Nick Lane

"Mitochondria are a badly kept secret. ...There are usually hudreds or thousands of them in a single cell, where they use oxygen to burn up food. ...[O]ne billion ...would fit comfortably on a grain of sand."

"According to mitochondrial gene analysis, man didn't interbreed with Homo Sapiens..."

"[T]he contends that ageing and many of... [its associated] diseases... are caused by... free radicals leaking from mitochondria during normal . ...As they burn up food using oxygen, the free-radical sparks escape to damage adjacent structures ...Many cruel inherited conditions... are linked with mutations caused by free radicals attacking mitochondrial genes."

"From around the mid 1990s, researchers discovered that is... governed... by the mitochondria. ...[T]he failure to commit apoptosis is the root cause of cancer. ...In cancer, individual cells bid for freedom ...Without , the bonds that bind cells in complex s might never have ebvolved."

"[A]ll multicellular plants and animals... contain mitochondria."

"[A]fter a decade of careful , it looks as if all known eukaryotic cells either have or once had... mitochondria."

"[T]he mechanism by which mitochondria generate energy, by pumping protons across a membrane (), is found in all forms of life... It's a bazarre way... This idea, however... won Peter Mitchell a Nobel Prize..."

"Different species have transferred different genes to the nucleus, but all species with mitochondria have... retained... the same core contingent of mitochondrial genes."

"[L]ife will probably get stuck in a bacterial rut elsewhere in the universe... we might not be alone, but will almost certainly be lonely."

"This membrane, so vanishingly thin, looms large... for bacteria use it for generating their energy."

"[[Bacteria|[B]acteria]], the simplest of cells, are... so complex that we still have almost everything to learn about their invisible organization."

"The possessors of... nuclei, the s, are the most important cells in the world. ...[A]ll plants and animals, all and fungi... essentially everything we can see with the naked eye, is composed of [them]..."

"In bacteria, the DNA forms into a long and twisted loop. The contorted tracks... close... to form a singular circular . In eukaryotic cells, there are usually a number of different chromosomes... each has two separate ends."

"[N]o bacteria coat their DNA with s: their DNA is naked. The histones not only protect eukaryotic DNA from chemical attack, but also guard access to the genes."

"The information encoded in DNA spells out the molecular structure of s. This, said Crick, is the 'central dogma' of all biology: genes code for proteins."

"The sequence of letters in a specifies the sequence of s in a protein. If the sequence of letters is changed—a —this may change the structure of the protein (...not always, there is some redundancy... technically degeneracy..—several combinations... can code for the same amino acid.)"

"s are the crowning glory of life. ...[T]he rich variety of life is almost entirely attributable to the... variety of proteins. ...Perhaps the most important group are the s ...biological catalysts that speed up the rate of biochemical reactions ...with an astonishing degree of selectivity for ...raw materials."

"The DNA code is inert... stored safely... For daily use the cell relies on disposable photocopies... made of RNA... composed of similar building blocks... spun out on a single strand rather than the... double helix."

"Does it make sense that life is cellular? Would you expect to find life being cellular elsewhere? I suspect that for organic life... it would be cellular."

"Whether or not it would be possible to drive the kind of protein machinery that you see in modern cells, like an ... that makes the energy currency of life... If it were just sitting there in a in a vent, can work out whether the natural... ion gradients in these vents would be... powerful enough to drive this machine to work. ...[Y]ou need to know what are the substrates, what are... the materials that it needs to operate? Where are they coming from? What's the concentration of them? You realize that you have no answer to any of those, and then what's the product? Well, it disappears off somewhere else, as well. So how can selection act if you've got stuff coming in from some unknown place and the product leaving to some unknown place? It made me realize that cellularization is important as a way of keeping the inside in and in keeping the outside out, and so I now have problems with the idea of seeing the entire vent as a kind of a living system."

"[T]here's a limit to just how far vents can take you... but... once you've gotten as far as , then you've freed yourself from a fairly small energy flow, a fairly tight and focused energy flow."

"It does seem to me, from our experience of life on earth that allows you to... step up, by probably orders of magnitude in just how much life can take over a planet."

"It would be a little disappointing if we didn't even find bacteria in our own solar system. I would be rather surprised to find what I would describe as large, morphologically complex life. ...It only arose once on earth. That doesn't necessarily mean that it's improbable... but it does raise some interesting questions about why, and... I think we can apply principles to it, and those principles effectively are why do bacteria and , as assistive groups to the bacteria... They're biochemically very complex. They're genetically very complex. They're kind of structured in a different way where they have large, complex metagenomes, but... I doubt very much that we'll ever find anything of the [morphological] level of complexity of a flea, composed of bacterial cells."

"One is pretty much the same as another stromatolite, to my eye. That probably gets the stromatolite biologists in a fury, I suspect..."

"I'm not particularly... eucaryocentric, but I do think there is a problem to solve there. ...There is a difference in morphology ..."

"To me it [we] means life as a whole, so I would include bacteria in we. ...Life on earth is a whole, yes I think so. We share the . We share the same cell structures. I feel quite a strong fellow feeling with bacteria."

"If we, meaning humans now... find life somewhere else, most people would be disappointed if it turned out only to be bacteria."

"What is [life] it? Would we even recognize it. What I imagine we would find would be cell-like things. Not a million miles away from bacteria, using , probably in water, not because it's the only way of organizing. It's just that carbon is very good at that kind of chemistry. It's very common in the universe. Water is ubiquitous. We know, from the principles of life on earth, that all this stuff works and we know that it's thermodynamically favored. ...[J]ust statistically, I would expect, maybe 900 times out of a thousand that life would be organized in a similar way to life here. That's not to say it can't be different. It's just probably... going to be similar."

"Now, if we get to complex life and we get beyond organic life forms into artificial intelligence, post-biological, then anything goes and maybe that's what we should be looking for."

"I would define complexity, not really as genetic complexity because if you take it purely as genetic complexity, E. coli... a single cell may have 4,000 genes but the metagenome, the pool of genes in E. coli around the place may be on the order to 30,000 or more... [T]hat's the level of complexity equivalent to the human genome, or even more complex than the human genome, but it's organized and structured in a different way. ...You might say that it's structured in a similar way to an ... but I think an ant colony has taken that level of Eusocial behavior a long way beyond anything you would see in E. coli. So I would define it as morphologically complex, meaning cells are larger and have a lot of stuff in them."

"[W]e are biochemically quite simple in comparison bacteria. Simpler than bacteria. In terms of our metabolic biochemistry we are really limited. ...[W]e have ...across the entire domain of s, about the same degree of metabolic sophistication as a single bacterial cell."

"They [bacteria] haven't used it [their more complex metabolism]... to give rise to more complex morphologies beyond the kind of stromatolite type structures, beyond s. That seems to be a limit. Some multicellularity, some degree of differentiation and complexity, but nothing... to compare with the flea."

"I think we share consciousness right across... not just even the animal world. I would see it going down even to the level of cells, some kind of flickering of consciousness. So I don't feel alone on earth, but I do think that there is something different about humans."

"We also have a power to destroy the earth, and... it's probably unique. ...Destroy ourselves, destroy a large part of life in earth, not the bacteria... If we take ourselves out, we'll give it five million years and it will be indistinguishable, apart from ourselves."

"I'm... interested in the principles of what governs the emergence of life on the planet, with a certain set of resources. Can we understand it? We'll never know what happened, so we'll never know how life started on earth. ...[I]f those principles are enormously difficult, if it turns out that it's a freak statistical accident, then there's little point in studying it and we will gain... very little. If, on the other hand, those principles are reasonable, intelligible, that we can study them in the lab and demonstrate that the steps that we propose are plausible and... we can demonstrate it, then I think that's as close to understanding the origin of life [as] we can get. ...[I]f those principles are generalizable, then as a scientist, that's... a pleasing thing. I'm not sure there's any more that's more pleasing to me, personally as a scientist."

"[W]e can't agree among ourselves, as an origins of life community, what were the conditions... under which life arose on earth. ...Within the field itself, probably the leading candidate... would be terrestrial geothermal systems, starting with and powered by UV radiation. There's been a lot of rather beautiful chemistry... in a terrestrial environment in some kind of geothermal pool... and cyanide chemistry, it works well as chemistry. The problem I have with that is that it doesn't link up very well to biochemistry of cells. I'm a biochemist and I would like to see some continuity between and , and there's not much there, to me. That doesn't mean that it's wrong. It's just that... [I] would like to see some continuity."

"What does life do then? ...it seems reasonable that the earliest forms of life were ic... [i.e.,] they grew from gases... found in normal geological environments through an energy flux which is equivalent to cells which we see today, which is to say, what all life does today. There's a very simple phrase from Mike Russell... "hydrogenate CO2"... [i.e.,] add onto to make organic molecules. That is the structure of in cells, and different cells can get hydrogen from all kinds places. They can strip it out of water. They can get it from , but it also comes bubbling out of the ground as hydrogen gas, and that seems to be the simplest form of life imaginable as... life on earth. It's reacting hydrogen and CO2, and they don't react easily. The way that cells make them react... is to effectively use an electrical charge on a ... [T]here are environments like deep sea s that provide... for free with an equivalent electrical charge across a barrier, and I think... that's the way to see the question."

"[Life is] a continuum. I think there are some phase transitions, probably, and the origin of... genetic information is probably one of them. ...[W]e are doing some modeling work to try and work out how evolvable... a geological system [can] be along the path to getting to cell-like things that... most people would understand as life. How far can you go down that line before you have genetic inheritance? ...[A] long way, but you get to a point where... it's no longer evolvable. ...[I]n our modeling, you can get to a point where you're capable of producing s capable of making copies of themselves with a degree of sophistication, but getting beyond that, to specializing to different niches and so on, I don't see the way, without genetic inheritance."

"I deliberately avoid having... [a working definition of life]. What I quote... is... from Peter Mitchell... a pioneer... of... , that essentially all cells, with very very few exceptions, are powered by... proton gradients across the membrane. So on one side of the membrane surrounding the cell you've got the high concentration on the inside, a low proton concentration [on the outside]. Protons are... the positively charged nuclei of atoms, so... [y]ou're pumping them out and... putting a charge on the membrane... That's as universally conserved across life on earth as the itself, which implies, as a mechanism, it's very early... [I]t's not something anyone ever predicted. It's not something that... emerges from a chemical understanding of the biochemistry of cells."

"It could be any of those [sodium, or other ion gradients]. The fact of life on earth is that it tends to use proton gradients, and we know particular environments that do use proton gradients, and the reason I think protons is because , which is to say the proton concentration, can modulate the reactivity of both and . Now sodium concentrations wouldn't do that, but protons, if you've got gas in alkaline fluids, hydrothermal fluids... what you've got coming out of these s, hydrogen is more reactive in alkaline conditions. It really doesn't want to push its electrons onto something else, but if it's in alkaline conditions it pushes its electrons onto something else, and the protons are left behind and they will react immediately with the hydroxide ions to form water, which is thermodynamically very favored, and so it's far more likely to push its electrons onto CO2 if it's in alkaline solution."

"Now CO2 itself... doesn't really want to pick up any electrons and become reduced to an organic molecule, but if it's in a relatively ic environment where there's s available, it picks up a negative charge. It doesn't want another negative charge. It's going to try and repel that, but if there's a proton around, it picks up the proton. Now it's neutralized the charges... pick up another electron, another proton. So it's much easier to accept electrons in an acidic environment. And this is the structure of these vents and it's the structure of cells, and it's how these earliest, most ancient cells we know about actually do fix CO2. They use the proton channel in the , which effectively locally acidifies an environment and allows this reaction to proceed. So I think that's fundamental, simple... works well, and it's testable in the lab."

"We've had some success and quite a lot of failure too. ...[T]he problem we're having... is reproducing the successes we have had. The big problem... for anyone working on this is that hydrogen gas is not soluble in water at atmospheric pressure. What we really need to do to make this work is to ramp up the pressure in the system to 300 bars and then we need a continuous flow. For this to work you need a across a barrier. Then it should work. We don't know, and we haven't got the funding to build a high pressure reactor. We're collaborating with a group in Utrecht to do that. ...If we can do that experiment and then it fails, then my confidence that this would be a suitable possible origin of life would take a serious knock."

"That's a question about the meaning of life... Why are we here? What are we doing? What's important to us? Why should we struggle to do anything, and I think most of the answers to those questions lie within society itself. ...I don't see a greater meaning, that we've been put here as a species, that we're exceptional in any way. We're just another species. We're very much similar to pretty much everything else, and I think what we've done that's good has been the achievement of society as a whole... [A] lot of people within society... humans have a need for an origins myth, and that origins myth, if it happens to bear some semblance to reality, I think a lot of people are genuinely interested to know what can we say about the origins of the Universe, about the origins of the solar system, about the origins of life. ...[C]an we as ...puny-brained humans come to, through logic, through experiments, through thinking about it, through observations, come to an explanation for how life came to be. It's a grand question. It would be wonderful to know the answer. I think a lot of people would love to know that answer, and I personally would love to know that answer, even if my own views on the subject turn out to be completely wrong."

"Yes I do think that... [viruses] are alive, not for the obvious reasons. ...I was invited to do some filming with the BBC... it was about cells, but they'd been asked to tell a story... about the viral infection of a cell, and I said, "Well I don't know anything about viruses," and they said "No, we just want to know a little bit about early evolution," and I said, "Great, I can talk about early evolution in cells, but I can't really talk about viruses." ...[T]hey said "OK, no problem," and they flew me out to Iceland to some black sand beach that I think had been used in some science fiction movie, and they said "Right, so Nick, what can you tell us about how viruses... drove the early evolution of life?" and I said, "Oh God, guys, come on!" and they said, "No, this is a film about viruses." So I had to think quickly... What I found myself saying was that viruses were parasitic on their environment and can afford to be very simple because their environment is very rich. They live inside cells. Everything that they need is provided for them, but plants are parasitic on their environment. They still need CO2. They still need water. They still need light. ...I wouldn't hesitate to call it [parasitism] a definition of life... [L]ife as a rule is parasitic on its environment, and the level of parasitism depends on the sophistication of the environment. So in that sense viruses use the richness of their local environment to make copies of themselves and they behave with the kind of low cunning that's characteristic of life. So I think of them as alive, yes."

"Viruses are quite sophisticated in the sense that they're forming virion particles and they're infecting other cells... s and things... selfish genes, I suppose in the broadest sense."

"s of some sort [lie between a hydrothermal vent system and a virus] in my mind. The trouble with viruses is that they do need a sophisticated environment to make copies of themselves. Same with selfish jumping genes, transposable elements and so on. They need to be in an environment where they can take advantage of something which is converting the environment into copies of themselves, and there's a rule... This is changing with the discovery of all these es, but as a rule you need some form of to convert the environment into copies of yourself."

"Now it's possible to have some kind of protocell with some form of metabolism without any genetic heredity. It's possible in principle. Is it alive?"

"I read some of those ideas years ago, , and thought it was thrilling. Over recent years I don't really see the need for a kind of genetic intermediary between an RNA level of genetic replication and some other form of replicator. ...[T]here's no suggestion that it's there in biology. There's no suggestion that I know from geology that is capable of giving rise to more complex systems, or to having an organic takeover. It seems to add in a layer of unnecessary complexity. So I much prefer to get straight into organic chemistry, and straight into as we know it."

"[W]hy is metabolism structured this way? There has to be thermodynamic underpinnings for it, otherwise it wouldn't happen. It had to have arisen in the absence of genes... in my mind and therefore there must be environments which are favoring protocells with this kind of metabolism, making copies of themselves... In my mind they have to get better at it, otherwise RNA is just never going to appear."

"Life as we know it has both, and the people who say s first are in effect saying, "Well, there's plenty of s, there's plenty of RNA. The environment's providing it for free," without worrying themselves too much about what kind of an environment is going to provide all of that for free, and by definition, an environment which is effectively metabolically sophisticated enough to provide s is non-living and therefore not part of the question, so they're just pushing it aside. I would say that the whole metabolic side is needed to give rise to genetic information and nucleotides in an RNA world in the first place, that it would be a dirty RNA world contaminated with s and s, and s and things..."