In Our Time - The Cell

Episode Date: September 13, 2012

Melvyn Bragg and his guests discuss the cell, the fundamental building block of life. First observed by Robert Hooke in 1665, cells occur in nature in a bewildering variety of forms. Every organism alive today consists of one or more cells: a single human body contains up to a hundred trillion of them. The first life on Earth was a single-celled organism which is thought to have appeared around three and a half billion years ago. That simple cell resembled today's bacteria. But eventually these microscopic entities evolved into something far more complex, and single-celled life gave rise to much larger, complex multicellular organisms. But how did the first cell appear, and how did that prototype evolve into the sophisticated, highly specialised cells of the human body?With:Steve Jones Professor of Genetics at University College LondonNick Lane Senior Lecturer in the Department of Genetics, Evolution and Environment, University College LondonCathie Martin Group Leader at the John Innes Centre and Professor in the School of Biological Sciences at the University of East AngliaProducer: Thomas Morris.

This BBC podcast is supported by ads outside the UK. Thanks for downloading the In Our Time podcast. For more details about In Our Time and for our terms of use, please go to BBC.co.com.uk forward slash radio 4. I hope you enjoy the program. Hello, all life on Earth has one thing in common, the cell. Around three and a half, four billion years ago, the first single-celled organism appeared in the oceans,

a microscopic bag of chemicals capable of reproduction. Every living thing alive today is its descendant and everyone from bacteria, from bacteria to the blue whale consists of one or more cells. The human body contains so many of them that up to 70 billion die and replace every day. So where did the cell come from? What goes on inside it? And how did the earliest single-cell creature evolve into a complex organism containing billions or trillions of cells?

With me, to discuss the cell are Steve Jones, Professor of Genetics at University of College London. Nick Lane, senior lecturer in the Department of Genetics, Evolution and Environment, also at University of College London. And Cathy Martin, group leader at the John Innes Centre and Professor in the School of Biological Sciences at the University of East Anglia. Steve Jones, would you begin by telling us a bit more

about what cells are? How does a biologist define them? I suppose it's a bit like what atoms are to a physicist. In other words, there's basic units from which everything else. is built. And rather like atoms, if you look more carefully at atoms, you find that actually within the atom itself, which seemed initially to be a single indivisible particle, which is what people thought about cells in the earliest days. There are all kinds of subtleties and structures unexpected within the cells. So they're the building blocks of life, really.

Can you give us an idea of the size of the cell? Oh, tiny. What's tiny in your terms? Might not be tiny in mind. Well, I mean, there are something like you in your noble frame contain something like 10 with 14 zeros after it cells, 13 or 14 zeros after its cells. So that shows how small they are. They're not, they vary in, there are some quite large ones.

Some of them... But we're doing about a thousandth of a millimeter sort of thing. Or less, yeah, for most of them. Some of them are quite large. Nerve cells can be very long, for example. But generally they're rather small. Of course, in your body, you have all those cells of your own.

but you have many, many more cells, 10 times as many, which aren't yours. You're much less human than you were on the day you were born. And that's because you've got 10 times as many bacterial cells as you have your own cells, which in turn means that the proportion of your body taken as a whole, which consists of human cells is equivalent to about one leg below the knee. All the rest is bacteria. So as well as those cells which make you, you have many, many more even smaller ones inside you. I'm already dizzy, Steve.

I'm thinking which leg I'll sacrifice, which is a good one. Can you give us an idea of the shape of these things? I think the very earliest cells... Because you're like to see them with little globe. Well, I think you're probably not far wrong when it comes to lots of them, red cells, for example, or in the blood, or white cells in the blood.

Others are much bigger. Some of them are almost visible to the naked eye. Yet more have extraordinary shapes like nerve cells, which can have long, branched. processes. Others can be some are almost square. They're very, you know, they're very pliable in what they can do.

So when and how did we come across them and how is the notion of their being a cell developed? Well, it actually happened in the year of the Great Fire of London in 1665 when, which is just after the Royal Society was founded. A moment of explosion of understanding, really. And a biologist called Robert Hawke, who'd invented one of the very earliest microscopes, compound microscopes and telescopes, began to look down the microscope. And he actually looked at cork.

And he saw these little holes and perforations down the microscope which had never been seen before. And he called themselves. And he called themselves because they reminded him of monastic cells, that monks were locked away. But of course, cork is dead. So he wasn't actually looking at a living cell at all. But a few years later, just five or six years later,

a Dutchman with a name Van Leuvenhike, did the same thing with a slightly better microscope. and saw that cells actually were alive, were motile. He did the experiment which every schoolboy biologist does. He looked at his sperm, and he was astonished, understandably, at what he saw. He made all kinds of, it was a rather a daring thing to do in 1670, whenever it was, and he made all kinds of explanations about why he'd done it.

But it was actually, really, that was the introduction to the cell as a living and extraordinary object. Nick Lane, I airily said at the beginning, following the three of you, I would say, It was 4 billion to 3.5 billion years ago and this appeared. Can you be a little more precise than that and tell us what you know about when it appeared the first cell and how it appeared and where it appeared? There you are. Well, it's tricky, actually. That's about as precise as we can realistically be. I mean, there are fossils, believe it or not, are things that look very much like cells.

And there are structures in the rocks as well, which look like what are called stromatolites. They're kind of great big structures of multicellular. and there are various chemical signatures which suggest life. But there's no, there's a kind of a gradient between non-living organic matter and living organic matter. And it's very, very difficult to place the origin. It probably was about that early, but there's been a lot of controversy about it, and it's difficult to prove it one way or the other. I suppose those distances are so vast that one, you know what I mean,

says, why three, why did it appear three and a half billion? that have two and a half billion or one and a half a billion or half a billion or at all? I mean, were conditions particularly, well, obviously they were. What were the conditions that made it appear in three and a half billion years ago? Well, again, there's a lot of arguments about it. I mean, one of the big differences between now and then is oxygen. I mean, we all need oxygen to live at all. And all, you know, large animals and plants and so on need oxygen.

But to produce the kind of chemistry that the very first cells would have needed, oxygen is very toxic to that. It just breaks everything down. So one of the important points about the early Earth is there wasn't any oxygen. That meant the chemistry of the oceans was quite different. There was a lot of iron, for example, in the oceans that we don't have anymore. And so, yeah, it's probably impossible. So we're looking for a time when there's no oxygen for these things to start?

Yeah. But the rise in oxygen, we know fairly certainly, was about two and a half billion years ago. And life started probably a billion years before, that but as I say it's uncertain. And you have a theory about where it might have started, don't you? Well, it's not my theory

but I certainly subscribe strongly to the ideas of Mike Russell. There's a particular kind of hydrothermal vent which would have been very common back then. Most people... At the bottom of the oceans. Most people are familiar with

vents. They've seen pictures of what are called black smokers, which are fantastic to look at. They kind of belt out this black smoke. And then there's a different kind, which is much less visually interesting. In fact, you could call them white non-smokers. Nothing really seems to be going on, but actually they turn out to be very rich in hydrogen gas and they turn out to have all kinds of interesting properties which are very analogous to cells, in fact.

And that's where you think it began. But do you think there was anything, is there anything inevitable about it, the formation of cell beginning then in those conditions? Is there a fluke element there? I think there's both. I mean, to begin to produce the kind of organic molecules required to have a cell, you really need to have, I think, all the condition is perfect, almost. You've got to have some kind of a driving force, which is forcing these things into existence.

And that's the kind of chemistry that people are studying now. But then there's the organisation of cells. There's the way in which everything is hooked up. There's the way in which large molecules form and interact with each other. and there we really know very little. We do know that quite large, complicated proteins, for example, ribosomes, for example, which are the structures which build more proteins, can pretty much self-assemble, but how those processes really work?

So that's the question that we really don't know the answer to, is how likely is that? Scientists like yourself today divide all cells into three types. Would you briefly just tell the listeners what these three types are, because we'll be using these three words quite a bit for the rest of the programme? Well, there's bacteria, the kind of bacteria that Steve was just talking about, that you find trillions of them on our bodies and so on. There's another type that looks exactly like bacteria.

I mean, down the microscope, they're the same kind of size. They're very simple structures. If you look inside them, you can't really see anything. They're called archaea. They were called archaea because they were thought to be the most ancient cells, which is, in fact, almost certainly not the case. They were misnamed in that sense. But it turns out that their biochemistry,

their genes, their properties are really completely different to bacteria. And so they form a separate domain. And then there's the third group which are eukaryotic cells. These are the cells that we have ourselves. Eukaryotic just means true nucleus. We have a large compartment where we store all our DNA. And there's all kinds of other things that these large complex cells have too. Thank you.

Cathy Martin, bacteria and archaea are both types of prokaryotic cell. Can you give us some idea of the basic. outlines of the basic cell, the prokaryotic cell? Well, I think most important, and I think one of the problems that people have grappling with when life emerged is that all of cells, all life that we know it is, is bounded by a membrane. So you have to have something that contains all the inside bits and organises it. Like a skin. Yes, and life had to emerge before you got that boundary, but I don't read to, but because

you have to have some boundary, it's very difficult to. to know when that came to being. But there is no life without cells in a particular structure. Sorry, I'm not quite clear about that, my fault. So there's no life that we can talk about on this programme as life in cells unless there's something with a structure around it, a membrane, like a little sac, like our skin, holding the thing inside, making it a contain. Yes, so even a virus which doesn't have a bounding membrane,

has to live inside living cells, have this membrane. because that's because you have to increase the concentration of all of the working parts of the cell and they have to be working independent from the external environment. Otherwise, it would all be too dilute and everything would move away and you wouldn't be able to get the processes to work. So it's like little hermetic, little sealed workshop, that they've got to be independent on that. And it's it, as we're going to find out, it's an extraordinary, complicated world inside this one-millionth of a thousandth of a whatever Steve said it was. Object you can never say.

Anyway, right, so we've got that. Yes, then inside the bag, there will be a series of processes. I mean, I tend to think in terms of metabolism, but there will be processes that assemble catalysts. Probably originally these were not organic catalysts. They were not proteins, but they may well have come from inorganic catalysts, but what life has done is to form proteins which will catalyze certain reactions. they will encourage the forming of certain bonds to make structures.

And within that process, there has to be a code. It's like an instruction manual, which gives the readout for the structure of the proteins, and that's RNA. And this is all in the basic cell. Yes, in the basic cell. We're not moving to anything more complicated yet. And the RNA is like the book of instructions, but your own. also have to have a place where the books are stored, a library,

and that's the DNA which is then read out to form the doing stuff, which is the RNA, which then encodes the proteins, which catalyze all the reactions. So inside this absolutely tiny thing, though, thousands of a millimetre, or 100,000, you said. It could be very few in the two-stead. You have all this going on. Yeah, and function.

And more. Well, let's have more. It's extraordinary. I mean, how it's... There must have been something pretty... recal before we didn't come instant cell. No, no, it can't have done because you have, you have to have, you have to have something that has some sort of selectable,

selectable advantage to it. So there has to be some sort of, something that encourages other things to happen, I think. Can you, so inside, can you just run down quickly, the things that are inside this membrane? So there's DNA. DNA, yeah. And that probably came after the RNA, but there's RNA, which is the code. The messenger, it's the message. It's the language, if you like, of how to do things. And then there are proteins which are made from the template of the RNA, which are the functional.

They're the catalysts that catalyze reaction. And the most important types of reaction are to produce energy. So that's respiration to take organic matter and to make energy. And the membrane isn't just a skin, is it? thinks the membrane is a contributor to this process as well. Oh yes, because across the membrane is the mechanism for generating energy. So that's generated by ionic gradients, proton gradients. So that's the way that the cell is able to generate energy.

And this is the single cell that according to the loose and bagggy time table that we have sort of ruled life for a billion and a half years. or was life for a billion and a half years. I mean, that's serious. That was life. Yeah. And these grew, they multiplied, they were everywhere, they were just in certain parts of the planet. Should we know anything about that?

They were in the sea, I think. They were in water. Charles Darwin said it was a small, warm pond, then it was probably in life. So they weren't turning into anything. They weren't turning into fish animal. Well, I think that's not. Just happy being, or not happy, unhappy,

maybe they didn't know about it. The guy who really put his finger on what makes life was a physicist, and physicists unlike biologists are very smart. He was a guy, most people have heard of him, Schrodinger and Schrodinger, who was in Dublin during the Second World War. He'd escaped from Germany. People have heard about Schrodinger's cat, which is both dead and alive. But Schrodinger wrote a book called What is Life?

And basically, he pointed out exactly that. Life is a little patch of order, or little patches of order, in a sea of chaos, and everything tends towards chaos. And the membrane is what made life, really, because it's like a dam across a river. Tiny, tiny little bits of energy can be built up by this famous proton pump, which are pumped in from outside

and increase the order inside. And this can read to a huge mass of energy, which can then do something interesting, like wiggle a tail or do some biochemistry. We move on. I don't think I've ever moved on a billion and a half years before, but it's rather than I. Time to move on.

It's a sort of power, really. We have a new type of cell, Steve. It's the eukaryotic cell. What's distinctive about it? How did it come in and why is it so important? Well, I mean, again, to take another rather phony analogy from physics, it really is a quantum jump. That life was very, very boring for its first.

It's actually the opposite of our own lives. Our own lives were very interesting for their first third. Then they became boring. Well, biological life was rather the opposite because the bacteria were the first conservatives, really. I won't put that in reverse, but they didn't do much for billions of years. They just sat there being bacteria. And one of the reasons for that was that they were energetically very inefficient.

But there was a sudden leap, and Nick Lane knows much more about this than I do, in which there was almost a takeover bid of one lineage of cell types, of another one. And one cell type engulfed. another type and more or less enslaved it and turned it into an energy machine, a mitochondria, as it's called. That produced immediately a quantum jump, an enormous jump in its efficiency. And from that we got what's called the nucleus emerged, and that really locks the library door. Okay, we're familiar with the idea nowadays. The library is that it is the DNA.

It's fragile stuff, but the nucleus does is lock it away, keep it away from the hurly-burly of the shop floor, which allows the size of the DNA to get larger, more information to be built up, and you really end up with a much more efficient and much more remarkable creature, the eukaryotic cell, which has got many, many more specialised machines in it than what we've heard about the bacteria.

Steve said you knew much more about it, so can you develop the eukaryotic cell? Was this, again, we all will be, I'm sure, we're listening. Was this going to happen? Was there something inevitable about it? Was it sort of kind of accident? Did it happen once? And then it developed problems that once happening? Yeah, I mean, this is actually, I think, one of the most fascinating mysteries at the moment at the heart of biology

because it did happen. We think once. The reason we think it happened once is that all... Somewhere on the sea bed. All plants and all animals and all fungi and all algae, everything large and complex, shares a common ancestor. And by definition, that common ancestor arose once. Now, again, we're uncertain when it happened. but basically if bacteria and archaea arose 3.5, 4 billion years ago,

eukaryotes were perhaps 1.5 to 2 billion years ago. So there's this 2 billion year gap where nothing happened, apart from, as Steve said, it was just boring. It was more of the same. There was a kind of an equilibrium on a planetary scale. And then you have this event which gave rise to the complex eukaryotic cell. Now, as Steve said, it seems to be related to the acquisition of another cell, which went on to be these energy genitals,

generators, the mitochondria, which were once bacteria themselves. And there's a strange thing about why should just one cell getting inside another cell make such a big difference? And it's to do with the way that cells respire across the cell membrane, as Kathy was saying. Bacteria are constrained by breathing across their membrane. So as they get larger, they have less membrane relative to the amount of proteins that they have to make. and eukaryotes get round that by having effectively multibacterial power. They can have a thousand bacteria inside them, and rather than each of those bacteria having all the overheads of a bacterium,

they get paired right down so they become specialised just to make energy. So to put it in very simplistic terms, I really apologise. These two come together and they're so efficient, they begin to dominate. Well, it's not so much efficiency as they just cast off the bottom. bonds that bacteria have. So bacteria, if they get larger, they become less and less energetic in effect. And what eukaryotes can do is become as large as they want and have as many bacteria inside them generating energy,

which became the mitochondria. So they have energy to waste. They can burn it. It's not efficient. They're actually, we calculated it. They have about 200,000 times more energy per gene available than bacteria do. It's an extraordinary difference. They can sustain a huge genome with, you know,

tens of thousands of genes which bacteria just can't do. So they're set off doing that, and the multiplicity of life gets underway from that very simple act of joining, presentation, one act as you think it might have been, one freak, almost act. Yes. In a word, yes. I mean, there's an awful lot of problems to overcome, which is why I think it probably did happen once. I mean, it could have kept on happening,

but, you know, cells that did that again got out competed, but there's nothing to sustain that and the more you look at it, the more you think it really did happen once. And so that focuses the mind on, well, what are the problems? And the problems are, well, how do... It's like a marriage where the husband and wife are stuck in the same room for eternity, practically. You've got to make it work somehow. You've got these cells inside another cell.

They're extremely intimate, and there's no escape, and they've got to make it work. Cathy, you gave us a rundown of the original cell. Can you give us an equally illuminating overview of the important structures inside the uriotic cell? Okay, so because you... Eukaryotic cell. Yeah, because you start to have... I mean, for me, coming as a, well, a sort of bichemist cell biologist,

I guess a lot of people would say that the separation of the genetic material into the nucleus is the most important thing. But I think actually subdividing the cell itself into separate little, bags, which allow you to do specialised metabolism inside the little back. So you've got the membrane around the outside, which allows you to have concentration of metabolites. But then inside the eukaryotic cell,

you've got many more sub-compartments where you can do specialised things. Is this because of the penetration? Because of the doubling up? Well, whatever you call it? Conjunctious. Where you have the mitochondrindic. Now, I'm a plant biologist,

so I think equally important. is the acquisition of the second endosymbion, which was the cyanobacterium, which allowed plant cells or algal cells to become photosynthetic. And that means that they became photoautotrophic. They're able to use light energy to fix carbon, and they started to produce oxygen, which then gave rise to oxidative growth, which is much, much more powerful than, I mean, they supplied, we wouldn't be alive today if there wasn't oxygen in the atmosphere.

So photosynthesis is a whole area of eukaryotic cells, which came from bacteria originally, but this allowed the invasion of the land and, yeah, provide the environment for other organisms. Sorry, I'm very sorry. And then there are other bags. So there's the nucleus itself, which is a kind of bag for dealing with what's being,

coming in increasingly complicated and large collection of instructions, of instruct protocols, if you like, in the library. And that's an enormous amount of organisation. It is like cataloging in a library. You have to be able to get the books out when you want to, read them when they're needed, and you have to be able to change the instruction, reading of the instructions according to environment and all this type of thing. And having it in a separate compartment and being able to divide it is really essential

to be able to do that in a specialised bag. And then you have other bags which don't have their own DNA, but things like peroxosomes and glyoxysomes, the whole endoplasmic reticulum. And in many cells you have an internal bag which is for water control, and that's called a vacuole as well. So there are many subsections of a eukaryotic cell

which make it really... It sounds like it's turned into a little city. That's right. And organisation is... It's quite extraordinary, isn't it? Steve, you did say quantum, believe, didn't you? And is that the correct phrase you, sir? I think so.

It really was a complete shift in the direction of life. I mean, it wasn't meant to happen, it happened. But it only had, as we've heard, it only happened once. It really opened the door to the machinery of evolution. And after that, everything else is detailed, really. Right. We've come to mitochondria, Steve. Mitocondria, Steve.

Well, mitochondria, as we've heard, These are the famous powerhouse of the cell One of the two, there are more than, probably more than two, symbiotic events, as they're called, where this famous takeover of one cell lineage by another happened. And a woman, a biologist called In Marculus, who died out of a go. She came up with this notion about 40 years ago now, and of course she was laughed at a court.

Unfortunately, she turned out to be right, because when people began to look at mitochondria, it was immediately clear that they had genes of their own, independent from those of the nucleus. And they didn't look like the genes in the nucleus. The genes in the nucleus, the DNA is a long, long, infinitely long, two-meter-long string in every one of your cells. Mitochondria are small, closed circles,

and bacteria have small closed circles, too. And what's actually happened is there's a constant war, really, between, you know, it's a billion-year-old war, between the mitochondria, who still, no doubt, yearn for their independent existence, and the nuclear genes. And what the nucleus has exceeded in doing is hijacking lots of the bacterial machinery,

move it into its own selfish, private little estate inside the nuclear membrane, and just leave the machine for generating energy. And that machine is biochemically quite complicated. It's a thing called the Krebs cycle, which is a big circular sort of roundabout. It's a motor, it's a motor. It's like a little electric cycle.

motor goes round and around millions and millions of times a second in your body. And that happens within the mitochondria, most of it. And within the mitochondria, there's a kind of pleated sheet which increases the surface to which these enzymes, these catalysts abound, and greatly increases

the thing's efficiency. Interestingly enough, mitochondria are probably the reason why we only have two sexes. And that's because the only more or less universal definition of being female is passing on mitochondria

because in humans, in nearly all other creatures, the mitochondria passed from one generation to the next through the egg, not through the sperm. And the reason you don't have male, female and something else is you might then have two different kinds of mitochondria get into a single individual and rest assured they would fight. And so that limits us to the boring dualism of men and women. So mitochondria are probably more fundamental than most people,

many people think. I keep asking these enormous questions, Nick. But is it possible to tell us in any way the origin of mitochondria? Are we back in the truly dark age? No, they were simply bacteria. We know roughly what kind of bacteria they were. They were called alpha-proteobacteria. They're still out there today as independent cells.

And it's not really that there was anything particularly special about them. It was the nature of the relationship. with the host cell, which is much more difficult to specify. But as Steve said, there are these problems with mixing mitochondria. So if both gametes, so if the egg and the sperm both passed on mitochondria, they would fight. Now, what's very strange is if you go back to the single-celled forms of life, so unicellular organisms, they don't have eggs and sperm. They have what's called isogamets.

gamets are exactly the same. You can't tell the difference between them. And yet one of them passes on the mitochondria and the other one kills its mitochondria. So you see these same processes happening. We don't know exactly what the reasons are. I mean, they fight, but why do they fight? How do they fight? What are the terms of the war? It's very difficult to know. But they're certainly far more profound in their influence on what happened next. Kathy, plant cells, you're an expert on plant cells, container structure with a similar origin, the chloropass. Can you Tell us about that, please. Okay, so, yes, so that is the site of photosynthesis,

so the site of fixation of carbon from carbon dioxide using light energy and the splitting of water to do that. And this evolved in cyanobacteria, and then the cyanobacterium is thought to have been engulfed in a similar process to the acquisition of the mitochondria by a primitive eukaryote, and so been able to adopt photosynthesis. I think there are problems with that rather simplistic model.

You have to probably think about some reason why this symbi-well, the engulfing, which might originally have been just feeding, like phagocytosis, why that should become a symbiosis. So that's a living together with mutual advantage. That's the definition of it. And I think there's some quite nice ideas. about how that might have happened. Basically, what the host cell gets from it is the carbon that's been fixed.

And there has to be, the bacteria have a different mechanism of making complex polysaccharides from fixed carbon to the host cell. And you can sell that by the mechanisms of the biocynthetic pathways for carbohydrates. so that bacterial processes are different. And it's possible that there had already been some transfer of DNA into the host cell in order from other symbionts that then allowed them to take real advantage of engulfing a cyanobacterium and start to use the carbon for their own carbohydrate synthesis.

Steve, I mean, there's all kinds of really quite extraordinary. facts emerging from these symbiosis. We've heard about two of them. Just a few years ago, it turned out that the malaria parasite, which kills five babies a minute, the malaria parasite actually has within itself something which is really quite similar to the famous chloroplast. Now, why should that be?

It's quite astonishing. It's a blood parasite, but it's got it there. And it just shows that the beauty of biology is its unexpected nature. That's quite unexpected, but what does that do? It means that possibly you can kill the malaria, parasite with, to put it crudely, weed killer, because some weed killers actually point themselves at the chloroplast to kill off weeds. So that's one of these extraordinary things about biology. You can be doing this apparently arcane bit of biochemistry and suddenly something

like that pops out. That's the joy of biology really. It's unpredictable. It's not like physics, which is, of course, dull. I'm going to let that pass, really. Steve, riskily, because I want to move on to Can you just be specific about how these amazing eukaryotic cells reproduce and pass on their DNA? Well, as the good Lord said, go forth and multiply, but they went forth and divided instead. They divide. One cell divide, all the way from single-celled eukaryotes to, of course, ourselves. We have the system where cells divide into two.

It's a process known as the cell cycle, and it's been known for a long time in its most crude outlines since the 19th century. It's been known that if you look at cells down a microscope, which you can do in a human cells in a dish, you can do that relatively easily. Plant cells is even easier. You will see at certain moments in their life cycle that things called chromosomes appear,

they're otherwise not visible, and they then move to opposite poles of this cell, which then divides into two, and the chromosomes then apparently disappear, and the cycle goes on. And that's asexual division known as mitosis, okay? Now, everybody in the world has only ever has one sexual experience, which is when the sperm and egg that made them get together.

And sperm and egg are made in a different way that's called meiosis. And just to show that we are a literary lot, that word meiosis is actually a literary term for minimizing something. Oh, that Queen Elizabeth is quite, the ship, Queen Elizabeth, is quite a nice boat, isn't it? You know, that's meiosis. And meiosis means reducing, reduction division. And what you can do is shine some ultraviolet light.

at a dividing cell and that measures the amount of DNA in the cell and what actually happens is when you can't see the chromosomes in a cell actually the amount of DNA doubles then the chromosomes appear in mitosis and the amount of DNA halves again

but in meiosis sperm and egg we have one doubling of DNA followed by two cell divisions so you've got half the amount there which gets together when sperm beats egg and Nick Lane can you just develop a little bit the impact of the evolution of the uricotic?

Uri erotic. Much nicer. Sounds like a cock group. I've been under a lot of rain in the north-western England. Right, let's go. They're really erotic, didn't you say? I'm sorry, what was the question? The question is, I'm not quite clear that we know enough about

how many things it led to this complicated cell, how it did set things off. Did it stop? We're talking still two billion years ago. Was there another billion year time lag or did it get going? The build start of life start from then. Well, actually there was another billion year delay or close on.

Again, the dates are uncertain. But cells themselves became enormously more complex, larger they had, all these internal compartments and so on that Cathy's been mentioning. But to get to multidis, to cellular organisms to get to plants and animals as we know them, that again was quite an abrupt transition. We think it's known as the Cambrian explosion.

And there's been a lot of work on, well, what happened before that explosion. Maybe things became larger. But that was a lapse of... Well, this was about 550 million years ago. Yeah. So we're getting... A billion and a half lapse again. From four billion years, we've got to 550 million years ago.

So, you know, three quarters of the time of the planet is basically single cells. And then suddenly, you see... multicellular organisms. Now, probably one of the main reasons for that difference was oxygen levels rose in the atmosphere. Probably on the back of what was called a snowball earth. So there was a global freeze around about 600 million years ago. In fact, it lasted for about 100 million years on and off. And that played havoc with all kinds of conditions and with life itself. And one of the outcomes of that seems to be that oxygen levels rose. And that just released the brakes. allowed larger organisms to exist. Can you tell us, Cathy, how protein manufacture goes on in these cells?

So basically, proteins are made from a code that's read out from the RNA. The RNA code is read from the library, the DNA. So DNA is transcribed into RNA. So it's copied by the nucleotide basis. that pair. And then the RNA is read off on a machine called the ribosome. And this basically brings in amino acids with a little adapter molecule, which can read off the code in the RNA and put things in a linear sequence. So basically, both prokaryotic cells and eukaryotic cells have ribosomes, which will read off the protein code from particular pieces of RNA.

that are transcribed from genes. So that's a common mechanism. The difference between eukaryotic cells and prokaryotic cells is that the reed off occurs in the cytoplasm, so that's in the non-nuclear region in eukaryotic cells, so it's separated from the DNA material. Whereas in bacteria, the RNA is transcribed and then translated more or less at the same time. So you get a string coming off from the DNA,

and then the ribosomes attach to the string of RNA and read it off. So that creates some logistical problems because you don't have this nice separation. And it also gives a lot more scope for control of the whole process of making RNA and then reading it off if you separate the two. Nick and Steve, both of you really, one of the most fascinating things

as this story goes on and all of it is, isn't it, is the way that cells begin to specialize. We have totipotent, and pluripotent and then unipotent. But can you tell us how this specialised, let's forget about when you started, but how it works? Well, essentially what bacteria do is they only have a handful of genes.

And so when you see different types of bacteria, they tend to have different genomes. So they have different libraries of genes. And what eukaryotes can do, because they have so many more genes, they can have a library of, say, 40,000 genes or something instead of 4 or 5,000, which is the maximum for bacteria. And so then you have the possibility of switching them on and off.

And so in effect, you can, by switching off three quarters of the genes and having just a quarter active, you produce a kidney cell. And if you switch off a different three quarters, you produce a liver cell and so on. So you can switch on cohorts or off. And so all the cells in our body have exactly the same genome, but they all specialize in different ways. And that's really then a series of master-stress. switches, which genes do you switch on and off in a very ordered process during development

to produce multicellular organisms as we know them? Is it possible? Can you take that on, Steve? And who's doing the switching on and off? Or what's doing the switching on and off? Well, I think just last week, actually, there was a series of very important scientific papers about this very question. And one of the great anomalies in genetics is how few genes there seemed to be. There seemed, after the sequence of human DNA, there seemed to be only about 24,000 genes

in the traditional sense, things that code directly for proteins. And that was really very baffing and rather embarrassing, you know, I mean, when I was a lad, when I was a student, one assumed that something's as beautiful and elegant as myself, for example, would demand hundreds of thousands of genes or even millions.

Now, that wasn't true. 98% of the DNA appeared to be junk. Now, we all knew that wasn't true, but we didn't know what was going on. And when they sequence the human genome, basically they had a very linear view, a one-dimensional view what was going on. Then it was clear, as Nick said, that actually we need a two-dimensional view because some things are switched on and some things are switched off in a complicated way.

And just last week, we turned to a three-dimensional view because it turns out that the switches which control these genes, which are in the junk, the junk is the switches, really, are often a long way away from the actual protein-coding molecule itself. So somehow the way that the DNA folds and the switch maybe gets close to the factory floor is going to be crucial. And that is going to be a really, really difficult problem to sort out. Cathy Martin, have we any idea of the number of specialisations which are available inside these cells? It really depends on the organism that you're talking about.

People tend to think of plant cells as being very unspecialised. They're little boxes, some with green and others without green. But in fact, plants tend to specialize at a biochemical level so that they will be metabolically very highly specialized. I think all of the main progressions that have occurred in higher organisms have required cellular specialisation. I'll give an example. And that's the formation of vascular tissue in plants.

So without having an ability to transport water, a plant can't grow on the land. we would just be restricted to things that look like mosses because you need to be able to transport the water up to the top of the plant. And so you had to have an evolution of first of all of long cells and then you had to have a process whereby they were waterproofed and that required a metabolic specialisation to be able to put a waterproofing material around the outside of the cell

and also that gave strength that waterproofing material is called lignin and it allowed plants to grow up to over 100 metres so then we start to get an extra dimension to life on earth at least on land. One point, because plants and animals evolve multicellularity separately. They became large and complex at different times, having both had single-celled ancestors. And one of the reasons that's important is that you have to start with a single cell and that cell then develops into the whole thing.

So you have each generation begins with a single cell. Thank you very much. Nick Lane, Steve Jones, Cathy Martin. Next week we'll be talking about the druids, the priests of ancient Britain written about by Julius Caesar. Thank you very much for listening. If you've enjoyed this BBC podcast, why not try others such as The Forum, the discussion programme about global ideas?

To find out more, visit BBCworldservis.com slash forum.