The Rest Is Science - How Evolution Is Shaping Cancer Research

Episode Date: March 26, 2026

In this very special episode Michael and Hannah look at some of the groundbreaking, jaw-dropping and hope inspiring projects that Cancer Research UK are supporting right now. From identifying tiny "flags" cancer cells show to using cancer's own evolution against it, they show why current research today will hopefully mean a better tomorrow for many. Cancer Research UK are the world's leading cancer charity, supporting research into the ongoing quest to better prevent, detect and treat the disease. ------------------- For more information about Cancer Research UK, their research, breakthroughs and how you can support them, visit ⁠⁠https://cancerresearchuk.org/restisscience ⁠⁠Cancer Research UK is a registered charity in England and Wales (1089464), Scotland (SC041666), the Isle of Man (1103) and Jersey (247). A company limited by guarantee. Registered company in England and Wales (4325234) and the Isle of Man (5713F). Registered address: 2 Redman Place, London, E20 1JQ. ------------------- Find The Rest Is Science all over the internet by ⁠⁠clicking here.⁠⁠ ------------------- Video Producer: Adam Thornton + Oli OakleyVideo & Social: Bex TyrrellAssistant Producer: Imee MarriottProducer: Simona RataHead Of Digital: Samuel OakleyExec Producer: Neil Fearn Learn more about your ad choices. Visit podcastchoices.com/adchoices

Welcome to a very special episode of The Rest of Science, because this episode today is produced in partnership with Cancer Research UK, our lead partner. Yeah, this is very exciting. Over the last few months, you all have heard us talk about cancer and dinosaurs, chickens, breweries, sea urchins. We haven't done naked mole rats yet. Oh, wait, yes, we have. Much to everyone's absolute delight, I think, the naked mole rats. The thing is, is that cancer is this incredible. incredibly rich vein of fascinating science stories. And so we wanted to take this opportunity to share a few of those with you.

Because underneath all of it, the patterns that keep on emerging is that cancer evolves, right? It responds to its environment. It competes for resources. And when we push back on it, it keeps fighting back. That's right. And so, you know, Hannah and I have been talking to the brilliant people at Cancer Research UK. In fact, you guys asked for this. I think one of the most common topic requests in the YouTube comments is I want to know more about what's happening with cancer research now. And Han and I are in a position to literally ask the people who are funding the big grand initiatives. So we're literally going to cover stuff that just started this month that's being funded by Cancer Research UK. Absolutely.

And for more information about Cancer Research UK, their research, their breakthroughs and how you can support them, you can visit cancer research UK.org forward slash rest is science. Or just listen to this show. Yeah, yeah. And you know what? If you support them, that'll give us more things to talk about because more research will be funded. So in a way, you're helping us. This is a little bit selfish.

Cancer, named after crabs, literally, like cancer, the astrological sign. Because when cancers were first found, they looked like these superiors. spindly crab-like things that grew in the body. And growth is their hallmark trait. They are cells that are growing out of control. Most of our cells know when to grow and they know when to stop. But in cancer, that's different. And it's different in thousands, millions of different ways, which is what makes it so hard to address cancer and figure out how to control it. Right. Because you hear this over and over again that cancer isn't just one one disease. It's many, many, many different types of disease, but all that are characterized by that very fast growing.

But then if you have the growth, right, if you have this biological entity that is growing in an environment, it does mean that you can tap into some of the things that we know about evolution in order to try and see how it changed over time. So when you're asking yourself this question, which is fundamental to cancer research, how do tumours grow, right? it kind of, you can rewind and start with the idea of what we know about evolution and see how it maps across. So, I mean, one of the most famous stories of evolution is when Charles Darwin, he's 26 years old, he heads off to the Galapagos Islands. He's kind of collecting stuff here, there and everywhere, like just, you know, hoovering up species, chucking him in a back and sending them back in the ship. Well, he drew pictures of them too, you know.

He did do. But I think there was also a lot of guns involved, if I'm honest. Anyway, he gets back to London and then he's got this sack of birds, right? Sounds awful, I'm sorry, but this was this was a different time, shall we say, 1800s. And he thought that he'd just, you know, he'd got some wrens, he'd got some, you know, blackbirds, whatever. But when he got them out, he realized that actually they were all finches. They were all different variations of the same family of birds. And some of them had the beaks were different on them.

So some of them had these really heavy-duty beaks that were like for crushing, kind of armor-plated seeds. Some of them have like really needle-thin beaks, but all of them had this common ancestor. And this was really the moment when he wrote the origin of the species to say that evolution had caused these birds to diverge. It was divergent evolution. And cancer plays the exact same evolutionary rules, but on fast forward. So they're doing exactly divergent evolution as well. A tumour might start in your body. It might start as one thing, but it's got different survival pressure. So instead of like different types of nuts, which it's adapting to, it might be that it's in a part of your body, there's limited oxygen,

or there's immune surveillance. Your body is sort of, you know, watching to take it down. Or it might be that you're attacking it with cancer treatment. So you're throwing chemotherapy onto the pile. But what it does in that situation is it continues to, as it's growing and growing and growing and it splinters and it mutates into this, you know, chaotic patchwork of like wildly different survival strategies. Cancer grows so quickly that evolution is happening very fast. And it's not even happening in just one way. It's not like a tumor is one species. You wind up with the whole ecosystem, which complicates eradicating the tumor so much. Totally. And actually ecosystem is the best way to think about this because, I mean, if you think about other ecosystems, I don't know, like a forest, say,

where you've got all these different kinds of competing biological entities that are kind of all growing at the same time, you can do something, you know, or something can happen like a forest fire, which will knock out loads of the life there, which I, the equivalent he would be treating the cancer with chemotherapy, but it's difficult to extinguish everything. And it may be that you have just some hardy element of that tumour ecosystem that manages to survive and then can really thrive because it's got, you know, this total freedom. You can't think of tumours as this little ball of identical cells really, right? You have to think of this as a sprawling, diverse, well, as you said it, ecosystem of different variants that will respond in different ways to whatever environmental

situation is going on around it. I mean, it's just incredibly difficult. There's no wonder there's no like universal cure for cancer. Yeah, exactly. You go to an ecosystem, you want to get rid of the mosquitoes. Great. Spray a bunch of d'et around. Except the tumor is the entire ecosystem. And yet it's embedded in an even larger ecosystem called a person.

And so figuring out how to target what we want to target and not what we don't want to, when what we want to target is not just one thing, it's incredibly complicated. Totally. Okay. So here now is some of the. research that's going on. So that's kind of what we know. That's how difficult the problem is. But some of the research that's been going on is try and map the different species that appear in the ecosystem, the different ways in which they evolve, the different response that

they get to different environmental stimuli. So there is this project that is called Tracer X. And this is read by Charlie Swanton. It's the world's largest lung cancer evolution study. So what they did is they took 850 patients and they sampled them. And they ended up sequencing 223 billion letters of DNA, right? So they took their tumours, they looked at the DNA of all of these tumors. I mean, this is like a massive scale, right? That's like, it's sort of you take the complete works of Shakespeare, you'd need 50 million of those on your shelf in order to talk about how many letters we're talking about here of sequencing of the DNA.

It's vast. But what they've done, what they've managed to do with all of this data is they have constructed these. these giant sort of evolutionary trees for these cancers, how they evolve, how they connect together, how one merges into something else. And what they've discovered from this, because they also know the treatments that people are given, is that if you just try and target the outer branches of the tree,

as it were, the sort of the edge cases of cancer, well then the cancer just adapts and sprouts, you know, sprouts new branches effectively. It's so adaptable and quick to change itself according to the environment that it's just you cannot use that as a tactic. But the kind of holy grail of this data, what it really demonstrated was that there are these universal mutations. They happen in the sort of the trunk of the evolutionary tree, as it were. These kind of things that come over, come up again and again and again, present in all of these cancer cells, you know, right from the beginning of their development. And that gives a really big clue, right?

Because if you can target the trunk of this evolutionary tree, well, then the whole thing comes down. It means that you've got way, even though you still have this mind-boggling number of variations, you have a hope at far more durable treatment strategies as a result of that. Yeah, and I love that word trunk. I love that the one thing all these different various cancer cells have in common is called a trunk, a trunkal mutation. Right, I'm going to be using that in future videos to describe things that are so foundational

that are shared by all these seemingly unrelated things, truncle. The word truncle sort of makes it seem as though it's this very obvious visual characteristic, as though you could just spot it and be like, well, okay, obviously there's the trunk. It's so much more complicated than that, right? It's only by mapping out all of this data that you can start to see these similarities. But the thing is, what they also knew, what they also discovered from Tracer, is that when you look at the very earliest sign, so when a tumour very first emerges before it kind of evolves into all of these different variants, what happens is that your cells on the outside,

they have these things called human leukocyte antigens. They're sort of like, think of them as little tiny flagpoles and they're showing the immune system what's going on inside the cell. And when a lung cell takes a kind of dark turn, a pre-cancerous turn, so not yet cancerous, but the very, very, very beginnings of something bad going wrong. It starts making these different proteins inside the cell, and that then impacts these flagpoles that appear outside called neo-antogens. Tracer X, this map of all of the different ways that cancer can involve, lung cancer in particular,

it really let us understand what those first neo-antogens look like. Essentially, it made them into red flags. So if you can look for these particular neo-antogens on the outside of normal healthy lung cells and you spot these red flags appearing, you know that that's the very, very earliest moments of this evolutionary path that these other patients have been on with their cancers.

This is like, something's about to happen here, here you go, and here is this literal physical signal that says, pay attention over here. So, I mean, that is the perfect candidate. it to create a vaccine for, which is exactly what cancer researchers have done. So there is this vaccine. It's called lung vax and it teaches your own immune system who the enemy is to watch out for those red flags before the whole process of evolution of these tumours actually gets going. And what this means is that you cannot, this isn't a treatment, right? This isn't sort of, oh, I'm sorry,

you know, you find yourself in this situation with a diagnosis, here's something we can do for you. This is before you've even developed lung cancer. So this is a vaccine for cancer. It's obviously phenomenal. Yeah. It's incredible. I should probably add that this is, this is in the early stages of a development. You can't, you can't sort of nip down to your local pharmacy just yet and get your lung vaccine. But, you know, this is hopefully something that will be available at some point in the not too distant future. And it's a vaccine, not for all cancers, but for some specific ones. Specifically, they're looking at lung cancers.

And so what does the vaccine do? It teaches the immune system to, what, see the red flags and then kill the cells that have raised them? Exactly, exactly. So kill those problematic cells. Right, because those cells are basically saying, I'm about to be bad. I'm about to go renegade.

I haven't yet. And yet this vaccine is like, we already know, we already know you're arrested for pre-crime, get out of here. exactly is the lung cancer version of pre-crime exactly but this is the point you know it's it's getting it for the pre-crime before it's kind of before it's gone off on that uninsane divergent evolutionary journey where it's like then you go then you're limited in the number of ways that you can you can prevent it but but knowing these really these earliest evolutionary signals what this means now is that there is a a blood test that can that can detect lung cancer or problematic cells in the in the lung

lungs way, way, way, way before existing lung scans, you know, up to a year before even the most sensitive scans can. Because if you are waiting to be able to visually pick up on a physical tumour in a scan where you're seeing through the human body, I mean, think about how much bigger that needs to be in comparison to just little tiny fragments of DNA floating about in your blood, which we now know will evolve into this much more dramatic and serious problem. Yeah, a dramatic and serious problem that's also really molten-tootness and harder to target.

Before it becomes a million different things, let's get it when it's just one. So if we go back to your mosquito analogy, I mean, if we're saying that the tumour, when it evolves fully, is like this really big dense, vibrant forest and you can't

just kill one species, one species, one species. Instead, imagine that you've got this, you're on this gardener and you want to keep your lawn perfect. You know, if you step away eventually it's going to become a forest, but you want to keep it absolutely perfect. So this is like, I mean, I'm maybe stretching the analogy slightly here. But this lung thing is like, okay, anything that is not a perfect blade of grass going, okay, it's out. We're not allowing this ecosystem to develop. Yeah, I think that's a good analogy. I was thinking

of an even worse one. I won't even get into that involved the creation story. And like, rather than, rather than destroying creation, just kill God in the first place. But you don't, you do want the healthy cells so I'm glad you do want the healthy cells your analogy is better yeah exactly here's the thing though okay so if that is how cancer starts I mean lung cancer in particular but if that's how cancer starts and how tumours grow and how we have to think of the complexity of this cancer problem it does also make you wonder about how not all of us have cancer all of the time I mean if this is like a tiny little signal goes a tiny bit wrong and then and then it's completely out of control and you're really in trouble, why isn't cancer worse, you know?

Exactly. And that question is one of my favorite questions. I did a video with Cancer Research UK 11 years ago. I think it was literally titled, why don't we all have cancer? And because of our partnership with them, we've been able to talk to great people, Dr. Claire, Sam, who I just kept talking to him about how he should have been Sam in the Lord of the Rings movies. Remember that? That was crazy. But they've been great resources. And some of the newest avenues of research when it comes to why don't we all have cancer

are really exciting. I love this one. It's looking at people who are called super avoiders. This is something that we're all really aware of, right? We know that there are risk factors for cancer. And yet, not everyone who is at high risk gets cancer. Okay? We all hear stories about, well, my grandmother lived to be 110 and she smoked every single day and she did all these things and she never got it.

And it can seem really unfair. It can seem like, how come, you know, where's the, is it luck? And so researching these super avoiders, these people who were high risk for a long time and just never got it could give us some really great insights. The first people to look at are just really old people. they've lived for a long time without getting cancer. Why? Let's rip them apart and look inside. Well, not right now, but let's find ways to do it more politely. Around like 85 to 90 years old, your risk of cancer mortality actually starts to go down. Meaning if you've made it that long, there's probably something about you that has allowed you to avoid or stop or something, avoid cancer. right now Cancer Research UK is funding a lot of projects that just started, including one called Team Atlas. So Team Atlas was just announced very, very recently, and so they're just starting this work. And they're being led by, this is a guy whose name is probably pronounced Paul Bastard.

Or Bastard. I don't, you can imagine by how I'm pronouncing it, how it looks to an English speaker, Paul Bastar, or something. Luckily, he lived his life in France, so, you know, he didn't have to It's life in France and didn't have to worry about people pronouncing it in the way that I might at first. Anyway, they're working on a cancer antibody Atlas. So they're specifically looking at the antibodies, the history of immune system behavior in people who are super old or people who have been at high risk for certain cancers and never got them. And they're looking at what antibodies that person's immune system has created over. their life. And in doing this, they're building an entire cancer antibody Atlas to see what immune system history and what antibodies might be correlated with avoiding cancers later in life. So they're

looking at people like centenarians. I love this word, by the way. And if you, if you will, do me a favor. Let me tell you some cool words. Of course. So, Centinarians are what we call people who are 100 years old or above, which of course leads to another kind of person, which is the super centenarian. And this is someone who's 110 or older. But there are words for people of all ages. Nonagenarians are in their 90s. Octogenarians are in their 80s. And we hear that word a lot because the U.S. government is very much run by octogenarians.

Of course. Septuagenarians are in their 70s. sexogenarians are in their 60s Quinquigenarians are people in their 50s Quadriginarians are people in their 40s All right, so I am now a quadriganerian I'm a person who's in his 40s Trisenarians are in their 30s

Vicerans are people in their 20s and denarians are people who are in their tens So do you have a denarian at home? I don't have a denarian. Not yet. No. I'm disappointed it's not a heptoginarian and pentagonarian, you know? Because if it's an octagonarian.

I know. The same goes for the names of large numbers where you're like, wait, like, how come we call it a non-illion? Or there's a lot of a like Novemberarian is some big word. I don't really know the rules, whether it's coming from Greek or Latin. I'm just here to report what we got. Okay, these centenarians, though, let me make sure I understand it. If you're looking at the antibodies that they've created over their lives, it's the idea not that the cells don't turn, but that their immune system is somehow extremely

capable at hunting down and killing and removing cancer cells before they become a big issue. Is that the idea? That's exactly right, which means that because cancer cells aren't just like a completely foreign invader, they are your own cells originally. that it's not just the antibodies that the researchers are looking at. It's what are called the auto-antibodies, the antibodies that attack your own cells. And in the case of cancer, they're your own cells, but you want them gone.

And so auto-antibodies are responsible for diseases like type 1 diabetes, rheumatoid arthritis, multiple sclerosis. Yeah. The leader of Team Atlas, Paul Bastard, he's actually, had this idea after studying what made people more or less susceptible to COVID-19. And he was looking at how auto-antibodies might play a role. And he actually went around on his bicycle collecting samples from people in Paris. Right. And so this is research that just literally launched, like was announced like four days ago as of the recording. What results come from that are,

you know, still unknown. But this is the kind of exciting stuff that's being funded. Okay, but if that's what's going on inside humans, though, humans managing to survive long periods of time without developing any cancer, even against the odds, there are other examples of animals who seem weirdly immune to cancer. There's actually a researcher from Oxford called Richard Pito or Petto, and he was thinking about this in 1970s.

He was working with mice, and mice get cancer way more frequently than humans do. And he was like, this doesn't make any sense. They've got less cells than we do. Shouldn't it be the other way around? Hannah, they have fewer cells? Oh, sorry.

And that's because you're the English literature grad. I know. Got her. Damn it. That's fine. You can have that one. I'll give you that one. But this is it, right?

If you extend that forwards, if you take massive animals, you know, whales and elephants, I mean, surely they've got, if you think every cell is like you're rolling the dice on the opportunity of creating cancer in your body, it doesn't make sense that they would actually have less cancer than we do, which tends to be the case. There's some whales in particular, bowhead whales, which are ginormous. There are thousands of times more cells than we do, but they can live up to 200 years. I don't know what the double, the double centenarian version is in your word.

duoscentinarian? I'll take that. These whales, they live to be 200 and they've got so many more cells than we do. If each cell, like you said, is a role of a die every year to see whether its growth comes out of control, then shouldn't these long-living, many more celled creatures get more cancer?

Right. So there's some work, there's a scientist called Alex Kagan, who is essentially trying to work this out, right? So looking at elephants in particular, which they appear to have this, amazing brute force defense mechanism by kind of carrying multiple copies of tumor suppressing genes so that they're constantly keeping rogue cells in check. And also there's the naked mulrat, of course, our favorite, which is almost entirely immune to cancer. And I think the idea is if you

can go in and you can work out what is going on in the biology of these creatures that stops either cancer from developing the first place or gives their bodies new weapons in order to attack it. Can you manipulate that into a form that you can use for humans? If you'll forgive me, my favourite thing about this is the kind of absurd ways in which they manage to collect data on these creatures. Because obviously, you know, if you're like, if you're studying a bow whale, you can't just like, or a blue whale, whatever it is, you can't just whip out and sort of, you know, grab one and pop it in your lab, you know?

This isn't like Richard Petto with his mice in the 1970s. Yeah, I mean, you could do that with a mouse, yeah, but whales, how do you study the whales? Even if you're, especially if you're like trying to work out how old they are, or this kind of thing. So what you have to do is they have these boats that go out to try and find whales, and they have sniffer dogs on the bow of these boats that are specially trained to notice when the whales surface, when they come up and, what's the word I'm trying to say? Let me go go.

Go-hole. Thank you. Can we just snip that up and just use that as a... Any time, anyone wants to swear. We're just plain Michael saying. Blow hole. Thank you. Okay.

There are these dogs that sit on the bow of these boats, and they're specially trained sniffer dogs to detect the aerosols that whales will give off as they surface through their blowholes. And so what they do is they end up finding these whales, following them, and then strapping cups to drones. It's completely wild, right? Strapping these cups to drones, flying over the whales blowhole and then waiting for it to just blast all these huge volumes of whale snots into the air that they catch in the cups and then bring it back to the lab.

Or the other thing that they do, and they want to work at how old these whales are, they manage to get hold of the earwax of these whales, which is sort of like, if you imagine the trunks of a tree, you know, sort of like gives you an indication of how old this whale is. I mean, they're massive and disgusting, by the way, you see. They're like 10 inches long. They're extraordinary. And so they basically count the rings in the earwax.

Effectively. In order to age the whale is. Well, sure, the whales aren't cleaning it out. They don't have cue tips. They don't have cutips. They don't have cutips. None of that in the whale community. But yeah, I mean,

between that, knowing how old the whale is and what's going on in the biology of the whale snart, essentially, I mean, the hope is that you are going to get one step closer to working out what these creatures are doing that allows them to stay cancer-free. If that's how tumours grow, why isn't cancer worse? After the break, we're going to talk about some of the ways that you might be able to catch cancer in the act, some of the clues that it leaves behind as it rampages through your body and some of the tools that we might have. And as Michael said, we're doing very early research here, right? Stuff that is absolutely cutting edge. But how we might be able to stop cancer in future. This is a special episode of the rest of science produced in partnership with

Cancer Research UK, our lead partner. Cancer Research UK is the world's largest charitable funder of cancer research and they are supporting much of the work that is driving progress. their research has already helped double cancer survival in the UK over the last 50 years and today they're continuing to save and improve lives around the world. The idea that cancer evolves is not theoretical. It's shaping research that's changing the future of cancer medicine. And we wanted to take this opportunity to talk you through the science of it, the incredibly deep, rich, intriguing science of what is going on with cancer research

using the opportunity that these guys are our partners. Yeah, yeah, I mean, we use them. Like, we talk to these people and we ask them questions, and we loved it so much that I love that we're now getting a chance to share all of this with you all. I mean, we asked them so many questions. We annoyed them, Michael, I think that was, I think. I don't think so. I think they like it.

I think they're afraid that it's annoying us, and they don't realize that asking questions is all we want to do. All we want to do. Morning, noon, and night. And now we have the answers here for you. And as always, for more information about cancer research, their research and their breakthroughs, visit Cancer Researchukuk.org

slash forward slash rest is science. And welcome back. This is The Rest is Science and sometimes we talk about dark matter, but right now we're going to talk about the dark genome. We certainly are. I will never get bored of you doing that face

to camera, Michael. Unfortunately, for those of people listening, they don't get the joy of it. It's a hack. It's a hack. It's a hack. Looking at the camera, it's like a whole, you say so much by doing it. You do. All these people listening on Spotify, you don't what you're missing out on?

You're missing out. You are, you certainly are. Okay. Here's the thing. You take human DNA, the human genome, and you sequence it. And actually, only about 2% of it goes on to do what people used to think, anything useful, right? They were like, okay, we're going to look for the stuff that builds proteins and cells

and whatever and like, let's find all of that stuff. And they were like, well, what's all this other 98%? This is just, this is junk. This is just dark genome junk. Anyway, what it is, what that 98% is, important to say, it turns out not to be junk. It turns out to be actually quite structurally important. It's a bit like, there's an analogy that I really like, which is, imagine if you were

looking at a skyscraper, the 2% is just the light bulbs, the bit that you can see, the bit that really tells you that it's there. and everything else, all of the steel work, the sort of the, you know, integration, the circuitry, etc. That's all embedded in the dark genome. But the thing about this, it has, instead of it being useful instructions, that 98%, it's like this attic full of evolutionary relics. It's got loads of broken machinery, stuff that doesn't work anymore. You know, inactive jumping genes. It's got sort of viral fossils of like viruses that you may have had in the past.

your ancestors had in the past that's then embedded into your DNA and locked in there. In fact, actually, researchers have pointed out that because there's millions of years of evolution, your genome actually has more viral DNA, more viral hitchhikers in it, than actual human genes. Okay. Yeah. Which is sort of a wild idea. Now, normally, your healthy cells, they keep that kind of creepy attic of the dark genome locked very tight. right this is why you don't end up you know accidentally growing an eyeball on your foot you know

sort of the kind of things that don't happen your body is good it knows what it's doing but the thing is is that as a cancer cell so as a cell becomes cancerous and it mutates in its and it's scrambling to survive what can happen is that those ancient viral sequences can be unlocked effectively the cancer can rummage around in the dark looking for spare parts and that it can use within that ancient viral DNA. And sometimes they can use your own DNA against you, essentially. Use your ancient viral DNA sequences to outwit the body's natural defenses. So maybe, I don't know, establish a new blood supply, for example,

or spread in unpredictable ways. So sometimes it's really advantageous to the cancer itself to use this dark genome stuff. Sometimes, though, when the cancer starts switching on these ancient, ancient viruses in your dark genome, they instead act like these massive flares that can be picked up that you can spot in your body, that draw the immune system's attention to it straight to the emerging tumour, your immune system will then try and attack it and kill it. There are lots of researchers in this area, but a couple of notable ones are Samra Terilich and George Cassiotis, who are now trying to explore this exact vulnerability to try and reshape

how we fight the disease. So looking for the products of these reawakened ancient viruses, you can hopefully create these blood tests. This is a little bit like lung vacs earlier, a blood test that gives you very, very, very early detection that there might be some cells where the cancer is rummaging around in the dark genome and trying to use some stuff that it shouldn't. But this is the hope that there may be more cancer vaccines in future. First of all, I just want to say these words all sound very cool, even though it's a bad piece of news to hear, to be like, come back from the doctor and say, they've been able to do a test now. My dark genome has been activated. That sounds like a superhero, though really it could mean that cancerous cells are taking advantage of all this extra stuff that you've got. You're made more out of history than you are nowstery.

And learning how that history, that dark genome, gets taken over allows us to detect what's happening sooner. Absolutely. Absolutely. You know, we're talking a lot about genetics, but I want to also cover work on, like, not genetics that's being done by Alejandra Bruna. By the way, from what I've heard, she also goes by Alex. Alex Bruna. Anyway, she's looking at this really significant difference between adult cancers and cancers

and children and young people. So in an adult, cancers can be identified by looking for genetic mutations. But in a very young person, in a child, there hasn't been time for these mutations to happen. And instead, what might be happening is a certain plasticity of cells where they can change. They can suddenly become resistant to treatment. They can act differently, not because of a change in their internal genome, but for other reasons. This gets us into another thing we should do a whole episode on, which is the difference between Darwinian and Baldwinian evolution.

But if we look at changes in the behavior and appearance of a cell that is not reflected in a change in the genome, we might be able to understand more about cancers in young people. She's looking specifically at ways of identifying the history of phylogenetic changes in a cell, looking at molecules not just in the genome. I mean, it's all so new. I don't know what the result is. And so as we learn more about cancer, we are learning more about ourselves.

And it goes the other way, too. As we learn more about ourselves, we learn more about cancer. As we learn more about the entire animal kingdom, we learn more about ourselves and about cancer. So a really huge kind of surprising connection to this work that Bruna is doing is the discovery of lizards who live in the Mojave Desert, who can change their color based on their environment to camouflage better in a way that happens faster than it genetically could. And yet, they change and then their DNA catches up and their children have this color. And so what's

happening for these lizards might be what's happening in cancers and young people, that the cell is plastic, meaning it can change, it can shape shift before the genome tells it to. And however that happens, we need to understand better to get insights into how cells can be cancerous and how to identify them in younger people. These are all the hopes, right? Because because as you said, or as we were talking about in the first half, one of the things that makes cancer so tricky is that it is your own body. You know, it's not like a foreign invader. It's not like a virus that is coming to attack you and you and you need to just get the alien out of you. This is your own cells. This is the reason why traditionally cancer treatments, certainly, you know, 50 years ago or whatever,

were really, really brutal. You know, there's that whole thing of burn it, poison it or cut it out and that's all you had, right? But inevitably, you're burning and cutting and poisoning, certainly historically, parts of your own real body too. You're always looking for these marginal, marginal differences. What is it that the distinguishing feature of this cancerous cell to this perfectly normal cell so that that's the only way you're ever going to be able to target a treatment that hits one rather than the other? And looking at the weird, crazy ways that cancer can actually behave is a perfect way to do that. Another example of exactly that. It was always really noticed that, I mean, tumours can do seemingly impossible things, right? So they,

they have this sudden explosive growth spurts, or they can develop this, you know, almost unexplained drug resistance, and the normal rules of biology don't seem to allow for this kind of mayhem. And normally, healthy cells, they keep their DNA, they keep it in these really neatly packed little chromosomes, right? Sort of like these very highly organized little instruction manuals that sort of packed away neatly in a whole library, right?

But if you're going to evolve as fast as possible, which is what cancer is doing, then you have to ignore that filing system. And instead, they just break the rules of biology by having these rogue circular loops of DNA that just float around the cell. I mean, it's just like chuck out everything. You know, you go into your library and all the books are on the floor. Right. That's the sort of the situation. Yeah.

The words inside the books are the same, but the pattern of the books is different. They're not shelved up anymore. Yeah. They're just everywhere. They're not in these chromosomes. They're just rogue circles. Right, exactly, floating around the place. So scientists, they call this ECDNA.

This is the stuff that allows tumors to just really rapidly divide, ignore all the biological stop signs. You know, as we said right at the very beginning, normally your body knows when to grow and when to stop. But also maybe what allows it to survive toxic treatments, which is, you know, why some chemotherapy stop working after a while because it gets this drug resistance. which is a nightmare for, you know, if you're on chemotherapy and it stops working after a while.

But there is a silver lining in this because this is a weird thing that cancer cells do, but it seems as though this ECDNA, these little DNA loops, only exist in cancer cells and never in healthy ones. So it looks like this might be one of those distinguishing features that you can use to directly identify the different. between a cancer cell and a healthy one, so that instead of using brute force, you know, go in and really cut it, burn it, whatever, you can, it's more like molecular judo that you can potentially use.

And that's it, you know, if you can turn cancer's own excesses against it, then maybe you can create drugs. And this is all, as we said, this is really, really, really, really cutting-edge research here. But maybe then you can create drugs that will selectively go in and kill the cancer alone while leaving everything else. Using its own behavior against it is a strategy and a line of research that I love,

because not only is it potentially really helpful, but it also just feels like revenge. Another fantastic new line of research that's being funded through Cancer Grand Challenges, which gets money from Cancer Research UK, is rewiring cancer cells. That's what they call it. And this takes advantage of the fact that cancer, you know, grows out of control. And so a lot of therapies and treatments try to stop that growth.

What if we did the opposite? What if we said, you know what? Go ahead. Like, have at it. Like, here's all that you need to grow. So imagine like a house plant. It needs a certain amount of water and light, let's say. All right?

And that amount that it needs is actually kind of a Goldilocks zone. Too little water and light? Not good. but too much also not good. And so what these researchers are doing, and as with all the things we talk about today, this is happening right now. They're looking at ways to rewire the cells

so that they grow so quickly. They actually kill themselves through stress of, okay, look, I know that I shouldn't be growing like this, but you're going too far, and I can't handle it, and I self-destruct. The spindly houseplants? Yes. Yes. I mean, that feels quite high risk in a lot of ways. Does it work? Do they know if it works? Well, that's exactly what they're trying to answer now. This isn't like, well, you know, we tried this 10 years ago and here's what we've learned. It's being done as we speak. I want to know a bit more about how this works, though. What does it mean to create the environment that it grows really quickly? Good question, because we're not talking about like feeding it extra cancer fertilizer or something, right? We're talking about reasons.

wiring the cell, triggering the mechanisms in the cancerous cell that cause it to grow out of control, but like over-triggering them to the point at which the cell can't keep up, starves itself, self-destructs. It's not like, oh, let's increase your cancer risk too high. No, no, no. We're just talking about when the cell starts growing out of control. We know that there are certain mechanisms at work there. Let's just let them at it to the point at which they outdo themselves. And other strategy is to stop that all together. And learning from both of those will help us because again, cancer isn't just one thing. Maybe sometimes you want to over-stimulate the growth mechanisms. Maybe sometimes you want to stop them. But this is, but this eventually is,

I don't know, maybe like a molecule or a drug or something that you give to a cancer patient, rather than just saying, you know, smoke as much as you possibly can to stop your lung cancer. Right. Or describing it. Yeah. Give all of your cells so many nutrients that the cancer ones have too much. No, no, no. It's not. The house plan analogy is not maybe very helpful. It's more like... It works to a level. To a certain level, but it's more like going to the plant cells and tell them, okay, I want you to grow 18,000 times faster than you're supposed to.

And they go, there's not enough food. I can't do this. I'm just going to shut down and it dies. I give up. I give up. You win, yeah. I guess in all of this, you're just looking for ways in. You're looking for distinguishing features that you can exploit.

You're looking for things that you might try and do to the cancer in order to attack it. So if it's, you're hunting for weaknesses, effectively. That's right. And we already automatically hunt for weaknesses, right? We have an immune system after all. And immunotherapies are strategies to treat cancer that take advantage of the immune system. They don't always work, though. And so there's some research happening right now into how to help the immune system attack cancer.

So one of the many types of lymphocytes we have in our body are T cells. And T cells learn to find certain antigens. An antigen, by the way, is something toxic or something foreign in your body that causes an immune response. Right? Like a virus. Oh, my gosh, it's a rhinovirus. You're going to get the cold unless the T cells come in and destroy it. So that brings us to what are called CAR T cells.

Carr, C-A-R. It stands for chimeric antigen response. A chimera is a combination of two things, broadly. And what researchers are doing in these trials and in their work is they're actually taking T cells out of a person's body and then they are implanting new DNA into that T cell that causes it to grow these new sorts of receptors that are chimeric. That means there's two things that they do at once. They can detect and attach onto antigens, these toxic or

foreign things, like, for example, a cancer cell. And then they also simultaneously get activated and kill that cell they've detected, the cancerous cell. So instead of waiting for the body to naturally develop these T cells, the T cells in your own body can be removed, isolated, changed by implanting new DNA in them so that they go, oh, I need to grow these things. And you can literally imagine them growing new, like, V-shaped things that happen to attach on to the characteristic properties of the cancerous cell. But also, once that happens, because

they put these back in your body, when that happens, the T cell goes, whoa, we found it, and I'm going to now destroy this thing I've attached to. Boom. The cancer's killed. So when you put them back in your body, your body doesn't just say, oh, thank you. Here's this T cell. We've got that. It starts to make more of the same. So it's to sort of copy that same system. That's right, because these are just your own T cells that are back in, but they've been given new instructions, but they've been given those instructions outside of your body by doctors. So in a way, these are like a kind of living drug. Right. It's a medicine that is alive and it is an incredibly complex thing. It's not like one wonder molecule. It is a living cell full of, I don't know, billions of molecules

and it's just using everything it evolved to do with some new instructions. It's a medicine made of your own self. It's like a literal part of you, a literal part of you that gets taken out of your body, taught a new skill and then re-implanted. Yeah, it's like, you know what? I want to do that for school.

Take my brain out, teach it things while I'm sleeping, and then in the morning put it back in, and now I've got the knowledge. Wouldn't that be nice? That's what these car T cells are. So that's actively being worked on, and it's very cool. Where's the research out with this one at the moment? Is this still theoretical?

No, no, CART cells have already been used to help children with leukemia, but the directions they want to go in now is how to make these work for more people and more different types of cancer. That's incredibly cool, because actually, I mean, vaccines work in a similar way, but it's all happening inside your body. It's putting in something that then your immune system learns how to unlock in a really benign way. and then has the new skill. But this is like level up, right?

This is like... That's right. I mean, not to go overboard with analogies, but a vaccine is like throwing a bunch of books into a classroom and hoping the kids read it and take the knowledge. Card T-cell therapies are taking the brains out of the kids, throwing the knowledge in there, and then putting it back in their bodies and being like there.

You learned it, and we didn't even have to wait for you to do it because not everyone's immune system learns from the vaccine. So let's just just... Especially. Yeah. Yeah. If you're already, you know, potentially under cancer treatment already, that, you know, it could be quite difficult to.

That's right. To overstress the immune system. Just this notion of sort of taking things out, doing like sub-diffusion, reinserting things. There's this other idea that I really like. It's called Trojanix. Okay. I don't know if you can guess where I'm going to go with this,

but it's essentially a Trojan horse. A Trojan horse. A Trojan horse. Okay. So you've got this Tuesday. in your body. And the other thing about, you know, the tumours, this ecosystem, there's all this stuff going on around it. But the tumour is unbelievably good at building this wall around itself that makes it incredibly difficult to penetrate. So your immune system, you know,

struggles to get in there. It's like, it's just, it has its own fortress effectively. There's this group of scientists led by Steve Pollard who were like, okay, well, fine, look, if cancer's going to have this sort of constant genetic shape shifting with this fortress, you know, whatever. Fine, we don't care. We're going to build a version of a Trojan horse. We're going to sneak past the guards. We're going to get into the tumour and then we're going to hit the self-destruct button. We're going to Trojan horse this thing. What they do is they take a virus that is actually viruses are already naturally brilliant at getting into human cells, as we know, given how much of us is old viruses, of our DNA is old viruses. And what they do,

is they hollow out all of the harmful viral parts. They just use the mechanism of getting into the cells. And then what they have then is this sort of empty, empty disguise, really, like a harmless looking disguise that is very good at getting into human cells but is not going to do anything. And then instead, they load it with these two specific therapeutic genes.

So one of them is like essentially a cancer-only switch. So something that was only going to activate, once it is deep inside enemy territory, making sure you're leaving the healthy cells alone, how you can tell the difference between the healthy cells and the cancer cells, that's all the stuff that we covered earlier on, right? That's sort of what you're trying to do. Once it slips inside of these cancer cells, then it has this self-destruct mechanism. So it kind of springs into action.

Once it knows it's inside cancer cells springs into action, and it's like this targeted lethal poison that effectively tries, tricks the cancer into killing itself. Wow. But what happens then, the fortress starts to decay. The immune system comes in in full force, storms the fortress, joins the attack, can really start to completely take this down. This is all just viruses, DNA, little bits of genetic material that, you know, trying to

use sub-diffuge and ancient Greek stories in order to trick it into death. That's so cool. I feel like I do a good job of coming up with these really fun strategies, but then to imagine that there are researchers who make it real. They say, yeah, let's create a Trojan horse that the tumor wants to bring in, and then it won't even just kill what's inside this impenetrable wall. It will break down the wall so the rest of the body's immune system can come in and help. But that's not just a story. They're building these. They're doing this. Yeah, they're literally doing this. So I should also add that then once this tumor is broken open and the immune system can see inside of it, then going back to what you were saying about the T cells

having this memory, then there has this permanent memory of the tumor's signature. So it offers this long term protection of this cancer ever coming back because any time this tumor sort of tries to pop up again, it's going to kill it. But as you say, this isn't just theoretical. This isn't just like, oh, this nice like pie in the sky idea. They're literally about to start these clinical trials for glioblastoma, which is this notoriously difficult type of brain tumor. And yeah, it works exactly like a Trojan horse does, getting inside, exploiting, exploiting the tumor from the inside out. Wow. So you were talking about the dark genome earlier and all this DNA, 98% of it in our bodies that just doesn't seem to have a role in like our day to day growth

and functioning. There's also another fact I love, which is that so many of the cells in our bodies are not our cells. Meaning, I'm made of a lot of cells that contain my DNA. And I feel like I can call them my cells. But in my gut, there's an enormous biome of microbes that help me in all sorts of ways.

And they don't have my DNA. They are their own separate organisms. We call them the gut biome, the microbiome in our guts. And for a long time, it was thought that they just helped with digestion, right? They take sugar molecules, break them down. They help us. They take what they want.

And, oh, look, they've made it easier for us to absorb the parts of the food we ate that we want. And that's true. But these microbes in our bodies that sit inside our digestive system are so numerous. To think that they don't have a bigger impact is, like, unbelievable. because we have, in fact, in our bodies, ten times more cells in our guts that are not our own than our bodies are made out of. What?

Does that make sense? Yeah. So there's a certain number of cells that are mine, that have my DNA in my body. And that gut biome that's living in there, it's this whole zoo of living creatures that I'm allowing to live in me, and it's not just one kind.

There's like 5,000 different species that live in there, And altogether they weigh like two kilos, like four and a half pounds of me is not me. You want to lose five pounds? Just declare that your gut biome is not you because it has different DNA. Point is we can't ignore the impact that's going to have on more than just digestion, including the immune system because it's encountering this stuff all the time. And so some research that Cancer Research UK is funding being led by Dr. Pippa Cori

as well as a biotech company called Microbiata, led by Dr. Trevor Lawley, they are looking at the gut biomes of different people and how that might correlate with how their immune system responds to fighting cancer and to immunotherapy. And so they're actually devising capsules, like little pills that you take that put the microbes in your gut biome that might help you respond better to immunotherapy to use your immune system to fight cancer. If you're not responding to immunotherapy, it might be that your gut biome hasn't prepared your immune system to do that. We need to harness the power of all these other animals in us to make our bodies stronger. Gosh, it's just absolutely phenomenal. I mean, the level of

complexity of biology never ceases to just amaze and overwhelm me. I mean, you're not just to, you think if yourself as one single entity, but you're not, you're an ecosystem of ecosystems, right, within which there are ecosystems themselves. I know, that's why we call it a biome. It's like the earth is a biome, but your body is also a biome and tumors are biomes. They are entire ecosystems full of many different creatures in a sense. And that's what makes this all so complicated, but also so in many ways fun. I mean, fun is a weird word to give it, But I think that's, I think that's, I think it's definitely scientifically interesting, right? There's, there's, there's no shortage of completely fascinating things to uncover.

New twists and turns around every single corner. But it's also, it's all, it's just like the most epic battle that is playing out on this unimaginably sophisticated, delicate, intricate battlefield that is just a war that we absolutely want to win. And the battlefield, as it were, stretches across so many things. I mean, we're not just talking about one molecule. We are talking about the earwax inside whales. We're talking about house plants and we're talking about lizards. And we're talking about microbiomes inside our bodies and cells that aren't even ours.

And we're having to learn about all of these things in order to understand cancer. You missed off naked mole rats. Yeah, naked mole rats move over. There's a whole ecosystem of other creatures and behaviors in this universe that we want to learn about. There certainly is. Well, we should tell you that Cancer Research UK is the world's largest charitable funder of cancer research, and they are supporting much of the work that is driving progress. Their research has already helped double cancer survival in the UK over the last 50 years, and today they're continuing to save and improve lives around the world. And for more information about Cancer Research UK, their research, their breakthroughs, and how you can support them,

visit cancer research, UK.org forward slash rest is science.