Nick Lane

"Whether you define life as living or not is really a matter of opinion... It's a continuum. You can draw a line wherever you want or healthier not to draw a line at all... I think there has to be some form of an environment capable of giving rise to some form of , which is capable of giving rise to nucleotides. ...They would put me in the metabolism first camp, but I dislike the tag... because I think it's simply about... the line across a continuum..."

"It's interesting... that life as a rule does not use UV radiation as an energy source, and the kind of chemistry that's being done using it doesn't resemble biochemistry as I know it... [T]he kind of environment that I'm talking about is deep sea s, and the question is, "Well, does it have to be deep sea? Could it... be same systems on land?" and they exist on land. They perfectly could. So it's perfectly feasible."

"[Yellowstone] are not alkaline thermal vents... There are vents... of this serpentinized hosted systems with alkaline fluids rich in gas. ...A place called The Cedars in northern California ...Ken Nealson is the guy. ...He's done a lot of work up in The Cedars."

"[On the :] It's a bit of a sterile conversation. I suppose I think of it as the cell. That's not to say that it can't act at the level of s. Of course it can. It does all the time. Any selfish gene is acting in it's own interest. I think the trouble with looking at selection only at the level of genes is it tends to downplay the importance of genetic conflict in a strange way... [I]f you have levels of selection you can have, for example... mitochondria... They were bacteria once. They're the power packs inside eukaryotic cells... [O]nce they get inside another cell, inside another originally, then they have an agenda of their own. They're making copies of themselves, and it's the speed at which the bacterium as a whole is making a copy of itself that means whether it tends to dominate in the population or not. It's not the individual genes. They will tend to throw away genes that they don't really need. And the host cell itself has got its agenda. It needs to make sure that it's getting benefits from this symbiont. It's not being taken over. It's not being eaten, and so it's... more intuitive to think of the interests of the cells themselves. And if you simply think of all of them as genes then you don't have that discrimination between the layers. Again, if you're thinking about s at the origin of life, the unit of selection in my mind is, "Can a cell make a copy of itself?" If you have a pure RNA world..."

"[Why a cell vs a gene or partial gene?] There's been plenty of work done on RNA replicators and they have a tendency to become smaller and simpler and effectively better able to make copies of themselves with whatever you provide them in the environment, and they end up with a thing called , which is basically the binding sequence of the which allows it to furiously replicate away. ...If you're providing in the environmwent an RNA polymerase and an infinite supply of s then... they become simpler and simpler, and faster and faster at copying. ...The trouble is there isn't ever going to be an environment that's providing that for you except in a cellular context... If you're selecting at the level of genetic replication, the replicators that are better able to make copies of themselves fast are those which are, in effect, the most selfish and the least likely to cooperate to try and convert the environment into ."

"The only way that you can really get a selfish replicator to be unselfish is to put it in a bag with a bunch of other selfish replicators, and then they're more or less obliged to cooperate."

"So if you think of it from a protocell point of view, the selfish replicators which are the best at making copies of themselves are necessarily those that are best able to make the entire protocell replicate itself."

"What I would say with some degree of certainty from the example of life on earth, is that if you simply have a population of bacteria... the chances of it giving rise to the kind of morphological complexity... we see in eukariotic cells, and we do not see in bacteria, is remote... because bacteria and archaea, if you look at the amount of , they dwarf the genetic variation that we see in Eukaryotes. They have explored genetic sequence space to orders of magnitude greater that Eukaryotes did, and despite exploring all of that space, they haven't come up with morphological complexity. ...[T]hey did through an endosymbiosis. ...It's rare between prokaryotes, rare to the point that we know of one example of free-living bacteria with bacterial cells living inside it. We know of two other examples where, there's a for example, which has inside its own cells... some gamma protein bacteria, with beta protein bacteria living inside them. It's a little bit of a strange system and it's hard to know, again, can you generalize from this, because it's all inside a Russian doll?"

"So there's one example of free living ... with bacteria living inside it. It wasn't . It's got a cell wall and it's not a . So they can get inside, but we can say for sure it's rare. What does it do? In a nutshell it changes the topology of the cell. It allows you to internalize respiration and it's not just internalizing the membranes. It's internalizing a genetic control system with in our own case, which by standard selection is whittled down to a kind of minimal unit required to do the job, and that in effect allows the nuclear genome to expand up to anything it wants to be. So... it's a structural change. It's not something which you can find by genetic exploration of the evolutionary space. It's something [in] which you change the topology of a cell. And once you've got that, you've got bacteria living inside another bacterial cell. You've got a fight on your hands! They've got to get along with each another somehow. So the chances of it going wrong is quite high. So I would imagine if we know of one or two examples now, there must have been thousands, millions, billions of cases of this over earth history. The fact that... all this searching across the earth that we've done for life, we find bacteria, we find , we find these candidate phyla. We're not sure what they are, exactly, but they seem to be very simple and probably s, and we see Eukaryotic cells, all the cases that appear to be potentially evolutionary intermediates, something slightly different, have turned out to be highly derived... from more complex ancestors."

"I would say that if there's a probability of life being cellular, which I think there is. Life being based, which I think there is. Life starting out with CO2 because it's so common in planetary atmospheres, and , which is very common, from the kind of s which I'm talking about... and liquid water. They need liquid water for , but we know of it on ... on Europa... [Serpentinization] is giving rise to alkaline fluids with hydrogen gas. Most hydrogen gas you find in planetary atmosphere are coming from serpentinization. , which is the mineral required for that... is ubiquitous in interstellar dust... So all of this pushes you down a certain avenue, and if that's correct it gives you bacteria... and if that's correct then bacteria have a structural problem, and they're not going to get beyond bacteria except with an endosymbiosis, and that in itself is improbable, unlikely... because it only happened once, to our knowledge, on earth."

"The s were acquired by a eukaryotic cell that was already a fully fledged eukaryotic cell."

"[A]cquiring mitochondria gives you a headache that can go wrong very easily, but here's an interesting problem in a nutshell. You look at a plant cell under a microscope, or an animal cell, or a fungal cell, or an or something, and you'll recognize the same structure in all of them. They've all got a nucleus. They've all got the s as straight chromosomes. They've all got s. They've all got s. They've all got complexes. They all do as a division mechanism. They all do as two steps where you first double everything and then half it twice. They all go through the same rigmarole. They've all got mitochondria. They've all got the same system, endoplasmic reticulum, things like that. ...[Y]ou could list page after page after page in a text book and it would be exactly the same for a plant, or a fungal cell, or an animal cell. Now they have really different ways of life. If you were to simply think, "Well, there's some inevitability that bacteria will give rise to complex life." ...You would imagine that a photosynthetic bacteria, a would give rise directly to photosynthetic , eukaryotic algae, but they didn't. It was by the intermediary of acquisition of a . There was a common ancestor of eukaryotes that was nothing like a cyanobacterium and nothing... quite like an algae except without the chloroplasts. So... why is it that we all have the same machinery inside, but we have such different lifestyles? Why don't we see multiple origins of complex life where cyanobacteria give rise to photosynthetic trees? Why don't we see predatory bacteria?"

"These are all lifestyles that exist in bacteria anyway. ...Photosynthesis obviously. The only eukaryotic lifestyle that does not exist at all in bacteria is ... the ability to engulf other cells, to grow around them. That's never been found yet in bacteria. It seems to require... a lot of energy, a large complicated system capable of changing shape and moving around. ...For whatever reasons it never evolved. I would say the reason was that you need mitochondria to get that large and complex in the first place."

"A single discovery tomorrow could disprove everything I'm saying now. That's quite thrilling. ...We have been looking for several hundred years since Leeuwenhoek and we've not found anything really shocking that falls out of the system."

"We all share this basic machinery in cells, and it's not related to whether you're photosynthetic or whether you're phagocytes or whether you are a fungus or whether you're an animal cell. We all share the same machinery. Why? The possibility is that it's not about adaptation to the external world, it's about adaptation to these s. These pesky bacteria that went on to become a mitochondria. Maybe this conflict of interest... [that] had to be resolved somehow was what was driving a lot the elaboration of cellular machinery. It's a kind of local... intimate conflict."

"I wouldn't expect populations of bacteria to give rise, without endosymbiosis, to complex morphology and the kind of intelligence that we have, elsewhere. I think that it would require (I'm going out on a limb here)... an endosymbiosis for the reasons I've been saying, and... that endosymbiosis is a) rare and b) likely to go wrong. So I can't put a number on how improbable it is. It's just that I would say that it's a factor that a lot of people would rather not think about. If you have an agenda where you'd like to find complex life out there, the SETI people for example... probably don't want to hear this kind of stuff. It says that it's less likely... it's not an inevitable outcome of physics."

"I think there's plenty of solutions to Fermi's paradox, that we don't need to add this as an extra one, but yes, this would be my favorite explanation for it, that there is no inevitability about complex life, that there's nothing in the laws of cosmology that say, "[Complex] Life will start." I think that there probably is something in the laws of cosmology lending itself towards bacteria, but the idea of more complex life... I certainly wouldn't see a Simon Conway Morris view, for example, that the origin of life is so complex that you require God to put everything in motion and then will take you all the way to humans."

"I said you [bacteria] are not morphologically complex, you are biochemically awesome."

"[I]t's interesting to me that the bacteriophages, the viruses that you find in bacteria, are not remotely similar to the ones that you find infecting archaea, which again are not remotely similar to eukaryotic viruses. ...They're different in their appearance. They're different in their mechanisms in which they force their... I mean the bacteriophages are these classic lunar module landing things... They are stunning things to look at. ...Some es look like bottle balls or postage stamps, strange shapes... They don't have any genes in common. They don't have mechanisms of entry into cells in common. They appear to be independently derived."

"That's why they [viruses] are not in the tree of life. They don't relate in a very direct way. ...[T]he tree of life now is not only about ribosomes. You can build trees from whole genomes, but viral genomes? They don't really fit in, in a way which makes sense to people."

"I've been asked on various occasions, "Why don't we, as an origins of life community, get together, think what a killer experiment is, and then go and build a or something, where we go and do the experiment?" And the answer to that is... [W]e can't agree with each other about what experiment would you do? ...[I]t is intrinsically a lot more complex, precisely because it's a continuum. We don't know. We don't agree about what environment, we don't agree about what kind of chemistry or biochemistry. We can't join these things up, and so it seems to me a much healthier environment is to be deliberately multiple about it. Not to say, "Ok, this particular world view is going to dominate." I think we have to have multiple views until we know more."

"I like philosophers. I think they can teach scientists how to think very often, and... there's a lot of sloppy thinking among scientists, and I think philosophers can be quite rigorous about it. It gets a lot of scientists cross with philosophers who don't engage with science, but I think there are more philosophers these days who are engaging in a serious way with science. I think they have important things to say."

"[Martin Rees] may be right. If we were to go back 5 million years, as intelligent apes, and ask ourselves "What is postbiological life?" I think the answer is it's not a concept that would possibly mean anything. So we've had... 4 billion years of life on earth, and it's come up with an enormous wealth and variation, but it's all organic and... the chances of it coming up with humans? I can't put a number on that. ...I don't think there's an inevitability that life, once it's started will give rise to a human-like intelligence or beyond that. I think there's nothing inevitable about it, and if we just go back a few million years on earth, there was nothing inevitable about it. So I, personally would still look for organic life, but... I'm not sure that would be the easiest thing to find. It may be that it's easier to find, yes, nano aliens or something."

"It requires that life elsewhere should be modeled along similar lines to life here, which is that it should be cellular, it should be carbon-based. It should be in water. If those things are not true, then there's no reason why that numbers game would apply anywhere else. But if those things are true, then yes, I think the fact that photosynthesis only arose once, that Eucaryotes only arose once, that what Nick [Nicholas J.] Butterfield calls organ grade multicellularity, which is to say quite serious differentiation with scores of different cell types and specializations. We don't see that in fungi. We don't see that in algae. ...[Y]ou see two or three different types of cell. So that's rare. It's in plants and it's in animals. It begins to look less likely. I think it's reasonable to say it's less likely, but I wouldn't like to rely too much or put too much weight on it."

"[On the controversy between and .] [T]he classic case of convergence would be the eye and the human eye, or ian eyes. ...The common ancestor they had had a light sensitive spot, they did have some regulatory genes in common... for example, but that had to effectively independently recruit all the rest of the genes required to make a camera type eye, and that direction of evolutionary travel was in parallel. It was convergent. We even see in some s... a camera-type eye in single-celled critters where there's a retina made from s. There's a made from mitochondria. There's a there. They don't have a brain. I don't know how they use this thing but... plainly it's a camera-type eye. ...It's a of some sort. ...I would see that as a completely independent origin of a camera-type eye, albeit without a brain. I would see the octopus' and mammalian eye as being convergence in the Simon Conway Morris sense... There are certain ways that you can make an eye, that work, and all the steps along the way have to be favored, and... perhaps there are seven or eight... fundamentally different types of eye that we see on earth, and most of them have arisen more than once, always from a common ancestor, generally, that had as a light sensitive pigment. So you're then into an interesting terrain or... How common are the right types of light sensitive pigment? They're chemically not so straight forward."

"I do like this quote from Simon Conway Morris that if the aliens call then don't pick up the phone. I'm not sure I'd really like to meet any of them very much. Perhaps... meeting bacteria would be the least scary... [T]he chances of meeting aliens is so remote that I haven't really troubled myself very much about it. It would be nice to think that if we did, somehow they would be a superior intelligence... they would have solved a lot of the problems of aggression and whatever else that humans have, but I fear not. I fear that it would be the opposite, that... natural selection has a knack of producing nastiness in intelligence."

"Does anyone care if there's an awful waste of space? It's a form of wishful thinking... We would love for the Universe to be full. ...Personally, I grew up on the Hichiker's Guide to the Universe, those kind of crazy science fiction yarns, or Star Wars or whatever it may be. The idea that the Universe is full of other intelligent beings, all kind of finding a way of getting along or having a war, but having some heroism thrown in, but... it's all human vision of ourselves thrown onto a cosmic scale. Do I believe any of it? No... Is there anything that I think, from my understanding as a biologist, that would tend to lead to that? No... Does it matter if it's a tremendous waste of space? Well, that's to say "What's the point of the Big Bang?" I don't know. The idea that the Universe may be completely empty apart from matter and energy? It would seem to be, perhaps, the default hypothesis. The fact that we find life is surprising. It would be nice if there were laws of the Universe that tended to give rise to life. Maybe there are at the level of bacteria. I don't see it at the level of large, morphologically complex beings... I think it's emotive. It's pleasing, but I doubt it's true."

"[M]ost of what I teach and interact with the students is more about life on earth and the principles governing evolution, and from my own point of view, the biochemical side, which is not normally part of the evolutionary biology... [I]t's relatively rare for me to discuss life elsewhere in the Universe with them."

"Thew problem here for me is that I'm in a biology department and is still somewhat frowned upon by a lot of biologists who would see it as a form of speculation. So the courses that I teach are about life on earth and they're not so much about life in the Universe... [I]t is something that I should develop, I think."

"There are people at UCL, Ian Crawford, who's doing a great deal for , but it's not something which is happening through my department. It's happening through s. It's not happening in biological sciences..."

"I've had long and sometimes difficult discussions, especially about the singularity of the origin of Eukaryotes... A lot of people don't like that. ...[I]t's not really about what does it say about the probability of life elsewhere, although it has things to say to that. It's really about life on earth, and a lot of people are very uncomfortable with the idea of improbability... I've had quite difficult discussions with some students about that, but rarely... about life elsewhere in the Universe."

"I see myself as a biologist or a biochemist, but... in the context of as a broader subject, it forces me to wrestle with physics, with cosmology, with chemistry, with geology, with earth sciences or planetary sciences, and that's a thrill. ...I think it's what most people are drawn into science in the first place for, because science, in its biggest sense, is what inspires people, and by the time that you've got to the level of doing a PhD, it's narrowed down so much that a lot of people are almost forced to lose their imagination, and their creativity as a scientist... I think astrobiology is a subject that puts all that back in, in heaps."

"No, we're not alone [in the universe]. We share it with lots of friendly bacteria [and this includes bacteria on other planets]."

"For decades, biology has been dominated by information—the power of genes. ...[Y]et there is no difference in the information content of a living protozoon and one that died ...The difference between alive and dead lies in energy flow ...the ability of cells to continually regenerate themselves from simpler building blocks."

"Even the laws of thermodynamics... can be recast in terms of information — Shannon entropy, the laws of bits of information. But this view generates its own paradox at the origin of life. ...Place information at the heart of life, and there is a problem with the emergence of function ...the origin of biological information. There are problems... in understanding why we age and die... diseases... and how experiences can give rise to conscious mind. ...A far better question ...what processes animate cells and set them apart from inanimate matter?"

"This book will explore how the flow of energy and matter structures the evolution of life and even genetic information."

"It is the movement that creates the form."

"Flux is a form of flow, but with one crucial difference. ...In biochemistry flux is the flow of things that are transformed along the way."

"[[w:Flux (metabolism)|[M]etabolic flux]]... Even a simple bacterial cell can undergo... a billion trnasformations per second... is... what being alive is."

"became the study of how... simple molecules were interconnected one into another. ...The [simple] molecules ...containing ...up to about twenty carbons, but most ...have fewer than ten."

"[B]iochemical pathways that produce the basic building blocks of life are... conserved across practically all cells."

"The double helix of DNA... is composed of two long chains [of 'letters'] that snake around each other... each strand providing an exact template for the other. ...[E]ach strand ...contains just four types of letter, with ...billions ...arranged down... the chain. ...3,000 million letters ...make up the human genome ...[T]he same — the same lines of code — can have different effects depending on the context."

"The is riddled with redundancy."

"The driving force of is thermodynamics. ...[I]n this context ...the chemical need to react (to dissipate energy) in the same way that water needs to flow downhill."

"If the Krebs cycle is ordained by thermodynamics, then it should take place spontaneously in some suitably propitious envirnonment, even in the absence of s."

"The inner logic of ... Much of it is imposed by thermodynamics; some is facilitated by catalysts. Some is refined by genes. And part stems from the vicissitudes of life itself, which forced evolution down improbable paths, while transforming our geologically restless globe from a sterile, anoxic planet into the living, high-octane world of today."

"In Transformer, Lane indulges in a great many of the banes of popular science writing... These kinds of over-earnest attempts to defang a complicated subject are an enduring mystery; the people who need them won't read the book, and the people who'll read the book don't need them. ...Fortunately, Lane’s discussion ...is itself very winningly animated, and that saves it ...Lane’s personal excitement ...goes a long way toward making ...biochemistry comprehensible ...[T]his is done through personalities; Transformer is as much about the people investigating the Krebs cycle as it is about the cycle ...That kind of personality pervades the book and makes it ...consistently fascinating reading."

"I read a book called The Vital Question. ...A few months later... I had also ordered Nick’s three other books, read two of them, and arranged to meet him in New York City. ...He is one of those original thinkers who makes you say: More people should know about this guy’s work. ...Nick is talking about how getting energy right at the cellular level explains how life began, and how it got so complex. ...I'm intrigued by the practical applications of Nick’s work. Mitochondria could play a role in diseases like cancer. ...[O]ur foundation’s global health team is talking to Nick about the potential implications for the fight against malnutrition. ...[T]here’s no telling whether his specific arguments will turn out to be right. But even if they don’t, I suspect his focus on energy will be seen as an important contribution to our understanding of where we come from, and where are we going."

"Nick Lane thinks life first evolved in hydrothermal vents where precursors of metabolism appeared before genetic information. His ideas could lead us to think differently about aging and cancer."