George Whitesides – The Origin of Life

this is a topic that is probably my favorite topic of all the things we're working on it's probably the hardest thing we've ever worked on and it's going to be as a talk a little different from what I think you're probably accustomed to in the sense that I'm not going to be able to give you an answer and in fact it's not even trivial to phrase the questions but I'm going to be trying to phrase the questions there are some issues that one can define pretty clearly but the underlying notion of where life came from or even what life is is just an extremely interesting question and I want to start with one of the meta issues which is particularly interesting to me as a chemist about this and it has to do with the way different subjects are are thought about so if you consider the question of science and big unsolved questions you can ask where do chemistry physics biology and so on stand and the scheme of things I think if you were to talk to most people about what physics does they would have a pretty clear answer that it's you know the origin of everything dark matter and dark energy and nuclear weapons and quantized space-time and all the rest of it and don't misunderstand me I am absolutely for quantized space-time I just don't have any idea what it means then you go to biology and biology does disease and differentiation and development and what's an animal and things of that kind and people understand that and then astronomy is stars god they blow up they make fantastic pictures and you go to chemistry and it's not completely clear what the answer is and there's a little bit the feeling that you get when you go to the what used to be called the UK I don't know what we will call it in the future where if you hear an announcement on the radio it will say the sciences and chemistry and that carries something with you so what does chemistry do it is true that it makes better glue but there are a series of problems and this is one where I think that the problems that chemistry must address fall in this category of being very big ones and I would argue that the origin and nature of life is not a biological question it's really kinetics and molecules and how they come together to make something that is completely unexpected it's really an interesting subject then there are others that come after that such as sentience and some of the problems that come up in the origin of life come up in the origin of sentience but it's a little bit more complicated subject so we're going to talk about it only very briefly only at the end now let me show you a couple of slides that I showed some of you before but I want to make a point about this if you look from left to right in these slides you understand that this is the natural order of things if you do the same thing the other way around it's the unnatural order and the question is we all say it's perfectly obvious that you don't D mix milk and coffee but it's worth the effort stopping for a moment and asking why it's obvious that you don't be mix no from coffee where it is not a trivial question I mean yes it has to do with mixing and it has to do with conversion of potential energy into heat and things of that kind but do stop for just a second and ask about it because it's very intimately connected to the subject I'm going to talk about which is the origin of life which has a little bit this character so I showed you this before which is we know how to make a chicken into chicken soup the question is can you make chicken soup into chicken and that's we don't know how to do that but it's a little bit even worse than that because it's really this so suppose you have something of this kind which is I think what many people would argue is the plausible prey for life and then you pour the chicken soup into it and out of it comes something like that and it seems very hard to understand how that can happen how do you go from a system that's disordered dilute contains all kinds of other stuff mostly other stuff how do you go from that spontaneously not only to a more ordered state but also to a state that has the characteristic that depending upon how you want to phrase it it's self evolving or self assembling we know how to do that once you get to life but we don't know how to do it at the very beginning and that's the reason at least one reason why I find the subject so interesting so the basic issue we know that molecules are not alive we know that the cell is molecules chemical reactions are not alive cells are Assemblies of reactions molecules but cells are alive so what happened how does a cell which is a collection of reacting molecules become alive and their various answers about that the one that I'm going to come back to is that I think that life is simply a name that we give to a certain kind of reaction that of reaction but that makes life in a sense a question of networks and we don't understand how that works let me give you a couple of questions to think about during the course of what comes from here so the first question is where and when and how did biological life art and we have a little bit of an idea about that but it raises an interesting question of could there be other kinds of life other than the life we know the second question is was the start deterministic or random and what I mean by that is in every planet that's a water planet and that has a distribution of elements is life inevitable is it something that will always happen or is this just a quirk that happened once per galaxy or once per universe or once for all of its recorded time and I think at the moment we don't know that there you can make guesses about each of these I don't think we know the answer so this has to do with statistics and probabilities and that has to do with knowing what these reactions are how does dissipation allow chaos to become order and we know that you can go from a disordered system to a more ordered system if the free energy of the system goes in the right direction amid this is the second law but having said that understanding how you coupled dissipation of free energy to the creation of order in detail is not at all a trivial question here so was it chaos or you know one of the questions you can ask us there's something else that we're missing in this weird you alive and not alive separate and I'll come back to this subject again at the end but we have two words for something which is not clearly a binary distinction I mean I don't know that there's a bright line in between life and not alive alive and not alive it may be a continuum and if it's a continuum what are the properties in between and what are the properties beyond either end these are questions that are very very important when one is thinking about other forms of life so those are interesting and there's a question of which is relevant to this subject which is early life and current life is current life a reflection of what happened at the beginning or was a really different at the beginning was evolution sufficiently large scale that the traces of what was the first of all being system totally different and I don't think at the moment we know the answer to that question and so the this is going to prove very relevant to one of the principal topics that I want to talk about in terms of the sociology of this field and then is life more than a name for just a set of molecular processes and there are people who feel passionately on this subject both ways so is life just like a flame in a sense and then finally if one like the there's have set off to study this how do we know when we've been successful you know what is the measure that you've gotten over some hump and you began you're beginning to see something that says that we sort of know what's going on so where did life start and we don't actually know queer but let's assume it started on this earth and when we actually have a pretty good idea the formation of earth itself the formation of the planet was about you know four-and-a-half 4.6 billion years ago that's fairly accurately dated the first this is the what's called the end of the period of heavy bombardment and ocean evaporators as represented by this what does that mean and it means that the things that were falling in in this period were big enough that you asked the question this object comes in falls through the atmosphere falls into an ocean what happens to the ocean and the answer is it evaporates so the surface of the planet is then covered with superheated steam for 100,000 years or something like that that doesn't sound like a really great place for something as fragile as a cell to come together the age of the oldest fossilized bacteria this is still a question of some debate but it's in this period so you know 4.2 4.3 - maybe 3.5 Jigar years ago and some of the oldest traces are in fact in western australia but there are arguments as to what's real and what's a geological thing this question how did different sets of molecules and reactions unite and a point which is actually quite an interesting point which is that you can argue that life emerged alarmingly early that is if this were something which was really a random event looking thinking about the difficulty of what has to have happened it seems that it must have happened pretty rapidly now it's true there's a lot of ocean and the billion years here there there is a lot but the fact that it happened as early as it did I mean the planet surface was barely enough to sustain things without boiling them all you know is raised some people to raise the question that maybe it came from somewhere else so called panspermia and if it did it doesn't really change the situation because you can then ask the question of where it started there you just don't know the timescale now in more detail there's some things here that are plausible but a little surprising to chemists first is that the planet at that point was largely a water planet there are people who argue about whether it was completely under water are mostly underwater it was probably mostly under water with some land above water probably 10% of the above water land that we now have the continental plates were probably unformed their discussion extensive volcanism because if there were plates it was thin relative to what we have now lots of geothermal activity the Sun was cool and very UV rich so there was a lot of stuff going on in the upper atmosphere that produced big gradients in oxidation and things of that sort there was continuing impaction which may have been important but both when a it's interesting that when even if pretty small meteor runs into the atmosphere you ask what happens to this stuff that's in front of the meteor as the meteor comes in and faster than the speed of sound and the answer is it just piles up so a meteor simply punches a hole through the atmosphere that's five kilometers across takes all that stuff ionizes it into a plasma and then smashes it into whatever it happens to run into and there's the potential for doing a lot of chemistry there but we don't know a lot about how that chemistry works we know something about the atmosphere there was maybe oxygen in the very upper regions probably the upper regions in fact were fairly oxidizing at the surface it was mostly co2 and n2 in water and there are arguments about how much fixed nitrogen and methane and oxygen there were probably a lot of methane from geothermal sources probably not a lot of oxygen who notice about this and then the oceans were acidic probably a pH 5 mildly reducing because they were bright red mostly iron and then there was a lot of what I call pond scum and pond scum means that the atmosphere had been swept off a number of times into outer regions of the solar system and subjected to this UV rich sun's radiation and what you tend to get under those circumstances or molecules like HCN which have the characteristic that they have a very strong bond and a small number of pieces because generally thermodynamically your you favor things entropically under those conditions that have broken up the molecule into the maximum number of pieces so when you see people doing synthesis in this area you'll find a lot of reliance on HCN and h2s and acetylene and things of that sort which seemed a little implausible and on earth they probably are but in this period in the formation of the planet they were probably okay so I put this picture up again to prejudiced you because I think this is what we're altima thinking about whether this was on land or under water I don't know but the virtue of having it on land is that it also accumulated the stuff that was falling down it was subject to UV radiation and it just seems like good sort of concentrator and reactor for a lot of things now we can ask a little bit now about life itself as we know it and a good question is one that we can answer what is the simplest cellular form of life right now and this is probably yet it's a organism known as micro plasma genitalium Ventnor has done a lot of work with this and you can look at the genome of this the genome is 5.8 mega bases and there are in the order of 800 proteins expressed and of those 800 proteins we know what in the order of somewhere between 550 and 6 Lemar and you can make guesses about some of the others but it just gives you a sense that this is a bag of molecules that make up this number of proteins which do whatever life does so that's the introduction now we're going to go on and talk about some of these other subjects and just to give you a little bit of orientation one of the disagreements in this community there's a schism right down the center between those who believe in what's called the RNA world which says that I don't fall in the RNA world so I'm going to put this in a slightly prejudiced way the RNA world says it is so obvious that life must have come from RNA which was both a catalyst in the memory molecule that let's just assume that there was RNA and then go on from there and then the other part this is B says I can't see how to get to RNA so I don't care whether there was a light it was a catalyst or the memory molecule I don't see how to get there and there's a quite a difference between these two points of view we'll talk about this a bit we'll talk about some of the results from our work in chemical fossils and about dissipative networks I'm just going to talk briefly at the end about information in the context of this subject so what does this cell do for a living it replicates itself and it makes the pieces for doing replication and controls that and the replication guys are the core of RNA world and the metabolism guys worry about where the pieces came from so the basic schema is that you start with and we all agree with this basic structure somewhere there are simple chemicals like h2s and co2 and HCN and then a lot of geochemistry and the geochemistry is intensely interesting and not really very well understood by current chemistry we don't know a lot about geochemistry but it's much more complicated than you would think so simple molecules make more complex molecules and that's fine somewhere there are precursors to RNA somehow the precursors to RNA become RNA RNA becomes DNA and we sort of know why that happened in terms of stability so that you can either start intellectually by saying we know about DNA we know a lot about RNA we can ask about that and let's just assume that this happens somehow because this is also satisfying and plausible and the other point of view says we know about this we know about this but we don't understand how to connect the two and those are sort of the two different approaches to the problem now what about the RNA world why is it so satisfying well RNA is a very interesting molecule let's start with DNA DNA is of course the double helix it's the memory molecule and we understand a lot about DNA it you know it contains information in base pairs but more to the point the cell puts in a lot of efforts to make DNA as a out of RNA because you get long terms to go with you that way long term chemicals to the liver but RNA has the characteristic that it looks a lot like DNA in terms of a sequence of bases which in many circumstances will base pair and also RNA as a catalyst so if it's both the catalysts and in principle both in principle of catalyst and in principle a memory molecule it must have been the thing that started off this particular approach and part of the evidence sort of favouring this is the ribosome which is of course a key molecule in replication of proteins and it has the characteristic that you can think of it depending upon your point of view as a matrix of proteins with RNA plastered in between or I think more plausibly as a giant catalyst made out of RNA with proteins stabilizing the whole business but it's you know it's a mixture of these two it's about half and half the problems with this point of view is that RNA a we can't figure out how to get there in my view further RNA is a catalyst but it's not a very good catalyst what it mostly does is catalyze reactions that involve phosphates and it isn't a very good it looks like it should be a good memory molecule but it isn't really so you know yes these are good steps along the way but it's not obvious that that's the final thing so one of the questions that you can ask there is the plausible question of okay so RNA isn't the right thing as we know it now and either for catalysis or for a memory but maybe we're missing some steps maybe there was something like RNA which would work better but it's disappeared through evolution and I don't think anyone has a good suggestions what that might be but it certainly is a possibility now the other approach is to say metabolism and there's been some absolutely brilliant chemistry done by Alberto Moser and Leslie Orgel and John Sutherland and Justin to do that many others who thought about the kinds of molecules that you can make in an organic laboratory and they have done amazing stuff and particularly I would point to issue Moser and sutherland peshan Moser had a very nice synthesis of vitamin b12 that involved nothing more than HTM so you made vitamin b12 which is a very complex molecule starting just from those pieces the trouble with that was that the synthesis which was absolutely brilliant also involved 20 years of very very skilled synthetic technicians in Zurich in well-defined laboratory conditions and whether that really tells you something about what could have happened in a wildly disordered planet I don't know I happen to think not but I could be wrong so this is an issue you can make very important things in Sutherland has even found a way of going from simple pieces directly to a base and as a precursor for RNA whether this applies or not is a question so the question - arcane conditions that is conditions in the para biotic world is that there's no obvious root RNA using this kind of thing or two proteins the laboratory conditions under which this all happened smokers and volcanoes and lightnings and toxic compounds don't bear much resemblance to what's going on up here and then there are a series of things having to do with concentration because if you're going to have two molecules react with one another at a finite rate they have to have some proximity to one another and if they're dilute present but dilute in an ocean what is the probability that you will get reactions that lead to the kind of thing that you want with the cell probably not high there are hints that I think are interesting and one is relevant to what I'm going to tell you later that there might be other ways of doing it so for example you can make peptides you can make proteins little proteins without having a ribosome and the most the method is probably most important now is something which is actually pretty complicated in its own right but it involves a piece of machinery in which the sequence of the protein is determined by the sequence of subunits protein subunits which instead of using RNA and activated activated amino acids use thio esters and this is one reason why christian to do is talked about the thio ester world this particular thing makes molecules of this sort and a bunch of other bacteria derived antibiotics that are illegal peptides but probably more important exactly the same kind of chemistry makes fatty acids which are the lipids that make up the cell membrane so it's a very successful reaction pathway now just a couple of points here and this is as a reminder something you already know when we talk about equilibrium systems in chemistry we sort of understand what we're doing we have pretty well established rules for doing we do understand the sources of free energy that could be used in origin of life so sunlight and radioactive decay heat in the center of the earth coming out at thermal gradients concentration gradients things of that sort it turns out that although there are many gradients in for example temperature between a kilometer down in the earth and the surface we don't have very good methods of harnessing oh that kind of energy free energy to do chemistry with and there is a point and this is for those of you who are students primarily to remember when we talk about free energy we write Delta g0 equals Delta H 0 minus T Delta s 0 and we phrased this in kilocalories per mole as if it were a fundamental property and actually that's the wrong way of writing the equation you should really write it as Delta G 0 over T equals Delta H 0 over t minus SS 2 minus Delta s 0 which is a statement of second law of thermodynamics so everything is basically the second law and there's no separate thing which is free energy is just entropy that runs everything the problem with this is that of course is all in equilibrium conditions and exactly how to think about something that might be a thermodynamics for a dissipative system we do not know even though some very smart people have thought about the problem so in a sense this issue begins to boil down to the nature of dynamic and dissipative networks and we don't have a very good understanding of these either theoretically or empirically and there's some important issues in Auto amplification and auto catalysis that I'll come to and there's a whole field of what we call systems chemistry and biochemistry which is a subject of active discussion but it is not correct to say that the field has solved its internal problems so then let me turn to some experimental results and we've taken the following kind of approach one is that we have been interested in looking at what I call RK and compatible chemistry that is chemistry that we have chosen in the hope that it might actually be directly relevant to the conditions of the Perry biotic earth as opposed to the conditions of a modern synthetic laboratory it's a different kind of chemistry and I'll give you a couple of examples just to give you a notion in a teepee and the origin of the potassium sodium gradient that characterizes all of life right now and then things like isoprenoids and the metallic cofactors I'm going to sketch an only sketch the area in which we spent the most work I've talked about this briefly here before but it's the issue of a thioester based Network and what one can get out of that in terms of self-organizing behavior and then finally a bit on information so molecular fossils the argument here is purely hypothetical and it may be wrong but the argument is the following that if you're thinking about the origin of life what you might want to do to trace back to whatever was going on then is to look at features that are common to all life now now maybe it evolved later but if it was a good idea at the very beginning maybe it's stock and what are some examples well all life has the characteristic that it has its high on potassium on the inside and it lives in an environment in which sodium is rich on the outside so in fact the storage of free energy in terms of the potassium sodium ratio is one of the great commonalities across life we look at this now and we say well that's obvious if you've got potassium and sodium you can make a storage battery by simply concentrating the dilute thing the problem with that is that of course before there was life there was no sin and there was certainly no thermodynamic analysis so something else has to have happened then polyphosphates that means ATP one can make a pretty clear case for that kind of come from thio esters I'm going to talk about that they're common throughout life ATP and the common cofactors are common throughout life where did these things come from and then these major metabolic cycles like the Krebs cycle and glycolysis and the light sensitive molecules that are used almost everywhere to harvest sunlight so porphyrins and retinol and Flavin's and things of that kind so let's start with ATP because that one it's easy this is of course the activating chemistry the equivalent of the chloride the carbonyl chloride in in all of synthetic chemistry that's used to activate oxygen and all one has to do is to take phosphate in the presence of urea on a hot rock and you heat it at a hundred degrees and what you see by capillary electrophoresis is this series of Peaks these sort of jagged peaks there each of which is another step longer polymer of polyphosphate so that it's not hard to take phosphate and condensed it into polymers and in fact there are organisms even now that use Polly phosphate as a principal energy storage source and so it's natural to say that triphosphate attached to some recognition handle could have been the origin of ATP that that seems ok the sodium potassium gradient this is more complicated but the question here is is there a way in which you could possibly have gotten to 2 media that were high in potassium and low in sodium even though the environment is very rich in sodium and poor in potassium and to do this you go to geochemistry and without going through the details very common rocks or basalts and fel sparse and zeolites of various sorts in clays these are all basically in Luminoso kate's of various kinds and if you take one of these mixtures you know you take a mixture of potassium sulfate and sodium sulfate and you put in a solution with something that becomes well you start with a molecular sieve and a mixture of sodium and potassium or alumina a mixture of sodium potassium allow these to convert into their stable form the crystals that are formed here the mineral that's formed here is 100 percent potassium essentially and with alumina it's a hundred percent potassium so as you can find geochemical processes which naturally crystallize things in terms of very high potassium forms so the idea would be that you start with the sodium potassium mixture of some kind you do a crystallization on the surface of a volcano and then you wash away the sodium that's left and what you're left with is a potassium rich brine and that would be the place where in this argument you would have started something and then although we haven't done isoprenoids I think you can make a good story there and the story suggests this idea of missing things the way isoprenoids are made in current isoprenoids for those of you who are not organic chemists are things that are derived from isoprene formally which is this c5 molecule and the way it's made now is a pretty complicated process by which you start with acetyl co a which is a thioester you make this rather complicated molecule by some processes that we understand and end up with this and it's all under tight control but it turns out that the most stable and most abundant olefin in c4 that you can make is isobutylene very stable molecule and formaldehyde very plausibly could have been formed by reaction of methane produced yo chemically with oxygen produced by fatah Lass's of water in the upper atmosphere so there was almost certainly formaldehyde there and a touch of acid makes this or precursors of this and then we know that acid that begins to form the bonds that form this so here I think what happened was a natural process that went this way that's evolved over time in this and that touches on the RNA issue and saying that there's no life that does this now it's been lost but the products have been preserved and it seems plausible that one could have started with RNA precursors something else that then evolved into RNA in the same way so one can work through a number of the the important catalysts that are present in everywhere you're EA's is the enzyme that hydrolyzes urea carbonic anhydrase is a key enzyme that catalyzes the equilibration of carbon dioxide and co2 carbon dioxide in carbonate the ferredoxin x' are really important in various ways in redox chemistry nitrogenated whatever these all have active sites that look just like minerals so the idea that they may have formed by just taking colloid in smokers and wrapping stabilizing proteins or something around them makes pretty good sense so I think one can find plausible ways of making a very large number of cofactors of cofactor containing enzymes from pieces that are either naturally-occurring colloidal minerals or simple molecules that could have been formed by the kind of processes that were familiar with now can you put all this together and here I'm giving you a kind of community view that probably the most plausible environment to think of for these earliest life-forms was this or maybe it was the deep smoker or maybe it was a dying see these have the characteristic that they concentrate because you have dilute solutions of things coming in they evaporate water in the heat and to get concentration you get UV irradiation you get colloidal catalytic minerals being produced you can imagine ways in which you get a high potassium brine there are a lot of pieces that come together into a story that is not a convincing story for anything but it's a start there is however a little glitch or at least in my view there's a glitch and you see it in for example metabolic processes that are common to all life basically such as the krebs cycle the krebs cycle if you look at it it has a couple of Saia esters that's good we're comfortable with bio esters although we don't know exactly how to make them there are things that are iron sulfur clusters those are colloids from Hot Springs they're these sulfur compounds were certainly not a CO CO a but they could have come from hot springs this could have come from evaporation there are other steps here's another colloid you know the pieces all look Orden together okay but the problem is this one that each one you can make an explanation for where it kind of come from but we don't have any idea of how it was all integrated into a piece high potassium brine isobutylene plus acid deep smoker a deep smoker probably hydrocarbon junk and deep smokers how does this all get together no idea I mean not a clue right now so we're moving having not declared success in point a moving on to the problem that I think is really the problem this is the were the era of the modern of the RNA world the field of the RNA world we're interested in this problem which is networks and are there alternatives to RNA in terms of memory and can you have a memory in a Cell that isn't based on RNA or DNA and we've taken an approach to this which is we'll see it's just say that the cell is a dissipative system it takes fuel which is glucose and other nutrients and oxygen and it burns them in a reactor it makes co2 and other forms of waste and what it does with that is to generate the components that make the cell and we're going to model that in terms of something which seems ridiculously far away which is a flame and a flame takes the reactant which is a methane rather than glucose and it takes oxygen and it burns them and it makes heat and light and co2 and water so how do you put all that together how do how do we learn something from this that is in any sense relevant to this and we're going to do it by using chemical engineering to model the cell with what those of you who are chemical reengineered will recognize as a continuous stirred-tank reactor except that a cell doesn't require stirring but it is so small that diffusive mixing is as fast as you need it to be now we're going to do one other thing here which is to try to deal with the problem of complex behavior and if you remember a cell has the characteristic that it grows and then it replicates and it grows and it replicates so there's a periodic behavior to it where else do you see periodic behavior of that sort and one of the places that I've always been curious about is that those of you who have seen and even worked with gas stoves that have these ring burners well notice that when you turn down the flame as the flame goes down you'll often get a rotating circular behavior very very interesting where does that come from and what's happening there is that as the flame goes down locally it will use up all the methane and but it will illuminate the flame lit next to it and it goes around in a circle and by the time flame comes back to here this will have gotten enough methane in it that it can go off again that's the sort of general process you're working just on the edge of instability so what we're going to do is to work with a flame in which in essence of flame in which we have a chemical reaction not a methane reaction but it's one in which we are going to try to get this kind of cyclic behavior and the system that we're going to work with the style esters and I'm going to tell you the result for those of you who organic chemists that are interesting and important the reason for working with this system is that bio esters have a remarkable characteristic which is this carbon sulfur bond can exchange with other carbon sulfur bonds essentially quantitatively rather than hydrolyzing which makes it an ideal system for working with an ideal reactant for working with system so this is another argument for the thio ester kind of world and ignoring the details the relative rates of hydrolysis of the system we studied in detail the relative rates of exchange reactions one file for another versus hydrolysis is in the order of a hundred thousand to one which is enough to do anything we need to do so it's a very very good reaction and I think a number of us have the intuition that the only reactions that have the robustness to contribute to the development of complexity or reactions that go and essentially quantitative yield so here's the reaction don't bother to look at it because it's too complicated to understand I just want to put it up there to make the case the following case that if I look at this as a long-term organic chemist I can't make any sense out of it it's too many things going on and I can write the differential equations and in fact solve them but or simulate them but that doesn't help me very much either so it's a problem that comes up fairly often in the chemistry of complex systems that you can get things to work empirical II but by doing so you don't necessarily learn everything your work so understanding and doing are not the same thing and what we've begun to appreciate is that there are other languages for thinking about these kinds of complex systems that make them much easier to work with and the one that we're pursuing at this point is control theory which is a language and approach to the simulation and control of complex systems such as for example a petroleum refinery and we've broken this problem up into pieces that actually can be understood and the entire system I'm going to show you all of this stuff consists of three steps there's a step that's an auto amplifying step in which once a set of reactions reaches a certain critical value a reaction goes off exponentially and for many complex behaviors you need auto amplification to set this off we need to trigger and the trigger is going to be composed of a process that makes the triggering molecule competing with another process that destroys the triggering molecule and there's a third step which is washing out of the reactor which enables you to control the concentrations of many of the pieces all at the same time those are the components and when you embody this in an actual device it's pretty straightforward a little complicated to do but syringes that feed the reactants into a mixer the mixer goes into a stirrer you measure products that come out and there's a lot of technical detail in this but the basic structure is very easy to understand and when you that this is the behavior you see that is if you look for example that the products you will see as you increase the rate at which you feed the reactants into the reactor a steady-state you change that rate you get to another steady-state you change that you've got to another steady-state you change you get to another one goes down and then you reverse that process here to here to here and you don't go back this way you go a different way so the system shows what's called by stability that is proceeding in one direction you get this series of behaviors and proceeding in the reverse of this behavior you get a totally different set of procedure of reactants reaction so by stability you see oscillations so the reactions show spontaneous oscillations like the division of cells and maybe completely unrelated but it's that kind of stability and you see something that I'll come back to which is that as you change the control parameter here which is the space velocity which is basically the range of which you feed reactants into the reactor you see this complex behavior over a range but when you make it faster or slower that behavior disappears so it's a behavior that's defined over in a limited set of circumstances and as many processes with life if you freeze me solid I don't work if you he'd be to a hundred degrees I don't work so I don't think it's worth the effort here to go through the details other than just to show a couple of essential features in the auto amplification reaction what one does is to start with a reaction that has a Thyle group you do chemistry which was designed and at the end of a single cycle of reaction to get to thousands it is amazingly difficult in chemistry to design such processes a very few of them explosion is one crystallization arguably as one may be electroless deposition but for reasons that i don't understand you just don't see very many auto amplifier or autocatalytic reactions and I think it's probably an area where there's great room for discovery the trigger is something to take one of these things and to hydrolyze it it's the file that starts the reaction and we can control how much of that's here by having a reaction that destroys that and you can see this is in red the concentration of this inhibitor as it's consumed the auto amplifying reaction does nothing so long as it's there as soon as it goes away the reaction goes off out the catalytically so that's the triggering process and then inhibition is related to kind of thing it's even more complicated to understand but this behavior here this is the first time that anyone has taken a system which is biologically relevant in the sense of containing kinds of chemistry that could have occurred and demonstrated a complex by stable oscillating behavior of the sort that you see here and it's quite interesting and their visit has got a number of people very excited now one thing that fits into this that is a broadly interesting subject to me is the issue of robustness what you find in these systems is that they do this oscillation but they do it only a very narrow range interestingly though you take related molecules which do not oscillate you put them in and they're entrained by the oscillating reactions so the whole system oscillates and so what you can do is to make a system that oscillates but over a much broader range of conditions by including a mixture of things which do what they do it raises a question which has to do with Darwin and we have a picture of Darwinian evolution which says that what life does is to optimize its behavior to make the fastest cheetah or the best beak for Goldfinch or whatever it might be an alternative view is to say that all of that is a view of life which is life as it is now in a highly optimized form and at the beginning what in fact we may have needed was the most robust reaction as possible which is actually a quite different set of processes and so these these kinds of things provide a very good way of studying that kind of thing now let me finish by just talking briefly about this question of memory because one of the characteristics of life is that it has a memory that's DNA and the characteristic of DNA is it's carefully tuned so that in each cycle of replication there's a certain amount of error those errors generate the mutations which allow the system to evolve so mutations and error big deal so when we think about memory and you know think about evolution we have to think about these kinds of questions and I raised these for you to consider as we go on here how do we know whether something is alive or dead I mean what's the criterion we're going to use this alive it can mutate and evolve if it's dead presumably it can't but is there a distinction that we can make between live and dead or not alive and we're talking about something of this sort ago I'll come back to this in just a moment but it's a frozen embryo alive it does no chemistry it doesn't evolve it doesn't do anything but you warm it up and it becomes palpably alive is there a point sharp point where something happens what about a virus or what about a city is the city alive it certainly can evolve it has a memory it can divide it can do all the other things that in principle a cell can do but it's certainly not a cell and then an interesting question that we're beginning to think about is if we have a hard time understanding how something becomes alive can we understand how things die and that's not so easy either because there's we think of death in a pretty straightforward way as the brain stops working but that doesn't have all that much to do arguably with whether something an organism is alive or dead because many organisms don't have live brains anyway so I'm going to show you just a couple of plots along this axis I'm going to have a live miss and I don't know what that is and along this axis I'm going to have complicatedness or complexity which are somewhat different and I don't know exactly what that is either but pictures of this would be in one sense of binary that is something is dead up to a certain point or it's not alive where a flip the switch flips and it becomes alive that's binary another would be something of this sort it would be sort of exponential or maybe to be sigmoid 'el if it's exponential it becomes more complicated it becomes more alive and you could then ask where we are in this or you could say and I think this is a kind of in the back of the mind interpretation that we tend to have which is that life started with nothing it got more and more complicated until it reached the ultimate crown of creation which is us and maybe that's right or maybe it's not right but then there are other things of this sort and the one that I think keeps cropping up is folded bifurcations and in a bolded bifurcation that governing equation that would be an exponential here actually looks like this and it has the characteristic that things are going along and going along and they're getting more complicated and then at a certain point something happens and it doesn't continue up in that direction it undergoes a transition it hops but then when you turn down the complexity it comes down here it doesn't reverse the path it does this it's by stable in that sense and I showed you an example of that with the biochemistry but it could this be what we should be imagining or should we be imagining this or we should we be imagining this I mean what what is the proper description of how something goes from not alive to alive and I don't think we have this is not a question of origin of life it's a broader question I don't think we have a good answer so when you're thinking about that I think most people who are scientists are now sufficiently marinated in the world of binary arithmetic that we tend to have a binary prejudice and I wanted to just do a quick comparison of binary as in integrated circuits with whatever it is that goes on with enzymes so when one thinks about an integrated circuit you're thinking about a collection of switches that are mostly on or off there's a common working fluid which is electrons everything works with electrons and everything works at a common voltage between the Raylan's and ground the function of this system is defined by the fixed topography of the system that is what's connected to what the switches are binary and they're really fast memory is capacitors or magnetic domains that are switched on or off that's a the system is in a sense non Boltzmann that is the on and off or equally energetic that's not quite true but we don't need to worry about it but the whole system is organized by a common clock though all the things go through steps in synchronous and that's a way of thinking about it biochemistry is fundamentally different it's not this it's this everything is sigmoid all the cell is a sac so the dimensions are set by diffusion there's no topographical organization there are multiple working fluids every compound in principle can influence every one of the other switches it doesn't slightly synchronized maybe you had sigmoidal responses it's very slow and it has memory embedded in DNA or RNA or maybe in networks so there are fundamentally different systems and should we think about them the same way how do we think about control and I don't want to go through any of this other than to point out that in biology you use control strategies that look like this for example for high amplification molecule a will go to D and B will be converted back to a but B will a catalyst for C goes to D and D will it be a catalyst for egos to F and if you look at an important reaction like forming a blood clot it looks like that why does it have that structure and I don't think we have any idea why it has that structure but it's a very interesting problem so I've raised with you a number of questions and I don't think that I can answer really any of them which is why it's such an interesting area but I think this final slide is one that's good leave the subject truth you can ask the question what is life and perhaps says with an electron and I mentioned this in the previous slide when I talk to my friends who are physicists and say what is an electron what they say is you can't ask that question you can't ask the question of what an electron is you can only ask the question of what and so it may be that we have a slightly confused impression with this subject of asking what it is as opposed to asking what it does and you come out with quite different answers when you think about two different things that way so it is a wonderful subject to think about it actually is one of the big problems in science it is something which I think only chemistry can do or chemical chemistry and chemical engineering and it's something for us to have a good deal of fun working with I can't at the moment think of a single application of this thank you very much for the invitation the answer to that is we don't know and if you ask what could another solvent be you can think of other solvents well let's say one of the characteristics of water is that you can put a hydrocarbon shell around water in terms of the lipid and make a compartment and that's probably necessary for life as it develops there are other solvents in which you could do that for example HCN the problem is that it's not so easy to make oceans of HCN and pure HTN has the characteristic that is a neat liquid but it blows up so HCN i think would have a tendency to go wrong my colleague Frank Westheimer ex-colleague Frank list I'm a wrote a paper at one point which he called Y phosphate and he simply went through all of biochemistry as he knew it and asked if there was anything that he could think of that could replace phosphate in water containing life and he came up with the conclusion nothing could replace phosphate so that doesn't mean you couldn't think of something else and but it does mean it's going to be a hard thing to do so my guess is that if you want to look for other forms other planets with life it's good to look for water and you know the figure which I think I've told some of you you hold your finger at that size roughly at about an arm's length and point in any direction and you see a billion galaxies that angle from tens of billion galaxies and each of those galaxies is ten billion stars and most of those are as well many of those stars will have planets and at least some of those planets are bound to be water so I think there's effectively an infinite number of water planets around there how long life lasts is a different question it may be there were no a billion year phenomenon but yep yeah the answer that's again a it's a neat question we don't know very many alkyl bents there are a lot more acidic vents that doesn't mean that a slightly idiosyncratic reaction couldn't have happened in alkaline ones and I agree that there's a lot of good chemistry that you can do in alkaline systems that you can't do in acidic systems on the other hand the whole ocean was acidic so that if you're doing something in event and it's then spewing out into the environment you'd have to do it in alkaline conditions and have it stable under acidic conditions yeah yep I agree I think they're very interesting and for those of you who don't follow this subject there is an argument that the initial life if you want to put it that way the initial cell was not a lipid container but it was a crack in the rock and the crack was lined with catalytically active minerals and it had stuff flowing by it and may have had a plug of hydrocarbon junk at the end but it didn't look at all like a cell as we now know it looked like a geological feature and it developed later on and it could have certainly developed in an alkaline environment yep absolutely yes the question is is their reaction chemistry that goes from the simple pieces that we can imagine to RNA are just dead RNA come by through something look like RNA but was simpler and easier to come by or did it just happen that you know some alkaline environment whatever coughed up RNA I don't see how you cough up RNA but John Sutherland thinks that it's possible and in specially controlled conditions he has made one base I think that's exactly right in fact and as I said to me life is like a flame that is it is a collection of reactions which has a certain set of properties and so reason we focus on reactions and entities is to in a sense provide a plausibility to things how could you have gotten complexity but a flame even a methane-oxygen flame is probably ten thousand reactions and we're very happy with a flame without ever knowing how a flame actually operates and my guess my if I had to guess I would say life is going to be like that so it is a series of processes and networks which have a property in their aggregate but maybe have different forms and they'll in between what's so interesting about life is a process you take methane oxygen you heat it and all of the free energy potential for injury there is dumped as heat what happens in life is that it is exquisitely good at taking that overall free energy gap and pulling off little pieces of it and using each little piece in a different way and the question is really how would you go from something that's a big gradient undifferentiated in us into a series of little ones that build constructively to something that becomes more complicated and I don't understand how to do that right now it's a common way that chemistry works I mean if you think about complex synthesis you do reactions and reactions and reactions and each one makes it more complicated piece and at the end a very complicated structure however each is separate it's run in isolation and the conditions are typically incompatible from one to another and so what seems to happen here maybe it this also occurred in a series of different thermal ponds or something of that kind it's just that we don't know so the question of how you break up something into these pieces that make stuff that fits together into a network that shows complex behavior is an interesting question and that system that I showed you with the network is probably not directly relevant to anything involving life except that the chemistry is the kind of chemistry that you could easily occur imagine occurring in an alkyl Inventor even in an acidic vent so it is not wildly out of out of whack with what might have happened so it's a small step one of the things which I've come to appreciate in this is that somebody's been studying chemistry for a long while there's an entire universe of stuff having to do with geochemistry it is critically involved in this story since this is undoubtedly where much of the free energy came from and the catalysts and the reactants and all the rest of that I don't know anything about it at all nothing and it's a it's a it's a glaring hole in this this subject right now we just don't know the chemistry so you and I are going to have a nice dinner together you

Channel: UNSW Science

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Keywords: Chemistry, Science, Harvard, UNSW, Life, Lecture, Professor, Whitesides

Id: OeiKUhWN1ME

Length: 66min 17sec (3977 seconds)

Published: Thu Nov 17 2016