From the Vault: Cancer and Evolution with Kat Arney

My name is Robert Lamb and I'm Joe McCormick, and today we're bringing you another interview that I conducted last week while Robert was taking a break from work. That's right. Once a year, I like to bury myself in some sacred imported soil and allow my my body to break down and the reconstitute itself so that I can rise once more and be up to the challenges of podcasting

in this day and age. Today we are going to be sharing the conversation that I had with the British geneticist and science communicator Cat Arnie talking about her upcoming book, Rebel Cell Cancer Evolution in the New Science of life's oldest betrayal, so a little bit of biographical information. Cat Arnie hosts the Genetics Unzipped podcast and she holds a

PhD in developmental genetics from Cambridge University. She was a key part of the science communications team at Cancer Research UK from two thousand four to co founding the charity's award winning science blog and acting as a principal media spokesperson. She's also the author of Hurting Hemmingway's Cats, Understanding How Our Genes Work and How to Code a Human and she's written for Wired, The Daily Mail, Nature Mosaic, New

Scientist and more, and presented many BBC radio programs. You can find Cat Arnie on Twitter at at cat Underscore Arnie a r in e Y and I should note that the book is coming out at different times in the UK in the US, so Rebel Cell can be found in the UK starting on August six, and then in the US. I believe it's coming out on September twenty nine, but you can go ahead and preorder it online. All right, Well, I'm I am in a rare position here because I am just like the listeners out there.

I have not heard this interview yet myself. So I am excited, uh to to to listen in as she sheds light on this, uh, this fascinating topic. Cat Arnie, thanks so much for joining us today on the podcast. Thank you for having me. It's an absolute pleasure. It's a pleasure to have someone on the show who has not only written a great book, but you are actually a podcaster yourself. So you're so you're used to this whole game talking into the mic with alone by yourself

in a room. Yeah. I've been making the Jannetix Unzipped podcast. I do have to say that through this time, we've we've deliberately made it a COVID free zone, so it is currently a COVID free genetics podcast. So that's been that's been a nice thing to do during during this time, I got to say I was listening to one of your episodes of the gene Lex un Zip podcast, the one about Maud Sly and Pauline Grows, which I thought was fantastic. Of course it connects to the book that

we're going to be talking about today. So personal endorsement from me of your podcast. Don't really like it? Thank you. Yeah, it's really fun. We we alternate. We do sort of

interviews with scientists who are working now in genetics. But I also really like to go back through those stories and dig out, particularly the untold women who were often they're doing the work, doing lots and lots of stuff, incredibly detailed observations and breeding experiments, and then basically didn't really get the credit for it, because until the middle of the twentieth century or later, women weren't really respected

as a scientist. So it's it's just a wonderful expliration you come up with all these incredible people, although of in the early century lots them do turn out to be eugenicists, but different podcast I think, yeah, So I think maybe a good place to start when talking about cancer. Of course, your book is about cancer, and specifically a

lot about the genetics of cancer. I wanted to maybe start off by talking about this strange kind of gut feeling or almost superstition that somehow, unlike other diseases, cancer is a modern synthetic, uh, some kind of perversion in some way against nature, and that it sometimes comes with this odd edge of moralism, that cancer is not just unfortunate, but it's somehow decadent and an indicator of something wrong

with our age. Parts of your book indicate to me that you've come up against this kind of thinking a lot as well. What do you think this sort of thinking signifies. I think it's absolutely fascinating. Cancer is not a new disease, and that really became abundant clear to me. So, just as a little bit of background, I spent twelve years working at Cancer Research UK, the UK's biggest cancer charity, answering lots of questions from the public, and all the

time this question comes up. It's like, why me, isn't it just a modern disease, Oh, it's all this stuff in the air, or it's stress. What what is it? And you start to look into what cancer really is, and it's it's ancient. It's hardwired into our biology because it's just cells doing what they're going to do. Cells multiplying, cells jostling for space, cells competing with the cells around them,

obeying the processes of evolution. And so when you really start to look, it's not surprising that you find cancer going all the way back through human history, all the way back through the history of animal life on this planet. But at the same time, when people start to become aware of cancer as a disease. They start to ask questions about, well, where did this come from? Why has it affected me? You start to get the Greek as people like Hippocrates who were writing about cancers in their

patients and saying, well, what has caused it? It must be the gods, It must be the humors. Something is out of whack in here. And then you start to get the slightly more religious thing of well it is it's fins visited on us. It is something to do with immorality, modern living. And then you bring up to today this we don't necessarily have such a strong religious view of it, but certainly the idea of almost wellness

as a religion. You've done something toxic to yourself and that's why you you now have cancer, and you look back at the history of cancer as a biological phenomenon, and that's simply not true. You know. It's it's basically like the dark side of life, rather than anything that

we have particularly brought on ourselves in our modern life. Yeah, that's one of the things I really loved about your book was the way you how you show cancer to be so fundamentally integrated with with with life itself or I guess, multi cellular life life um. And so so maybe we should focus on on a couple of these ideas in particular. One of them, I guess, is the idea of modernity, right, the idea that that cancer is

something that was very rare until recently. You make an argument against and people have argued this, but you make an argument against this in the book, and you cite some both some reasoning about why a lot of cancers wouldn't necessarily show up in the kinds of remains we can examine, and then pointing out examples that we do find in fact in the human record and physical remains

of human society and prehistory. Yeah, it's the classic thing in biology that you find what you're looking for, and people have not been looking for signs of cancer in ancient remains. And the thing about cancer is that that when you're thinking about ancient remains that we find mostly you're talking about bones, and particularly when you get very ancient, you're talking about fossilized bones. And not every cancer leaves

its trace in the bones. So when you're thinking about cancers that affect the soft tissue, you may never see the traces of a cancer that killed someone. Also, you know, ancient remains don't turn up in beautifully aged, matched structured populations, so you can say, oh, this is exactly the population that was alive at the time. This is exactly the

number of cancers in this population. I think some people have argued that the fact that cancers are rare in ancient humans is an argument that cancer was very, very rare. But I slightly feel the other way around. I feel like the fact that the more people start looking for cancers in human and animal remains from from way way back, the more cancers they start to find suggest that it

was more common. We will never know how how common it was, because you can't do, you know, a lovely epidemiological study on the sort of stuff that you can get out of the ground. You get what you get and you get on with it, basically. But I do think that cancer is not an exclusively modern disease. I will say, certainly it is more common as we live longer. So another of the things I go into you later in the book is the idea that there's almost a

sort of a shooting up point. After you have got to a certain age, your risk of cancer does significantly go up. So if you think about ancient populations when there were many, many, many more things that we're going to kill you, your chances of getting to an age where you could dive cancer before something else got you were smaller. So it's not surprising we find fewer ancient

remains with cancer. But when you think about some children have been found with types of cancer that are very very rare in populations, and the fact that we have found them at all suggests that this is a disease that has always been with us, and it's not exclusively a confection of modernity. It's it's basically, you know, it is with us and always has been. And what about the part of the misconception that views cancer is something that is uniquely kind of human and maybe associated with uh,

with the synthetic products of human industry and all that. Like, this ties into the idea that sharks don't get cancer, right, that there's a widespread belief that for some reason, animals that don't engage, you know, don't live in cities and drive cars and eat processed food and stuff, won't get cancer. But they do. Yeah, this really blew my mind. I can see over on my bookshelf. I'm so tempted to

go and grab it. But there's a book where someone has gone through all the different species that have been known to have cancer in In some cases it's many examples, in some it's just a few, but it's pages and pages and pages. Is everything from like odd wolves to zebras, and almost every branch of the animal kingdom develops cancer. There are a couple of really weird exceptions. So one is comb jellies. Comb jellyfish don't seem to get cancer,

never been detected. And also sponges really weirdly resistant to sponges. There's this guy in in Arizona, guy called Carlo Malei, who is zapping sponges with enormous amounts of radiation like that would kill a human, and they're just fine. They just shrug it off. So there are some species that are cancer resistant, but pretty much everything else, to a greater or lesser extent is and humans aren't even the most susceptible species. There are some that are much more

susceptible to cancer than humans are. So this idea that it's it's just a modern disease, it's just a human disease. It just doesn't stack up. You know. Yes, there are things that we do in our modern lives that increase the risk of cancer, and our lovely living to a nice old age is a major risk factor. You know. Thank god we don't all die in childbirth and of

infectious diseases before our tenth birthday. But you know, we are we are not, you know, unique and wonderful when it comes to cancer again, it's it is just part of life. There are some other interesting observations you mentioned in your book about what might create a specific propensity

for cancer in certain species versus others. One that I recall is that you mentioned that it's cancer seems to be more prevalent in species that have been through a genetic bottleneck at some point in the relatively recent past. So like, if their breeding population was reduced to a pretty small number at some point, they tend to be

more susceptible to cancer. Is that correct? Yes, so that does seem to be the case, which suggests that there are genetic factors at work, because if you shrink a population down to a very small what's called an effective breeding size, you've got quite a small population that's all breeding with each other. You do start to get a pile up of mutations being passed from generation to generation,

which might be increasing the risk of cancer. One of my favorite species in this case is the Syrian hamster, which all the Syrian hamsters pretty much that in pets and and abs all over the world, are descended from one litter of hamsters, and they are incredibly cancer prone because they're just massively in bread um. But yeah, every every species, some more than others and some much less

than others. So elephants very surprisingly, you'd think when you think about it logically, animals that are very very big, they have lots of cells, they live for a very very long time, you would think that elephants should be riddled with cancer by the time they die, but they are not. They are amazingly resistant and really long lived animals like bowhead whales, even some of the really long lived bats, brand bats that live for forty years, very

resistant to cancer. So they have evolved mechanisms that enable them to live these very long, luxury lifestyles and be resistant to cancer. Whereas you have very small rodents, things that live fast and die young, why bother you know you're going to be around for a couple of breeding sea reasons and then near out and humans are kind

of in the middle. You know, we live for many decades, we reach our childbearing years in between our sort of twenties to forties, hang around for a bit after, and then the risk of cancer does start to go up. So you know, this is when you put humans in the context of all of life, you start to understand how our evolution as a species is intrinsically tied to

our as a species risk of cancer. But you do have to separate that from personal risk of cancer as well, and that's a that's kind of a bit hard to get your head around, so talking about evolutionary risks versus personal risks. So one of the most interesting ideas in your book that that you keep returning to is a framework for thinking about multicellular life through the analogy of a society, that a multicellular organism is a society of cells. Could you explain this way of thinking in and some

of the implications that extend from it. Yeah, this really really blew my mind when I started to understand this. So, this idea of cells as a society, it goes about quite a few decades. A lot of things I discovered while I was researching the book are quite old ideas that have got you know, subsumed or left behind in this this rush to just understand cancer as a purely genetic disease. But the idea is that cells and organisms and individuals in a species, they live in societies, and

there are rules of societies at every single level. You know, things like do the job you're meant to do, don't take more than you need, clean up after yourself, all these kind of things. There are rules to societies that make societies work productively. And you start to look around at groups of cells that are in tissues and in organs in your body. You look at societies like ants

and bees. You look at colonies, you look at troops of chimps and herds of deer, and you look at human societies and they all work in the same way. And this particularly an idea that I was influenced by. There's a researcher in Arizona called Athena Actipis, and she works a lot on social cooperation and cheating, and the

idea that cancer cells basically cheat in society. They are cheaters, They take more than they need, they produce waste, They proliferate out of control, they don't die when they're meant to. They are not good cells. Now, if every cell in your society was doing that, it would just be you know, mad Max style dystopia. Nothing would work, Your body would not function. But you can get away with being a cancer cell and cheating and keeping going and keeping going

because to a certain extent, cheaters do prosper. And it's the same in many animal societies. So one of the lovely examples that I found was these cape honey bees. So this just wonderful examples. So cape honey bees, they

have a classic honeybee population structure. You have the queen, and you have all the workers, the female workers, but the queen is the only one who gets to reproduce, and so all the workers are busy doing all the work in the hive, and the queen's just cleaning around basically like ah ha um, and you know, popping off

to reproduce when she feels like it. But there is a genetic change, single genetic change that means that these worker bees can become queens and they start to just sit around, you know, cleaning it up, and eventually the hive starts to collapse under the weight of all these cheaters, and it's just a single genetic change that enables them

to do this. And actually some of these queens will go off to other hives and start to infect them and turn them into cheaters as well, and it's almost like a bee cancer, I suppose, because ultimately it leads to the destruction of the hive. And you say, well, why would the bees have this, Why would it be so fragile that one genetic change can disrupt it like this?

And it turns out that where the bees live it's very, very windy, So there's a risk that if you just have one queen and that's all you get, your queen could get blown off course and you might lose he totally and then your hive would collapse anyway. So the ability to flip into queen mode it's really useful for the bees for their evolutionary survival, but it comes with a risk. And it's the same with cells. So we

need to be able to make new cells. You need to regenerate millions of cells in your body every day, millions of cells in your skin, your blood, your bowel. You need to be able to heal yourself. If you're wounded, you need to be able to grow from one cell into an adult human. Cells need to reproduce, they need

to do stuff. Flip side of that is that they can sometimes go out of control because it's the same mechanisms that make cells grow and multiply in the right way that they kind of harness and hijack when they decide to cheat and grow out of control in the wrong way. So that's interesting. You're sort of showing how cancer is one side of an evolutionary balance where on one hand, you've got you know, as your ability to do something good goes up, the risks associated with those

same genes that code for that also go up. So we know on one side what the downside is. We can see tumors and cancer. And you're saying that the the the goods that make those risks worthwhile are basically being able to proliferate quickly in in cell growth. And this would have to do not just with growth in youth, but in healing and things like that. Yeah, exactly, And you see this. This starts to explain the differences across species because if you if you cut a mouse, mice

heal amazingly fast. Their cells just basically knit themselves back together. It's it's absolutely incredible. Um. One of the stories that I discovered when I was talking to a researcher in Santa Barbara who's trying to work with the animals in the zoo to understand their cancer risks. She's she went to the zoo and said, can I get a little bit of skin from your giant tortoise? And they were like, hell no, we cut a tortoise. It takes a year to heal, and tortoises live for a very long time.

They're incredibly cancer resistant, but they the flip side of that is that they don't heal very easily. So humans again somewhere in the middle. We don't heal as fast as mice. We live much longer than mice. So there's there's all of this stuff is a trade off about the evolutionary journey that your species has taken. And one of the things that I sort of took this to its logical conclusion, and I was like, if there's aliens,

aliens would get cancer. There's very unlikely that they would not if they obey the general rules of evolution, And this idea that, like cells, organisms living in a society behave according to the rules of that we know make a good society. I don't think there's any reason why aliens wouldn't get cancer. She's like, that's a bit of a that was a bit of a sort of late night thought. I think, because all that's necessary is that they exist by cell division, right, I mean that's pretty

much it. Yeah, yeah, exactly if you have cells and your cells are doing cell division, and also if you have evolution by natural selection, which is basically the engine that drives cells to to proliferate and be selected for and to keep going, and species to keep proliferating and keeping going, then yeah, you probably could get cancer. And

that's what we generally see across the entire animal kingdom. Well, thinking about aliens getting cancer makes me think of another interesting part of your book, would was about difficulties in classifying what appears to be some form of uncontrolled cell growth in animals, or even not animals, other organisms that are very different from us. So can you look at what's going on in a clam and say that it has cancer? Yeah? Probably, But what about a mushroom or

in an algae or something yeah, this was This was interesting. So, you know, what is cancer and when is cancer is an interesting question. And when you get to more organized animals, and particularly mammals, we define invasive cancers as cancers that kind of break through the sort of molecular I guess you'd call it like saran wrap that's around your organs and your tissues. They break through this membrane, and that's

what we call invasive cancer. But really, you know, the phenomenon of cells growing out of control is all over the place. You can see it in plants when they get gals. You can see it in in fungi. You can see it in all sorts of things. And what are the interesting quest ens is you know something like endometriosis, which is a condition where you get rogue tissue within the body and it's sort of it grows and its spreads and it bleeds and it's very very painful. It's like,

but that's not cancer, it's not invasive. But actually, when you look at that kind of tissue, it has lots and lots of the kind of mutations and changes we'd expect to find in cancer. But that's not cancer, and that's in humans. So this this idea that mutations, it's not just what makes cancer. Uncontrolled cell growth is not just what makes cancer. It's it's sort of this this invasive, aggressive, evolving characteristic that really is what we can classify as

as cancer. All Right, we're going to take a quick break, but we'll be right back. And we're back. So maybe we should shift to talking about the history of our understanding of the approximate causes or maybe better to say, the risk factors for cancer where it comes from, whether

that's there's an hereditary component and an environmental component. Uh, there's a part in the book where you mentioned this thing that was called the Daily Mail Oncology Ontology blog, which I really appreciated because so the idea was this was an attempted list of all the things that either cause or cure cancer, according to the Daily Mail. And

that made me say, I've got to admit something. I read a lot of science and medical news from my work, and I have all but completely turned off my recognition system for articles about, you know, new supposed causes or cures for cancer, because this was already like a cliche to the point of being a hack joke for comedians in the nineteen nineties. Is there something we should learn from this, like the way that we get this conditioned

kind of numb reaction to these types of news stories. Yeah, that's we used to get a lot of that when I was at cancer a set k. You know, I think the stupid this one was that water gives you cancer, and also that turning on turning on the light at night to go to the bathroom gives you cancer. So you know this, this is really really frustrating. So there's kind of a couple of there's a couple of things to dissect because it's also comes down to like what

what is actually the nature of cancer? And the way that cancer has been thought about for a very long time is according to what scientists like to call the somatic mutation theory of cancer. So this is this idea that cells pick up changes in their DNA and their genome that the instructions that they used to do what they do. They pick up these changes, these mutations, and that enables them to do more bad things. And then they pick up more and they do more bad things.

So it's this gradual accumulation of nasty mutations turns nice, well behaved cells into aggressive cancer cells. And we can start to see some of the characteristic fingerprints that different agents leave in the genome. So we can see, for example, cigarette smoke or ultra violet light from the sun, we can see those characteristic fingerprints of damage in the genome.

What that doesn't necessarily tell us because when you start looking closely at a cancer or even in fact at normal tissue, you start to see these changes and mutations everywhere. So this kind of simplistic model that it's a hit in this green and a hit in this green, and a hit in the stree and a hit in the street in a bang, that you've got a cancer cell is nonsense because loads of healthy cells such as peppered with mutations and loads of things do damage our DNA,

and that's kind of like it's mostly fine. So it's a bit more of a sophisticated understanding of yes, there are things that damage DNA. A lot of them we know about, some of them we don't know about yet. Researchers are trying to figure out, you know, how do we match chuck these signatures of damage to things that are in the environment alas mostly the most single, most damaging thing you can do for your DNA is breathe oxygen, literally just being alive. The processes of life in your

cells damage your DNA unfortunately. But then if all your cells are to some extent, you know, more or less messed up. Everyone's got a few mutations here and there, some more than others. What is it then that tips a cell into becoming a cancer cell? If everyone's a bit weird, what makes that cheating cell kind of slip the bonds of good society and really start going for it?

And that really is is an evolutionary question that cell has involved the capacity to do that, And so I think it's it's far too simplistic to say, oh, well, you know your cancer was absolutely caused by smoking, that was it. It's like, well, that was a risk factor and it certainly didn't help, but there were many other things. And also many people who do smoke don't get cancer. So it's like we've got to be more sophisticated in understanding what makes normal cells become damaged and what makes

kind of sad cells become really bad cells. Yeah, this is an important point about thinking about risk factors instead of causes. And I know that that's it's infuriating to people especially. I think if you don't have a lot of like training in a statistics oriented field, that it just doesn't feel very comfortable to think about, especially something that's a really important life and death issue like cancer in terms of probabilities. You want to know like what

it was or what what did it? Yeah, exactly. I think the best analogy that I really came up with is, and this is spoilers. Now, if anyone's seen Agatha Christie's murder on the Orient Express where and I am this is a massive spoiler, but come on the books, like really older should have read. Now see the movie with Albert Finn's great But it's a murder, but all the people involved they all have a stab, so you never know who actually was the murderer. So it's it's kind

of like this. So you know, we have lots and lots of genes that we know are implicated in cancer. There are lots of things that can damage our DNA. There are lots of things that can like improve the environment of our tissues or not. We know that things like you know, keeping keeping well and healthy and doing all the boring healthy living stuff that helps to keep your your body healthy, makes your cells more likely to

fall into line. But saying exactly like it was that thing, you know it was, it was that sunny holiday in marbea in that damage that skin cell that gave you cancer, as I you know, that's that's simply not possible. So trying to say oh, it's this, Oh it's that, do this, don't do that, I think is it is not terribly helpful because at some point we've just got to get on and live and try and negotiate the risks that

we're happy with taking. Right at the same time, you do point out how there are certain factors that increase your likelihood so far above the baseline that maybe at that point it even though you still can't quite say it's a cause, it's something closer to a cause. And one I think one common example given would be tobacco. Remember you mentioned another example in the book about uh, just chronic exposure dermal exposure to soot in chimney sweeps.

I believe it was. Yeah, this was the first example of someone actually showing that something a substance in the environment could increase the risk of cancer. And this is an English surgeon called Percival Pot who had a purely professional, interest in the scrutums of young boys, purely professional, because he was interested in chimney sweeps in London. Now this was in there, and chimney sweeps were basically sent naked up the chimneys by gang masters to clean the chimneys.

So they were exposed to a lot of soot, and they noticed that they started to get these cancers in their genitals, and they were called soot warps, and these were very very very nasty cancers, really horrible kind of stuff. And Pot realized that it was the soot that these boys were being exposed to that was causing these cancers. And he said, right, you know, we've got to get nice in Germany that all the chimney sweeps have these nice kind of tight fitting uniforms so they weren't being

directly exposed on their skin. And he was like, right, we've got to get those in. Got to protect these boys, stop sending them naked up the chimneys. M Alas it took over a hundred years for people to actually change in Britain because the gang masters were like, no, those those uniforms are too expensive. It'll make our sweeps too expensive,

you know, they're they're cheap, we don't really care. So that was really tragic that they managed to link this cause to these very horrible cancers, and there was something that everyone knew could be done that was helping in other countries and nope, nope, it didn't happen for a

very long time. Um. But yes, that Percival part is kind of the father of this idea of external sources of carcinogenic chemicals, I think, but I think it has stuck in the imagination that like it's all external, it's all from from something you've done, or something you've got, or something you've touched or eaten or been exposed to.

Well to go to the other side. So there's a part of your book where you explored I think we actually mentioned this earlier about your podcast episode about Maud Sly and Pauline gross and in the role, for example of the research of maud Sly in establishing that there is a hereditary component to cancer that I think at the time you say that, you know, the primary argument was about two different major theories of external causes, whether

cancer was caused primarily by inflammation or by infectious agents and parasites. Is that correct. Yeah, So at the beginning of the twentieth century, the early twentieth century, there was this idea that cancer was either all caused by external things like certain things in the environment, or it was viruses. Mostly there were a couple of good examples in animals where you could take viruses exposed the animals to them

and they would develop certain types of cancer. So the first one was a guy called Peyton Rouse who discovered a virus that caused cancer and chickens. So by the sixties everyone was just obsessed with the idea that it was viruses. And now you know, we really understand that there are families that are affected by multiple cases of cancer, that cancer can be to some extent influenced by the

genes we inherit. But really this was a wast a completely separate, parallel strand running up through the first half of the twentieth century, and it was work in mice

in families. In the podcast, we talk about the story of mord Sly who bred all these mice together to show cancer could be inherited, and then the story of Pauline and Gross, who was a seam stress who meant a scientist, and she said, you know I'm going to die young, and he mapped out all her family because so many members of her family were affected by the same types of cancer. And it took, you know, decades until they pinned down the particular gene fault that was responsible.

But yeah, they're all these lines were like running a completely separate to each other until it all started to coalesce together in this understanding that you know, there are things that damage our genes. There are genes in ourselves that make ourselves replicate that that stop ourselves from dying. This is good normally, but they can go wrong. They can be mutated, they can be changed, we can inherit

versions that affect their function. And it all sort of started to coalesce into this very sensible idea of of how cancer starts. But I think it just became very very focused on the genes and the cells just yes, single genes, shopping lists of genes and changes, and forgot to look at this broader picture of the environment in which cells are, the society in which they're living, how they can interact with each other, cheat, overcome expand push

against each other. This more. I hate to use the word holistic because it sounds really kind of hippy dippy, but you know, it's it's part of our bodies. It's not an external alien thing. These cells obey the rules of our bodies to to a certain extent, they cheat the rules to another extent, but it's all kind of part of one piece. And we've just focused on on genes and molecules for the past couple of decades. I think, far,

far too much. All right, we're going to take a quick break, but will be right back with more than all right, we're back. So you mentioned in the book that you believe that the future of our resistance against cancer and medical treatments of cancer are going to rely on quote shifting towards a new way of evolutionary and ecological thinking about cancer. So I assume there you're connecting to the ideas you were just articulating. But could you

expand on what you mean by that. Yeah, So, as all the sort of strands of cancer research over the past that of one years started to coalesce on this idea that that cancer starts when cells pick up certain genetic mutations and they go out of control. And then we started to get to this idea that then well, the way you treat them if you find the molecules the genes that are making them go out of control, and you target them with drugs, and that's going to

be the way we're going to cure cancer. And there's been so much, so much effort, money, research, time, patients, lives, in clinical trials have gone into testing these very molecularly targeted drugs, and you know, some in some cases there have been incredible success stories. So for example, a drug called gliveck for treating a certain type of leukemia is incredibly successful. It targets a very specific genetic fault in the cancer cells, and it is it was game changing

and it continues to be game changing. But lots and lots of the other drugs that have been developed along these lines, they have not transformed survival in the way that we would hope they've They've eked out, you know, in some cases months, in some cases, you know, a few years. In one case, I saw a paper that said nine days increase in survival with this particular incredibly expensive targeted drug. And you're like, these are not cures. These these are these are the magic bullets that we

were promised, and they are not cures. And in virtually all these cases, the campcer comes back. And why does it come back because of Charles flipping Darwin? You know, it's it's evolution. You hit something, you get rid of most of the cells that are sensitive, and you've still got a core of resistance because you've got so much genetic diversity in that population of cancer cells. And so they start growing again, and this time they're resistant to

the drug. So maybe you try another drug, same thing happens. You get rid of the sensitive cells, you've still got a core of resistance, and they grow back, and eventually

you run out of options. And there's time now to think about cancer in a much more evolutionary and ecological way, as you say, thinking about well, if we know that this process of evolution is at work, that if you get rid of the sensitive cells, the resistant ones come back, Like, well, why don't we try and approach this in a different way. Why don't we try not to knock them all out?

Why don't we try and balance these populations, keep them suppressed, keep them under control, much in the way that say a farmer would try and control the pests in his crop, rather than completely trying to nuke them all from orbit or eradicate every single last grasshopper, you know, and understanding the ecology the tissue biology, So you know, are you actually causing more damage to tissues by treating with drugs

or radiotherapy or surgery. How can we minimize that so that it doesn't encourage cells to to cheat even more in a damaged environment. So it's this this idea is starting to come through, But I think I think it does take a bit of a subtle and sophisticated understanding of cancer as an evolutionary process within the tissue environment of the body, rather than just like these are some rogue cells that have gone wrong and they're growing out of control, and we just need to hit them with

enough magic bullets and they'll go away. You know, the classic cure for cancer that we've almost been sold it's I don't think it's it should look like that, um because we tried that and it's not really working. So I think we need to try a different approach. This way of talking about tumors is reminding me of something you mentioned earlier in the book actually, which I thought was really interesting image that stuck with me. The idea

of a hypothetical hyper tumor. I'd never considered this before, but the idea that a tumor can get a tumor. Yeah. So again, it's the thing that really jumped out at me researching this book is that cancer is a microcosm of evolution. It's it's a crucible of evolution. A dumpster fire of evolution is probably the best way of putting it. Cancer is a dumpster fire of evolution, Thank you, um.

But yeah, everything, every innovation of life that you see on Earth, cancer can evolve because you have a very large, genetically diverse, popular lation of cells that have got lots of opportunity to try stuff out. So you know, it's not surprising that even within a horrible cheating atmosphere of a cancer you might get some really really badass cells that will start proliferating even more and actually suppress the original tumor by just out competing them in a Darwinian sense.

And then there's some really wild things that I discovered. So the most crazy innovation is that a guy is a guy called Kenneth Pienta in Baltimore has discovered that cancer cells have invented how to have sex. This this really blew my mind. Because the implications are massive. Here. We have this idea that cancer cells they just they reproduced basically by splitting into that's fine, you know you have one cancer cell, it becomes two, it becomes for

all of that kind of thing. There's no transfer of information between cells and after that. But he's discovered with these prostate cancer cells that they fuse together and become resistant to treatments. And then they start kind of budding off little cells that are resistant to treatment. And you're like, what you know that looks like sex, I mean for a very poor value of sex, but that you know, that's the biological process of Sex's two cells fusing together

and and creating more. And you're like, whoa, because that's a way of genetically combining forces. And again it's an evolutionary innovation. Sex has evolved on this planet multiple times. You know, it's not unheard of. And if you have enough rolls of that dice, as might happen in in a cancer you know, weird, weird, weird, our stuff is going to happen in there. Um. It's just it really is mind blowing. Every innovation of life. Cancer cells, you know,

at some point somewhere might have a go at. And so when I realized this, when I realized that, you know, cells can have sex, cells can do all these kind of crazy evolutionary things. They can smash their chromosomes out, they can glue themselves back together. It's all kind of crazy. And then I started learning about the thing that was just really incredible. So, right, imagine there's a disaster movie happening. Right, you know what happens in a disaster movie. Everything's going wrong.

You've got the guy and you've got the girl, and what do you do when your world's ending, right, You have sex basically, So that's like a last ditch attempt for cancer cells to try and come up with some kind of evolutionary innovations that are going to get them out of trouble. But then there's one more thing that happens at the end of a disaster movie, right, you leave the planet. Sure, yeah, and like and cancer cell

do this, and this is absolutely incredible. So so this is where we get to infectious cancer, the idea that it could actually be contagious. Yeah, so this is this is kind of spooky and scary because it's a very medieval idea that cancer is contagious. That you catch it from someone. And I will say that in certainly in humans, there's no contagious cancers that we know of. But the first example was the Tasmanian Devils. So this was back

in the nineties nineties. The Tasmanian Devils, they're all in Tasmania, Southern Australia. They're very cute animals, but like they're evil. They're very you know, they're they're placid more or less around humans, but they absolutely hate each other. So when you get to Tasmanian devils together, they're just like, really,

go for it now, biting each other's faces. And researchers started to notice that these animals were getting big tumors in their faces and in some cases it was killing them, and that they're already endangered as it is, and this cancer started sweeping through the populations and I was like, oh no, what we're going to do. And a woman in Australia, she was working for the for the government in a hospital. She's she was looking at cancer samples

from humans and looking at the chromosomes. It was a way back then of identifying the kind of cancer you might have. And so she started looking at these Tasmania devil cancer samples. Now, the thing about human cancers is every human cancer is a one off. It's a unique evolutionary event. It starts in you, it grows a new it evolves in you, and it it dies in you one way or the other. When she was looking at these devil cancers, like they're all the same from every animal.

The chromosomes were absolutely the same, and it's like, that does not happen. That is that? And she was like, this is a contagious cancer and uh. And eventually they kind of pinned it down and it said, yes, it was cancer cells transmitting from one devil to another through that mechanism of biting and fighting and scratching. So it's a you need with a contagious cancer. You need to have a mechanism of transfer to get the cells from one organism to the other. So with the devils, it

was it was biting and fighting. Um. And then there was another cancer, contagious cancer, which were allowed to talk about dog genitals. Oh yeah, just I just did so. Yeah, so there's a dog genital cancer called canine venereal tumor as CTBT and so yeah, it's again when when dogs have sex. It's not pretty, but they get kind of tied together in the the gentleman and lady department, and that can cause some injury. So again you have a mechanism for cancer cells to try its fer from one

dog to the other. And this cancer it transmits through populations. And there's a woman called Elizabeth Murchison who's in Cambridge University. She started studying the devils and then she started studying these dogs and they discovered that these cancer cells in the dogs have been around for thousands of years. The first dog with that cancer lived and died thousands of years ago, and it's gone all over the world. And that's like, it's like the oldest I don't know, it's

like the oldest mammal. I suppose. It's just incredible. Um this they've worked out what kind of dog it was. It was, you know, a little kind of dog with like pointy ears and a sandy coat, and it's amazing. So when you're saying it's the oldest mammal, in a way, you're saying that the tumor is in a sense of part of that original dog. It is that dog. It is that dog's body exactly the tumor arose in the dog.

It's got the genome of the oridge, an old dog, like seriously messed up, I mean, and these cancers are now evolving independently in different dog populations all over the world. But yeah, it's it's an incredibly long lived organism. I suppose, so that that was one devil cancer which was relatively recent a dog cancer, and then they found a new second devil tumor that had arisen even more recently. So

that's very unlucky for the devils. And they think it's because again they're quite an inbred population, so with this this fighty bity mechanism of transfer, so you've got quite high probability that this might happen. And then there's all these weird shellfish that have cancer and seem to transfer it between each other by shedding cancer cells into the sea, which is just disgusting. Um. It has made me rethink my idea of swimming. But there's some really incredible examples

of transmissible cancers in nature. And again I think the more we look, the more we're going to find. You know, each one of these papers just gets published and less and less impressive journal is more and more, more and more turn up. But there are some examples in humans, and I talk about a couple in the book. So

there's one which is they're absolutely horrendous. Is a guy called Chester Southam who was in New York, I think in the fifties, and he was doing experiments on prisoners, mostly black prisoners in the US, people in care homes can existing cancer patients. People are very desperate and not consenting to these experiments properly, and he was putting cancer cells into them and in some cases they did developed humors. Mostly they didn't, which shows the human immune system will

fight these cells off, but some of them did. And also there's a very sad story of a woman who developed melanoma. And at the time, this is around about the sixties, I think it was an idea that you could transplant some cancer cells into someone to get an immune reaction going uh, and then give that kind of blood back to the patient and it would help to treat their cancer. It's sort of an early idea immunotherapy, so basically getting someone's donor immune system to generate some

antibodies to neutralize the cancer when you donated them. And so this woman's mother said all right, I'll do this. You transplant me with a bit of my daughter's cancer, I'll generate the antibodies, and then you can take my

blood and give it to her. And unfortunately, the daughter actually passed away very quickly, and a few weeks later it was discovered that the mother actually did have the cancer growing in her and and then shortly after that, the mother passed away from the cancer that had killed her daughter. And you're like, it's rare. Um and probably because they were related, you overcome the problems of immune rejection,

but you're like, oh, well, it could happen. Ah. And then there's the most absolutely disgusting one, which is this is really sad and awful but also gross. Um. So, there was a man who walks into an HIV clinic in Colombia complaining of feeling very unwell. And so he had HIV for a long time, so his immune system was very suppressed. He hadn't been taking his medication, and

he was feeling very unwell. And they looked in his body and they found all these little nodules in his body and and they were like, well, these don't look like human cells. This is very weird, and well, maybe it's a parasite or something. And they gave him some some treatment, and he went away and and he came back and he's like, it's still no better, and there's

more and more of these weird things. And they looked more closely, they got them analyzed, and it was he'd been infected by tapeworm, but the tape worm had a cancer and the cancer had infected the man. And you're like, whoa, that is a just the stuff of nightmares. Um. Be highlights how powerful the human immune system is at the best of times. And see it's like, oh my god. You know, also tape worms can get cancer, so it sort of highlights a lot of the principles at work here.

And very sad for that man, but unfortunately he couldn't be treated in the time. Um and it's like, this is an incredible biological phenomenon really that we were only just starting to understand. Yeah, I mean, these are all just unbelievable examples. And and go in the column of you know, the case you make that we should shift towards that thinking of cancer in an evolutionary and ecological way instead of a purely molecular way. So if that's

the dark side. What about thinking about cancer and an evolutionary and ecological way gives you hope? Do you see lines of research extending from that framework that give you hope for the future and of cancer treatment and and the fight against cancer. Yeah, so you know, you can get very sort of nihilistic about this, and I, oh, yeah,

resistance always emerges. Evolution is is so powerful. But then I look at the kind of researchers that are really getting to grips with evolutionary therapy, and it's a growing bunch. It's all started, particularly I think from the Mopic Cancer Center in Tampa and Florida and a man called Bob Gattenby and his team there, and they are just really incredible people. So I mean, I'm a biologist, I am biased,

I will say against mathematicians and physicists. But it turns out the secret the secret weapon in the war on cancer is as So there you go. So he's brought together all these mathematicians and biologists and they're actually doing evolutionary modeling on cancer populations, trying to understand the rise and the fall of resistant and sensitive cells, trying to go, okay, if if resistance is going to emerge when you treat.

Can we predict how that's going to happen? How do we kind of let cell populations balance them cells out and stay in control rather than just you know, nuke it from orbit, which is kind of the conventional idea about cancer therapy. And so they've they've done a most successful clinical trial so far as in prostate cancer and it's it's an absolutely fascinating trial of an approach that

they call adaptive therapy. And the way it works is you assume that within any cancer at any size, there are going to be sensitive cells to the drug and there's going to be resistant cells to the d and it's a drug called abiratarone that they use. And so what you do is you you also have to have a marker that will tell you how much tumor is in anyone's body at any given time. And for protect cancer,

we have quite a good marker. It's called p s A. So you can look at someone's p s A level in their bloodstream and say, okay, that's a proxy for how much cancer is in their body. And so they start treating this these men with prostate cancer advanced prostate cancer, so they're there probably their their life expectancy is, you know, about eighteen months on this drug before it starts to get really gnarly for them. And and they treat them with this drug and it starts to work and their

tumors start to shrink. And then the difficult bit is you wait till it's shrunk to half the size it was, and then you stop treating and you wait. So the idea is you've knocked down all the insitive cells, or as many of them as you. You feel the urge too, and there's still some sensitive cells there which are keeping the resistant cells in check. And then you wait and

you wait for them to grow back. But because being resistant to the drug is kind of it's it's it's not very good for you, these cells are less fit. They struggled to grow as much. So it's the sensitive cells that grow back, and so you treat them again. And so you ride this kind of roller coaster of start the drug, let the tumor shrink, stop the drug, let the tumor grow. Start the drug, let the tumor shrink.

And they have men who have been on this regime for four years, I mean gradually, in the end the tumor does the cancer does start to evolve because that population of resistant cells does start to get bigger, very

slightly every time. But this is you know, if this was a drug and you were saying, I've gone from average eighteen months through to four years, you know, if this was a drug, the industry would just be throwing itself trying to to get this, you know, get this to the clinic, get this to work, get this to everyone. So that was that was a really powerful demonstration of an evolutionary therapy of understanding and accepting you've got these cell populations in there and they're kind of how to

balance them. There are other sort of adaptive strategies, evolutionary strategies. This one called the Suckers gambit, which is where you treat cancer cells with a drug that you want them

to develop evolved resistance too. But you know that for them to have evolved resistance, they have to have activated certain molecular pathways, they have to have gone down an evolutionary route in one direction, and then you hit them with another drug that they can't get out of, so you're sort of you you get them into a blind

evolutionary end. It's like a double punch. Yeah, exactly. You know, there's there's lots of ideas out there about using the drugs we have, maybe even using drugs that are less less good I suppose less potent, less, less toxic, because you don't want to just nuke everything. You want to start thinking about how to balance cells, how to control cell populations. But this comes to the really difficult thing, which is the psychological element of this, because this is

not the cure for cancer that we were promised. This is not the magic bullet, This is not eradicated from your body. There may be some approaches where we actually can and you know, the earlier you can diagnose cancer if you can treat it with surgery. Um, some cancers can be treated really effectively and cured at an early stage.

But for cancers, once that evolutionary process has really kicked off, you have to approach them with an evolutionary mindset, and that may mean driving them to extinction with the right combination of sort of extinction events at the right time. But it's a it's not going to be this kind of perfect cure that I think people want, that we've been led to expect, and it certainly won't be one magic bullet drug that like, Yep, that's it. That's that's

the cure. That's it. We can now sell this and give it to everyone because, as I said, you know, every every individual cancer is a is a one off, it's a special snowflake. It's an individual evolutionary event. So we need to understand that where is it going, what's it doing, what are what are the contingencies in there? And how can we either drive this cancer to extinction or drive it to a place where we can control

it for the rest of someone's natural lifespan. And you know, that's not a cure for cancer, but to me, that's you know, I think that's getting there. Yeah, I really like that. Thinking of the body not like as a malfunctioning car with a part that needs to be replaced or fixed, but as an environment with natural populations within it that in the relationships between them need to be managed. Yeah, sort of tending the garden is the idea, but you

can take the ecological thing further. There are different sorts of cancers, you know. Some are lush, exotic rainforests that are really going for it. Some are arid deserts, some are more like you know, kind of neatly tendered gardens. But we've got to understand what each person's cancer is really like and how it's behaving. Not just a shopping list of mutations that you can try and fire magic bullets at, but a much more holistic understanding and accepting

that evolution is going to happen, always has done. That's why we're here, that's why the diversity of life is here. But if we can harness it and work with it, then I really think we can start to make some progress in in some of these most difficult advanced cancers. Alright, I guess we will wrap it up there. But again, the book is Rebel Cell. It's a fantastic reed. We we really think you'll like it. And also you can

check out cats podcast, the Genetics Unzipped podcast. Is there anywhere else they should look for your work right now, Cat um, my first book, Herding Hemmingway's Cats, is available. I've got another book called How to Code a Human and you can find me at on Twitter. I'm Cat Underscore Arnie. Pretty much. Yeah, every everything's pretty much the al Right, Well, that does it. Thanks again to Cat Arnie for joining us for this discussion. Again, if you're

trying to look her up. You can find her on Twitter at at k A T underscore A r n e Y. And if you're looking for her book, Rebel Cell Cancer, Evolution and the New Science of Life's Oldest Betrayal. UH. The UK version is coming out on August six. The US version is coming out on September twenty nine. You can pre order now, I believe, if not, keep an eye out for it, and you can also look it up on her website at Rebel Cell book dot com or check out her work on the Genetics on Zipped

podcast at Genetics on zip dot com. It's just such a great book title. I just keep coming back to how much I love that book title. It really is great and uh, and it has some resonance throughout the book with some other themes and metaphors she discusses in there, such as the Society of Cells. So, Robert, I really do recommend you read it if you get a chance. I I really enjoyed this one, all right. I'll have

to look forward in September. In the meantime, everyone out there would like to listen to additional episodes of Stuff to Blow your mind, Well, you can find us absolutely wherever you get your podcasts and wherever that happens to be. We just asked that you rate, review, and subscribe. Those are three things that you can do. It just really helps out the show. Another thing you can do is just,

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