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Welcome to the Scientific American podcast “Science Talk” posted on July 31, 2013. I'm Steve Mirsky. On this episode -
Adam Rutherford: It's history. This is a branch of science which is effectively trying to recreate history.
Steve Mirsky: And that is science journalist and author Adam Rutherford. His new book is Creation: How Science is Reinventing Life Itself. Hm. A book called Creation by a guy named Adam. Anyway, Adam has a degree in evolutionary biology and his doctorate is in genetics, specifically of the eye. He's a familiar presence on TV and radio in England where he's an editor at the journal Nature. We spoke by phone on July 25th.
Adam Rutherford, finally a book that answers the burning question - are you related to Ernest Rutherford?
Adam Rutherford: [Laughs] What? That's one single footnote. It's actually my favorite footnote in the whole book which is those two words. No relation.
Steve Mirsky: No relation. [Laughs] That was it.
Adam Rutherford: No relation.
Steve Mirsky: No. It's an excellent footnote but the book is studded with a lot of really good footnotes -
Adam Rutherford: Thank you.
Steve Mirsky: - some of which we'll get to. This is a - I'm not just saying this because I know you - this is really terrific book. This book should be required reading for biology and chemistry undergrad students. I think all science journalists should also read this book. You learn so much and you're also exposed to so many concepts that make you reconsider things that you might have thought you already understood.
Adam Rutherford: Thank you so much, Steve. That's very kind.
Steve Mirsky: Why don't we start with the title, Creation, and then your subhead is How Science is Reinventing Life Itself. Am I correct - the title is a bit provocative purposely?
Adam Rutherford: Oh no, that would never be something that I would do at all. Maybe a tiny little bit. I was in an interview with an Irish radio host a few months back who asked me the same thing and my answer was, “Well, you know, religion doesn't have the monopoly on words, including the word 'creation.'” And I thought it was a really apt way of describing the two things that I'm trying to do in this book which is to understand the origin of life in the first place by scientists trying to recreate it and current attempts to genetically modify organisms or create entirely new organisms using synthetic biology as also a form of creation. And the host replied and said, “Yeah, well, that's a good example except for the fact that your first chapter is called 'Begotten, not created' which is definitely a religious phrase.” I was like, “Yeah, okay. Snafu there.”
Steve Mirsky: I think that host has a point. And there's a sentence very early in the book where you say it does not take a great leap of faith to see that we are closely related to certain other organisms like chimpanzees which also struck me as a bit of throwing down the gauntlet on your part.
Adam Rutherford: It's pretty gentle, though. I was - in writing the book, I was - I had a lot of conversations with friends and my editor about how much of that sort of conversation about the truth of evolution versus creationists, how much of that should be in the book. And there is a lot of discussion of evolution in the book, but we kind of came to the conclusion quite rapidly that this was not what this book was about. It's a distraction from what the book was about. And basically, our starting point was if you're a creationist, if you invoke a religious basis for how life began on Earth, then this probably isn't the book for you.
Steve Mirsky: Although, as Ernst Mayer said in one of his books, “If you're a creationist, you really should read this book just so you know what you're arguing against.”
Adam Rutherford: Yeah, well, that is true but then again, arguing with creationists' is a lot of fun but not a lot of use. We call them zombie arguments. You can knock them down. You can knock them down and they just get up again because you're not really arguing about the same thing.
Steve Mirsky: Right. And there are other very good books that are devoted to laying out the evidence for the fact of evolution so there's no reason for you to rehabitulate in yours.
Adam Rutherford: Absolutely. Why Evolution is True, I think, is my favorite of the recent space of these, by Jerry Coyne and he does this amazing thing where he describes the wonder of evolution in incredible story telling skills and then points out why this is - why this shoots a giant hole in some creationists nonsense.
Steve Mirsky: Right. And I have a podcast interview with Jerry Coyne about that book. If you search our website, you'll be able to find that podcast which you can then enjoy after this one. So, let's get back to your book. What compelled you to write the book?
Adam Rutherford: My academic background was in genetics and evolution of biology so my first degree was evolutionary genetics and I went on to do a PhD in genetics. And then I became a journalist at Nature. And during that time, half of the things I was writing about, amongst the other things I was doing, was genetics and evolutionary biology, of course, ‘cause that was my beat. And I think I was waiting for the right idea to emerge for me to write a book about it. It struck me that in the 10 years between leaving the lab and when I started writing the book that genetics and molecular biology had really blossomed in a way that enabled us to seriously address those two questions that are the basis of the book - the two spines of the book.
One is answering the origin of life itself or getting towards an answer for how life evolved on earth in the first place. And the second thing was, you had the emergence in the sort of post-genetic modification world of this new field which we call synthetic biology which is really only five years old - five or six years old. And I felt that this was a really - it was really the right time to say, “Well, look. Here is a piece of work which is gonna be, for the time being, a definitive discussion for the mainstream of those two subjects.” ‘Cause, you know, they're both really fascinating.
And one of them's incredibly important from a sort of political point of view and an engineering and global point of view and the other one is incredibly important from a pure intellectual point of view. So, yeah, that was the motivation really.
Steve Mirsky: And from an economic point of view, the former - the synthetic biology aspect of the book - is very important for the future of global economics as well.
Adam Rutherford: Yeah. I think that's right. The argument I make in the book is that this industrial revolution has already begun. That we've witnessed the beginning of the second, great industrial revolution in the last few hundred years and it is the synthetic biology one. And that we're already just beginning to see the actual, real fruits of synthetic biology.
One of those stories which Scientific American has covered many times is the emergence of a synthetically generated artemisinin, which is a chemical that is used to treat Malaria. And a team over in California in San Francisco have produced the synthetic yeast which produces artemisinin at a far greater rate than how it can be normally formed. And they have begun to distribute this and it'll hit the markets very soon as the most effective treatment for Malaria. So that, I think, is the high watermark so far. But I think it's only gonna grow.
Steve Mirsky: I wanted to point out just very quickly that one of the other really great footnotes in the book discusses your own research background, your symmetry research.
Adam Rutherford: [Laughs] Yeah. No, that was when I was an undergraduate, actually. It was in the summer of my second year when I was working at a lab in University College London, just down the road from where I'm sitting right now. And there was a - it was a very popular field emerged within evolutionary biology during the '90s which was this concept called Fluctuating Asymmetry. And it was the idea that symmetry in organisms was a measure of fitness and that you could establish how healthy or sexually attractive an animal was by how symmetrical they were or how much they deviated from perfect symmetry.
So, I was working on this fly called the Stalk-eyed fly - 'cause it has its eyes on the ends of stalks; really imaginative name - and I think I measured about 3,000 of these guys. We starved them during their development and measured that starvation in order to try and induce asymmetry in their eyestalks. And I measured about 3,000 of them and the answer was “no.” No, there was no more symmetry.
Steve Mirsky: Laughs] Right.
Adam Rutherford: It was an incredibly dull project but intellectually, it was wonderful.
Steve Mirsky: And you note that the world of science took - paid little attention to that study.
Adam Rutherford: We got a paper out of it. I got a paper as an undergraduate.
Steve Mirsky: As an undergraduate, that's the most important thing about that work.
Adam Rutherford: I was pretty pleased. Yeah.
Steve Mirsky: So, you were mentioning the Malaria treatment work. I want to get back to that, ‘cause that’s in the second part of the book. Let's talk a little bit about the first part of the book which is the attempt to understand the origin of life on Earth. And I think the - page 102 I have marked here - I think this is the key sentence related to the first part of the book. “These clever experiments don't show what actually happened in the origin of genetics but they show what might have happened.”
So, why don't we take off from there and talk about the attempt to understand the organ of life.
Adam Rutherford: Yeah, yeah. So, it's - obviously, it's history. This is a branch of science which is effectively trying to recreate history. And until someone invents a time machine - come on, physicists; we're waiting - we won't be able to understand exactly what happened for 3.9 billion years ago. So, what we do is we observe what life does now and we look at the things that are absolutely common amongst all life forms and we postulate that those things are basal.
Those are the things that happened in the first organism, the first cell, the thing that we call Luka, the last universal common ancestor. And so we look at those as being the most fundamental things that life does and we try to recreate ways in which those properties emerge. And some of those things are genetics - RNA, DNA and some of them are metabolism type things so more complex biochemistry. What we do is we try experiments in which those properties that we see in life now, those properties emerge spontaneously or in the test tube or in the right conditions. And so, we inch closer to understanding what happened the first time without being able to observe it completely.
Steve Mirsky: And we can't know for sure ever if what we wind up observing is what actually happened. It's just the proof of concept that it could have been what happened.
Adam Rutherford: Yes, I think that's right. A day will come, at some point, where a scientist or a team of scientists will get a - will generate something which is akin to a cell. And it will have many of the fundamental parts, working parts, that existing cells have because they would have engineered the system to look like that. Again, like you say, that isn't necessarily a demonstration that that is what happened the first time, but what it is is a plausible model of what happened the first time. One of the points I make in the book is this - we have this amazing tree of life.
We have shared genetics across every living organism that we've ever known about and they all point - cell theory, genetics, and Darwin evolution - they all point to a single origin for all life on Earth - the thing we call Luca. But that isn't to say that life hasn't emerged many times on Earth. And all we can say definitively is that it only survived permanently once and that is - ended up with us - us having this conversation. But we don't know whether life emerged many, many times 3.9 billion years ago or even earlier that wasn't destroyed or out competed. Or with the amount of meteoric activity that was happening at that time, the Earth could have been sterilized many, many times over. But what we do know is that life only survived once and that is us.
Steve Mirsky: And if it has emerged again since the advent of the life that we're part of, as Darwin pointed out, it would have been gobbled up.
Adam Rutherford: Yeah. It's an interesting question then. People often ask me that when I talk about the book now. “If we saw it emerge once, then why haven't we seen it emerge many times since?” Well, I think the best answer is that it would be outcompeted incredibly rapidly because of how successful life, as we know it, is.
There is this concept - I think you guys have talked about it maybe on the podcast before. There is a concept called the Shadow Biosphere which is a sort of popular idea that there might be a different tree of life that we haven't observed that exists on Earth and that doesn't use exactly the same biochemist and genetics that we have. And that would indicate that there were two origins of life events that happened on Earth and two have survived. Now, it's a really interesting idea. It's really interesting for astro-biologists because it gives them a way of thinking about how life might have emerged in the rest of the universe other than on Earth.
But I'm a little bit dismissive of that in the book because while it's an interesting idea, it's just fiction at the moment. It's a speculation. We have absolutely no evidence that the Shadow Biosphere exists and I wanted to focus the book on things that we know exist.
Steve Mirsky: Let's talk just a little bit about the kind of work that's available to do because of our understanding of the structure of DNA and RNA in terms of origin of life research and then let's talk a little bit about Jack Szostak's work.
Adam Rutherford: So, you mean like, in terms of how we're beginning to think about how RNA evolved in the first place and how it turned to DNA?
Steve Mirsky: Exactly.
Adam Rutherford: Yeah.
Steve Mirsky: It's really fascinating. These questions couldn't even be asked intelligently from a mechanistic point of view until about 50 years ago.
Adam Rutherford: Yeah. That's exactly right. So, we're still in - we're 60 years since -
Steve Mirsky: Since Watson and Crick.
Adam Rutherford: Yeah. But we're also 60 years since the publication of um, Stanley Miller's iconic experiments and I think - I've got a feeling that was July 1953. So, we're probably having this conversation very close to the publication of that iconic experiment which was the biggest sort of fillip in the idea of life emerging spontaneously on the Earth four billion years ago.
Steve Mirsky: Do the quick summary of Stanley Miller for anyone who hasn't heard of it.
Adam Rutherford: Yeah, of course. He was - I think he was 22 or 24 or something like that. Super young. And he said to his supervisor, Harold Urey, who was a Nobelist already, he said that he wanted to emulate the conditions on the early Earth to see what would happen, to see what would emerge and to see if you'd get life emerging. And so he set up this intricate glassware, which is kept in scripts in Jeffery Barter’s lab - who was one of his students - and I've had a good look at it and it's absolutely beautiful.
But what he had - he had this sealed glassware and inside it had some of the chemicals that they thought were present at the time of the early earth. So, things like carbon dioxide, water and hydrogen and so on. And heated it and there was a spark of electricity also - 10,000 volts worth - and Miller's supervisor Urey said, “Well, let it run for six months and if nothing happens, we'll take it apart and do some real work instead.” And he set it off and after a few days, the liquid inside went from clear to a sort of pinky and then very soon after that, it went a very dark brown color so they stopped and took the liquid out and analyzed it using 1953 technology. And they established that from these very basic chemicals like carbon dioxide and methane and hydrogen that actually, they had reacted and turned into - they detected five amino acids.
And amino acids are the building blocks of proteins and all life is made of or by proteins, right? So, from non - from molecules that weren't required for life, they had generated biomolecules and this was an incredible thing. In 2010, they rediscovered these samples from '53 and reanalyzed them using 21st century kit and they established that they found - he'd actually manufactured all 20 of the amino acids that all life forms are based on. So, it was this incredible idea that complexity, in terms of molecular structure, in terms of biomolecules, are things that actually can spontaneously emerge if the conditions are right. And so - it is iconic and it's an important experiment but it's also been a great contributor to what I argue is the incorrect version of how the origin of life started on this planet.
And that, I think is - my big conclusion at the end of the first half of the book is that the one we talk about. That when you talk about the origin of life, people generally say, “Primordial soup” or “Primeval soup” and my argument is that cannot be right - that the primordial soup is not the correct model for how the origin of life began. Miller's experiment was a wonderful and iconic experiment but I think really helped perpetrate that idea that primordial soup was the origin of life and I don't think that can be right.
Steve Mirsky: Yeah. Talk about what you think can be right.
Adam Rutherford: Right. So, this is a - it's a slightly - it's not that it's unpopular but it's just an idea that hasn't really been discussed enough yet and the problem with primordial soup is that from a basic, thermo-dynamic point of view, this is a chemical reaction which has happened and will not happen again. So, if you get your ingredients right on a warm little pond, as Darwin described it, or as any of the other models of how life spontaneously emerged on Earth, once those chemicals have reacted, they will stop reacting. That's the end of that process. And that is the one fundamental thing that life doesn't do.
Life is a continual chemical reaction where we extract energy from our local environment and use that energy to do all the things that living involves. And so whilst we don't really have a robust definition of life, I think the one - the sentence that most accurately describe what living is is that it's the opposite of decay. From a chemical point of view, at least. If you let chemistry happen in a primordial soup it while happen once, everything will react, and then it will stop and it will never happen again whereas - and when we die, our metabolisms will stop and we become one with the universe. We'll submit to the will of the second law of thermo dynamics.
But whilst we're alive, whilst each of ourselves are alive and while every living thing that has passed this on for four billion years, is this process where we're actually taking energy from the environment, using it and then passing that on to reproduce. And so the primordial soup can't be right because it doesn't make sense from that point of view. So, then you as the question, “Well, where do we see this type of behavior?” And I think it's people don't talk about it enough because it's very modern. This is very cutting edge science.
It was only in 2010 that a model or a location on Earth was discovered where this type of thing might happen, where you might begin to see the type of chemistry evolving into biochemistry that is actually what we see in cells and those are these so-called white smokers - deep, underwater, hydrothermal vents that were discovered in 2000. And they have this sort of biochemistry - well, no - they have this chemistry which looks a little bit like our most basic biochemistry, the way we generate energy, in our cells. And so that became the speculation of a much better model for where life began. And since then, we now are beginning to have experiments which are using what happens in a white smoker as its basis. And we don't have results from them yet so we expect to see them in the next few years. But that's basically where we're at.
Steve Mirsky: So, there's a lot of available, chemical constituents and a constant source of outside energy there.
Adam Rutherford: Yes, although it's not the - it's not the source - it's not the heat which is driving it so much. It's in the same way that's one of the reasons it's using electricity to generate life in the first place doesn't really work because we don't - life doesn't run off of electricity. If runs off biochemistry. And so what the key - the key thing that life does is it generates energy by using, in its most fundamental form, what we call a proton gradient. So, inside our mitochondria, which are the powerhouses of cells, there is a chemical process which is called the Krebs cycle.
You'll note that I didn't actually mention the Krebs cycle in the book because I decided it was too complex to get into and I - I'm __ about this for weeks and then I thought, “You know what? I'm just gonna leave it out.” So, I talk about it, but I don't name it. But the Krebs cycle, which generates all the energy that all cells uses - one of the processes that generates all the energy that all cells use - relies on having more protons, hydrogens without an electron on one side of a membrane than the other. And because there's this gradient, this imbalance, they flow across this membrane and that is the basis of the energy generation system that all cells use - kind of like a water turbine. And what you see in these hydrothermal vents is you see gasses bubbling up from a rip in the ocean floor and some of those gasses include hydrogen.
And as the gasses are emerging, they also drive pores - like, percolates into the molten rock and they form these towers. But the structure of the towers, when you look closely, is that they have microscopic pores in theme which are sort of cell sized, in fact. And so you begin to see, well, you've got these currents swirling around. You've got hot and cold water all around these vents and you've also got gasses present which include things like protons and you begin to see that you might get, very easily, more protons on the outside of one of these little pores than on the inside. And as soon as you begin to see that, you say, “Oh, hold on a minute. You know what this begins to look like? This begins to look like what basic metabolism is like in cells.”
And there are lots of other things happening in those areas where you look at them and think, “Well, this is beginning to look like a really good model for how we might think the first biochemistry evolved.” And then the more you look, the more you begin to see - well, actually, then later on, you might speculate that this is also the emergence of things like RNA and eventually DNA and cell membranes. And all of a sudden, we're talking about a really complete model of getting from the transition from chemistry to biology. 'Cause that's really the fundamental of this question.
Steve Mirsky: Right. So, the constant influx of energy - even though it's hot down there - isn't the heat. It's the presence of the protons constantly bombarding the system.
Adam Rutherford: Exactly. Exactly. The heat helps cause the flow of the maintenance of imbalance in the system - the disequilibrium is what we call it - but really, it's what chemicals are present and in what quantities relative to each other that appears to be the driving force behind what we might see the emergence of a metabolic process.
Steve Mirsky: Yeah. It's crucial to look at this from a non-equilibrium point of view. I'm reminded of the title of Prigogine - Illya Prigogine, Nobel Prize winning chemist. His famous book is From Being to Becoming.
Adam Rutherford: Nice.
Steve Mirsky: And it's the same kind of thing. If you look at it in an equilibrium situation like the insides of Stanley Miller's vessel, well, that's nice but then nothing happens. So, you have to look at it from this system that's - the development of a system that can keep going is the key.
Adam Rutherford: That's right. I tried a number of analogies to try and explain this and the one I included in the book, which I quite enjoy, is a gambling hole. So, you go to a casino and everyone knows that in the long run, the casino always wins. The house always wins. And if you're a gambler, you will lose over time. But what life is is a sort of continual breaking even against a house and it's been continual for about four billion years.
So, when you die, you get kicked out and the energy contained within your cells, it gets returned to the house. It gets - your energy becomes part of the universe and what we adhere to the rule - the second law of thermodynamics. But during your life, you're in ordered stated, a state in which we extract energy from the environment and hang on to it. It's sort of like sitting at the Black Jack table and managing to stay there for the whole night without getting kicked out.
Steve Mirsky: And for the creationists that like to say that we're violating the second law of thermodynamics, that's not the case because we have a constant influx of energy that's coming in from that giant ball of thermonuclear reactions 93 million miles away.
Adam Rutherford: Exactly. And also, we produce a lot more chemical energy in our waste than we take in. So, the system works absolutely perfectly. That's why we call them laws. They really are un-negotiable. And it's difficult to explain that to a creationists ‘cause they’ve got a different set of laws which are non-negotiable.
Steve Mirsky: Right. Let's talk about Jack Szostak just a little bit and his membranes.
Adam Rutherford: Yeah, sure. So, that's another key component of the cell is the fact that you have to contain all the guts, right? 'Cause otherwise, they just dilate. They just float away. And that's been the focus of his work up at Harvard for the last few years.
How do you see the emergence of a complex membrane? 'Cause we don't tend - I think when you teach - certainly, at school age, when you think about cell membranes, they're sort of very - you just think of them as balloons, right? It's like a balloon and the interesting stuff is on the inside and the membrane is just what keeps it all in place. But as you learn more, you realize that these are incredibly complex, sophisticated sort of customs and exercises is how I like to describe it. Because they're monitoring what comes in, what goes out and constantly maintaining the relationship between the cell and the outside world, which is absolutely essential.
So, how does such a complex thing emerge? Well, we don't know the answer to that yet but he's been working with some simple versions of the molecules that make up the cell membranes and with remarkable ease, if you get the ingredients right, they just pop together. They just assemble into cell like structures. And it's because of the shape of the molecules he's using, they just begin to look like that. And then he's driven that question even further by then introducing the types of molecules that we see in modern cells - so biolipids.
And when you introduce them into the mix, they outcompete the simpler molecules. So, you've got - just that process from simplicity to more complexity - which is a bit more like modern cells as we see them - and it happens in a really Darwinian way. It's breathtaking stuff he's doing up there.
Steve Mirsky: And he's even seen how you can drive the division of these vesicles.
Adam Rutherford: Yeah, yeah. I've actually done that with him. I made a TV documentary a couple of years ago for the BBC and was in his lab and we put together what he calls protocells where you just mix them up, you shake them up and then you look at them under the microscope. And you look - they're cell shaped and they're cell sized. And then we just got a little like, air gun - you know, like one of those aerosol cans that you use to clean the crud out from the keys in your keyboard - and held it about a meter away from the slide under the microscope where you had these little protocells.
Squirt it with just the tiniest blow - puff from this aerosol. The cells wobbled about and then they did the thing that all cells do which is, they split in two. And they split in two in exactly the same way that cells divide in living things. Now, that isn't the process, right? He's not suggesting that this is cell division being observed here.
But it does look a lot like it. And just like we were talking about a minute ago with how we begin to emulate the process, we begin to look at what modern cells do and try to work out how that process or that chemistry - that biochemistry emerged in the first place. That's exactly what we're doing in this experiment. They behave a little bit like cells. And so then you add the complexity into the mix and you try and get them to behave more and more like cells but they've emerged in your lab rather than from an organism.
Steve Mirsky: We'll be right back after this word from Kerry Smith at the Nature podcast.
Kerry Smith: This week - a tiny thermometer measures temperature inside cells. How humans evolved the ability to digest milk as adults and what to expect from a career move to the Middle East. Listen in at Nature.com/podcast.
Steve Mirsky: That's it for part 1 of our conversation with Adam Rutherford: about his new book Creation: How Science is Reinventing Life Itself. You can get it as your free audiobook by taking advantage of the offer at www.audible.com/sciam. We'll be back soon with part 2.
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