Why is life the way it is?
Taking a closer look at where complex life began
Transcript
Professor Cait MacPhee FRSE 0:22
Everybody welcome to the Royal Society of Edinburgh. And also, for those who are joining us online, welcome. We’re thrilled to have you join us for this event, which we hope will be interesting and stimulating. Now I’ve got a bit of housekeeping before we start. Right. You can see from the signs on the above the doors the exits from this room. In the event of a firearm, there is no fire drill planned. So if an alarm goes off, then we need to leave the room properly, exit through the way that you came in and out onto the street. If there is no exit through that door, go through this one brilliant. So you’ll have the chance to ask questions of our speaker and all of our panellists, but we’re going to pause that until the second half of this session. So please think about your questions and reserve them, and then there will be plenty of time for discussion later. So when there are time for questions and answers. Please raise your hand and a microphone will come to you. If you’re joining us online, please put your questions into the chat box, and they will be relayed to us by one of the members of staff from the Royal Society of Edinburgh. So I’m Cait McPhee. I’m a member of staff at the University of Edinburgh, and I am a biological physicist, and it’s my very great pleasure to welcome our speaker for this evening, who is Nick Lane, who is joining us from UCL, where he is a professor of evolutionary biochemistry and Director of the Centre for life’s origins and evolution.
Professor Cait MacPhee FRSE 2:01
And Nick specialises in evolutionary biochemistry and the origins of life, best known for his research and the role of mitochondria in the emergence and evolution of complex life and energy constraints on early life forms and eukaryotic life. Also on our panel is Sean McMahon. Sean is an astrobiologist, and His research focuses on finding life out there. He’s also one of the CO directors of the UK Centre for astrobiology. And then we have Victoria Martin, who is a particle physicist, experimental particle physicist, who works with the Large Hadron Collider, and her research primarily focuses around the action of the Higgs boson. So particle physics, astrobiologist, biological physicist, evolutionary biochemistry. So I’ll invite my panellists to join me on the stage now.
Professor Cait MacPhee FRSE 2:59
Nick is going to be giving us a lecture tomorrow as part of the Gifford lecture series on Why is life the way it is, but we are about to get a preview of his lecture to start us off with the discussion. So thank you, Nick.
Professor Nick Lane 3:12
Well, thank you all for coming. It’s a pleasure and an honour to be here. So yes, this discussion is really set around my Gifford lecture tomorrow, which is, I believe, the first in a new series of stand alone Gifford lectures from more of a scientific rather than a natural theology perspective. So I’m very honoured to be delivering that now. My title for the talk tomorrow is, Why is life the way it is? And you may think that’s a bit of a peculiar title. What way is life and what way would we expect it to be? The way I’m coming at it is really I’m puzzled by genes and the role that genetic information has played in biology over many decades. Now, as not, I’m not knocking genes in any way, but the way that we’ve ended up perceiving biology is really as a kind of branch of information science. So we have now, when we’re thinking about evolutionary history, literally 10s of 1000s of full genome sequences, and we compare these sequences, and we think about structuring a tree of life and the history of life on Earth, and is fundamentally about information flow. Now the problem here is if, if the history of life is really about about information flow and genes are effectively digital sequences, then genetic information, or information, biological information, could exist in any other medium. It doesn’t have to be DNA. It doesn’t even it doesn’t have to be the kind of molecules we’re dealing with. And we, of course, there are physical constraints. On the way that life might evolve on different planets, different systems and so on. But the assumption is, effectively, that what evolution does is search genetic sequence space and find answers to particular problems, and over time, we’ll come up with pretty much every answer that’s imaginable or physically workable. So life could be any way you could imagine it, any way that it could work. It’s just enough time for evolution to take that path. Then we look at the history of life on Earth insofar as we know it, and there’s plenty of big uncertainties about that, and it shows something really quite perplexing, because life originated again. There’s no specific dates, but around 4 billion years ago, give or take, a few 100 million years either way, but certainly by 3.83 point 7 billion years ago, there’s fairly good evidence that there was life on Earth. We then have a period of, you know, a billion years or so, during which most metabolism seems to arise. Photosynthesis is a little bit more more difficult. And then we have a midlife crisis in the history of life on Earth, the great oxidation event and the snowball Earth. So a real punctuation on a global scale. And then nothing much seems to happen again. It’s actually called the boring billion during which period the eukaryotic cell arose. So eukaryotes are all complex. Life on Earth is composed of this one cell type, plants and animals and algae and fungi and so on, all composed of this cell, the eukaryotic cell, and we share basically all the same kit. If you look at an animal cell or a plant cell under a microscope, they will be really quite hard to distinguish from each other. There are certain plant cells have chloroplasts and they have vacuoles and so on, but they all have a nucleus. They all have endomembrane systems, so things like the endoplasmic reticulum, Golgi apparatus. They all have mitochondria. They all have straight chromosomes. They all have the nuclear membrane with the same the same proteins that make up the pores in the membrane. They all have the same structure to the nuclear membrane. They all do sex, mitosis and meiosis. So it’s incredible, the things that that complex cells all have in common. And you wouldn’t expect that if, if you know an algal cell in an ocean, as a single cell entity in an ocean, you would expect that it would probably have derived from a cyanobacterium, which is a photosynthetic bacterial cell. But no, it actually came from an ancestor that was not photosynthetic, that shared all the same stuff that our own cells have, that then acquired a cyanobacterium late on, which became chloroplasts and gave rise to the plants. So there was something very odd about the history of life on Earth, and it seems to be a constraint, and it’s not my contention. Tomorrow will be if we simply think about the way that bacteria and archaea, the two prokaryotic domains, have explored genetic sequence space. They have explored it more comprehensively than the eukaryotes ever did, and yet there was no straight line, no trajectory towards greater complexity. Instead, we see this singular endosymbiosis, where some archaeal host cells acquired bacterial endosymbionts That went on to become our own mitochondria and changed the potential endpoints of evolution. It’s not necessarily that it changed anything much immediately, but 1,000,000,002 billion years down the line, the end points were plants and animals and complex life. So these are themes which are really astrobiological themes. They’re about life in the universe. Would we expect to see this same kind of thing somewhere else? Is it a freak accident of life on earth? What is it that constrains bacteria in our care? Because, from their point of view, they got stuck in a rut for 4 billion years. Would that happen on other planets, elsewhere in the universe? Well, to know that, we’d need to know what’s the likelihood of life starting this way on earth, and what were the constraints that prevent bacteria from becoming more complex? So these are the themes that I’m going to talk about tomorrow. And I’m not going to give a very I’m going to give a clear answer in terms of probability, because I don’t think we can yet. I would like to leave you with some questions, but I also would like to frame this whole question that we can by understanding life on Earth better and with the right granularity, we can frame questions about how life ought to be elsewhere in the universe, which is testable. It may be wrong. Of course, most scientific hypotheses are wrong, but at least it’s something to test. It’s some way of thinking about it. There’s there’s no prima facie reason to assume that life elsewhere in the universe would necessarily be hugely different to life that we find on Earth. So these are themes that I’d like to throw at you in this I hope we will discuss tonight. Thank you.
Professor Cait MacPhee FRSE 9:48
Thank you very much. You’ve said a singular event, yes, how do we know it’s a singular event and it hasn’t happened multiple times, independently even, and ending up at the same point it’s.
Professor Nick Lane 10:01
Um, so it could have done. We don’t know that it didn’t, but there’s no evidence that it did, which is to say we can see all eukaryotic cells, and they all have basically all of this kit, which means that they inherited it. The only reasonable explanation is that they inherited it from a common ancestor. So they’re monophyletic, and by definition, therefore, had a single common ancestor. Now, people have been looking all around in all kinds of strange and weird and wacky environments to try and find other forms of life. And some people, Paul Davis, for example, has been talking on a shadow biosphere for two decades. People have really gone out of their way to find forms of life that we know nothing about. And occasionally we’ve come across they, not me personally, have come across whole groups of bacteria and archaea which are really quite different to two most known bacteria in archaea, much more simple, probably engaged in symbioses and things, but still recognisably bacteria and archaea. We’ve come across eukaryotes called pico eukaryotes, which are tiny, bacterial size things. So there’s plenty of variation out there, but we’ve never found other forms of complex life. So it’s possible it could have happened on hundreds of occasions, but every time it disappeared without trace. So again, it’s really difficult to put your finger on what’s the probability of these things. All we can say for sure is it doesn’t appear to be a kind of an inevitable outcome of searching genetic sequence space and ending up with complex life in multiple different ways.
Professor Cait MacPhee FRSE 11:39
And does that mean we wouldn’t be expected to be happening on a daily basis, now that we should have things popping up and then disappearing again, where you have some sort of uptake event,
Professor Nick Lane 11:48
I think the I don’t think it would be happening on a daily basis. No. The reason for that is if my ideas, that I’ll talk about in more detail tomorrow, are true, which is to say you require an endosymbiosis between prokaryotes. And what that does, effectively, is internalise respiration, along with the genetic kind of control unit that you need to control respiration, which is a massive electrical charge on membranes on a tiny scale. So you internalise the genes, you internalise the membranes, and those two things together give you the potential to take evolution in a different direction and much further. But the starting point is you’ve got two prokaryotic cells with someone side in the other one. It’s a long evolutionary distance to be working out this is not something that appears overnight. I mean, it doesn’t necessarily have to take more than millions of years, maybe not even millions of years. Evolutionary time is is very difficult to quantify, because we tend to do it by measuring divergence of genes, and we assume a clock, and the clock is accurate some of the time, but definitely not accurate all the time. So there’s all kinds of confounding factors.
Professor Cait MacPhee FRSE 13:07
Okay, and so what do you think Sean this means for searching for life out there?
Dr Sean McMahon 13:14
Well, I suppose it comes down to whether you think that the particular kind of endosymbiotic event that gave rise to eukaryotes was something that was, in any sense, a consequence of any particular factor in the environment that we might then be able to assess how many other planets have that factor, or whether you think it was really just random chance. And I guess with other kinds of endosymbiotic events, like the origin of chloroplast, which I think has happened several times, right in different lineages, I lineages, they do seem to happen more than once. But then, is there something you think that’s particularly special about this, one endosymbiosis event that gave us mitochondria such that it’s especially unlikely to happen?
Professor Nick Lane 13:54
Yeah. I mean, chloroplasts were acquired by a fully fledged eukaryotic cell that already had a nucleus, that already had, you know, it was a large cell, probably a phagocytic cell that was capable of engulfing other other cells as well. And as you say, there have been multiple secondary endosymbioses Where an algal cell with chloroplast gets taken up by a phagocyte. So now it’s got, sometimes they have as many as six membranes around these things, and they come up with crazy, crazy kind of transport systems for getting getting things in and out. So it becomes mad. But there’s plenty of examples of this kind of madness among the algae. And yes, you’re right, it doesn’t seem to be particularly difficult to do that, even saying that it doesn’t appear to be completely straightforward, because these have all already got the chloroplast. So the distance from an endosymbiosis to an organelle like a chloroplast appears to be long and hard. So we know of only two examples, the mitochondria and the chloroplast, the primary. The acquisition of chloroplasts, which were definitely started as bacteria and ended up as an organelle. But the reason I think the chloroplasts were easier and less meaningful in a strange way, is that because they were acquired by a fully fledged eukaryotic cell, that kind of difficult step in evolution to go from a prokaryote to a complex cell, had already happened. So for a prokaryote to pick up another prokaryote, they’re tiny. It’s not much bigger than the first thing. It doesn’t have a machinery for taking them up. There’s no, I mean, that you can imagine benefits, but you can also imagine all kinds of costs. So it’s altogether more tenuous.
Dr Sean McMahon 15:36
If I could follow up, how do you see the role of the nucleus in all of this? I mean, there’s a long list of things that you mentioned that eukaryotes all have, or all did have, and some sometimes have, secondarily lost. It seems as though, from your perspective, the key event in the origin of eukaryotes was the acquisition of mitochondria, rather than the acquisition of the nucleus. But how do those two things interact?
Professor Nick Lane 15:56
Yes, I wouldn’t use the words acquisition for the nucleus. Some people would, because some people have argued that the nucleus is also an endosymbiont, that, for example, there was a delta proteobacterium that picked up an archaeon that became the nucleus, and then it picked up an alpha proteobacterium and became the mitochondria. So there’s, there’s plenty of ideas out there. I don’t think that’s true. Other people do. So, I mean, there’s plenty of arguments in evolutionary biology. The reason I don’t think it’s true is that, in general, an endosymbionts, once it’s inside another cell, its population has been reduced drastically from whatever it was out there to whatever it is in here, and for the nucleus, just one. And what that means is they, pretty much anything put inside a kind of captive environment, loses genes, loses weight. You may say they don’t swell up and steal all the host cells, genomes. So I think that the nucleus evolved in the context of of early eukaryotic cells. Did it arise before mitochondria or after mitochondria? I would say after mitochondria. The reason is, what’s a nucleus doing for you? You can say, well, you put the DNA in it. Why did you do that? Well, to protect it in some way. Protect it from what? Protect it from shear stresses, from free radicals. There’s all kinds of ideas what you might want to protect your DNA from. But then you would say, Well, why didn’t bacteria do the same thing for the same reasons? Why? If it’s an advantage to put a membrane around it and protect it, why wouldn’t? Why wouldn’t you see it happening? And at least some bacteria, not everything, but somewhere there’s nothing, nothing like that. So you got to think of a reason why it would not happen in bacteria, and why would happen in in what amounts to a bacterial like cell, but with an endosymbiont? And there are, there are theories out there. I don’t know if they’re right or not, but, but for example, if the back, if the mitochondria, the early proto mitochondria, some of them are dying, spilling their DNA into the host cell, as a host cell picks it up by standard lateral gene transfer. Which they do? They like to pick up DNA and build it in there would be all kinds of bacterial parasites in there, genetic parasites that could potentially cause havoc in this so whether that’s true or not, it’s kind of immaterial. What matters is it’s not something that a cell that didn’t have endosymbionts, it would not face that problem. So that kind of thinking, I think, is the right way of addressing the question that will be a selective pressure to put a membrane around you and separate transcription from translation, because there’s a cost. You know, in bacteria, they come back, they transcription is where you’re reading a copy of your gene, and translation is where you’re converting it into a protein. And bacteria very often do the same. They do them both simultaneously. They couple transcription and translation, so it’s really fast, and you carry it by having a by having a nucleus. They did the transcription inside the nucleus, and then they ship out the RNA over there somewhere, out into the cytoplasm, and then do the translation over there. So it’s a big time cost in doing that, and so there had to have been a big reason that forced them into doing it in the first place. I just found
Professor Cait MacPhee FRSE 19:18
that question out, though. So from the direction of the questions that you’re asking, it sounds like we’re looking for life out there that looks very similar to life down here. Is there a reason to think it would be the same, and especially if it’s a very unlikely event that occurred for the generation of eukaryotic cells?
Dr Sean McMahon 19:33
Well, we could ask a similar question about the origin of life itself, where, again, we don’t know if it required special, one off unique circumstances, or whether it was something that happened multiple times, perhaps in different ways, and it might be that our form of life somehow out competed its rivals, or ended up monopolising some resource that made it the winner. And we won’t really know the answer to that until we start actually finding. If we start finding evidence of life in other worlds, and then we can start to see whether the basis of that life is very similar to what we have, in which case there might be only one way of doing it or very different. So I would say that one of the motivations for looking for life on other worlds, particularly in places like Mars, where we could actually grab hold of it and analyse it, is to better understand the origin of our own form of life and how special that was. I forgot what your question was.
Professor Cait MacPhee FRSE 20:26
Sorry, should you be looking for something different, potentially? Should you be open to seeing something
Dr Sean McMahon 20:32
Yes, we should be looking for things that are different. And anybody, everybody in astrobiology is very much aware of the need to think outside of our own limited experience of what life can be like. And it’s sort of, it’s almost the first thing we talk about in the classroom we’re raising the next generation of astrobiologists, is what features of life should we take to be fundamental, and which ones should we take to be sort of local contingencies that might be different somewhere else. And of course, we don’t know the answer, right, but at least we’re thinking about it. So yeah,
Professor Victoria Martin 21:00
but John, then I’d ask, like, what are they? What are the fundamentals you think life has to be like? Well, have to be exothermic.
Dr Sean McMahon 21:09
Some of it comes down to just some semantics of what you’re willing to allow the definition of life to include. So it might be things like the ability to reproduce and pass on heritable genetic code, the ability to undergo Darwinian evolution. There are definitions that involve metabolism as well, which I guess might be favoured.
Professor Nick Lane 21:40
Would you think it should be carbon based.
Dr Sean McMahon 21:44
I mean, my own view is not necessary, not in there’s no logical necessity. But it might just be a fact about chemistry. What I mean is that all of the key properties and behaviours that we have learned to associate with life, it might just turn out to be the case that it’s only carbon chemistry that can instantiate those but that’s,
Professor Nick Lane 22:04
I mean, that’s my feeling. It’s not that it’s the only possible way of doing it, and we can have artificial life, robots and whatever, which are not built that way. But if you think about a planet, kind of bootstrapping itself up from a non living planet to a living planet, silicon doesn’t really cut it. Silicon oxides of, you know, sand. You’re trying to build something out of sand. When CO two is, in my mind, like a Lego brick is there in an atmosphere. You pick one, one brick, and you add it on to something. You pick it and it’s got such strong bonds, it’s able to form really complex molecules. Nothing else can do chemistry as well as carbon does and water. Again, it’s such an astonishing solute, solvent that that I you know, it may it’s not that it’s impossible for it to be any other way. It’s just that probabilistically, it seems to me, carbon is also abundant as water. So these things are going to happen time and time again just for chemical reasons.
Dr Sean McMahon 23:04
So we need to keep exploring and keep an open mind about what we might find, and not set up our detection missions in such a way that they’re only able to detect a very narrow kind of line. But at the same time, we’ve got good reasons for thinking that, as you say, carbon is very widespread, water is very widespread. So it’s not as if we have any reason to think that our form of life is particularly chemically unique to our solar system or anything like that.
Professor Cait MacPhee FRSE 23:35
So we were talking before the start of this, and I know there are two questions that we were tapped on. One is, how do we define that something is living in the first place? First place? So what? What is? What? When do we decide it is life? And the other one that we were talking about was the anthropic principle, whether the conditions in the universe that we can observe the way they are, which is apparently very finely tuned to allow life to occur, and is it only there are only those possible conditions. So, Victoria, do you want to take that second on the anthropic principle?
Professor Victoria Martin FRSE 24:05
Yes. So, so I have to say, as a, as someone that doesn’t do biology at all. I mean, my, my understanding here is much more simple, but the anthropic principle is the idea that we are here. We are here to look at this beautiful complexity that is life, and why is that? So? As a particle physicist, I’m trying to look at the detailed properties of inside the atom. Basically, how did the processes that take place down at that tiny, tiny, accessible scale that the scale that we can only see at the moment, either by doing the kind of physics that I do at the Large Hadron Collider, or conversely, by looking out into the universe and looking for kind of astronomical. Astronomical is that the right word? Astronomical observation. Equations. So a good example of trying to explain the anthropic principle is water actually. So water, H, 2o as we all know, has hydrogen. That’s one of the main things in it. And a hydrogen atom is very simple. It’s just a proton and an electron, but because of the charge of the proton, the electric charge of the proton and the electric charge of the electron, that’s why we call it electric charge. It there’s a very specific distance, and also due to quantum physics, but there’s a very specific distance that the electron is typically away from that proton. And if we tweaked things just a little, if we changed the amount of attractive force between the electron and the proton, it the the hydrogen atom might be smaller or it might be bigger, and that would change the chemistry. And a more specific example is we also have heavy hydrogen. So heavy hydrogen doesn’t just have a proton, it also has a neutron in there. And if we tweaked not just the attraction between the electron and the proton, but if we tweaked another force that’s important in describing atoms, it’s something called the strong force, and it keeps protons and neutrons kind of together in the nucleus and the atom, not the nucleus and the cell, the nucleus and the atom. If we tweaked it just a little bit, that’s that strong force that keeps that middle of the atom together, and the different force that keeps the electron circling on an orbit around the nucleus. If those were tweaked just a little bit, the hydrogen atom wouldn’t be that common. Instead, we’d start making helium atoms, which are more protons and neutrons together, and then we wouldn’t have all this hydrogen to make water. And then we couldn’t make Okay, many steps later, beautiful, complex life on Earth, and then we wouldn’t even be able to observe it. We wouldn’t even be able to observe that. We weren’t here to see it. So if we tweak things a little, maybe our universe wouldn’t have the same chemistry. Maybe it wouldn’t have not just the same chemistry, but the same physics, and therefore we wouldn’t even be able to see it in the first place. So a related idea I’ll just bring in here is the idea of the multiverse. So this is a theory that a lot of my theoretical colleagues quite like, which is also related to the anthropic principle. Maybe multiple universes were created, I don’t know how, maybe in the Big Bang, maybe another way, but only some of them, just where the conditions were just right, allowed to grow, allowed to grow into the complexity that we see in our current universe. That allowed to make star forming regions, allowed to make individual particles, allowed to make stars. I’m not saying this in a coherent order here, but allowed to grow the complexity that then we could get a rocky planet going around a mid sequence star that could then start to make cells and eventually make eukaryotes. So, yeah, I think it’s for me, it’s quite compelling that we just happen to be in this really nice universe where we can get to this space where life is possible.
Professor Nick Lane 28:31
Do you think the… presumably, there’s two possible solutions here. One is a multiverse, where you have slightly differently tuned cosmological constants in different universes, and they have completely different endpoints. Some of them are unlivable. Some of them look like ours. Or the alternative is there is only one universe, and those cosmological constants are tuned that way for a reason, and that reason maybe some physics that we don’t yet see underneath what links these things together. Or the alternative, of course, God did it in the first place. So what’s your thinking there?
Professor Victoria Martin FRSE 29:12
She’s very clever. Is God? So, no, I would like to be open minded, because, you know, I don’t have any way of testing either of those theories right now, possibly, I think that that multiverse idea, where everything was slightly different and we we ended up, you know, we evolved because we were in the one that was right, seems more appealing because it’s less kind of having To tune things perfectly. But, no, I Yeah. I’m not at the stage where we’re not at this stage in particle physics or astronomy, where we can start to test, test these things. We can just see that these things are nicely balanced to give us the physics and the chemistry that we observe.
Professor Cait MacPhee FRSE 29:58
Thank you. And to return to that question about when you’ve defined something as being alive or life?
Professor Nick Lane 30:06
I mean, I have spent years resisting anybody who says, tell us what life is. When does it become alive? If you can’t answer that question, then you don’t you don’t even know what you’re studying, and we can’t. There is no two people in this room would have the same definition of what life is, and the standard one which gets used, which you kind of alluded to already, is called the NASA working definition of life, which is a self sustaining chemical system capable of undergoing Darwinian evolution, I think, is roughly that. So I have problems all the way along there self sustaining. What does that mean? I mean, these are smart people. They know that self sustaining is not self sustained, but it’s somehow capable of taking things from the environment to help it sustain itself, but, but I think it’s focusing on the organism rather than the environment, and you need an out of equilibrium environment for it to be sustained. So I think it’s, it’s looking in the wrong direction immediately. And then, of course, the WAGs say, Well, you know, a rabbit is not alive by that definition, because only a pair of rabbits can undergo evolution by natural selection. So you know, so many of these, these ideas, they fall flat on their face if you think about them. And that’s not to denigrate the people who said them, because people are looking for a practical way of going about asking these questions. And the real problem is that we’re always talking about a continuum. And I’ll say tomorrow evening, my own take is increasing. I’ve evolved in this direction. I would now say things that I not only didn’t really think or believe 10 years ago, but I certainly wouldn’t have dared to say them 10 years ago, because I would have feared being an idiot publicly. Perhaps I am still. I don’t fear that so much anymore. What I’m getting at here is, if you start with CO two and hydrogen, and they’re reacted under fairly limited set of conditions, so let’s say 50 or 60 degrees centigrade, and ideally with a with the pH gradient. But I won’t, I won’t go there. Now, what you will get are carboxylic acids that are basically the same things that life uses. And if you start with those carboxylic acids, you can make amino acids from them, basically using exactly the same steps that life uses, but just with metal ions as a catalyst. And you can make sugars from there as well. Again, with just metal ions as catalysts, you can make fatty acids that way, not every step of the way. We’ve been trying to do this for a while. Nucleotides, more problematic. We can do some of it, but not all of it. But the bigger picture here is that a lot of a lot of metabolism, as we know it, has been done in the lab as a few steps at a time, never flux through an entire network, which is what we have to look for. I think we’re a long, long way away from achieving that in the lab. But if you just put in effectively one thing and look to see, what do you get out? If you try and push it through a number of reaction steps, what do you get out? You could get all kinds of mess out of a system like that. What do you actually see are known intermediates down known biochemical pathways. And we keep on seeing this same thing. And what that seems to say is that this is just favoured chemistry. It’s spontaneous chemistry that if you have got the right driving force, this is what will happen. And again, it I find it a little troubling. Is very similar to the anthropic principle, because it effectively says, you start here and you get out, you get out life as we know it. Why is that? Well, you could say, Well, God put the laws of the universe in motion. Or you could say, well, there’s something about the chemistry of CO two. That means it’s a planar molecule. You need to bend it slightly to get it to react, and then this bit’s going to react and it’s going to produce this and before you can more or less follow this chemistry through bond by bond and try and work out what you’re most likely to get. And it’s very limited in my own case, but you do find yourself coming up with this idea that the kind of spontaneous chemistry that you would see in a non living system, in a hydrothermal vent which is not alive, is going to resemble life’s chemistry to an uncanny and rather alarming degree, alarming in the sense that, yes, you can call it. People call it the thermodynamic god. I’m not religious, I should say. But it’s, it’s, I find it this, these themes very interesting. I think it’s very similar to the anthropic principle. And. That it seems to have a direction, and it seems to have an end point, and if you tuned it differently, you wouldn’t go there. So it seems to even biochemistry seems to have been rather perfectly tuned to produce life. And there isn’t a multiverse solution to that
Professor Nick Lane 35:16
problem, different planets. Maybe that’s a well, if the chemistry is the same on those different planets, and so far as so far as we know, it should be both physics and chemistry is the same across the known universe,
Professor Victoria Martin 35:32
I think, I think that’s an assumption that most physicists would make, yeah, maybe what is different in different planets is the the amount of different elements that are there. I mean, yes, so there could be, you know, if there was more, what’s I add? I don’t know what phosphorus or something. There’s a lot of phosphorus on Earth, right? That’s a bad example. No, it’s probably a very good, okay, that’s a good example. You see, I’m learning then maybe, then maybe there would be different processes that could contribute in a different way.
Dr Sean McMahon 36:01
But I think it’s a mistake to get too hung up on definitions of things, because lots of things are hard to define. What’s more useful is to think about what are the properties that we’re going to use as our heuristic to search for this thing? And one of the things that’s troubling about work in the origin of life like the work that Nick does, is it keeps telling us that those very things that we wanted to use as our signature that we look for, that there are actually non biological ways of making that thing, and some of them, in some cases, they had to happen abiotically. They had to happen without biology. Along the road to biology, we wouldn’t be here if those things weren’t possible, non biologically, even things we don’t understand sometimes.
Professor Nick Lane 36:39
And actually, just as I mean, the origin of life field is Riven with disagreements. But what is clear to everybody is that on a on a comet, we find organic molecules and we get the same, you know, some the same amino acids. Sometimes we get nuclear bases. We see the same thing. If you start with cyanide in a Darwin’s warm pond, you get the same sets of amino acids and bases and so on. If you start in a kind of simulating a deep sea hydrothermal vent, you get the same things again. So regardless of the actual reaction pathway that gets you there, regardless of your starting point, you end up with this subset of favoured molecules that life is using, plus a bunch of other things often as well. And so then you have this question
Professor Nick Lane 37:23
that goes against what you were saying earlier, about this being comparatively rare event where something emerges that can then reproduce. When you’re saying that the pathway seems to be directed to form these particular molecules, this is the end point we’re always going to arrive at.
Professor Nick Lane 37:36
So yes, and there are patterns in the genetic code that I will talk about tomorrow as well, which also suggests it arose from metabolism, and it arose through direct interactions in metabolism. But I’ve already said is very difficult to get flux through a biochemistry, biochemical network. We can do a few steps here, a few steps there. I think we’re literally decades away from having a system which can drive detectable amounts of purine synthesis, for example, starting with CO two and hydrogen, going right the way through this network. And once we’ve once we’ve got nucleotides, you then need to polymerize them to get RNA, or some equivalent. But I think we would get RNA, and from there, you need to have selection start. You need to get ribosomes. You need to, you know, you’ve got all of this machinery in cells. Now, the fact that we see favoured chemistry at the very beginning of this, in some sense, you’d have to to get all the way down here, but, but it doesn’t mean to say that ribosomes are inevitably going to emerge from a system, I think it potentially is likely that they will. And I suppose there’s inevitably a bias that why would you work on the origin of life if you didn’t think it was a soluble problem? So there’s some self selection going on. There’s
Dr Sean McMahon 38:58
an interesting kind of methodological issue here, that when you try to explain why some historical event happened the way it did, you try to come up with plausible seeming explanations, and the very act of doing that makes those events that you’re invoking seem as if they were likely to happen, but you’ve got no alternative if you’re trying to explain why something happened, than to come up with a plausible story why it would happen that then makes it seem sort of inevitable.
Professor Nick Lane 39:23
Yes, I mean, we can go back to water, for example. You know, it’s an astonishing solvent, and we don’t really know very well what water is doing in cells and the structural properties around proteins. There’s all kinds of things that water is doing that. Do other solvents do it? Not to my knowledge, they don’t do it nearly as well. So what exactly is it about the chemistry of water that allows all of this stuff to happen? It seems, again, favoured in some way. It’s hard to put your finger on exactly what it is. It’s definitely worth spending a lot of time. And trying to figure out, what on earth is water doing in this system, and is it really indispensable, or is it simply that it’s abundant and other things could do the same job
Professor Cait MacPhee FRSE 40:10
in the 20th century that physics was done. It was finished. We knew everything there was to know. We don’t understand water. So something else that we touched on very briefly was the going beyond the generation of a self replicating system, but a self replicating system that can think and that can interact. So this what is thought, What is consciousness, and how does that know?
Professor Nick Lane 40:36
So this is another thing I’m going to touch on briefly at the end of my talk tomorrow, and I’m not going to touch on consciousness properly, because that’s well, I can’t answer it anyway. But the reason I’m even interested in it is that it turns out that anaesthetics affect mitochondria, which, which I didn’t know. It’s a few beautiful things here. Nobody knows how anaesthetics work. We’ve been using them for 200 years, and we don’t know how they work. Well, again, there’s ideas out there, but none of them have been proved, and they’re all a bit dodgy. So I become interested, because I’m interested in mitochondria, and if anaesthetics are affecting mitochondria, then, why would that be? Is it simply that they that there’s a kind of an energy failure that they prevent ATP synthesis, so the system shuts down? That would it will be important if it’s true, but it’s a bit dull. The interesting thing to me, though, is that you can anaesthetise single celled organisms. You can anaesthetise amoeba. Well, suppose we don’t really know if we anaesthetise them or not, but they’ll stop moving around, and when you take the anaesthetic away, they’ll start again. So in behaviorally, it’s similar. We’re working on fruit flies, and you can do exactly the same thing with fruit flies. They will go to sleep and they’ll wake up again, all of which kind of says it’s not just about neural nets. There’s something at a deeper level, perhaps a cellular level, that anaesthetics are interfering with. And mitochondria, of course, were bacteria once they were acquired in this endosymbiosis of the origin of the eukaryotic cell that I was talking about. And so the membranes inside mitochondria that are generating this electrical charge, which anaesthetics are playing with, is the plasma membrane in bacteria, the membrane which surrounds the cell. So it’s the interface between the outside world and the inside of the cell. It’s what some very smart people working in recent years on consciousness through a thing called the free energy principle, which, again, is something that, as my ears prick up as soon as someone says, free energy. So, so this is the idea that, effectively, outside the cell, there’s all of this stuff happening, and inside the cell you’ve just got molecules, you’ve just got metabolism happening somehow, it has to interpret what’s happening out there and understand it well enough that you can behave better than random. You can move over there or stay where you are or do something, and it’s better be better than random, otherwise you’re just going to die. And I think most biologists would agree that feelings, in some sense, are real. We don’t know what they are. We don’t know physically what they’re made of, but they seem to be real. They seem to have evolved. And if they evolve by natural selection, and I don’t doubt that, then what selection must be able to see them? They must be physical. If natural selection can physically select this over that, because it’s better than that we should be able to measure it. The thing is, we don’t know what we’re measuring, and what we try to measure is firing of neural nets, but that’s not relevant to an amoeba. So I just find myself thinking about, what does a bacterial cell need to do if it wants to make a decision and it’s got, I mean, extraordinary number of chemical reactions going on inside about a billion a second, second after second after second, all of these chemical reactions, it must be chaos, but it’s not chaos. Somehow. It’s really well organised and ordered in phase and synchrony in some way. So how does that happen? And most people would say, well, genes which code for enzymes which but it’s, you know, you’ll still die if you take the oxygen away, you it’s really about the drivers of flux through metabolism. So what’s doing that in the end, it’s the membrane potential, which is driving ATP synthesis. It’s driving the energy, but it’s also being generated by metabolism, and it depends on, is there oxygen out there? Is there food out there? Is it too hot for me? Is there a metabolic poison out there? So actually, what respiration is doing is effectively matching metabolism to the environment. It’s effectively giving you, in some sense, a readout you said, Who? Was doing the reading earlier on, slightly more problematic, but it’s giving you information on your state in relation to the world. And it’s a single readout, in the sense that it’s basically, it’s the it’s the electrical potential on that membrane, and possibly the moving of charge on that membrane. So it’s, it’s telling you your overall state is so is that right? Is it wrong? I have no idea. Is it what it has is some explanatory power, which is to say, if, if you try and do everything as a bacterial cell by, by, effectively, feedback loops, positive, negative feedback loops, and you say, okay, I can detect there’s not enough oxygen. So I’m going to go over there, but you have a different system, which is saying, No, there’s plenty of food here, though, so stay here. And a different one which says, but there’s a metabolic poison, so go over there. And another one which is saying, It’s a bit hot here, maybe you should think about going over there. And another one that says, but I’ve got lots of iron. I’m really healthy. I’m quite young. I haven’t really, you know, I haven’t. Haven’t become decrepit yet, so I can handle all this stuff. So you’ve got all of this kind of conflicting signals, and somehow you’ve got to make a decision, fire up your flagellum and paddle over there, if that’s what you want to do. So I think that the information processing going on in bacteria is way beyond what we would normally ascribe to them. We would normally just say it’s all hard wired feedback loops. And I think it requires much more than that for them to operate. And I think the kind of things we’re dealing with then is the output of metabolism, the membrane potential, the electrical charges, potentially, the movement of charge, the fields generated by which are giving you a read out of your state. And and that can then be the simplest possible, imaginable form, if you like, of an idea of a feeling I’m good or I’m bad, I should stay or I should go. So that’s how I was thinking about that.
Professor Cait MacPhee FRSE 46:52
Okay, so we’ve touched upon a number of elements that are going to be discussed during the lecture tomorrow. So we’ve discussed both the apparent inevitability of a living system coming into being, and also the extreme unlikelihood of it happening in the first place, and that the conditions of the universe are ideal for this happening, but maybe not in the multiverse and alternative universes. And we should be looking for life as we know it out there, but potentially it looks like something else entirely. So there are lots of questions still to be answered, and we now want to answer your question. So does anyone have any questions for our panel? And can you please wait for the microphone to come to you? Yes, in the middle here,
Speaker 4 47:41
Professor lane is very keen on mitochondria. Now let’s say a spaceship lands in Princes Street, gardens, out steps the pilot, it’s an interesting creature, and it’s interesting because it’s big, and if you’re big, you’ve got problems with surface area to volume. And the way that we’ve solved Well, the surface is where you take energy from the environment and turn it into something you want to use ATP for us or whatever. So you need a big, big surface. And the way we solve that problem is mitochondria. Now, can you think of other ways in which you solve the same problem without having mitovonchondria? Or, yeah,
Professor Nick Lane 48:30
I can, but they, I don’t think they’re very easy. So what we actually see there are giant bacteria out there, and these giant bacteria can be larger than eukaryotes cells, and they always have what’s called extreme polyploidy, which is to say, literally 10s of 1000s of copies of their complete genome right next to the membrane. Pretty much always right next to the membrane. So that’s what mitochondrial DNA does as well. You’ve got a tiny genome. It’s got effectively, no genomic weight. It doesn’t take much effort to copy it. It doesn’t take much kind of energy to express it and to make proteins from it. So you got it was a bacterial genome once, but you’ve lost all of these overheads. So on multiple occasions, we found giant bacteria with extreme polyploidy. The problem seems to be that just being bigger for a bacterial cell is not, not very helpful. It slows you down. Just being larger is no benefit. And and then, why do they have extreme polyploidy? I think it’s basically because to be a bit bigger and to have a transport network where you’re transporting things over there very often is not going to give you much payback until you’ve really got a system that’s working, it’s much easier just to duplicate your genome and do the same job right next to each other. That’s the kind of shortcut to make yourself bigger, and then you don’t need to transport things around the place. So we see this repeatedly. We also see in bacterial plasmids. So you. Think, okay, so why couldn’t you just put a lot of plasmids next to the membrane? There will be a solution to the problem. So well, it wouldn’t actually be a solution to the problem, because what we if you’ve got multiple plasmids next to the membrane then, and you’ve got a really big membrane now with a large surface area, if what you require these these genomes to do is to control the electrical potential on the membrane in our own cells, of mitochondria fused together into a network, and so you might have a single mitochondrion, branching mitochondrion inside a cell. If you prevent that from breaking back down into individual mitochondria, the cell will die. The reason it dies is that the mitochondrial network effectively breaks down. It doesn’t it doesn’t function. Well, why is that? We don’t really know. But if you’ve got hundreds of genomes all contributing to a shared phenotype, which is to say, the membrane potential of this and you accumulate mutations in those those genomes, then there’s no way of saying, Okay, well, you’re broken, you’re broken, you’re broken. You’re broke. I’m going to break you down. If you fish in the network again and you end up with one copy of mitochondrial DNA in a little sausage shaped mitochondria that they show you in the textbooks. And if it can, if it can generate a membrane potential, it’s good, it can rejoin the network. If it can’t do that, then it sits there limply and gets targeted for breakdown by what’s called mitophagy. So it’s a kind of a genotype phenotype relationship. So a giant bacterium that put a load of copies of its plasmids right next to the membrane would break down. For that reason, what you’d have to do would be invaginate the membrane and enclose it inside a compartment so that it was capable of having its own genotype phenotype relationship. Now that’s in principle, possible. In practice, it’s never been seen, nothing like it has been seen. And endosymbiosis kind of solves the problem much more simply.
Dr Sean McMahon 51:55
No, it’s more that we started out by saying that the origin of mitochondria was also something that’s never been seen and something that we only know it. We only know it’s happened because it happened once, as far as you know, once in our history of also, what I really like about the question is that it draws attention to this problem of having key steps in the evolution of life that seem to involve very improbable events, because it means there could be lots of other very improbable events that would give you a completely different kind of life that we’re never going to see in the lab, because they’re very improbable. And we look at our own history and see events like that, it should just make us it’s another thing that should make us open minded about different ways things might be.
Professor Nick Lane 52:35
I mean, I completely agree with you about being open minded. I’m not. The reason I’m not is not that I’m it’s not that I’m closed minded as such. I am very willing to be wrong. I would like to be wrong. I think it’s really important as a scientist to be wrong and to be the first to admit you wrong. But I think there’s a tendency to go the other way and to say, Well, you’ve got no imagination. Life could be all of these different things. And you small minded person are saying it’s got to be this way for this little reason and that way for this little reason. And you know, I just lack imagination. And to some extent, that’s true. Obviously it’s true, but I do think that there’s something scientific about saying, Okay, well, why? And we kind of agreed with this earlier on, why is it? Does it have to be this way? Now, what I’m effectively claiming, in terms of the mitochondria is that life requires charges on the membrane surrounding a cell. Now I’m uncomfortable with that. It’s Is it true? The reason I wondered about it in the first place is, why on earth is life set up this way? Why on earth does life, all life, on earth, pump protons across a membrane and then power everything else by the protons coming back through molecular machines. It’s an incredibly complex system. It’s really hard to imagine how it started in the first place. So it became an obsession. So why does it work that way? At the origin of life, I’ve come to think that it’s actually about making hydrogen react with CO two. It’s nothing to do with ATP synthesis, nothing to do with molecular machines. It’s about the basic mechanics of chemistry. How do you get these two fairly inert gases which thermodynamically will react with each other, but kinetically are very stubborn. So now a difference in proton concentration across a membrane, in principle, can make that happen. And then what I was saying, which I think is a slightly stronger idea, then how do you know, as a bacterial cell, what all of your metabolism is doing? So if you were to say life is going to be carbon based, it’s going to be in water, it’s going to be the same kind of intermediates along a metabolic pathway. It’s maybe not exactly the same, but these kind of things. Things, and it’s going to have to be at a tremendous pace, a billion reactions a second in a single bacterial cell. How do How are you going to establish control over that system? And this is where things like a membrane potential is beginning to give you something that feels to me more real, more believable as a force that would be generalizable for life.
Unknown Speaker 55:20
In the spirit of bringing in, yes, I beg your pardon. Do we have more questions? Please? Yes.
Speaker 5 55:31
Thank you for the for the discussion. I had a question about the professional aliens sort of take on the monophyletic origins of eukaryotic cells, if, if we have these certain set of rules, not rules but but dynamics that will always sort of push life in a certain way, because of constraints on earth or because of the availability of elements, wouldn’t every time life gets created look the same. So like, in the sense that if I take sugar, milk and flour and make a pancake today and do it again tomorrow in a year’s time, how would you know that these are not how would you know they’re the same stack of pancakes, so they’re different pancakes? So, so wouldn’t the monophyletic origin also, in a way, prove that there is a set of fundamental rules and how life gets created? That’s a
Professor Nick Lane 56:23
very interesting question. My instinct is that there are too many weird and wacky things at the level of protein structures to say that it was this convergent evolution that in the endoplasmic reticulum, there’s all of these proteins. They do the same job, and in terms of the amino acid sequence that makes them up they all share. So for there to have been multiple origins of pancakes, multiple origins of eukaryotic cells are then convergently evolved towards the same thing, because they’re forced to, because that’s how you make a pancake. That’s putting a lot of faith in convergent evolution, more than I would have so I think it really is shared ancestry, but it’s a good point. And I would have said, if we were to find life on Mars and it had a similar but different genetic code, I would have said 10 years ago, that was evidence for contamination between Mars and Earth, and the chances of two different forms of life having a similar genetic code would be astronomically unlikely. Now I’m obliged to say, because of the nature of my own hypothesis, that I think it will be likely that they would be similar. I’m very uncomfortable with that conclusion. But if you know this is the interesting thing about any scientific hypothesis, it pushes you into a corner. And then you either think, Okay, I’m in the wrong place here, or you think, right well, I honestly think I’m in the right place, in which case it’s an interesting
Professor Cait MacPhee FRSE 57:53
Further questions, yes, please.
Speaker 6 58:00
I think you’ve described how carbon formed early forms of organic acids and this and that, and you’ve talked about life, but my personal interest is, how do you get from that to the double helix in DNA? To me, DNA is a weird and wonderful thing. I mean, am I not correct in the early days with somebody who thought there might be a triple helix or something else? So how can is it something to do with the chemistry of carbon that you must have a double helix? Because, as they understand it, you look at a bit of a leaf of a tree or a dog or something. We’ve all got these double helix so I’m sort of floundering. Is, how did the double helix arrive?
Professor Nick Lane 58:50
Again, it’s a very good and difficult question, and we don’t have an answer, and I specifically don’t have an answer, but we are thinking about it in broad terms, because most people think RNA came before DNA, and RNA, it can form a double helix, but not a long one, and it tends to form more interesting molecules that look a bit more like a protein. They’re twisted on themselves. They do all kinds of interesting things. So there’s been an idea in the origin of life field for decades called the RNA world, where RNA is effectively copying itself, but also doing all kinds of catalysis. And I’m not a big fan of the RNA world, but it’s very clear that RNA is really central in biology. And I would also agree it’s probably likely that RNA came before DNA, in which case, then you’ve got this question of so what were the driving forces? You start out with random bits of RNA. We know the end point. We know you have different types of RNA. So you have messenger RNA which makes there’s the code for making the proteins, but we also have ribosomal RNA which make up the ribosomes, and then transfer RNA which binds amino acids and as part of the machinery for making the proteins. Yeah, and then DNA. So what are the forces driving that divergence? Now, the DNA double helix is incredibly stable, far more than an RNA helix is, and it’s partly and this goes back to Crick and Watson’s original papers. They commented, you cannot get a double helix because of that hydroxide group on ribose. So you take out the hydroxide, now it’s deoxyribose, and you get a stable double helix. I think they were slightly wrong, but the idea is basically basically true. So Crick also came up with a really interesting hypothesis called the wobble hypothesis, where he considers alternative because at the third position you sometimes see alternative binding of different bases and the hydrogen bonds are slightly different. And Crick seems to have asserted that these are too close and therefore won’t happen. These are far enough away that they could happen. Therefore these are the places where we will see wobble. And he was basically corrected by the whole lot. He just seems to have been intuition that this is too close. I don’t know why he thought it was too close. So there’s an awful lot of distance you can go by knowing the distances between atoms in these things, and to some extent, those bases are included in DNA because they will form something which is so stable as a double helix. But again, it’s a little bit anthropic principle, like, isn’t it?
Professor Victoria Martin 1:01:31
Isn’t it minimising your free energy? I
Unknown Speaker 1:01:33
guess it is. Yeah, I think that was a very bad answer. But anyway,
Unknown Speaker 1:01:41
other questions please Yes.
Speaker 5 1:01:51
Thank you. Thank you. Fascinating discussion. My question at its core is pretty basic, how would the panellists define natural selection like, what is it? The other parameters for the finding life that have been suggested, they’re all quite easily recognisable, like a self sustaining unit, even if we question that, it’s maintain maintains integrity over a short period of time. And a was the third one. There was anyway, the natural selection one I’m I’ve always been fascinated by, how do we define, how do we think about natural selection? And I think a really interesting way of framing that that’s coming out of this discussion is, what would it look like? What are we looking for? If we look for natural selection as a way of defining what life is, and then that takes me to we can only recognise natural selection in time change over time that matches a changing environment, and does that then mean that we could only recognise life in other places, or life different from our own over time, that if we were looking at it in a specific sliver Cut of time in the present, then we couldn’t define it as life, because we couldn’t say that it had natural selection.
Professor Cait MacPhee FRSE 1:03:27
So this notion of your alien coming down and landing in the spaceship and being a big blob, if we only see that,
Professor Nick Lane 1:03:36
I mean if we only see that, I think you know if it’s live or especially if it’s got a gun. But do you want to have a go at natural selection?
Dr Sean McMahon 1:03:44
Yeah. So if you have a population of entities that can vary amongst themselves in some respect, that confers a higher or lower probability of reproducing, and when they reproduce, they pass on those very properties, then that population will undergo natural selection, such that, over time, the more successful variants tend to propagate, and the less expensive variants tend to get, sort of weeded out. That’s not really a definition, but it’s it’s a little story about what natural selection is. It’s something that we observe only in populations and not not in individuals like the rabbits you were talking about earlier, but just on the point about natural selection as a bio signature, there is a paper that proposes an experiment that you could do with a land emission on Mars, where, a bit like the Viking experiments in the 1970s you would inoculate, or you would take a soil sample and you would Add some nutrients to it and look for the growth of the microbes by looking for the activity of respiration. But then you would keep doing it. And what you would observe with a soil sample on earth is that depending on the nutrient that you supply and the conditions that you create in your experiment, initially only some of the microbes in the. Population will be good at metabolising that nutrient and growing in that set of conditions. But if you keep doing it over time, you should find that the population actually evolves to get better at metabolising the nutrient that you’ve given it, and so you’ll see an improvement in the rate of respiration over successive generation. So that’s actually an experimental design based on that for detecting life by looking for evolution, because microbes evolved fast enough that you can observe it over days and weeks. It’s a bit of a niche idea, but it
Professor Nick Lane 1:05:28
is out there. Just one thing to say about natural selection is I’m in a department of evolutionary biology full of population geneticists, and it rubs off. And one of the, one of the, I mean, one of the problems that I have with the RNA world, for example, is that when people have done experiments of natural selection on RNA, what tends to get selected, the fastest replicators, they’re actually it goes back to Sol Spiegelman in the 1970s and they became known as Spiegelman’s monsters. And you can start with almost anything. You can start with a whole virus, and you can give it nucleotides, and you give it the RNA polymerase praise enzyme, and you end up effectively evolving towards the binding site for the RNA polymerase enzyme. So it makes copies of itself at a furious pace, but it doesn’t involve greater complexity. It doesn’t involve kind of coding for metabolism or anything like that. Only if you put these things so they share a fate inside a cell, for example, or inside some other kind of compartment, so that the only way they can make a copy of themselves, as if the larger entity can make a copy of itself. The cell is capable of replicating, and selection is not at the level of the bits of RNA sequence inside it is at the level of the cell reproduction. Then, in principle, you can, you can get evolution by natural selection. So this is again, stuff that goes back decades. It’s pretty much all theoretical, mathematical population genetics. I don’t think anyone’s ever really done it as an experiment, but the idea that as soon as you’ve got genes, anything can happen, natural selection will take you to wherever you want to go, is lazy. At the very least, it doesn’t work that way. There’s constraints on what can or cannot evolve, and we don’t know those constraints well enough.
Professor Cait MacPhee FRSE 1:07:33
Further questions. Do we have any questions online? Okay, if you are watching online, please put any questions in the chat? Yes, please.
Speaker 7 1:07:44
So we open with the idea that endosymbiosis spent life or career exploration of genetic phase space. When you look at sort of the limits to life in extreme environments, you find that eukaryotes generally sort of go toe for toe with the prokaryotes, except for the high temperatures, where eukaryotes sort of had this hard limit, about 60 degrees Celsius, where we see prokaryotes Galloway do it 122, any intuition as to why endosymbiosis seems to have hampered eukaryotes with this one extreme.
Professor Nick Lane 1:08:12
I mean, they’re just simply much larger, much more complex, less robust. Don’t have I mean, some fungi and plant cells have a cell wall. The yeast, which can get up to about 65 degrees. It’s fungus with a cell wall. I guess it’s just simply, the more the more complex moving parts you have, an endomembrane. You know, the membranes are five nanometers thick. It’s five millionths of a millimetre. And eukaryotic cells are absolutely stuffed with these things. You heat them up and you go through all kinds of phase transitions, or they will fall to pieces completely. But also their permeability to ions will change above certain temperatures. So bacteria and archaea are fairly small, fairly simple, limit the membrane area. They’ve got very effective pumps and so on. So they’re basically, they’ve evolved to deal with what we would call harsh environments. And eukaryotes, effectively, don’t go there. They can become animals instead, run away. Bacteria, don’t go there.
Unknown Speaker 1:09:19
Further questions, please, yes, there’s one in the middle as well.
Speaker 8 1:09:26
Yeah. So the Fermi Paradox suggests that if life exists, then why can’t we see it in our galaxy? Because with technology not much more advanced than ours, a planet could colonise the entire galaxy in around a million years, and there are probably billions of planets in our galaxy that we’re aware of. So where is it as the questions so the question here is, do you believe the limitation is in our past, or as in our biological past, or since we’ve become sort of intelligent?
Professor Victoria Martin FRSE 1:10:02
We go at that. I want to have a go at this. I do so do I believe it’s in our past or its future. I mean, I think that is telling us that there is not hyper intelligent life like we are very close by to us. Otherwise, we really would, would have seen it, which would probably suggest that life is, as we’ve been discussing, or or intelligent life, quite rare, quite a rare process that has only happened once on Earth. And I think that’s probably what I would take away from that. Also, they might just be really far away. I haven’t seen them yet,
Unknown Speaker 1:10:48
hyper intelligent like us.
Professor Victoria Martin 1:10:50
Hyper intelligent like
Unknown Speaker 1:10:51
us, stupid like
Professor Victoria Martin FRSE 1:10:55
both. We have the power to
Professor Nick Lane 1:10:58
be both. There’s one thing out there they would inevitably destroy themselves, but if they’re anything like us.
Professor Cait MacPhee FRSE 1:11:05
So we’re talking about a long timescale as well, though. So as you say, is it just the fact that things have finished before we’ve even started looking, or things are going to start long after we’ve
Professor Victoria Martin 1:11:14
gone so yeah, I mean, that’s true. We’ve only had the technology to to kind of look for other intelligent life for the past, not the past century. I mean, probably less than, less than that. So that might also give us a restriction from how many civilizations we might have been able to see there are
Professor Nick Lane 1:11:38
people like Abby Loeb out there who say they’re all around us.
Speaker 3 1:11:41
My favourite hypothesis about this is that they are all around us and they just want nothing to do with it.
Professor Nick Lane 1:11:48
I think, in relation to the Fermi Paradox, Leo Szilard answered him, apparently at the time, and said, They live among us. They call themselves Hungarians. He was Hungarian. Further
Unknown Speaker 1:12:07
questions, please. Oh, sorry if I missed one.
Speaker 9 1:12:16
Further Yes, thank you. I have a question about the chirality of the molecules, so the DNA, RNA and proteins that the life uses tend to be all homochiral, and Wouldn’t that suggest like a monophyletic development, or that there’s been a selective pressure of selecting that particular molecule and not the other chiral molecule?
Professor Nick Lane 1:12:44
I’m happy to have a go at that. You might want to have something to say. I think the there was a beautiful experiment done quite recently on on what’s called chiral induced spin selectivity on magnetic surfaces, suggesting and this was from some people who disagree with me about the origin of life. They’ve got their starting with cyanide. And as you go along this pathway, one of the intermediates along this pathway is capable of crystallising out and concentrating to quite high concentrations on mineral surfaces. If those surfaces are magnetic, then you tend to select for one chiral form over the other chiral form. And if you repeat this cycle of kind of washing it off and crystallising it on again, the surface becomes more magnetic, and you select more strongly for the chiral forms. So I you know this, I don’t think they can be right, because I don’t agree with their chemistry, but I you know, the experiment is real and it’s beautiful. It’s a beautiful piece of work. And maybe I’m just completely wrong. Anyway, I don’t have a kind of an alternative hypothesis at the moment to this, but it did get me thinking about it. And one thing which has become clear is, if you, if you’re starting with metabolism, and you’re making 20 different amino acids, and you’re you’re imposing chirality in those pathways to make all 20, the likelihood of you ending up with the same chirality every time is very small, and it will be very messy. It’s far more reasonable to say there’s actually, if you’ve got a if you’ve got a proto, you’ve got tRNA, and you’re beginning to make peptides. If the sugar is right handed, then you tend to select for the left handed amino acids. So it’s just a matter of the way that the effectively the gloves fit together in a line. So there’s only one point in metabolism that you would need to impose chirality, and that’s in sugar synthesis, because that goes all the way through to ribose, and that says what the backbone of RNA is, and that says what the chirality of amino acids is going to have to be. So. Yeah, so, so it’s become a, I think is a problem at the at the beginnings of metabolism. I don’t have an alternative. I love the idea that it’s magnetic fields. I love the and the fields they were using were on Iron sulphur minerals, which is exactly the kind of thing I think about. We’ve been doing some experiments to see if we can select for one form, one chiral form or the other on Iron sulphur clusters. But so far, we haven’t succeeded. But that one point in metabolism, did it have to be a D sugar or an L sugar? Was it selection, or was it a random choice at that point? I don’t know. I think it could have been either way. There are people like George Church and others who were trying to make mirror life, which has been banned in some places, I think it’s kind of an interesting, interesting question. My feeling is that it’s it’s probably not under selection, that it’s pretty much a random decision, but it’s probably only one in all of metabolism, where you make that random decision and everything else follows. Yeah, I think
Speaker 3 1:16:03
that sounds sounds right to me. I think it’s it’s a bit like which side of the road we drive on. We can all decide to drive on the left, or we can all decide to drive on the right. Either of those is going to work just fine. What we can’t have is some people driving on the left and some people driving on the right. That’s going to be chaos. And it was probably the same in biology. So it just kind of had to pick one further questions, please, yes.
Speaker 10 1:16:29
Has it something to do with our existence and even that of complex life on earth being just a blink of an eye compared to the 14 billion year age of our universe?
Professor Victoria Martin 1:16:41
So actually that was something we were discussing before we came on. And I think, yes, I think we currently live at the kind of high point of the universe where we’ve had long enough for the universe to evolve, to make stars, and then for those stars to collapse, and then for them to combine into black holes and brown dwarfs that then can react and make even, even more complex elements, and then we can form the main sequence stars that our Sun is one of. Eventually we were actually talking about, like, how will it all end as well? And there are lots of different theories there, but possibly the universe will just expand and expand and expand forever, and then we just won’t be able to see we, you know, if, if Earth was still existing at that point, we would drift so far away from the Sun that there would be no light and heat on Earth to sustain life, but eventually even the earth might just drift into lots of little pieces of of not sand, but of different things. So there is no life anymore. So I do think that we’re sitting at this, this beautiful time, 13 point 8, billion years after the beginning of everything, where we happen to live in a great planet that managed to make life, but if we’d done this, I don’t know, 6 billion years ago, well, earth wouldn’t be here, but we wouldn’t, you know, the kind of planet that would have been there, wouldn’t have the same complexity to allow this. And if we do this in another 13 point 8 billion years, then probably we also don’t have a planet that’s just got the right constituents to make life as we know it here now, my feeling so I don’t have proof for all of these things, but Just to
Professor Cait MacPhee FRSE 1:18:41
expand on that a little bit. So as I understand it, I might have it wrong, and a billion years is quite a long time, but almost as soon as the Earth cooled enough to sustain life, life came into being pretty fast, as I understand, at least simple life. So does that again, add to the idea that it can it’s fairly easy to do easy. I mean, when I say quick, I know I’m talking about millions and millions of years.
Professor Nick Lane 1:19:07
You can apply the anthropic principle to this as well, which is to say, Well, we had to be on a planet where it was fairly quick. We don’t know. I mean, you touched on one thing earlier on, about the relative timing of things. How is the origin of eukaryotes driven by an environmental change? Or was it? Was it a pure chance? Roughly, was, I think you said, and the answer to that, I’m actually going to probably finish my talk tomorrow with this, because we don’t know the dates of anything with very much certainty. So 20 years ago, I was writing a book called power, sex, suicide. And at the time the it was actually about mitochondria. You knew that. And at the time, in. Far as there was an agreed date for when eukaryotes arose, it was around about 2 billion years ago. And this goes back to Lynn Margulis, who said, well, there was the great oxidation event, when there was a massive upheaval and a lot of oxidised iron on the surface of the planet. So eukaryotes arose soon after that. And she talked about an oxygen holocaust that all the anaerobes got wiped out. There’s not much evidence for that, but the idea that the conditions change leading to eukaryotes became was a persuasive one. The dates coming from phylogenetic trees pushed it. So the you know, the weight of evidence was suggesting 1.2 to 1.5 billion years ago, that would be any if you ask people in the field doing phylogenetics, they’d say 1.2 to 1.5 so where seven or 800 years, million years after the after the great oxidation event, in which case it doesn’t look as if it’s following hard on the heels of it, those dates are drifting. Earlier. Again, one of the more persuasive papers was 1.9 to 2.1 so if they’re right back right after the great oxidation event, and we don’t know when photosynthesis arose, that drifts around in time as well. It could have happened immediately before the great oxidation event and then a catastrophic, global kind of conflagration happened because oxygen accumulated and oxidised everything. Or it could have happened more than 3 billion years ago, or 3 billion years ago. And then there’s these little traces of oxygen. They call them whiffs of oxygen. So if you were to take two extreme views of this, one of them, you have photosynthesis fairly early, followed by a billion year gap, and then then the great oxidation event, followed by another nearly a billion years. And then eukaryotes, then a few 100 million years, and then animals, the train of causality that’s implied by that says none of these things had anything directly to do with each other. Whereas, if what you have is photosynthesis arises right before the great oxidation event, then you have this global conflagration, and eukaryotes arise immediately afterwards, and then you have one and a half billion years before you get to animals. The implied causality is really different, and we don’t know yet. We don’t have any certainty about which of those dates is correct. I’m inclined to think eukaryotes arose quite soon after the great oxidation events. And what that would say, everything I’ve said, I don’t disagree with but I but are you, which is to say they’re monophyletic, for sure, but you could have a set of environmental conditions that pushes types of cell together in ways that they hadn’t been pushed up next to each other before, and then it happens pretty quickly. In other words, it’s not that improbable when the conditions are right and off you go. But then you’ve got this tremendous, long wait before you get to animals. So now you’ve got a different bottleneck that says, Okay, well, eukaryotes wasn’t the main bottleneck, but there’s another one.
Professor Cait MacPhee frse 1:22:50
Now we have a very quick point, and then we’ve got time for one more question. So if you have a burning question,
Speaker 3 1:22:55
was the proto mitochondria and an aero an aerobe?
Professor Nick Lane 1:23:01
That’s a loaded question, which I’m going to just unpack a little bit for you. So all modern eukaryotes, I mean, all of us, are aerobic, but there are also anaerobic eukaryotes out there as well, and they mostly live in stagnant muds and places like that, and they don’t use oxygen at all. Or sometimes they use oxygen occasionally. They’re called facultatively aerobic. Now, if eucharis had arisen in an anaerobic environment and had stayed there for a long time, they would undoubtedly have lost aerobic respiration. So they can’t have started in an anaerobic environment if it had been the other way around. And they started in an aerobic environment, and then different ones, kind of, later on, adapted to an anaerobic environment, then you would predict that the different anaerobes would not have much in common with each other in multiple and it seems that they do have a lot in common with each other, which says they weren’t in an aerobic environment either. So they were probably in an environment where it was between the two, kind of on the edge of a stratified ocean, just between anoxic down here, aerobic up here, and you’re just playing your business around.
Speaker 3 1:24:11
But it’s sort of implying a requirement for oxygenic photosynthesis beforehand, I guess is what I was hinting at,
Unknown Speaker 1:24:18
I would say. So yes,
Unknown Speaker 1:24:19
we got one final burning question.
Speaker 11 1:24:28
Hi. So we talked before about the problems with definitions and why life is very hard to define and you need to use a working definition. But to go back a little bit, you mentioned consciousness. So I was wondering in this context, what your work and definition of consciousness is? Because when you talk about it in terms of like interactions within the environment and sense and in decision making, that feels like, almost like a kind of like control theory, almost like cybernetics definition. And I was just wondering what your working definition
Professor Nick Lane 1:24:58
is, again, I don’t have one. So. I is going to be very frustrated by my answer. And consciousness is, you know, is all things to all people. And what I really focused on is, is what is a feeling, because that’s, that’s what’s being called the hard problem in consciousness. And we simply don’t really have a physical explanation for what a feeling actually is. Is it a if it’s a depolarizing neuron, if it’s generated by a depolarizing neuron, what is it about calcium ions or sodium ions or potassium ions crossing a membrane? What exactly just happened then? And if it’s a neurotransmitter, why this one, but not that one and so on? So there’s nothing in chemistry as we know it that can explain that. But this is a really limited aspect, I would say, of consciousness. And I you know, by by saying, Could bacteria have the simplest imaginable form of a feeling or agency in that sense? Because I was, I would say that the ones which can paddle away can do something if you can sense your environment sufficiently quickly that you can do something about it. So that’s a form of embodiment, for a start, and it’s a form of agency at the level of the organism that goes over there or stays here. So the terms that we would use very confidently with humans, I find myself not having an alternative word to use for what bacteria would be doing, which I find quite interesting. I imagine it must be, again, frustrating for a lot of people, and I think it’s the other big aspect of consciousness would be self awareness, and I don’t know, I certainly wouldn’t impute that to a bacterial cell. It seems to me that any sufficiently intelligent system would more if it’s embodied, would more or less have to become self aware because, you know, it’s like watching a chimpanzee in front of a mirror. It’s got to figure out, after a while that that’s me. So. So I suspect that self awareness is is a product of a complex nervous system, and AGI will become self aware once it’s embodied as a robot, but I’m sceptical about whether it would ever have feelings as we understand them. You could potentially find a way of programming something equivalent in I’m not saying it’s impossible, but I think it’s I think our own feelings are a product of the wet wear of metabolism.
Professor Cait MacPhee FRSE 1:27:19
Well, we’ve gone all the way through, from origins of life, selection of chirality, through to consciousness, feelings and artificial general intelligence. So I think we’ve covered a fairly wide swathe there. So if you’ll join me in thanking our panellists, you night,
Professor Cait MacPhee FRSE 1:27:45
and a reminder that Nick is going to be giving the Gifford lecture tomorrow evening as well. So thank you very much for joining us this evening and travel safely home. You.
Transcribed by https://otter.ai
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