Welcome back. Today we're going to talk about the origin of life. And you'll notice I say origin not origins. And that's because life on this planet or every species we know about, they're all related. They all use the same genetic code, they all use the same amino acids for their RNA. All the basic composition is the same. It seems that life arose once, and we don't where and we don't know how, but that's whet we're going to try to start to explore in this lecture. Begin by reminding you what the early earth was like, a violent place, very hot. Volcanically active, probably a very thick atmosphere. And somewhere in that environment, we think life arose. So, we're going to talk about efforts to synthesize life. Look at the origin of cells. And then finally take some of the things that we're learning about the origin of life on Earth and think about what that might mean in terms of first the possibility that life arose elsewhere and came here, and then its implications for life elsewhere. So, let's begin by talking about synthesizing life. And this is an area there's been a lot of experimental progress in the past decade or so. As there have been real advances in molecular biology and biochemistry that enable experimentalists perhaps not to revive Frankenstein as shown here, but start to explore whether or not we could create life in a laboratory. And use that as a way of understanding how life may have arose in the early universe. When did life arise? Well, life arose early. And we know that because we see fossils, and they're prokaryote fossils. Remember, those are bacteria life fossils, the simple, smaller cells. And these micro-fossils date back to 3.7 billion years ago. That's relatively soon after the earth cooled. So, it seems as if almost as soon as the Earth became habitable, within a couple hundred million years of that, life arose. Now, the idea of how life arose and some of the firsts have serious scientific explorations to this, date actually back to the 1920s. To Oparin and Haldane, who developed a basic framework, though while the details turn out probably not to be right, provide a framework for thinking about the whole problem. They began by thinking that, well, we know that water's essential to life. Life probably began, formed in the oceans. We know that the early Earth had very little in the way of continental land mass. It was mostly ocean. They assumed at the time that the early earth had a reducing atmosphere, made of molecular hydrogen, water, ammonia, methane, carbon dioxide. And they thought what might happen was there'd be a few chemical reactions taking place somehow inside a membrane. These would absorb chemicals, grow, divide, obtain energy by fermenting the molecules around them. The UV light would help synthesize these organic compounds. These compounds will survive because this early Earth was Oxygen free. And they imagined that these early life forms sitting in these membranes would eat up the available fuel, the available organic compounds. And when they were done utilizing the available fuel, they'd be forced to evolve and find new ways of making fuel and hence photosynthesis would begin. Lots of the details here aren't right. But I think as we see, over 100 years ago made remarkable progress in providing a basic framework for starting to think about this problem. The next big step forward in understanding this was the famous Urey-Miller Experiment. What they decided to do was reproduce what they at the time thought the early Earth was like. They took a vial with water, methane, ammonia, hydrogen, no oxygen because we think, we know the early Earth was oxygen free. Oxygen only arose in large quantities about 2 billion years ago. They added sparks simulating the lightning that was taking place. Let the experiment run, and after about a week, more than 2% of the carbon in certain versions of this experiment were converted to amino acids. And this gave people real hope that it will be possible to spontaneously generate life in the early earth. Form these amino acids, and then somehow assemble them into proteins, RNA and DNA. Well, this experiment was fundamental, and it was you know, really shaped the way people think about things. But we now recognize that it was in some ways limited. Limited in two ways. We, it was very hard to make progress from going from the things that came out of the amino acids that formed in the experiment. That the concentrations they did and the broad mix they did to see how that would form right away of assembling something as complex as DNA. And also, the conditions in the experiment were not a very good match to what we think the early earth was like. We think the early earth's primordial atmosphere was actually carbon dioxide dominated. Think something more like Venus, you know? We, if we look at the Earth's crust. There's as much carbon dioxide available for the Earth's atmosphere as there is in Venus'. And this early atmosphere probably had relatively too little methane. And if you run the same experiment without the methane and with carbon dioxide, you get very little in the way of amino acid production. Now, the Urey-Mi, Miller experiment, well might be reproduced in conditions at the earth surface. It might be a better way of reproducing conditions near hydrothermal vents, which is one of the places where we think like could have arisen. So, where do we think life arose? Well, we know it happened fast and was soon after the Earth cooled. And there are a number of possible sites where it might have happened. Darwin, when he wrote his famous Origin of the Species books, speculated that life arose in shallow tide pools. He talked about a little warm pond where life might arise. We don't think conditions back then are very much like the tidal pools today. But other more plausible sites are these deep sea hydrothermal vents that I've already mentioned. And when we talk about extremophiles in two lectures we'll see that this is a fascinating environment that we'll see has many early forms of life. And rather special physical conditions. Wet clay surfaces look promising. Another intriguing site is deep underground. The Earth's surface was a pretty hostile place. Recall that when we talked about the formation of the Solar System. That in the early history of the Solar System, the Earth was constantly being bombarded by things like large planetesimals that would form the moon, and smaller rocks that come raining in, heat up the surface, and would destroy all surface life. So, perhaps if life can arise deep underground, that might be a safer place for life to begin to flourish. And then after the earth's violent history or violent bombardment slows, life might then emerge from the surface. Another possibility that we'll turn to at the end of the lecture is that life might have arisen on Mars, and then traveled from Mars here. How? It's difficult to see how we go from amino acids to the complex forms of life we see today. Even when we look at the simplest lifeforms, the simplest prokaryotes are actually remarkably complex. They have complex membranes with very sophisticated mechanisms for transporting materials from the outside of the cell, inside. They have this very complicated rich process in which proteins are assembled using ribosomes and various forms of RNA. It's hard to see how we could take a container of amino acids, shake them for a long time, and just hope by random chance that the amino acids will happen to bond in just the right way in this dilute leaker that, beaker that I'm shaking to make life. It could work out the probabilities and it's remarkably low. We would not expect life to originate in the entire age of earth, even on multiple planets over, multiplied over the age of the earth. We don't know what's the right way to think about what came first. People debate this. Is the first thing that happened that we formed replicating molecules like RNA and DNA, or is the first thing that happened that we had metabolic processes capable of drawing energy from the environment. It seems that we need both, we need both the chicken and the egg, and it's not clear how we make that happen. We don't know what is the pathway from the simplest chemistry to complex life. Talk in a few moments about some of our current ideas we'll work. We're trying to understand what are the intermediate steps as we go along the process of going from fairly simple chemicals, things like the amino acids up to life that can survive and propagate and evolve. We don't know all the intermediate steps along the way, and we don't know if there are bottle necks. We'd like to know as life, is forming life easy or hard? If I start with many planets whose properties are broadly similar to the Earth. And one of the things we've learned in the past several years is that there are likely other habitable planets out in our galaxy. In fact, there are probably hundreds of millions of planets whose properties are perhaps capable of carrying at least some forms of life that we know of on Earth. And given these initial conditions, how often will life arise. Is life hard or easy? Something that we still don't know. So, let's start with what we do know. Modern cells are really complicated. You've got this really complex system where every piece depends on every other piece. And if we just try to make a cell with a cell wall like we have, and without the complex transport mechanisms, that wouldn't work. If we tried to make a cells without the, all the pieces of the needed body, take today's cell remove a few pieces of the biochemistry, the whole system wouldn't work. You know, we think about the, so called, you know, central dogma of biology, DNA requires RNA as RNA makes proteins, we need all these pieces. And how we, it's very hard to see how we go from our soup of amino acids to this complex cell. We don't know what early life was like. But I think, we have to speculate that early life was simpler than what we see today. And that makes reconstructing the history hard. Because we can't simply find you know, something in our environment today and say. This life form. Is the same as early life. We suspect that whatever early life looked like, it was the easiest thing to make, not the form of life that would best survive in four billion years of competition. And as new forms of life, and as life developed new tricks on how to do biochemistry. Modern life takes advantage of these new tricks and out evolved the simple life that formed early on. So. What happened? Well one possibility is the first thing that happened is we had a self-replicating molecule that could evolve, and this molecule existed just in a fluid, it wasn't enclosed in a cell. And we just start out with something that could replicate. And one step forward in exploring this hypothesis, was worked on by Speigelman, where he found a form of a Qbeta virus, an RNA that can reproduce in the presence of the appropriate enzymes and building blocks. And show that you might be able to construct kind of an RNA like world that would keep reproducing itself. The problem is with just reproduction and without the ability to catalyze proteins you had no way of getting these building blocks. You had one piece of the puzzle, but not the whole story. A challenge for any reproducing molecules, it's hard to come up with something that could be copied with pretty high fidelity, reproduce before it gets degraded and could self-assemble itself. Now there have been some progress on going up the latter of self-assembly. We experiments have shown that the ribose sugars could be polymerized from formaldehyde. Adenine can be made by boiling hydrogen cyanide. So we can make some of the pieces and start thinking about could we self assemble them into a reproducing molecule. A lot of recent work over the past couple decades has gone into thinking about early life as operating in an RNA world. Thinking that the fundamental step is not to make DNA, but to make RNA. And that's because RNA can do the whole job on it's own. It can both characterize, carry information and catalyze reactions. So you can have the whole process of biochemistry happen without DNA. And in fact, if you look at how biochemistry works, RNA really sits in the center. And we see things when we look at certain forms of RNA that's look somewhat like fossil tails of an earlier biochemistry. So as you all probably know, we all have tails, because we were once primates, descended from primates with tails. And in humans, in our ancestors, tails were not selected for, but what we're left with at the base of our spine, there's a little coccyx that's the remnant of a tail. When we look at parts of biochemistry, we see similar fossils. Nuclides at the end, for example, of a nucleotide reck, relic in vitamin B12, that seems to suggest there was a hook to, for the biochemistry to connect to. It looks like these RNA pieces were once part of a complete biochemistry. And we can see when we look at things like DNA substrates. The DNA substrates are made out of RNA substrates. So it looks as if we started with an RNA only based chemistry and then evolution found a way of converting the RNA only based chemistry to our modern biochemistry that makes use of DNA. DNA has the advantage of having a much lower error rate when you, when it copies itself. So getting, once you can get to DNA, that's going to be selected for for keeping a species form consistent not not having deleterious mutations. And a big step forward in the notion that RNA and RNA world could operate was the discovery catalytic RNA by Catchen Altman. And all these pieces pointed to or point to early life emerging perhaps in this RNA world. Another hint is when we look at the structure of the ribosome. Really, the fundamental machinery for making proteins that, the right ribosome itself is made up primarily of a, of really these RNA pieces that suggests that it is close to one of the original ore pieces of biochemistry. So, how do we get to RNA? How do we get from simple chemistry to RNA? How do we, assemble these nucleotides? And this is something where there's been significant experimental progress recently. Interesting work suggesting possible roots for assembling these nucleotides. And then once you've assembled these nucleotides, we know of at least two plausible roots of gluing together the nucleotides, polymerizing them to make long chains. One root that looks very promising is clay. A clay surface serves as an effective place to stick different nucleotides together, and tie them together into an RNA chain. So there's been interesting arguments suggesting that life arose out of a lump of clay, a notion that has a certain biblical resonance. Another intriguing possibility is that we could make, take that vial of dilute nucleotides and concentrate them by freezing them. This is actually an experiment you can do in some ways at home. Take some food dye, put it into water. Put that water into your freezer. What you will find is that the food dye is more soluble in the water state than the ice state. So as you cool it, and ice forms on the outside of your glass, that water, the food dye will want to stay in the liquid state. So you'll initially end up with a crust of ice and the food dye concentrated towards the center of the glass. And as you freeze it more and more, the food dye will get more and more concentrated. And if you do this experiment properly, you'll find that you can start out with dilute food dye and end up with an ice crystal with almost all the food dye concentrated right in the center. The same thing will happen with nucleotides. They're more soluble in the liquid state than in the solid state. So we can enhance their concentration by cooling it. And it turns out that this is another potential pathway to getting high concentrations and effective polymerization of the nucleotides into RNA. Now, no one has yet done the experiment where they have taken nucleotides put them on clay, put them on into cooling water, and freeze it and found a pathway, where in the laboratory they can start with nucleotides and produce a self replicating molecule. But the fact that we do see these effect of polymerization suggest that perhaps these are roots that given enough time and enough experiments are able to polymerize things like RNA. So, let me ask you a question. Thinking about perhaps what you learned in high school about biology. One of things I learned was this central dogma of biology, that DNA makes RNA, makes proteins. And based on what you've heard, do you think that the central dogma applied to early life? Think about that, and we'll be back in a moment.
