Ep 1 - The First Cell

How did life begin from non-life?

In this episode of From Cells to Us… How!?, we go all the way back—before biology had a name—to explore how chemistry on early Earth may have produced the first living systems.

We talk lightning, oceans, RNA, and the messy, improbable process that eventually led to life. No textbooks. No prerequisites. Just curiosity.

Transcript

Jackie 0:02

Hello, I'm your host Jackie Mullens, 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. So come with me as we traverse the deepest cosmos, plunge into ancient oceans and pick apart the first bits of life. Let's dive in. Have you ever wondered how life started? How life, uh, finds a way as Jeff Goldblum so eloquently put it, well, that has consumed my waking and sleeping hours for so many years, and I put a lot of time and effort into researching the answer in a chronological timeline for my ease of knowledge, and now I'd like to share all my hard work with anyone else who's curious. Let's start at the beginning and I mean the very beginning, nearly 4 billion years ago, beginning. Welcome to the Hadian Eon named after Hades. God of the underworld. Just think of that Disney movie Hercules. The guy with the blue fire hair. Yeah, his crib. Those Ghosty skeletons. The slimy souls. Yet that's what's Earth is being compared to. I think you get where this is going. Earth was not a hospitable place to live. I'm talking volcanoes. Earthquakes. I mean, it was literally a molten ball of liquid hot magma. The moon hadn't even parted its way from Earth yet it was still clinging to our horrible little sphere, just waiting for that giant impact to come and have it break off, you know, only to stick around like a college kid in their parents' house after graduation. The moon is like, you see the rents out there in the solar system. No thank you. Not a fun place to live. Land kept trying to form and this. Fiery ball of HE double hockey stick kept whacking it down like it was mbe. Mutombo in the cereal aisle? No, no, no. Not in my house or, I guess the basketball court if you want to be nitpicky. Alright, well I think you get the picture, low. Lo and behold, some spunky organic molecules formed into the first cell. How you might ask and what the heck is an organic molecule? You may also ask great questions. Let's get to the answers. Here's a quick chemistry crash course. Stick with me for like two minutes. Everything is made of atoms. When atoms combined, you get molecules. An atom plus an atom is a molecule. So many of you will know. H2O is water. I mean, at least if you've seen water, boy, H2O is a molecule, two hydrogen atoms and one oxygen atom. Now, one more term before we move on organic. In chemistry, organic just means contains a carbon atom. That's the whole definition. If a molecule has carbon in it, it's organic. So H2O is not organic'cause it has no carbon. Quick side note, this has nothing to do with organic food at like Whole Foods. That's farming practices. In chemistry, all food is organic. Because all food contains carbon. So have fun and mess with some organic food snobs for me. Will you? You can completely claim your food is organic too, and you know, that's such discounted rates. Okay, so why does this matter? Why do we care about carbon specifically? Well, carbon is so important. That there's an entire branch of chemistry, organic chemistry, dedicated just to it. Like six degrees of Kevin Bacon. Everything comes back to carbon. And Kevin, so why is a whole branch of chemistry dedicated to it? Well, carbon makes four strong bonds, four of them. Imagine that. It's like having four arms. You'd be able to do so much more cool stuff. So if you like got to pick your very own building helper, you know, who would you pick someone with? One arm, 2, 3, 4. And some of you clever ones out there are like Jackie, other elements can form four bonds too and correct. You are you awesome nerd, but they are not as strong. So it's like have a builder with four suction tentacles or you know, four baby arms. Take my strong arm. Take your pick and carbon. With those four tentacle arms can bond with basically any other elements. Carbon is like that person you knew in high school that got along with everyone, the goths and the theater kids and the jocks like obviously this is all before Katie Heron and Regina George's showdown, which straightens out the whole click issue. And on Wednesdays, carbon wears pink, basically. Carbon doesn't discriminate. It bonds with who's ever around and that versatility, that's what makes life possible. But why does that make life possible? Well, it means carbon can build complex structures with those four strong bonds, rings, chains, scaffolds, whatever you need. D-N-A-R-N-A, glucose, proteins, fats, all the stuff on the nutrition label that like you count all organic molecules built on carbon backbones. Basically all the molecules that make life. Alive are organic molecules, and that's all because of Carbon's ability to make four strong bonds with basically anything. Okay, so we have organic down. But as we zoom out and look at the early earth in the Haiti on Eon, we don't see any organic molecules. Just inorganic. Inorganic molecules don't support life, and life is the answer we are trying to get to. So what we have to figure out next is how do we get from inorganic to organic? How does carbon start building? How does it start grabbing things with its powerful tentacle arms, and start building life? Well, here's the cool thing about carbon. Once it gets going, it starts grabbing everything and building like a snowball rolling down a hill. So it's not that carbon can form complex molecules, it's that under the right conditions. It almost has to. But I said once it gets going, you need energy to start this building machine. You need something to push that big tentacle, snowball beast down the mountain. So what does that well, on early Earth, that energy? Well, it came from lightning UV radiation, volcanic heat, hydrothermal vents. So any one of these energies or all of them could have been the thing that pushed that carbon snowball down the mountain to start making organic molecules. So Earth made the first step toward life, organic molecules. But did this just happen on earth? Let's zoom out for a second, and I mean, way out. We're now floating in space. We have our organic molecule detector out, and guess what we find? Organic molecules are everywhere on Mars, on comets, on Saturn's Moon, even floating in space between the stars. Weirdly enough, the ingredients for life are available everywhere. It's basically like the universe is handing out life starter kits. You get a starter kit, you get a starter kit, everyone gets a starter kit, which begs the question, was life inevitable? Was it bound to happen? And some scientists think yes. Given Earth's condition and enough time, life wasn't a miracle. It was chemistry's destiny. That tentacle snowballed carbon just teetering on a mountain was obviously going to get pushed, and we just happened to be on the planet where the cosmic slot machine hit the jackpot. But armed with this knowledge. Maybe we weren't the only ones to hit the jackpot. If starter kits are everywhere in the universe, maybe jackpots aren't as rare as some think. It's like if you found pizza dough, tomato sauce, and cheese in every kitchen in the world, you'd expect to find some pizza, right? Well, the counter argument to this is solid. Having organic molecules, I mean, it isn't the same as having life. We're finding the ingredients, but not the finished product yet. Like if I gave a baby pizza dough, sauce and cheese and left. I'd expect when I came back there would just be a mess, not a pizza, unless it's like a super Italian baby with a mustache and a chef's hat. So organic molecules are everywhere. But going from organic molecules to self-replicating life, I mean, that's a huge leap. Now the leap is huge, but it was for earth too, and the fact remains organic molecules, the pizza dough, sauce, and cheese. Have been floating around the universe for billions of years, has that been enough time to create the ultimate prize of life? You know, or in this case, cosmic pizza. Has the ingredients maybe come across a chef ready to cook as opposed to babies, even if it hit a million babies before? That's just something fun to think about. So let's pause and recap where we're at. Earth started as a nightmarish ball of lava. The hadian eon not exactly hospitable. Everything is made of atoms, and when atoms combined, you get molecules. Carbon is our MVP. It can form four strong bonds with almost anything, making it perfect for building complex structures. Organic molecules are just molecules. With the atom carbon in it, and they're everywhere in the universe, not just earth. So the big question, how do we go from simple organic molecules floating around to actual living cells? That's what we're tackling next. So let's see where we're at on that journey. On that journey to life. We went from inorganic molecules to energy pushing carbon to form organic molecules. But here's the gap. We've got our pizza dough, sauce, and cheese. We don't have the pizza yet. I. We've got organic molecules, but we don't have a cell yet because there's a huge difference between organic molecules and a cell. A cell is the smallest unit of life, and life is the answer we're trying to get to. Right? That's the whole point of this podcast. So what makes a cell, what's the bare minimum checklist? Well, it needs four things. It needs protection, it needs instructions, it needs fuel, and it needs the ability to make copies of itself. Reproduction. Check those four boxes and boom, you have a cell, check those four boxes and you have life. I. Now, here's what's amazing about early life. One organic molecule was so incredibly special that it checked off three of those boxes at once, and that organic molecule is called RNA. RNA could store genetic information. The instructions act like an enzyme to catalyze chemical reactions. Don't worry about all those fancy words. It's just fuel and it could copy itself. Reproduction. The only thing RNA couldn't do was protect itself. It needed help for that. So our mission is clear. We need to figure out how simple organic molecules assembled into this wonder organic molecule, RNA. Kind of like how four random musicians became the Beatles. You've got the talent, you've got the instruments, but getting them in the same room, playing the same song, I mean, that's the hard part. And we need to find out how RNA ended up safely inside a protective membrane. Get those two things together. RNA plus a membrane, and you've got the first cell with all four boxes checked. So let's start with RNA. What is it and how did it form RNA or rib nucleic acid is the genetic material. DNA is our genetic material, but in the first cell, it was RNA. So, does anyone remember those nerd ropes? The long licorice, like things with nerds stuck to it with like 800 million grams of sugar. That's basically what RNA looks like at the molecular level. The gummy rope is the sugar phosphate backbone with carbon rings, and the nerds stuck to it are the nucleo bases. A UGC. These are also made with carbon. You see how important carbon is? I take it. So just like nerds give the rope its flavor and its personality. The nucleo bases A UGC give RNA. Its genetic information, just like the gummy rope holds the nerds in a specific order. The backbone holds the bases in sequence. Without the rope, the nerds would just scatter everywhere, useless. And without the nerds, you just have a boring gummy string, you know, no information. Now what we're trying to understand is how the separate gummy rope and separate nerds formed into a full, delicious nerd rope, or how organic molecules formed into RNA. You can imagine it by like trying to make a nerd rope by throwing sugar and gelatin and you know, loose nerds into a warm pond, just chucking'em in there and hoping that they assemble into a full nerd rope. That's basically what early earth was trying to do. Billions and billions of attempts. Carbon acting like a drunk chemist, just mixing whatever it could grab, you know, like, let's try a little bit of this. That doesn't work. That's this. Until finally an RNA molecule was configured just right. So how did that happen? What made the nerds attached to the gummy rope, the nucleo bases, to the phosphate backbone? There's two dominant hypotheses. One that this transition, well, it was made here on earth, organic molecules, water and energy. And the energy was lightning. UV radiation, volcano heat, hydrothermal vents. Here's the key. These energy sources, they don't just sit there like looking dramatic. Energy breaks, chemical bonds, and when those bonds snap back together, they don't always return to their original form. Sometimes they reassemble into something new, something more complex. And a quick sidebar on hydrothermal events because they're really important. These are underwater hot springs cracks in the ocean floor where super heated water shoots up from the deep within the Earth's crust. The water is loaded with minerals. It dissolved on the way up. Iron, sulfur, hydrogen gas, methane, which makes sense. You know, when you think about it, hot water shooting through the earth's crust is bound to take some of those rock minerals with it. Kind of like if you ever turn on an old faucet and the water comes out like red or orange. That's iron from the old pipes getting mixed in with the water. It's the same idea, but instead of rusty pipes, it's earth's crust and instead of your kitchen sink, it's the bottom of the ocean. But why does that matter for life? When this hot mineral soup hits the cold ocean water, it creates these dramatic structures called black smokers or white smokers, underwater chimneys that look like they belong on like another planet. I'm sure lots of you have seen these in pictures without even realizing it. They look like some crab in the abyss is just stone stacking. For fun, it looks pretty cool. But why do scientists love these vents for the origin of life theories? Well, they provide everything early chemistry needed in one spot. Heat, minerals, chemical gradients, all that fun stuff. It's like earth. Set up a chemistry lab at the bottom of the sea, and here's the cool part. They're actually still around today supporting entire ecosystems in complete darkness. Tube worms, giant clams, eilish, shrimp, bacteria, all living off chemistry instead of photosynthesis. No sun, sunlight, no plants, just minerals and heat doing all the work. It's life powered by Earth's internal chemistry. And that's exactly what early life would have needed if life can thrive there. Now, maybe that's where it all began. So the hypothesis that RNA formed on Earth, well, that came after a study done by Miller and Yuri all the way back in 1952. They simulated these early dramatic earth conditions in a lab, and they found that in these hostile conditions, organic molecules, well, they could be synthesized from simple inorganic molecules. So let's clear that up. First of all, it's amazing. They created a bottled HA on eon like kudos. Second of all. What an amazing outcome. I mean, basically they showed that the building blocks of life can form naturally from non-living matter in the right conditions. This supports the hypothesis of Agenesis, which is life arising. From non-life. I mean, it doesn't prove it. Miller and Yuri made organic molecules not life, but showing that the first step is possible was big So they technically didn't make RNA, but showing that the first steps were possible. I mean, that's huge.'cause you can't build RNA in a universe where organic chemistry doesn't happen spontaneously. So basically the hypothesis is saying the first RNA probably formed due to early earth's act of conditions. So lots of energy, lots of chemicals bouncing around, lots of time and lots of attempts. To roll the dice and get it right, you know, most of the roles bup kiss, but keep rolling for a few hundred million years and eventually you hit the jackpot because Earth isn't a genius. It's a casino that never closed. So the second hypothesis on how. RNA could have been made is way more fun. It's called the Panspermia hypothesis, where it's believed that the complex organic molecules needed for the genetic material were already synthesized in space. So yeah, all that extreme conditioning, yeah, that already happened in space. Then they hitched a ride on a comet or meteorite into the Hades like condition of then Earth, which could have started the chemical reaction for the origin of life. So quick side note on chemical reactions. A chemical reaction is when atoms break apart from one molecule to recombine into new ones like burning wood, the woods atoms break apart, grab oxygen from the air and form CO2 and water that releases energy as heat and light, so you know the next time you're roasting Malow, take a second to thank those atoms who changed for you to enjoy that gooey goodness. Maybe drop in a molo or two. Pour one out for your atom homie. But also don't pour one out for your atom homie, because no atoms are harmed in the making of chemical reactions. Just rearranged. All right. Back to the panspermia hypothesis that RNA could have come from space. There is good evidence to support this claim. We've actually found RNA building blocks in Meteorites in 2022, a team led by Japanese scientists, Dr. Oba, discovered all the nucleo bases needed for RNA and DNA inside space rocks that fell to earth. We found the ribos, the sugar backbone of the RNA in meteorites. Basically they found the nerds and part of the gummy rope. So it's not just speculation anymore. We have proof that the ingredients for RNA can form in space and hitch a ride to earth on asteroids. So maybe life didn't start on scratch from earth. Maybe the universe was making care packages. Cosmic IKEA kits full of pre-made molecular furniture and just dropping them on every rocky planet with water, earth. Got the delivery, put the pieces together and boom. Life assembly completed. So there are the possibilities on how RNA was formed, whether it happened on earth or space or both. The result was the same. We got RNA. But I want to be crystal clear in the fact that we don't know completely how RNA was formed, how exactly the nerds attached to the gummy rope or the nucleotides attached to the phosphate backbone. But honestly, knowing what we know about Earth. 4 billion years ago is nothing short of amazing. So, no, we don't have a step-by-step guide on how RNA formed. We're piecing together a 4 billion year old puzzle where most of the pieces dissolved in the ocean eons ago. But scientists have shown that nucleotides can form under early earth conditions. They can spontaneously link together and RNA can catalyze its own replication. We've got the receipts for the individual steps, just not the full IKEA manual. And honestly, the fact that we've figured out this much about chemistry that happened before anything was even alive to witness is pretty wild. So let's pause and recap about what we've learned. A cell needs four things. Protection, instruction, fuel and reproduction. RNA is incredible because it does three of these jobs. It stores information, catalyzes reactions for energy and copies itself. RNA kind of looks like a nerd. Rope, sugar phosphate backbone, gummy rope with nucleo bases. Nerds attached two ways RNA could have formed. Either they were made on earth through energy from lightning vents or UV rays, or made in space and delivered via meteorites. We do have evidence for both Miller and Yuri proved Earth could make organic molecules, and we found RNA building blocks in actual meteorites. So we've got our RNA, but what did it actually do? What were those instructions storing? Now, before we move on, I want to clarify something about RNAs instructions. I stated before that the genetic material of a cell was like the recipe book for the cell, the instructions, but. Wait, what instructions could RNA be giving before the cell even existed? Like how can RNA strand direct a cells function when there is no cell yet? It's a paradoxical question indeed. And here's the answer. In modern cells, genetic material acts like the conductor of a symphony. DNA or RNA is the conductor, and the symphony is all the complex activity. The cell carries out hundreds of instruments playing intricate melodies. But early RNA, early RNA was conducting a very different performance Picture, a conductor standing alone in an empty concert hall, and they're just staring down a single tuba player. And that tuba player was just playing the same note, over and over and over, and that note replication. Now to be fair, the tuba player was doing a few other things, the storing information, and helping with basic chemistry. But the main gig, the thing that mattered the most for life to get going. Replication, copy yourself. Make more spread. That was the most critical note because without replication, nothing else matters. You could store information perfectly. You could do chemistry till you're blue in the face, but if you can't make more of yourself, game over. No complex metabolism, no building proteins, no cell division machinery. Just one tuba focusing on that one essential note. Copy. Copy. And here's the beautiful part that one note. It was enough because once you have self-replicating, even crude self-replication, you have heredity variation, selection, you have evolution. And evolution takes that one lonely tuba player and over hundreds of millions of years builds it into a full orchestra. Okay, so we have a general idea on how these RNA strands are getting created, and we have. Three boxes checked for our cell instructions. Fuel reproduction. But there's a problem. This amazing triple threat RNA is floating around bear open alone, basically like a Jaws victim just sitting there. Easy prey. Naked. RNA doesn't last long in these early earth harsh conditions it needed protection, which brings us to the cell membrane. The last box to be checked the membrane is what kept early genetic material. RNA Strands nerd ropes safe. From the turmoil going on around it. This was so essential, but how did it happen? Well, actually, the first membranes were already around. They were just floating in the primordial seas. They were made of fatty acids, and because of their structure, they just spontaneously formed vesicles. Basically soap bubbles at the nano scale. Only two molecules thick. And here's the cool part. Each fatty acid molecule has two parts. A head that loves water and a tail that hates it. And when you throw these in the water, they automatically arrange themselves like an Oreo cookie. The two heads are the cookie wafers, the chocolate, and they're facing outward. And they're touching the water on both sides. The tails are the cream filling in the middle, the delicious part, and they're hiding from water, and they're sandwiched between the two heads. Now, wrap that Oreo structure into a sphere. That's your vesicle. A protective bubble with a double layer membrane formed automatically by chemistry. No instructions needed, no intelligence required. Just fatty acids doing what fatty acids do in water. So how do we know this actually happened? Did we check the tape or something? Well, no, but the next best thing in 2001, a scientist, Jack Tack, decided to test it. He set up a lab simulation with early fatty acids and RNA floating around in water, just mixed them together and watched. Do you know what happened? The fatty acids spontaneously form vesicles, those little Oreo bubbles with no help, no instructions, just chemistry doing its thing, and then completely by accident some of those soap bubbles trapped. RNA inside. Just scooped it up as it closed. RNA on the inside protected membrane on the outside, holding everything together, all four boxes checked. Protection instructions, fuel reproduction. That's it. That's the first cell. Not speculation, not theory. It was demonstrated in a lab. We did it. So we have our first cell, RNA being the big part and the membrane keeping the RNA safe. But okay, so like did this just keep happening on accident? Well, no. Now we have evolution coming into play. Those vesicles containing functional RNA now had a strong selective advantage to surviving because, you know, think about it, picture you. An organic molecule, an RNA strand, let's say, and you're floating in this giant body of water and you're eating an apple. Then a bunch of other organic molecules start drifting towards you. You know no one can really move. They brush up against you. One kind of takes your apple, there goes your energy. Another one passes over. Black smoker, hydrothermal vent, and just breaks apart. Right there, right there in front of your face. Another one starts drifting to the surface and the UV radiation from the sun just bursts it open too. I mean, there's no ozone layer around the earth yet, folks, so it's just organic molecule carnage. Then you drift uncontrollably into this fatty acid bubble as it completes its circle surrounding you. It's cozy. It trapped you in the right temperature. It's protecting you from the UV rays and no other RNA strand can take. Your apple. Life is good. Life is new. This protective bubble is clearly the way of the future. So how did natural selection take this one extra safe cell and make more? How did they streamline this process? So we didn't have to wait for a piece of RNA to randomly float into a forming vesicle every single time? Well, the solution to that is reproduction. Enter, you know, stage left right above wherever the ability to replicate the entirety of the cell and transmit information. You know, RNA could copy itself, but it was messy about it. It was like a medieval scribe who'd had one too many ails out of those cool, ale horn cups probably. And now he's drunkenly trying to copy a manuscript by candlelight. You know, most of the words are probably right, but they're smudges. Misspellings in the occasional, completely wrong letter, but the book still gets copied. Mistakes and all. Well, these Mr. Magoo like early cells, they're just trying to get by and figure things out floating around. They pick up little bits of fatty acids, what their membrane is made of from the surrounding water, because fatty acids naturally want to join existing membranes. Kind of like those iron shavings near a magnet. You know, you move the magnet and all the iron shavings just kind of rush toward it. That's how fatty acids acted around membranes. They were just drawn automatically. Well, eventually too many fatty acids joined and the membrane would get too big and just kind of pinch off and split like a water droplet getting so big it divides into two. And here's the key. If that tuba playing, self-replicating, RNA had already copied itself once, twice, however many times there would be a few RNA strands floating around inside. So when the membrane split, both halves might snag an RNA strand as a stowaway when those membranes completely went their separate ways, each had its own RNA strand, its own genetic information, its own instructions. And that would be early replication. Not perfect, not planned, not even guaranteed. Sometimes one half got all the RNA and the other half got nothing and just died. But sometimes, sometimes both. Halves got RNA and those were the protocells that survived. That's natural selection at work. Okay, so let's back up and look at the big picture for a second. What I'm actually describing are protocells. This is when RNA was king. In fact, the time was called RNA World Hypothesis, RNA, stored genetic information and could do chemical work. It was actor, director, and screenplay all in one. So the RNA was running the show in warm little ponds, tide pools, or hydrothermal vents. They're dividing as stated above, but not perfectly, which is good because perfection would mean no change, no adaptation, no evolution. The copy errors that they were making, well, some of them were features not bugs. The proto cells that are better at copying RNA and holding themselves together, will they survive and win. They get to produce more and life moves forward. Life finds a way and. But then things start changing. RNA is king. Sure. But RNA is exhausted. It's doing everything. It's storing information, catalyzing reactions, copying itself. It's chemically unstable, fragile, breaking apart. Breaking down constantly. It's like King Henry, the six. If you're into history technically in power, but weak, inept, and barely holding it together at the start of the war of the Roses, a better system will need to happen if life is to continue and over hundreds of millions of years. It did. And here's the thing, RNA didn't upgrade itself alone. It got help workers, employees, molecules that could do chemistry. RNA, couldn't handle molecules that could protect RNA, stabilize it. Expand what was possible, those molecules, amino acids, and the chains that they formed. Peptides. So how did amino acids get involved? How did RNA go from doing everything alone to managing a team and what did those early peptides actually do? Well, that's a story for our next episode when RNA stops being the lone touba player and starts building an orchestra. So let's do a quick recap to sum up the beginning of life. Super quickly carbon naturally bonds with everything.'cause that's just what carbon does. Add energy from lightning and volcanoes. Some UV rays give it a few hundred million years and an entire ocean to work with. And chemistry just figures it out and life does indeed find a way. Simple molecules become complex molecules. Complex molecules start copying themselves. And once you have copying, even messy copying, you have evolution. Game on life, on, you know, go earth, but before you leave or click off or whatever, I have one question for you. Now you have the knowledge to make your own educated assessment on how life began. I'd like you to consider which hypothesis you find more convincing about the origin of life. Did life emerge from earth's own primordial seas, or did it arrive from space like a cosmic chia pet? Just add water and watch it grow. In the beginning of next episode, I'll tell you what I think on the matter. Thank you 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