精华：基因与跨代记忆遗传 | Oded Rechavi 博士

欢迎收听《Huberman Lab Essentials》，在这里我们会回顾过去的节目，为大家带来最有效、最实用的基于科学的心理健康、身体健康和表现提升工具。

Welcome to Huberman Lab Essentials, where we revisit past episodes for the most potent and actionable science based tools for mental health, physical health, and performance.

我是Andrew Huberman，我是斯坦福大学医学院的神经生物学和眼科学教授。

I'm Andrew Huberman and I'm a professor of neurobiology and ophthalmology at Stanford School of Medicine.

接下来是我与博士的对话。

And now for my discussion with Doctor.

Oded Rechavi。

Oded Rechavi.

Oded，非常感谢你来做客。

Oded, thank you so much for being here.

这是我的荣幸。

Totally my pleasure.

今天，我最想聊的是你在实验室里探索的那些令人惊叹的问题，这些问题对我们每个人的生活都极其重要。

Today, I mainly want to talk about is the incredible questions that you probe in your lab, which are incredibly significant for each and all of our lives.

我想大多数人对基因是什么、RNA是什么等都有基本的了解，但也许你可以用非常基础的语言给大家解释一下。我先说明一下，我认为大多数人都明白，如果父母双方都是蓝眼睛，那么他们的孩子有蓝眼睛的概率比棕眼睛更高。但大多数人通常也理解并接受，如果一个人花了一部分人生，比如说学习建筑，那么当他们有了孩子，我们假设，并没有真正的遗传原因会让他们的孩子因为通过父母的DNA继承了这些知识而在建筑方面更擅长。

I think most people have a general understanding of what genes are, what RNA is, and so on, but maybe you could explain to people in very basic terms, and I'll just preface all this by saying that I think most people understand that if they have two blue eyed parents, that there's a higher probability that their offspring will have blue eyes than brown eyes, but most people generally understand and accept that if they spend part of their life, let's say studying architecture, that if they have children, that there's no real genetic reason, we assume, that their children would somehow be better at architecture because they contain the knowledge through the DNA of their parents.

他们可能会在家里接触到这些，这就是所谓的天生与后天培养，但那是后天培养，而不是遗传知识。

They might be exposed to it in the home, so called nature nurture, so nurture in that case, but that they wouldn't inherit knowledge.

今天，我希望你能给我们解释一下，为什么眼睛颜色被认为是遗传的，而知识却不是，以及这引出的众多有趣问题，包括一些证据表明，与我们可能认为的相反，某些类型的知识在细胞和系统层面上是可以遗传的。

Today, I'm hoping you can explain to us why eye color, but not knowledge is thought to be inherited, and the huge landscape of interesting questions that this opens up, including some evidence that contrary to what we might think, certain types of knowledge at the level of cells and systems can be inherited.

DNA是遗传物质，是包含在我们每个细胞中的遗传指令。

So DNA is the material, the genetic instructions that is contained in every one of our cells.

我们拥有的整套基因被称为基因组。

We have the set of genes containing the entire set is called the genome.

这套指令存在于我们身体的每个细胞中。

And this is present in every cell of our body, the same set of instructions.

基因由DNA和染色体组成。

Genes are made of DNA and chromosomes.

它们包含在染色体中。

They are contained in chromosomes.

染色体是DNA和使DNA凝聚的蛋白质，因为每个细胞中有大量的DNA，你需要将其压缩。

Chromosomes is the DNA and the proteins that condense the DNA because we have a huge amount of DNA in every cell that you need to condense it to.

就像线绕在线轴上一样。

Sort of like thread on spool.

对。

Right.

大量的DNA，必须压缩起来。

Huge amounts that you have to condense.

我们身体里的每个细胞都有相同的基因组，相同的DNA。

And we have the same genome, the same DNA in every cell in our body.

用一个类比来理解这个过程会比较好。

It's good to have an analogy to understand how it works.

这就像宜家的说明书，你身体的每个细胞里都有一本，告诉你如何制造家里需要的一切，比如椅子、厨房、画。

This is like the IKEA book that you have in every cell in your body, the instructions to make everything that you need in your house, the chairs, kitchen, the pictures.

但每个房间需要的东西都不一样。

But in every room you want something else.

所以厨房里需要适合厨房的东西，厕所里需要适合厕所的东西。

So in the kitchen you want things that fit the kitchen and in the toilet you want things that fit the toilet.

所以你只需要取出其中一页说明书，也就是教你怎么做椅子的那一页。

So you only remove one particular page of instructions, which is the instructions of how to build a chair.

然后把它放到客厅里。

And this you place it in the living room.

明白吗？

Okay?

而厕所里就放厕所需要的东西。

And the toilet you put in the toilet.

所以基因组就是制造一切东西的说明书。

So the genome is the instruction to make everything.

这就是那本宜家手册。

This is the e care book.

而在每个细胞里，我们只取出制造某一件家具的说明书，这就是RNA。

And in every cell we we take just the instructions for make one particular furniture, and this is the RNA.

最后，你就能造出一把椅子了。

And then at the end, you'll build a chair.

椅子就是蛋白质。

The chair is the protein.

这适用于一种特定的RNA，也就是信使RNA。

This is true for one particular type of RNA, which is messenger RNA.

实际上，这只是细胞中RNA的一小部分。

In fact, this is just a small percent of the RNA in the cell.

所以我们的基因组很大，但其中只有不到2%编码这种信使RNA。

So we have a very big genome and less than 2% of it encodes for this messenger RNA.

然而，基因组中有很多部分会被转录成RNA，这些RNA有其他功能。

However, a lot of the genome is transcribed to make RNA that does other things.

其中一些RNA我们了解，但很多我们还不清楚。

Some of these RNAs we understand and many of them we don't.

我觉得这个描述很美，而且宜家并不是本播客的赞助商，所以用宜家目录来比喻DNA完全没问题。

I think it's a beautiful description, and IKEA is not a sponsor of the podcast, so it's totally fair game to use the IKEA catalog as the analogy for DNA.

具体家具的具体说明就是RNA，而家具本身则是蛋白质，这些蛋白质基本上是通过信使RNA从RNA制造出来的。

The specific instructions for specific pieces of furniture is the RNA, and the furniture pieces being the proteins that are essentially made from RNA using messenger RNA.

对。

Right.

好的。

Okay.

尽管身体的所有细胞都含有相同的基因，但基本上有一个非常重要的例外，那就是体细胞和生殖细胞，这样说对吗？

Despite the fact that the same genes are contained in all the cells of the body, is it fair to say that there's basically one very important exception, which is somatic cells versus germ cells?

你介意跟我们分享一下这两者的区别吗？

And would you mind sharing with us what that distinction is?

是的，每种细胞类型都不同。

So yes, every cell type is different.

我们有腿部的细胞。

We have cells in the legs.

我们有大脑的细胞。

We have cells in the brain.

在大脑里也有。

We have in the brain.

我们有产生多巴胺的细胞，产生血清素的细胞，等等。

We have cells that produce dopamine, cells that produce serotonin, and so on.

但我们可以区分体细胞和生殖细胞，这是一个非常重要的区别。

But we can make one very important distinction between the somatic cells and the germ cells.

生殖细胞被认为是唯一能传给下一代的细胞，下一代就是由它们产生的。

The germ cells are supposed to be the only cells that contribute to the next generation, out of which the next generation will be made.

所以我们每个人都是由精子和卵子结合而来的。

So each of us is made just from a combination of a sperm and an egg.

这两种就是生殖细胞。

These are two types of germ cells.

然后它们结合，就形成了一个受精卵。

And then they fuse and you make you you you get one fertilized egg.

从这个细胞开始，身体的其他部分都会发育出来。

And out of this one cell, all the rest of the body will develop.

而发生在体细胞里的变化，也就是那些不是生殖细胞的细胞，应该只留在体细胞里。

And what happens in the soma, which are all the cells that are not the germ cells, should stay in the soma.

不应该能够传递给下一代。

Should not be able to contribute to the next generation.

这一点非常重要，被认为是后天获得性状和记忆等特征遗传的主要障碍之一。

This is very important and is thought to be one of the main barriers for the inheritance of acquired traits, inheritance of memory, and so on.

因为，比如说，就像你提到的学习建筑学的例子，如果我学了建筑学，信息就储存在我的大脑里。

Because, for example, like the example that you gave with learning architecture, if I learn about architecture, the information is encoded in my brain.

而且因为我的脑细胞不能把信息传递给精子和卵子，因为信息应该存在于不同神经元之间的突触连接中，特别是在形成的特定回路中。

And since my brain cells can't transfer information to the sperm and the egg because the information is supposed to reside in synaptic connections between different neurons, in particular circuits that developed.

所以，大脑不应该能够把信息传递给下一代。

So what happens is the brain shouldn't be able to transfer to the next generation.

更简单的例子，如果你去健身房锻炼肌肉，你知道你的孩子必须自己锻炼。

Even simpler, a simpler example, if you go to the gym and you build up muscles, you know that your kids will have to work out on their own.

这种捷径是不会发生的。

This shortcut won't happen.

这是我们凭直觉就知道的事情，即使我们没有生物学背景。

This is something that we know intuitively, even if we don't have any background in biology.

这和我们一开始说的有关，身体里的每个细胞都有自己的基因组，而下一代只能由精子和卵子中的基因组结合而成。

This is connected to the fact that, as we said at the beginning, every cell in the body has its own genome, and the next generation will only form from the combination of the genomes in the sperm and the egg.

即使你碰巧在某个脑细胞中获得了突变或DNA的改变，那也没关系，因为这种突变没有办法转移到生殖细胞的DNA中，从而传给下一代。

Even if you somehow acquire the mutation or change in your DNA in one of particular brain cells, it wouldn't matter because this mutation, there's no way to transfer it to the DNA of the germ cells that will contribute to the next generation.

我想稍微休息一下，感谢我们的赞助商Eight Sleep。

I'd like to take a quick break and acknowledge our sponsor Eight Sleep.

Eight Sleep生产智能床垫套，具备降温、加热和睡眠追踪功能。

Eight Sleep makes smart mattress covers with cooling, heating, and sleep tracking capacity.

确保你获得良好睡眠的最佳方法之一，就是保证睡眠环境的温度适宜。

One of the best ways to ensure you get a great night's sleep is to make sure that the temperature of your sleeping environment is correct.

这是因为，为了入睡并保持深度睡眠，你的体温实际上需要下降大约1到3度。

And that's because in order to fall asleep and stay deeply asleep, your body temperature actually has to drop by about one to three degrees.

而为了醒来时感觉精神焕发、精力充沛，你的体温实际上需要上升大约1到3度。

And in order to wake up feeling refreshed and energized, your body temperature actually has to increase by about one to three degrees.

Eight Sleep会根据你的个人需求，整夜自动调节床的温度。

Eight Sleep automatically regulates the temperature of your bed throughout the night according to your unique needs.

我睡Eight Sleep床垫罩已经快五年了，它彻底改变并提升了我的睡眠质量。

I've been sleeping on an Eight Sleep mattress cover for nearly five years now, and it has completely transformed and improved the quality of my sleep.

最新的Eight Sleep型号是Pod五。

The latest Eight Sleep model is the Pod five.

我现在睡的就是这个，我非常喜欢它。

This is what I'm now sleeping on, and I absolutely love it.

它有很多很棒的功能。

It has so many incredible features.

比如，Pod五有一个叫自动驾驶的功能，这是一个AI引擎，能学习你的睡眠模式，然后根据不同的睡眠阶段调整你的睡眠环境温度。

For instance, the Pod five has a feature called autopilot, which is an AI engine that learns your sleep patterns and then adjusts the temperature of your sleeping environment across different sleep stages.

如果你打鼾，它甚至会抬高你的头部，还会做其他调整来优化你的睡眠。

It'll even elevate your head if you're snoring and it makes other shifts to optimize your sleep.

如果你想试试Eight Sleep，去eightsleep.com/huberman，可以享受最高350美元的折扣，购买新的Pod五。

If you'd like to try Eight Sleep, go to eightsleep.com/huberman to get up to $350 off the new Pod five.

Eight Sleep发货到全球许多国家，包括墨西哥和阿联酋。

Eight Sleep ships to many countries worldwide, including Mexico and The UAE.

再说一遍，去 eightsleep.com/huberman 就能省下高达350美元。有一个观点，我替你说出来吧，这个观点可以追溯到拉马克和拉马克进化论，非常有争议，对吧？

Again, that's eightsleep.com/huberman to save up to $350 There is this idea, and I'll say it so that you don't have to, that dates back to Lamarck and Lamarckian evolution, very controversial, right?

也许甚至不只是有争议，我觉得对某些人来说甚至有点冒犯。

And maybe not even controversial, I think it's very like offensive even to certain people.

这个观点就是获得性遗传，也就是说一个人可以通过某些活动改变自己，比如去健身房锻炼。

This idea of inheritance of acquired traits, the idea that one could change themselves through some activity, use the example of going to the gym.

我们也可以举个例子，比如一个人成为耐力跑者，然后决定和另一个耐力跑者生孩子，他脑子里想的是，因为他们跑了这么多，不仅仅是因为他们一开始就偏向跑步，而是因为他们实际跑的距离，他们的后代不知怎么就会成为出色的跑者。

We could also use the example of somebody who becomes an endurance runner, then decides to have children with another endurance runner, and has in mind the idea that because they did all this running, and not just because they were biased towards running in the first place, but because of the distance they actually ran, that their offspring somehow would be fabulous runners.

我们认为这个拉马克式的概念是错误的，那么我们应该怎么谈论获得性遗传呢？

This Lamarckian concept is, we believe, wrong, so how do we talk about inheritance of acquired traits?

我们应该用什么恰当的语言来构建这个讨论？

What's the proper language for us to frame this discussion?

拉马克，这就是他所相信的，他认为进化就是这样进行的。

Lamarck, this is what he believed, and he thought this is how evolution progressed.

后来，达尔文证明了实际上是自然选择。

Later, Darwin showed that it's really natural selection.

选择那些已经具备特定品质的生物，是根据它们在特定环境中能否生存来决定的。

The selecting of the organisms that already contain the particular qualities are selected based on whether they survive or not in particular environments.

因此进化得以推进，这些生物变得更常见，并最终占据主导地位。

And therefore the evolution progresses, they become more common and take over.

这跟拉马克的观点非常不同。

This is very different.

这是两种不同的解释。

Two different explanations.

最常见的对比例子就是长颈鹿的脖子。

The most common way this is contrasted is the neck of the giraffe.

这是经典的例子。

This is the classic example.

按照拉马克的说法，当树很高时，长颈鹿必须伸长脖子去吃树上的叶子。

According to to Lamarck, the giraffes had to stretch their necks towards the trees to eat when the trees were high.

正因为如此，它们把长脖子这个特征传给了后代，所以后代也有长脖子。

And because of that, transmitted these traits, long necks, to their children who also had long necks.

而根据达尔文的说法，只是碰巧生来就有长脖子的长颈鹿因为能吃到东西而存活下来。

And according to Darwin, just that a giraffe that happened to be born with a long neck survived because it ate.

所以这是遗传的、可继承的物质，虽然当时不知道遗传学，但就这样占据了优势。

So it's genetic heritable materials, didn't know about genetics, but take over.

而其他拥有不同遗传物质的长颈鹿就都死了。

And the rest of the giraffes that have different heritable materials just die.

所以这就是自然选择与获得性状遗传之间的对比。

So this is natural selection versus inheritance for quieterans.

然后我们再回到那些关于获得性状遗传的研究。

And then we go back to these studies about inheritance of acquired traits.

为什么这不可能发生，也有理论上的问题。

There were also theoretical problems of why this can't happen.

要实现这一点，必须突破一些障碍。

Barriers that have to be breached for this to happen.

你可以把它归结为两大障碍。

And you can narrow it down to two main barriers.

第一个障碍，我们之前提到过，就是体细胞和生殖细胞的分离。

First barrier, we mentioned it, this is the separation of the soma from the germline.

对。

Right.

体细胞可以随着经历而改变。

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

但精子和卵子，也就是所谓的生殖细胞，却不能。

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

就是这个意思。

That's the idea.

或者说，它们与体细胞的变化是隔绝的。

Or they are isolated on what happens in the soma.

最早想到这个障碍的人叫魏斯曼，奥古斯特·魏斯曼，那是在十九世纪。

The man who first thought about this barrier is called Weismann, August Weismann, this was in the nineteenth century.

所以今天它被称为魏斯曼屏障。

So it is called today the Weismann Barrier.

体细胞和生殖细胞是分开的，只有生殖细胞能把信息传递给下一代。

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

这也被称为生物学的第二定律。

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.

自然选择是第一定律。

So natural selection is the first one.

这是第二定律，因为它对我们身体的运作方式太重要了。

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

另一个主要的屏障叫做表观遗传重编程，也就是我们细胞获得的那些变化。

The other main barrier is called epigenetic reprogramming, which is that we acquired our cells.

我们细胞中的遗传物质会获得各种化学变化，但这些修饰在代际传递中大部分会被抹去。

The genetic material in our cells acquires all kinds of chemical changes, but these modifications are largely erased in the transition between generations.

所以在生殖细胞中，也就是精子和卵子中，以及在早期胚胎中，大部分修饰都会被去除，这样我们就能根据遗传指令从头开始。

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.

这一点非常关键。

And this is crucial.

否则，按照这个理论，其实并不清楚是否真的如此，因为在某些生物体中，这种情况并不真正发生。

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

我们就不会按照物种典型的遗传指令来发育。

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

所以为了保持这一点，我们清除所有这些修饰，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这样的。

And this is in mammals and in humans.

这大体上是正确的。

This is largely true.

精子和卵子中的大部分修饰都会被移除，大约百分之九十。

Most of the modifications in the sperm and in the egg are removed, so about ninety percent of them.

所以，我的理解是，这样做的好处是清除一切，回到最初的计划。

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

拿宜家家具的比喻来说，说明书是发给每个人的，对吧，或者说发给每个细胞的，对吗？

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

不同的细胞只用某些特定的说明，比如皮肤细胞、神经元、肝细胞，或者其他任何细胞。

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.

在生物体的一生中，这些特定的说明会有所调整。

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

所以，也许这个想法就是拿起说明书，把上面所有的铅笔和钢笔标记都擦掉，把主人用过的或添加的那些额外的小修改都擦掉，然后回到原始的说明书。

Okay, so maybe 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

对，因为如果你想恢复说明书，你希望它有潜力做出所有的家具。

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

你不想让它只局限于你在某个房间里做的那几件。

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

所以，对这个理想的抵制部分是基于理论上的理由，因为有这些障碍和争议。

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

另一方面，人们真的很愿意相信它，因为如果你能通过改变自己的生物学来改变你的孩子，这会给你的生活赋予意义。

On the other hand, 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，可以理解为什么很多人希望这件事发生。

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

就连著名的物理学家薛定谔，他在44年写了一本非常重要的书，里面谈到了遗传物质。

Even Schrodinger, the famous physicist, so he wrote a very important book in '44, and he talks about the heritable material.

书中还谈到了进化，他说，获得性状的遗传是站不住脚的。

It also talks about evolution, and he said, Inheritance of acquired trait is untenable.

这种情况不会发生。

It doesn't happen.

他写道，这非常非常令人难过或不幸，因为不像达尔文主义或自然选择那样令人沮丧，无论你做什么，下一代都会根据精子和卵子中的指令出生，你无法影响它。

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 met you can't influence it.

当然，你可以给孩子钱和教育，但你无法在生物学上影响它。

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

不过，还有一点要提的是，还有其他机制可能传递信息，包括RNA在代际之间的传递。

However, there's one additional thing to to mention, which is there are also other mechanisms that might transmit information, including transmission between generations of RNA.

RNA有不同的类型，不仅仅是编码蛋白质信息的信使RNA，还有其他调节基因表达的RNA。

And there are different types of RNA, not just messenger RNA, which encodes for the information for making protein, but also other RNAs that regulate gene expression.

而且我觉得近年来，在哺乳动物领域，RNA作为一种可能在代际间传递信息的分子，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.

所以我觉得这是前沿领域。

So I think this is the cutting edge.

还有很多需要理解的地方，但RNA在这方面潜力很大，我们稍后会解释，但首先得从线虫说起。

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 go to worms first.

我们的听众中，很多人，甚至大多数，都关注人类、人类生物学和健康等等，但我怎么强调模式生物的重要性都不为过，它们在很大程度上帮助我们了解了人类健康，尤其是在细胞的基本功能方面。

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.

在我们开始详细描述线虫之前，你能向普通听众解释一下什么是模式生物，以及你为什么选择或决定研究一种特定的线虫来探索这些迷人的话题，而这些话题毫无疑问在人类身上也有一定程度的体现？

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 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?

模式生物是指一种生物。

Model organisms mean that it's an organism.

有一个庞大的研究人员群体，他们联合起来，创造所有资源、工具和积累的知识。

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

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。

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

我们之所以能通过研究这些动物来了解人类，是因为我们都从同一个祖先进化而来。

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.

我们和它们共享很多功能，也共享很多基因。

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

它们身上有些特征比人类更明显，更容易研究。

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

另一个重要的原因是，当然，我们可以对它们做实验。

Another important reason to sending them, of course, is you can actually experiment on them.

我们不能对人类做那些实验，但可以改变它们的基因，做各种事情。

We can't do this to humans, the things that we do to these animals, and we can change their genes, do all kinds of things for them.

研究线虫的社区，

The community of people that study C.

他们给每一个神经元都编了号、起了名字，所以世界两端的两个实验室可以发表关于同一个神经元的论文，并且知道在两个不同的实验室里，那是同一个神经元。这在任何哺乳动物模型，比如小鼠，或者人类身上，都极其困难，这给线虫研究带来了巨大的优势。

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, mouse, or certainly in humans, and has posed huge challenges that give great advantages to studies of things like C.

线虫。

Elegans.

C.

C.

线虫秀丽隐杆线虫总是有九百五十九个细胞，其中三百零二个是神经元。

Elegans nematode always has nine fifty nine cells, out of which three zero two are neurons.

从八十年代起，我们就有了它的连接组，就像一张地铁图，告诉我们哪个神经元和哪个神经元相连，而且这个连接组是固定的。

We have a connectome since the eighties, like a subway map that tells us which neuron talks with which other neurons, and it is the same.

不仅如此，这种线虫是透明的，所以我们可以用特定的工具直接看到神经元放电。

Not only that, the words are transparent so we can actually see the neurons fire using particular tools.

我们还可以用光遗传学来激活基因或沉默基因。

And we can activate genes and silage genes using optogenetics.

除此之外，我们对这种线虫的遗传学，也就是基因组，也有很深入的了解。

On top of that, we have great understanding of the genetics of the worm, the genome.

C.

C.

秀丽隐杆线虫是第一个在人类之前完成基因组测序的动物。

Elegans is the first animal to have its genome sequenced before humans.

而且我们知道，每条母虫大约能产下250条幼虫，这些幼虫的基因几乎完全相同。

And we know that each mother produces about two fifty babies, which are almost genetically identical.

我们还知道在哪里培养它们。

And we know where we grow them.

环境是高度可控的，我们把它们养在只有细菌的培养皿里。

The environment is very controlled, we grow them in the plate with just bacteria.

所以我们可以很容易地区分先天和后天的影响。

So we can easily separate between nature and nurture.

线虫的世代周期只有三天。

The generation time in silicons is three days.

三天。

Three days.

所以一个博士生期间就能完成几百代线虫的实验。

So you can do hundreds of worm generations in one PhD.

这一点非常重要。

This is very important.

不仅如此，每条线虫都会产生数百个基因相同的后代，所以你的实验会有很好的统计数据。

Not only that, every worm will produce hundreds of progenies that are genetically identical, so you will have great statistics for your experiment.

在蠕虫中，我们现在有非常明显和确凿的证据表明获得性性状是可以遗传的。

In the warm, we now have very obvious and clear cut proof that there is inheritance of acquired traits.

以至于我认为表观遗传学领域几乎没有人反对这一点。

So much so that I don't think that anyone pretty much in the epigenetic field argues against it.

我想快速休息一下，感谢我们的赞助商AG1。

I'd like to take a quick break and acknowledge our sponsor AG1.

AG1刚刚推出了他们的最新配方，叫做AG1 Pro。

AG1 just launched their newest formulation called AG1 Pro.

现在，你的第一次订阅可以额外享受20%的折扣。

And right now you can get an extra 20% off your first subscription.

AG1采用了经过临床验证的AG1配方，包含维生素、矿物质、益生菌和适应原，并添加了三种重要的新成分：一水肌酸、HMB钙和肌肽锌。

AG1 takes the clinically backed AG1 formula, which is a blend of vitamins, minerals, probiotics, and adaptogens, and adds three important new ingredients, creatine monohydrate, calcium HMB, and zinc carnosine.

它含有五克一水肌酸，以支持肌肉力量和表现以及大脑健康；HMB钙支持肌肉恢复并减少肌肉分解；肌肽锌则支持和改善你的肠道内壁。

It has five grams of creatine monohydrate to support muscle strength and performance along with brain health, calcium HMB to support muscle recovery and reduce muscle breakdown, and zinc carnosine to support and improve the lining of your gut.

这些成分里，有些我之前就已经在单独服用了，跟AG1配方是分开的。

Some of these ingredients I personally was already taking separate from the AG1 formula.

所以现在看到它们都出现在新的AG1 Pro里，我觉得特别好。

So it's great to see all three of them now in the new AG1 Pro.

你可能知道，我大概十四年来每天都坚持喝AG1。

As you may know, I've been taking AG1 every single day for about fourteen years now.

也就是说，我早就发现它并开始每天服用，那时候我甚至还不知道播客是什么。

That means I discovered it and started taking it daily long before I even knew what a podcast was.

我一直在喝，也一直在播客里推荐它，因为它确实是个很棒的配方。

I continue to take it and back it here on the podcast because it is an excellent formula.

现在有了AG1 Pro，它就更好了。

And it's now even better with the AG1 Pro formula.

限时优惠，你去drinkag1.com/huberman，用优惠码backtoroutine，首单订阅AG1 Pro就能额外享受八折优惠。

For a limited time, you can get an extra 20% off your first subscription to AG1 Pro by going to drinkag1.com/huberman, and using the code backtoroutine.

对，就是数字2，back，数字2，routine。

So that's with the numeral two, back, numeral two, routine.

只要去 drinkag1.com/huberman 就行了。

Just go to drinkag1.com/huberman.

你在 C. Elegans 上做的第一个实验是什么？

What was the first experiment that you did on C.

那个实验让你确认了后天习得性状的遗传是真实存在的？

Elegans that confirmed for you that inheritance of acquired traits is real?

我们想测试一下，线虫是否能够产生跨代的抗病毒能力。

We set to test whether worms can produce transgenerational resistance to viruses.

这些线虫不像我们一样有专门的免疫细胞。

These worms don't have dedicated immune cells like we do.

它们没有 T 细胞或 B 细胞。

They don't have T cells or B cells.

它们通过一种能摧毁病毒的 RNA 来防御病毒，这种 RNA 叫做小 RNA。

They defend themselves from viruses using RNA that destroy viruses, and these are called small RNAs.

2006年，两位研究 C. Elegans 的研究人员...

2006, two researchers that were studying C.

线虫研究方面，安德鲁·法尔和克雷格·梅洛因为发现了一种通过小RNA调控基因的机制而获得了诺贝尔奖。

Elegans, Andrew Feire and Craig Melo, got the Nobel Prize for showing that there is a mechanism that regulates genes that happens through small RNAs.

他们发现，如果你给线虫注射双链RNA分子，这些RNA会关闭与其序列匹配的基因。

What they've shown is that if you inject the worms with RNA molecules, are double stranded, they shut off the genes that match in sequence to this RNA.

这就像从宜家手册里拿出咖啡桌的具体说明书，然后把一份副本插回手册里，这样一来，你就阻止了原页面的表达，相当于抹掉了原来的那一页。

So sort of like taking the specific instructions for the coffee table from your IKEA handbook, and you insert a copy of that into the book, and in doing so, you prevent the expression of, you sort of erase the original page.

解释得非常到位。

Perfect explanation.

他们发现，双链RNA，也就是有两条链的RNA，是引发反应的关键，它导致小RNA分子的产生，而这些小RNA分子实际上会找到信使RNA并将其摧毁。

They found that double stranded RNA, RNA that has two strands, is what starts the response, leading to the production of small RNA molecules, which are the ones that actually find the messenger RNA and leads to its destruction.

让它沉默，最终就不会产生蛋白质了。

Silence it so you don't get proteins in the end.

因此，在人们发现这一机制在包括人类在内的许多生物中都保守存在之后，他们获得了诺贝尔奖。

For that, they got the Nobel Prize after people found that this is conserved in many organisms, including humans.

现在已经有相关的药物了。

And now there are now drugs.

这个诺贝尔奖是2006年才颁发的。

This was only in 2006, the Nobel Prize.

那篇论文是98年发表的。

The paper was published in 'ninety eight.

现在已经有利用这种机制的药物了。

There are now drugs that use this mechanism.

这叫做RNA干扰。

It is called RNA interference.

RNA会干扰基因的表达和功能。

RNA interferes in the expression of a gene and the function of a gene.

这也叫基因沉默，因为这些RNA让基因沉默，而不是让基因表达，所以基因的功能就不会显现出来。

And it's also called gene silencing because these RNAs enforce the silencing of genes instead of the genes being expressed, are silenced and you don't manifest their function.

他们揭示了两件非常重要的事情。

They've shown two very important things.

你不仅能在注射的细胞或组织中看到效果，还能在蠕虫的全身看到效果。

You don't only see the action in the cell that you injected or in the tissue that you injected, but you see it all over the worm's body.

它会扩散。

It spreads.

这还包括生殖细胞。

This includes also the germ cells.

所以，如果你把双链RNA只注射到体细胞里，哪怕是头部，你也会在生殖细胞和下一代中看到效果。

So if you inject the double stranded RNA just to somatic cells, even to the head, you will get also the effect in the germ cells and in the next generation.

后来，他们发现，你只需要让线虫吃那些能产生这种双链RNA的细菌，这种双链RNA和基因沉默效应就会从摄入的地方——也就是肠道，因为细菌是被吃进去的——传播到身体的其他部分，甚至影响到下一代。

Later, they've shown that you can just take worms and feed them on bacteria that produce this double stranded RNA, and that the double stranded and the silencing would move from the site of ingestion from the gut, the bacteria are eaten, to the rest of the body, and also to the next generation.

这一点完全没有争议。

This is not controversial at all.

这是每个研究线虫的生物学家每天都会做的常规操作。

This is being done routinely every day by any C.

全世界的线虫生物学家都在这么做。

Elegans biologist in the world.

这个实验已经被重复了无数次。

This has been replicated a million times.

我刚开始做研究的时候，想看看除了人工的双链RNA之外，一些自然的性状是不是也能通过RNA，也就是小RNA，跨代传递。

When I started my work, wanted to see whether in addition to artificial double stranded RNA, some natural traits can also transmit across generations because of RNA, because of small RNAs.

对，因为注射RNAi或者短的自由RNA，或者让线虫待在一个充满抑制性RNA的环境里，这是一种实验，跟线虫经历了某件事然后把获得的性状传给后代，是完全不同的。

Right, because injecting RNAi or short end free RNAs, is, or putting worms into an environment with an abundance of inhibitory RNAs as an experiment is very different than worms experiencing something and then passing on that acquired trait to their offspring.

在我看来，这两者差别很大，因为一个是极端的操作，用来揭示一个基本原理。

It's a world apart, in my opinion, because one is extreme manipulation that illustrates an underlying principle.

另一个是理论上在自然世代更替中会发生的事情。

The other is something that, in theory, occurs in the passage of generations just naturally.

我们是从不太人工的往更人工的方向走。

We're going from the less artificial to the more artificial.

好处是，就像模式生物一样，越人工的东西，你越容易确切知道你自己做了什么。

The advantages, just like with model organisms, that the more artificial it is, the easy it is to you know exactly what you did.

只引入一个因素，然后就能追踪结果。

Just now introduce one factor, and you can follow the result.

所以这总是一个权衡。

So this is always the trade.

事实上，这很可能就是这些小RNA最初进化的原因，用来清除病毒和其他寄生性基因组元件，这是一种对抗它们的机制。

In fact, this is probably the reason that these small RNAs evolved in the first place, to get rid of viruses and other parasitic genomic elements, and this is a mechanism to fight them.

我们用一种荧光病毒非常清楚地证明了这一点。

We demonstrated this very clearly using a fluorescent virus.

如果病毒成功复制，线虫就会变绿。

If the virus replicates successfully, the worms just turn green.

如果病毒被消灭，线虫就保持黑色。

And if the virus is destroyed, the worm stays black.

这很简单。

This is very simple.

这是一个明确的界限。

It's a clear cutoff.

我们取了一些线虫。

We took worms.

我们用荧光病毒感染它们。

We infect them with a fluorescent virus.

它们会把它摧毁。

They destroy it.

这个实验以前也做过。

This also has been done in the past.

但接下来我们做的是，把蠕虫后代中制造小RNA的机制给中和掉了。

But then what we did is we neutralized the machinery that makes small RNAs in the descendants of the worms.

所以它们从一开始就无法自己制造小RNA，因为它们根本没有制造这些小RNA所需的基因。

So they cannot make small RNAs from the start on their own because they just don't have the genes that you need to make these small RNAs.

然后我们问，如果我们用病毒去感染这些蠕虫，会发生什么？

And then we ask, what will happen when we'll affect these worms with the vows?

它们会变绿还是变黑？

Will they be green or black?

它们无法自己制造小RNA，所以它们无法自我保护。

They can't make their own small RNAs, so they can't protect themselves on their own.

它们要想保持黑色，不让病毒复制，唯一的办法就是继承它们父母的小RNA。

The only way for them to stay black, for them not having the virus replicate, is if they inherit the small RNAs from their pet.

而这正是实际发生的情况。

And this is exactly what happens.

所有蠕虫的后代，尽管它们没有制造小RNA所需的基因，却都是黑色的。

All the worms' progeny, although they don't have the gene that is needed for making the small RNAs, are black.

它们感染了病毒。

They sign the virus.

这种情况还会持续好几代。

And this also continues for additional generations.

明白吗？

Okay?

所以，亲代蠕虫实际上把某种东西放进了后代的遗传指令中，这给了它们——我们姑且称之为一种优势——但如果它们遇到与亲代相同的情况，这种优势就会显现出来。

So the parent worms effectively put something into the genetic instructions of the offspring that would afford them, let's call it an advantage in this case, but afford them an advantage if they were to be confronted with the same thing that the parents were.

对。

Right.

而且我们确切知道这种优势是什么。

And we know exactly what this advantage is.

这个优势就是与病毒基因组匹配的小RNA，它们会在下一代中直接把病毒切碎。

The advantage is small RNAs that match the viral genome, then just chop up the virus in the next generation.

而且我们能在后代中识别出这些小RNA，也就是那些抑制性RNA，尽管它们没有制造这些RNA的机制，只是因为继承了它们。

And we can identify these small RNAs, in the the the inhibitor RNAs in the descendants, although they don't have the machinery to make it just because they inherit it.

我们可以通过测序来识别它们。

We can identify them by sequencing.

RNA测序，就像DNA测序一样。

RNA sequencing, which is like DNA sequencing.

你实际上能得到RNA分子的真实序列。

You actually get the actual sequence of the RNA molecules.

而且我们可以看到，这些小RNA与病毒对应，而且只有当它们的父母感染过病毒时，它们才会继承这些小RNA。

And we can see that they correspond to the virus, and they inherit in small RNAs only if their parents were infected with them.

确实，在哺乳动物中，RNA和小RNA也可能介导压力保护或有害效应的跨代传递。

It is true that also in mammals, RNAs and small RNAs are a lending candidate for something that could mediate the transmission of stress protection, or also of harmful effects that transmit between generations.

也许RNA就是这样的媒介。

Perhaps RNA do it.

当我们谈论记忆的遗传时，想想这个真的很有意思。

And it's very interesting to think about it when we talk about inheritance of memories.

某种大脑活动能不能至少在这些方面传递呢？

Can brain activity of some sort transmit, at least in these words?

我说过，诺亚，我多次声明过这一点。

I said, Noah, I said this disclaimer multiple times.

对于哺乳动物，我们还不清楚。

Mammals, we don't know.

时间会告诉我们答案。

Times will tell.

在蠕虫中，我们知道很多。

In worms, we know a lot.

那么蠕虫能传递大脑活动吗？

So can worms transmit brain activity?

它们有这种特异性吗？

Do they have the specificity to do it?

我觉得任何能把RNA传给下一代并影响下一代的组织都很有意思。

I think that any tissues that transmit RNA to the next generation and affect the next generation is interesting.

肠道、肌肉，所有组织都是，但大脑能整合环境和内部状态的信息，还能提前思考。

The gut, muscles, everything, but the brain can synthesize information about the environment and about internal state and can also think ahead.

最引人遐想的说法是，你可以用大脑，在综合考虑很多因素之后，去规划你想象的命运。

And the most provocative thing you can say is that you could plan how somehow the fate of your of your imagination using your brain, you know, after taking many things into the code.

这是在不跟他们交流的情况下。

This is Without talking to them.

对。

Right.

不交流。

Without talking.

对。

Right.

我们又回到这个说明书了。

Again, we go back to this instruction manual.

这就像根据你自己的经历，把某些东西写进说明书里。

It's like writing something into the instruction manual based on your own experience.

对。

Right.

我们要明白，大脑使用的语言和遗传的语言是不同的。

We have to understand that the brain uses a different language than the language of inheritance.

它把信息储存在突触里，也就是不同神经元之间的连接中。

It keeps information in synapses, in the connection between different neurons.

当你学习新东西时，你会加强某些连接，削弱其他连接，从而以不同的方式重新连接你的神经系统。

When you learn something, you make some connections stronger and some other connections weaker, and you wire nervous system in a different way.

另一方面，任何可遗传的信息都必须经过一个瓶颈，也就是一个细胞——受精卵，因为我们都从单个细胞开始。

On the other hand, heritable information of any sort has to go through a bottleneck of one cell, the fertilized egg, because we all start from just one cell.

所以问题是，你能不能或者会不会把这种自由结构的信息，也就是突触和大脑结构中的连接，翻译过来？

So the question is, can you or do you translate the information, this freely structured information of synapses and the connection between brains in the architecture of the brain?

你能不能以某种方式把它转化为可遗传的信息，转化为分子形式？

Can you somehow translate it to heritable information to a molecular form?

你可以教虫子，即使它们只有三百零二个神经元，你也能教它们一些关于世界的简单事情。

You can teach worms, even though they have just three zero two neurons, you can teach them simple things about the world.

比如，你可以拿一种虫子喜欢的气味。

For example, you can take an odor that the worms like.

虫子有成千上万的嗅觉受体，它们能识别很多很多很多种分子。

The worms have thousands of odorant receptors, and they can recognize many, many, many molecules.

它们能闻到这些气味，从而找到食物或避开敌人。

They can smell them so they can find food or avoid enemies.

你可以拿一种虫子喜欢的气味，把它和不好的东西配对，比如饥饿，然后虫子就会学会讨厌这种气味。

You can take an odor that the worms like and pair it to something bad, like starvation, and then the worms will learn to dislike this odor.

我们不知道这种学习是否一定涉及突触强度的改变。

We don't know that this learning involves necessarily changing in the strength of synapses.

这是一种可能，但也不一定就是这样。

It's a possibility, but it doesn't have to be the case.

也有可能只是这种特定气味的受体被移除了，而它们就是这样生存的。

It could be that just the receptor for this particular odor is being removed when they and this is how they live.

现在它们就没有这个受体了。

Now they won't have the receptor.

它们就闻不到了。

They won't smell.

它们就不会喜欢这个气味了。

They won't like the odor.

这是一种可能性。

This is a possibility.

这种事情，也许可以传给下一代，虽然还没有人令人信服地证明过，因为只需要一个RNA来控制这个特定的受体。

This type of thing, you can perhaps, not that anyone has showed it convincingly, transmit to the next generation because all it would take is an RNA that will control this particular receptor.

明白吗？

Okay?

有人已经证明了类似的事情，不是在秀丽隐杆线虫里。

People have shown things like that, not in C.

但在哺乳动物中，有人已经证明了类似的事情。

Elegans, but people have shown things like this in mammals.

他们说，你学到某些东西后，到了下一代，某个特定的受体可能会被破坏或改变，从而传递这种反应。

They said that you learn certain things and then just in the next generation, a particular receptor would be mutilated or would change, and this would transmit the response.

一方面，这可能是真的。

And on the one hand it could be true.

另一方面，你需要明白，他们需要证明——而且目前还没有足够令人信服的证据——信息究竟是如何从大脑传递到生殖细胞，然后在下一代中又从生殖细胞传回大脑，到达需要起作用的受体的。

On the other hand you need to understand, they'll need to prove, and this wasn't done convincingly enough yet, how exactly does the information transfer from the brain to the germ cells, and then in the next generation from the germ cells back to the brain to where the receptor need to operate?

这是一个挑战。

And this is a challenge.

这是该领域目前的状况，即这是需要被证明的事情。

This is the current state of the field that this is something that needs to be proven.

我们在秀丽隐杆线虫中做的是，

What we did in C.

我们证明了大脑可以通过小RNA与下一代沟通，并且这可以改变行为。

Elegans is we showed that the brain can communicate with the next generations using small RNAs, and that this can change behavior.

而且这不需要任何语言之间的翻译。

And it doesn't require any translating between any language.

这很简单。

It is very simple.

我们展示的是，如果你拿一只线虫，只改变它大脑中小RNA的产生，那么下一代的行为就会不同，即使你没有动它们的大脑。

What we've shown is that if you take a worm and you change the production of small RNAs just in its brain, in the next generations, their behavior will be different, even though you don't mess with their brains.

这是我们2019年发表在《细胞》杂志上的一篇论文。

This is a paper that we published in 2019 in Cell.

我们展示了，你只需要操纵线虫大脑中内源性天然RNA的产生，这些RNA本来就会产生，但你改变了它们的数量。

We showed that you just manipulate the production of endogenous natural RNAs in the worm's brain that are always made, but you change their amount.

这会改变下一代线虫寻找食物的能力，不仅影响一代，而是影响三代。

And this changes the capacity of the worms in the next generation to find food, not only in one generation, but three generations down the road.

其作用机制是，干扰大脑中这些小RNA的产生，最终会影响生殖细胞中某个基因的表达。

And the way that it works is that perturbing the production of these small RNAs in the brain affects in the end the expression of a gene in the germline.

这个基因叫做SAGE-2。

One gene is called SAGE-two.

我们可以做各种对照实验，通过操纵这个基因的活性，观察它也会影响行为。

We can do all kinds of controls where we manipulate activity of the gene and see that this also affects behavior.