Nick Lane: evaluation

Transcript context

…There are so many aspects of this story, so many possible answers I could give there. In terms of eukaryotes, giant bacteria, the likelihood of life, a lot depends on observation. We simply don’t know enough about what’s out there. So it’s not necessarily experimentation. If I assert that giant bacteria are always going to have extreme polyploidy with multiple copies of their genome, and you find an example that’s not like that, my ideas are already breaking up. So that’s useful to know. For the origin of life, I really wish I could come up with a convincing reason why I should go down in a submersible to a deep-sea hydrothermal system like Lost City. I would love to go to Lost City. But the trouble is that the ocean chemistry is completely different now to what it was 4 billion years ago. It’s now full of oxygen. It’s full of bacteria and things as well. But the ocean chemistry is different because there’s oxygen. There’s no iron, there’s no nickel in the oceans. You can go to a vent like Lost City and the walls are not made of catalytic minerals anymore. They’re made of aragonite and brucite, so calcium carbonate and magnesium hydroxides and things like that. So the chemistry it can do is very different, and there’s lots of bacteria living there. I would gain, beyond just the sheer amazement of seeing it, there’s not a lot it would be able to tell me. What we’re actually doing is experiments in a lab in an anaerobic glove box where you exclude the oxygen. So you can do these experiments reacting hydrogen and CO2. How many of the molecules in biochemistry can we produce that way? It’s slow and laborious, and you get small amounts and sometimes you get contaminations. Sometimes you have to start all over again. It’s slow work, but it’s moving forward. It’s not just us, either. There are other groups around the world. Joseph Moran’s group, for example, has done a lot of really nice biochemistry along these lines. That’s moving forward, but we’re talking decades before we’re getting to the level where we can say, “Right, we can drive flux through all of metabolism, and here’s the set of conditions that will do it.” Certainly some years. There are big crux points, like making purine nucleotides where there are 12 steps in this synthetic pathway, and all the intermediates are unstable and break down easily. It has been done in things like methanol, so not in water. In water, stuff breaks down. We’re trying to do it. It’s difficult. I believe we’ll get there, which is why we’re trying to do it, but maybe we won’t, in which case, again, the hypothesis is wrong. You’ve got to wake up every morning and think the hypothesis could be wrong. It’s beautiful, it makes sense, but there are so many beautiful ideas killed by ugly facts. There’s no good believing that you’re right. You’ve got to believe you’re probably wrong and keep going anyway. s beautiful, it makes sense, but there are so many beautiful ideas killed by ugly facts. There’s no good believing that you’re right. You’ve got to believe you’re probably wrong and keep going anyway. The other thing which I’m excited about at the moment is work on anesthetics and mitochondria, it turns out - I heard this from a guy called Luca Turin a few years ago now—who pointed out to me that anesthetics affect mitochondria. I had no idea that anesthetics affect mitochondria. They do. We’ve been doing experiments on it, and it seems not fully established yet, but it does seem as if their main effect is mitochondria. Anesthetics work on all kinds of things, including things like amoeba. It doesn’t prove anything but it’s beginning to say, if you can make an amoeba unconscious, then was it conscious before? Not as we understand consciousness. The way we would understand consciousness is really about neural nets, a nervous system, and all the complexity of human consciousness. That’s what we primarily think about. But there’s a deep problem which goes back. It’s the mind-body problem, but it was framed by David Chalmers as the hard problem of consciousness, which boils down, as my understanding of this is, to more or less that we don’t know what a feeling is in physical terms. You can understand the information processing of a neural network. But if you feel miserable or you feel pain or you feel love or whatever it may be, what actually is that in the chemistry of the system? The problem is that you have all of these neural nets firing and some of them are conscious. We’re aware of what we’re thinking about. Others, which seem to have all the same properties in terms of the neurons—they have synapses, they have neurotransmitters, they depolarize, they pass on an action potential—but we’re not conscious of it. It’s non-conscious information processing. So there’s this question. If anesthetics affect things that don’t have neural nets, and feelings are something that we can’t define in terms of a neural net, could it be that feelings are somehow linked more broadly to life? So why would they be? The way I think about this is as an evolutionary biologist. The first question is, would we think that the feelings are real? I would say yes. Do we think that they evolved? I would say yes. I think any evolutionary biologist would say yes to those questions. If it’s real and it evolved, then natural selection must be able to see it and act on it in some way. In other words, there’s something physical about it that can be selected for. I don’t think there’s anything controversial about that statement. But if it’s physical and real and has been selected on, the implication is we should be able to measure it. It has to offer an advantage for selection to act on, and if it’s a physical process, it should be measurable. But we don’t really know what we’re trying to measure here. I then revert back to thinking, what would a bacterial cell need to do? This is just back-of-the-envelope thinking. I immediately think about metabolism. What’s the difference between the inside of a bacterial cell and the outside world? The inside is metabolically alive. This is just back-of-the-envelope thinking. I immediately think about metabolism. What’s the difference between the inside of a bacterial cell and the outside world? The inside is metabolically alive. It’s doing stuff with its chemistry all the time, and it’s at a colossal rate. A bacterial cell will have about a billion reactions every second in this metabolism. I’m immediately left wondering, how is it all controlled? How do you get this cell to have a coherent behavior so it decides, “I’m going to crawl over there”? How do you even know what state you’re in? How do you synchronize all of this biochemistry? Probably most people’s answer to that would be metabolic regulation of one sort or another. But that’s not really the driver. The driver in the end is the thermodynamic drivers. How many electrons do you have? That’s in the form of food or NADH or whatever it may be. How much energy do you have in the form of ATP? These are the things that are going to synchronize reactions in the same phase. The problem there is when you’re dealing with molecules, you’re dealing with tens of thousands of them, so you’ve got a large statistical sampling which is time-consuming to figure out. But there is a better way of doing it, which is to say, if you’re taking electrons from food in NADH and you’re passing them to oxygen, but you’re generating a membrane potential and that’s driving ATP synthesis, you can measure the rate of change and the membrane potential and the fields that would be generated, electrostatic and electromagnetic fields. That’s going to give you a handle on your state, on your metabolic state in relation to the outside world. Is there enough food there? Is there enough oxygen there? Is it too hot? Is there a virus? Do I have enough iron to be able to do all these reactions? You’ve got all these potentially conflicting feedback loops, and you’ve got to make a decision. Just thinking loosely about how a bacterial cell is going to behave, you find that you’re already framing it in terms of, as an entity, as a cell, it’s got to make some decision about what to do. It’s got to integrate all this information and make a coherent decision as a self, as an entity. Is that free will? Probably not in any way that we recognize it, but it makes a decision in relation to its environment, and the outcome is survival or not. What I think a feeling is then is effectively the electromagnetic fields generated by membrane potential, which is telling you what your physical metabolic state is in relation to the environment you’re in. That leads me to a question. If consciousness is somehow about mitochondria, are the mitochondria in that sense just really simply an ATP-generating engine, and you interfere with the way they make ATP and so anesthetics work by effectively giving you an energy deficit so the brain closes down? That would be dull if it were true, but it would be useful to know if it were true. Much more exciting would be, do mitochondria generate the kind of fields that I was talking about in bacteria that are giving some indication of your status in certain mitochondria, certain neurons, and the anesthetics interfere with that?…

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