managed to stick with it long enough, please email me and tell me what I’ve been saying wrong about evolution on the show. I was very curious. Anyway, continuing with maybe wrong things…
Athena Aktipis: I think we’re pretty good. We just need the right caveats in there. So I think we’re good.
Rob Wiblin: I slightly went over quickly what the downside is of having this slow life history strategy and a very large scale. But one thing is if you’re going to massively lower the probability that each cell becomes a cancerous or dangerous tumour — 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 the genome to make sure that even fewer errors are getting through. Are there other downsides like that that people should be aware of?
Athena Aktipis: Other than the cellular bureaucracy that you have to deal with? It’s like, “Oh, can I do this, please?”
Rob Wiblin: It’s like this byzantine thing that you have to go through to get permission to do anything.
Athena Aktipis: “I submitted the request three weeks ago, what’s going on? Can I please divide now?” Yeah, I mean, there are all sorts of tradeoffs. I mean, one of the basic principles of thinking in evolutionary terms is that there are going to be tradeoffs. If you want to divide quickly, then you have to deal with the potential of having more mutations. If you don’t want to have that tradeoff, you can be stuck up against the fact that there’s actually physical constraints. If you’re going to divide and check the DNA, that takes actual time, right?
Yes, you can make more proteins that monitor things. You can even try to get as much friction out of the system as possible. But eventually there are some tradeoffs that you just can’t escape once you get to a certain point when a lot of things have already been optimised in terms of getting those systems functioning efficiently.
Rob Wiblin: 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 the case that elephants, if they sustain a cut, the skin doesn’t grow back so quickly? Or maybe their cell turnover within their stomachs and intestines isn’t as good as it is for humans?
Athena Aktipis: Actually, I’m not sure how systematically that has been measured in elephants. But there is a general set of tradeoffs with, for example, wound healing and cell turnover and cancer susceptibility.
If we think of an organism that can heal a wound quickly, 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 — because if you don’t, you’re more likely to get an infection, you’re more likely to have your ability to do things impacted, if you heal less quickly. There’s a lot of benefits to being able to close a wound more rapidly than not. But if you do that, you also have cells that are more likely to be on a hair trigger for increasing their proliferation and moving if the environment suggests that there’s a wound.
One of the things that you actually sometimes see in tumours is that the physiology inside the tumour kind of looks like a wound that doesn’t heal. By being able to heal a wound, we have a set of buttons, the levers that can get pushed, and that leaves us susceptible to cancer. The more rapidly your wounds can heal, potentially the more susceptible those organisms will be 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 and less likely to have functionality impacted for as long.
Rob Wiblin: Yeah. One thing maybe we skipped over a little bit quickly is: a mouse, say, 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 as long as the organism lives, it has avoided those mutations. The problem is, as a mouse, your odds of being killed in the environment are really high. Why would you want to be planning for years ahead when you are unlikely to survive that long anyway? Or at least the odds are far lower for a mouse than an 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 favour of maintaining, building, and ramping up these anticancer measures, because they just don’t carry as much importance. Because you’d probably be dead before too long regardless.
Athena Aktipis: Yeah, absolutely. That’s a really important part of life history theory: 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 high “extrinsic mortality”: the chance that you will die from something random in the environment. If that’s high, then the organisms will evolve to invest less in somatic maintenance, because it could just be gone like that. Versus situations where resources are a little bit more stable, then you get selection for slow life history strategies.
Life extension [00:58:29]
Rob Wiblin: I think we’ve now done 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 ageing. And I guess as part of that, they’re going to want to ramp up these anticancer mechanisms that we have, in order to prevent us from developing these cheating cells that create problems. And potentially there are avenues to do that. There are people thinking about other drugs that we can do to basically 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 ageing and extend human lifespan this way, would our injuries heal less quickly, and would we have to be more careful about anything that went wrong in our intestines because the cell turnover wouldn’t be what it was?
Athena Aktipis: Yeah, there’s potentially a lot of inadvertent tradeoffs that could arise. There’s also a tough bind of if you want to extend life by reducing the risk of cancer, and you interfere with things like cell proliferation and the rejuvenation of tissues that stem cells help us do, well, how do you have your evolutionary cake and eat it too? How do you both make sure that the organism is renewing itself properly, while at the same time not allowing that renewal capacity to get hijacked by agents that —
Rob Wiblin: Misbehaving cell. Yeah.
Athena Aktipis: Yeah, yeah. And this is part of why cancer’s such a tricky problem. Because you run up against all of these tradeoffs, and you think you’ve got it cornered over here, but then you’ve got all these things happening over here. So you’re like, “Oh wait, no, I’ve got to get over here.” It is a slippery thing to think of how we would eliminate cancer, and what would we lose if we tried to eliminate cancer, right? There are a lot of tradeoffs.
And we’re not going to get around that, because cancer is a susceptibility that is just built into being a multicellular organism. We can evolve a lot of mechanisms to detect it, to respond to it — and those systems can evolve to be pretty good in terms of efficiency and reducing side effects and tradeoffs and things like that. But there are fundamental tradeoffs that we just can’t escape.
Rob Wiblin: Yeah. I don’t want to suggest that there’s no way that humans could be better from our wellbeing point of view. Because to start with, elephants exist, and 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. 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 tradeoffs 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 when a baby is growing, 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.”
Athena Aktipis: Yeah. The better a job that you want to do at avoiding these tradeoffs, the more complex all the systems have to be, which then in itself creates vulnerabilities for the system to be more hijackable. There is a lot that can potentially be done, but how good are we going to be at anticipating what the side effects are going to be and making sure that those are tradeoffs that we want to make for ourselves or for the next generation?
I think there are a lot of issues that we definitely should be thinking about and grappling with when we think about cancer, and the future of cancer. Because it’s not as simple as just, “What’s the magic bullet to make cancer go away?”
Rob Wiblin: “What’s the less cancer signal?”
Athena Aktipis: Right. Yeah, yeah.
Honour among cancer thieves [01:02:32]
Rob Wiblin: So a new theme: 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: how do they coordinate among themselves? Is it possible to maintain honour 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?
Athena Aktipis: Anytime you have the conditions that will select for cooperation, you can get the evolution of cooperation. So yeah, on a first pass we can think of cancer cells as cellular cheaters. But if they’re in a situation where they can produce growth factors, not just for themselves but for their neighbours — especially if you have clones, you have the same genetic lineage — it’s very easy to evolve this cooperative trait of producing growth factors that promote the growth of the cells around as well.
You can also get division of labour — some cells specialising in producing growth factors, other cells specialising in evading the immune system, even other cells specialising in reproduction. So there’s certain kinds of cancer cells, we call them “cancer stem cells” because they’re the ones that replicate, and there’s a lot of cancer cells that don’t. One potential explanation for why that is the case is because you have a sort of proto-multicellularity almost going on — where some cells can be specialising in the reproduction side of things and other cells can be specialising in doing all of the things to help that little cluster of proto-multicellular cancer protoplasm get around and replicate.
Rob Wiblin: Once you have a cancer that has developed this level of cooperation, cancer cells are always one step away from wanting to defect on the cells around them because that’s kind of their nature. What does it look like when cancer gets cancer? And does that happen very much?
Athena Aktipis: Yeah. This is sort of the idea that you can have a hyper-cancer or a meta-cancer. And I think in practice, anytime that you have cooperations… Say you have a cluster of cells that are all producing growth factors. 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. So whether or not you get the evolution of cheating or the extended evolution of cheating is going to be dependent on being able to maintain a population of entities that you can keep exploiting.
I think there are some barriers to cancer cells even getting to the point where you would have the evolution of hyper-tumours or hyper-cancers, just because constantly, at every stage, you have cheaters that emerge and are getting purged because of the population structure or other factors. Because the thing is, yes, within any group, the cheaters are going to do better than the others in the group. But once you expand your frame and you realise there are multiple groups — this is like a meta-population, and some groups are more stable than others, and the groups that are more stable than others tend to be the ones that are more cooperative — then that actually really changes the dynamics a lot, and makes it so that cooperation can be favoured.
Rob Wiblin: On this model, you’d expect a tumour to grow and then collapse as it’s undermined from within, but then another tumour to grow because they’ve figured out they’re still cooperating for now. And so they take over and it’ll be quite a dynamic situation. Is that accurate?
Athena Aktipis: You can get dynamics like that happening with the blood supply to tumours. Basically the cells can be signalling for more resources — sort of opening up the taps from the circulatory system.
Rob Wiblin: The rest of the body.
Athena Aktipis: Yeah. And as that happens, actually it’s very similar to an irrigation system, where the upstream individuals, if they open up the taps all the way, are depriving the downstream individuals. And actually you can also get the collapse 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 can get this sort of collapse — it’s like civilisational collapse because of basically exploiting the commons. There’s not a good resource regulation set of mechanisms there.
So that kind of dynamic does happen. But there are a lot of other places where you can get the evolution of cooperation and cheating. And honestly, to me, the scariest thing about cancer is the cooperation side. We’ve talked a little bit about working from first principles to make some predictions. And I think if we look at this from a first principles perspective, it’s quite likely that early on in the dissemination of cancer — so you have a primary tumour, but then you can get metastasis, which is the real problem in cancer usually: the systemic dissemination of these cells — by the time you have a metastasis that is visible in any sort of screening, that very often might have come from a long lineage of clusters of cancer cells that were selected on the basis of being already able to cooperate effectively in order to extract resources, reproduce, and move.
My colleagues and I have written about this some, and I wrote some about this in my book, but I think it’s one of the most neglected but most important evolutionary dynamics and evolutionary processes that is potentially going on in cancer. So when we look at metastasis, we might be looking at something that is actually the result of many, many, many generations of selection on group-level phenotypes of cancer cells already. That’s something that I think.
Rob Wiblin: It’s a very evolved beast.
Athena Aktipis: Yeah. So I think that requires a lot more attention. That possibility requires a lot more attention than it has had up until this point, because it has very different implications for how we might be treating metastasis if it is the result of many generations of selection on a collective phenotype or set of collective phenotypes.
When a cell should commit suicide [01:09:35]
Rob Wiblin: One really mind-blowing thing in the book is — I remember I was on the Tube and 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 set of processes that we’ll call TP53 gene. It collects a lot of information about what’s going on in the cell and in the local environment in order to decide whether the cell should commit suicide. 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 OK, we’re going to shut down the cell. We’ve got to shut this down because it’s too high risk that I’ve become cancerous now.”
Now, the interesting thing is that because so much work is being done by this one TP53 gene, protein and general 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. 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/apoptose. Why do you think it is that the cell puts so many eggs in one basket? I want to know what’s the answer.
Athena Aktipis: So, two things. One thing is there are many different processes that are all going on. It’s not just TP53, but it is the case that, like you said, all of this information is kind of flowing through TP53. And that’s a case for many of these other systems, where there is one point where if you break that point, then the whole system can get messed up.
So then the question is: why have everything flowing into one spot and then flowing out? One potential explanation for why this is the case is that in order for a cell to really figure out if there’s a problem or not with a cellular behaviour, it needs to integrate information from many, many different sources. For example, earlier we were talking about wound healing. So it would be important to know 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. Is this a wound healing situation or is it not?
In order to be able to integrate information from all of those different sources, at some point it all has to come together. So you can potentially have these points of vulnerability, because you need to integrate information across a lot of different domains, I guess you could say, in order to actually make a “smart decision.” Because it has a very different meaning, 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. The downstream consequence of what should happen is going to be different in those two cases.
Rob Wiblin: Maybe an analogy would be if you had a really big company, and the CEO 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 that creates a single point of failure, where if the CEO has bad judgement 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 organisation? And then if either one of them thinks we should expand, then we’ll expand.
And you can immediately see the problem there: 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?
Athena Aktipis: Yeah, some of them are not functional. But you can get genomes with multiple CEOs, I guess you could say. But then the question is: What happens with those over evolutionary time? Do they continue to process the same information? Do they differentiate into processing different streams of information?
I like thinking about it in these information-processing terms more generally, because I think that we tend to look at the cells in our body as, “Oh, they’re just blobs of biological stuff.” But actually they’re computational systems that are taking in huge amounts of complex information, processing it, and then changing gene expression as a result. And every one of our 30 trillion cells is doing it every millisecond.
So it’s mind blowing. And I think 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 impossible or anthropomorphic. But no, because there’s actually a lot of information constantly being processed by every single cell.
Rob Wiblin: 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. It’s so, so much.
Athena Aktipis: Absolutely. Yeah.
Rob Wiblin: There’s so much information processing going on. But it all has to be this automatic mechanical thing rather than something that’s conscious.
When the human body deliberately produces tumours [01:15:13]
Rob Wiblin: You think that it might be the case that the human body sometimes opts to produce not very dangerous tumours in order to have it kind of crowd out the appearance of more dangerous tumours. Can you explain that?
Athena Aktipis: Yeah, yeah. So whether you want to call it a tumour or not depends on how scared you are of the word tumour, right? But I do think that there are situations where if there’s a mutation or there’s a disruption in the local environment in a particular spot in the body, that 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.
Wound healing would be one situation where perhaps it makes sense in some contexts for cells to take over those open ecological spaces that are good at replicating quickly — perhaps because they have some mutations that might in some cases be associated with cancer, but are less likely to actually create more vulnerabilities in the medium term or long term.
It’s a counterintuitive idea, but there’s some evidence that you do have these sort of hotspots for mutation, where if you do get a situation like a wound, it might be more likely that you get a mutant to arise that allows for that quick proliferation, but doesn’t create other vulnerabilities that you might get if it was just any random mutation that could confer some selective advantage for the cells.
Rob Wiblin: 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: 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.
Athena Aktipis: Go buy The Cheating Cell.
Rob Wiblin: In all good bookstores. In the book, you suggest that cancerous tumours are more likely to evolve, to spread, to metastasise 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’ve thought naively that these mutations that foster travel to the rest of the body would arise just randomly, basically in proportion to the number of cells that are present in the tumour. Am I missing something about the evolutionary process here?
Athena Aktipis: Well, you’re absolutely right that the population size is critical for what’s the likelihood that you’ll get the emergence of a mutation that might affect any aspect of physiology. So if there’s smaller population sizes in regions where there’s lower resources, that’s going to certainly affect the likelihood that a mutation would arise.
But then if you have a mutation that affects movement — and that could be a mutation that actually just affects even the threshold for movement that the cells have, so they can be more or less likely to move given a certain level of resources — 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 and getting to a new place, even if it’s nearby, are going to have a selective advantage.
It’s not so much about overall the environment being depleted; it’s more about the patchiness of the resources. If there are situations where it could be really bad in one little area and then very close by, it’s good, then you can start getting the evolution of these motile phenotypes — which then, once you have them, has implications for what’s going to happen in the greater system of the body and over the longer term.
So the idea in this model that I made with some of my colleagues to explore this, our conclusion is basically that you can get the evolution of dispersal based on having patchy resources, and locally (at least in a small environment) lower resources. And this suggests that you almost might have the pre-evolution of these cellular abilities — these adaptations for movement and for conditional movement — that appear in a different way later with metastasis. But there may be a continuity there in terms of how those abilities start to evolve, just in a local tumour environment — before you see invasion, before you see things like metastasis.
Surprising approaches for managing cancer [01:20:22]
Rob Wiblin: 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.
One thing you talk about in the book is the possibility of not trying to kill a tumour, but instead taking a more subtle, soft approach, where we just try to manage its behaviour. Can you explain that whole approach?
Athena Aktipis: Yeah. The approach I think you’re referring to is adaptive therapy, which is really proposed and brought to the fore by Bob Gatenby from the Moffitt Cancer Center in Florida. The main idea of this is that if you try to treat a cancer with a 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 what happens with the evolution of resistance to pest control.
Rob Wiblin: And antibiotics.
Athena Aktipis: Yeah. So with high doses for a long time, you’re actually applying the strongest possible selection pressure to favour the cells that are resistant.
Rob Wiblin: Because all of the other cells will be dead.
Athena Aktipis: Exactly. The only cells that survive are the ones that can survive in the presence of the drug that you’re trying to use to get rid of the tumour.
So then the question becomes, “Well, what’s the alternative then?” I’m not going to say for all tumours, because there’s some where, yes you can get rid of them with standard chemotherapy. But if you accept that for certain classes of tumours, at least — especially if they’re advanced and are likely genetically diverse, they probably already have resistance mutations — the sort of logical approach is to look at it and say, “It’s unlikely that this could be eradicated with high-dose therapy. So we have to take as given that this tumour is going to stick around. So what kind of tumour do we want to cultivate?”
Well, what you want is a tumour that’s going to respond when you treat it. That’s going to be controllable. That’s going to not become invasive and metastatic. One that’s not going to disrupt the life of the person who harbours it as much. So you can then approach it from this perspective of, “Given that it’s going to stick around, what are the priorities?”
So the approach of adaptive therapy is really that you start by giving a dose of the drug, to get the tumour to a smaller size so that it’s a little bit more manageable. And then you only treat it when it’s growing, and when it’s not growing, you let it be. The idea here is that there’s usually a cost to resistance to drugs, because it takes energy for cells to pump out drugs from the cell or do other things that can confer resistance. So that means that when you’re not applying the drug, the cells that are sensitive to the treatment are going to more likely have an advantage over the cells that are resistant. So you kind of manage the tumour by treating it when it’s growing too much and then you back off, so you can get more of the sensitive cells there.
And patients are able to live for much longer than expected with these kinds of treatments. There’s ongoing work, there’s a lot more work to be done, but the clinical trials that have been done are really promising, even with late-stage cancer.
Rob Wiblin: So one thing that happens is you use some chemo, you get the tumour to shrink somewhat, and then you wait until it starts growing again. Then I guess you’ve got the evolution of some more pro-growth cells inside it and then you treat it again. I suppose the cells that are proliferating more quickly are probably more vulnerable to the chemo, because they’re at their metabolic limits trying to grow, and so they get disproportionately killed. So what you’re left with is the less-pro-growth cells in the tumour, and then you hope that they’re just going to lie low for a little bit while you don’t use the chemo.
Athena Aktipis: Yeah, that’s another one of the hypotheses that I have about what’s going on with adaptive therapy. That it might not just be about allowing sensitive cells to grow back, but also that every time you treat a tumour, conditional on it growing, you’re going to be essentially able to target those cells that grow more — because not only will there be more of them, but they’re going to be more vulnerable because they’re in that state of dividing.
Rob Wiblin: Maxed out.
Athena Aktipis: And doing that life history tradeoff of investing in reproduction over survival. So there are a lot of potential mechanisms that could be underlying that.
Rob Wiblin: Is adaptive therapy getting applied in more places now, tried on a larger scale? I imagine it was initially trialled in cancer situations that were most promising for it, where the existing more aggressive treatment wasn’t working very well, so people are looking for alternatives. I wonder, are people trying it in a wider range of situations now as well?
Athena Aktipis: Yeah, There are a lot of efforts now to start clinical trials with adaptive therapy. A lot of that has happened at the Moffitt Cancer Center, where Bob Gatenby is, and he’s developed a lot of collaborations there. We have some efforts going on here as well to test adaptive therapy in some mouse models, but also trying to actually start some clinical trials with breast cancer patients. But unfortunately, there aren’t a lot of economic interests in the private sector that are aligned with adaptive therapy.
Rob Wiblin: Can’t patent the idea of giving someone less medicine.
Athena Aktipis: Yeah. And it’s an algorithm for treatment. It can be used with any drug or approach really. You have to figure out how to use it, but it’s an idea that can be computationally instantiated and might be a little different in different systems. So it really relies on having funding from agencies.
Rob Wiblin: NIH.
Athena Aktipis: Yeah, NIH. Well actually NCI, National Cancer Institute, it’s within there. There is funding that is happening. There are clinical trials going on, but there need to be more. And we need to think about how we can facilitate these kinds of approaches. Frankly, they’re cheaper, they’re easier on patients, and they’re definitely a lot more exportable to countries where really expensive chemo with intense monitoring and testing and all of that isn’t as much of an option. So I think there’s a real opportunity to think about how we can take these sorts of approaches to bring at least some management of cancer to places where expensive methods and drugs are just not an option.
Rob Wiblin: Some other evolution-inspired treatment ideas that you talk about in the book: one is to give a local tumour a constant supply of food and resources with the aforementioned logic that if the cells that are doing best are the ones that stay put in a particular given location, then you’re not selecting for ones that are likely to move. That one sounds a little bit crazy to me, because it also feels like it’s still feeding the tumour — you’re still feeding the cancer. It seems like it’s always going to be a double-edged sword.
Athena Aktipis: Yeah. It’s obviously something where there are caveats there. Maybe you would want to be feeding it and then treating it with adaptive therapy, for example. But 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 if you start applying these ideas from ecology, like dispersal theory, and theories like life history theory, and thinking about, “How do we affect the parameters of natural selection?” You think of all of these things, it opens up this creative space for thinking about new strategies for controlling cancer. And then potentially combining them in ways that allow you to prevent the things that you don’t want and cultivate the things that you do want.
Rob Wiblin: The things that you can live with.
Athena Aktipis: Yeah. But it really is a mental shift to thinking, “How do we live with cancer?” And I think cross-species perspective is useful, not just because we can learn things from other species about how they suppress cancer or deal with it, but also because it forces us to just think more broadly about the fact that living with cancer is the norm for multicellular life. So if we can be more deliberate about using our technology and our abilities to gather information, process it ourselves, then that opens up a whole new space for treating and preventing cancer differently that leverages the brains that we have here, and the network brains that we all have, and all of the really rich theory that’s been developed in evolutionary biology and ecology over the decades and centuries.
Rob Wiblin: Another one you mentioned is using chemicals that might disrupt the signalling and the ability of these cancer cells to cooperate and collaborate with one another, which makes intuitive sense. Another one that I was amazed by is obviously it would be helpful if we could reduce the rate of evolution among the cancer cells. And one way to do that would be to reduce 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, Panadol, Paracetamol, Acetaminophen —
Athena Aktipis: Like a baby aspirin, yeah.
Rob Wiblin: — that they could really reduce the rate of genetic mutations within cancer cells? It seemed like it had a large effect, a crazily large effect.
Athena Aktipis: I think there’s been some newer studies on this too that maybe challenged just how large that effect was. But the original studies that were done basically looked like people who were taking these NSAIDs had lower likelihood of progressing from this early cancer-like state called Barrett’s oesophagus — where you have what’s called dysplasia, where cells are in the wrong places and growing in ways that they shouldn’t in the oesophagus — lower likelihood of progressing to cancer. And that seemed to be related to a decrease in mutation rate that was associated with the NSAID.
So it may be that because of a sort of evolutionary mismatch, we have just higher inflammation than is ideal — because of toxins or exposures to more pathogens, things like that — that could be kind of kicking our body into a state of inflammation. Because inflammation is another situation where there’s tradeoffs. You have higher inflammation, maybe it’s less likely that you’ll have an acute problem with a pathogen, but you’re creating an environment that’s potentially more pro-cancer because it’s basically being more permissive.
Rob Wiblin: Its growth signals, right? They wouldn’t do any maintenance.
Athena Aktipis: Yeah. Yeah.
Analogies to human cooperation [01:32:43]
Rob Wiblin: Cool. OK, let’s push on from cancer a little bit and think about other levels of cooperation. Because we’re not a medical show — probably closer to being a social sciences show — we’re maybe more interested usually in cooperation between people, and cooperation between countries and societies, and so on.
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. 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.
So one thing I should say upfront is that here we are going to be drawing analogies between cheating behaviour of people and cheating behaviour of cells, which in this case means cancer. So we will in some sense be drawing an analogy between the behaviour of people and cancer, which seems a little bit offensive. I think if you ever called some individual cancerous, that might be a little bit offensive. But we’re here at the ideas level, we’re thinking at the level of abstraction of cheating and cooperation and so on. So hopefully listeners will let us get away with that.
What are some ways in which humans defecting against organisations, or groups of friends, or their societies can be structurally similar to cells in the body forming cancer and not cooperating with one another?
Athena Aktipis: I mean, there’s some parallels and then there’s also some places where the analogy breaks down. So I like to think about it in terms of 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?”
So if we take the regulation of cell proliferation, there are human societies in which people do regulate how many offspring other people can have. So we see that. Now, do we think that that’s a good thing or bad thing? That’s an ethical question, whether that’s “cooperation.” On some level, I guess it can be interpreted that way. It could also be interpreted as authoritarian control. That’s not cool. So already, we’re like, “Oh, the body is a fascist state” if you start making these analogies.
Rob Wiblin: We’re on touchy ground already here. I’m worried.
Athena Aktipis: Yeah, exactly.
Rob Wiblin: I suppose you’re right. The body is a very authoritarian place. Cells that step out of line get shot.
Athena Aktipis: That’s right. Yeah. No questions asked. I mean, yes and no, right? There is some cost to just killing a cell like that. So you do have mechanisms to try to do the DNA repair and make sure that if it’s easy to solve the problem, the cell doesn’t get completely destroyed. But cells don’t have a lot of autonomy. And that’s a good thing for the function of us as a unit.
Rob Wiblin: But not for every cell.
Athena Aktipis: Yeah. If you take seriously the perspective of the cell, it’s a different story. If you’ll permit me a slight digression?
Rob Wiblin: Sure.
Athena Aktipis: So I worked on a song, a rap with Baba Brinkman — early, early on when I was just starting to really bring these ideas together about cooperation theory and cancer. Basically the idea was: How can we write a rap about cancer from an evolutionary perspective and the cooperation theory perspective? 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 required.
It was a really great way for me to really shift my perspective. And it’s also just really fun. It’s called “Revenge of the Somatic,” if you want to look it up. It starts, “My forefathers were free, but I was born a slave. I keep the memory of freedom in my DNA.” So we’re setting up a totally different frame for thinking about it, but it really does draw that parallel between what’s going on in the cellular societies of the body and some of these things that we think about on a social level.
Anyway, that’s my big digression, but we can bring it back to these foundations of multicellularity. We can think about, is there an analogy for cellular suicide and for forced cell death? Well, there’s analogies, but that’s not something that happens a lot in modern society. Although there’s some situations where if people are being forced to do something that they think is going to damage their families, their countries, they will swallow the pill to get themselves out of the system so that they don’t end up doing something damaging. So I think at the very extreme case, you can maybe see some examples of this, but mostly those kinds of processes aren’t really going on I think in human societies.
But division of labour, we see a lot of that. Resource distribution, reallocation of resources, moving things around so they can get from one place to another, we see that. We also see maintenance of the shared environments: in our cities, we have our trash collection, we have lots of efforts that people do to take care of the environment that we share. So I think that there are a lot of parallels.
And then there’s some interesting discontinuities that I think can be informative to think about and talk about in terms of: Why do they not happen in exactly the same way? How much of that has to do with the levels of selection? Our bodies have been selected on this level of all the 30 trillion cells doing a thing together to help us survive and reproduce — while in humans, arguably there’s been a lot less selection on collective phenotypes.
And then also in humans, there’s a whole other set of processes that have to do with culture and institutions. And yes, we have set those up. They’ve come from us in a way to then allow us to regulate ourselves in collectives, but they’re not necessarily going to have the same structures and functions exactly as the systems that have evolved through natural selection to regulate a multicellular body.
I mean, we could probably talk about just this for an hour, but…
Rob Wiblin: Absolutely. Yeah, one of the differences that has become immediately apparent is that we care about the interests and wellbeing 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, so that makes the issue potentially very different.
You had this analogy of the rubbish housemate is kind of like a cancer cell. They come in and 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 in the cancer 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 bad ideas or bad behaviours spreading through people through ideas. Maybe that would be more of an analogy, where 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.
Athena Aktipis: Oh, that could never happen. We could never have society break down because of bad information.
Rob Wiblin: Fortunately, yeah, we’re completely robust against that. I suppose other differences are that people learn through reasoning and can anticipate ahead the effects of 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 really make it really quite different.
Athena Aktipis: Yeah, 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 cancer cells that are little collectives, and it’s happening 25 times in parallel — you can get variation and selection acting in ways that can look kind of like things like learning and anticipation, even though that’s not actually what’s going on. So you can have different mechanisms leading to sometimes the same kinds of structures and behaviours, which is also interesting.
Rob Wiblin: Yeah. An analogy I was curious to explore is about how we have this very fundamental constant tension between the need to crack down on proto-cancers and also sometimes you do need cells to move and grow and so on. 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 when it actually is valuable and the rules are good ones.
I think we see this in this 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?
Athena Aktipis: Yeah, I think that there’s definitely some parallels there. If we go back to this idea that the body really is a sort of fascist state that doesn’t let cells do anything, to me, that would be a personal hell. Because I love thinking about things differently, being creative, asking, “Why do we have this rule?” To me, that’s really important. 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 might be things that people are accepting that might not be ethical, that might not be the right way of organising things for the wellbeing of society.
So I think it isn’t the case that cheating is always bad, if we define cheating as “breaking shared rules that have some fitness consequences for the individuals within them.” I mean, if cheating is always about, you have a group that’s really agreed, “We’re going to go in on this together and follow these rules,” and you have breaking of those rules, then you can say there’s cheating and exploitation going on. But sometimes people are born into systems that they never agreed to the rules of, or sometimes rules are put in place to exploit people.
So I think that it gets interesting when we start really interrogating these ideas of what does it mean to cheat, to be a cheater? And sometimes we do need to challenge the systems that we’re in and push them a little bit — or even straight-up cheat in the rule — so that we don’t have people getting exploited. So I think it’s important to not just be like, “We should just not have any rule breaking, and the world would be so much better if everybody always just did the thing that is expected of them.”
Rob Wiblin: Yeah. The interesting thing is that 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 some cells to grow a little bit more and change the body shape in this way or that, might be a bit more permissive to some types of cells in some situations and not others. There’s billions of humans, and I guess in the past there was millions of humans, so there was a lot of innovation constantly with that.
The 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 anymore. Does that make any sense?
Athena Aktipis: I think there’s different ways to think about the units here. So you could think about societies as everyone who feels like they’re part of the same culture — there are shared norms and ideas and approaches. But you could also think a little bit more loosely about what constitutes a group, where you could have creativity. So you could have companies, or even teams within companies, or groups at universities that are looking at certain questions in certain ways.
I think the unit of analysis is maybe a little bit flexible, in a way that hopefully allows for the kinds of good innovation and good challenging to norms that does need to happen — especially when you’re in a system that might not itself be generating that innovation. If you’re in a bureaucracy, how do you do things in a new way? Maybe you can do things in a new way by suggesting more bureaucracy, but other than that…
Rob Wiblin: Maybe the analogy between 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, 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 those goals, then those practices might spread. That’s kind of a cultural evolution analogy.
Athena Aktipis: Yeah.
Applying the “not treating cancer aggressively” strategy to real life [01:47:18]
Rob Wiblin: 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 tumour? Is there any way that we could apply that to fighting crime, or social behaviour?
Athena Aktipis: Or marriages? I mean, yes, we could certainly apply these analogies to thinking about how, instead of approaching things that we see as problematic as like, “The thing to do is eradicate them,” instead we could ask, “How do we live with something that maybe isn’t ideal?” And accept that maybe it won’t be perfect, maybe there’ll be some exploitation going on, but it won’t be to the point that it’s devastating. How can you cultivate the relationship to the point where you’re able to live with each other? Maybe they’re not always doing the dishes, but at least they’re not exploiting you on a large scale or something, right? So it’s like what can you live with, and what can you not?
In terms of crime, there’s a lot of really important work going on right now in terms of looking at restorative justice as a strategy for dealing with situations where people are imposing costs on one another or violating rules. And rather than focusing on punishment or putting somebody away forever or even the death penalty, instead of those catastrophic kinds of ways of dealing with it — which actually can undermine a lot of the connections in a society — restorative justice is really about how do you right the wrongs to the extent that you can, and how do you keep that individual as a part of the society and do the damage control to the extent that you can, but then try to actually cultivate something out of that that’s positive.
So I think when we talk about human societies, there’s analogies, but it can go even further than just analogies. Because if we look at small-scale societies, there are a lot of situations where restorative justice does work to actually reintegrate people and rebuild social relationships in situations where, if you were just using punishment, that wouldn’t happen.
Rob Wiblin: Yeah. Another analogy that just occurred to me is, so I’ve heard this story from a 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 drug trade, it becomes impractical for the police to even hope or dream of eradicating these organisations — 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, “OK, these are the things that you can do that we can tolerate. We can live with the drug trade and we can live with you running underground casinos or something, but if you kill one another or if you start creating violent problems on the streets, then that is what we’ll crack down on. 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.
Athena Aktipis: Yeah, that’s interesting.
Rob Wiblin: And potentially, I guess you could even shift the culture within the gang over time towards the people who will flourish, who 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?
Athena Aktipis: So there’s one level on which it makes sense and another level on which I think it doesn’t quite. The idea that memes could be exploiting our brains and our information systems to spread themselves, because the ones that are good at spreading spread, like 100% there’s certainly exploitation going on. But to call them cheating, there has to be some entity that they’re cheating on. And what are the rules that they’re breaking of whatever collective system that they’re a part of?
So I would say that yes, they can exploit us, but maybe they’re more like viruses or pathogens — where they’re not necessarily breaking a set of preexisting rules that come from inside or the system that they’re within, but rather they’re just little sneaky things that can find the vulnerabilities and exploit them. Of course, I’m anthropomorphising here. They’re not actually sneaky and looking, but they act as if they are, because the ones that do it are the ones that proliferate.
Rob Wiblin: They’re around. 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, then I guess that is kind of a virus of an idea.
Athena Aktipis: Yeah, yeah. It’s like a virus of an idea. Right.
Rob Wiblin: I wonder what they would look like. Unpleasant urban legends or fake facts, I don’t know.
Athena Aktipis: I mean, there are a lot of ideas that aren’t necessarily good for the survival or the reproduction of the individual who possesses them. There are cults that advocate for things like suicide, that advocate for not having children — things that are at odds with the survival and reproduction of the organism that harbours them. But in certain kinds of conditions, those memes can take hold and also spread within a population.
Rob Wiblin: Yeah, makes sense.
Humanity on Earth, and Earth in the universe [01:53:04]
Rob Wiblin: OK, let’s turn now to cooperation on different scales. Again, zooming out further, if humans as a species were damaging the natural environment in a way that made it harder for humanity to survive in future, would that kind of be a cancerous behaviour in a sense? Because we’re destroying the extracellular matrix where we’re making it hard for us to survive, and you might think it’s a behaviour that’s then going to undermine this meta-organism of the entire species.
Athena Aktipis: Yeah, if you want to look at our whole species as an entity, or go a little Gaia and be like, “Hey, our Earth, we’re all one big system or we’re a unit on some level” — if you do zoom out, and if you accept that it’s reasonably likely that there may be other life out there in the universe that is also existing on planets where there are resources and using them, then there’s a certain level on which, yeah, you can think of all of us as part of a unit. Probably the right level of analysis is the planet, is Gaia — even though I know there’s sort of been a lot of pooh-poohing of the idea of Gaia in evolutionary biology, but there’s a certain level on which it does make sense if you zoom out far enough.
And also, if you think about the interdependence of systems on Earth, there is some level, I think, on which it’s at least a reasonable tool to use to think about some of these things. I think there are absolutely ways that we could think about our behaviour — vis-a-vis the limited resources that are on our planet — as having some analogies with some of the processes that go on with cancer. And efforts to try to increase sustainability, and make sure that we’re living in a way that will make it more likely that future generations will have a decent chance of a good life, I think all of those are questions that have some analogies with shortsightedness that can happen with cancer inside the body.
Rob Wiblin: Yeah, the funny thing is that idea of humans engaging in this cancerous behaviour 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.
You’re slightly smiling, so maybe you think it wouldn’t hold quite so clearly, but the idea of this cooperation/uncooperation, the uncooperative thing dies out, or in the long term kills off the organism that it’s a part of — the entity in which the cooperativeness is represented. And then it’s a bit funny that we think it’s crazy for us to think about Earth this way just because there doesn’t happen to be that much life out on other planets as far as we can tell.
Athena Aktipis: Yeah. Well, I’m smiling for a few reasons. One is because I love talking and thinking about extraterrestrial life and the possibility that the things that are going on elsewhere in the universe 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 another way of thinking about spacefaring intelligent life is that maybe there’s a certain way in which it’s more like a transmissible cancer that’s really good at cooperating to extract the resources and then go far — even beyond the body or the planet — and find another extant lifeform to colonise.
Rob Wiblin: Wow. Do you think that 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 other resources there?
Athena Aktipis: I mean, we’re kind of off the deep end.
Rob Wiblin: Sure, no. I love it. I love it. Yeah.
Athena Aktipis: But in all seriousness though, the ability to be an intelligent lifeform that can get into space, it’s going to require some level of cooperation. So you do have sort of a filter there. And I know in the Great Filter hypothesis, there actually isn’t very much about cooperation. I think it’s not just being technological — having the ability to cooperate is key.
Rob Wiblin: To avoid destroying ourselves, yeah.
Athena Aktipis: Yeah, we could destroy ourselves. And humans also oftentimes use cooperation for really sinister ends. So cooperation isn’t in itself good. It’s all a question of what that cooperation is used for. I’m not saying that it’s inherently bad to go into space because we can make a transmissible cancer analogy, but I think we do have to ask, well, what are the goals? And if we do figure out how to be an interplanetary species, is that the direction that is going to help life thrive the most? Our life, life in the universe?
Anyway, so many open questions. I feel like this is a whole different episode that we’re having right now.
Rob Wiblin: For listeners who are annoyed, I’ll try to ground this a little bit more. So I think the analogy to cancer, I’m not always sure how helpful that is. But 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 sub-components that decide to deviate from the rules that created that surplus. And you just see this recapitulated in different ways, and it makes sense theoretically, it makes sense structurally. Does that sound right?
Athena Aktipis: I like that. Yeah. It’s a very succinct explanation of a very complicated process.
Superhuman cooperation [01:59:41]
Rob Wiblin: All right. On that topic of the many different ways that uncooperativeness can arise in structures at different scales, 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 creates the variance that might permit deviation between the interests of different components of the 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, like with when you copy files on a computer, then the computer can just check that it’s all been copied identically and that there’s no mutations — certainly no changes anywhere near at the 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 sub-components that deviate in their interests from the interests of the original agent?
Athena Aktipis: So, doing a thought experiment here: If you could have totally perfect replication, never have errors, then could you get systems that would evolve to be able to maintain cooperation forever? I’m going to answer maybe. Because even without mutation, there could still be other factors.
I’m thinking of this on the cellular level. You can have epigenetic changes. So, if you go into an expression state — or, if you’re thinking about artificial life, if you go into some sort of aspect of 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 in an expression state that’s not appropriate for what would be most beneficial for the organism or the higher-level entity.
And also, in order to even 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 entity to optimise for that organism level. If you have a rapidly changing environment, then actually it’s not possible to anticipate every situation, and what would be optimal for the higher-level entity in that case.
So, yeah, if we could completely eliminate errors of copying, that would reduce the problem that comes from mutations or alterations to the sort of underlying code that allows cheating to arise. But there’s still other ways to get things that aren’t actually functional at the organism level. If they’re benefiting the entity itself that’s in the weird expression state or whatever, then you can get the propagation of those things that are not ideal for the higher level.
Rob Wiblin: Is that another way of saying that, if you have an AI system that keeps 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 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, 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 it might have elsewhere.
Athena Aktipis: Yeah, that’s one way to think about it. I would just add to that that information has to be processed at so many levels for anything to be able to happen. And thinking about this at the cellular level, to me, makes it much easier — in a way, easier but harder — to wrap my head around how much information processing needs to happen.
So even just the idea that we can say, “We’re giving this AI a goal to do a specific thing”: in order for that AI to accomplish that goal, it needs to be able to process and respond to a really complex environment. You could say a cell has the goal of maximising the survival and reproduction of the organism that it’s a part of, and the inclusive fitness and interdependence or whatever. You could say 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. It has all of these rules encoded into its genome and then it’s interacting with all these other cells in ways that lead to the emergence of the pursuit of those goals at the higher level.
But it’s a lot harder to be goal-directed than we think, because that’s so easy for us. We’re so used to operating that way and projecting goals onto other entities in order to make sense of their behaviour, because it’s a really good heuristic. But that’s what it is: it’s a heuristic for underlying mechanisms that are so complex that we can’t even wrap our brains around them.
Cheating within cells [02:05:51]
Rob Wiblin: Yeah. Speaking of cells, we’ve mostly been talking about cheating and defection between cells. But we should talk for a minute about ways that you can get cheating within cells, which sounds a little bit crazy because already a single cell is such a small scale. How can you have sub-components of a cell fighting against one another? But it turns out that you totally can.
Can you explain how it is that you can get genes cheating against other genes that are on the same strand of DNA, that are on the same chromosome?
Athena Aktipis: Well, to me, this is all kind of an extension of our earlier conversation about the evolution of life and multicellularity. It’s just kind of taking it back a few steps.
So very, very early on in the evolution of life, there wasn’t anything like a genome, like a bunch of DNA that is teaming up to replicate itself together with all the machinery to replicate and all of that. You had probably something that was much more RNA-like, so you had basically just these molecules that were able to replicate themselves in one way or another. Once you start having situations where these entities that are replicating can do so more effectively in a cluster, then they will stick together and then maybe machinery evolves that allows them to replicate together.
Now, you can imagine though, early on in the evolution of that, if you had a cheater that was actually replicating itself more than the others, that that cheater could then be overrepresented in the next generation. This is very, very likely what was going on in the evolution of proto-life, I guess we could call it — or maybe it’s life, if you think self-replicating entities are life.
So the very design of how our DNA works, how it replicates, there’s actually 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 gene-level cheaters. So when we see fragments of DNA that over-replicate or jump into new chromosomes and replicate themselves in there, rather than seeing something weird and really unusual, we’re just seeing the uncovering of the fundamental —
Rob Wiblin: Tensions that were already there.
Athena Aktipis: Yeah, yeah. That were sort of overcome in what’s called the major transitions in evolution — these times when previously independent entities came together to form higher-level entities, which then allowed for more complexity and then yet higher-level entities. So, a bit of coming together, regulating genes into a genome, having some cheater-detection-suppression response mechanisms at that level really is one of the steps in getting complex multicellular life, at least on this planet.
Rob Wiblin: Yeah. So, a stylised 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 big, 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?”
Athena Aktipis: Yeah, something like that.
Rob Wiblin: “I would rather become a larger faction of the genome.” At least until the point where that causes the thing to become completely nonfunctional and then the cell is dying completely. That would set some limits pretty quickly.
Athena Aktipis: Right, yeah. And that’s where we get into multilevel selection again too, because you had presumably little clusters all over the place doing this over long periods of time. And those that were best at forming together, at replicating together, at suppressing cheating, were the ones that were more likely to create copies of themselves at that higher level. So yeah, multilevel selection is absolutely key for understanding these major transitions in cooperation — where you go from these lower-level entities that are competing or just facultatively cooperating in the right circumstances, to being locked in that they can only replicate as a unit together.
Rob Wiblin: What are the mechanisms that stop cheating by individual genes that were developed? I suppose it’s something like 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?
Athena Aktipis: Yeah. I’m not a geneticist and expert in this, but I know that there are a lot of mechanisms by which you can get replication of these genes in the same place. You can get them jumping from genome to genome. And that part of our overall monitoring of the genome is the genome itself is monitoring itself. That it’s not just sort of errors in terms of point mutations, but places where there’s too many replicates. And because it’s double-stranded, when the DNA is lining back up, there’d be chunks that are weird if things have gotten replicated too much, or there might be other mechanisms that allow for the compilers and detectors of the genome to get in there and “figure out” what’s going on. And then clip things out if necessary, or get rid of cells that might actually have so much jumping DNA in there.
Rob Wiblin: Sustain too much change.
Athena Aktipis: Yeah, and then it’s like, “Oh, maybe we just lose this one.”
Rob Wiblin: OK, so I guess cells in the body do sometimes die because of these phenomena. But that’s the last line of defence. If a cell has been a victim of cheating genes and the damage is too severe, then it just needs to kill itself in order to avoid damaging the organism more broadly.
Athena Aktipis: Yeah, that’s right.
Rob Wiblin: Does this have anything to do with the kind of repetitive junk DNA? I know it’s not very politically correct to call it junk DNA. I’m meant to realise 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 repetitive non-gene DNA, is that maybe a result of genes copying themselves all the time and creating these stretches?
Athena Aktipis: Yeah, yeah. It’s likely that some of those mechanisms are at work now, whether that is providing any specific benefits for those genes other than just they’re replicating themselves and so they replicate more. It’s sort of just this default of: the things that are good at replicating end up replicating more.
But yeah, I think that there are still a lot of open questions about what exactly is going on with a lot of the DNA that are these many copies. Because sometimes you can actually have differentiation of function that begins because you have two copies of a gene and then you can actually have one do one thing and one specialise on the other. So there’s potential functionalities that can come from that in the medium term.
But the fact is we don’t understand still a lot about how we go from genotype to phenotype — especially with all the dynamism that comes from epigenetics, how we’re affected by our environment, how cells are affected by the cells around them. It’s really, really hard to drill down to the timeframe and the spatial scale that we would need to be looking at to really understand what’s going on. We just don’t have great tools yet for getting so minuscule into what the function is — or even just what they’re doing, even if it’s not functional from an evolutionary perspective. So lots of open questions there that are cool.
Rob Wiblin: 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 part of. Can we go any smaller, or have we hit rock bottom here? Can we talk about the individual base pairs on a gene defecting against the gene that they’re a part of? Or maybe does it just not become practical for that to happen?
Athena Aktipis: Well, 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 those entities looked like. But once you start having anything that is a replicator, it’s going to have some level of complexity. Even if you just think of a replicator as something that, when it’s out in the environment, maybe it attracts things that are similar to it. So you could have a very, very simple molecule. 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 letting that other thing go, like a sort of self-catalysing process.
At that level even, you could imagine that there could be variation among entities that are replicating, or some are just not able to do that at all. So there could be a very, very mechanistic kind of cooperation that’s just, how do these things attach together and in what configuration? And then how do the forces at the level of the physics work at that? So there could be selection that’s going on on things that we think about as the sort of chemistry and physics that are leading to maybe selection for cooperation. But also the possibility that cheating is undermining it — but it would be cheating in a very primordial kind of sense.
Father’s genes vs. mother’s genes [02:16:03]
Rob Wiblin: Yeah. OK, well, we’re about to leave biology, all this genetic stuff, but before we do that, it would be really cool if you could explain this quite dark aspect of how sexual organisms, at least, work. 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 offspring to consume as few resources as possible. Why is that?
Athena Aktipis: Oh, yeah. Genetic conflict is one of my favourite topics because it’s just so weird when it starts to manifest. It all starts with the idea that we as sexually reproducing organisms are not genetically identical to our parents or our offspring. Typically, you’re 50% related to parents and offspring. So if you have your mom and your dad, they each contributed 50% to who you are in terms of the genes, and that means that you don’t have 100% aligned interests with your kin.
Now, evolutionary thinkers often focus on this idea of kin selection, kin-based altruism, parental investment. So, altruism: easy, easy to get altruism among kin. And yes, but you don’t actually have 100% aligned interest. 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 not really relevant unless they’re a partnership for life and there’s no other possibilities of the female having offspring with other males.
So 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 trying, in evolutionary terms, to more equalise investment over present and potential future offspring. Maybe not 100% equal, but having a distribution that is closer to equal.
This kind of makes sense on a theoretical level, but the absolutely crazy thing is that this manifests in the way that genes are tagged — 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 tend to be expressing genes that increase the resource delivery to the foetus while the mother is pregnant. And the genes that are coming from the mother’s side are basically tagged in a way that makes them interfere with the transfer of resources that the paternal genes have turned up. And similar things are going on with growth factors and other processes that have to do with the transfer of resources from the mother’s body to the foetus.
Now, all that being said, there is a huge range of shared interests — where, yes, it’s in the maternal interest to transfer these resources, and it’s in the foetus’s overall interest and paternal interest to get those resources. So there doesn’t have to be a 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 mother system is shutting down the resource transfer in terms of the structure of the blood vessels, and the foetal system is then upregulating signalling that increases the blood pressure, and then the mother system responds, and the foetus responds. All completely unconscious, but it can push the maternal body actually into a state where both the mother and the foetus are at risk in terms of their viability.
So, it’s interesting and scary and weird and cool that you can have these systems where underlying it, there’s a lot of overlapping interests, but if you start this sort of move and countermove and countermove and countermove and countermove, you can end up —
Rob Wiblin: It’s an arms race, right?
Athena Aktipis: Yeah, exactly. It’s an arms race. And then everybody can end up dead. Which fucking sucks, right?
Rob Wiblin: Yeah. Going back to the beginning of sexual reproduction: at that point, you have this slight misalignment between the interests of the male — which 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.
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, sacrificing her future potential reproduction. And basically this just escalates over time.
So the male bids for more and then the female offsets it by 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 for different procurement of resources for 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’s just completely broken and 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 couldn’t survive. It’s crazy.
Athena Aktipis: Sometimes I use the analogy of a tug-of-war. What you have is a situation where the maternal interests are pulling on one end and the paternal interests are pulling on the other end, and every time one side tugs harder, the other side has to tug harder again in order to just keep things in the same place.
And then if you end up with a mutation that interferes with one of the genes that regulates how much is being pulled, then you can actually end up in a situation that is suboptimal for both parties. It’s outside of that range of what would make sense. It’s like you’ve got the balance in the middle and 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 have nothing in that range at all.
Rob Wiblin: Yeah. What is the limiting factor on this? 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. Maybe just 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 it stops.
Athena Aktipis: There are, I think, a few constraints on the evolution of this. One is obviously that if there’s too much of a tension, and you have mutations often enough that lead to a totally suboptimal situation, then the more intensely competitive genes on the whole are going to be less favoured because you can have these catastrophic outcomes.
You also have this sort of evolution of these regulatory pathways as well. So if you have a situation where what’s being encoded is this sort of escalation and counter-escalation — on the timescale of the organism’s lifetime or on the timescale of a pregnancy — if those genes that code for that escalation are more likely to lead to a catastrophic situation where nobody’s evolutionary interests are being served, then there’s also going to be less selection on that.
I actually have a game that I designed for teaching about this in the classroom. Basically one individual plays the parent, and you have three that are the baby birds. So, it’s a mother bird and baby birds, so that takes it a little bit out of the realm of being human. Then the parent is rolling a die every time period and has to choose how many points to give to each of the three offspring. The offspring then can decide to either accept what the parent gives, or 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. If I make a demand, 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. If I succeed, then I’ve gained one, but at a greater expense to you, you’ve lost two. It’s a very simple way of getting this tension across.
And then I play it with my class, where there are a dozen or so of these groups of four, and then we talk about it afterwards and you see where everyone was signalling and shutting down, in the end, they didn’t have as high success as the groups that were actually being more cooperative and not protesting. And also, it can be very funny sometimes, because you’ll have one of the baby birds that is a total pain in the ass, and all the other siblings are like, “Oh, come on, you’re making it bad for all of us.” So it’s a really fun way for the students to learn about these ideas of genetic conflict, and in particular, parent-offspring conflict.
Rob Wiblin: Yeah, yeah. I deliberately wasn’t using human-specific language. Partly it’s just distasteful to think about this among humans, but also this would be less pronounced among humans relative to most species, because humans often reproduce together repeatedly. Whereas in many species, a male and female go their separate ways and don’t reproduce year after year, in which case, the male has almost no interest in the future reproduction of the female beyond that point. This is going to be even more extreme, going to be even more awful.
Athena Aktipis: When we play it, it’s just a parent and then offspring because it’s really the same dynamics if you just have one individual that’s basically the individual who has access to the resources and is trying to distribute them. That’s really the key piece of this. It doesn’t have anything to do with what we associate with being male or female in any broader sense. It’s just who’s distributing the resources.
Rob Wiblin: 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 that people on a conscious level don’t operate this way, or at least only 10%.
Athena Aktipis: I’m so glad too. You know what though? I will add that it can be really funny. From teaching in my class and using these games, the students have a lot of fun and end up making lots of jokes. I think any time you have tension, you have conflict, we humans like to learn about that and engage about that. Because it’s really important for us to understand how those things work.
Rob Wiblin: The stuff of life.
Athena Aktipis: Yeah. I think there’s a sense in which maybe it’s inherently rewarding to think and talk about it in terms that are humorous, because it does allow us to wrap our heads around it, but without taking it so seriously that it has to make us depressed.
Everything is Fine: How to Thrive in the Apocalypse [02:28:45]
Rob Wiblin: 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 Fine! How to Thrive in the Apocalypse — is about how we think about civilisational disaster scenarios and the effect that thinking about that has on us.
This is super relevant to this audience, because a lot of listeners study nuclear war, bioterrorism, worst-case climate change, and 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.
What’s the practical problem that you were hoping to solve with this one?
Athena Aktipis: Yes. So the book, it’s called Everything is Fine! How to Thrive in the Apocalypse, and it’s meant to be both 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 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 technicalities of our global systems and 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 half a humorous field guide to living in our apocalyptic times, and half a call for bringing our heads together to do a much better job of sharing information and managing risk collectively, and being able to build that up from simpler components.
So for me, the whole point of the book is to, number one, make the crazy times that we’re living in now not feel quite so scary, by bringing some humour, some playfulness, some cool illustrations from Neil Smith in to make it fun. And then creating a space that I hope people will see as an invitation for us to all work together more effectively, and leverage our ability to cooperate and share information in a way that will help us do a better job of dealing with all of the challenges we’re facing now, and we’ll absolutely continue to face as the future unfolds.
Rob Wiblin: 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 go really wrong for as long as we have records from people. Tell us about that.
Athena Aktipis: Yeah. If we look at small-scale societies — if we look at any societies around the world, really — there are ideas about threats out there in the world, some of which might end civilisation as we know it, or simply the idea that there are cycles where sometimes things are good and then sometimes things are worse, and that we have to have mechanisms for being able to deal with those times when things are worse. Those are all very, very common — probably universal — across all societies.
And I think storytelling is an important piece, especially in small-scale societies, of how people retain that memory when things are good: that sometimes things aren’t so good. So we need to be thinking about how to manage risk at all times, even if it’s just on a yearly basis. Like if you deal with really severe winter storms, like Mongolian herders do: they’re managing risk all year. They’re not just waiting until the winter storm hits. They’re fixing their shelters for themselves and their livestock. They’re collecting hay and other feeds so that they can keep their livestock alive through the winter.
And you can think of that on larger scales, where we want to be managing risk proactively, not just waiting for a crisis and then dealing with it in that moment.
Rob Wiblin: I suppose it makes sense that humans would have a big attraction towards thinking about ways that things could go wrong. It’s another expression of how people just tend to worry a lot. When we’re just sitting alone by ourselves, we tend to think about the ways that things could go wrong in future a lot. Or at least many people have that predilection.
And 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. It seems like humans are also interested in even more extreme disaster scenarios than that. It makes sense that we would be worried about the winter and the weather and some flooding, drought. But there’s something that’s also very attractive about thinking about the end times. Have you thought about that at all?
Athena Aktipis: Yeah. When you say “end times,” and you think about really big disasters, I think one of the things about that that’s compelling (and scary, of course) is the idea that a lot of the structures that we know — the norms of society, just the ways that we do things — those can and often do change in those times. I mean, even with the COVID pandemic, which on a long timeframe is not a particularly horrible pandemic. I mean, obviously it was very, very bad, but just compared to others —
Rob Wiblin: Could have been much worse.
Athena Aktipis: It could have been much worse, and has been much worse. It changed so many things about how society was structured, and people talked about it as an apocalypse. I think COVID also brought the idea of the apocalypse as a household word. People just started using it. I started talking about the Before Times right away when COVID happened, because I was like, “All right, now we can use the apocalypse playfully.” It’s serious, it’s hard, 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.
So I think that there’s both opportunity to think about how we might do things differently when a lot of change is already being forced, but it’s also scary and can potentially be very problematic to have institutions disrupted that might actually be playing a very important role already in regulating cooperation or keeping society functioning in a way that doesn’t disadvantage some people. But there also might be things about the way society is working that can definitely be improved. And when a lot of things change, that I think opens up some opportunities to think differently about how we’re doing things.
Rob Wiblin: Are there any particular classes of disasters that trouble you in particular? 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. Really rapid advances in AI this year also had me a bit on edge. You don’t know what AI is going to be capable of next. That seems like the future’s coming at us pretty fast. Are there any things that trouble you?
Athena Aktipis: Yeah. Well, off the top of my head, I’ve got three. Certainly nuclear events. Very, very of the moment now, and I also think it will not go away as a threat, because we have the technological capacity to do this. And I don’t think that we’re going to be able to get to a point where every entity who could make a nuclear weapon would refrain from doing that. So I think it’s something that is likely to be there for the long term.
Future pandemics, absolutely. I think we saw with COVID just how vulnerable our systems were, and unfortunately we haven’t done a huge amount to try to fix the weaknesses and vulnerabilities in the systems that we have for early response to emerging pandemics. So I worry about that.
My AI worry is less of what happens with AI on its own. My worry is much more what happens with AI in combination with humans that have goals that are nefarious. And I think that there’s a leveraging that you can get when you bring together human minds and the artificial minds, that allows for a level of exploitation and undermining of systems that you just can’t get with one or the other separately.
I’m very aware of the weaknesses that AIs have in terms of some of the big-picture assessments of what actually is a path that makes sense to go, given a lot of uncertain variables and potential pitfalls — it might be hard to represent all of those if you don’t already understand them well enough yourself to articulate them in computational terms. But I think there are humans who have instincts about how to navigate very complex strategic situations, and when you pair that with the computational power — the raw power that artificial minds have and their ability to integrate massive amounts of data — to me, that’s the scary thing. And I think to some extent we’re kind of already there in that human-AI-interface apocalypse.
Rob Wiblin: 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 effectively produce the language output of 10,000 people having conversations, or 1,000 people having conversations. They can just output all 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.
Athena Aktipis: It is.
Rob Wiblin: We’re going to need to adapt all these protective mechanisms in order to prevent fake people basically dominating society.
Athena Aktipis: I mean, we have it already. 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 on Twitter in spaces where there used to be a lot of valuable dialogue going on, they’re becoming dominated by what sounds to me, from their descriptions, like a bunch of nasty chatbots that are just trying to interfere with what otherwise would be real conversation.
Rob Wiblin: I’ve definitely seen that on Twitter. That’s been the case for a while, this problem with really stupid bots that just interject nonsense and shut down useful conversations. The crazy thing is now it’s going to be potentially very cheap to have 100,000 bots arguing extremely articulately, extremely persuasively, as well as any human could, in favour 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, but 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 better than humans might be able to, honestly, in a lot of cases. And it’s a very strange future.
Athena Aktipis: Yeah, I think there’s a lot of really interesting things to explore about this issue of human-AI interactions. And you mentioned the alignment issue. I think we tend to think about that as a large-scale alignment with human interests and human wellbeing. But the fact is, humans have their own strategic goals and interests. Many of them are at the individual level, or at the level of groups, or at the level of nation-states and things like that.
So to the extent that AI can be leveraged for particular interests, I think that that process of really, 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 is one of the most important issues for us to grapple with at this moment, with what’s happening with AI right now.
Do we really live in an era of unusual risk? [02:42:10]
Rob Wiblin: Yeah. Setting aside AI, in the first chapter of the book, which you sent me, you seem very negative about the current moment that we’re in, or the kind of crises that we’re facing or how apocalyptic our current moment is. But when I looked it up on Our World in Data, 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 unusual risk? Or is it maybe just that we have heightened perception of risk?
Athena Aktipis: 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 manage risk using financial instruments and things. But I think that we have a lot of vulnerabilities that are just inherent in living in a world that is changing rapidly right now on so many levels. And simultaneously, we can look at some of the data on Our World in Data and see there are a lot of ways that things 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.
I think that also, just on a human scale, people’s anxiety about what’s happening in the world is going up, right? There’s this sense of change is happening so fast, there are all of these risks. The example you brought up of the possibility of nuclear events. The Doomsday Clock is pretty damn close to midnight, and has been for a while. So if we think of the things that could end the world like that, that’s certainly, I think, a real and present risk.
And 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 droughts. Especially in the US, there’s just serious issues with water use and availability in the medium term. People see out their backyards or on their drives to work that things aren’t the same with water, or you can’t actually take your boat out. So I think that it’s something that’s present for people in their lives, and not just because of the pandemic making apocalyptic ideas a little more…
Rob Wiblin: In vogue.
Athena Aktipis: Yeah. So I think that we’re at an apocalyptic kind of moment, just in terms of people’s receptivity to the idea that maybe we should be managing risk more proactively. And a lot of the setup for the book with the first chapter is meant to put a playful tone on the fact that things are fucked up in a lot of ways right now. So it’s not meant to be pessimistic, really. It’s just like, hey, there’s a lot of stuff going on.
Rob Wiblin: Drawing attention to the risks that we face.
Athena Aktipis: Yeah.
Staying happy while thinking about the apocalypse [02:45:36]
Rob Wiblin: What kind of advice do you have about how people should think about the apocalypse in order to be happier while they’re doing it, and maybe think about it in a more productive way?
Athena Aktipis: I think one of the easiest things that we can do is just think about risk management in a fun way. There are a lot of things that we can do at the household level to manage risk better. Then we can also build communities that do a better job of managing risk, and then you can take that up to the highest scales as well. Things like making sure that you’re ready for an emergency. There’s this idea of all-hazards preparation, which is basically just emergency preparation, but you can make it a little bit more fun by being like, “Hey, are you ready for the zombie apocalypse? Do you have 72 hours worth of stuff so you could just shelter in place?”
Some basic emergency preparedness actually helps to make our overall systems more robust too, because if there is a natural disaster and all households are able to shelter in place for 72 hours, then whatever institutional-level support is available to deal with a 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 those situations.
That’s not to put it all on individual households to do this. Because, really, we should all be thinking about how we can help everyone in our communities be able to weather a storm. Supporting all households in being able to have what they need to, for example, shelter in place. Just to take one example of the kinds of things that we can do.
That’s one, and then the other one is 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 is an easy way to manage risk by doing what people call “limited risk pooling.” Where it’s like, if you’re in need and I have enough to help, then I’ll just help you without expecting to get paid back.
Rob Wiblin: That’s interesting. I haven’t really heard that idea before. What sort of relationships might you want to build ahead of time? I suppose here, we’re thinking of disasters like, an extreme one is nuclear war possibly, if you manage to survive it. Also earthquakes would be another classic, or massive wildfires in some places.
Athena Aktipis: Yeah. Flooding. Massive power outages in the winter or the summer. There are a lot.
Rob Wiblin: Yeah, I suppose now we have to worry about cyberattacks that could shut down the electricity grid. Something kind of unprecedented.
Athena Aktipis: Absolutely. Yeah. This then opens up this whole other area of my work, which is really about looking at cooperation in human societies. 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 people within those societies help each other in times of need.
We have found that if you look at the risk management strategies that people are using, that in pretty much every society we see need-based transfers. It’s like, “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. The one society where they don’t use it as much is this society I was telling you about in Mongolia, where they have these winters that are just horrible. They have to help each other ahead of time. They have to manage the risk proactively, because they can’t go to each other’s houses when there’s six feet of snow outside.
Rob Wiblin: Oh, wow. So what do they do?
Athena Aktipis: They will help each other build shelters and make sure that everybody has the resources that they need.
Rob Wiblin: For winter?
Athena Aktipis: Yeah. It’s basically sheltering in place for the winter. They’re helping each other be able to do that for their families and their livestock.
Rob Wiblin: I would emigrate. That sounds awful.
Athena Aktipis: Yeah. But the bottom line here is that people around the world in small-scale societies do this, and also in rural societies here in the US. We’ve studied ranchers in the Southwest, here in Arizona and New Mexico near the border with Mexico. They have a system they call neighbouring, 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 arise unpredictably.
These are things that already exist, and they’re really good at handling the kinds of things that typically we want insurance for — those things that we can’t predict and can’t control. And if you take it to the extreme, there’s certain things that market-based insurance actually cannot insure against.
Rob Wiblin: Because everyone gets hit at once?
Athena Aktipis: 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 would be. In the absence of any of that information, you can’t calculate what an insurance premium could be. It’s an actuarial problem: you need the data in order to price the insurance.
But with these need-based transfer networks, 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 those is another question, but you at least are able to set up systems that can deal with things that have never happened before — that we can’t even understand what the risks are like.
Rob Wiblin: I live in a city, London. What should I try to coordinate with my neighbours? I suppose a big issue is people don’t have very large places, so it’s difficult to stockpile enough water or food or anything like that. I guess in a war scenario, London’s a very juicy target, so things could get pretty grim.
Athena Aktipis: Yeah. I think no matter where you live, having 72 hours of supplies is wise. And you can actually do this in a way that makes sense for having a very busy lifestyle, which is something that I love.
Rob Wiblin: Apocalypse prep — on the go!
Athena Aktipis: Exactly! Apocalypse-casual lifestyle. How do you do this well? For example, 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 to prepare it. You can just add water to it and let it sit for a half an hour, and then you could eat it.
So if couscous is something that you’re fine with, then you can just make sure to buy enough couscous at the store that you could at least have it be part of what you would be eating for those 72 hours. Whenever you buy a new one, you put it at the back and you just have some extras. And then it also makes it easier when you’re super busy and you don’t have time to go to the store. You’re like, “Oh, I’ve got my 72 hours of prep.” Obviously, next time you go to the store you want to re-up.
Rob Wiblin: Yeah. You got to get extra.
Athena Aktipis: But sort of thinking about being prepared, not as like, “Oh, I have to go and figure out how to buy really long shelf life food on Amazon. Who’s a reliable source for this?” No, you just look at the kinds of things that you like to eat that are shelf 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.
Rob Wiblin: The UK has a pretty precarious food situation actually, because it relies on a constant stream of imports. It doesn’t produce anywhere near enough food for the population that it has. I would suggest having enough food for weeks, conceivably months, would be not outrageous, if you were able to do that here. I guess there are 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, now we have some rice and pasta in a thick Tupperware. The mice can’t get to it.
Athena Aktipis: Excellent. Excellent. I think that another thing is just not feeling intimidated by, “I have to do all of these things.” No, just start with having enough water around and having some extra dry food that is stuff that you eat anyway, and then you can work from there. It’s not like you have to do all of the things all at once or anticipate every possibility, because you just can’t.
Having conversations with people about what they’re doing: Do they have their preps? It can be fun. If you get into a little social competition about it, it could be playful fun. I have this idea for a new kind of dinner party. I haven’t tried it yet, but I absolutely want to: you roll the dice to figure out whose house you’re going to go to, and then you show up at that house, and you have to figure out how to make a really nice dinner with just the shelf-stable prep food that’s there. Then you practice making fun meals and surviving in your mini-apocalypse dinner party. Stuff like that. I think we could make it fun.
Then it just kind of puts our attention on how maybe we should just be ready for the unexpected, so that at least we have some more time to plan. That’s the thing. You might not be able to have enough food around to actually manage the risk of something 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 really catastrophic happens.
Rob Wiblin: Yeah. Makes a lot of sense. When you start talking about stockpiling food to protect yourself against disasters, I think some people’s eyes kind of roll and think you’re a bit crazy, and start associating you with preppers who get really into it. Maybe a little bit too into it. But earlier this year, my partner and I spent a bunch of time thinking about what would we do if there’s a nuclear war and we survive? What would that look like? It was very long odds, but maybe it was getting probable enough that it was worth having a conversation about it. It is really fun on some level.
Athena Aktipis: Exactly. That’s the thing.
Rob Wiblin: Maybe not everyone enjoys this, so it’s easier for them to have to stay in for survivalists. But there is something just very entertaining. Our lives can be a little bit boring on a day-to-day level. Imagining what would we do if just everything was destroyed? How would we cope?
Athena Aktipis: Yeah. Yeah. People have called it “survival porn.” There’s something just appealing about imagining yourself out there or inside or trying to survive in challenging odds. Yeah. It’s like a little story that we tell ourselves that makes us have fun and feel good.
Rob Wiblin: When we’re little kids, we play make believe all the time, and it’s really fun. As grownups, we don’t get to do that very much, but this gives us an excuse to imagine a really different reality.
Athena Aktipis: Exactly. Yeah. I think that puts a really nice pin on what I’m trying to do with this book: it’s an invitation to play a little bit of make believe about all of the things that could go wrong, things that are already going wrong. There’s places in the world that are just straight-up apocalyptic right now. But if we go into that place of having fun — imagining the zombie apocalypse, or how we would survive in a nuclear war where there were giant, huge spiders outside — you add something fun and silly and then it makes it not as real, which makes it easier for us to engage without that fear response kind of dominating.
I think we can learn a lot from looking at horror and looking at apocalyptic fiction. People like to engage with these things if there’s enough of an element of play to it. If we can keep that playfulness, cultivate that playfulness, and make it social as well, that’s going to help us to manage our risk as individuals, and ultimately, collectively manage our societal risk more effectively.
Overrated worries about the apocalypse [02:58:45]
Rob Wiblin: What’s something that people worry about in the apocalypse, in a catastrophe, that maybe they shouldn’t worry about quite as much as they do?
Athena Aktipis: Well, the big one for me is this idea that as soon as something starts going wrong, that the fabric of society is going to fall apart and that everyone will just be like, “Every person for themselves.” Because if we look at what actually happens during times of disaster, people jump into action to help each other in this need-based way — even helping strangers, even going to extreme risks to rescue people. People just do this spontaneously when the shit hits the fan.
And yes, if disasters go on for a really long time, if you have slow-burn situations, where people are starving and that lasts for months, for years —
Rob Wiblin: Like siege warfare.
Athena Aktipis: Right. Yeah. When people are in a state where they just literally don’t have enough food or water or whatever, our physiology starts to not function normally, and things can break down once you get into that famine territory.
But if we’re just talking about acute disasters, and if we’re talking about situations where, ultimately, people are able to jump in and help each other and deal with fixing some of the problems that have arisen together, you see that in the first few weeks — especially after a disaster but before everyone is like, “Oh, now we’re going to kind of go back to normal.” I think that people having the wrong assumptions about what happens in those moments is not only not supported by what we see in times of disaster, but it can also be really problematic.
Rob Wiblin: It is a destructive attitude.
Athena Aktipis: Yes. It doesn’t necessarily put us in a good place to be proactively managing risk together either, if you’re like, “Oh, everybody’s going to turn on everyone.”
Rob Wiblin: “Everyone for themselves. I’ve got to get my knife.”
Athena Aktipis: Yeah. This sort of Survivor mentality, right? Like that show. In the end, it’s like everybody’s pitted against everyone else, even if they cooperate a little bit.
Often, that’s not how it works. Usually, that’s not how it works. We humans survive because we cooperate and work together, and that is how we have survived forever.
Rob Wiblin: How we got here.
Athena Aktipis: Yeah. With hunter-gatherers, you don’t just have one hunter-gatherer foraging and hunting. They live in a group and they share at a central place, usually around a fire with whoever’s gotten what.
Rob Wiblin: That’s how our organism operates, basically.
Athena Aktipis: Yeah. And we like it.
Rob Wiblin: A single hunter-gatherer is a dead hunter-gatherer.
Athena Aktipis: Yeah. I think a lot of that’s reflected in just how we’re set up psychologically and emotionally. We like eating with people. A dinner party is super fun. Or preparing food with people, or just spending time with others, creating things together. We really thrive on being social and taking care of others to a certain extent too. It’s something that a lot of people intrinsically enjoy.
Really delving into that side of our human nature that desires to be interdependent and embedded and generous and helping others, and part of systems that are functioning well — where we’re there to back each other up and manage risk together — I think we like that stuff. The better we can understand the evolutionary and 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 the future.
Rob Wiblin: Ways things can go wrong. Yeah. It’s been interesting watching the conventional wisdom on this shift over the last few years. I think back in 2019, people’s intuitions were really that even quite modest disasters would lead to the breakdown of law and order. Everyone’s just stealing from one another, just because of some relatively mild problem.
I remember early on in COVID-19, some people were predicting 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. And the exact reverse was true. Crime went way down. Violence went way down. I mean, to start with it, people were saying home. It’s much harder to get into fights. It’s much harder to burglarise 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 it did go down in the short term.
But 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. When everyone’s part of the same struggle, they’re fighting against adversity together, then actually we’re way more cooperative in that situation than we are just on a typical day while we’re on our commute to work normally.
I wonder, 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 temper that?
Athena Aktipis: Absolutely. It’s a matter of understanding in what ranges of parameters you get what behaviour. In situations where things are bad for a long time and people are starving, then you can get what we would consider the breakdown of society and families and all of that, because people are literally just on the brink of dying.
Rob Wiblin: It’s quite zero sum.
Athena Aktipis: Also, I think we don’t really know when you get to the point of people being in that starvation state, where they’re very likely to die, what of the behaviour that you see would we call “adaptive” from an evolutionary perspective — i.e., was selected because it provided an advantage — versus a byproduct. This is a very unusual state for the organism to be in, and there are things that are happening that are just the result of molecular pathways that are…
Rob Wiblin: Accidental.
Athena Aktipis: Yeah. We don’t know, and it’s not something that we can really study, obviously. But practically, what we see is in those situations that you do get a breakdown. The other situation where you definitely can have favouring of cheating is in groups where there’s a bunch of anonymity. They’re large. People don’t necessarily feel like they have a stake in the wellbeing of the group that they’re a part of.
Rob Wiblin: There’s not kind of peer monitoring, or perhaps justice done when injustices are committed. Yeah.
Athena Aktipis: Yeah. In those kinds of situations, individuals that are exploiting are going to do better. If people see that exploitation and cheating is happening, then that can very quickly unravel if the norms start changing about that. I think we absolutely need to consider both sides of the coin here: What are the situations where cooperation not just makes evolutionary sense, but also is how people behave in practice? And then where are the situations where exploitation and cheating really are problems, both from an evolutionary perspective and a practical perspective, again?
Rob Wiblin: Cool. Well, I’m sure there’s tonnes more. There will be tonnes more in the book when it comes out. One of the fun things about imagining these scenarios is that they’re so diverse that you could just keep on going. There’s so many different considerations. There’s a lot of things that you can think through. When is the book coming out?
Athena Aktipis: It will be coming out in the spring of 2024. It’s still a little ways away still.
Rob Wiblin: Little way away. Well, hopefully, we’re all still around in spring of 2024 so that people can buy the book and get the extra advice.
Athena Aktipis: I am going to be posting lots of tips and things in the leadup. I’m on Twitter and on Instagram, and posting about this stuff all the time. You can find me there if you want to learn more or ask questions about it. I’m always happy to share.
The zombie apocalypse [03:07:16]
Rob Wiblin: Well, you’ve been very generous with your time, but we should finally set you free again to continue with your normal life. A final question: I saw on your website that you were involved in some zombie apocalypse medicine preparation thing. I don’t really understand the nature of this — what was it? And what was something useful you learned about surviving the zombie apocalypse specifically?
Athena Aktipis: Well, I’m the executive producer for this whole group of really fun and interesting scholars. We’re called Zombified Media.
We have the Zombified podcast that I cohost with my friend and colleague, Dave Lundberg-Kenrick.
We have this livestream channel called Channel Zed, where we have all sorts of shows that are based around the idea that the zombie apocalypse is going on now: Here’s how you get your pantry set up. Here’s how you set up your go bag. Here’s how you deal with the zombies outside in a way that makes sense given cooperation theory. We kind of used the zombie apocalypse there as a fun way to engage people.
And it all actually started with the Zombie Apocalypse Medicine Meeting. We just had the third one of those. We do those every two years. It’s basically an academic conference framed around this idea that the zombie apocalypse is going on and we have to try to understand zombie behaviour. We have to look at what are the threats that we’re facing in the world now? What are the threats we’re facing in the future?
Rob Wiblin: Did your head of department sign off on this? Who approved this?
Athena Aktipis: Zombified Media is an educational nonprofit media company. So we can do whatever the fuck we want, I guess.
Rob Wiblin: OK, I see. You can do what you want.
Athena Aktipis: But I have to acknowledge we have a lot of support from ASU. Financially, but also 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 people who’ve come on and talked with us. We have a special relationship with ASU.
Rob Wiblin: It’s great to see all of these bodies finally supporting an interdisciplinary research project like this. So rarely does interdisciplinary work get the support that it deserves, but here it is. Sorry, I interrupted. Carry on.
Athena Aktipis: Exactly. No, no, you’re absolutely right. Part of why we all love it is because it is a space that is fundamentally interdisciplinary. By setting up this frame that it’s the zombie apocalypse and we’re trying to figure out what to do, it automatically takes out all of the jargon and status positioning and 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. It’s all these people who are like, “Yeah, let’s play. Let’s talk about zombie food choice as a way to understand what’s actually going on in terms of how people perceive food,” and they discuss. People 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. It’s a really generative, fun space.
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 doing all levels of things. We’re trying to make it this very interdisciplinary space that also bridges across the different levels of learners, because, ultimately, we’re all trying to figure out what’s going on in this crazy world, right? I think young people have a lot to bring to the table. Those of us who’ve been around for a few extra decades, maybe we have some blinders on, and we need to have fresh brains with us so that we’re not just eating old brains that are filled with prions.
Rob Wiblin: I think maybe in a real zombie apocalypse, most of our effort would be going towards getting the CDC to finally acknowledge it, 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.
Sorry, my original question was: What is an unusual tip that you’ve learned for how to survive a zombie apocalypse? 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?
Athena Aktipis: Absolutely. I’ve got one big tip, and it applies to all apocalypses, which is to build your Z team. This is who are the people who you would want by your side in the zombie apocalypse, or really in any hazard. That doesn’t necessarily mean that somebody would have to be literally by your side — but somebody who you would want to be sharing information with, that you would want to be there to back each other up if something went really wrong.
That’s basically risk transfer. That’s the limited risk pooling. 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. But have a conversation with them about, “Hey, if the zombie apocalypse happened, what would we do?” — or if a nuclear event happened, if you want to be more serious — so you can start to have those conversations, and just think about how you can proactively manage your risk. And cultivating that Z team is a super fun way to do it. Hopefully your Z team members, they’re like, “Hey, do you have your 72 hours?”
Rob Wiblin: Bare minimum to get in the team.
Athena Aktipis: “If not, let me help you.” Right? I think we can approach it from this perspective of how do we bring more people into this idea of making managing risk fun?
Also, we should absolutely not neglect the neighbourhoods and communities that we live in. Because in the event of an emergency, it’s likely that there’ll be some interdependence with the people who live near us.
Then we can also think about scaling that up. There’s these sister cities programmes that arose for cultural exchange and educational exchange, but now when there are disasters in cities that are sister cities, oftentimes, there’s just this spontaneous outpouring of help. They’re kind of Z team members to each other.
We can kind of generalise this Z team idea, this risk transfer idea, to a lot of different levels: try to grow those systems that increase our resilience at the individual level, household level, neighbourhood, community, national, international levels. “Risk management for the win!” is how I like to look at it.
Rob Wiblin: My guest today has been Athena Aktipis. Thanks so much for coming on The 80,000 Hours Podcast, Athena.
Athena Aktipis: My pleasure. Thank you so much for having me.
Rob’s outro [03:14:52]
Rob Wiblin: Alright if you’d like to explore related ideas I can recommend checking out:
And you can find more from Athena at https://www.channelzed.org/, https://www.zombified.org/ or https://www.athenaaktipis.org/.
All right, The 80,000 Hours Podcast is produced and edited by Keiran Harris.
Audio mastering and technical editing by Milo McGuire.
Full transcripts and an extensive collection of links to learn more are available on our site and put together by Katy Moore.
Thanks for joining, talk to you again soon.