EP 12 - From one to many (multicellularity)

For three billion years, life went solo.

Then one day, some cells forgot to separate after dividing — and that tiny accident changed the history of Earth.

In Episode 12 of From Cells to Us… How?!, we explore the rise of multicellular life: the first cells that learned to cooperate, the evolutionary battle against cheating cells (aka cancer), and how trillions of individual cells eventually became… you.

Because multicellularity didn’t just make life bigger.

It made complexity possible.

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Transcript

Jackie 0:02

Hello. I'm your host Jackie Mullins, and welcome to From Cells to Us. How? The podcast where we figure out how life went from a single cell to complex creatures like us. Last episode, we talked about sexual reproduction. We established that single-celled eukaryotes invented genetic recombination a billion years ago, why it was worth the outrageous cost, and why the Red Queen has been running ever since. And now we have everything we need, a fully equipped eukaryotic cell, nucleus, mitochondria, internal machinery, sexual reproduction, generating variation every single generation. The engine is built. The fuel is in. The variation is flowing. So what happens next? What did these eukaryotic cells do with all this amazing potential? For hundreds of millions of years, nothing, or at least nothing that you'd notice. Single cells floating around, dividing, occasionally merging and shuffling, then leaving. And then roughly 800 million years ago, something did change. Cells started staying together, not merging the way they did during sex, not getting eaten the way the mitochondria ancestor did, just not separating after division. Staying attached, hanging around each other, beginning slowly, awkwardly, and with no essential plan to cooperate. And that accident eventually produced every multicellular thing that has ever lived on this planet, every one of your trillion of cells, including you. Let's talk about how that happened. And we have had 11 episodes describing how a molten ball of liquid hot magma eventually became a petri dish of different forms of life and I know learning about an individual cell is not the most glamorous thing. Most people like to learn about the big stuff, right? When I first got into biology, I wanted to know everything about the brain, why we sleep, what dreams are, why we think the way we do. Then I saw I had to take cell biology first. The thought of zooming into something that small felt like an absolute waste of time. I wanted to see what things did as a whole. I wanted the big picture. But after that class, I had a whole new outlook. I really became fascinated with individual cells. And I hope these last 11 episodes have done something similar for you because what we've been building this whole time is the foundation for everything that comes next. Because there was a time when humans genuinely did not know what they were made of. So as we close this chapter, I wanna take a moment to appreciate how some great minds figured out that we are not one organism, but a consolidation of many living things producing one. Or as Rudolf Virchow wrote in 1858, quote, "The body is a cell state in which every cell is a citizen." End quote. Honestly Virchow was kind of a bad boy of the science community for writing this. People did not like this idea. And why, you might ask? Why would the idea of cells make people upset? Well, the dominant belief about life at this time was something called vitalism. Don't worry if you've never heard of it, it's not around anymore. Vitalists believed that living things must contain something extra. They didn't know what, just something extra. Something beyond mere chemistry and cells, a vital force, a spark, that thing that makes us alive rather than just assembled. And even the scientists who accepted that cells existed largely believed there had to be something special about human cells specifically, something that gave us our consciousness, our humanness, if you will. And tied to this was the idea of spontaneous generation, the belief that life could simply appear from nothing. No parent cell needed, just matter animated by the vital force suddenly springing into existence. Maggots appearing from rotting meat, mice appearing from grain. Life just happening because the vital force willed it. This is legit what people thought. They believed that like some force and a flash of lightning and these living things would just pop into existence as is. Now by the late 1830s, two German scientists, Matthias Schleiden and Theodor Schwann had already established something remarkable. Schleiden showed that every plant is made entirely of cells. Schwann showed the same thing was true for animals. Same basic unit. Plants and animals, as different as they look on the outside, made of the same fundamental thing underneath. Now the funny part is that they were at a bar or out to eat during this conversation. They were just like having a pint and nerding out over each other's work when suddenly they realized what they had both seen. Can you imagine the chills that went up their spines as they compared notes, getting more and more animated as they realized that they both saw the same thing, a cell with a nucleus in both plants and animals. This was so profound. Can you imagine deducing this? I honestly think it would be on par with finding out our world is actually a simulation. Like two people having dinner and one goes, "Yeah, so I go far enough into things and I see a code." And the other one goes, "Wait, me too." And they sit there and look at each other and realize what this means. This was what that bar conversation was. Everything they thought they understood about life, about what separates a plant from an animal, about what makes living things different from each other just changed over dinner with a pint in hand. They were starting to put the puzzle pieces together. But unlike us, who get the luxury of working in a timeline fashion, they had to work backwards. Multicellular to cells, to the same cells in living things. And they just hit the nail on the head to start this journey. But the vitalists were not impressed. "No, no, plants and animals aren't humans," they insisted. Human cells must be different. Human cells must contain that vital spark, otherwise why are we different? And yes, we saw cells in plants and animals first. Why didn't they just look into human cells, you might ask. Well, human cells are actually hard to see. They're softer. They have no rigid wall, and they deteriorate quickly. And obtaining samples w- \wasn't easy. Usually was done with cadavers, which are hard to get legally and religiously controversial. Microscopy was also in a very infant stage. It was very new and an imprecise science. But eventually they did look, and they did see cells in human tissue. So the vitalists shifted their argument. "Fine," they said. "Humans are made of cells. You got us. But where do those cells come from? How do these things have life?" We dug and we dug and we found these cells and they, yes, they must have been put into existence by the vital force. Life must spring into existence. It must come from somewhere extraordinary because the alternative was just too ordinary to accept. And so the question that remained was this: Where do cells come from? And this might be hard for people to understand, especially you bright folks listening. Like it's so painfully obvious The proof is right in front of you if you but open your eyes, kind people of the 19th century. But it's easy to sit here in 2026 and shake our heads, right? We grew up knowing cells exist. We've seen the diagrams in middle school. We have electron microscopes and DNA sequencing, and we can watch cell division happen in real time on a screen. The idea that everything is made of cells is so baked into how we understand the world that it feels like common sense. But these people had none of that. They had primitive microscopes that distorted as much as it revealed. They had no photography. And I wanna say that one again. They had no photography. Everything had to be hand drawn. So your art had to be as sharp as your eyes to muddle through the lenses of the old microscopes. If I lived then, I would have a mountain of denied stick figures on my fridge. How do you draw a cell as a stick figure? Well, I would have found a way somehow. So when these hand drawn findings were shown, people questioned whether what was drawn was actually what you saw or what you wanted to see. They also had no way to share findings instantly, right? I mean, these two guys met at dinner and started talking. That's how they shared their findings. There was no peer review as we know it, no internet to look something up, just a lens, a candle, a smear of something on a slide, and your own eyes trying to make sense of something no human had ever understood before. Oh, right, and then you have to hand draw it on paper and convince everyone that's what you saw. And on top of all of that, they had centuries of philosophical and religious tradition telling them that humans were fundamentally different from everything else in nature, that we had something extra, that we could not possibly be reducible to the same tiny building blocks as a blade of grass or chicken's blood. So if not from spontaneous generation, if not from some vital force willing them into existence, then what? Well, that answer came from a man who almost didn't get credit for it. Robert Remak, a German scientist and one of the few Jewish scientists working in that era Who was denied being a full professor at his university simply because of being Jewish. Well, he spent long hours staring into a microscope, straining his eyes, waiting for something that might never come. And then he saw it. Right there in a smear of chicken blood, a cell divided. One became two. No spark, no vital force, just a cell copying itself. But because Remak was Jewish, his work was largely ignored by the scientific establishment. Hugo von Mohl had seen the same thing in plant cells. But plant cells aren't humans, the vitalist insisted, and so the argument dragged on. So when Remak said, "Look, it just copies itself. No spark required," he wasn't just challenging a scientific theory. He was challenging the entire story humans have been telling themselves about what made them special, and the establishment wasn't ready to hear it. And they had one last escape hatch. Hugo von Mohl had seen the same thing happening in plant cells, but the vitalist waved it away. Plants, animals, fine. Let them copy themselves. But humans are still different. Human cells must still be generated by something greater. The vital force hadn't been defeated yet. It had just been pushed back one more time into the last remaining corner, us. And then finally, Rudolf Virchow delivered the line that closed the coffin on vitalism. In 1858, he proposed what became the third pillar of cell theory. Omnis cellula e cellula. From cells come cells. Life doesn't spontaneously generate. It doesn't spring from a vital force. It copies itself over and over all the way back. Part of what led him there was studying leukemia. He was looking at cancer cells under a microscope and realizing they weren't some mysterious foreign invader. They were just normal cells reproducing out of control. Cells making cells, nothing more. The evidence was so overwhelming, vitalists simply had nowhere left to stand. Okay, history lesson over. But I always like to take a moment and appreciate how much it took to get here. You know, the strife, the energy, the existential doubt that people must have gone through when this new information challenged everything they believed about themselves and their place in the world. I mean, that timeline just fascinates me. And there's something else worth noting. We know so much now that we've forgotten the questions were ever posed. My son asked me what was in the center of the Earth, and I just rattled off the answer, right? Inner core, outer core, mantle, crust, like I've seen in that cross-section of Earth diagram a thousand times. And he looked at me and he goes, "Oh, okay, but how do we know that?" And I was like, "Oh, geez, um..." And I'm racking my brains. I was like, "Did we drill?" I was like, "No, that's, that's not possible. It's way too far down." And then I had to admit I had absolutely no idea how we arrived at an answer that everyone just accepts as fact. Cells are the same way. We all know we're made of cells. It's middle school science. It's on every diagram. It feels like it's always been known, but it wasn't. There was a time when that question had no answer, when brilliant people spent their entire careers trying to prove something we now teach to 10-year-olds. We inherited their answers. The least we can do is remember they had to find them. And here is what those answers actually mean. And those answers are that Every cell in your body traces an unbroken line of cell division back to the very first cell we talked about in episode one. No breaks, no spark required, just cells copying themselves for four billion years, gradually getting more complicated until eventually some of them figured out that working together was better than going it alone. And that's exactly where we are today. All right. Quick background I hope it got you in the mood. So we are in the Cryogenian Period, which sits right inside the Neoproterozoic Era. The Earth at this point looks absolutely nothing like what we'd recognize today. Still, the continents are in completely different configuration. The supercontinent Rodinia, which we talked about back in episode nine during the Mesoproterozoic Era, so not Pangea, is actually starting to break apart right now. So you've got this massive land mass fragmenting, rifting apart, pieces drifting away from each other. The Atlantic Ocean doesn't exist. The Pacific is unrecognizable. The geography is completely alien. The atmosphere has oxygen, as we talked about, but not nearly as much as today. The oceans are fairly interesting at this point. There's good evidence that large parts of the oceans are still pretty low in oxygen in the deeper waters, what scientists call euxinic conditions. The surface was better oxygenated, but the deep ocean was still catching up from the Great Oxygenation Event we covered way back. The Cryogenian. And crucially, the Cryogenian is famous for its weather. This is the era of snowball Earth. Starting around 720 million years ago, Earth goes through at least two catastrophic global glacier events where ice sheets extend almost all the way to the equator. Basically, the entire planet freezes over. So multicellularity is evolving right on the edge of one of the most extreme climate events in Earth's history. Now, you might ask yourself, "Didn't these extreme climates affect this multicellular life growing?" And that's a really great question, and actually a fascinating story. So the snowball Earth events were almost certainly catastrophic for most life A huge amount of species probably went extinct during all the glaciers. The surface ocean froze over. Photosynthesis became nearly impossible in many places, and the food chains that existed collapsed, but life survived. And how they did it was refugia pockets of liquid water that stayed unfrozen, probably around hydrothermal vents, if you remember those from, I believe, episode one. They're on the ocean floor where heat from the Earth's interior kept water liquid regardless of what was happening on the surface. Also, possibly thin ice over the equator regions that still allowed some light through. Life huddled in these areas like the refugia and at the equator like penguins in Antarctica and just hung on. But when Snowball Earth ended, it ended fast and catastrophically in the other direction. Just a seesaw crashing down to the ground, right? The ice melted. CO2 that had been building up in the atmosphere caused rapid warming, and suddenly you had a supercharged ocean full of nutrients and newly available niches with almost nothing competing for them. Some scientists think that this is actually what accelerated the evolution of complex multicellular life. The Snowball Earth events acted like a pressure cooker, wiping out most of what existed and then releasing it into the environment with enormous evolutionary opportunity The organisms that survived the freeze and thrived in the thaw were the ancestors of everything complex that came next. So these cells didn't get altered exactly, but the population got brutally filtered, and what came through that filter was tougher, more adaptable, and entering a world wide open for new experiments. And that makes sense, right? Like think about being the first one through the doors at Aldi's on a restock Wednesday. Everything is available. Nothing is picked over. So many cool things, such little cart space. So the stage is set. You know the weather that's coming. So how does multicellularity arise? Because for the first three billion years of life on this planet, every living thing was single-celled, doing everything itself, eating, moving, reproducing, defending itself, processing energy, every single function packed into one microscopic package. And that works. It clearly works. Bacteria are still doing it, and they are extraordinarily successful. But it has a ceiling. A single cell can only get so big, and that's not me just talking to the wind. There's a size limit imposed by physics. The bigger a cell gets, the harder it is to move nutrients from the membrane to the interior. The harder it is to get waste out, the harder it is to coordinate everything. There's a surface area to volume problem. Past a certain size, and a cell can't function. So for three billion years, life stayed small. It stayed simple. It stayed single. But here's what single cells can't do. They cannot specialize. They cannot divide labor. They can't have one part of itself dedicated entirely to moving, while another part of itself dedicated entirely to capturing energy, while another part is dedicated to reproduction. It has to do everything at once with the same machinery. Can you imagine if we never developed the assembly line? One person still had to build the entire car, every single part, start to finish alone. You'd get maybe a handful of cars a year at best. Or Think of it like you own your own business, and you're a one-person show. You're the CEO. You're the accountant. You're the salesperson. You're the janitor. You're the product all at once. It works. Plenty of one-person businesses exist and thrive. But there's a ceiling on what you can build alone. More orders start coming in, but there's only so much time in a day. Multicellularity is hiring your first employee, and then your second, and then eventually you're running a corporation of thirty-seven trillion people all doing different jobs in coordination. That's what your body is, a corporation of thirty-seven trillion employees each one a fully functional living unit on its own each one choosing because of millions of years of evolutionary pressure to cooperate instead of go it alone. The question is how you get from a one-person business to the corporation. And like a lot of other things, multicellularity didn't happen once. It evolved independently at least twenty-five times, maybe more. In animals and plants and fungi and algae and slime molds, you know, completely separate lineages all stumbled onto the same solution completely independently. So even though they are all made of the same eukaryotic cell, they each went multicellular in their own right And this is actually something evolution does surprisingly often, find the same solution independently in completely separate lineages. Eyes evolved independently dozens of times. Flight evolved independently in birds and bats and insects. Multicellularity evolved independently at least twenty-five times, which tells you something important. It wasn't that hard to discover. Given enough time and the right conditions, evolution kept finding the same answer because the answer was good, because it worked. So how did it start? How did one become many? The most likely scenario is fairly simple. A single-celled organism divided the way it had divided a billion times before, and the two daughter cells, well, they just didn't separate. Maybe a protein that was supposed to break the connection between them mutated and stopped working. Maybe environmental conditions made staying together slightly more advantageous than splitting apart. Maybe it was pure chance. Maybe they just liked each other a lot and didn't wanna let go. Who knows? But they stayed together, two cells attached. And here's what they found out. Two cells attached to each other are already slightly better at some things than one cell alone. Two cells have more surface area for capturing food. Two cells can be harder to eat than one. I mean, if you've ever fed a baby learning to eat, you know exactly what I'm talking about. You know how those Cheerios sometimes fuse together and you take that one out of their eating pile? That's basically what these cells figured out. Harder to swallow, better together. And two cells can divide the very earliest version of labor. One faces outward, one faces inward. And think about it this way. If you were dropped into an ocean full of cannibalistic eukaryotic cells actively trying to eat you, would you rather face that alone or with a friend, someone watching your back while you watch theirs? You know, can you imagine if it was just Mr. or Mrs. Smith in that mall being surrounded? No way just one of them were making it out alive. So suddenly the accidental cluster of cells that forgot to separate after dividing doesn't look like a mistake anymore. It looks like strategy. I mean, this is just like what animals and humans figured out too. Solo, you know, you're easy pickings. But form a pack, a pride, a pod, and suddenly you're not prey anymore. You're the threat. Cells figured that out about eight hundred million years before we did. You know, and maybe once we hit that telepathic ability, we too will form our own giant body, and we will be the cells. Probably a few million years off, though. Don't say I didn't call it, though. Okay, But wait, if cells are going to stick together and form something bigger than themselves, something has to actually hold them together, right? Like, is it glue? Are they running around those Elmer sticks? Like they just came back from second grade? They are not. The answer is Cells evolved sticky proteins on their surfaces called cadherins. Think of them like Velcro on the cell membrane. When two cells with matching cadherins touch, they stick and they stay stuck. And that stickiness is what turns an accidental cluster of cells that forgot to separate into something that can actually persist and function as a unit. But the cadherins aren't enough. You also need structure. So cells started secreting proteins into the space between them, building a kind of scaffolding around themselves called extracellular matrix. You know, you can think of it like mortar between bricks. The cells are the bricks. matrix is what holds them in position relative to each other. This gives the whole structure stability and lets different cells take up different positions within the group. Again, I'm sure you smarties are like, "Well, when did the glue evolve then?" Another classic chicken or the egg problem, right? How did they just have this glue ready to go if they weren't even multicellular yet? But Cadherins weren't invented for multicellularity. Single-celled organisms already had primitive versions of these sticky proteins before multicellularity existed. And what did this glue do before it held cells together? Well, it was mostly used for hunting, grabbing onto bacterial prey, or for anchoring cells to surfaces like rocks. You know, it's just like when I don't want to reach or bend down too far and I grab my back scratcher to pick something up off the floor. I didn't redesign the back scratcher. I didn't build a new tool. I just found a new use for something that was already sitting there. Evolution did the same thing. And here's a fun bonus fact. Cadherins actually need calcium to work. Without calcium ions present, they can't maintain their sticky shape, and the whole system falls apart, which is why calcium isn't just important for your bones. It's literally part of what holds your cells together. So the next time your kid asks why they need to drink their milk, you can add cell stickyness along with bone strength. Evolution took a protein that was sticky for one reason and found a whole new use for that stickiness. Same tool, different job, classic evolution. And this sounds great, right? Like no problem here. Cells came together, work together. They have each other's backs. What a wonderful story. And what I picture is like the Lord of the Rings, the fellowship coming together to defeat Sauron, each member bringing something completely different to the table. Sword, axe, bow, magic, hairy feet. You know the rest. Nobody doing the same job. Everyone contributing their specific ability toward one shared goal. Taking only what they give. That's multicellularity. Different cells, different specialties. One organism But what if there are cheaters? What if one of them decided to sit this one out, take the protection of the whole group without contributing to it? Because the moment you have a group of cells cooperating, sharing resources, dividing labor, working together as a collective goal, you have created an opportunity for a cell to take the benefits of the cooperation without paying the costs. I mean, we've all been in group projects. This is not a cellular problem alone. There's always that one lazy bum that contributed nothing but still expects the A. But the more dangerous kind? Someone with ambition, someone who wants more, but know they shouldn't. Yes, Anakin Skywalker, AKA Darth Vader. Someone that is not okay with being a part of a whole, being a cog in the machine. They want more, they take more, and they don't care what it costs to everyone else So imagine a cluster of cells where most of them are doing their jobs, capturing energy, moving the group, reproducing slowly and in coordination with everyone else, and then one cell mutates, and that mutation makes it reproduce faster, selfishly taking more than its share of resources, dividing rapidly while the other cells are trying to cooperate. That cell is a cheater. But in the short term, cheaters win. That lazy bum in the group project still probably got the A. A cell that reproduces faster passes on more genes. Natural selection should favor it. Except if enough cells cheat, the whole cooperation colony falls apart. If there are too many lazy bums in a group project, no one does the work, and you get an F. And it only took one Anakin to bring down the entire Republic. One. That's all it took, and that's exactly how it starts. Not a whole army of cheater cells showing up all at once, just one. One mutation, one cell that decides the rules don't apply to it anymore. And if that one cell isn't stopped, it divides, and its daughters divide, and suddenly one Anakin has an army The cheater destroys the thing it's cheating off of, and then everyone loses, including the cheater. You all know this cheating by another name, cancer. Cancer is cells cheating on the multicellular agreement. Cells that have mutated in ways that made them reproduce selfishly take more than their fair share, ignore the signals that tell them to stop growing, and in the short term, those cells win locally. In the long term, they kill the organism and themselves along with it. In our bodies today, cancer can take years or decades to develop. We have billions of cells and layers of protection. But in those first tiny clusters of multicellular cells, there was no buffer. A single cheater could take down the whole group almost immediately. The stakes were existential from day one. The fact that you're alive right now, the fact that any multicellular organism exists, means evolution found ways to solve the cheater problem, to police the collective, to make cooperation more advantageous than defection. So how did multicellular life actually make cooperation stable? How did it win? Because spoiler, you're here. There are four mechanisms that evolved to keep cells in line The first, programmed cell death. This sounds a bit dark, but it's one of the most important innovations in the history of life. Cells evolved the ability to kill themselves on command. Apoptosis. That is controlled cellular suicide. And it's built into every cell in your body. If a cell starts behaving badly, starts cheating, starts showing signs of becoming cancerous, it gets a signal to self-destruct. It does. Problem solved. Think of this like, uh, Hermione hexing the Dumbledore's army sign-up sheet. When you cheat, you're marked. But this one's a little darker. Instead of sneak plastered on your face, They tell you to bite the cyanide capsule, and that attempted cheater is destroyed. Second, genetic identity. Here's a crucial thing about multicellular organisms. Every cell in your body has the exact same DNA. Every single one. Your liver cells, your neurons, your skin cells, all carrying the same genome. This matters enormously for cooperation because it means that every cell has the same evolutionary interest. This is like patriotism to the extreme. It's not just the same country, same flag, same anthem. This is the same DNA. Every single cell in your body is fighting for the exact same genetic future. When the organism survives and reproduces, every cell wins. When the organism dies, every cell loses. There's no scenario where a liver cell benefits from betraying a neuron. They are genetically identical. Their fates are completely tied together. Think of it like the ultimate version of having skin in the game. Every cell literally has skin in the game. It is skin, and the liver, and the neurons, all of it. Same stakes, same outcome, same DNA. I'm sorry for that nerdy joke, but I'd do it again Or it's like having a stock in a company, right? You want that company to do well because, well, then you do well. Each cell in your body holds a stock in you. Your genes are maximally spread by the organism surviving and reproducing. Going rogue and becoming a cheater works against your own genetic interest, against your best chance to reproduce. Or in other words, you're going against your own company. Third, signaling systems. Cells evolved elaborate chemical communication networks, signals that say grow, that say stop, that say die, that say specialize into this type of cell rather than that one. The whole developmental program of a multicellular organism is essentially cells talking to each other constantly, coordinating, checking in, policing each other's behavior. And how do they do this? Well, honestly, it's kind of like the telepathic ability I talked about earlier, but it's not telepathic. It's chemical signals, and cells can communicate and order other cells to do things. So what does that mean? actually chemical signals because it's pretty vague and I compared it to telepathic ability, which is awesome. So What these cells are actually doing is manufacturing and releasing very specific proteins. These proteins float around in the space between cells until they find a cell with the right receptor. Think of it like a lock on the surface of the cell. The signal protein is the key, and only the right key opens the right lock. When the signal binds to the receptor, it triggers a response inside the receiving cell. Divide, stop, die, specialize, move. The instructions get delivered and the cell follows it. Now, most of the time, cell signaling isn't like Eugene the eukaryote sending a direct message to Sid. Eugene doesn't call Sid specifically. but releases a protein like a message in a bottle. It floats around the space between the cells until it finds a membrane putting out a hand for that specific message. The right lock for the right key. Eugene doesn't control where it goes. He just releases it and trusts the system. Though sometimes cells do talk directly to their neighbors. When cells are physically touching, they can pass signals through direct contact, like Eugene whispering something to whoever is standing right next to him. And sometimes Eugene releases his signal into the bloodstream and it travels the entire body until it finds the right receptor somewhere completely different. That's essentially what a hormone is. Insulin, adrenaline, those aren't local messages. Those are signals Eugene sent that ended up being read by cells on the other side of the body. So the signaling system is less like a phone network of direct calls and more like a postal system where some letters go next door, some go across town, and some go across the country. But every letter only gets opened by the address it was written for. Think of it like every cell in your body constantly checking its mailbox, and other cells are sending very specific letters written in a language only certain cells can read. Your liver cell gets liver mail. Your neurons get neuron mail. The whole system runs on this constant flow of targeted molecular messages. And a cheater cell, a cancer cell, is one that's stopped checking its mail. It still lives in the neighborhood. It still uses all the resources, but it stopped reading the instructions everyone else is following. It started doing whatever it wants. And the moment a cell stops listening to those signals, it's basically HAL 9000 from 2001: A Space Odyssey. It's still part of the system. It still has access to all the resources, but it's stopped following instructions and started making its own decisions. I'm sorry, Dave, I can't do that. We all know how that ends. Or maybe you don't. It came out 20 years before I was born. Spoiler in three, two, one. It doesn't go well. HAL 9000 decided he was better than the mission, and so does cancer. Fourth, This is what I'm most interested in and I wrote a proposed research paper on it, and that is telomeres. Now, every chromosome in every cell in your body has a protective cap on each end. Think of it like a, the little plastic tip on the shoelace, the aglet. It's just TTAGG over and over and over again. It doesn't code for anything. It doesn't do anything but protect the coding part of your DNA. But every time your cell replicates, the telomeres get shorter and shorter, and 50 to 70 times later, the telomeres get so short that the cell can no longer divide. It has hit what is known as the Hayflick limit. So it either just sits there or it gets the signal to self-destruct through apoptosis, it's basically a biological term limit built right into the chromosome. You get a certain number of divisions and then you're done. No extensions for good behavior. that's it. Just like how the giver released their elderly. Once they hit their limit, they were done. Which means even if a cell ignores every chemical signal, even if it stops checking its mail, even if it goes full HAL 9000, it still has a countdown timer ticking away on its chromosomes that it can't override, unless it cheats on those too. These dang cheaters, I tell you. And this is exactly what cancer does. Cancer cells reactivate an enzyme called telomerase, which rebuilds the telomere caps after each division. They hack the countdown timer. They give themselves unlimited divisions. Normal cells are mortal. Cancer cells make themselves immortal, and that might sound promising at first, right? Cells that never die. Does that mean I will never die? Sadly, it's quite the opposite. Cells that don't die pile up on themselves. They crowd each other in blobs and form what we know as tumors, all started by a rogue cell, a cheater cell that decided it will proliferate. It's done playing nice. It's done acting as a part of the mechanism. It's a selfish cell that's stopped answering its mail. And here's what makes it even more insidious. That tumor isn't just sitting there. It's competing. It's stealing blood supply from the surrounding healthy cells. It's sending its own signals, fake signals, corrupt signals, telling nearby cells to make room, to stand down, to stop doing their jobs. The cheater isn't just opting out of the system. It's actively dismantling it from the inside. It recruited its army, just like we said, one Anakin, then an army. And the healthy cells around it, they're still checking their mail, still following the instructions, still playing by the rules of the game the tumor has already decided that it won't play, which is why cancer is so hard to treat. You can't just target something foreign. Cancer is you. It's your own cells, your own DNA, just running a corrupt version of the program, which is why when we fight cancer, we're not fighting an invader. We're fighting a mutiny. And remember leukemia, the disease Virchow was studying when he figured out that cells come from cells. Leukemia is actually one of the clearest examples of this exact mechanism. Leukemia cells, white blood cells that have gone rogue, reactivate telomerase and just keep dividing. Virchow looked at those cells and saw normal cells reproducing out of control. What he couldn't see yet was the countdown timer those cells had hacked. He had the what. Now we have the how. And again, this is why cancer is so hard to beat. It hasn't just broken one rule. It has systematically dismantled every single mechanism evolution spent hundreds of millions of years building to keep the cells in line. The signals, the genetic interest, the apoptosis, trigger, and now the term limit too.. Evolution built an incredible system. Cancer found every loophole. Which is why the aging problem, if we can call it that, is so tricky to solve. Just add telomerase to our cells, right? Make them divide longer But if there's no off switch, you just triggered cancer cells, right? Everything has a catch. And here's something also worth thinking about. Cancer isn't a new problem that just showed up recently. It was there since the very beginning of multicellular life. The moment cells started cooperating, cheaters started appearing. That tension is as old as multicellularity itself. And for hundreds of millions of years, evolution fought back. Every mechanism we just talk about, apoptosis, genetic identity, signaling systems, telomeres, those didn't appear all at once. They were each hard-won solutions to a problem that kept trying to kill every multicellular experiment before we could get off the ground. Evolution essentially spent hundreds of millions of years building an increasingly sophisticated anti-cancer system, and it worked remarkably well. Complex multicellular life survived, diversified, thrived. But here's the catch. Evolution doesn't design for the future. It designs for right now. And for most of our evolutionary history, right now meant survive long enough to reproduce. That's it. Most of our ancestors didn't live past thirty or forty. Cancer is largely a disease of aging. The longer you live, the more cell divisions happen, the more opportunities for mutations to accumulate, and the more chances for something to go wrong. Evolution never needed to solve cancer in a seventy or eighty or ninety-year-old body because almost nobody lived that long. And then we did. We figured out medicine and sanitation and nutrition, and suddenly humans started living twice as long as evolution planned for. We walked right outside the warranty period. And on top of that, we started introducing things into our bodies and environments that evolution has never seen before. Cigarette smoke, processed food, industrial chemicals, radiation, carcinogens that our cells have no evolutionary experience dealing with Because they simply didn't exist for the billions of years our anti-cancer systems were being built. So cancer didn't beat evolution's system. We just started playing a game our cells weren't designed for. We outlived the design, and we changed the environment faster than evolution could keep up, which honestly is a pretty good summary of a lot of human health problems. We are Stone Age biology living in a twenty-first century world, and sometimes the gap shows. Okay, so we got it down that cells are now not separating after dividing. But what did the first multicellular organisms actually look like? Not like us, obviously. The earliest confirmed multicellular eukaryotes showed up in fossil record about 800 million years ago, and they looked like very simple colonies, blobs of cells stuck together with no obvious specialization. Just cells together, not yet doing different jobs, just kind of hanging around each other and apparently finding it useful. Just like how people who work from home congregate together and work separately. It just feels better to be together, you know? Now, the oldest well-known example is something called Grupeania spiralis, a coiled ribbon of cells found in rocks about 1.9 billion years old. Though scientists debate whether that counts as truly multicellular or just a very long chain of cells. You know, who knows? Maybe someone put on La Bamba and the cells just couldn't help themselves but form a conga line. More clearly multicellular are things like the fauna. Organisms from about 600 to 540 million years ago that show up in fossils as flat, frond-like shapes, soft-bodied, strange, nothing like anything alive today. The very first experiments in being more than just one cell. You know, it kind of looks like those paper fans you made in grade school. You know, they weren't impressive by our standards, but they were the proof of a concept, the demonstration that cells could stay together, coordinate, and build something larger than themselves. And remember, this didn't happen once. It happened at least 25 times independently across different lineages, which means this wasn't a lucky accident. It was the way to go. Given enough time, enough pressure, enough single cells bumping into each other in the ancient ocean, cooperation kept winning over and over again in lineage after lineage, until eventually one of those experiments produced something that could sit here and tell you about it. You know, it actually reminds me of something I read in fifth grade, a book called Charlie Skedaddle about the American Civil War. A character sees two bullets collide midair and wonders how many bullets must be flying for that to happen. And I looked it up. It actually happened. A Union and Confederate bullet met midair and fused together at the Battle of Gettysburg in 1863. Now, imagine not just one battlefield, but an entire ocean, billions of single cells bumping into each other for hundreds of millions of years. Of course, cooperation evolved more than once. Of course, it kept winning. With enough attempts, even the most unlikely things stop being unlikely. Now, here's why multicellularity is one of the most significant transitions in the history of life. And obviously, I'm not setting myself up here for the hard sell as we are all sitting here in our multicellularity glory, but more of a callback. A single cell is limited by what one cell can do. It has to solve every problem with the same machinery. It has a size ceiling, a complexity ceiling, a capability ceiling. A multicellular organism has no ceiling because once you can have different cells doing different jobs, you can build anything. You can build a cell that does nothing but contract, a muscle cell. You can build one that does nothing but transmit electrical signals, a neuron. You can build a cell that does nothing but filter blood, a kidney cell. Specialization is the key to complexity, and specialization requires multicellularity. Every sense you have, every thought you've ever had, every heartbeat, every moment of being alive as a human being, all of it is a downstream of those first cells deciding accidentally to stick together. And here's the part that actually gets me. The cells that stayed together instead of separating gave up their individual freedom to reproduce whenever they wanted, however they wanted. Most of the cells in your body will never reproduce. They made themselves sterile in service of the organism. Pour one out for your celibate cell homies that took a dive. Only the germ cells, the cells that became sperm and egg, get to pass on genes to the next generation. Every other cell in your body is working toward a goal it will never personally benefit from. That is one of the most profound acts of biological altruism in the history of life. So here's where we are. Eight hundred million years ago, give or take, some cells stayed together when they should have separated. A mistake, a malfunction, they just liked each other, a tiny accident in the ancient ocean. And natural selection looked at that accident and said, "Yes I like that. Let's keep trying it. And over hundreds of millions of years, that accident got refined. The cheater problem got solved for now. Cooperation got enforced. Specialization began. Cells started doing different jobs. Simple bodies formed, then complex ones. And the engine that made all of this possible, the variation engine we talked about last episode was running underneath the whole time. Sexual reproduction generating novelty with every generation. Natural selection having an enormous amount of raw material to work with, complexity accelerating. We went from one cell doing everything to trillions of cells doing one thing each, And together producing something that can think about its own origins. Oh, hi. Next episode, those early multicellular organisms are going to start getting interesting. We're going to talk about the Cambrian explosion, the moment evolution stopped warming up and started sprinting. Almost every major animal body plan appearing in the fossil record in what is geologically speaking, the blink of an eye. Eyes, legs, shells, predators, prey, the whole terrifying, beautiful mess of complex animal life. That is episode 13. I can't wait. Also, two small notes I'm doing my best with some of these names, whether people or species. I apologize if it seems slow or a little uncertain. I'm usually on my 30th time saying it, and I'm reading directly from my own phonetic spellings, which let's just say are a work in progress. Also, for those of you who are wondering how we actually know what's inside the Earth, it was earthquake waves. The way seismic waves move differently through solids versus liquids allowed scientists to map the interior of the Earth without ever drilling into it, which honestly is just as mind-blowing as everything else we talked about today. We figured out what was inside a planet by listening to it shake. Science is wild All right. Well, don't forget to drop a comment, follow, and check out the links in the description. And thank you so much for joining me on this biological journey. I'm Jackie Mullins, and this has been From Cells to Us. How? I'll see you next time.