A Nick Lane Book Review??

Power, Sex, Suicide: Mitochondria and the Meaning of Life

The following is a silly little book review I wrote for some friends on discord, years ago. I just stumbled across it again and thought it was fun.

You wanna talk about mitochondria? I've been dying to talk about mitochondria for three weeks now. Here we go!

This book should have been called abiogenesis, multicellular organisms, mitochondrial DNA, complexity and metabolism, apoptosis and sex, gender, aging, and why life is energetic, adaptionistic, and not informational and random (Gould can suck it). That will serve as our little outline here.

First things first, the structure. The whole book is written in a kind of back and forth dialogue. The author asserts something, or asserts what a theory says, and then goes through the history of the tests and debates that were done to figure out why or why not the assertion holds. The whole thing builds pretty well on itself, and it rewards you for remembering what was said throughout. Not surprisingly for a book that features a lot of evolutionary history, the subjects stack. You're gonna hear for instance how cell suicide evolved, and then you're gonna hear how evolution used that as a part it already had lying around for other purposes.

The full verdict before I regurgitate a bunch of the content is that this was really engaging if you like biology (probably my favorite science subject, but I need to sample more). If I had realized the audiobook was sixteen hours before I got halfway through, I might not have started though. Take that for what you will. It's narrated by a British guy, which of course boosts the rating. I'm comparing it to another book I really liked, Behave by Robert Sapolsky. Using that as the baseline for a 9/10 biology book, this is probably a nice 7.5.

We repeat the holy mantra: The mitochondria are the powerhouse of the cell.

This is important because it's what allowed life to climb an ascending ramp of complexity. Before the evolution of eukaryotic (true nucleus) cells, there was almost two billion years of boring slimeworld, where nothing existed but slime. Simple, single cells and colonies of bacteria and archaea.

Of course, this is all just what I recall and what the book claims, so none of this is gospel. But on we go.

All life generates its energy by pumping protons across an energy gradient, thus maintaining their 'proton motive force'. Bacteria and archaea are limited in scaling potential because they use their own external membrane for this. As they grow in size, their internal volume scales cubically, and thus they face major efficiency drop-offs trying to maintain the proton motive force and pump into such a large area. But mitochondria on the other hand can scale their surface area along with their internal volume, because they are these little endosymbiotic power packs. If you need more energy, just print more power packs. Scaling unlocked. Eukaryotes have way more DNA and complexity.

That's the basics. Let's quickly cover a few things. Lane believes that abiogenesis did not begin with an RNA world as many others do, but rather that the proton gradient itself began first. So rather, energy and chemistry came first, not information. That's neat for philosophical reasons, but I won't go on too much of a tangent. This theme of vitalism and the driving force of energetic efficiency throughout evolutionary history is a recurring theme. It is for instance what leads us into mitochondrial DNA. Why do the mitochondria have DNA at all when there is a constant reproductive pressure to jettison it? Life is all about replicating, remember, and the more DNA you have the slower you replicate, and thus decrease in your population share (evolution is also about populations percentages, not individuals).

The answer is that the nucleus makes an inefficient, sort of bureaucratic manager of mitochondrial function. There is only one of it, and many mitochondria. So by the time it gets wind of some dysfunction and sends out a barely discriminate signal to fix it, it is A) behind schedule, and B) not targeted enough to reach the specific mitochondria who have the problem. Solution? Put a control box INSIDE the mitochondria itself that measures and modulates production.

A constant balance has to be maintained because if the proton pump backs up, that's bad. It releases free radicals or something. This bit was complicated.

We skipped multicellularism, so let's go back to that. There's some stuff about how mitochondria might have gotten inside a bacteria. Suffice to say, it was either to share a mutually beneficial style of respiration on different complimentary chemicals (the hydrogen hypothesis, iirc) or because it was a parasite. Lane leans toward the former.

But once you got one inside the other, then you needed a way of punishing defectors so you could maintain a proper multicellular lifeform. Unlike in colonies, where people are free to leave any time, all higher forms of life tend to punish that business with a brutal and efficient death (apoptosis) which begins inside (hence why it is sometimes called a form of suicide, though not always voluntary) and then packages the corpse up for neat consumption.

Of course I'm skipping over the fact that for a very long time you had eukaryotes before you had multicellular eukaryotes. You got all kinds of neat new things like predators which you didn't have before. Apparently eukaryotes can maintain enough energy to have big complex cytoskeletons that let them monch on smaller dudes.

And so on.

But by the time that had been going on for a while, mitochondria are, remember, still endosymbiotes. These are symbiotes that live inside. Another way of saying completely selfish, individual organisms all their own. So these little guys, if they are trapped inside a larger cell, can no longer live outside though. And if that cell is damaged and can't duplicate itself, they want a way to go on replicating anyway. So the theory goes, they figured out a way to coax their host cell to recombine with a buddy, thus giving them more breathing room and also fixing or covering up the previously damaged DNA. This is what we call sex. Cellular recombination.

The mitochondria do this coaxing with certain chemical signaling methods that, poetically, also happen to be what later on became the method of apoptosis. Cytokine runaway feedback loops and whatnot. Once again, I am fuzziest on the detailed biochem, which I think you'll forgive me for.

Later on, multicellular organisms could no longer allow the selfish mitochondria to prompt cellular recombination so they turned it into a weapon of self destruction, which is generally tied now to whether or not the cell is being efficient. The reason we have two sexes and not none or a billion like certain fungi, is, to make a long, long story short, because only the mother passes on her mitochondria. There are mechanical reasons for this, but basically, the cell cannot construct new mitochondria purely from DNA. There is a direct physical continuity of the population of mitochondria that have their own unique DNA and are separate lifeforms yes, since the very beginning of the merger.

Because the cell cannot construct new mitochondria, children must get fully formed copies, and due to some game theory and weird evolutionary dynamics, in order to stop competition, the balance ended up with a certain stalemate between mitochondrial populations with drawbacks on both side. There are penis sparring hermaphroditic fish who fight to decide which loser has to be the female, because being the female is more energetically taxxing and sucks from the nucleus' perspective. On the other hand, there are types of trees which are constantly trying to switch gender to female because they want to pass on their mitochondria, and that's the only way (certain viruses that use mitochondrial DNA as hosts also force a female gender). Ultimately, the reason for the two sexes is kind of a neat yin and yang of evolution itself.

Because the mitochondrial DNA evolves much, MUCH faster than the nuclear, it is constantly at risk of creating a mismatch with the nuclear DNA. Thus you need to be able compare the two systematically, and for that to work, you can't have heteroplasmy (mitochondria from two donors). You need a single donor, the mother.

This fact that the mitochondrial DNA evolves so fast brings us to aging. The problem is, according to Lane, not about telomeres or any of that nonsense. All kinds of exceptions exist to those supposed rules. But in the animal kingdom, aging IS strangely consistent. Mice get the same exact diseases as us, they just get them faster. So there appears to be a unified, underlying cause. Wouldn't you know it? He thinks it's mitochondria (not just him ofc, this is not a fringe book it's mostly presenting his field's emerging consensus).

The idea is that as metabolism slows down, as it does with scale, animals age slower because they reap the rewards of that ole eukaryotic scaling law. Larger animals have less surface area relative to their internal mass, and thus lose heat slower. They don't have to turn their cellular crank as fast, and as a result do not produce as many free radicals (damaging, escaped and unstable atoms that got out of the proton pump) or as much mitochondrial turnover, leading to deleterious mutation. You can't just cut down your free radicals also because they are used as an important signal for modulating energy output by the mitochondria. So you've got a nice catchy twenty-two. You have to put out energy efficiently to survive, but the only way to keep track of that output and know if you need to commit cell suicide or modulate output is by watching the leakage of these damaging, escaping particles.

Birds and bats apparently get around this to some extent, and live much longer than they should because they keep more mitochondria on hand in general (and they can also decouple their respiratory chain, but I won't be discussing this). The author gives an analogy here. Imagine that you have a factory with fluctuating needs (the cell), and you have to decide how many people (mitochondria) to staff it with. You can keep a minimal staff, in which case when higher demand comes around the people will be overworked and, in their resentment, break some of the equipment (produce free radicals and mutations) or you can overstaff it for the quiet periods but have plenty of workers not overstressed when you need to ramp up for the holidays. That's what birds and bats and some others do because their evolutionary strategy necessitates constant access to high energy for the muscles (IE: flight).

This was important because a lot of people just thought free radicals served no purpose, because biology is random and adaptionism is racist (hence my insult at Gould, the jewboy commie prince of this worldview). But free radicals DO serve an important regulating purpose.

Of course, information is however important to life, especially the eukaryotic. Whereas bacteria and archaea reproduce via lateral gene transfer and thus really can't be said to experience selection at the level of the gene (there was of course discussion of Dawkin's book on this subject, 'the selfish gene') this is not the case for sexed eukaryotes, who do not have lateral transfer. Then you get into stuff like the disposable soma theory (that's you, you kamikaze vehicle for genes you).

All of this culminates in a recapitulation of Lane's striking and plausible prediction that life is plentiful in the universe, but actually still very lonely.

The reason is that while life is not uncommon, mitochondria are. They are a very unlikely, macro-adaption of non-darwinistic means. They did not arrive by any repeatable, incremental steps, and nor does the evidence suggest they did it more than once (whereas, say, we believe photosynthesis evolved a couple times, iirc). Rather, mitochondria only came about because a whole-ass archaea apparently wiggled its way inside a bacteria in just the right circumstances at just the right time during the mass crisis of the oxygen event.

There was only slime. Boring slime. For two billion years. And it might have stayed that way--indeed likely DID stay that way in the vast majority of the universe. Hence a lively universe, but one lonely and devoid of intelligent, multicellular organisms like ourselves. Something poetical about that.

And we’ve covered all I can think to recall now, so that will end this monstrous post. I'm moving on to shorter books.