基因与跨代记忆遗传 | Oded Rechavi博士

你甚至可以把它们切成200块。

You can even cut them to 200 pieces.

每一块都会长成一条新的蠕虫。

Each piece will grow into a new worm.

太神奇了。

Wild.

它们还有带叶状结构的中枢大脑，甚至退化的眼睛。

And and they have centralized brains with lobes and everything, and even this degenerate eyes.

他研究过这些蠕虫，并说他可以教它们某些事情，通过将某些刺激配对来建立关联——我记不清他具体是怎么做的了。

He studied these worms, and he said that he can teach them certain things, associations by pairing all I don't remember exactly what he did.

我想他可能是把光或者电和

I think it was either lights or electricity with

电击它们。

Shock them.

用其他东西来对它们进行电击。

Which would shock them with with other things.

他能训练它们学习并记住特定的事情。

And he could train them to learn and remember particular things.

比如，它们可能在水箱的一侧被电击，没错。

Like, they might get shocked on one side of the tank Exactly.

然后避开水箱的那侧。

And then avoid that side of the tank.

是的。

Yes.

那么我想问题是，如果它们被撕成碎片，它们的后代是否会在从未经历过电击的情况下就知道要避开水箱的那侧。

And then I guess the question is whether or not they're ripped apart cells and their subsequent generations will know to avoid that side of the tank without having ever been exposed to the shock.

对。

Right.

也就是说，它们是否从未接触过电击，或者新一代的头部能否学得更快。

So without ever been exposed to shock or whether the new generation, the new heads will be able to learn faster.

这是另一个可能发生的微妙之处。

That's another subtlety that might happen.

这就是他说发生的事情。

And this is what he said happened.

他说他可以教它们一些东西，然后切掉它们的头，新的头和完整的脑会重新长出来，并且保留着记忆。

He said he can teach them certain things, remove cut off their heads and new heads with all the brain will grow and that it will contain the memory.

这正是争议的开始，而不是结束，仅仅是个开端。

This was the start of the controversy, not the end of it, only the beginning.

接着，他说了一件更疯狂的事情：他可以训练它们学习某些东西，然后把它们切碎，放进搅拌机里，喂给其他蠕虫，因为它们是食同类的。

Then he said something even much wilder, which is he can train them to learn certain things and then just chop them up, put them in a blender, and feed them to other worms because they are cannibalistic.

它们会互相吞食。

They eat each other.

而记忆会通过进食传递。

And that the memory will transfer through feeding.

这听起来

This sounds

真是一个极具戏剧性的领域。

Such a dramatic field.

是的。

Yeah.

顺便说一下，这开创了这个领域。

And, by the way, this this opened the field.

于是，人们不仅在涡虫身上，还在金鱼、鱼类和某些啮齿动物身上做了实验，进行这种记忆-大脑转移的实验，植入大脑。

So people did experiments then not only in planaria, but in gold flea, fish, and certain rodents and did this memory brain transfer assays implanting brain.

而这是在他们产生一个想法的时候，即某些记忆可能是分子形式的，这非常吸引人。

And this is in the back when they they had an idea that some memories could be molecular, could have a molecular form, which is very appealing.

这简直像科幻小说。

It's almost like science fiction.

你可能会在试管里拥有一个记忆，这与我们通常对记忆的理解完全不同——记忆通常分布在神经元回路中，编码在特定突触的强度上，等等。

You could have a memory in a tube, unlike the way we think about memory normally, which is something that is distributed in neuronal circuits and encoded in the strength of particular synapses and so on.

但认为你可以把记忆简化为一个分子并进行转移的想法，非常非常有趣。

But the idea that you can take a memory and reduce it into a molecule and transfer it around is very, very interesting.

这就是为什么它吸引了如此多的人。

So this is why it attracted so many people.

这最终导致了一场灾难。

This ended up in a catastrophe.

因此，国立卫生研究院展开了调查。

So there was an NIH investigation.

没有人能复现任何结果。

No one can replicate anything.

这是一团糟。

It was a big mess.

尽管总有一些科学家说，是的，我们可以复现这个和那个。

Although there were always scientists who said, Yes, we can replicate this and this.

所以他们一直躲在幕后。

So they were in the background.

麦康奈尔的研究是不同的。

McConnell stuff was different.

再次，人们认为他们无法复现，存在一些问题，但并不是所有人都无法复现，有些人确实复现了，这并不一定意味着要完整复现整个实验。

Again, people thought that they couldn't that there are problems replicating, but it wasn't necessarily but some people replicate, it wasn't necessarily about replicating the whole thing.

但问题是，这种记忆的转移是特异性的，还是一种普遍的敏感化作用？

But the question was, did the memory that transfer is specific or is it an overall sensitization that transmits and so on?

对。

Right.

你可以想象，传递的可能是对电击的过度敏感，而不是电击发生的具体位置。

Like you could imagine that what gets transmitted is a hypersensitivity to electricity as opposed to the specific location that the electricity was

或者更进一步，仅仅是一种普遍的警觉性增强，让你对任何事情都学得更快。

Or or even more than that, even just, you know, a hypersensitivity engine in in general, more you're more vigilant, and you'll learn anything faster.

这也是一个可能的解释。

That's also a possibility.

嗯。

Mhmm.

但他的问题并不在于被指控。

But his problem wasn't the accusation.

更糟糕的是，他被大轰炸客盯上了——那些长达十五年向众多科学家寄送炸弹信件的恐怖分子。

It was much worse that he was targeted by the Unabomber, these terrorists who sent letters with bombs to many scientists for fifteen years.

他的助手，又是他的助手，我想，爆炸了，这就是他的研究路线终结的原因。

His assistant, again his assistant, I think, exploded, and this is how his line of research ended.

就在几年前，来自波士顿的研究人员迈克·莱文和他的博士后塔尔·沙姆拉特重复了麦康奈尔关于切断头部的一些实验，但使用了非常先进的设备和自动化追踪系统。

Just recently, a few years ago, a researcher from Boston, Mike Levin, and his postdoc, Tal Schomrat, replicated some of McConnell's experiment with the cutting of the head, but using very fancy equipment and automated tracking.

他们表示，他们能够重复部分他的实验。

They could say that they can replicate some of this, his his experiments.

真的吗？

Really?

是的。

Yes.

他们那个实验室里不拆包裹吗？

And they don't open packages in that laboratory?

他们有一些有趣的故事。

They have they have interesting stories.

你应该请迈克来一趟。

You should have Mike over

是的。

Yeah.

我对他的部分工作有些了解。

I'm familiar with his with a bit of his work.

我现在才知道他们做过这个实验。

Now I didn't realize they had done that experiment.

所以，他们几年前就发表了这项研究。

So so they published it yet a few years ago.

这非常有趣，但当然，他们并不知道这是如何发生的。

And this is very interesting, but, of course, they they don't know how it happens.

机制尚不明确。

The mechanism is unclear.

麦康奈尔走得比这更远。

McConnell went a step further than this.

令人着迷的是，这些实验都是在七十年代和八十年代进行的。

And what's fascinating is that these these are experiments that were done in the seventies and eighties.

他说，他不仅能通过切碎的动物转移记忆，还能将那些已学习过的动物分解成不同的组分。

He said that he cannot only transfer the memories through chopped animals, But he can take the animals that learned and break it down into different fractions.

比如仅DNA、仅RNA、仅脂肪、蛋白质、糖类。

So just the DNA, just the RNA, just the fats, the proteins, the sugars.

他说，能够传递记忆的组分是RNA。

And he said that the fraction that transmit the memory is the RNA.

这非常、非常有趣，因为这比我们今天对RNA的所有认知要早得多。

And this is very, very interesting because it was a long time before everything that we know about RNA today.

我很快会介绍我的研究，解释我们做什么，然后你会看到，你真的可以用RNA喂食蠕虫，并引发许多现象。

I'll soon go into my research, explain what we do, and then you'll see that you can actually feed worms with RNA and have many things happen.

大家都公认这是真的。

Everyone knows this is true.

这就是为什么重新回到这个领域进行研究如此吸引人。

This is why it was so appealing to go back to that and study.

顺便说一句，当时这个实验已成为广为人知的知识，人人都知道这个实验。

By the way, at the time it became popular knowledge, everyone knew this experiment.

1984年有一集《星际迷航》讲过这个。

There's a Star Trek episode about it from 'eighty four.

还有漫画书和书籍都提到过这个。

There are comics books about it, books about it.

所以当时很多人都在吃RNA，因为他们认为记忆里含有RNA。

So this was very and people were eating RNA because they thought that there's RNA in memory.

这当然是完全无稽之谈。

This was, of course, complete nonsense.

但正是这些言论在那几年引起了巨大轰动，也是直到最近它仍如此污名化的原因之一。

But but this was it made a lot of noise in these years, is part of the reason it was so toxic until recently.

你根本不敢碰这个话题，因为它被视为伪科学，就像李森科、卡默勒那些东西一样。

You couldn't touch it because it's it it was considered pseudoscience like Lisenko, like Kammerer, and all of this.

所以这完全是没人敢碰的禁区。

So this was just something you you didn't wanna touch at all.

然后我们又回头研究记忆或后天性状在其他生物、哺乳动物乃至人类中的遗传问题。

And And then we go back to these studies about inheritance of memory or inheritance of acquired traits in other organisms, in mammals, in humans.

除了这些事件留下的阴霾之外，还存在一些理论上的问题，解释了为什么这种情况不可能发生，以及必须突破哪些障碍才能实现。

And aside from the dark cloud that these episodes left, there were also theoretical problems of why this can't happen, barriers that have to be breached for this to happen.

你可以谈论许多不同类型的障碍。

And you can talk about many different types of barriers.

你也可以将它们简化为两个主要障碍。

And you can also narrow it down to two main barriers.

第一个障碍，我们已经提到过。

First barrier, we mentioned it.

这就是体细胞与生殖细胞之间的分离。

This is the separation of the soma from the germline.

对。

Right.

体细胞会根据经验发生变化。

The somatic cells, they can change in response to experience.

而精子和卵子，也就是所谓的生殖细胞，则不会。

The sperm and the egg, the so called germ cells, cannot.

这就是这个观点。

That's the idea.

或者说是体细胞发生的事情被隔离了，明白吗？

Or they are isolated on what happens in the soma, okay?

第一个提出这个屏障概念的人叫魏斯曼。

The man who first thought about this barrier is called Weismann.

奥古斯特·魏斯曼是十九世纪的人物。

August Weismann is what is in the nineteenth century.

所以今天这被称为魏斯曼屏障。

So it is called today the Weismann Barrier.

体细胞与生殖细胞的分离，只有生殖细胞能将信息传递给下一代。

Separation of the soma from the germline, only the germline transmit information to the next generation.

这也被称作生物学的第二定律。

And this is also called the second law of biology.

所以这是非常、非常根本的。

So this is very, very fundamental.

所以自然选择是第一个。

So natural selection is the first one.

这是第二个，因为它对我们如何运作、对我们身体如何工作至关重要。

This is the second one because it's so important to how we work, to how our bodies work.

顺便说一下，魏斯曼认为，如果环境直接对生殖细胞产生影响，那么这种影响或许能传递给下一代。

Weismann, by the way, thought that if you will have direct influence of the environment on the germ cells, then perhaps this could transfer to the next generation.

所以他的观点并没有他提出的屏障所暗示的那么严格，但大多数人对他的记忆并非如此。

So he wasn't as strict as his barriers suggest, but this is not how most people remember it.

但他认为这是不必要的。

But he thought that this is unnecessary.

自然选择有可能解释一切，他将其比作一艘在海洋中航行的船。

It's possible that natural selection can explain everything and he compared to a boat which is in the ocean.

它正在航行，帆已经张开，因此你无需假设它装有发动机。

It is sailing and it has a sail open so you don't have to assume that it has an engine.

风正在吹拂。

The wind is blowing.

你不需要假设其他因素。

You don't have to assume other things.

自然选择可能就足够了。

The natural selection might be enough.

所以这个屏障仍然存在，但并不完全如此。

So this barrier is still standing but not entirely.

它在某些生物中非常丰富。

It is rich in some organisms.

我们稍后再深入讨论。

We'll go into that in a second.

另一个屏障是，要理解这个屏障，我们必须谈谈表观遗传学。

Other barrier is the we have to to understand the other barrier, we have to talk about epigenetics.

我们必须定义表观遗传学以及它是什么。

We have to define epigenetics and what it is.

表观遗传学是一个被人们严重误用的术语，连这个领域的人也动不动就说一切都是表观遗传学。

And epigenetics is another term which people misuse horribly and say about everything that is epigenetics, even people from the field.

这个术语本身是在20世纪40年代由康拉德·沃丁顿提出的，他讨论了基因与其产物之间的相互作用，这些相互作用最终导致了表型的结果，以及基因如何影响发育。

The itself, the term was defined in the 40s by Conrad Wellington, and he talked about the interactions between genes and their products that, in the end, bring about the phenotype of the consequences and how genes influence development.

后来，人们发现了改变基因活性的不同机制，并开始将这些机制称为表观遗传学。

Later, people discovered mechanisms that change the action of genes, the different mechanisms, and started talking about these as epigenetics.

例如，DNA由四种基本元素组成。

For example, the DNA is built out of four basic elements.

这些是A、T、G和C。

These are the the AT, G, and C.

对吧？

Right?

它们可以通过化学方式被修饰。

And they can be chemically modified.

因此，除了DNA序列中所包含的信息外，你还拥有碱基修饰所带来的额外信息。

So in addition to just the information that you have in the sequence of the DNA, you also have this information in the modification of the bases.

研究得最多的常见修饰是胞嘧啶（C）的甲基化，即在C上添加一个甲基基团。

The most common modification that has been studied more than others is modification of the letter C of cytosine, methylation, addition of a methyl group to this C.

而且这可以被复制。

And this can be replicated.

因此，在细胞分裂并复制其遗传物质后。

So after the cells divide and replicate their genetic material.

在某些情况下，这些化学修饰也可以被添加、复制并保留下来。

In certain cases, also, these chemical modifications could be added on and replicate and be preserved.

对于那些不太熟悉基因、基因结构和表观遗传学的人来说，我们可以这样理解：你提到的四种核苷酸碱基C、G、A、T，通过甲基化这样的过程，就像是取原色并稍微改变其中一种，略微调整色调，从而极大地扩展了颜色组合的可能性。

For those who aren't as familiar with thinking about genes and gene structure and epigenetics, could we think of these, you mentioned the four nucleotide bases, CG, A, D, but could we imagine that through things like methylation, it's sort of like taking the primary colors and changing one of them a little bit, changing the hue just slightly, which then opens up an enormous number of new options of color integration.

是的，正是如此。

Absolutely, it's

只是增加了更多的组合、更多的方式、更多的信息。

just more combinations, more ways, more information.

除了DNA的修饰，还有包裹DNA的蛋白质——组蛋白——也会被修饰。

There are the modifications of the DNA, and also there are the modifications of the proteins which condense the DNA that are called histones.

因此，它们也会被许多不同的化学物质所修饰。

So they are also modified by many different chemicals.

再次强调，甲基化是一种非常常见的修饰，乙酰化甚至血清素也会作用于组蛋白。

Again methylation is a very common modification acetylation even serotonin, the serotonin of histones.

血清素。

Serotonin.

对。

Right.

这是几年前发表在《自然》杂志上的一篇新论文。

This is a new paper from Nature from a few years ago.

能改变DNA吗？

Can change DNA?

不是DNA本身，而是包裹它的蛋白质。

Not the DNA itself, but the protein that condenses it.

就像我之前打的比方，线是如何缠绕在线轴上的，本质上就是这样。

Essentially how, in the analogy I used before, of how the thread is wrapped around the spool, essentially.

是的。

Yes.

这决定了DNA的致密程度，以及基因是被更多还是更少地表达。

And this determines the degree of condensation of the DNA, whether the gene is now expressed more or less.

这是一种影响基因表达并实现基因功能的方式。

This is one way to affect the gene expression and bring about the function of the gene.

还有许多其他方式。

There are many additional ways.

这并不是唯一的方式。

It's not the only one.

当这一切开始被阐明时，人们开始谈论表观遗传学。

So then when all of this was starting to be elucidated, people talked about epigenetics.

他们开始讨论这些修饰。

They started talking about these modifications.

忘记了最初的定义。

Forgot the original definition.

当人们提到表观遗传学时，他们谈论的是甲基化之类的东西。

And when people said epigenetics, they talk about methylation and things like that.

再强调一下，我们可以想象一对相同的双胞胎，也就是所谓的同卵双胞胎。

And again, to just frame this up, so we could imagine two identical twins, so called monozygotic twins.

我们还可以更进一步说，他们是单绒毛膜的，因为他们处于同一个胎盘囊中，因为双胞胎也可能在不同的囊中发育，早期环境略有不同。

We could go a step further and say that they're monochorionic, because they were in the same placental sac, because twins can be raised in separate sacs, slightly different early environments.

假设这对双胞胎被分开抚养。

Let's say those two twins are raised separately.

其中一个经历了某些事情，另一个经历了不同的事情，他们吃不同的食物等等，通过表观遗传机制，比如甲基化、乙酰化、血清素产生等，其中一个双胞胎的某些基因表达可能会相对于另一个被增强。

One experiences certain things, the other things, they eat different foods, etcetera, and there is the possibility through epigenetic mechanisms that through methylation, acetylation, serotonin production, etcetera, that the expression of certain genes in one of the twins could be amplified relative to the other.

对吗？

Correct?

我们知道，即使在遗传上完全相同的双胞胎，他们看起来也不同，而且确实存在差异。

So we know that even totally identical twins, genetically, they're identical, but they look different and they are different.

我们都经历过这种情况。

We all experience it.

这可能是由于这些表观遗传变化造成的。

And this can happen because of these epigenetic changes.

明白吗？

Okay?

或者也可能是因为其他机制，因为基因会对环境做出反应。

Or it can happen because of other mechanisms because genes respond to the environment.

基因并不是孤立存在的。

Genes don't exist in a vacuum.

基因需要被转录因子激活。

Genes need to be activated by transcription factors.

有许多复杂的机制负责使基因发挥作用。

And there's a lot of machinery that is responsible for making genes function.

因此，我们是遗传物质与环境的结合体。

So we are a combination of our genetic material and the environment.

所以当人们谈论表观遗传学，只关注修饰时，他们的说法也不完全准确。

So when people talk about epigenetics and talk just about the modification, they're also not exactly right.

我对表观遗传学的定义是遗传，这种遗传要么发生在细胞分裂过程中，或者更有趣的是，如本播客所讨论的，发生在代际之间。

My definition of epigenetics is inheritance, which occurs either across cell division or, more interestingly also for this podcast now across generations.

不是因为DNA序列的改变，而是通过其他机制。

Not because of changes to the DNA sequence but through other mechanisms.

我认为这是最严谨的定义，能帮助你理解你在谈论什么。

I think this is the most robust definition that allows you to understand what you're talking about.

那么问题来了：如果确实如此，那么究竟是哪些分子在代际之间传递信息？

And then the question is: If this happens, then what are the molecules that actually transmit information across generations?

是这些对DNA或包裹DNA的蛋白质的化学修饰吗？

Are they these chemical modifications to the DNA or to the proteins that condense the DNA?

还是存在其他传递信息的因子，以及哪些分子可以做到这一点？

Or are there other agents that transmit information and which molecules can do it.

实际上，我认为当今最有趣的参与者是RNA分子。

And I actually think that the most interesting players today are RNA molecules.

明白吗？

Okay?

但在深入这一点之前，我想说明一点：当我们讨论表观遗传继承或获得性性状遗传的障碍时，除了我们之前讨论过的体细胞与生殖细胞的分离之外，另一个主要障碍被称为表观遗传重编程，即我们获得的细胞。

But before I go into that, I just want to say that when we talk about the barriers to epigenetic inheritance or the barriers to inheritance of acquired traits, In addition to the separation of the soma from the germline that we discussed, the other main barrier, it's called epigenetic reprogramming, which is that we acquired our cells.

我们细胞中的遗传物质会经历各种变化，也就是我们之前讨论过的这些化学修饰。

The genetic material in our cells acquires all kinds of changes, these chemical changes, modifications we discussed.

但这些修饰在代际传递过程中大多会被清除。

But these modifications are largely erased in the transition between generations.

因此，在生殖细胞、精子和卵子中，以及在早期胚胎中，大部分修饰都会被移除，以便基于遗传指令从零开始。

So in the germline, in the sperm and the egg, and also in the early embryo, most of the modifications are removed so we can start a blank slate based on the genetic instructions.

这一点至关重要。

And this is crucial.

否则，根据这一理论，实际上是否如此并不明确，因为在某些生物体中这并不会真正发生。

Otherwise, according to the theory, it's not clear that's actually true because in some organisms it doesn't really happen.

我们将无法按照物种典型的遗传指令进行发育。

We will not develop according to the species' typical genetic instructions.

因此，为了维持这一点，我们会清除所有这些修饰，重新开始。

So to preserve this, we raise all these modifications and start anew.

这在哺乳动物和人类中是如此。

And this is in mammals and in humans.

这在很大程度上是正确的。

This is largely true.

精子和卵子中的大部分修饰都会被清除，大约有90%。

Most of the modifications in the sperm and in the egg are removed, so about 90% of them.

有些会保留下来，这可能很有意思。

Some remain, which could be interesting.

所以，如果我理解正确的话，其理念是：清除一切、回归原始蓝图是有一定优势的。

So the idea, if I understand correctly, is that there's some advantage to wiping the slate clean and returning to the original plan.

在宜家家具的类比中，说明书是发给每个人的，对吧？或者说发给每个细胞的？

In the context of the IKEA furniture analogy, the instruction book is the one that's issued to everybody, okay, or every cell, right?

只有某些指令会被特定细胞使用，比如皮肤细胞、神经元、肝细胞，或其他任何细胞。

Only certain instructions are used for certain cells, say a skin cell, or a neuron, or a liver cell, or any other cell for that matter.

在生物体的生命周期中，这些特定指令会有所调整，对吧？

Through the course of the lifespan of the organism, those specific instructions are adjusted somewhat, okay?

所以，就像宜家家具一样，有时候他们给你七个而不是八个特定的螺丝，或者数量是对的，但你装错了位置，这就稍微改变了整个结构的运作方式。

So maybe like IKEA furniture, sometimes they send you seven, not eight of particular screws, or they send you the proper number, but you put them in the wrong place, and it sort of changes the way that the thing works a little bit.

一旦假设家具可以繁殖，但在这种将家具类比为细胞或器官的比喻中，当它与另一个生物交配时，需要进行复制，因此想法是获取指令，然后清除所有铅笔和钢笔的标记，删除所有主人添加或引入的额外修改，恢复到原始指令

Once that, assuming furniture could reproduce, but here in the analogy of the furniture as the cell or the organ, in that mates with another organism, that needs to be replicated, and so the idea is to take the instruction, but go through and erase all the pen and pencil marks, erase all those additional little modifications that the owner used or introduced to it, and return to the original instruction

手册。

book.

对，因为如果你想恢复指令手册，你希望它具备制造所有家具的全部潜力。

Right, because if you want to bring back the instruction book, you want it to have all the potential to make all the furnitures.

你不希望它仅限于你所制作的特定那些家具。

You don't want it to be restricted to the ones that you made in the particular

房间。

room.

所以这本质上与后天获得的性状和特征相反，用我们生物学圈内的说法，就是基于谱系经验的特征，但指的是你父母的经历，对吧？

So it's essentially the opposite of acquired traits and characteristics based on your, what we say in biology geek speak, lineage based experience, but what your parents experience, right?

在某种程度上，我们希望消除这一切，回归到他们提供的基因本身。

In some ways we want to eliminate all that and go back to just the genes they provided.

是的。

Yes.

但事情没那么简单。

But it's more complicated than that.

事情比这更复杂，因为即使在哺乳动物中，我们也有一些非常显著的例子，表明某些标记会被保留下来。

It's more complicated than that because we have some very striking examples, even in mammals, where some of marks are maintained.

例如，经典的例子是基因组印记。

For example, the classic example is imprinting.

基因组印记是一种非常有趣的现象。

Imprinting is a very interesting phenomenon.

DNA的工作方式是，你从母亲和父亲那里各继承了一套染色体。

The way DNA works is that you inherit a copy for every chromosome from your mother and your father.

因此，作为人类，你体内的每个细胞中都拥有每条染色体的两个拷贝。

And then you have in every cell of your body two copies, if you're a human, of every chromosome.

因此，每个基因都有两个副本。

And then so every gene is represented twice.

这些不同的基因版本被称为等位基因。

These are called alleles, the different versions of the genes.

而人们认为，一旦进入下一代，你所继承的两个拷贝是平等的。

And the thought is that once you enter in the next generation, the two copies that you inherited are equal.

无论你是从母亲还是父亲那里获得它们，都没有关系。

It doesn't matter whether you acquire them from your mother or from your father.

对吧？

Right?

但在某些情况下，这确实很重要。

There are some situations where it does matter.

有一小部分基因被称为印记基因，这些基因是否来自母亲或父亲确实很重要。

There a limited number of genes that are called imprinted genes where it does matter whether you inherited from your mother or your father.

这通过表观遗传继承实现，而不是因为DNA序列的改变，而是因为这些化学修饰在代际间的维持。

And this is happening through epigenetic inheritance, not because of changes to the DNA sequence, but because of maintenance of these chemical modifications across generations.

正如我回忆起哈佛大学凯瑟琳·杜洛克出色的研究那样，特别是在大脑中，有证据表明某些细胞只含有来自母亲或父亲的完整基因组。

And as I recall from the beautiful work of Catherine Duloc at Harvard, that especially in the brain, there is evidence that some cells contain the complete genome from mom or the complete genome from dad.

而且在你的一生中，这种状态也可能发生改变。

And it can also switch during your life.

所以她的研究显示，在你生命的早期，表达母源或父源拷贝是不同的，而当你更成熟时则不然。

So her work showed that early on in your life, it's different whether you express the maternal or paternal copy than when you're more mature.

所以父母和孩子们请注意，那些说孩子更像你或更像我的人，这种相似性可能会随着一生而改变。

So parents and children take note, you know, for those of you that are saying, oh, you know, the child is more like you or more like me, that can change across the lifespan.

如果你在思考自己的家族谱系，想知道是否从母亲或父亲那里继承了某种特质，当然，可能是两者都有，也可能只来自一方——我认为父母们时常会这样观察和描述他们的孩子。

And if you're thinking about your parental lineage and wondering whether or not you, quote unquote, inherited some sort of trait from mother or from father, it can be, of course, both, or it can be just one or just the other, which I think most parents tend to see and describe in their children from time to time.

就像父亲那边的特征，或者就像母亲那边的特征，对吧，对于

That's just like the father or that's just like the mother, Right, for

是的。

right.

但重要的是要知道，在这种情况下，环境并没有起到作用。

But it's important to know that in this situation, their environment played no role.

这仅仅取决于它传给了母亲还是父亲。

This was just whether it passed to the mother or the father.

并不是母亲或父亲经历了什么影响了这一点。

It's not that something that happened to the mother or the father affected this.

所以这略有不同。

So this is slightly different.

问题是，环境是否能改变可遗传的物质？

The question is now can the environment change the heritable material?

因此，理解养育与天性之间的区别非常重要。

So it's very important to understand that there is a difference between nurture and nature.

这非常容易让人困惑。

And this is very confusing.

人们往往不太容易察觉这一点。

People are It's a little subtle.

比如，有人告诉我，他们养马多年，很清楚某匹马有特定的性格。

So, for example, people tell me I'm growing horses for many years and I just know that this horse has a particular character.

它和另一匹马非常不同。

It's very different from the other horse.

因此，这就是表观遗传继承。

And so this is epigenetic inheritance.

不，这可能只是由基因决定的。

No, it could be just genetically determined.

是的，这匹马继承了一套不同的遗传指令，所以它有所不同。

Yes, this horse inherited a different set of genetic instructions, so it is different.

这不一定与表观遗传有关。

It doesn't have to be about epigenetics.

表观遗传继承意味着父母的环境以某种方式改变了后代。

Epigenetic inheritance means that the environment of the parents somehow change the children.

这里有两大障碍，即无畏的瓶颈，我们需要思考是哪种分子以及它们如何被跨越。

And there are these two main barriers that are fearless bottlenecks that we have to think what type of molecule and how they can be bridged.

一种可能性是，只有少数化学修饰能够存活下来，大约占百分之十左右。

So one possibility is that it's really this limited number of chemical modifications that survive, which is about ten percent or so.

这可能非常有趣。

That could be very interesting.

并不是一个小数目。

Not a small number.

不是一个很小的数字，但也许吧。

Not a small number, but perhaps.

也许吧。

Perhaps.

明白吗？

Okay?

这是一种可能性。

This is one possibility.

另一种可能性是存在其他机制。

The other possibility is that there are other mechanisms.

目前在人类中，尚不清楚究竟什么会被传递，是否能够传递，以及是哪种分子在起作用。

The situation now in humans is that it's just really unclear what transmits, if it can transmit, and which molecule does it.

我们稍后会讨论其他生物，那里的情况要清晰得多。

We'll talk later about other organisms where it is a lot more clear.

但在人类和哺乳动物中，有许多环境改变后代的例子。

But in humans and in mammals in general, there are many examples for environments that change the children.

是否需要借助表观遗传机制来解释这一现象，目前尚不明确。

Whether you need to invoke an epigenetic mechanism to explain this phenomena, this is unclear.

首先，很难将先天与后天因素区分开来。

First of all, it's hard to separate nature from nurture.

其次，因为这一机制尚未被理解。

And second, because the mechanism is just not understood.

因此，有一些经典的例子。

So there are classic examples.

在人类中，世界各地曾发生过饥荒和饥饿时期，比如荷兰、中国和俄罗斯，研究人员开展了大规模的流行病学研究，观察下一代的情况，发现孕期经历饥饿的女性所生的孩子在许多方面都不同。

In humans, there were periods of famine, starvation in different places in the world, in The Netherlands, in China, in Russia, where people did huge epidemiological study to study the next generations and saw that the children of women who were starved during pregnancy are different, Different in many ways.

他们的出生体重不同，葡萄糖敏感性不同，而且患某些神经系统疾病的风险也更高。

They have different birth weight, glucose sensitivity and also some neurological higher chances of getting some neurological diseases.

这些发现已在大规模研究中得到证实。

And this has been shown in very large studies.

是否存在这样一种情况：饥饿或某种困难、感官挑战或生存挑战反而导致了适应性特征？

Is there ever an instance in which starvation or hardship of some kind, some challenge, a sensory challenge or survival based challenge led to adaptive traits?

是的。

Yes.

在不同生物体中确实存在。

There are in different organisms.

这可能是权衡的结果。

It could be as a result of a trade off.

因此也可能存在负面影响。

So there could be a downside as well.

但例如，我想到了两个例子。

But for example, there are two examples that come into mind.

其中一个例子是，如果你对雄性小鼠或大鼠施加压力，我不太记得了。

One of them is that if you stress male mice or rats, I don't remember.

这是瑞士苏黎世联邦理工学院伊莎贝尔·曼索伊的研究成果。

This is work of Isabelle Mansoy in the ETH in Switzerland.

你可以通过多种方式对雄性施加压力。

If you stress the males, you can do it in many different ways.

我不太记得他们具体是怎么做的了，但你可以把它们和母亲分开。

I don't remember exactly how they did, but you can you can do you can separate them from their mothers.

你可以进行社会挫败，还有各种其他方法。

You can do social defeat, all kinds of things.

下一代的应激水平会更低。

Then the next generations are less stressed.

它们表现出更少的焦虑。

They show less anxiety.

所以，压力的阈值更高了？

So, the threshold for stress is higher?

是的。

Yes.

然而，我认为它们会有记忆缺陷以及其他可能的代谢问题。

However, I think they have memory deficits and other Which may metabolic

应对压力的优势。

an advantage for dealing with stress.

有可能。

Could be.

我没有直接的证据，但有一些潜在的想法是，我们把思维锚定在过去、现在或未来的能力，在某些情境下似乎非常适应。

It I could don't have any direct evidence of that, but there's some simmering ideas that, you know, our ability to anchor our thoughts in the past, present, or future seems very adaptive in certain contexts.

在其他情境下，它可能让我们陷入反复思虑，而无法适应性地活在当下。

In other contexts, it can keep us ruminating and not adaptively present to our current

另一个例子是尼古丁暴露，我认为这是来自马萨诸塞大学的奥利弗·兰多的研究，这些不是我的研究，但它们提高了下一代对类似药物的耐受性。

Another example is that nicotine exposure, this is, I think, the work of Oliver Rando from UMass, if I'm not mistaken, these are not my studies, but they improve the tolerance exposure to similar drugs in the next generation.

这里有趣的是，这种效应非常非特异性。

The interesting thing here is that it's very nonspecific.

所以你用尼古丁处理它们，但在下一代中，它们不仅对尼古丁更耐受，还对其他药物，比如可卡因或……更有耐受性。

So you treat them with nicotine, but then in the next generation they are more tolerant to nicotine, but also to other, I think cocaine or

这对我来说挺有道理的，因为显然尼古丁会激活胆碱能系统、多巴胺能系统、肾上腺素等等。

That sort of makes sense to me because, yeah, obviously nicotine activates the cholinergic system, the dopaminergic system, epinephrine, and etcetera.

你可以想象存在交叉效应，因为其他药物如可卡因、安非他命主要作用于儿茶酚胺，即多巴胺和去甲肾上腺素。

And you can imagine that there's crossover because other drugs like cocaine, amphetamine mainly target the catecholamines, the dopamine and norepinephrine.

在这项特定研究中，如果我没记错的话，他们表明即使使用拮抗剂阻断尼古丁受体，这种可遗传效应仍然会发生。

In this particular study, if I remember correctly, they show that this happens, this heritable effect, even if you use an antagonist to block the nicotine receptor.

哇。

Wow.

这更多是关于异源物质清除和肝脏功能的传递，而且非常非特异性。

It's something more about clearance of xenobiotics and hepatic functions that is transmitted and is very nonspecific.

我特别喜欢你今天举的所有例子，尤其是这一个——我希望正在听的人知道，我此刻正微笑着，因为生物学有时实在太深奥了。

What I love about all the examples you've given today and especially that one is, and I hope that people, if you're just listening, I'm smiling because biology is so cryptic sometimes.

你知道，最明显的机制往往并不是真正起作用的那个。

You know, the obvious mechanism is rarely the one that's actually at play.

对。

Right.

人们总是问，为什么？

And people always ask, well, why?

为什么会这样？

Why is it like this?

我总是说，有一点我非常确定的是，我在设计阶段根本没被征求意见。

And I always say, You know, the one thing I know for sure is that I wasn't consulted at the design phase.

如果有人声称他们被咨询过，那你绝对要远远躲开

And if anyone claims they were, then you definitely want to back away very

快点。

fast.

这其中可能涉及太多权衡，太多权衡了。

And there could be so many trade offs, So many trade offs.

比如，我们研究过，还有很多其他人也研究过这些效应。

So for example, we studied and also many other people studied effects.

这些研究是在线虫中进行的。

These are in worms.

我们稍后会深入探讨这一点。

We'll deep into that in a second.

但为了说明，当它们挨饿时，下一代的寿命会更长。

But to show that when you starve them, the next generations live longer.

我认为这可能与其他因素如生育能力存在权衡。

And this, I think, could be a trade off with other things like fertility.

所以下一代可能更易患病、生育力更低，或许正因为死亡率高，它们反而活得更久。

So the next generations are more sick and less fertile, and perhaps because of death, they live longer.

所以这未必是件好事，明白吗？

So that could be it's not necessarily a good thing, okay?

我不希望带你偏离主题，因为你正在为我们展示的这一切实在太精彩了。

I don't want to draw you off course, because this is magnificent, what you're doing and splaying out for us here.

但你还记得吗？几年前，确实发生过一个非常悲惨的案例。

But do you recall, was a few years ago, it actually ended very tragically, it was an example.

我想是在圣地亚哥县发生的。

I think it was down in San Diego County.

那里有一个类似邪教的团体，痴迷于永生。

There was a cult of sorts that were interested in living forever.

于是他们进行了阉割，男性自我阉割，认为保持某种青春期前的状态，或倒退回伪青春期前状态，就能延长寿命。

And so they castrated, the male self castrated in the idea that somehow maintaining some pre pubescent state or reverting to a pseudo prepubescent state would somehow extend longevity.

认为性行为会限制寿命，这种观点在一些较为古怪的长寿圈子里一直流传。

The idea that sexual behavior somehow limited lifespan, this has been an idea that's been thrown around in the kind of more wacky longevity communities.

他们还剃光了头发。

They also shaved their heads.

他们都穿着同样的运动鞋，然后在哈雷波彗星到来之际集体自杀，但这只是众多追求某种永恒生命——显然这不是延长寿命，而是缩短生命——的邪教中的一个例子，这些邪教往往通过限制热量摄入来实现。

They also all wore the same sneakers, then they also all committed suicide, right as the Hail Bop comet came But through that's just, but one example of many cults aimed at sort of, that obviously was not life extension, that was life truncation, but aimed at kind of eternal life, or some sort of, through caloric restriction.

没错，这个邪教也非常推崇通过热量限制来延长寿命的理念，这或许最终会被证明是正确的，我认为这仍存在争议，因此关于间歇性禁食等话题的争论不断，但众所周知，吃得过多会缩短寿命。

That's right, this cult also was very into the whole idea that by, through caloric restriction, we can live much longer, which may actually turn out to be true, I think it's still debated, hence all the debate about intermittent fasting, etcetera, but also it is known that if you overeat, you shorten life.

这一点是明确的。

This is clear.

众所周知，一个物种中体型较大的个体比体型较小的个体寿命短得多，比如大丹犬和吉娃娃就是例子。

It's known that big bodied members of a species live far shorter lives than the smaller members of a Great Dane versus a Chihuahua, for instance.

所以这些说法中都含有一些真相的碎片，但在我看来，真正的问题是：背后的真正机制是什么？为什么这种机制会存在？

So there is some sort of shards of truths in all of these things, but it seems to me that the real question is like, what is the real mechanism, and why would something like this exist?

对。

Right.

在生物学中，问‘为什么’是非常危险的。

And why questions are very dangerous in biology.

对吧？

Right?

是的。

Right.

但也很有趣。

But very interesting also.

在代谢变化和营养方面，有许多例子表明，无论是过度进食还是饥饿，都会影响下一代。

And so when it comes to metabolic changes and nutrition, there are numerous examples where you either overfeed or starve and get effects in the next generations.

有时，根据你如何操作，产生的效果会相反。

Sometimes the effects contrast depending on the way you do this.

虽然我们在哺乳动物中并不这样做，但研究表明，母亲或父亲的饥饿或过度进食会改变下一代的体重、葡萄糖耐受性以及繁殖成功率。

Again, we don't do any of that in mammals, but people show that starving or overfeeding the mothers or the fathers changes the body weight of the next generation and also the glucose tolerance and also reproductive success.

因此，确实存在某种影响，某种东西在传递，这一点是明确的。

And so the fact that there's an effect, that something transmits, this is clear.

问题是，这有多神奇？是否需要新的生物学和表观遗传学来解释它。

The question is how miraculous is it and whether you need new biology and epigenetics to explain it.

我这么说是什么意思？

What do I mean by that?

如果你影响了下一代，它并不一定非要通过卵子或精子，并涉及表观基因组。

If you affect the next generation, it doesn't necessarily have to go through the oocyte or the sperm and involve the epigenome.

你在动物发育过程中改变其新陈代谢，显然会对其产生影响。

You change the metabolism of the animal as it develops and obviously it will affect it.

例如，你让怀孕的女性挨饿，就像那些著名的饥饿研究中发生的那样，婴儿已经在子宫内，直接暴露在环境中。

You, for example, starve women that are pregnant, as happened during this famous starvation studies, The baby is already in utero, exposed directly to the environment.

所以这甚至不是一种可遗传的影响。

So it's not even a heritable effect.

婴儿本身受到了影响。

The baby is itself affected.

这是一种直接的影响。

It's a direct effect.

非常有趣，也很重要，具有许多含义，并且将与遗传学区分开来。

Very interesting, important, and has many implications, and it will be separate from the the genetics.

你必须考虑到这一点，才能理解正在发生的事情。

You have to take it into account to understand what's going on.

并不一定需要一种新的遗传生物学。

Doesn't require necessarily new biology, a new new biology of inheritance.

不仅胚胎受到影响，胚胎在子宫内时就已经具有生殖细胞。

Not only is the embryo affected, the embryo while in utero already has germ cells.

所以这同时也影响到下一代。

So it's also the next generation.

因此它直接暴露在环境中，你并不一定需要新的生物学理论来解释它。

So it's directly exposed and you don't need any new biology necessarily to explain it.

而且它也不一定涉及表观遗传学或其他类似机制。

And it doesn't have has to involve epigenetics or epigenetics, etcetera.

对我来说很清楚，在雌性胎儿体内，她将来会产生并可能被精子受精的全部卵子已经存在。

It's clear to me that in the female fetus, the total number of eggs that she will someday produce and potentially have fertilized by sperm exist.

但在男性中，精子周期为六十天，这让我产生疑问：雄性胎儿在母体内时，是否已经开始产生精子，还是仅仅存在能发育成精子的原始细胞？

But in males with a sixty day sperm cycle, leads me to the question, do fetal males, males as fetuses, living as fetuses, in their moms already start producing sperm or it's the primordial cells that give rise to sperm?

我不是专家，所以不想深入讨论具体时间点，但母亲的暴露确实最终会影响精子父亲遗传信息的传递。

So I'm not an expert, so I don't want to go into the details of exactly when But, in yes, exposure of the mother also affect eventually the transmission of genetic information for the sperm's father.

还有许多例子表明，父亲的压力会影响精子，并影响下一代。

And there are also many examples of just stressing the fathers affecting the sperm and affecting the next generation.

如果你追溯到F2代，也就是不看子女而是看孙辈，那么这就确实是真正的表观遗传效应，因为你研究的是下一代从未直接接触过原始刺激的现象。

There if you to the F2 generation, if you go two generations down the road not to the kids but to the grandkids then it is a real epigenetic effect because you examine something that happens although the next generation was never exposed to the original challenge.

因此，当我们谈论通过父系传递的表观遗传时，通常指的是两代人。

So when we say about epigenetic inheritance through the paternal lineage, the founders, talk about two generations.

而当通过母系传递时，则涉及三代人。

And when you go through the mother, it's three generations.

只有在需要引入真正的表观遗传机制时，才需要这样讨论。

To talk about, when you need to invoke some real epigenetic mechanism.

而在哺乳动物中，相关证据要少得多。

And there the evidence becomes much more scarce in mammals.

有一些例子，说服力或强或弱。

There are examples, more or less convincing.

这个领域正在快速发展和改进。

The field is evolving and improving a lot.

因此，现在人们使用前沿技术，比如体外受精（IVF）或胚胎移植，以确保真正遗传的是遗传信息，而不是环境因素，并且这种影响是通过生殖细胞传递的。

So for example, now, people use the cutting edge is to use IVF, in vitro fertilization, or transfer of embryos to make sure that actually it's the heritable information and not the environment or and that it goes through the germline.

这正是目前正在进行的研究。

So this is something that is being done now.

有一些研究

There are studies

你指的是三亲试管婴儿技术吗？就是从母亲那里获取DNA，从父亲那里获取精子，然后把母亲的DNA植入一个新的细胞质？

You're talking about the three parent IVF where they take the DNA from mom, the sperm from dad, and they take the DNA from mom and put it into a novel cytoplas?

或者

Or

不是。

No.

完全不是。

Not at all.

或者你取精子并进行转移和受精

Or you take the sperm and transfer it and fertilize

一个卵子。

the an egg.

所以是标准的体外受精？

So standard IVF?

是的。

Yes.

标准的体外受精。

Standard IVF.

对。

Yeah.

你可以用很多不同的方式来做。

You can do it in many different ways.

但这种观点认为，可以将母亲的环境与父亲的遗传或环境分离开来，从而将自然与 nurture 分割开来。

But this idea that you separate the the environmental the environment of the mother from the inheritance or or the environment of the father and to to control and separate nature from nurture.

环境变成了培养皿。

The the environment becomes the culture dish.

是的。

Yes.

对。

Yeah.

所以这个领域正在进步。

So the field is improving.

人们进行的实验具有更高的标准，样本更多，控制得更好。

People do experiments that have a higher end, so more replicates and better controlled.

也有一些关于效应传递的例子。

And there are some examples for effects that transfer.

至于人们是否相信这一点，取决于你问的是谁。

And it depends who you ask whether people believe it or not.

许多遗传学家并不相信这一点。

Many geneticists do not believe it.

但也有很多人相信。

And many people do believe it.

这取决于不同的学术群体。

And it depends on the community.

由于多种原因，存在强烈的抵触情绪。

There are strong resistance for many reasons.

其中一些是合理的，另一些则不太合理，但这些都是科学过程的一部分，因为这挑战了既有教条。

Some of them are justified, some less justified and are part of the scientific process and how things work because it's challenging the dogma.

因此，这本身非常有趣。

So this is very interesting on its own.

如果你问心理学家，许多心理学家相信存在可遗传的创伤之类的现象。

If you ask psychologists, many psychologists believe that there's heritable trauma and things like that.

而群体遗传学家则较少这样认为。

Population geneticists, less so.

所以这真的取决于具体情况。

So this really depends.

我认为我们现在正处于一个阶段，尚不清楚这种现象是否真的发生，以及发生的程度如何。

And I think that we are just at a point in time where we don't really know whether it happens and to what extent.

我们需要更大规模的研究。

And we need bigger studies.

即使你考虑正常的遗传学研究，人们试图理解复杂性状的遗传基础，比如几乎任何涉及大脑的性状。

Even if you think about normal just genetic studies where people trying to understand the genetic underpinning of complex traits, like anything that involves the brain pretty much.

我们现在知道，你需要研究非常多非常多的人。

We now know that you need to study many, many, many people.

因此，这些大规模的全基因组关联研究和大型遗传学研究通常涉及数十万人口。

So now these big genome wide association studies, big genetic studies involve hundreds of thousands of people.

还没有人对表观遗传学进行过这样的实验。

No one did an experiment like this for epigenetics.

这要复杂得多，因为你还需要考虑环境因素。

It's much more complicated because you need to also take into account the environment.

我甚至不确定我们该如何设计这样的实验。

I'm not even sure we know how to design such an experiment.

这非常、非常具有挑战性。

It's very, very challenging.

对这一理想的抵制部分源于理论层面，因为存在这些障碍和争议。

The part of the resistance to the ideal is based on theoretical grounds because of these barriers and because of controversies.

另一方面，确实有很多人希望相信这一点。

On the other hand, there's people really want to believe it.

人们非常希望相信这一点，因为如果你能通过改变自己的生物学特性来影响你的孩子，这会在某种程度上赋予你的生命意义。

People really want to believe it because it sort of gives your life meaning if you can change your biology your kids through changing your biology.

从心理上讲，我能理解为什么很多人希望这种情况真的会发生。

Psychologically I can understand why many people want this to happen.

就连著名的物理学家薛定谔，也在1944年写了一本非常重要的书。

Even Schrodinger, the famous physicist, wrote a very important book in '44.

这比双螺旋结构的发现还要早。

So this was before the double helix.

这本书叫《生命是什么？》

It's called What is Life?

这实际上是一本推动许多物理学家投身分子生物学的著作。

This is actually a book that drove many physicists to establish molecular biology.

它非常重要。

It's very, very important.

他谈到了遗传物质。

And he talks about the heritable material.

书中也谈到了进化。

It also talks about evolution.

他说，不幸的是，拉马克主义或后天性状的遗传是站不住脚的。

And he said, unfortunately, Lamarckism or inheritance of acquired trait is untenable.

这种情况不会发生。

It doesn't happen.

他写道，这非常令人遗憾，因为与达尔文主义或自然选择不同，后者虽然悲观——无论你做什么，下一代都只是根据精子和卵子中的遗传指令诞生——但拉马克主义至少给人以改变的希望。

And he writes, this is very, very sad or unfortunate because unlike Darwinism or natural selection, which is gloomy, doesn't matter what you do, the next generation will be born based on the instruction in the sperm and the egg.

你无法影响它。

You can't influence it.

当然，你可以给你的孩子钱和教育，但你无法从生物学上影响它。

Of course, you can give your kids money and education, but you can't biologically influence it.

还有一件事让我着迷，原因有很多，那就是伴侣选择。

You can also one thing I'm fascinated by for a number of reasons is partner selection.

我的意思是，某种程度上，我们以为自己想找个善良的人。

I mean, in some ways, you know, we think, oh, we we wanna find someone who is, you know, kind.

顺便说一句，数据显示，善良确实是最重要的特征，我们曾邀请大卫·博斯做客播客，讨论女性如何选择男性，人们都看重善良。

That does seem to be, by the way, the primary feature, at least in the data tell us, we had David Boss on the podcast, how women select men, that people are kind.

还有资源潜力。

There's also resource potential.

还有男性和女性的美貌或审美吸引力等等。

There's also beauty or aesthetic attractiveness in males and females, etcetera.

男性、男性、女性、女性，视情况而定，但就繁殖而言，精子、卵子、男性、女性，显然是这样。

Male, male, female, female, as the case may be, but in terms of reproduction, sperm, egg, male, female, obviously.

因此，我们正在选择多种特质，但 presumably，我们潜意识中也在选择与活力相关的多种特质，因为如果我们与某人生育后代，这些特质就会被保留下来。

So we're selecting for a number of traits, but presumably subconsciously, we are also selecting for a number of traits related to vigor, and in the idea that if we were to have offspring with somebody, that those traits would be selected for.

对。

Right.

在秀丽隐杆线虫中，我们确实有相关研究，稍后我会告诉你，不过在那之前，我们先聊聊蠕虫的约会行为。

And we actually have work on that in nematodes that I'll be happy to tell you about in a second after we The dating in worms.

太棒了。

Fantastic.

因为我们已经理解了其机制。

Where we understand the mechanism.

我们稍后，或者几分钟后，在深入探讨蠕虫之前，会详细讲这个。

And we'll go into that in a second, or in a few minutes after we dive into the worms.

但没错，关于种群遗传学如何运作的原始计算，为了简化问题并进行数学推导。

But yes, the original calculations of how population genetics work to simplify things and to do the math.

当时假设的是随机交配。

It would be easy, it was random mating.

当然，事情并不是这样的。

Of course, it doesn't work like that.

所以这使情况变得复杂，因为我们知道。

So it complicates things because we know.

而且有一些研究探讨了人类可能具备某种感知免疫兼容性的能力，类似这样的事情，我不太了解，我不是这方面的专家，但是

And there's research about potential capacity to somehow sense immune compatibility and things like this, which is, I don't know, I'm not an expert on that, but

我也不是，但我的理解是，当然我们熟悉自己选择的其他特质，比如潜在的养育能力，一个人是否可靠，这些都能预示他们作为父母的养育能力。

Neither am I, but my understanding is that of course we're familiar with the other traits we select for, like potential nurturing ability, whether or not someone is reliable, predicts something about their nurturing ability, and for offspring potentially.

我的意思是，你可以在这些事情之间画出联系，即使没有直接证据，但它们看起来非常合乎逻辑，对吧？

Mean, you can draw lines between these things without any direct evidence, but they seem so logical, right?

比如，一个善良的人可能也会留下来，或者在这些事情上诚实，这说得通；但认为我们会选择某些我们尚未察觉的生物特质，比如免疫功能或其他形式的强健性，我认为这是生物学中一个非常有趣的方向。

That somebody kind who might also stick around, or be honest in these kinds of things that it makes sense, But that one would be selecting for certain biological traits like immune function or some other form of robustness that we're not aware of is I think a fascinating area of biology.

这就是哺乳动物研究目前的状况。

So this is where the work in mammals stands.

然而，还有一件额外的事情需要提及，那就是除了对DNA和包裹DNA的组蛋白进行化学修饰之外，还有其他机制可能传递信息，包括跨代传递的RNA；RNA有多种类型，不只是我们之前提到的编码蛋白质信息的信使RNA，还有其他调控基因表达的RNA。

However there's also one additional thing to mention which is that on top of chemical modifications to the DNA and the proteins that condense the DNA which are called histones, There are also other mechanisms that might transmit information including transmission between generations of RNA and there are different types of RNA, not just the RNA that we mentioned before, the messenger RNA which encodes the information for making protein but also other RNAs that regulate gene expression.

我认为近年来，在哺乳动物领域，RNA作为可能在代际间传递信息的分子，已经成为了焦点。

And I think that in recent years also in the mammalian field, RNA as the molecule that has the potential to transmit information between generation took center stage.

所以我认为这是最前沿的领域。

So I think this is the cutting edge.

我们还有很多需要了解的地方，但RNA在这方面具有巨大潜力，这一点我们稍后会解释，但首先我们得

A lot more to understand than know, but RNA has a lot of potential for doing that, as we'll explain soon, but we have to

先从线虫说起。

go to worms first.

感谢你对遗传学、RNA和表观遗传学的精彩概述，这本质上是对这个非常有趣且表面上复杂的领域的全面介绍，但你已经为我们大大简化了它。

Thank you for that incredible overview of genetics and RNA and epigenetics, and it was essentially a survey of this very interesting and on the face of it, sort of complex field, but you've simplified it a great deal for us.

在我们转向讨论线虫之前，我想在《休伯曼实验室播客》中明确一点：我们即将讨论的内容，是这个播客历史上首次深入探讨所谓的模式生物。

In our transition to talking about worms, I would like to plant a flag in the Huberman Lab Podcast, and say that what we are about to discuss is the first time that anyone on this podcast has discussed so called model organisms.

我或许曾经提过果蝇，或者蜜蜂与咖啡因、花朵偏好的研究，但那通常只是顺带一提，我们会很快转回人类话题。

I may have mentioned a fly paper here or there, or a study on honeybees and caffeine and flower preference at one point, but typically that's done in passing, and we quickly rotate to humans.

我知道，我们的许多甚至大多数听众都关注人类、人类生物学和健康等问题，但我必须再三强调模式生物的重要性，以及它们在多大程度上帮助我们理解了人类健康，尤其是在细胞的基本功能方面，对吧？

I know that many, if not most of our listeners are focused on humans and human biology and health, etcetera, but I cannot emphasize enough the importance of model organisms and the incredible degree to which they've informed us about human health, especially when it comes to very basic functions in cells, right?

我的意思是，有人可能会争论，比如小鼠的端粒研究，真的能得出与人类相同的结论吗？

I mean, one could argue, okay, and there's been some debate, telomeres in mice, did that really lead to the same sort of data in humans?

当然，确实存在这些情况，但模式生物至关重要，而且一直以来都是如此，它们基本构成了我们对人类健康认知的绝大部分基础。

Okay, there are those cases certainly, but model organisms are absolutely critical and have been, and basically inform most of what we understand about human health.

所以在我们开始详细介绍蠕虫之前，你能向普通观众解释一下什么是模式生物吗？

So before we start to go into the description about worms per se, could you just explain to a general audience what a model organism is, right?

它们当然不是在摆姿势拍照，那么‘模式生物’到底是什么意思？常见的模式生物有哪些？你为什么选择研究这种特定的蠕虫来探讨这些显然在人类身上也存在的迷人课题？

They're not modeling, they're not posing for photographs, obviously, what that means, and what some of the general model organisms are, and why you've selected or elected to work on a particular type of worm, to study these fascinating topics that there's zero question also take place in humans at some level.

因此，能在这里代表模式生物发言，我感到非常荣幸和高兴。

So it's a real pleasure and an honor to represent the model organisms here.

我真的很高兴听到你这么说。

I'm really happy just for that.

这完全值得，因为正如你所说，模式生物极其重要，我们通过它们学到了大量关于生物学的知识。

It was worth it because, as you said, model organisms are extremely important and we learn so much about biology through them.

模式生物指的是许多研究者共同研究的生物体。

Model organisms mean that it's an organism that many people work on.

所以有一群人专门研究这个。

So there's a community of people that work on.

人们研究许多类型的生物，但并不是每种生物都有人研究。

People study many types of organisms, but not around every organism.

有一大批研究人员共同整合资源，创建了所有工具和积累的知识。

There's a huge community of researchers that combine sources to create all the resources and the tools and the understanding that accumulate.

在生物学发展的短暂历史中，只有少数几种模式生物。

There are just a handful of model organisms in short history of the field of biology.

时间并不长。

It's not so long.

我们通过它们了解了生物学的方方面面，包括许多重要的疾病，如人类疾病。

We learned about every aspect of biology through them, including many important diseases, human diseases.

这些是大肠杆菌，

And these are E.

噬菌体，即细菌的病毒，果蝇，以及一种叫做秀丽隐杆线虫的蠕虫。

Coli bacteria, phage, which is a virus of bacteria, flies, worms that are called C.

秀丽隐杆线虫。

Elegans nematodes.

这就是我们在实验室研究的东西。

This is what we studied in the lab.

鱼，也就是斑马鱼。

Fish, which are called zebrafish.

这是一种特定的

It's a particular

这是斑马鱼，或者类似的名字。

This is danio danio or something.

对。

Right.

当然，还有模式生物小鼠。

And of course, there are also model organisms and mouse.

还有重要的植物。

And also plants, important plants.

研究最深入的是拟南芥。

The most studied one is the Arabidopsis.

是的。

Yeah.

或许现在研究得少一些了，但非人灵长类动物仍然存在。

And perhaps less so nowadays, but nonhuman primates.

主要是猕猴、狨猴和松鼠猴。

Macaque monkeys, marmosets, squirrel monkeys mainly.

这些我不知道该怎么准确定义，但属于新兴的模式生物。

These I I don't know exactly how to definition this, but emerging model organisms.

有许多新兴的模式生物，也形成了相应的研究群体，包括我们之前提到的涡虫——这种再生能力极强的扁形动物，是研究再生的理想模型。

There are many model organisms that are emerging, and there are communities that are formed, including also around the planaria that we mentioned before, this flatworm that regenerate is a great model for studying regenerations.

如果我们能再生出新的头部，那将不可思议。

If we could develop new heads, it would be incredible.

我们可以从这些生物身上学到很多。

And we can learn from these organisms.

我们之所以能通过研究这些动物来深入了解人类，是因为我们都起源于同一个祖先。

And the reason that we can learn a lot also about humans by studying these animals is that we all evolved from the same ancestor.

因此，我们在功能和基因上与它们有许多共同之处。

So we share a lot of our functions with them and also a lot of our genes.

C。

C.

秀丽隐杆线虫和其他模式生物各有不同的优势，为我们所用。

Elegans and the different model organisms have different advantages that serve us.

它们有时具有一些更明显的特点，便于我们研究。

They sometimes have some things that are much more apparent in them that we can study.

例如，学习和记忆最初主要在一种名为海兔的蜗牛中进行研究，许多发现都是在这里做出的，因为它的神经元很大，容易观察和分析。

For example, learning and memory was largely studied in the beginning in a snail, aklesia, where many of the discoveries were made because it has big nuance that you can easily study and examine.

而且，是的，蜗牛会学习。

And, yes, snails learn.

对。

Yes.

它们会学习。

They learn.

甚至C.

Even C.

秀丽隐杆线虫，这些我们研究的线虫也会学习，而且它们比其他生物更简单，另一个重要的原因是，我们实际上可以对它们进行实验。

Elegans, these nematodes that we study learn, and they are much simpler than another important reason to sending them, of course, is you can can actually experiment on them.

我们不能对人类做这些我们对这些动物做的事情。

We can't do this to humans, the things that we do to these animals.

我们可以改变它们的基因，为它们做各种各样的事情。

And we can change their genes, do all kinds of things for them.

而且在某些情况下，抱歉打断一下，我认为您接下来会告诉我们，比如在C.

And in some sorry to interrupt, but in some cases, I think you're going to tell us, for instance, in C.

Elegans中，特定细胞类型的分布是如此固定，以至于你可以观察几条不同的线虫，研究C.

Elegans in particular, the presence of particular cell types is so stereotyped that you can look at several different worms, and you can, the community of people that study C.

Elegans的科学界甚至为每个神经元编号并命名，使得世界两端的两个实验室都能在论文中讨论同一个神经元，确信它们研究的是同一个神经元，这在任何哺乳动物模型，比如小鼠，或人类中都极难实现，也带来了巨大挑战，但为像C.这样的研究提供了巨大优势。

Elegans is literally numbered and named each neuron so that two laboratories on opposite sides of the world can publish papers on the same neuron, knowing that it's the same neuron in the two different laboratories, something that is extremely hard to do in any mammalian model, a mouse, or certainly in humans, and has posed huge challenges that give great advantages to studies of things like C.

秀丽隐杆线虫。

Elegans.

是的。

Yes.

所以，秀丽隐杆线虫。

So C.

秀丽隐杆线虫现在是我们研究的明星。

Elegans, this is the star now of what we study.

它们是线虫，一种微小的圆虫，长度仅一毫米。

These are nematodes, small worms, round worms that are just one millimeter long.

所以肉眼看不见它们。

So you can't see them with the naked eye.

必须在显微镜下观察。

Have to look under the scope.

它们在自然界中生活在哪里？

Where do they live in the natural world?