尼克·莱恩——我们所知的生命在化学上是必然的

今天，我正在与尼克·莱恩交谈，他是伦敦大学学院的进化生物化学家。他有许多著作和论文，帮助我们以能量流动的视角重新构想生命的四十亿年历史，并解释了从生命最初如何形成到真核生物的起源，再到我们今天看到的生命运作中的许多偶然性。所以，尼克，也许一个好的起点是，为什么真核生物在你对生命为何如此的世界观中如此重要？

Today, I'm chatting with Nick Lane, who is an evolutionary biochemist at University College London. And he has many books and papers which help us reconceptualize life's four billion years in terms of energy flow and helps explain everything from how life came to be in the first place to the origin of eukaryotes to many, contingencies we see today in how life works. So, Nick, maybe a good place to start would be why are eukaryotes so significant in your worldview of why life is the way it is?

嗯，首先，谢谢邀请我。这很有趣。我喜欢谈论这类话题。那么，真核生物是什么？基本上就是构成我们的细胞，但也构成植物、阿米巴原虫、真菌、藻类等。

Well, first, thanks for having me here. This is this is fun. I love talking about this kind of thing. So so eukaryotes what's a eukaryote? It's basically the cells that make us up, but also make up plants and make up things like amoeba or fungi, algae.

所以基本上，你能看到的所有大型复杂生物都是由这种称为真核细胞的单一细胞类型组成的。我们有一个细胞核，里面包含所有的DNA和基因，然后还有各种细胞器、细胞膜等。所以这些细胞里基本上有很多装备。奇怪的是，如果你观察植物细胞或真菌细胞内部，在电子显微镜下它们看起来和我们的细胞一模一样，但它们的生活方式完全不同。那么，如果它们进化成在海洋中进行光合作用的单细胞藻类，为什么会有所有相同的装备呢？

So basically, everything that's large and complex that you can see is composed of this one cell type called the eukaryotic cell. And we have a nucleus where all the DNA is, where all the genes are, and then all all those kind of machinery, cell membranes, and things. So it's just basically a lot of kit in in in these cells. And the weirdness is if you look inside a plant cell or a fungal cell, it looks exactly the same under an electron microscope as one of our cells, But they have a completely different lifestyle. So why would they have all the same kit if they evolved to be a single celled algae living in an ocean doing photosynthesis?

它们仍然拥有和我们细胞相同的装备。所以我们知道，因为它们共享所有这些特征，它们在地球生命史上只出现了一次。可能有多重起源，但没有证据支持这一点。如果有，也消失得无影无踪。所以我们有这个大约二十亿年前发生的奇点，大约在地球生命史二十亿年的时候，这件事发生了一次，从而产生了地球上所有的复杂生命。

It's still got the same kit that our cells have. So we know that because they share all of these things, they arose once in the whole history of life on Earth. There could have been multiple origins, but there's no evidence for that. If there was, it disappeared without trace. So we've got this kind of singularity, which happened about two billion years ago, about two billion years into the history of life on Earth, and this thing happens once that gives rise to all complex life on Earth.

嗯。

Mhmm.

我想你可以从中得出的一个结论是，细菌和古菌在基因库方面实际上比真核生物有更多的基因和更强的适应性。只是单个细菌细胞内的东西少得多，但有这么多不同类型的细菌细胞，总体上它们探索了基因序列空间。对吧。它们有四十亿年的时间来尝试，但从未想出这个窍门。他们说这不在基因里。

And the the one thing which I I I guess you could conclude from that is bacteria and archaea, in terms of their genetic repertoire, they're actually they've they've got a lot more genes, a lot more versatility than eukaryotes do. It's just that a single bacterial cell has much less in it, but there's so many different types of bacterial cell that, overall, they've kind of explored genetic sequence space. Right. They had four billion years to have a go at that, and they never came up with a trick. They said it's not in the genes.

这不是关于信息的问题。还有别的东西在控制它。我认为那就是我们细胞中这些称为线粒体的能量包的获得。

It's not about information. There's something else which is which is controlling it. And that's something I think is the acquisition of these power packs in our cells called mitochondria.

现在让我们回到生命的起源。你有一个非常引人入胜的故事，设想最初的生命形式是与地球地球化学过程连续的？你能简要复述一下这个故事吗，我想问

Now let's go to the origins of life. And you have this really compelling story where you imagine that the first life forms were continuous with earth's geochemistry? And if you can recapitulate the story a little bit, and I wanna ask

一个问题。我是说，我先告诉你我是怎么走到这一步的。因为我最初是研究线粒体的。嗯。这让我进入了真核生物的进化领域。

a question. I mean, I'll tell you how I got there first. Because I I started out working on mitochondria. Mhmm. And that took me into the evolution of eukaryotes.

真核生物获得了这些内共生体，它们变成了线粒体，并改变了进化的潜力。它不会立即改变一切，但改变了终点可能的位置。是的。它允许这些大型复杂细胞的进化，最终形成多细胞生物和我们。所以现代线粒体实际上在做的是呼吸作用。

And eukaryotes acquire these endosymbionts that that that become mitochondria, and they change the potential of evolution. It doesn't change everything immediately, but it changes where the endpoints can be. Yeah. And it allows the evolution of these large complex cells and eventually multicellular organisms and us. So what a modern mitochondria are actually doing well, what they're actually doing is is respiration.

它们为自己产生能量。它们还做很多其他事情。但我们可以考虑的主要是它们是能量生产者。它们源自细菌，而细菌以完全相同的方式产生能量。它们通过在膜上产生电荷来产生能量。

They're generating energy for themselves. Doing They're plenty of other things as well. But the the the the main thing we can think about is they're the energy producers. And they're derived from bacteria, and bacteria produce their energy in exactly the same way. They're generating energy by generating an electrical charge on the membrane.

这个电荷很小，但膜非常薄。所以电荷大约是150到200毫伏。但膜的厚度是五纳米，也就是百万分之五毫米。所以如果你把自己缩小到分子大小或站在膜旁边，你会体验到每米3000万伏特的电压，相当于一道闪电。这就是膜两侧电压的力量，是巨大的。

And that charge, it's small, but the membrane is really thin. So the charge is about a 150 to 200 millivolts. But the membrane is five nanometers in thickness, so that's five millionths of a millimeter. So if you shrank yourself down to the size of a molecule or stood next to that membrane, you would experience 30,000,000 volts per meter, which is equivalent to a bolt of lightning. So that's the that's the the strength of the force of of the of the voltage across the membrane, which is colossal.

它是由非常复杂的蛋白质泵送质子穿过膜产生的。然后是ATP合酶，这又是几乎普遍存在的，它是一个旋转的纳米马达，位于膜中。这是极其复杂、有趣的机制，并且被普遍保守。它就像核糖体，蛋白质构建因子一样保守。几乎遍布所有生命。

And it's generated by really sophisticated proteins that pump protons across the membrane. And then it's ATP synthase, which is again pretty much universal, and it's a rotating nanomotor that sits in the membrane. This is colossally complex, interesting machinery, and it's universally conserved. It's as conserved as, say, a ribosome, the protein building factors. It's pretty much everywhere across life.

所以你好奇，生命到底是怎么变成这样的？如果它在所有生命中都普遍保守，看起来它直接追溯到所有细胞的共同祖先。所以问题是，它最初是如何产生的？是的。这对我来说实际上非常激动人心，因为它作为研究人员是通往生命起源的一个途径。

So you wonder, how on earth did life come to be that way? And if it's conserved universally across life, it looks like it goes right back to the common ancestors of all cells. And so there's the the question, how did it arise in the first place? Yeah. And that that was actually for me tremendously thrilling because it it it's a way in as a researcher to the origin of life.

它问道，这些能量生成系统最初是如何产生的？而我的切入点实际上是由比尔·马丁和迈克·拉塞尔打开的通道，他们在2000年代初共同发表了一些惊人的论文，指出深海热液喷口不像顶部冒烟的黑烟囱，而更像一个矿化的海绵，有许多孔隙，其结构类似细胞。早期海洋呈酸性，而这些喷口涌出碱性流体，整个系统内发生混合。因此，你至少可以想象这里有一个孔隙，其大小和形状有点像细胞。外部有酸性海水渗入。

It says, how did these energy generating systems arise in the first place? And and and my way in was really the the gates were opened by by Bill Martin and Mike Russell, who around the early two thousands were publishing some amazing papers together where they were saying that in in this deep sea hydrothermal vent, rather than it being like a black smoker with a chimney with smoke belching out of the top, it's like a a mineralized sponge with lots of pores that are cell like in their structure. And you've got an acidic early ocean, and you've got alkaline fluids coming out of these, and you've got mixing going on in this whole system. And so you could at least imagine that you've got a a pore in here, which is a bit like a cell in terms of its size and its shape. And on the outside, you've got acid ocean waters percolating in.

内部则有这些热液流体。所以存在一个屏障。你有内部和外部，外部有更多质子进入，可能驱动做功。这非常像细胞的结构。另一个问题是，这些矿物是什么？

And on the inside, you've these hydrothermal fluids. So you got a barrier. You've got an inside and an outside, and you've got more protons outside coming in, potentially driving work. So it's very much like a cell is structured. And the other thing is, what are these minerals?

你有这种矿化海绵，其孔隙中含有矿物。我们认为早期地球上的矿物中含有大量金属，比如硫化铁或硫化镍等。这之所以重要，是因为植物细胞以及自养细菌所做的是，它们摄取二氧化碳和氢气，将它们反应在一起，基本上制造出所有生命的基本构件。植物从水中获取氢气。

You got these these mineralized sponge that pours with minerals. Well, the minerals we think on the early Earth would have been a lot a lot of metals in there. So things like iron sulfide or nickel sulfides and things like that. Now the reason that's important is that what plant cells do, but also what autotrophic bacteria do, is they take c o two and they take hydrogen and they react them together to basically make all the building blocks of life. Now plants do the plants get the hydrogen from water.

H₂O，它们从水中取出H₂并丢弃氧气，后者积聚在大气中。但细菌通常做的是，它们有氢气从热液喷口冒出，它们直接以气体形式摄取氢气，与CO₂反应，制造所有生命的基本构件。那么它们用来做这个的酶是什么？它们经常使用这些你在早期海洋中能找到的相同金属，如镍、铁等。

H two o, they take the h two out of water and throw away the oxygen and that collects in the atmosphere. But what what bacteria very often do is they've got hydrogen bubbling out of a hydrothermal vent. They just take the hydrogen straight as gas, and they react it with c o two, and they make all the building blocks of life. So what what are the enzymes that they use to do that? Well, they're very often using these same metals that you would have found in the early oceans, nickel and and iron and so on.

它们如何驱动氢气和CO₂之间的反应？它们利用这种膜电位，即电化学势，外部和内部质子之间的差异来驱动这项工作。实际上，是为了驱动氢气和CO₂反应生成有机物并促进生长。所以这一切在我介入之前就已经基本就位了。这来自迈克·拉塞尔和比尔·马丁。

And how are they powering the the the reaction between hydrogen and c o two? Well, they're using this membrane potential, the electrical potential, the difference in protons between the outside and the inside to drive that work. So effectively, to power the reaction between hydrogen and c o two to make organics and drive growth. So so this is all this was all kind of in place before before I came along. This was coming from Mike Russell and Bill Martin.

细节非常不确定。是否真的能以这种方式驱动任何生物化学也非常不确定。但这是一个激动人心的想法，因为你在一个地质环境和我们所知的细胞之间存在连续性。如果它确实以这种方式出现，那么它就会说明，这就是为什么细菌膜上有这种电荷，因为它从一开始就存在于热液喷口中。它从最初就一直驱动着工作。

And the details are very uncertain. And whether or not you can really drive any biochemistry that way is very uncertain. But but, you know, it's a thrilling idea because you've got a you've got a continuity between a geological environment and cells as we know them. And that if if if it did emerge that way, then it would say, well, here's why bacteria have got this charge on their membrane because it was there in a hydrothermal vent from the beginning. It always powered work from the very beginning.

这就是为什么最终，产生真核生物的内共生会使你摆脱在膜上产生电荷的限制。现在你在真核生物中将其内部化，你就可以自由地变得更大、更复杂。所以，你从思考为什么真核生物特殊这个谜题，转向思考行星系统、生命起源、哪些力量将催生生命、这将如何约束生命，以及我们是否会在其他行星上看到相同或不同的现象？其运作的根本原因是什么？所以它实际上变成了天体生物学，并且这是一个视角上的激动人心的转变。我自己的背景实际上与线粒体生物学有关，曾经还涉及器官移植。

And that's why in the end, an endosymbiosis that gives rise to eukaryotes would give would allow the it's kind of free you from the constraints of generating a charge on a membrane. Now you internalize that in eukaryotes, and now you're you're free to become large and more complex. So so so you've gone from, you know, thinking about a puzzle about why eukaryotes are special to thinking about planetary systems and thinking about the origin of life and what are the forces that are gonna give rise to life and how would that constrain life and would we see the same things on other planets or something different? What are what are the fundamental reasons that it works this way? So it becomes astrobiology, really, and and and it's a it's a thrilling change of perspective to come from my my own background was to do with mitochondrial biology, actually an organ transplantation once upon a time.

而在针尖上旋转，你最终研究的是生命起源。这真是太神奇了。

And spinning on a pinhead, you end up working on the origin of life. It's fantastic.

是的。我的意思是，这太迷人了。所以为了我自己和观众的理解，我们来梳理一下这里的内容。你在这些孔隙中有了细胞的类似物，有了某种东西来浓缩这些有机物的积累，使它们不会全部扩散到某个巨大的原始汤中。因此，这就是为什么你认为像某些原始湖泊并不是发生这种情况的地方。

Yeah. I mean, it's it's so fascinating. So just to recapitulate for my own understanding in the audiences, let's just break down what we have here. So you have the analog of a cell in these pores, you have something which concentrates the buildup of these organics so that they don't just all diffuse in some big primordial soup. And so this is why you think like some primordial lake is not where this happened.

它必须集中在某个实体中。然后你有了化学渗透梯度，一个质子梯度，驱动工作。具体来说，它有利于二氧化碳的固定，并驱动与氢气的反应来制造有机物。然后沿着这层膜，你有了催化剂，基本上是早期的酶。所以你有酶，有细胞，有质子梯度。

It had to be concentrated in some entity. Then you've got a chemiosmotic gradient, a proton gradient, drives work. And specifically it favors the fixation of carbon dioxide and to drive the reaction with hydrogen gas to make organics. And then you've got along this membrane, you've got catalysts, which are basically early enzymes. So you've got enzymes, you've got the cell, you've got the proton gradient.

然后故事基本上是你用CO2和H2制造非常简单的有机物，然后这些简单的有机物被重新催化，制造越来越复杂的有机物，基本上就像是TLDR（太长不看版）的新陈代谢、脂肪酸和核苷酸，一切都有了。是的。

And then the story is basically that you make very simple organics with CO2 and H2, and then those simple organics are then re catalyzed to make more and more complex organics and like basically TLDR metabolism and fatty acids and cleotides, everything Yeah.

基本上就是这样。是的。那么，那么，那么如果你让氢气和CO2反应，你会得到什么？你得到的是所谓的克雷布斯循环中间体。所以是羧酸，只由碳、氢和氧组成的小分子，末端有一个有机酸基团，链上可以是两个、三个、四个、五个碳单元。

That's basically it. Yeah. So so so so what do you get if you react hydrogen and c o two? What you get are what are called Krebs cycle intermediates. So carboxylic acids, small molecules made only of carbon, hydrogen, and oxygen with this organic acid group at the end, which can be two, three, four, five carbon units in the chain.

这是你的基本构建块。你向其中加入氨，你就会得到一个氨基酸。你加入更多的氢，你就会得到糖。你让氨基酸与糖反应，你就会得到核苷酸。这里有很多步骤，但这是生物化学中所有生物合成的基本起点。

And this is your basic building blocks. You you add on ammonia to this, and you you get an amino acid. You add more hydrogen on, and you're gonna get a sugar. You react amino acids with sugars, and you're gonna get nucleotides. There's lots of steps along here, but this is the basic kind of starting point for all of biosynthesis in biochemistry

然后如果你制造脂肪酸，由于它们不同侧面的亲水性，它们会自发地形成膜，如果它们被创造出来的话。

Then if you make fatty acids, they will sort of spontaneously, because of the hydrophilic nature of their different sides, they will spontaneously form the membrane if they're they're created.

我就是这个意思。你看，克雷布斯循环中间体是短链羧酸，而脂肪酸是长链的。对，链上有十个、十二个甚至十五个碳原子，而不是四五个。

That's what I say. You know, Krebs cycle intermediates are short chain carboxylic acids. The fatty acids is a long chain. Yeah. You know, you're ten, twelve, 15 carbons in the chain instead of four or five.

它们会自发形成——通常不是单独作用，但如果与其他长链碳氢化合物混合，就会自发形成双层膜。我们在实验室里做过这个。它非常稳定，可以在70度、90摄氏度的温度下，pH值从7到12的范围内，甚至在钙、镁离子和其他盐类存在的情况下制备。这样就能制造出带有双层膜的囊泡，基本上和细胞膜一样。是的。

And they will spontaneously, not just alone usually, but if you've got other long chain hydrocarbons mixed up with them, then you will form a bilayer membrane spontaneously. We've done this in the lab. And it's pretty robust to you know, you can you can make these things at 70 degrees, 90 degrees centigrade across a range of pH from around about pH seven up to about pH 12 and in the presence of ions like calcium and magnesium and other salts and so on. So you can and you make a a vesicle with a bilayer membrane around it, which is basically the same as a cell membrane. Yeah.

它们是非常动态的结构。总是在相互融合、分裂，有点像裂变成两三个。在显微镜下看，它们是非常非常活跃的。

They're amazingly dynamic things. They're always fusing with each other and breaking apart, kind of fissioning, separating into two or three. And, you know, they're they're very, very dynamic things under a microscope.

你可能会想象生命是这样产生的，就像弗兰肯斯坦那样的时刻，东西突然被激活然后就活了

You could have had imagined that life is this like, there's like Frankenstein like moment where things zaps alive and then now

我讨厌这个想法，但是

you I hate that as an idea, but

继续说。是的。所以另一种说法是闪电创造了这些有机物等等。而这里的故事是，你看到的每个生命形式都与某个东西连续相连，而那个东西又与其他东西连续相连。是的。

go on. Yeah. So that's the alternative where like the bolt of lightning makes these organics, etcetera. And here you have this story where every life form you see is continuous with something, which is continuous with something. Yes.

最终就是完全与自发的化学反应连续相连。所以这是思考进化的一种非常有趣的方式

Which is eventually just continuous with entirely spontaneous chemical reactions. And so that they're just a very interesting way to think about the evolution

生命的一个方面是，细胞内部实际上是还原性的，也就是说内部有电子。而外部相对是氧化性的。外部，你把这些质子泵出去，所以外部是酸性的。

of life. One thing, you know, a cell is effectively it's reduced inside, which is to say the it's got electrons inside. And and outside is relatively oxidized. And outside, it's rather you pump all these protons out. It's acidic outside.

内部是碱性的。内部是还原性的。这就像地球一样。地球的所有电子都在铁中，在地核和地幔中，内部相对碱性。这就是这些热液喷口中的碱性流体。

It's alkaline inside. It's it's it's it's reduced inside. That's like the Earth. The Earth is all the electrons are in the iron, in the core, in the mantle of the Earth, relatively alkaline inside. That's the alkaline fluids in these vents.

外部相对是氧化性的。海洋中有大量的二氧化碳。所以细胞就像一种小电池，其结构与地球相同。

The outside is relatively oxidized. You've got all the c o two in the ocean. So the cells are a kind of little little battery with the same structure as the earth.

对。

Right.

如果你观察热液系统，细胞膜就像地球的地壳，地壳就像膜，内部和外部之间的物质交换是通过热液系统进行的。

And if you look in a hydrothermal system, the cell membranes around you know, the the the earth, the crust of the earth is like the membrane, where you have traffic going between the inside and the outside is the hydrothermal systems.

正是这样，而且

That's exactly And the

这些热液系统中的孔隙也是类似细胞的小实体。所以你在多个尺度上不断看到相同的模式，因此地球是一个巨大的电池，产生着微小的活细胞迷你电池，这是一个相当美丽的想法。我的意思是，你不能让自己过于纠结于一个比喻，但这确实是一个美妙的意象。

pores in these hydrothermal systems are little cell like entities as well. So you keep having on multiple scales the same kind of so the idea that the earth is a giant battery that produces little living cell mini batteries, it's a rather beautiful idea. I mean, that you can't allow yourself to get too hung up on a metaphor, but it's a beautiful image.

是的，100%。所以基本上，地球就像一个巨大的细胞。然后从热液喷口那里，会冒出一个小泡泡，

Yeah. 100%. So just basically, you've got earth as this sort of like giant cell. And then this like from the hydrothermal vent, this little bubble pops off that's

就像冒出来的地球迷你复制品。

Bubbling like off mini copies of the earth.

是的。这真是个迷人的理论。所以我想理解的是，生命运作方式中哪些部分是偶然的，哪些是你预期即使在外星发现生命也会共有的？听起来你在说，碳、化学特性，这些显然是构建生命的基础。质子梯度，有没有其他方式可以构建这种驱动工作的化学渗透梯度？

Yeah. This is such a fascinating theory. So the thing I wanna understand is what part of life, the way it works now is contingent and which would you expect to be shared even if you found life on another planet? So it sounds like you're saying, look, carbon, the chemical profile, that the this is just the obvious candidate to build life on top of. Proton gradients, is there another way you could build this sort of chemiosmotic gradients that drive work?

对吧？就像我们有其他化学物质用于电池。

Right? Like, we have other chemistry for batteries.

原则上是的，你可以用钠离子代替质子，但这非常不同。因为如果你从二氧化碳开始，首先要意识到碳在其化学反应中表现极佳。它能与各种分子形成非常强的键，从而构建复杂有趣的分子。我实际上把二氧化碳看作一种乐高积木，你从空气中抓取它，然后把它绑定到某物上。你可以这样一块一块地构建，最终造出像DNA和RNA这样真正有趣复杂的分子。

Principle, yes, you could use sodium ions instead of protons, but the but but but it's very different. Because what you'd if you're starting with with with carbon dioxide, and and the first thing to realize about that is carbon is extremely good at the chemistry that it does. It's forming, you know, very strong bonds with all kinds of molecules so you can form complex interesting molecules. And you're effectively I think of c o two as a kind of a Lego brick that you pluck out of the air and you bind it onto something. You can build things one brick at a time that way, and then you can build really interesting complex molecules like DNA and RNA from doing that.

硅做不到这一点。所以，通过智能设计，你可以制造非常复杂的人工智能机器人等等，但整个过程需要人类来完成。但如果你思考生命如何在一个没有智能设计者组装一切的星球上起源，你需要能进行那种化学反应的分子，而二氧化碳就是杰出的例子。水则无处不在。

Can't do that with silicon. So you can you know, with intelligent design, you can make really complex AI robots, whatever it may be, but the whole thing requires humans to do it. But if you're thinking about how would life start on a planet where where where there aren't, you know, there isn't an intelligent designer who's putting it all together. You need molecules that can do that kind of chemistry, and c o two is the is the outstanding example. And water is everywhere.

嗯，你知道，氢、氧，这些都是宇宙中非常非常常见的元素。所以你会在各处持续遇到同样的化学反应。根据近年来系外行星的发现，如果我们推断尚未观测到的数量，银河系中湿润的岩石行星或卫星的数量可能大约在200亿到400亿之间。

Well, you know, hydrogen, oxygen, these are all elements that are very, very common in the universe. So you're gonna keep on getting this same kind of chemistry everywhere. We know that there are from from from discoveries of exoplanets in recent years, if you extrapolate how many we've not seen yet, the number of wet rocky planets or moons in in, say, the Milky Way is probably in the order of twenty, thirty, 40,000,000,000 of them.

你预计其中有多大比例会存在非真核生命？

What fraction of them would you expect to have a non eukaryotic life?

我的意思是，我来试着推测一下。我认为如果在一个湿润的岩石行星上存在类似条件，就会产生这类相同的喷口，因为发生的化学反应是相同的。你会遇到氢

I mean, I'll go I'll I'll take a punt here. I would expect that if you've got these same kind of conditions on a wet rocky planet, you're going to be producing these same kind of vents because it's the same chemistry that's going to happen. You're gonna be dealing with hydrogen

喷口并非偶然出现在

vents are not contingent in

不。这些喷口是由一种叫做橄榄石的矿物产生的，这种矿物在星际尘埃中非常常见。地球的地幔就是由这种橄榄石矿物构成的。啊。而且它会与水发生反应。

your No. The the vents are produced by a mineral called olivine, which, again, is really common in interstellar dust. And the mantle of the earth is made of this mineral called olivine. Ah. And it will react with water.

当它与水反应时，反应很慢——如果你把一块橄榄石放进一桶水里，你不会看到太多变化。但如果在海底的压力、较高的温度等条件下，就会产生大量的氢气，存在于碱性流体中。这就是这些热液喷口的本质。是的。

And when it reacts with water, it's it's it's slow if you were to put a lump of olivine in a bucket of water. You're not you'll not see very much. But if you're dealing with the pressures down at the bottom of the ocean and warmer temperatures and so on, you're producing, you know, bucket loads of of of hydrogen gas in alkaline fluids. So that's what these hydrothermal vents are. Yeah.

所以任何湿润的岩石行星都会产生这些喷口。有证据表明火星早期存在海洋时就有这些喷口。现在也有证据显示在冰卫星上，比如土卫二和木卫二，也存在这种现象。这在我们太阳系中正在发生。

So any wet rocky planet will produce these vents. We there's evidence for them on Mars from the early days of Mars when there were oceans on Mars. There's evidence now on moons, wet the icy moons, Enceladus and and and Europa. This is going on in our own solar system right now.

对。所以如果有两三百亿个类地行星，假设其中很大一部分都有这些岩石构造，那么它们很可能也有这些喷口。那么，你的观点是不是认为其中相当一部分行星上的生命也活动在

Right. So if there's twenty, thirty billion Earth like planets, which have presumably some big fraction of them have these vents if they all have these rock formations. So like, is your view that a notable fraction of them have life that also operates in the

会是肯定的。任何湿润的岩石行星都会有相当程度的肯定。如果你从二氧化碳和氢气开始，我的意思是这种代谢是热力学上有利的化学反应。同样的化学反应会持续发生，因为如果你让氢气与二氧化碳反应，然后再与另一个二氧化碳分子反应，分子中会发生反应的部分是相当可预测的。

would be yes. Any wet rocky planet would have a decent yes. And if you're starting with c o two and hydrogen, what I'm saying is the metabolism is fave thermodynamically favored chemistry. This same chemistry will just go on happening because if you react hydrogen with c o two and then with another c o two molecule, the parts of the molecules that are going to react are quite predictable.

那么，这是一个天真的问题，但有什么理由认为不存在导致替代代谢的替代化学途径呢？

So so this is a naive question, but what is the reason to think that there's no alternative chemistries which lead to alternative metabolisms?

也许在非常不同的条件下，你可能会得到不同的结果，但如果你有基本相似的条件，你……另外一点是，我们知道即使化学过程非常不同，你最终还是会得到基本相似的分子子集。从陨石上看到的有机物来看，化学过程完全不同。你处理的是氦自由基，但你仍然能看到氨基酸，仍然能看到核碱基等等。所以存在一种趋势。这些分子基本上是稳定的，并且倾向于在广泛条件下形成。

Perhaps under very different conditions, you could end up with a but if you've got essentially similar conditions, you're and the other the other thing is we know that even with very different chemistries, you end up with basically a similar subset of molecules. From from the kind of organics you see on meteorites, utterly different chemistry going on. You're dealing with helium radicals, but you're still seeing amino acids and you're still seeing nuclear bases and so on. So there's a tendency. A kind of these are molecules which are basically stable and tend to be formed under a wide range of conditions.

所以有200亿个类地行星，有水还有这些岩石

So 20,000,000,000 earth like planets with water and these rocks

不一定是类地行星，但要有水和岩石。

in Not necessarily earth like, but wet and rocky.

如果你必须凭空想一个数字，就说这个比例的行星有核苷酸，你会说多少比例？

If you just had to pull a number out of nowhere and just say, this fraction had nucleotides, what fraction would you say?

我会说一个相当大的比例。比如超过1%？是的。我的意思是，我……我会想象是50%左右。真的吗？

I would say a substantial fraction. Like over 1%? Yes. Mean, I I I would imagine 50% or something. Really?

我的意思是，你说让我从帽子里抽一个数字，我正是在照你说的做——从帽子里抽数字。我认为这种化学反应会反复给你相同的核苷酸。再说一次，我知道

I I mean, I'm pulling you say pull a number out of a hat. I'm doing exactly what you're saying. Pulling number out of a hat. I think this kind of chemistry is going to give you the same nucleotides repeatedly. Again, I know

你只是，我们只是，你知道的，随便聊聊。但是，

you're just we're just, you know, chatting here. But,

就像，是的。

like Yeah.

根据这个故事，相当复杂的有机物在整个宇宙中极为丰富。

According to this story, pretty sophisticated organics are extremely abundant through the universe.

对吧？这并不是说它们在高浓度的海洋中聚集。在热液喷口中，你有一个持续的流动，并且在这个喷口内的孔隙中，在细胞内部基本上附着在壁上。所以在一个喷口系统内，你最终可能会有非常高浓度的物质，但不一定在海洋、大气或其他任何地方。

Right? That's not to say they're collecting in an ocean at a high concentration. What you have in a hydrothermal vent is a continuous through flow and and within pockets within this vent, within the pores within this vent, bound to the walls pretty much within cells. So within a vent system, you could have very high concentrations of things ultimately, but but not necessarily in the oceans or in the atmosphere or anywhere else.

是的。我猜你可能有原核生物然后它们就接管了。我的意思是，我们确实有过这个。对吧？它们曾在海洋中大量繁殖并改变了大气成分。

Yeah. I I I guess you could have prokaryotes then who did just take over. I mean, we did have this. Right? We had that like kind of proliferated through the oceans and changed the composition of the atmosphere.

我的意思是，不仅仅是大气，还有整个地质学。数百种矿物基本上是生命的产物。

I mean, not just the atmosphere, but also the whole the whole of geology. Hundreds of minerals are basically the product of life.

所以你的观点是，如果从根本瓶颈来看，从地球化学到早期生命是容易的，早期生命通过原核生物改变整个地球组成也是容易的。如果这两件事都很容易，而银河系中有100亿颗行星处于中间阶段，这是否意味着存在大约100亿颗行星

So your view is that the fundamental bottleneck to that, if you carry out sort of fundamental bottleneck, you can go from geochemistry to early life is easy, early life to just changing the entire composition of the earth through early prokaryotes is easy. And if those two things are easy and then you've got 10,000,000,000 planets in the Milky Way that we've to the middle step, does it imply that there's like on the order of 10,000,000,000 planets

就像思考，你知道，要从核苷酸到RNA和DNA以及核糖体，还有分子机器。所以这里也有很长的差距。仅仅拥有核苷酸，这是进一步发展的必要条件。

that like think, you know, to to to get to nucleotides, from nucleotides, you've then got to get to RNA and DNA and and ribosomes and, you know, molecular machines. So there's a long gap there as well. So just having nucleotides, that's a that's a kind of it's a requirement to get any further.

我明白了。那么你认为其中有多大比例，你不得不凭空

I see. And then what fraction would you again, you had to pull

捏造一个数字。嗯，显然比例会更低。没错。

a number out of the air. Well, a lower fraction, obviously. Right.

超过十亿分之一？

Over a billion?

我意思是，我想说，乐观地看。我愿意相信这些过程会在相当大比例的行星上推动生命出现。是的。或者卫星上。而且我预期遗传密码会有相似性。我预期很多代谢过程看起来会相似。

I I mean, I I would like to be, let's say, optimistic. I would like to think that that that these processes are going to drive life into existence on on on a substantial proportion of these planets Yeah. Or moons. And and I would expect that there would be similarities in the genetic code. I would expect there's a lot of metabolism would look similar.

我预期它们会有膜电位驱动这类工作，因为这很有趣，你知道，如果你处理二氧化碳和氢气，你会遇到相同的基本问题。如何让它们发生反应？是的。是的。

I would expect that they would have a membrane potential driving the kind of work because it's fun you know, if you're dealing with c o two and hydrogen, you've got this same fundamental problem. How do you make them react? Yeah. Yeah.

但是，基本上，银河系中有数亿颗行星，它们很可能拥有类似核糖体、DNA和RNA的东西。

But so, basically, there's hundreds of millions of planets in the Milky Way, which, like, presumably have something like ribosomes and DNA and RNA.

RNA，是的。我我我那是我的那是我的想法。我我不我不我我我认为我们谈论的是严肃的行星驱动力，推动着相当确定性的化学反应，这些反应会产生相同类型的中间产物，这些中间产物将具有相同的化学性质和相同的反馈机制。它们会将事物推向相似的方向。现在，距离二氧化碳固定到遗传学的距离越远，相似性就会越少。

RNA, yes. I I I that that's my that's my own thinking. I I don't I don't I I I think we're talking about serious planetary driving forces, driving fairly deterministic chemistry that's going to give you the same kind of intermediates, which are going to have the same kind of chemistry, the same kind of feedbacks. They're going to push things into similar directions. Now the further from c o two fixation towards genetics you get, the the less similarity there's going to be.

所以这恰好是ThorKetch播客的第101期。显然，这还不包括我们在频道上发布的片段、短视频和其他内容。所以到现在，要跟踪所有这些数据变得有点困难。但由于Google Sheets内置了Gemini，我能够将我们的频道数据导入电子表格，并向Gemini提出任何我想回答的问题。例如，鉴于一些片段也在同一频道中，很难评估我们完整剧集的模式。

So this happens to be the hundred and first episode of the ThorKetch podcast. And, obviously, that doesn't include, you know, clips and shorts and the other content that we put out on the channel. So at this point, it's gotten a bit tough to keep track of all of this data. But since Google Sheets has Gemini built in, I was able to just throw our channel data into a sheet and ask Gemini whatever questions that I wanted answered. For example, it's hard to evaluate patterns for our full episodes given that some of the clips were in the same channel.

所以我只是让Gemini创建了一个名为内容类型的新列。然后他们想出了一个公式来区分这两种不同类型的内容。另一个例子，我很好想看看我们做了多少关于不同主题的剧集。我没有为此制作任何历史标签，但我只是能够让Gemini使用每集的描述来分配主题，然后将所有内容汇总在一起，按类别进行细分。Gemini让你能够将这些大块的非结构化文本转化为你可以实际汇总和计数，并用作不同公式基础的数据类型。

So I just asked Gemini to make a new column called content type. And then they came up with a formula to do this to distinguish between the two different types of content. Another example, I was curious to see how many episodes we had done about different topics. And I didn't have any historical tags that I'd made for this, but I was just able to ask Gemini to use each episode's description to assign topics and then sum everything together to get a breakdown by category. Gemini lets you turn these big chunks of unstructured text into the type of data that you can actually sum and count and then use as the basis of different formulas.

Sheets中的Gemini现在可供Google Workspace用户使用。我觉得它对我的播客很有帮助，你可能也会发现它很有用。好了。回到Nick。这不是我的倾向，但如果我是个有点敬畏上帝的人

Gemini in Sheets is now available for Google Workspace users. I find it helpful for my podcast and you might find it helpful as well. Alright. Back to Nick. This is not my inclination, but if I was a sort of a God fearing person

嗯。

Mhmm.

我听到这个会想，哇。这某种程度上是对智能设计的证明，宇宙的法则就是偏爱这种化学过程，它导致了生命，至少根据这个故事，如此强烈以至于很难抗拒这种形成。好奇你所说的解释是什么意思。

I would hear this and I'd be like, wow. This is a sort of vindication of intelligent design where the laws of the universe just favor this chemistry, which leads to life, at least according to this story, so strongly that it's hard to hard to resist this formation. Curious how what you mean by interpretation.

我的意思是，我同意你的看法。我觉得这几乎有点令人不安。我必须说，我也不是一个有宗教信仰的人，但我也不反对宗教。我完全不是一个好战的无神论者。我反而欣赏宗教对意义的探索、对起源的追寻，我对这种探索有着某种共鸣。

I mean, I agree with you. It it I find it a little almost disturbing. And I I have to say, I'm not I'm not a religious person either, but I'm I'm neither am I I don't object to religion. I'm not a I'm not a militant atheist at all. I I rather I I I like the fact that religions have searched for meaning, search for origins, and I've I have some kind of fellow feeling with that search.

我想在某种意义上，这与我个人所理解的小写的真理是一致的。但就这与神的概念一致而言，这个神会是一个自然神论的神，它有效地设定了宇宙的法则并让其运行。然后它们就任其自行发展。你知道，这其实是爱因斯坦所理解的神。就大多数人理解的神而言，我认为大多数人从神那里寻求慰藉，寻找对他们有意义且与人类有关联的东西。

And I I suppose truth in some sense in this with a small t in my own case. But insofar as this is is is is consistent with the idea of a god, the god would be a deist god that effectively set the laws of the universe in motion Right. And they they're left to play out. Now, you know, this is kind of Einstein's god, really. In terms of what most people understand by gods, I think most people look for comfort in god and are looking for something which is meaningful to them and who's been involved in humanity.

所以这是一种非常冷酷的神，就像是热力学，设定了宇宙的法则并让其运行。是的。可重复地产生相同的事物。是的。你可以用一种有神论的自然主义方式来解释它，但我不认为很多人能从这种视角中获得多少安慰或意义。好的。

And so this is a very cold kind of goddess thermodynamics, sets the laws of the universe in motion Yeah. Reproducibly gives rise to the same kinds of things. Yes. You could interpret it in a kind of theistic natural theistic way, But I don't think many people would get that much comfort or meaning from that way of seeing Okay. The

那么一个非常基本的问题。如果生命不仅在所有这些岩石行星上很丰富，而且几乎是必然存在的，那么我们没有到处看到外星人的瓶颈 presumably（很可能）就是真核生物，它们导致了复杂性。

So very basic question. But if life is not only abundant but almost inevitable in all these rocky planets, then the bottleneck to not seeing aliens everywhere presumably is eukaryotes, which lead to complexity.

是的。嗯，可能不止一个瓶颈，但在我看来，真核生物是最大的一个。是的。

Yeah. Well, there's probably more than one bottleneck, but eukaryotes is, in my own mind, the big one. Yes.

所以实际情况会是，在数十亿个可能产生真核生物的潜在行星中，只有在地球上发生了这种偶然事件。

So it would actually be the case that out of billions of potential planets were that could give rise to eukaryotes, only on earth does this chance occurrence happen.

我不会那样认为。好吧。我的意思是，只有在地球上？不，我不这么认为。

I wouldn't argue that. Okay. I mean, only on earth. No. I don't think so.

当然。当然。但我想我会坚持的一点是，有一种卡尔·萨根式的宇宙观认为，一旦你有了生命——你知道，我们几乎是在谈论生命根据化学和热力学等法则必然出现——然后生命就产生了。那么它是否会继续发展，并不可避免地产生复杂生命、人类和智能？这是一个美好的想法。

Sure. Sure. But is is there I suppose what I would dig my heels in a little bit is is is there's a a kind of Carl Sagan cosmological view that that once you've got you know, we're talking about the inevitability almost of life arising according to these laws of chemistry and thermodynamics and so on, and you you get life. And and then is it gonna roll on and inevitably give rise to complex life and to humans and to to to intelligence? It's a it's a beautiful thought.

如果宇宙是这样运作的，那将非常美妙，但我们在地球上所知的是，你有二十亿年的停滞期，然后出现了真核生物这一明显的单一事件，之后又经过漫长的间隔才出现动物。而如果你把时钟倒回两百万年前，那时也没有人类。没错。

It would be lovely if that was how the universe worked, but what we what we know on Earth is that you have two billion years of stasis where you'd and and then and then this apparent singular event where eukaryotes arose, and then another long gap before you get to animals. And then if you roll back the clock two million years, there aren't any humans around either. That's right.

我们只是锦上添花。为什么成功的细胞内共生事件据说这么难发生？

We're just we're just the icing. Why is supposedly this hard to have this successful endosymbiotic event?

嗯，有多个原因。我的意思是，其中之一是原核生物——让我说清楚，古菌和细菌——它们是非常小的东西。所以仅仅让另一个细胞进入你内部已经是一件困难的事。细菌中偶尔有吞噬细胞可以吞没其他细胞，但这相当罕见。而一旦你让这些细胞进入体内，

Well, there's there's multiple reasons. I mean, one of them is that the the prokaryotes, let me just say, archaea and bacterial, well, they're pretty small things. So just having another cell inside you is already a difficult thing to do. It's not and there are no there are occasional phagocytes in bacteria that can engulf other cells, but that that's pretty uncommon. And once you got these cells inside you,

你知道，它可能已经发生了

you know, it may have that

可能已经发生了数十次。有一些初步证据表明，古菌——有一个很好的例子，盐古菌似乎从同一来源获取了一千多个细菌基因，这暗示它们可能曾经有一个内共生体，但后来失去了。所以问题是，它出错的频率有多高，以至于你失去了你的内共生体？我猜更可能的结果是你获得了一堆基因，然后失去了你的内共生体。它 simply doesn't work out.

may have happened scores of occasions. There's some tentative evidence that suggests that that Archaea I mean, there's one nice example where the halo Archaea seemed to have acquired more than a thousand bacterial genes from the same source, implying perhaps they had got an endosymbiote that they then lost later on. So the question is, how often would it go wrong and and you lose your endosymbiote? And I I guess that would be the more likely outcome is that you pick up a bunch of genes and you lose your endosymbiote. It it simply doesn't work out.

所以很难确切知道这里的所有瓶颈是什么，但已经进行了一些建模工作来观察，好吧，你得到了一个内共生体。如果你没有内共生体，或者你有内共生体，你会生长得更快吗？而如果你是内共生体，你在外面或 inside 会生长得更快吗？在圣塔菲这些人研究的大多数条件下，答案是，嗯，如果你不参与共生，你会做得更好。只有在某些条件下你才会表现得更好。

So so it's it's hard to know exactly what are all the bottlenecks here, but there there have been some modeling work done to to see, okay, you get an endosymbiont. Are you gonna grow faster if you don't have the endosymbiont or you do have the endosynbound? And if you're the endosynbound, are you gonna grow faster if you're outside or if you're inside? And under most conditions that that these people have looked at there at Santa Fe, the answer is, well, you you do better if you're not part of the symbiosis. Only under certain conditions will you do better.

所以不出所料，最终结果就是行不通。对吧。我猜

So predictably, the endpoint is it doesn't work. Right. I guess

考虑到地球历史上存在过的细菌和古菌数量如此庞大，你知道，有数不清的万亿万亿万亿个这些微生物存在。在很多情况下都发生过内共生现象。但只有一次成功了。所以这个概率必须得，就像，备注一下，是极其极其困难的。

given how many bacteria and archaea there are, you know, through Earth's history, there's like trillion trillion trillion of these running around. And there's many situations in which there was an endosymbiosis. And in only one case, it succeeded. So the it would the odds would have to just be, like, remark it was trying to be, like, extremely, extremely tough.

这里有一个生动的理解方式。我们知道细菌和古菌长什么样。人们一直在研究这些东西并发现新例子，十年前发现了一个叫做阿斯加德古菌的类群。它们相对比较像真核生物，也就是说它们内部的蛋白质和基因与真核生物的相当相似。它们是很有趣的细胞。

Here's a vivid way of seeing it. We know what bacteria and archaea look like. And we we you know, people have been studying these things and finding new examples, and there's a there's a group discovered ten years ago called the Asgard Archaea. And they're they're relatively eukaryotic like, which is to say they've got proteins in there and genes that that are pretty similar to eukaryotic ones. And they're they're interesting cells.

它们有长长的突起，可能能在内部移动囊泡。所以它们在做一些真核生物做的事情。但如果你看它们的内部结构，并不复杂。完全不像真核细胞。如果你看它们的基因组大小，基本上就是标准的原核生物基因组大小。

They've got long processes, and they can possibly, can move vesicles around inside them. So they they're doing a few eukaryotic things. But if you look at their internal structure, it's not very complex. It's nothing like a eukaryotic cell. And if you look at their genome size, it's basically a standard prokaryotic genome size.

大概只有四五千个基因。所以这些无论如何都不能算是真核生物。然后你看看真核细胞，我在开头说过。你在显微镜下观察植物细胞、动物细胞、真菌细胞、藻类或阿米巴原虫，它们都有相同的结构，这有点奇怪。为什么一个生活在海洋中的单细胞藻类会拥有和我肾脏细胞完全相同的装备？

You're talking four, five thousand genes. So the the these are these are these are not eukaryotic by any stretch of the imagination. And then you look at a eukaryotic cell, and I said this at the beginning. You you you look at a plant cell or an animal cell or a fungal cell or an alga or amoeba under a microscope, and they've all got the same stuff, and it's kinda weird. Why would a single celled algae living in the ocean have all the same kit that one of my kidney cells has?

嗯，最简单的理解方式是，这不是对外部环境或生活方式的适应，而是对内部选择压力的适应。如果你从宿主细胞和内共生体之间为寻找共存方式而斗争的角度来思考，你可以论证细胞核的起源——有各种来自线粒体的遗传寄生虫迫使你采取措施保护自己的基因组。这样你就可以构建很多真核生物起源的历史，这被称为真核发生。所以你从内部有一个细胞的简单细胞开始，最终形成了到处都一样的细胞结构，所有这些内膜系统等等。

Well, the easiest way to understand that is to say, well, it wasn't adaptation to an external environment, to to a way of life. It was adaptation to an internal selection pressure. If you think about it in terms of a kind of a battle between between the host cell and the endosymbiote for for for finding a way of living together, you can argue for the nucleus arising, that there's all kinds of genetic parasites coming out of the mitochondria forcing you to do something to protect your own genome. So there you can construct a lot of this history of eukaryogenesis, it would it's called. So that you start with simple cells with a cell inside and you end up with with the same cell structure everywhere, all these endomembrane systems and everything else.

好的。所以我想我们这里试图弄明白的更广泛的问题是，如果这个故事是真的，生命无处不在，但真核生物产生智能生命——据我们所知，在我们的光锥中只有一个地方正在发生智能生命探索宇宙的事情。为什么是这样？现在你可能会说，看，瓶颈在于真核生物，就像成功的内共生非常困难，然后还需要持续下去。但这到底解决了什么根本问题？

Okay. So I guess the broader thing we're trying to figure out here is if this story is true, there's life everywhere, but eukaryotes giving rise to intelligent life, which is about to go through, you know, explore the cosmos is as far as we can tell happening only in one place in our light cone. So why is that? And now you could you could say, well, look, it's the the bottleneck is the eukaryote and the it just like very hard to get a successful endosymbiosis, which then continues over time. But what is the fundamental problem this is solving?

解决基因组问题的关键正在于此。没错。

What's solving the problem that in order Genomes. Exactly.

所以为了形成多细胞生物体，实际上你是从一个单细胞衍生而来的，对吧。这样就限制了所有细胞之间发生冲突的可能性。比如有很多多细胞黏菌的例子，细胞聚集在一起可以形成像柄状的结构，将孢子释放到环境中，但它们基本上会争斗，因为彼此基因不同。所以从单细胞开始发育，细胞间的基因争斗就比它们聚集在一起时要少。

So to to to have a to have a multicellular organism where effectively you're deriving from a single cell Right. And and that restricts the the chances of effectively all the cells having a fight. There's plenty of examples of multicellular slime molds, for example, where the cells come together, and they can form structures like a stalk, for example, which which loosens Yeah. Spores into the environment, but they basically fight because they're genetically different to each other. So you start with a single cell and you you develop so there's less genetic fighting going on between the cells than there would be if they come together.

但这就意味着，如果你想要实现复杂的功能，比如肝脏执行一种任务，肾脏执行另一种，大脑又执行另一种，所有细胞都必须拥有相同的基因，但你在肝脏中表达这些基因，在大脑中表达那些基因。因此你必须拥有一个大型基因组。拥有大型基因组的唯一方式就是拥有线粒体和真核细胞。没有多细胞细菌能达到这种复杂程度的例子。

But that means then if you wanna have complex functions, if you wanna have a liver doing one thing and and kidneys doing something else and the brain doing something else, All of the cells have to have the same genes, but you you you express this lot in the liver and that lot in the brain. So you must have a large genome. The only way you can have a large genome is by having mitochondria and having a eukaryotic cell. There are no examples of this level of sophistication of a multicellular bacterium.

很有趣的是，你需要大型基因组的原因实际上就是为了把所有鸡蛋放在一个篮子里，这样体内的每个细胞都有动力去减少

That's quite interesting that the reason you need a large genome is actually just to put all your eggs in one basket so that every cell in the body feels incentivized to make the sort

争斗的风险程度。

of risk amount of fighting.

是的。没错。它们都转而最好地让生命延续下去。好的。

Yeah. Yeah. Yes. They make the they all instead best make the sugar life continue. Okay.

但我想说的是，好吧，真核细胞解决了大型基因组的问题，并让细胞变得更大。为什么我们如此确信这是解决这个问题的唯一方式？如果数十亿行星都达到了这个前体阶段，难道没有一个能找到线粒体之外的替代方案来让自身变大吗？这确实是一种信念。是的。

But the the thing I was getting at is like, okay, the eukaryotic is solving large genome and it's allowing the cell to get much bigger. Why why are we so confident that this is the only way this problem could have been solved? It just seems if there's billions of planets which have like got into the precursor stage here, none of them can find an alternative solution to mitochondria for just letting themselves get bigger. That is belief. Yeah.

我明白你的意思。

I know where you're coming from.

这让我有点怀疑，我们是否因为只观察到一种解决问题的方式，就假设必须只有一种方式来解决这个问题。而问题本身似乎并不是这样。你只是想要一个更小的基因组副本位于呼吸作用位点旁边，对吧？这就是基本问题。

It kinda makes me wonder whether we're like because we've only observed one way to solve the solution, we're sort of assuming that there must be only one way to solve the solution problem. Whereas the problem itself doesn't seem like, okay. You just want, like, a smaller copy of your genome sitting next to the site of respiration. Right? That's, the basic problem.

难道就没有其他方法解决这个问题吗？

Like, there's no other way to solve that?

是的。嗯，也许有，但我认为我们必须考虑某些事情发生的概率。所以如果你想拥有一个巨型细菌，地球上确实存在一些巨型细菌。至少有六七个不同的、毫不相关的物种进化出了巨大的体型。它们都有一个共同点，那就是它们具有所谓的极端多倍体性，也就是说它们实际上拥有数万个完整基因组的副本。

Yeah. Well, maybe there is, but I think we have to look at the probability of certain things happening. So if you wanna have a giant bacterium, there are a bunch of giant bacteria around on earth. There's at least six or seven different quite, you know, unrelated species that have have evolved giant size. And the thing that they all have in common is they have what's called extreme polyploidy, which is to say they have literally tens of thousands of copies of their complete genome.

所以它可能是一个小基因组，但我们说的是一个三兆碱基的基因组，大约有3000个基因，而你拥有数万个副本。有时候，最大的那些甚至有七万到八十万个完整基因组的副本。复制和表达所有这些基因组的能量需求是巨大的。在内共生中，我们仍然有极端多倍体性，但我们已经剔除了所有不需要的基因。所以共生实际上是基于互补性。

So it may be a small genome, but we're talking a three megabase genome, so kind of 3,000 genes in it, and you've got tens of thousands of copies. Sometimes, you know, the very largest one have, you know, seven or 800,000 copies of their of their complete genome. The the energy requirements for copying all of and expressing all of those genomes are colossal. What we have with an endosymbiosis, we still have extreme polyploidy, but we've whittled away all the genes that you don't need. So a symbiosis is based on effectively complementarity.

是的。你有一个共生体为宿主细胞做某事，而宿主细胞则从内共生体那里获取或回报某些东西。所以这是一种基于相互需求的关系。

Yeah. That you've got a symbiote that's doing something for the host cell, and the host cell is taking something or giving something back to the endosymbiote. So it's a kind of a relationship which is based on mutual needs.

没错。

Right.

其中一个变得非常小，这使得另一个可以变得非常大。所以共生可以实现这一点。现在可能有多种方式实现共生，但没有相关例子。所有这些例子都是关于非常大的细菌，它们都具有极端的多倍性。它们都没有发展出复杂的运输网络，能够有效地摄取物质并将其输送到那里。

One of them becomes much smaller, that allows the other one to become much larger. So a symbiosis will do it. Now there could be multiple ways of having a symbiosis, but there's no examples on it. All of these examples of a a very large bacteria and they all have extreme polyploidy. None of them have come up with a complex trafficking network where you you effectively take things in and you ship it over there.

是的。只是没有足够的基因空间

Yeah. There's just not enough genetic space

来正确实现这个功能需求。基本上就像是你需要一个更小的基因组副本，只与呼吸相关，分布在整个膜上，并且在整个膜上有许多副本。我想我只是...是的。对我来说这似乎很难

to do to the feature request correctly. It's basically like you want a smaller copy of the genome that is only relevant to respiration sitting at sitting across the entire membrane and many copies of it sitting across the entire membrane. I guess I'm just Yeah. It seems hard for me

你对此表示怀疑...是的。同样的事情会

to You're incredulous that this Yeah. Same thing will be

在数十亿颗行星上发生。因为如果有其他方式解决这个问题，那么你会预期的是，一旦进化到原核生物阶段，它们有其他可以占据的生态位，只要它们能向复杂性发展，这个问题就会以某种方式得到解决。然后你就会拥有真核生物...智慧生命。

On like the billions of planets. Because if there was another way to solve it, then what you would expect is that as soon as you get to the stage of prokaryotes that have other niches that they could colonize if only they could drive towards complexity, this would somehow be solved. And then you'd have eukaryotes...intelligence.

我想说几点。第一，有一个叫做奥格尔第二法则的东西，意思是进化比你更聪明。是的。所以，当然，我不能说没有其他可能的方式发生。但说'哦，你知道，进化太聪明了'也是一种敷衍的说法。

I mean, a couple of things I'd say. Number one, there's a there's a thing called Orgel's second rule, which is that evolution is cleverer than you are. Yeah. So, yeah, of course, I cannot say that there's no other way that it could possibly happen. But it's also hand waving to say, oh, you know, evolution's so clever.

宇宙如此之大。肯定有另一种方式可以实现。好吧。你知道的，动动脑筋告诉我它会如何运作。因为我...你知道，我不能说这是唯一可能的方式。

The universe is so big. There's gotta be another way that it can happen. Okay. You know, engage your brain and tell me here's how it's gonna work. Because I I'm you know, I'm I cannot say it's the only way it could possibly happen.

对。

Right.

但我所说的是，你知道，湿润的岩石行星很常见。它们无处不在。你会遇到同样的情况。会有二氧化碳。会有相似的生物化学过程。

But what I've said is that there's a the you know, wet rocky planets are common. They're everywhere. You're going to have these same things. You're going to have c o two. You're going to have a similar biochemistry.

你会产生带有膜电荷的细菌细胞。这限制了它们。而在地球上我们所知的每一个似乎变大的例子中，都存在一个可能每次都会概率性发生的限制。是的。它们最终总是走向极端多倍体，而不是形成复杂的运输网络。

You're going to give rise to bacterial cells that have got a charge on their membrane. That constrains them. And every example that we know on Earth where they seem to have got bigger, there's a there's a there's a constraint that probably probabilistically happens every time. Yeah. That they always end up with extreme polyploidy, and they don't end up with sophisticated transport networks.

这并不是说每次都必须这样发生。也许有办法绕过它，但这并不容易，因为它们在地球上并没有经常这样做。对。它们在地球上根本没有这样做过。地球上唯一成功的例子是它们演化出了真核生物。

So that's not to say it's gotta happen that way every time. Maybe there's a way around it, but it's not an easy way around it because they haven't done it regularly on Earth. Right. They haven't done it at all on Earth. The only occasion where it worked on Earth was where they came up with eukaryotes.

这并不是说这是唯一可能的方式，但如果你试图剖析还有什么替代方案，我想不出任何替代方案。好吧。我能力有限。我想不出任何方案。但是，但是，你知道，如果你认为有一些，那么你告诉我它们可能是什么，然后你去检验它们。

That's not to say it's the only possible way of doing it, but if you try and dissect what are the alternatives, I can't think of any alternatives. Okay. I'm limited. I can't think of any. But but but, you know, if you think there are some, then you tell me what they might be, and you test them.

所以，你知道，有一个层次，我经常遇到这种情况，这很公平。因为如果我仅仅向你断言宇宙其他地方的生命会是这样的，你知道，我从小就看《星球大战》和《星际迷航》，还读《银河系漫游指南》。我和任何人一样热爱宇宙充满各种奇观的想法。所以我不喜欢我的立场，即实际上它相当有限，你在其他地方会看到同样的事物。是的。

So it's you know, there's there's a there's a level and I get this a lot, and it's fair enough. Because if I just if I assert to you that life's going to be this way somewhere else in the universe and, you know, I grew up watching, you know, Star Wars and Star Trek, and I and and and reading Hitchhiker's Guide to the Galaxy. I love the idea that the universe is full of all kinds of stuff as much as anybody. So I don't like my position of saying, actually, it's quite limited, and you're gonna see the same kind of things elsewhere. Yeah.

我，我，这不是一个我梦想拥有的立场或什么的。这只是我通过了解地球上的一切生命而被逼入的立场。也许我只是错了，但我想如果你只是说，啊，你被你的想象力限制了，你错了，因为你只是想不到。嗯，那就不再是科学了。现在我们谈论的，你知道，只是想象力和空谈，但不是科学。

I I it's not a position that I I, you know, dreamt of having or anything. It's just a position that I've been forced into by everything that I've learned about life on earth. Now maybe I'm just wrong, but but I suppose if you if if you simply say, ah, you're you're limited by your imagination, you're wrong because you just can't think of it. Well, that's not science anymore. Now we're talking about, you know, just imagination and hand waving, but it's not science.

是的。所以，我是在给出概率上的理由，说明为什么事情会是这样。我想说的是，如果你有一千个有生命的行星，也许其中999次生命都会以相同的方式存在，因为它是碳基的。它会依赖水。它会由细胞构成。

Yeah. So so I I'm giving reasons why probabilistically it's going to be this way. I would what I would say is if you've got, you know, a thousand planets with life on, maybe life is gonna be the same way 999 out of a thousand times because it's gonna be carbon based. It's gonna be water. It's gonna be cells.

它会涉及电荷。它会包含氢和二氧化碳，并且你会面临相同的限制条件。但也许在某个其他情况下，会出现我从未想到过的完全不同的东西，并且在非常不同的条件下。但这有一种概率性的事情，你知道，碳是如此普遍。水是如此普遍。

It's gonna be charges. It's gonna be hydrogen and c o two, and you're gonna face the same constraints. But maybe one other occasion is something completely different that I never thought of and under very different conditions. But there's a kind of a probabilistic thing that, you know, carbon is so common. Water is so common.

会一次又一次地遇到相同的限制条件。

Are going to keep seeing the same constraints again and again.

嗯。如果相当一部分岩石行星确实至少应该有有机物和细胞等等，感觉我们很快就能弄清楚这个故事是否正确，对吧？因为显然，如果那部分最终被证明是真的，并且我们在其他地方也没有看到真核生物，那么整个图景就会获得更多的可信度。但是，嗯，我不知道。

Mhmm. If it's the case that a significant fraction of Rocky Planet should have at least organics and cells and so forth, it feels like we should be able to learn pretty soon whether this story is kind of correct. Right? Because obviously if that part ends up being true and also we don't see eukaryotes elsewhere, then the whole picture is lent a lot more credence. But like we I don't know.

我们是不是快要前往几颗卫星，看看能否在那里找到一些有机物等等？

Are we about to go to a couple moons and see if we can find some organics there and so forth?

那可能需要我们一段时间。但是，是的，我们已经知道例如在土星的卫星之一——恩克拉多斯上存在有机物等等。几年前卡西尼号飞掠时，有从冰层裂缝中喷出的羽流，但水中溶解着有机物。还有氢，你知道，有机分子，pH值大约在8或9左右。所以这意味着在那大约五公里厚的冰冻表面之下，有一个液态海洋。在那之下，有热液系统产生碱性流体，这些流体使海洋呈碱性，并且发生着类似的化学反应。

That may take us a while. But, yeah, we already know that there are organics in so on Enceladus, for example, one of the moons of Saturn, when Cassini flew by some years ago, there are kind of plumes coming through cracks in the ice of water, but with organics dissolved in in in the water. And hydrogen and, you know, organic molecules, pH is around about eight or nine or something. So it implies that underneath that frozen surface, which people say is about five kilometers thick, underneath that, there's a liquid ocean. Underneath that, there are hydrothermal systems producing alkaline fluids, which have made the oceans alkaline, and it's the same kind of chemistry going on.

所以我们知道这些羽流中有有机物。我们不知道冰层下面是什么。我确实认为，去这些地方钻探冰层并看一看的诱惑最终会战胜我们。总会有人说，哦，我们不应该把我们自己系统的细菌带到那里。我倒是会说，你知道，来自地球的细菌在像恩克拉多斯这样的地方可能会生存得非常好。

So we know there's organics in these plumes. We don't know what's under the ice. I do think that the the incentives to go to these places and drill into the ice and have a look will get the better of us. There will always be people saying, oh, we shouldn't introduce bacteria from our own system into there. I would have said, you know, bacteria from the earth would probably survive extremely well in a place like Enceladus.

所以它

So it

能知道就太好了。是的。而且我完全支持探索，真的。

would be lovely to know. Yes. And I'm all in favor, really, of exploration.

Labelbox 拥有一个庞大的领域专家网络，他们称之为对齐者，帮助他们生成用于训练和评估前沿模型的数据。为了准备这期节目，我请 Labelbox 帮我联系了他们的一位化学专家进行快速辅导。我和 Neil 聊了聊，他是一位目前从事化学机器学习模型研究的研究员。那么第一个细胞分裂是如何发生的？

Labelbox has this massive network of subject matter experts, who they call aligners, to help them generate data for training and evaluating frontier models. In order to help prep for this episode, I asked Labelbox to connect me with one of their chemistry experts for a quick tutoring session. I got to chat with Neil, who's a researcher that's currently working on chemistry ML models. So how did the first cell division happen?

我猜想，这只是我的推测，但在这些热液喷口中，你有水流下去，氢气冒上来。而且这些水不会完全以线性方式流动。会有一些剪切力。会有一些左右的运动。所以我猜想，也许你可以开始考虑剪切其中一些细胞，将它们分裂

I suppose, and this is just me speculating here, but in these hydrothermal vents, you've got water flowing down with the hydrogen bubbling up. And this water is not just gonna be flowing in a completely linear fashion. There's gonna be some sheer. There's gonna be some side to side movement. So I suppose perhaps you could begin to consider shearing some of these cells, splitting them

然后我我记得他说过，就像，分裂的第一个版本可能是，就像，膜自然会以同样的方式分裂，就像气泡如果变得太大就会分裂一样。是的。Neil 考问了我对氧化还原化学的理解，就像他审问模型以确保它们对所有科学主题形成非肤浅的理解一样。Labelbox 在许多不同领域都有像 Neil 这样的专家，从化学（显然）到数学、编程，甚至创意领域。了解更多请访问 labelbox.com/dwarkesh。

in And I I remember him saying that, like, the the first version of division might have been, like, membranes naturally will split the same way, like, a bubble will split if it gets too big. Yes. Neil quizzed me on my understanding of redox chemistry, the same way that he interrogates models to make sure that they are developing a non superficial understanding of all the scientific topics. Labelbox has experts like Neil in a bunch of different domains, from chemistry, obviously, to math, coding, even creative fields. Learn more at labelbox.com/dwarkesh.

帮我理解复制因子是如何在这个世界中产生的，因为你有这些独立的孔洞，它们各自通过这些自发过程积累着自己的有机物。但最初，至少没有共享的遗传。这不像如果有一个非常成功的孔洞，它就会导致出现更多完全像它一样的孔洞。

Help me understand how replicators arise in this world because you've got these independent pores and they're each individually accumulating their own organics through these spontaneous processes. But initially, at least there's no shared inheritance. It's not like if there's a very successful pore, it then causes there to be more pores that are exactly like it.

想想我称之为这些孔洞内的原始细胞。所以你认为你制造的有机物是自组织的。对。脂肪酸双分子层膜会形成。是的。

Think what I would call protocells inside these pores. So you think think that you're the organics that you're making are self organizing. Right. A fatty acid bilayer membrane will form. Yeah.

而获得正反馈真正需要的是在这个原始细胞内制造有机物，并使该原始细胞生长并复制自身。它会复制自身是因为化学反应——如果化学反应是确定性的，就意味着你将得到这样的化学结果。如果你通过系统中的氢压驱动这个化学反应，你只会制造出两倍的分子，它们会分裂成两个，现在你就有了两个原始细胞。所以这里存在一种遗传形式，即它们获得相同的分子，因为这实际上是你唯一能做的事情。

And what you really need for positive feedbacks is to be making the organics inside this protocell and for that protocell to grow and to make a copy of itself. Now it will make a copy of itself because the chemistry if the chemistry is deterministic, it says this is the chemistry you're going to get. If you drive that chemistry through by the pressure of hydrogen in the system, you're just gonna make twice as many molecules, and they're gonna divide in two, now you've got two protocells. So there's a form of heredity to that, which is they they get the same molecules because that's effectively all you're allowed to do.

抱歉，那么发生的情况是，这个东西出芽然后定居到另一个孔中？

And sorry, what's happening is that so the thing buds off and then settles into another pore?

是的。

Yes.

我明白了。好的。懂了。这在这个过程中发生得相对较早？是的。

I see. Okay. Got it. And this happens relatively early in this process? Yes.

所以复制子的出现相对较早。

And so the rise replicators happens relatively early.

我在这里会犹豫使用‘复制子’这个词。这些是生长的，我会说是生长的原始细胞，它们有效地制造更多自身。你可以称它为复制子，但我更倾向于将‘复制子’这个词用于更像RNA的东西，这将是复制子的常规术语，即你实际上是在精确复制序列

I would hesitate to use the word replicator here. These are growing, I would say growing, protocells that are effectively making more of themselves. You could call it a replicator, but I would prefer to use the word replicator for something more like RNA, which would be the conventional term for a replicator, where you are literally replicating the exact sequence

我明白了。

I see.

关于这种RNA。

Of this RNA.

那么，我们何时才能从基因的视角出发，将基因视为一个连贯的复制单位？

And so at what point do we get to the gene's point of view where the gene is the coherent unit of replication?

越早越好。也就是说，如果你有这种决定性的化学反应，它会驱动生长并制造更多细胞，但这同时也是一条死胡同。你无法做其他任何事情。你完全依赖环境。你无法进化成更复杂的东西。在某种程度上你可以，但基本上，你总是会得到相同的结果，同样的环境总是会给你同样的东西。

The sooner the better, which is to say, you if you've got this deterministic chemistry, which is going to drive growth and make make more cells, it's also a dead end. You can't do anything else. You're entirely dependent on the environment. You can't you can't kind of evolve into something more complex. You you to some extent, you can, but basically, you're always gonna get the same and the same environment will always give you the same thing.

一旦你开始引入随机的RNA片段，你就拥有了所谓的可进化性，也就是说你可以开始抵抗环境。你可以开始做一些不仅仅由环境决定的事情。你可以进化、改变，最终摆脱事件的束缚并做其他事情。所以一旦有了基因，你就有潜力做几乎任何事情。是的。

Soon as you start introducing random bits of RNA into this, then you've got what you call evolvability, which is to say you can begin to resist the environment. You can begin to do things which are not just dictated by the environment. You can evolve and change and leave events in the end and do other things. So as soon as you've got genes, you've got the potential to to do almost anything. Yeah.

如果你有裸露的RNA片段，通常会发生的情况是，它们会因为复制速度而被选择。它们只是不断地复制自己。它们不会变得更复杂。它们不会编码新陈代谢。它们只是不断地复制自己，这是一条死胡同。

If you've got naked bits of RNA, what tends to happen is they they they're selected for their replication speed. They they they just go on making copies of themselves. They don't become more complex. They don't encoding metabolism. They just go on copying themselves, and and and it's a dead end.

是的。如果你把它们困在生长的原始细胞内，那么实际上，它们共享着相同的命运。如果其中一些能够使原始细胞生长得更快，那么它们就会获得更多的自身副本，因为它们在这个原始细胞内。原始细胞生长得更快。它复制了自己，并且仍然与之相关联。

Yeah. If you're trapping them inside growing protocells, then effectively, they're sharing the same fate. And if some of them are capable of making that protocell grow faster, then then they will get more copies of themselves because they're inside this protocell. The protocell is growing faster. It makes a copy of itself, and it's still associated.

所以，实际上你得到了我们今天在细胞中所知道的选择，即基因是复制者，但被繁殖的系统是细胞。

So so you've got actually selection as we know it in cells today, whereas where the replicator of the genes, but the system which is being reproduced is the cell.

所以您这种线粒体优先的观点有助于解释为何存在两种性别。也许您可以重述一下那个论点，但我好奇的是，如果有一个原核生物进化出有性生殖的世界，

So your sort of mitochondria first viewpoint helps explain why there's two sexes. Maybe you can recapitulate that argument, but I'm curious if if there was a world where prokaryotes had evolved sex,

您认为

do you

它们是否很可能只进化出一种性别？

think that they would have likely evolved just one sex?

我我要稍微展开说一下，因为你看——线粒体与性别有什么关系呢？它们与性别的关系实际上在于雌性性别，这甚至适用于单细胞生物，它们没有配子间的明显差异，也就是说没有卵细胞和精子之类的结构。它们会产生小型能动的配子，看起来更像精子。两种性别都会这样做。

I I'm gonna unpack that a little bit because see so so so so what have mitochondria got to do with sexes? So what they have to do with sexes is effectively the female sex, and this goes even for single cells things that don't have any, you know, obvious differences between gametes, which is to say they don't have oocytes and sperm or anything like that. They produce little motile gametes that look more like sperm than anything else. Both sexes would do that.

嗯。

Mhmm.

但根据定义，雌性性别会传递线粒体。嗯。而雄性则不会。这是一种近似说法，并不总是成立，存在例外情况，但这是生物学中的一个经验法则，即雌性传递线粒体DNA。

But by definition, the female sex passes on the mitochondria Mhmm. And the male does not. And that's a kind of that's a that's an approximation. It's not always true. There's there's exceptions to that rule, but it's a kind of a rule of thumb in biology that the females pass on the mitochondrial DNA.

为什么会这样呢？通过有性生殖，你实际上是在增加核基因组的变异，并使其经受选择，优胜者得以留存，而比原本更差的则被选择淘汰。所以你是在有效增加核基因、基因组的变异，然后选择有效的部分。嗯。至于线粒体，它们并不这样做，它们是无性繁殖地代代相传。

So why would that happen? With sex, what you're doing is you're increasing the variance in the in the nuclear genome, and you're subjecting that to selection, and the the winners are coming through that, and and and everything which is worse than it would have been gets eliminated by selection. So you're effectively you're increasing variants on nuclear genes, the genomes, and and then and then and then selecting for what works. Mhmm. With the mitochondria, they're not doing they're not they're they're passing on asexually down the generations.

线粒体基因组非常小，但存在多个拷贝。所以问题在于，如何保持其纯净？如何防止它随时间退化？因为假设你有100个线粒体DNA拷贝，其中两个发生了突变，但仍有98个正常运作，这两个突变的代价是什么？其实并不大。

There is a very small genome, but there's multiple copies of it. And so the question is, well, how do you keep that clean? How do you prevent that from degrading and degenerating over time? Because if you've got let's say, if you've got a 100 copies of mitochondrial DNA and two of them acquire mutations, but you've still got 98 which are doing their job fine, what's the penalty for those two mutations? It's not very much.

你几乎不会注意到它们。是的。所以，随着时间的推移，你又积累了几个突变，可能会逐渐退化。这个过程被称为穆勒棘轮效应，但基本上这些突变因为被其他干净拷贝补偿，所以在某种程度上避开了选择压力。那么如何清除这些随时间累积的突变呢？

You'll hardly notice them. Yeah. So so so now you acquire another couple of mutations, and you you can degenerate over time. It's a process called Muller's ratchet, but it's basically it's it these mutations are kind of somewhat screened from selection by being compensated for by clean copies that you have of other other copies. So how do you get rid of those mutations that are building up over time?

答案是，你需要增加线粒体基因的变异度。你需要有效地将这些突变体分离到某些细胞中，而将野生型分离到另一些细胞中。是的。你可以通过多轮细胞分裂来实现这一点，但如果只有一种性别传递线粒体，这会更有帮助。你已经在进行采样了。

Well, the answer is you what you need to do is increase variance of mitochondrial genes. What you need to do is effectively segregate into these cells all the mutants and into those ones, all the wild type ones. Yeah. So you can do that by by multiple rounds of cell division, but it helps if you've got two that effectively only one sex passes on the mitochondria. You're already sampling.

所以你已经在增加变异度，并且提高了选择的可见性。这基本上是关于线粒体基因的质量问题。

So you're already increasing the variance, and and you're increasing visibility to selection. You're basically it's about it's about the quality of mitochondrial genes.

你能帮我理解为什么线粒体的单亲遗传有助于增加变异吗？

Can can you help me understand why it's the case that uniparental inheritance of mitochondria helps increase variants?

因为我们在讨论细胞间的变异。假设你有100个细胞，它们都来自同一个亲本，如果你随机地将所有线粒体不加改变地分配给单个细胞，那么它就和你完全一样，是完全克隆的。但如果你取一小部分，比如随机取10%给这个细胞，随机取10%给那个细胞，随机取10%给另一个细胞，那么这个细胞可能恰好获得了所有好的拷贝，是的，而那个细胞可能恰好获得了所有坏的拷贝。

Because of so so so we're talking about variants between cells. So if you imagine that you have a 100 a 100 cells and you they all come from the same parent, let's say, and you randomly give each cell you know, if you give all the all the mitochondria that you have kind of straight into a single cell without without changing any of the ratios there, then then it's exactly the same as you are. It's it's fully clonal. But if you give if you take a small subsection of those and you say you take a random 10%, you give 10% to this one, a random 10% to that one, a random 10% to this one, randomly, this cell is going to happen to have got all the good copies Yep. And this cell is going to happen to have got all the bad copies.

现在你对这100个细胞进行选择，问它们表现如何？获得所有好拷贝的那个细胞表现良好，能够存活下去。所以你实际上是在增加下一代细胞间的变异度。而那些获得所有突变体的细胞，它们会受到打击。是的。

And now you subject these 100 cells to selection and say, how are you doing? And the one that got all the good copies, that does well, that that that gets on. So so what you're doing is increasing the variance between this kinda next generation of cells. So the ones that got all the mutants, they they get hit. Yeah.

而那些获得所有清洁拷贝的，它们表现不错。父母双方既有突变又有清洁拷贝，但你怎么区分它们呢？嗯，所以这基本上是关于取样的问题。还有单亲遗传，也就是说这是一种取样形式。你只取两个父母中一方的线粒体。

And the ones that got all the clean copies, they do alright. The the parent had got both the mutations and the clean copies, but how do you, you know, how do you distinguish between them? Well so so it's about sampling, basically. And uniparental inheritance, which is to say it's a form of sampling. You're taking the mitochondria only for one of the two parents.

所以你不会混淆父母双方都有的修复突变。你是在取一个子集。是的。所以你总是在增加子细胞之间的变异，而单亲遗传基本上就是给你一个子集。

So you're not mixing up mutations that repair both parents had. You're kind of taking a subset. Yeah. So you're you're you're always increasing variance between the daughter cells, and and and uniparental inheritance is basically giving you a subset.

那么为什么有两种性别的问题。嗯，你解释了为什么存在只有一个父母传递线粒体的进化生态位。是的。所以至少有两个生态位。一个是传递线粒体，一个是不传递线粒体。

So then the question of why there's two sexes. Well, you explained why there's this evolutionary niche for only one parent to pass on the mitochondria. Yeah. So there's at least two niches. One is passed on to mitochondria, one is don't pass on to mitochondria.

所以一旦你确立了这两种，你就可以问，为什么没有超过两种性别？是的。然后你就可以说，嗯，只会重复这两种中的一种。这是两种基本的

So once you've established those two, then you can ask the question, why aren't there more than two sexes? Yeah. And then there then you can just say, well, there would just be a repetitive one of these two. These are the two fundamental

我是说，更复杂，但但我的意思是，关于两种性别的事情是，你可以说这是所有可能世界中最糟糕的情况。

I mean, more complex, but but I mean, the thing about two sexes is is you could say it's the worst of all possible worlds.

对。

Right.

所以，再次，如果我们把它从人类身上拿开，这样我们可以不带感情地看待它。你有这些，你知道的，单细胞生物游来游去，它们都在产生配子。配子看起来彼此相同，它们会以同样的方式融合进行有性生殖，它们会排列染色体。你知道，它们基本上做的和我们完全一样，但是在单细胞尺度上。但有两种性别意味着你只能与50%的种群交配。

So, again, if you kind of let's take it away from humans so we can be dispassionate about it. You you got you got these, you know, single celled critters swimming around, and they're all producing gametes. And the gametes look the same as each other, and and they'll fuse in the same way as sex, and they'll line up the chromosomes. You know, they basically do exactly the same thing that we do, but on a single cell scale. But but having two sexes means that you you can only mate with 50% of the population.

另外50%与你性别相同，不会接受你的配子。是的。如果你有三种或四种性别，那么你就能与更大比例的人口交配。对吧。而有些真菌，它们实际上没有性别，但它们有交配类型，有些真菌可以有27,000种交配类型，这都是为了远系繁殖，所以你可以与几乎任何东西交配，但你

The other 50% is the same sex as you and and is not gonna accept Yeah. Your your gametes. If you have three sexes or four sexes, then you'll be able to mate with a larger proportion of the population. Right. And some fungi, they don't really have they they still have two sexes, but they have mating types as well, and you can have 27,000 mating types in some fungi, which is all about outbreeding so you can mate with just about anything, but you

如今的大学校园，你知道，我们可能正在经历其中的一部分。哦，是的。正在变得真菌化。

college campuses today, you know, we're probably getting some portion of that. Oh, yeah. It's becoming fungal.

是的。所以从这个意义上说，两种性别是所有可能世界中最糟糕的，你只能与...如果只有一种性别，如果每个人都是雌雄同体，你可以与每个人交配。对吧。如果你有三种性别，你可以与三分之二的人口交配，依此类推。那么为什么是两种呢？

Yes. So so two sexes then, in that sense, is the worst of all possible worlds you can only make with if you had only one sex, if everyone was a hermaphrodite, you can make with everybody. Right. And if you had three sexes, you could make with two thirds of the population and so on. So why two?

嗯，这个根本区别在于一方传递线粒体，而另一方不传递。除此之外，如果你有多个交配类型，仍然是一方传递线粒体，另一方不传递。所以在这些有多种交配类型的真菌中，存在一种等级秩序，占主导地位的一方会传递线粒体，而较不占主导地位的一方则不传递线粒体。所以你最终会得到非常复杂的系统，可以想象执行这一点相当困难。你知道，事情可能会出错。

Well, this this fundamental difference that one is passing on the mitochondria and the other is not. Beyond that, if you've got multiple mating types, you still have one passes on the mitochondria and the other one doesn't. So in these fungi that have all of these mating types, there's a kind of a pecking order that the dominant one will pass on the mitochondria and the less dominant one doesn't pass on the mitochondria. So you end up with really complex systems that you can imagine that it's pretty hard to enforce this. It's pretty you know, stuff can go wrong.

系统越复杂，出错的可能性就越大。所以我想从这个意义上说，为什么最终是两种性别？部分是为了最小化错误。

The more complex the system is, the more it will go wrong. So I guess in that sense, why do you end up with two sexes? It's partly minimization of error.

你们有一个非常有趣的讨论，关于这不仅解释了为什么有两种性别，还解释了卵子和精子为何以特定方式发育、在成熟前复制次数不同等具体差异。我想知道你是否能概括一下。

You have this really interesting discussion about how this not only explains why there's two sexes, but the particular differences in why eggs and sperm develop the way they do, why there's different amounts of replications before they are mature, etcetera. I wonder if you can recapitulate that.

所以一旦你有了这个根本区别，即使在单细胞生物中，一方性别传递线粒体，而另一方不传递。是的。所以雄性不传递他们的线粒体。然后这开始解释，你知道，多细胞生物中生殖细胞系性质之间的性别差异。所以是的。

So as soon as you've got this fundamental difference, even in single celled critters that one of the sex es passes on the mitochondria and the other one doesn't. Yeah. So males do not pass on their mitochondria. And and and then this is beginning to explain, you know, differences in multicellular organisms between the sex between the nature of the germline. So Yeah.

在某种意义上，男性并不真正拥有像女性那样的生殖细胞系。所以在女性的生殖细胞系中，你会制造这些卵母细胞，并有效地将它们冷冻保存。你会精心照料它们。你会尽可能地将它们关闭。你试图保护它们免受突变的影响。

In some sense, male men do not really have a germline in the sense that that women have a germline. So in the in the in the in the female germline, you you make these oocytes, and you put them on ice effectively. You you you look after them. You you you you switch them off as much as you can. You try and protect them from mutations.

你实际上是溺爱它们，而男性则只是大规模生产充满突变的精子。我的意思是，遗传学家詹姆斯·克劳有一句很好的话，他说在人群中，没有比生育能力强的老年男性更大的遗传健康危害了。那么，为什么你要一直大规模生产精子呢？嗯，部分原因是你不需要传递线粒体。嗯。

You you molycoddle them effectively, whereas whereas men just mass produce sperm full of mutations. I mean, there's there's a lovely phrase from James Crow, who's a geneticist, who said there's no greater genetic health hazard in the population than fertile old men. So so why would you go on mass producing sperm all the time? Well, part of it is you don't have to pass on the mitochondria. Mhmm.

所以你让自己能够大规模生产精子，然后得到相同的结果。其中一些充满突变，但很多并不是。你大规模生产它们，而且，你知道，很可能一切都会顺利。因为例如，游得最好的那些更有可能成功。这并不完全正确，但你可以大致这样理解。

So you're freeing yourself up to mass produce sperm, and then you've got the same things out. Some of them are full of mutations, but a lot of them aren't. You mass produce them, and and and, you know, the chances are it's gonna work out okay. Because the ones that can swim best, for example, are the ones that are more likely to. That's not strictly true, but you can imagine it along those lines.

但在卵母细胞的情况下，对于卵细胞，你正在传递那些线粒体，你不想在线粒体DNA中积累突变，你想尽可能地将它们关闭，尽可能地将它们冷冻保存。这很大程度上是两性最终如何变得彼此不同的差异所在。

But in the case of oocytes, in case of the egg cells, you're passing on those mitochondria, you don't wanna be accumulating mutations in that mitochondrial DNA, you wanna switch them off as much as possible, keep them on ice as much as possible. That very much the differences between how the sexes end up kind of becoming different to each other

对。

Right.

归根结底是你的生殖系统受到哪些限制。

Boils down to what are what are the constraints on on on on on your reproductive system.

是的。好的。那么我们来谈谈Y染色体，它也是不重组的。现在就像女性卵细胞试图最小化复制次数以保持线粒体DNA的质量并防止错误一样。为什么Y染色体不发生同样的事情呢？

Yeah. Okay. So let's talk about the y chromosome, which is also not recombined. Now just the same way that female egg cells try to minimize the amount of duplications in order to preserve the quality of the mitochondrial DNA and prevent errors. Why Why isn't the same thing happen with the Y chromosome?

为什么所有这些精子复制过程不应该导致Y染色体出现各种错误呢？

Why shouldn't all this sperm duplication be resulting in all kinds of errors in the Y chromosome that

嗯，确实会出错。好吧。而且Y染色体是退化的，

Well, it does. Okay. And the Y chromosome is degenerate and

我对这个标题感到恼火。是的。但我的意思是，确实存在，

I annoyed that the title Yeah. But I mean, there are,

你知道，有些物种已经完全失去了Y染色体，但它们仍然有性别区分，因为这并不严格依赖于Y染色体。我的意思是，如果你纵观整个进化过程中的性别决定机制，会发现这有点奇怪，比如两栖动物的性别是由温度决定的。所以雄性会在比雌性更高的温度下发育，有时则相反。而且，你知道，鸟类与哺乳动物有不同的性染色体。所以性染色体是在多个不同的进化场合中独立演化出来的。

you know, there are some things that have lost their y chromosome altogether, and and they still have sexes because it's not strictly dependent on the y chromosome. I mean, again, if you look at what determines sexes across the whole canvas of evolution, it's kinda weird because amphibians, for example, have temperature dependent sex determination. So males would develop at a higher temperature than females, or sometimes it's the other way around. And, you know, birds have different sex chromosomes to to mammals, for example. So sex chromosomes have evolved on multiple different occasions.

那么Y染色体在做什么呢？Y染色体基本上编码一种生长因子，这种生长因子会激活其他生长因子。在胚胎发育过程中，你能分辨两性之间最早的区别并不是Y染色体和SRY基因的激活，而是生长速度。在我所在的伦敦大学学院，有一位名叫乌尔苏拉·米特瓦克的女性，她整个职业生涯都在研究这个问题，她在二十世纪六十年代发表了大约15篇《自然》论文。

And what what's the y chromosome doing? Well, the y chromosome is basically encoding a growth factor, and that growth factor switches on other growth factors. And the the the earliest difference that you could tell between the two sexes in in in embryonic development is is not the activation of the y chromosome and the SRY gene. It's actually the growth rate. And and there's there was a there was a woman at at UCL where I am called Ursula Mitvak who spent her career she she had about 15 nature papers in the nineteen sixties.

她研究这类问题。她认为生长速度是一个共同点，Y染色体基本上是在说‘快速生长’。为什么要快速生长？部分原因是你没有任何限制去损耗自己的线粒体，因为你不会将它们传递下去。所以你可以快速生长，如果你是雄性，快速生长会有优势。

She worked on this this these kind of questions. And she saw the growth rate as a common denominator, the the y chromosome is basically saying grow fast. Why would he grow fast? Well, in part, you can grow you don't have any constraints on trashing your own mitochondria because you're not passing them on. So you can grow fast, and there'll be an advantage to growing fast if you're male.

你会获得资源，生长得更快。如果你是雌性，你不想长得太快，因为你需要有效地隔离生殖系以保护卵母细胞留给下一代。在完成这一点之前，你不想损耗自己的线粒体。所以，你知道，在你开始快速生长之前，会有一个延迟阶段。

You're gonna get the resources you grow faster. If you're a female, you don't wanna grow so fast because you need to effectively cordon off germline to preserve the oocytes for the next generation. Until you've done that, you don't wanna trash your mitochondria. So you you've got a, you know, a delay phase before you you can start growing fast.

有意思。女性就是这样活得更长吗？

Interesting. Is this how women live longer?

乌苏拉·米特瓦克认为情况正是如此。嗯。我们并不确定这是事实，但雌性比雄性寿命更长确实相当普遍，不仅人类如此，你知道，在果蝇中通常也是这样。

Ursula Mittvak argued that that was exactly the case. Mhmm. We don't know for a fact that that's true, but it is it's it's quite common that females live longer than males, not just in humans, but but in, you know, in Drosophila as well, they do usually.

假设人类进化在未来十亿年里自然延续，没有人工通用智能和人类基因编辑等等。你预期的平衡状态是Y染色体会完全消失，然后通过其他方式决定性别和性别相关特征吗？

Suppose that evolution on humans just continued naturally for the next billion years and, you know, we didn't have AGI and human gene editing, etcetera. Is the equilibrium that you'd anticipate that the Y chromosome would then just fade away altogether and there'd be some other way of determining sex and sex dependent characteristics?

嗯，确实存在这种情况，而且在某些物种中Y染色体已经完全消失了。

Well, there are, and it has disappeared altogether in in some species.

嗯。

Mhmm.

通常保留的是一个基因，这个基因会导致不同的生长速率。

And usually, what you retain is one gene, which which which causes a different rate of growth.

我明白了。

I see.

所以实际上，Y染色体确实是退化的。它失去了大部分基因。关于穆勒棘轮效应，即在没有性行为或重组的情况下发生的退化现象，有两个影响因素。其中之一是种群规模。在细菌中，如果种群规模小且无性繁殖，那么该种群中就会积累突变。

So so really, the the y chromosome, yes, it's degenerate. It's lost most of its genes. The thing about Muller's ratchet, which is the degradation of of things when when you don't have sex or you don't have any recombination, there's there's two factors that influence it. One of them is the population size. So in bacteria, if you've a small population and they're not sexual, then you you accumulate mutations in that population.

但如果种群规模大得多，越接近无限大的种群规模，它们就不会都积累相同的突变。因此整个种群将会保持良好。这可以追溯到几十年前的人口遗传学研究。但另一个在人口遗传学中较少探讨的因素是基因组的大小。对于细菌来说，如果将它们的基因组大小增加到真核生物级别的规模，就无法维持更大的基因组。

But if you've a much larger population, the closer you kind of get towards an infinitely large population, they're not all going to accumulate the same mutations. And so the population as a whole is gonna be fine. And this this kinda goes back decades in population genetics. But the other thing which is less less explored in population genetics is the size of the genome. So so if you with bacteria, if you increase their genome size up to eukaryotic sized genomes, you can't maintain a larger genome.

你会在那个基因组中积累突变，它会再次缩小。而对于Y染色体来说，是的，它缩小了。与其他所有染色体相比，它是一个非常小的染色体。所以真正的问题在于你能维持多少基因处于良好状态？对于Y染色体，基本上只需要几个基因。

You'll accumulate mutations in that genome, and it'll shrink again. And with the with the y chromosome, yes, it shrunk. It's a tiny it's a tiny chromosome in comparison with all of the rest. So so it's really is how many genes can you maintain in a good state? And with the y chromosome, basically, you only need a couple of genes in there.

基本上就是SRY基因在说长得更快。

There basically is is the SRY gene is saying grow faster.

我明白了。

I see.

你只需要那个基因保持功能正常，然后在生育或不育男性层面上的选择会淘汰那些SRY基因失效的个体。所以并不是说你有一个突变拼凑体，你可以让Y染色体退化到几乎什么都没有，但仍然保持功能。

And you only need that to remain functional, And then selection at the level of fertile or infertile men will kinda weed out the ones that have got a nonfunctional SRY gene. So it's not as if you've got a patchwork of mutate you can afford to degenerate your Y chromosome down to almost nothing, and you'll still be functional.

我的意思是，这很有趣，因为你刚才说同样的事情也发生在 mitochondrial DNA 上，它是一个微小的基因组。并且随着时间的推移不断缩小，从最初被吞噬的细菌开始。

I mean, it's quite interesting because you were saying that the same thing happened to the mitochondrial DNA Which is a tiny genome. And has shrunk over time starting from the original bacteria that was engulfed.

它已经从大约三、四千个基因减少到我们案例中的37个基因。所以你看，如果种群规模很小，你就无法维持一个大基因组。我是说，种群规模很重要。如果你是一个自由生活的细菌，在野外有百万种群规模，现在你寄居在另一个细胞内，而且是个小细胞，现在你的种群只有五个。所以你会积累突变，无法抵抗它们，因此会丢失基因，基因组就会缩小。这就是线粒体发生的情况。

It's gone down from, say, three or 4,000 genes to, in our own case, 37 genes. So it's you know, you cannot sustain a large genome if you're inside you know, I say I said, but population size matters. If you're a mighty con if you were free living bacterium living out there in the wild with a population of a million, and now you shelter inside another cell and it's a small cell, now you've a population of five. So you will accumulate mutations and you can't resist them, so you'll lose genes, so your genome shrinks. That's what happened to the mitochondria.

你就是无法维持细菌大小的基因组。

You just can't maintain a bacterial size genome.

所以也许值得解释为什么性比横向基因转移更可取，从系统性地汇集和并行搜索基因空间的角度来看。既然性有这种优势，而细菌又有某种前身，为什么它们没有完全获得这种能力？是不是仅仅因为与它们的体型不兼容？

So maybe worth explaining why it's the case that sex is preferable to lateral gene transfer in the sense of being the systematic pooling and parallel search across gene space. So if there is this advantage of sex and then bacteria have some antecedent to it, why didn't they just get the whole thing? Is it just like it's not compatible with their size?

我认为它们不需要它。它们所做的是横向基因转移，基本上就是从环境中随机拾取DNA片段。这可能比那更险恶一些。你可以杀死旁边的细胞，获取它的DNA并加载进去。这种情况确实会发生。

I think they had no need for it. So so what they do is lateral gene transfer is basically you you pick up random bits of DNA from the environment. It can be a bit more sinister than that. You can kill a cell next to you and take its DNA and load that in. That does happen.

但大多数情况下，你是从环境中拾取DNA片段，通常是小片段，大约一个基因的大小。而且只有在有点压力时才会这么做。如果情况对你不利，你就会拾取DNA片段，将其整合到你的基因组中，然后希望最好。我猜对大多数生物来说，大多数时候这不会奏效。但对其中一个有效，然后它们就会占据优势。

But for the most part, you pick up bits of DNA from the environment, usually small pieces, usually kind of one gene's worth or something. And you'd only do that if you're a bit stressed. If if if things aren't going well for you, you you you will then pick up bits of DNA, bind it into your genome, and hope for the best. And I guess for most critters, most of the time, it's not going to work. But for one of them, it does, and then they will they will take over.

所以它有点加速了对变化环境的适应。嗯。那么为什么它们只使用一个基因？这有两种看法。你有一个细菌大小的基因组。

And so it it kind of speeds up adaptation to a to a changing environment. Mhmm. So why are why are they only using one gene? There's two ways of seeing this. You you you've got a a bacterial sized genome.

它相当小。是的。如果你保持基因组小，你会复制得更快。拥有一个庞大笨重的基因组是一种劣势。真核生物有这个特点，这是一个有趣的问题。

It's pretty small. Yeah. You're gonna replicate faster if you keep that genome small. It's a kind of a disadvantage to have a big unwieldy genome. Eukaryotes have that, and it's kind of an interesting question.

为什么你会拥有如此庞大笨重的基因组，复制需要更长时间，而且你知道，细菌其实非常精简。它们会丢弃不需要的基因，从而生长得更快。但现在环境变了，你又需要这些基因了。那该怎么办？你就直接获取它。

Why would you have such a big unwieldy genome that takes longer to copy and longer you know, bacteria are really streamlined. They get rid of genes they don't need, and then they can grow faster. But now the conditions change, and now you need these genes. So what do you do? You pick it up.

你只需随机获取基因并祈祷好运。拿到对的基因，就能重新出发。所以细菌的基因组规模很小。可以说它们拥有的是一个小基因组，但却有一个庞大的泛基因组，也就是它们能获取的所有基因。嗯。

You just pick up random genes and hope for the best. Pick up the right one, and off you go again. So so bacterial genome sizes are small. They've got what you'd say is a it's a small genome, but then a large pangenome, which is a kind of the all of the genes they have access to. Mhmm.

所以一个大肠杆菌细胞可能只有三到四千个基因，但却能获取三到四万个基因。

So an E. Coli cell might have three or 4,000 genes in a single cell, but access to 30 or 40,000 genes.

是什么让这个宏基因组得以保留？为什么为什么大家不都收敛到当前所需的这种精简状态？我是说，

What is keeping the metagenome around? Why is it why why doesn't everybody just converge to this streamlined thing that is needed for the the current I mean,

我认为宏基因组得以保留的原因在于，不同菌株的大肠杆菌，或者任何细菌，都生活在不同的环境中。比如你肠道里有共生细菌，皮肤上也可能有大肠杆菌，环境截然不同。

I think what keeps the the metagenome around is is the fact that different strains of E. Coli, whatever bacteria they may be, are living in different environments. So you could have a commensal bacteria living in your gut. You could have bacteria's E. Coli living on your skin, very different environment.

还有非共生的致病性大肠杆菌，它们的行为方式又不一样。它们的基因组差异可能高达50%。是的。所有这些情况并存，它们还能互相借用基因。

You can then have noncommensal pathogenic E. Coli, which are, you know, behaving differently. Again, they can differ in 50% of their genome. Yeah. So you got all of these things going on side by side, and they can all borrow genes from each other.

这基本上发生在同一物种内部——虽然对细菌来说'物种'具体指什么并不明确。嗯。所以细菌进化的动态就是：保持小基因组的同时获取大泛基因组，不断进行基因借用和匹配等等。通过保持自身基因组小巧，它们有效地保持了竞争力。

And this is basically within the same species, whatever species exactly means with bacteria. It doesn't quite have a meaning. Mhmm. So so so this is the the kind of dynamic of bacterial evolution is they retain small genomes with access to large pan genomes, and they're forever borrowing matching and and so on. And and they they they effectively remain competitive by keeping their own genome pretty small.

是的。然后真核生物基本上抛弃了那种方式，拥有了更大的基因组。于是问题就来了，如果你试图用一个真核生物规模的大基因组，然后继续从环境中获取小片段DNA，那么替换正确基因的几率就会降低。

Yeah. And then eukaryotes kinda threw all of that out and got larger genomes. And then the question is, well, if you try and do that with a large genome, a eukaryotic sized genome, and then you go on picking up little bits of DNA from the environment, the chances of you replacing the right gene gets lower.

我明白了。

I see.

所以基因组越大效率就越低。到了真核生物阶段，它们拥有大基因组。为什么会有大基因组？我认为是因为它们获得了内共生体变成了线粒体。现在你有了更多可用的能量。

So it just becomes less and less efficient the bigger your genome is. So by the time you get to eukaryotes, they have a large genome. Why do they have a large genome? I would say it's because you acquired this endosympathetic they become the mitochondria. Now you have a lot more energy available.

真核生物能容忍更大基因组有多种原因，但归根结底是你有能量来处理它，这是细菌从未真正拥有的。所以现在，水平基因转移不足以维持这种更大的基因组。你需要更系统化的方法。于是你整合整个基因组，将所有内容对齐，在它们之间进行交叉。现在是系统化的、互惠的，你可以在更大基因组中维持基因质量。

There's all kinds of reasons why eukaryotes will tolerate a larger genome, but the bottom line is you've got the energy to do something with it, which bacteria never really had. And so so now, lateral gene transfer is just not good enough to maintain this larger genome. You're gonna have to do something more systematic. So you pull on an entire genome, you line everything up, you cross over between them. Now it's systematic, it's reciprocal, and you can you can maintain the quality of genes in a much larger genome.

所以细菌从未需要这样做。

So bacteria never had the need to do that.

没错。读您的书时，为了缓解我的无知，我试图想出一个类比。请告诉我这个类比在哪些方面很幼稚。同时也感谢您今天容忍我所有其他幼稚的问题。但在硅谷，也许一个适合我们的类比是，比如说一个GitHub代码库。

Right. As I was reading your book, just to ease my own ignorance, I was trying to come up with an analogy. And so please let me know in which ways it's naive. And also thanks for tolerating all my other naive questions today. But here in Silicon Valley, maybe an analogy that will work for us is to think about, let's say a GitHub repository.

然后

And then

我现在已经超出我的理解范围了。基本上你

I'm already out of my depth now. Basically you

就是有一个代码库，然后你有进行版本控制的方法。通常的做法是，这可能类似于有性重组，就是有人创建一个所谓的新分支。在那个分支里，他们可能会做一些修改，这些修改组织在他们试图更改的功能旁边。然后，当维护者查看代码时，他们可以看到这里是原始代码的样子，这里是对那部分代码的修改。

just have this code base and then you have ways in which you do version control. So the usual way this is done, and this may be analogous to sexual recombination is that somebody makes what is called, they make a new branch. In that branch, they might make changes which are organized next to the function that they're trying to change. And then, so when the maintainer is looking at the code, they can see here was what the original code was at this point. Here's the modification to that point of code.

你看到差异，然后如果看起来合理，就可以把它合并回去。所以这里的类比可能是，你知道，沿着相关基因组织的有性重组。你看到这个等位基因，你看到那个等位基因。然后我猜这里的进化是维护者，它推动其中一个固定下来。无性繁殖、带突变的克隆的类比是，好吧，你分叉仓库，然后做一个随机更改。

And you see the diff and then you can merge it back if it seems sensible. And so the analogy here might be, you know, sexual recombination that's organized along the relevant gene. You see this allele, you see that allele. And then I guess evolution here is a maintainer, which is then driving one of them to fixation. The analogy for asexual reproduction, cloning with mutation would be, okay, you fork the repository, then you make a random change.

你只是改变一些随机变量。你改一个词，改一个比特。几乎每一次，这都会是有害的。即使它没有害处，也没有合并功能。所以这些不同的，你有数百万个仓库，它们又衍生出数百万个其他仓库。

You just change some random variable. You change a word, you change a bit. And almost every single time, this will be deleterious. And even when it's not deleterious, there's no merge functionality. So these different, you've got millions of repositories that they're then spawning millions of other repositories.

即使其中某个仓库有所改进，也没有系统性的方法可以将这些改进合并在一起。我的意思是，

And even if some improvement has been made on one of them, there's no systematic way in which the improvements can be merged together. I mean,

听起来非常相似。是的。

it sounds quite similar. Yes.

是的。最后是横向基因转移。所以这里的类比可能是，好吧，你有一个用于编辑网页的仓库，另一个用于控制航空软件的仓库。你做的就是从这个网页编辑软件中随机取一段500行的代码序列，直接放到飞机管理软件的随机位置。没有系统性的组织，比如这里是相关功能的位置，这里是

Yeah. And then finally lateral gene transfer. So here the analogy might be, okay, so you've got one repository for, let's say editing web pages and another repository for controlling airline software. And what you just do is you take a random 500 line sequence in this web page editing software, you just put it in a random point in the airplane management software. And there's no systematic organization of like, here's where the relevant functionality is and here's like

嗯，有一点是这样的，横向基因转移时，你通常会将其末端与你已有的东西匹配。嗯。我对编码了解不够，无法给出一个可比较的例子。但本质上，你是在拾取一个模块，它在某种程度上与你代码的这个部分有相似之处，能够适配进去。

Well, there is a bit, which is to say with lateral gene transfer, you would normally match the ends to something you've got already. Mhmm. So I I don't know enough about coding to to to to give a to to give a comparable example. But effectively, you would be picking up a module which had had some resemblance in terms of, okay. It fits into this part of the code.

是的。所以你只会把它放进去，它在那里可能有用也可能没用。嗯。但这并不完全是随机的。它有点像是插在一个你知道曾经有过或可能有类似东西的地方。

Yeah. So you'd only put that in, and it may or may not be useful there. Mhmm. But it's not just completely random. It is kind of it's it's plugged into a place where you know you have something like that that used to be there or could be there.

所以它并不是完全随机的，但与此同时，你并不知道自己放进去的是什么。

So it's it's not it's not just random, but at the same time, it's you you don't know what you put in.

那么我猜，说实话，我确实不太理解为什么横向基因转移不会产生与重组类似的好处。

So then I guess, honestly, don't really have good intuition for why lateral gene transfer does not produce similar benefits to recombination.

这其实只是一个规模问题。如果你拾取一段随机的DNA，嗯，你的基因组会变得大10倍。

It's really just a scaling thing. If you if you pick up a random piece of DNA Yeah. You've got a you've got a genome which is 10 times larger.

我明白了。好的。

I see. Okay.

然后，你知道从环境中拾取DNA的速度能有多快？你需要拾取10倍多的量才能做到。你有能力拾取10倍多的量吗？这样做还有代价，就像突变一样，你根本不知道插入了什么。它几乎可以是任何东西。

Then, you know, how fast can you pick up DNA from the invite? You know, you'd have to pick up 10 times as much to do that. Do you have the capacity to pick up 10 times as much? There's also a penalty for doing it, which is to say, like a mutation, you've got no idea what you're plugging in. It could be almost anything.

你知道你要把它插在哪里。你插的地方是对的，但那个卡带里到底是什么？你其实并不知道。所以你做得越多，你自己也会退化得越厉害。我明白了。

You know where you're plugging it. You're plugging it in the right place, but what's in in that cassette? You don't really know. So the more you do of it, the more you will degenerate yourself as well. I see.

所以做这件事有某种成本和收益。

So there's there's kind of costs and benefits to to to doing it.

如果你经营一家前沿科技公司，你就知道招募全球顶尖人才有多么重要。但这需要驾驭错综复杂的美国移民体系。你不仅没有时间亲自处理这件事，你也没有那种隐性知识来最大化成功的概率。但鉴于卓越人才至关重要，你不能在签证批准上冒任何风险。你需要与最优秀的团队合作。

If you're running a frontier technology company, you know how essential it is to recruit the world's best talent. But this requires navigating the Byzantine US immigration system. Not only do you not have the time to deal with this yourself, you just don't have the tacit knowledge to maximize the probability of success. But given how critical exceptional talent is, you can't take any risks with visa approval. You need to work with the best.

Lighthouse处理一切事务都比你可能做到的更好、更快，而且他们只需要你提供最少的输入。Lighthouse深谙移民机器的各种门道。他们知道如何包装出版物和奖项，如何构建与基准的薪酬比较，以及如何将所有内容整合成一个最具说服力的故事。他们甚至优化了微小的细节，比如在起草支持信时使用的语气，以帮助美国移民官员理解科技和初创公司的重要性。像Cursor、Together AI和Physical Intelligence这样的公司都已经在与Lighthouse合作。

Lighthouse handles everything better and faster than you possibly could, and they do it all with minimal input from you. Lighthouse knows the nooks and crannies of the immigration machine. They know how to frame publications and awards or how to structure comp comparisons versus benchmarks and how to put everything together into the most compelling story possible. And they've even optimized the tiny details, like the tone they use when they draft support letters to help US immigration officials understand the importance of tech and startups. Companies like Cursor, Together AI, and Physical Intelligence are all already working with Lighthouse.

你可以访问lighthousehq.com/employers加入他们。好了。那么，也许最后问一下，什么样的实验或审问方法能让我们获得关于这个故事最多的信息？

You can join them by visiting lighthousehq.com/employers. Okay. So maybe to close this off, what is the experiment or method of interrogation which would give us the most amount of information about the this story?

是的。我是说，这个故事有太多方面了。我可以给出的可能答案太多了。我的意思是，就真核生物、巨型细菌、生命的可能性而言，我认为很大程度上取决于观察。我们根本不知道外面有什么，了解得还不够。

Yeah. I mean, there's so many aspects to this story. There's so many possible answers I could give there. I mean, in terms of eukaryotes, giant bacteria, the likelihood of life, I think there's a lot depends on observation. We simply don't know enough about what's out there.

是的。所以这不一定是简单的实验。如果我断言巨型细菌总是会拥有，你知道，极度的多倍体，带有多个基因组副本，而你发现了一个不是这样的例子。那我的想法就已经开始站不住脚了，所以知道这一点很有用。是的。

Yeah. And so it's not necessarily experimentation simply. If I assert that giant bacteria are always going to have, you know, extreme polyploidy with multiple copies of their genome, you find an example that's not like that. And already my ideas are breaking up, so useful to know. Yeah.

关于生命起源，你知道，我真的很希望能找到一个有说服力的理由，让我乘坐潜水器下到像失落之城这样的深海热液系统。我很想去

For the origin of life, you know, I 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

失落但

Lost But

问题是现在的海洋化学环境与四十亿年前完全不同。现在充满了氧气。也充满了细菌之类的东西，但因为存在氧气，海洋化学环境是不同的。海洋中没有铁。也没有镍。

the trouble is that the the ocean chemistry is completely different now to what it was four billion years ago. It's now full of oxygen. It's full of bacteria and things as well, but the ocean chemistry is is different because there's oxygen. There's no iron. There's no nickel in the oceans.

所以你可以去像失落之城这样的地方，但那里的墙壁不再是催化矿物构成的。它们是由文石和水镁石组成的，也就是碳酸钙和氢氧化镁之类的物质。因此它能进行的化学反应非常不同，而且那里有很多细菌生活。所以除了亲眼目睹的震撼之外，我能获得的信息并不多。

So you can go to event like Lost City, and the walls are not made of catalytic minerals anymore. They're made of aragonite and and brucite, so kind of calcium carbonate and magnesium hydroxide and things like that. And so the chemistry it can do is very different, and there's lots of bacteria living there. So I would gain beyond just the sheer amazement of seeing it. There's not a lot it would be able to tell me.

所以我们实际上是在实验室的无氧手套箱中进行实验，排除氧气以便进行这些氢气和二氧化碳的反应实验。通过这种方式我们能产生多少生物化学分子？这个过程缓慢而费力，产量很小。有时会受到污染，有时不得不从头再来。你知道，这是项缓慢的工作。

So so so what we're actually doing is experiments in a lab in a in an anaerobic glove box where you exclude the oxygen so you can do these experiments from reacting hydrogen and c o two. How how many of the molecules in in biochemistry can we produce that way? And it's slow and laborious, and you get small amounts. And and sometimes you get contaminations, and sometimes you have to start all over again. And, you know, it's it's it's slow work.

但它正在向前推进。也不仅仅是我们。我的意思是，世界上还有其他研究小组。例如约瑟夫·莫林的研究小组就沿着这些方向做了很多很好的生物化学研究。所以这方面正在取得进展，但我认为我们还需要几十年时间才能达到可以说“好了

But it it's it's moving forward. It's not just us either. I mean, there's other groups around the world. So so Joseph Morin's group, for example, has done a lot of really nice biochemistry along along these lines. So so that's kinda moving forward, but I I think we're talking decades before we're we're getting to the level where we can say, right.

我们可以驱动整个代谢通量。嗯。这就是能够实现的条件集。当然还需要一些年。有一些关键难点，比如制造嘌呤核苷酸，这个合成途径有12个步骤，所有中间体都不稳定且容易分解。

We can drive flux through all of metabolism. Mhmm. 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's 12 steps in this synthetic pathway, and all the intermediates are unstable and break down easily.

这是在甲醇等物质中进行的，而不是在水中。在水中，物质会分解。所以我们正在尝试这样做，这很困难。但我相信，我认为我们会成功，这就是我们尝试的原因。

It it's being done in things like methanol, so not in water. In water, stuff breaks down. So we're trying to do it. It's difficult. So we'll I I I believe, I think we'll get there, which is why we're trying to do it.

但也许我们不会成功，那样的话，假设就是错误的。你必须每天早上醒来时想，这个假设可能是错的。它很美妙，看起来有道理。但你知道，有太多美好的想法被丑陋的事实扼杀了。

But maybe we won't, in which case, again, the hypothesis is wrong. We you've gotta wake up every morning and think, you know, the hypothesis could be wrong. It's it's it's beautiful. It might it makes sense. But, you know, there's so many beautiful ideas killed by ugly facts.

所以坚信自己是对的并没有好处。你必须相信自己可能是错的，但仍然继续前进。另外，目前让我兴奋的另一件事是关于麻醉剂和线粒体的研究。几年前我从一个叫卢卡·都灵的人那里听说，他向我指出麻醉剂会影响线粒体。我之前完全不知道麻醉剂会影响线粒体。

So there's no good believing that you're right. You've gotta believe you're probably wrong and keep going anyway. And then the other the other thing which I'm excited about at the moment is is is work on anesthetics and mitochondria. It turns out I heard this from from a guy called Luca Turin a a few years ago now who pointed out to me that anesthetics affect mitochondria. I had no idea that anesthetics affect mitochondria.

但它们确实会影响。我们一直在做实验，虽然还没有完全确定，但似乎它们的主要作用对象就是线粒体。麻醉剂对各种生物都起作用，包括像阿米巴虫这样的生物。这并不能证明什么，但它开始提出一个问题：如果你能让阿米巴虫失去意识，那它之前是有意识的吗？按照我们对意识的理解，并不是。

Well, they do. We've been doing experiments on it, and and and it seems not fully established as this yet, but it does seem as if their main effect is mitochondria. And and anesthetics work on all kinds of things, including things like amoeba. So it's already saying it doesn't prove anything, but it's beginning to say, well, if you can make an amoeba unconscious, then is it con was it conscious before? Well, not as we understand consciousness.

但我们理解意识的方式实际上与神经网络有关。是的，还有神经系统以及人类意识的所有复杂性。这是我们主要思考的。但有一个深层问题，可以追溯到心身问题，但大卫·查尔默斯将其表述为意识的难题，按我的理解大致是：我们不知道从物理角度来说，一种感觉究竟是什么。

But the way we would understand consciousness is really about neural nets. Yeah. And nervous system and and all the complexity of human consciousness. That's what we primarily think about. But there's a deep problem which which goes back I mean, it's it's the mind body problem, but but it was it was framed by David Chalmers as the hard problem of consciousness, which boils down as my understanding of this is more or less, we don't know what a feeling is in physical terms.

所以你可以理解神经网络的信息处理过程，但如果你感到痛苦、感到爱或其他任何感觉，这在一个系统的化学层面实际上是什么？我认为问题在于，所有这些神经网络都在放电，其中一些是有意识的，我们能意识到自己在想什么。而其他一些，从神经元的角度看似乎具有所有相同的属性。

So you can understand the information processing of a neural network, but what actually if you feel miserable, you feel pain, or you feel love or whatever it may be, what actually is that in the chemistry of a system? And I suppose the problem is that you have all of these neural nets firing, and some of them are conscious. We're aware that of of what we're thinking about. And others, which seem to have all the same properties in terms of the neurons. They have synapses.

它们有突触，有神经递质，会去极化，传递动作电位，但我们并没有意识到它们。这是无意识的信息处理。所以这就是问题所在。

They have neurotransmitters. They depolarize. They pass on an action potential, but we're not conscious of it. It's it's it's nonconscious information processing. So so there's this question.

好的。那么，如果麻醉剂会影响没有神经网络的东西，而感觉又是我们无法用神经网络来定义的事物，是否可能感觉在某种程度上与生命有着更广泛的联系？为什么会这样呢？所以，再次说明，我作为一个进化生物学家是这样思考这个问题的。

Okay. So if if anesthetics affect things that don't have neural nets and and 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 to life? So why would they be? What would've so so so, again, the way I think about this is as an evolutionary biologist.

第一个问题是，我们是否认为感觉是真实存在的？我会说是的。我们是否认为它们是进化而来的？我也会说是的。我认为任何进化生物学家都会对这些问题的回答是肯定的。

So the first question is, would we think that that that that 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 those questions.

如果它是真实的并且是进化而来的，那么自然选择必定能够察觉到它并以某种方式作用于它。换句话说，它具有某种可以被选择的物理特性。再次强调，我认为这个说法没有任何争议。但如果它是物理性的、真实的，并且已经被选择过，那么这意味着我们应该能够测量它。它必须提供某种优势，以便自然选择能够作用。

If it's 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. Again, I don't think there's anything controversial about that statement. So but then if it's physical and real and has been selected on, you know, the implication is we should be able to measure it. There should be it it has to offer an advantage for selection to act on.

而且，如果它是一个物理过程，它应该是可测量的，但我们并不真正知道我们在这里试图测量什么。因此，我又回过头来思考，好吧。一个细菌细胞需要做什么？这只是粗略的思考。我立刻想到了新陈代谢。

And and if it's a physical process, it should be measurable, but we don't really know what we're trying to measure here. So I then kinda revert back to thinking, okay. What what would a bacterial cell need to do? And this is just just kind of back of the envelope thinking. And I immediately think about metabolism.

细菌细胞内部和外部世界有什么区别？基本上，内部是新陈代谢活跃的。它一直在进行化学反应，而且速度极快。一个细菌细胞每秒大约有十亿次新陈代谢反应。

What's the difference between the inside of a bacterial cell and the outside world? It's basically you know, the inside is is 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 in this metabolism.

因此，我立刻想知道，这一切是如何被控制的？你如何让这个细胞具有一致的行为，让它决定‘我要爬到那边去’？是的。你甚至如何知道自己处于什么状态？你如何协调所有这些生物化学过程？

So I'm immediately left wondering, how is it all controlled? How do you have how do you how do you get this cell to have a coherent behavior so it decides I'm gonna crawl over there? Yeah. How do you even know what states you're in? How do you kind of synchronize all of this biochemistry?

大多数人对此的回答可能是某种形式的新陈代谢调节。但那并不是真正的驱动力。最终的驱动力是热力学驱动因素。你有多少电子？这以食物、NADH或其他形式存在。

And 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 is is the thermodynamic drivers. How many electrons do you have? That's in the form of food or NADH or whatever it may be.

食物中以ATP形式存在的能量有多少？这些是将在相同阶段同步反应的因素。问题在于，当你处理分子时，你面对的是成千上万的分子。因此你需要进行大规模的统计抽样，这很耗时。但有一个更好的方法，就是说如果你从食物和NADH中获取电子并将它们传递给氧气，但同时产生膜电位并驱动ATP合成，你实际上可以测量变化速率以及膜电位和将产生的场——静电和电磁场。

How much energy do you have in the food in the form of ATP? These are the things that are gonna synchronize reactions in the same kind of phase. And the problem there is when you're dealing with molecules, you're dealing with with tens of thousands of them. So you got a kind of 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 and NADH and you're passing them to oxygen, but you're generating a membrane potential and that's driving ATP synthesis, you can actually measure the rate of change and the the the membrane potential and and and the the the fields that will be generated, electrostatic and electromagnetic fields.

这将让你了解你的状态，你相对于外部世界的代谢状态？而且，你知道，那里有足够的食物吗？有足够的氧气吗？是不是太热了？有病毒吗？

That's gonna give you a handle on your state, on your metabolic state in relation to the outside world? And, you know, is there enough food there? Is there enough oxygen there? Is there is it too hot? Is there a virus?

我有足够的铁来进行所有这些反应吗？所以你有一堆可能相互冲突的反馈循环，你必须做出决定。所以，你只是粗略地思考一个细菌细胞会如何行为。你会发现你已经把它框定为一个实体，一个细胞。它必须就做什么做出某种决定。

Do I have enough iron to be able to do all these reactions? So you've got all these potentially conflicting feedback loops, and you've got to make a decision. So you you're just just thinking loosely about how a bacterial cell is gonna behave. You find that you're you're you're already framing it in terms of as an entity, as a cell. It's got to make some kind of decision about what to do.

它必须整合所有这些信息，并作为一个自我、一个实体做出连贯的决定。这是自由意志吗？可能不是我们认可的任何形式，但它会根据其环境做出决定，而结果是生存与否。所以我认为感觉实际上是膜电位产生的电磁场，它告诉你你的物理代谢状态相对于你所处环境的情况。但这让我想到了一个问题。

It's gotta 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 and and and the outcome is survival or not. So what I think a feeling is then is effectively it's the it's the it's the electromagnetic fields generated by membrane potential, is telling you what your physical metabolic state is in relation to the environment you're in. But but that leaves me to a question.

所以，如果意识在某种程度上与线粒体有关，那么线粒体在那个意义上是否仅仅是一个ATP生成引擎，而你干扰了它们制造ATP的方式，因此麻醉剂通过有效地造成能量不足来起作用。大脑就会关闭。如果这是真的，那就太无趣了，但如果这是真的，知道这一点会很有用。但更令人兴奋的是，线粒体是否会产生我在细菌中谈到的那种场，这些场能给出某些线粒体、某些神经元中你状态的某种指示，而麻醉剂干扰了这一点。如果这是真的，那将非常神奇。

So if if if 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 deficits. The brain closes down. That would be dull if it were true, but it will be useful to know if it were true. But much more excitingly would be do do mitochondria generate kind of fields that I was talking about in in bacteria that are giving giving some kind of indication of your status in certain mitochondria, certain neurons, and the anesthetics interfere with that. That would be magical if that were true.

那将是一个全新的研究方向，这将非常棒。而且你知道，测量场非常困难。很容易测量到你不知道真正在做什么的人为产物。我们需要更多物理学家在这个领域工作，你知道，进行艰难的计算。我们需要更多关于实际是什么的数据，它真的只是在这些呼吸复合体中的一个，复合体一吗？

That would be a whole new direction of research, which would be fantastic. And we you know, it's very difficult measuring fields. It's it's very easy to to measure artifacts that you don't know what you're really doing. We need more physicists working in this area to, you know, do do the hard calculations. And we need more data on, you know, what what actually is is it really just in one of these respiratory complexes, complex one?

所以有很多标准的分子生物学我们可以做。他开始指向这个想法，是的，复合体一的工作方式有些特别，这可能与产生场有关，而场可能与麻醉剂的工作方式有关。这很有趣。科学的美妙之处在于它真的很有趣。这是我一直在努力传达给我实验室里的人们的一点。

So there's lots of standard molecular biology that we can do. And he's beginning to point to this idea that, yes, there's something going on about the way that complex one works, which may link to generating fields that may link to how anesthetics work. And that's just fun. The thing that's great about science is it's really fun. It's one thing I'm always trying to get across to the people in my lab.

你不能忘记乐趣。如果它变成了苦差事，那你最好离开，因为你在别处能赚更多钱。你在别处会过上更好的生活。但如果你真正关心的是科学和实验，那它必须是有趣的。你必须真正享受去那里做那些事的过程。

You can't forget the fun. If it becomes drudgery, then you best go because you'll make much more money somewhere else. You'll you'll you'll have a better life somewhere else. But if what you really care about is is the is the science and the experiments, it's gotta be fun. You gotta really enjoy wanting to go and do that.

而且，而且，而且我必须说，对我来说最棒的一点是，它一直很有趣。

And and and I have to say one of the great things for me is is it's always been fun.

是的。通过阅读你的书，间接感受到那种感觉真是太棒了。

Yeah. And it's been great to vicariously get a sense of that feeling from reading your books.

谢谢。

Thank you.

对于观众来说，这次对话与尼克的书《关键问题》最为相关。所以我建议如果你想更好地理解这里的论点，就去读那本书。书中有更多细节——太

For the audience, this conversation has been most coupled with Nick's book, The Vital Question. And so I would recommend getting that if you want to better follow the argument here. And there's a way more detail there that- Too

多了，但

much, but

那会很有帮助。我认为，这就是我之前告诉你的，感觉这是一个小众的书籍类型，不幸的是这类书非常少。一边是教科书，是的，可以用2000页来学习分子生物学，但一个好奇的外行实际上根本没有机会这样做。另一边是基本上只是关于科学家的轶事或科学史的轶事。这个发现者真的很反复无常，他是如何管理实验室的，他的父母是怎样的，但它从未真正谈论到相关的实际科学。

that would be helpful. And I think one, this is the thing I was telling you earlier that it feels a niche of books, which unfortunately there's just very few of. So there's textbooks, which yeah, can spend 2,000 pages learning about molecular biology, but a lay person just as practically, who's curious, is just practically not going to get a chance to do that. On the other end, there's what are basically just like anecdotes about scientists or anecdotes about the history of science. This one discover was really mercurial and here's how he ran his lab and here's how his parents were like, but it never really talks about the actual relevant science.

而像这样一本书确实填补了中间的阐释空白。

And a book like this actually does fill the explanatory middle.

是的。谢谢你。没错。我的意思是，我认为物理学家非常擅长撰写关于宇宙大问题的书籍。是的。

Yeah. Thank you. Yes. I mean, I I think that I think that physicists are very good at writing books about the big questions of the universe. Yeah.

而且，有一大批读者喜欢被一本书震撼心灵，即使你无法完全理解，因为你知道它很难懂。对吧。我们究竟是如何了解大爆炸、黑洞运作、背景辐射或其他任何事情的？对于生命，你知道，生命的起源、行星上生命的轨迹、复杂生命是否必然出现，还是大多数地方只会停留在细菌阶段——这些都是大问题，宇宙级别的问题。但并没有多少人写这些内容，试图带你走到我们所知的最前沿。

And there's a there's a large readership for for having your mind blown by a book that you're not gonna understand everything because you know it's difficult. Right. And and how do we know anything at all about the Big Bang or how black holes work or background radiation or whatever it may be. And with life, you know, the origin of life or the the the trajectory of life on a planet and whether we get complex life inevitably or whether we're gonna get stuck with bacteria in most places, These are big questions, you know, universe sized questions. And there's not many people writing about them and trying to take you to the edge of what we know Right.

就像物理学家经常做的那样，只是说，你看，我是这样看的。这是我眼中的问题。你必须尽量诚实地说，好吧，我是这样看的，或者别人有不同的看法。

In the way that the physicists very often do and and just say, well, you know, here's how I see it. Here's the questions through my eyes. And you gotta try and be honest and say, okay, not I see it this way or the people see it differently.

是的。顺便说一句，大语言模型的存在使得阅读这样一本书的过程变得更加可行和高效。我和几个朋友组成了一个读书俱乐部，我们不是生物学家，算是这个领域的门外汉。所以我确实鼓励大家，对于这样的书，看看是否能组建一个读书俱乐部之类的，因为可以和大语言模型多交流，我们借助大语言模型重温了很多非常基础的化学和生物学知识。比如，为什么在早期环境中，当一侧是碱性一侧是酸性时，二氧化碳和氢气的反应会受到促进？

Yeah. By the way, the fact that LLMs exist has made the process of reading a book like this much more feasible and productive. So I had a book club with a couple of my friends and we're we're not biologists, we're sort of lay people to this audience. And so it was I do encourage people for a book like this to see if you can just like form a book club or something because and just like to talk to LLMs a bunch because there's just a bunch of extremely basic remedial chemistry and biology that we were able to recapitulate with the help of the LLMs. And so, you know, this whole thing of why is the c o two and h two reaction incentivized when one side is alkaline and one side is acidic in this early environment?

你只需和大语言模型一起回顾基础化学知识。

You just go through the remedial chemistry with the LLM.

是的。我的意思是，我在书中尽力解释了这一点，但看来我做得并不太好。

Yes. I mean, I did my best to explain it in the book, and it seems that I didn't do a great job of it.

不。不。不。你只是

No. No. No. You just

这这非常，有太多细节了，而且而且，你知道，你无法避免这一点，因为问题中就是这样的，而生物学的问题就在于它极其复杂。你知道，物理学家看生物学时会觉得，这太难解释了。而生物学家们拥有所有这些术语，却常常迷失在术语中。而我我我天生就试图寻找简单的共同点，这让我很适合去写这些东西。但当然，我可能总是过度简化，或者可能做得不够好，没有简化到位。

It's it's very there's so much detail, and and and, you know, you can't avoid that because it's there in the questions, and this is a problem with biology is it's incredibly complex. And, you know, physicists look at biology and they think, well, it's too hard to explain. And biologists who've got all of these terminology and often get lost in the terminology. And and I I I find myself by nature trying to find simple common denominators, and that lends itself into writing about them. But, of course, I probably oversimplify all the time, or maybe I fail and don't simplify it enough.

但你会与之角力，尝试着去处理，实际上对我来说，和你以及读书会的其他人交流真的很有趣，看看你们在哪些地方感到困惑，在哪些地方有收获。你知道，我我会把这次的经验融入到下一次写书时。我会试着弄清楚，好吧，我怎样才能做得更好？

But you wrestle with it, and you try to And make it and it's actually it's genuinely interesting for me to to talk to you and the other guys in the book club to see where you were struggling with it and where you were. You know, I I will I will build this into next time I'm writing a book. I'll try and figure out, okay. How how do I do that better?

尼克，这次谈话太棒了。是的，谢谢你为我们提供了生物学和化学的补习指导，同时也探讨了许多关于生命最有趣的问题。

Nick, this has been great. And, yeah, thank you for the the guide through both the remedial biology and chemistry, but also through many of the most interesting questions that you could ask about life.

非常愉快。非常感谢。

Been great fun. Thanks a lot.

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那么，下期再见。

Otherwise, I'll see you on the next one.