你的免疫系统如何运作以及如何增强它 | 马克斯·克鲁梅尔博士

所以，如果我们确实在生物学意义上是纯净的出生。

So that if we are indeed born pure, in the biological sense.

对，对，为了今天的讨论，我们就先这么假设吧。

Yeah, yeah, Let's just keep it there for sake of today's discussion.

而且，你知道，等我们到了32岁的时候，我们身上已经布满了各种突变，就像我们看到的那样。

And, you know, by time we are, you know, 32 years old, we are a mosaic of mutations, as it appears we are.

如果免疫系统能够监控身体多个区域，比如比较不同器官，或者就在同一个器官系统内部，然后说，你知道，突变细胞或者非纯净细胞的数量，也许是一种更简单的判断方式，已经超过了某个阈值，通过测量，比如足够多的受体里有了某些东西，细胞就会说，好吧，你知道吗？

If the immune system could surveil multiple regions in the body, maybe compare organs, or maybe keep it within organ system and say, you know, the number of mutated cells or not pure me cells would be one way to do it more simply perhaps, has exceeded a certain threshold, measured, I don't know, like enough receptors have something in them that the cell goes, okay, you know what?

我要开始战斗了。

I'm gonna fight.

是的。

Yep.

对吧？

Right?

就像士兵一样，他们可能听到子弹呼啸而过，但他们会立刻暴露位置并发动攻击吗？

In the same way that, you know, soldiers, you know, they might hear a shot whiz by, but then do they necessarily reveal their location and launch an attack?

不会。

No.

但如果攻击足够猛烈，他们就会反击。

But if it's enough of an attack, they'll fight back.

对。

Yeah.

似乎应该有某种方式，让免疫系统能够量化全身或局部器官的情况，或者在一段时间内进行整合。

It seems like there should be some way to That the immune system could quantify either body wide or local organ, or over some period of time, they could integrate over time.

我不得不相信这样的机制是存在的。

I have to imagine that such a mechanism exists.

我知道你是搞神经生物学的。

You're coming from neurobiologists, I know.

神经生物学里就有这种适应机制。

And so there is that in neurobiology of accommodation.

对吧？

Right?

我总讲一个故事，我去过法国一个叫厄克拉斯的小村子。

I always tell the story of I went to this little village in in France called Euclace.

如果你知道这个名字，厄克拉斯是一种很有名的奶酪，就在这个镇子生产，味道特别臭。

If you know the name, Euclace is a kind of a famous cheese that they make in this town, and it's super stinky.

而且只有那个镇子做这种奶酪，产量还很大。

And they make it only in that town, and they make a lot of it in that town.

所以开车进镇的时候，就像有人脚臭得不行。

And so when you drive into that town, it's like somebody has the worst foot odor.

特别明显。

It's striking.

真的扑面而来。

It really hits you.

但在镇上待了大概一个小时后，

But after being in town for like an hour

你

you

就闻不到了。

don't notice it.

对。

Yeah.

这就是神经适应，你紧张的时候也会这样。

And that's neuronal accommodation where you're nervous.

跟你说的差不多，鼻子里的传感器会想，好吧。

There's the same kind of thing you're talking about where the, you know, the sensors in your nose can become they're like, okay.

我闻过了。

I've seen it.

闻过了。

I've seen it.

现在没了，所以我要忽略它，这样鼻子才能闻到其他危险或别的东西。

Now it's not anymore, and so I'm gonna tune that out because then your nose has the potential to smell other dangers or other stuff.

对吧？

Right?

所以这就是神经系统。

So that's the nervous system.

我觉得你的思路完全正确，我们也是这样认为的——免疫系统在识别危险时，其实是在观察信号随时间的变化。

I think you're exactly right where you're going with this is, and we think this is true, that the immune system is you know, for danger, it's looking for something that you would call like, it's how it's seeing the signal over time.

比如说，一个病毒入侵，你的T细胞识别到了它。

So a virus may, let's say your T Cell recognizes a virus.

你之前从未接触过这种病毒，然后它突然出现并开始复制，数量变得非常多。等到你清除它之后，数量又会降到几乎为零。

Well, you're looking for something that you've had nothing of before, and then all of a sudden the virus comes in and starts replicating, and you have a lot of And then at some point, if you get rid of it, it'll come back down to next to nothing.

在这个过程中，你的免疫系统会发起反应，并记住这个病毒，这样下次再遇到时，就能更快地应对，防止你生病。

And in that period, you mount an immune response, and you learn it, and so the next time around, you'll be faster to respond to it and keep you from getting sick.

这是一种信号类型。

That's one kind of signal.

但自身物质可能有两种信号，我是这么想的。

But self can have either one of two signals, think.

一种是你从出生起就一直拥有的东西。

One of them is that you've had it your entire life.

所以像胰岛素这种蛋白质，我们通常认为，当你摄入糖分时，它的信号会有些上下波动，但会维持在一个范围内。

So that amount of protein, maybe insulin, which we think in general, it has a little bit of signal up and down as you have a sugar, but there's a range for that.

所以你的身体会适应那个范围，而识别胰岛素的T细胞活性很低，它们只会对这种水平产生很低的反应，这背后有完整的故事，但基本上它们会识别那个水平。

So your body gets used to that range, and the T cells that see insulin, they are very low, they're gonna only be very low reactive to that, and there's a whole story behind that, but basically they're gonna see that level.

但免疫系统也可能把一些缓慢上升的东西当作自身物质来处理。

But you can also have things that the immune system is gonna wanna treat like self that maybe do a slow rise.

它们不会像病毒那样出现高峰。

They don't have this peak that you have with the virus.

比如一个突变细胞，可能只是比正常水平高出一点点，持续几个月，然后它分裂成两个细胞，现在比正常水平又高了一点。

And so like a mutant cell, and maybe it's just a tiny, tiny bit above normal for months, and then it makes two copies of its cells, and now it's a little bit higher than normal.

我认为免疫系统在癌症方面的一个缺陷就在于此，你所做的事情——我试着按这个方式生活，但这并没有经过实验验证——就是你的状态是什么，免疫系统就会帮助你维持那个状态。

And the immune system has, I think, one of the deficits with cancer is exactly that, that things that you do, and this is sort of like I try to live my life a little bit this way, but it's not validated by any experimental stuff, is the idea that whatever you are is what the immune system is gonna help you be.

如果它朝这个方向缓慢变化，免疫系统就会接受。

If it's a slow direction this way, it's gonna be okay with that.

它不喜欢的是那种剧烈波动。

What it doesn't like is like big spikes.

这大概就是你想问的那个信号。

And that's maybe the signal that you're asking about.

就是说，有没有可能真的发展到你会产生反应的程度？

Like, could you actually get to the point where you'd reactive?

癌症的问题就在于它发展缓慢又隐蔽。

The problem with cancer is that it is slow and nefarious.

它是随着时间的推移慢慢长大的。

It grows over time.

我觉得我们的身体天生就能适应缓慢的变化。

And I think we're made to absorb slow change.

因为如果昨天它没让我们生病，今天多一点也没让我们生病，那它很可能只是一种发育上的变化。

Because if it's not causing us to be sick yesterday, and a little bit more of it isn't causing us to be sick today, then it's probably just a developmental change.

可能是一种新的细菌。

Maybe it's a new bacteria.

可能是一种，你知道的，共生的东西。

Maybe it's a you know, that's commensal.

只要它不伴随——再说一次，病毒有两个共同特征。

As long as it doesn't accompany, again, viruses have two features in common.

第一，就是它们出现时的那种爆发性增长，但同时它们也会在那个窗口期造成损害。

One, one is this spike of of, you know, appearance, but they also cause damage in that window.

所以你会看到这些信号，我认为免疫系统——我说免疫系统是因为有些细胞会看到损伤，有些细胞会看到入侵的额外蛋白质，然后它们就像你的大脑一样交换信息。

And so you have like these cues that I think the immune system, and I say the immune system because it's some cells are gonna see the damage and some cells are gonna see the additional proteins that come in, and then they exchange information just like your brain.

你知道，大脑有这种有线连接的细胞网络，它们在空间上是固定的。

Know, talk about the fact that the brain has this wired, you know, set of cells that are wired in space.

它们从你的大脑一直延伸到全身，比如到某块肌肉。

They're, you know, across your body from your brain all the way to a muscle, let's say.

而免疫系统则有一群细胞，它们此刻就在我们体内四处游走。

Immune system has this collection of cells that are, they're literally crawling around us right now.

我们以前做过，现在也还在做很多成像研究。

And we used to do, we still do a lot of imaging.

如果你观察一块皮肤，就能看到免疫细胞真的在不停地巡视我们。

If you look in a piece of skin, can see the cells, the immune system are really, really surveying us.

它们到处爬来爬去。

They're crawling around.

但它们会像神经元一样聚集在一起，形成突触。

But they get together like neurons and they can form synapses.

一个细胞可以对另一个说：这是我看到的。

And one can say to another one, this is what I saw.

另一个细胞就说：哦，你看到了那个。

And the other one says, oh, you saw that.

哦，我，你知道，我刚刚才看到这个。

Oh, I, you know, I'm just seeing this.

它们可以形成一个细胞群，就像我们组织里的小型神经中枢一样，然后它们会判断：这个很危险。

They can form a cluster of cells that basically get together like a neural, a little mini brain in our tissue, and they can say, this is bad.

我们必须采取行动。

We've to do something about that.

但我觉得慢性炎症不会触发这种反应。

But I think the slow burn doesn't do that.

慢燃反应就是那种细胞觉得‘情况没那么糟’的情况之一。

The slow burn is one of the ones where the cells are like, it's not that bad.

我知道这可能不是你直接的研究领域，但最近我注意到人们对胸腺的兴趣越来越大了。

I realize this perhaps is not your immediate area of research, but recently I've been seeing a lot more interest in the thymus.

就是我们年轻时有的那个器官，随着年龄增长它会消失，现在大家对胸腺特别感兴趣。

This organ that we have when we're young and it disappears as we get older and there's a lot of interest in the thymus.

也许是因为我们在这个播客里从来没详细聊过胸腺，所以想请你给我们科普一下，它是什么、有什么功能，以及为什么它可能值得关注——我是说，也许再过几年，我们都会去储存自己的胸腺细胞。

Maybe because we've never covered the thymus on this podcast in any amount of detail, if you could just educate us a bit, what it is, what it does, and why it might be interesting as a I mean, maybe we, in a few years, we'll all be banking our thymic cells.

也许真会这样，我知道已经有人在注射一些未经FDA批准的胸腺肽了。

Maybe we will be, I know some people are already injecting non FDA approved peptides that come from the thymus.

我不是建议任何人这么做，但确实已经有人这么做了，毕竟这就是2026年的互联网。

I'm not recommending anyone do that, but people are already doing it because that's the internet in 2026.

对，这挺糟糕的。

The bad, yeah.

胸腺到底是什么？

What's the thymus?

它有什么作用？

What does it do?

为什么大家对它这么感兴趣？

Why this interest?

对。

Yeah.

好，我可以先退一步讲。我之前提到过T细胞这个词。

Well, I can back up one step, and I've used the word T Cell before.

而T细胞最初就是指胸腺细胞。

And T Cell originally was thymus cell.

所以，对于那些可能没去过医院抽过血的人来说，如果你在医院抽过血，你会得到红细胞，这些细胞负责在体内运输氧气。

So for those that maybe don't, you know, have gone to and had blood taken, you know, if you have blood taken in the hospital, whatever, you'll get red blood cells, and those are the cells that carry oxygen around your body.

然后还有白细胞，它们分为两种类型。

And then you have white blood cells that come in two flavors.

嗯，其实不止两种，有很多种类型。

Two well, they come in multiple flavors.

现在我们先说两种。

For the moment, we'll talk about two.

一种叫B细胞，另一种叫T细胞。

One one are called B cells and one are called T cells.

T细胞之所以得名，是因为胸腺。

And T cells were named because of the thymus.

胸腺这个器官挺有意思的，而且它的历史也很有趣。

So the thymus is this funny organ, and it has a funny history.

实际上，我最近在写Substack的文章，有一篇计划明天发布，就是关于胸腺的，因为它真的应该获得诺贝尔奖。

In fact, I'm writing these Substack these days, and I'm writing one that's supposed to be released tomorrow about the thymus because it really should have gotten the Nobel Prize.

有一位科学家还健在。

There's a guy who's alive.

他大概97岁了，住在澳大利亚，做了一项非常了不起的实验。

He's like 97 years old in Australia who did this remarkable kind of experiment.

以前有个时期，心脏有问题的小孩来做手术时，医生在开胸过程中会发现心脏附近有一个巨大的白色器官，像是长出来的东西。

There was this time when kids that had heart issues would come in for surgeries, and they would discover this enormous whitish organ as a growth near the heart as they were taking the body, you know, as they're cutting open.

而在此之前，所有的尸检大多是在成年人身上进行的。

And all the autopsies up to that point had been done mostly with adults.

在成年人身上，那里只有一个小小的东西。

And in adults, there's only this small little thing there.

所以他们当时想，天哪，心脏旁边这个过度生长的东西是怎么回事。

And so they were like, my god, part of the heart thing is this overgrown thing.

他们其实不知道它有什么作用。

They didn't really know what it did.

于是他们就把这个东西切除了。

And so they would remove it.

孩子们做完手术就回家了，这通常是探索性的心脏手术，但孩子们还是回家了。

And the kids then go home, and it was usually exploratory heart surgery, but the kids would go home.

结果，他们并没有死于心脏病，反而很多人死于机会性感染。

And far from, you know, dying of heart disease, many of them would die from, like, opportunistic infections.

他们会感染各种各样的疾病。

They would get all these infections.

他们得了流感之类的病。

They get flu and and etcetera.

所以就有迹象表明，切除这个器官可能去掉了免疫系统的关键部分，导致他们对细菌特别敏感。

And so there was this hint that maybe this removal had taken out a critical part of your immune system, had made it so you were super susceptible to bacteria.

于是，有个叫雅克·米勒的人，他现在是澳大利亚一位和蔼的七十多岁老人，当时他在英国，他拿了一堆老鼠做实验。

And so this guy named Jacques Miller, who's this nice seven year old codger in Australia, At the time, he was in England, and he basically took a bunch of mice.

等这些老鼠刚出生，他就把它们的胸腺——就是那个小小的白色器官——给切除了。

And then when they were newborn, he removed their thymus, the same little whitish organ.

果然，那些老鼠长大过程中看着还行，但最后全都死于细菌感染。

And sure enough, those mice, they basically grew up okay, but then they all would succumb to bacterial infections.

实际上，其中几只还长了肿瘤，当时有人注意到了这个现象，但后来被忽略了。

In And fact, a few of them even got tumors, which was kind of noted at the time, but forgot.

之所以会这样，是因为胸腺是制造所有T细胞的地方。

And the reason why that is is because the thymus is the place that makes all your T cells.

而这个过程是通过一条相当复杂的路径完成的。

And it comes from a kind of a convoluted pathway.

还记得我们说过免疫系统的干细胞住在骨头里吗？

You remember how we talking about how the stem cells of your immune system lives in your bone?

这些干细胞住在骨头里，通过血液跑到胸腺，然后变成T细胞。

Well, are stem cells that live in their bone and they travel through your blood to the thymus and become T cells.

它们之所以要这么做，是因为胸腺是个非常特殊的地方，能用各种不同的方式向它们展示你基因组里的所有基因。

And the reason they need to do that is that the thymus is this kind of super special place that is able to present to them, to show them all of the genes in your genome in various different ways.

所以进入胸腺的T细胞在发育过程中，每个都有10的11次方种不同的受体来识别不同的东西，你肯定不希望其中任何一个对自己反应太强。

And so the T cells that come in there, the T cells are developing, they each have a possible 10 to the eleventh different kinds of receptors to smell different things, and you don't want any of these to come out that are too reactive to you.

你不想产生那种会跑去攻击你的胰腺或者大脚趾之类的T细胞。

So you don't wanna produce T cells that are gonna go off and kill your pancreas or kill your big toe or anything.

你要保持免疫耐受。

You wanna maintain tolerance.

所以要确保免疫系统不会太激烈。

So you wanna make sure that you don't make the immune system that's too harsh.

所以胸腺的作用不仅是生产T细胞，还要以某种方式教育它们，只让那些传感器调校得恰到好处的T细胞出来，这样才能让你保持自我。

So the thymus has the role of producing T cells, but also of educating them in some ways, of only letting the ones that come out that have sensors that are correctly tuned to let you be you in that way.

回到故事的重点，你刚才问到了衰老的问题。在儿童时期，胸腺非常大，因为那时免疫系统还在发育中，它需要从母体免疫的保护下走出来，先进行一些发育，然后突然爆发，开始能够应对你一生中会遇到的各种细菌和病毒。

Now to the point about the story, and you were asking about aging, is that in kids, those are really big because at that point we were talking about the developing immune system, it has to go from living under the veil of your mother's immunity, and then it needs to let some development happen, and then it needs to burst out and start to be able to react against whatever bacteria and viruses you're gonna see over life.

所以胸腺的输出量非常大。

So your thymus has this huge output.

从三个月到六个月大，一直到四五岁，但逐渐减少，身体会制造大量的T细胞。

So as they're like between really from three to six months old and into your four or five years age, but tapering, your body makes tons of T cells.

这很可能是因为你接触到了各种各样的细菌和病毒，所以你需要建立一套免疫细胞库，其中一些细胞对自身抗原反应很弱，但也能对环境中不同的东西产生反应，包括那些需要防御的病原体。

And it's because probably what you're talking about, you're getting exposed to all kinds of different bacteria and viruses, and so you need to make that collection of immune cells that both, some of them see self at low levels, but then they also can maybe react against different things in the environment, including the ones you need to defend against.

然后，因为我觉得我们后来不再需要那么多T细胞了，甚至可能不想要那么多，胸腺就开始萎缩了。

Then what happens is, because again, I think we're not needing that later, and maybe we don't even want that, the thymus involutes.

它会变得非常非常小，所以在老年人身上，它就像个小不点。

It gets super, super small, so that in aged people, it's like tiny.

所以它不再产生新的T细胞了。

So it's not putting out new T cells.

这就是为什么人们对那些肽类物质以及其他恢复胸腺活力的方法感兴趣的原因。比如在癌症治疗中，难道你不想有一大堆新的T细胞涌入体内，精准地针对肿瘤吗？

And so the reason why there's interest in like these peptides, but all these other approaches to like revitalize the thymus is that like in cancer for example, wouldn't you like to have a whole bunch of new T Cells that could come into you, flood in there with exactly the specificity for the tumor?

如果肿瘤已经成功让你体内其他正常的T细胞认为它是正常的，那你可能需要一批新的细胞进来，重新识别它。

If the tumor has managed to teach all your normal cell, your other T cells in your body that it's normal, maybe you need a source of new material to come in and do that.

主要有两种方法。

And there's really two ways.

我记得你不久前和亚历克斯·马尔钦聊过，他肯定提到了在体外改造细胞，赋予它们特异性。

Think you mentioned you talked to Alex Marcin not too long ago, and I'm sure he would have talked about engineering cells that you can engineer on the outside and give them specificity.

但更自然的方式，可能是让胸腺再产生一些T细胞，并确保它们一出来就能对抗肿瘤或其他需要防御的东西。

But the sort of like, if you will, the more natural route to that might be to let the thymus make use some more T cells and make sure that as they come out, you make sure that they can react against this tumor or whatever it is you need to defend against.

这个器官一直很吸引人，因为它是我们关心的所有细胞类型——也就是T细胞的起源。

It's always been a fascinating organ from the sense that it's the origin of all the cell types that we care about, the T cells in that case.

但它确实会随着年龄增长而衰退，这让我们在晚年更容易受到一些影响。

But it does have this like aging hit, you know, sort of aging effect that seems to make us a little bit more susceptible to things later in life.

而且，我们也可以争论，这背后是否有重大的进化设计，还是说只是不再需要了。

And, you know, again, we could argue about what whether there was a big evolutionary design behind doing that or whether there just wasn't needed.

因为如果你活到30岁就死于箭伤，那也就不需要了，但你现在有了新的基因技术。

Because if you got you had to 30 and you died of an arrow wound, you know, you know, and but you give them new genes.

从进化角度来看，你算是赢家。

You're you're a winner in the evolutionary sense.

你说呢？

You know?

我很喜欢这种观点——既然你已经完成了繁衍，那我就简单讲个小故事。

I love this this stance on, well, if you've already reproduced, I'll just give a brief vignette.

我们是通过共同的朋友大卫·费尔瑟姆认识的，他是加州大学圣克鲁兹分校一位非常出色的发育生物学家，他的妻子索菲·萨拉玛也是一位杰出的生物学家，都是我们的共同朋友。

We were introduced by our mutual friend, David Feltham, who's a phenomenal developmental biologist from UC Santa Cruz and his wife, Sophie Salama, also a phenomenal biologist, a mutual friend.

几年前，我在戴夫的实验室里，因为我们长期合作，一起发表了不少论文，当时他正在做一些注射实验。

And years ago, I was in Dave's lab because we were longtime collaborators and published a bunch of papers together, and he was doing some injections.

我要给你惹麻烦了，戴夫。

I'm gonna get you in trouble, Dave.

他现在已经不这么做了。

He doesn't do this any longer.

对，我也要跟你一起给他惹麻烦，因为

Yeah, I'm gonna join him to get you in trouble, because

他当时在做一些注射，可能用的是花青染料。

we've He was doing some injections, a and he might have been using, might have been using, cyanide dyes.

所以算是比较常规的工具。

So it's kind of conventional tool bag.

就是把一小块晶体放在固定的组织里，不是活体动物什么的。

You put a little crystal in a piece of tissue that's fixed tissue, so it's not a live animal or anything.

然后放进冰箱，荧光染料就会标记出通路中的一组神经元。

And then you put it in the fridge, and then the fluorescent dye would label a set of neurons in a pathway.

我走过去看到戴夫在做这个，他居然没戴手套。

And I walked over and I saw Dave doing this, and he wasn't wearing any gloves.

我当时想，这可是碳花青染料啊。

And I thought, these are carbo cyanide dyes.

氰化物。

Cyanide

我就说，戴夫，你不想戴个手套吗？

being And I said, Dave, don't you wanna put on gloves?

他直接从显微镜上抬起头看着我。

And he literally looked up from the microscope at me.

我永远忘不了那一幕。

I'll never forget.

他说，我已经成功繁殖过了。

And he said, I've already successfully reproduced.

然后他又继续做他的事了。

And he went back to doing it.

那是他的实验室。

And it's his lab.

其他人都遵守安全规程。

So and everyone else was following safety protocol.

别去追究他了。

Don't go after him.

他现在已经不这么做了，各位。

He doesn't do this any longer, folks.

但你们中间有一种很有意思的心态，因为他来自细胞生物学领域。

But there's an interesting mindset among you, because he comes from cell biology.

是的，

Yeah,

对。

yeah.

兰迪·谢克曼的实验室。

Randy Schechman's lab.

两人读研时都在诺贝尔奖得主的实验室里受训。

Both trained in Nobel Prize winning laboratories as graduate students.

所以我觉得很了不起的是，这种'既然你已经成功复制了，那真的没必要了'的态度。

So I find it remarkable that this stance of, well, if you've already successfully reproduced, really aren't needed.

但他的孩子现在要么毕业了，要么在上大学。

But his kids are now graduated or in college.

所以这不仅仅是创造后代然后死去，还有养育下一代的问题。

So there is this thing about raising the young too, and not just creating them and then dying.

同意。

Agreed.

我觉得活得更久一些也有它的适应优势。

I think there's a fitness associated with being older than that.

再说一次，我这么说可能只是纯粹从我们今天的生命形态是从何而来的角度去考虑。

And again, when I say that this, it is maybe just taking this from a purely like what would have been the source of what we are today?

你知道，当时对他们来说，自然选择的压力会是什么？

You know, what would have been the selective pressures on them?

这有点像戴维斯说的，自然选择的压力就是让你的基因传递下去，我的后代必须出生，然后活到一定年龄，因为大多数人类在出生后的一段时间内都相当脆弱。

And it would have been a little bit like Davis saying, gotta, you know, the selective pressure is to get your, you know, for my genes to be passed on, my offspring have to be born and then have to get to some age because most humans are born pretty incapable for a period.

不像长颈鹿，生下来就能站起来，一个小时内就能跑。

It's not like giraffes where they drop off and they, you know, drop out and within an hour they're running.

所以那段养育孩子的时期，我认为给人类带来了更大的压力，需要更长久地保持健康。

So that period of raising children, I think, creates more pressure in humans to, you know, to successfully be healthy longer.

但我想，也许有一种负面的观点，就是那种认为你可能没有那么多压力去保持健康的想法。

But I guess just, you know, there may be a negative viewpoint, but that concept that maybe there isn't as much pressure for you to be healthy.

与之相伴的一个想法是，我们早期想要超级高效的一些东西，实际上可能对我们随着年龄增长不利。就像我提到的那个问题，我们的嵌合体现象，对一切来说都是一个真正的干扰因素，因为它创造了一些很难防御的东西，我认为，那就是衰老的背景。

And going with this is the idea that some of the things that we wanna be super efficient early on might actually be bad for us as we get, like I think this issue that I brought up, our mosaics, is a real confounder to everything, because that creates something that is quite hard to defend against, I think, that aging backdrop.

而免疫系统中那些在早期需要高度反应的部分，在面对50岁、70岁或更老这个新现实时，可能会产生一些代偿性的问题。

And some of the immune system that is really gonna be important to just be super reactive early on may have some compensatory problems when faced with that new reality of a 50 year old or 70 year old or whatever.

看起来，嗯，看起来要复杂得多。

Looks quite, you know, looks quite more complex.

但在基因空间里，你肯定希望，在基因空间里，你拥有的基因能够选择出，比如说，一个免疫系统，或者甚至只是你的身体系统，确保你能活到30岁，对吧？

But you would have you would have definitely wanted in gene space, you know, in a gene space that the what genes you have to select for, you know, an immune system, let's say, or even just your body system that makes sure that you get to 30, let's say, are you?

再说一次，这并不是说如果我们理解了这些缺陷就无法克服它们，但这就是我支持基础研究的原因：要理解它们，就必须提出一些问题，而其中90%可能都是死胡同。

And it's, again, there's that isn't to say that we can't overcome some of those deficiencies if we understand them, but here's my plug for basic research is that to understand them, have to ask some questions that are almost 90% of them are gonna be dead ends.

你不能只假设这一件事，而是必须通过实验来排除它。

You know, you cannot hypothesize this one thing, but you gotta do the experiment to like eliminate that.

这是我认为人们并不总是理解科学的一点：在我或其他人取得的所有发现背后，都有成百上千的失望。

And this is one of the things that people I don't think always understand about science is that for all the discoveries that I've made or other people have made, there is hundreds and hundreds of like disappointments.

你会认识到这一点，当你一天结束时从实验室回家，你什么都做对了，但答案却不是正确的那个。

And you'll recognize this where you just go home from the lab at the end of the day and you've done everything right, but the answer isn't the one isn't the right one.

对。

Yeah.

一个对照实验就能把你的整个项目搞砸。

One control experiment can Well nuke your whole project.

嗯，确实有这个问题。

Well, there's that.

显然要有对照。

There's obviously control.

显然你得把实验做好，控制好变量，但结果可能就不是你预想的那样。

There's obviously that you have to do the experiment well and have it controlled, but but the answer just could be not the one you thought.

而且，我们只能先设想，然后去验证它是不是真的，更重要的是去证明它不成立。

And and, you know, we can only imagine stuff and then try and see if it's true, more importantly, to prove that it's not true.

所以好的实验，可以说是那种‘杀手级’实验——如果想法是错的，实验就能把它推翻；但如果结果符合预期，那它就很厉害。

And so the better experiments, kind of call them killer experiments, The ones that kill idea if they're wrong, if the idea is wrong, but it's killer because if it turns out the way you hope it will.

再说回衰老这些话题，我们每个人都能凭直觉去理解，不管你是专业科学家还是在家自学的爱好者。

Again, when we get to some of these aging things, there's a lot of intuition that we all can put into this, whether we're professional scientists or at home scientists.

但很难说直觉，比如你认为世界应该怎样运作，实际上就是世界运作的方式。

But it's really hard to say that intuition, like your idea about how the way the world should work is in fact the way the world does work.

你知道，我因为年龄的关系，希望某些事情会发生。

You know, I wish that because of the age certain things would happen.

那挺好的。

That's lovely.

但实际情况可能非常复杂，用‘巴洛克’这个词来形容，就是整个系统可能以一种完全奇怪的方式配置，一开始并不符合我们的直觉。

But it could be super, the word was baroque, you know, like, it should, the whole system could be configured in a completely weird way that doesn't really initially make intuitive sense to us.

这也是为什么有些发现对我们来说如此重大。

And that's also why some of those discoveries are so big to us.

我们会想，天哪，我没想到这个看似简单的系统竟然这么复杂。

We're like, oh my god, I didn't realize that this system that seems like it might be quite simple is so complicated.

这个世界真是太奇妙了。

The world is so strange.

嗯，我刚开始研究神经生物学的时候，大脑，实际上整个中枢神经系统都被认为是免疫豁免器官。

Well, when I started in neurobiology, the brain, actually the entire central nervous system was considered an immune privileged organ.

是的。

Yes.

那里本来不应该有免疫细胞的。

There weren't supposed to be immune cells there.

多亏了卡拉·沙茨在主要组织相容性复合体方面的出色工作，还有本·贝雷斯。

And thanks to the beautiful work of Carla Schatz with the major histocompatibility complex work and Ben Beres.

本·贝雷斯。

Ben Beres.

我还没提到他们所有的学术后辈，比如贝丝·史蒂文，等等等等。

And I'm failing to mention all their scientific offspring, Beth Steven, and on and on.

他们要是把本的所有学术后辈都列出来，那得花掉剩下的整集时间。

They would take the rest of the episode to name all of Ben's scientific offspring.

没错。

Sure.

还有卡洛斯也是。

And Carlos too.

你倒是挺方便的。

You're a convenient one.

对。

Right.

那些问题我没参与研究，但当时我就在那些实验室里。

I didn't work on those issues, but I was in those labs when it was happening.

我们现在知道，免疫系统在整个生命周期中都活跃地存在于中枢神经系统中，发挥着关键作用。

We now know that the immune system is active and alive in the central nervous system throughout the whole lifespan serving critical roles.

是的。

Yeah.

有两个问题，其实严格来说是三个，都是比较实际的问题。

There are two things that, well, three really that are somewhat practical questions.

我先从最基本的开始讲。

I'll start with the most basic one.

从机制层面来说，为什么少睡一两个晚上，免疫系统对抗感染的能力就会明显下降？

Why is it at a mechanistic level that if you miss a night or two of sleep, that your immune system seems so less effective in fighting off infections?

我们知道具体发生了什么吗？

Do we know what's happening?

是不是因为腺苷这种让人犯困的物质积累太多，从而抑制了T细胞的功能？

Is it like you've got so much adenosine, which is the sleepy molecule and like that adenosine inhibits T cell function or something?

我们真的了解吗？

Do we actually know?

因为我觉得大家都清楚，如果连续几个晚上睡不好或睡不够，就更容易生病。

Because I think all of us are familiar with the fact that if we don't sleep well or enough for a couple of nights, we're much more susceptible to getting sick.

对。

Yeah.

从机制上，我们有没有搞清楚为什么会这样？

Is there a mechanistic understanding of why that's so?

我觉得有一些零散的认识。

I think there are bits and pieces of it.

一些很好的研究显示，晚上睡觉时会发生一些你可能觉得奇怪的事情。

I think some really nice work shows that at night, a few wacky things, when you're asleep, a few, what you might've thought would be wacky things happen.

其中一个现象是，很多免疫细胞会回到骨髓里，而组织里则会涌入大量从骨髓出来的中性粒细胞，它们似乎在全身各处沉积胶原蛋白。

And one of them is that a lot of your immune cells clear back to the bone marrow, And tissues become populated with a bunch of neutrophils that come out of the bone marrow and seem to be depositing collagen around your body.

所以我认为睡眠有很多修复性的作用。

So there's a lot of things that I think are reparative about sleep.

我自己对这个问题思考了很多，可能你对自己的睡眠也有类似的体会。

I've thought about this a lot in my own life as probably you have with sleep.

当然，问题之一是：我们为什么需要睡眠？

Of the questions, of course, is why do we bother to have sleep?

我想只能这样理解：我们的身体如此强大，能量消耗也如此巨大，白天会产生各种副产品，到了某个时候，你就需要一个清理阶段。

And I guess I can only imagine it's because our, you know, we've created, these bodies of ours are so capable and they're so energetically consumptive, they make all these byproducts during the day that at some point you just need a clean up phase.

这就是对睡眠的一种解读——它只是需要一次重置。

And that's one interpretation of sleep, it just needs a reset.

所以免疫系统确实在重置。

So the immune system is definitely resetting.

而且正如我所说，有证据表明，很多细胞会进入组织进入一种静止状态，它们可能暂时不打扰那些修复过程，甚至允许这些修复过程顺利进行。

And as I say, there's evidence that a lot of the cells go kind of quiescent into the tissues, and they may leave you alone for those reparative processes and actually allow those.

关于这方面的数据，目前有很多研究在进行，但我还不能说我已经得出了结论。

In terms of the data on there, there's there's a lot of studies that are being done, and and I can't say that I've come to a a conclusion about that.

这就涉及到这样一个问题：是已知的，还是我不知道，还是根本没人知道？

This is this comes in the question of, like, is it known, or do I do I not know it, or is it does nobody know it?

我觉得这可能是那种大约有十拨人知道，但彼此意见不一的领域之一。

And I'd say this is might be one of these areas where about 10 factions of people know it, but they don't agree.

对。

Mhmm.

你明白吗？

You know?

所以事情总有各种不同的说法。

So there's variations on things.

但我觉得，比如免疫细胞在夜间回到骨髓这个数据，还是比较可靠的。

But I I think the data, for example, that immune cells dive into the bone marrow at night is is pretty solid.

这说得通。

That makes sense.

它们具体在做什么，以及从长远来看，这为什么重要——就像你刚才提到的那些事，从……嗯，但我觉得，晚上发生的一些事情确实能提升你的认知能力。

What they're doing and why that's important in the long sense of like what you're talking about everything from, well, but I think it's, you know, the things that happen overnight, definitely your cognition improves.

这是免疫系统的作用，还是神经元的作用，还是两者都有？

Is that immune or is that neuronal or both?

我觉得是……对，

I think it's Yeah,

跟淋巴引流免疫系统有关。

something in the lymph plumbing immune system.

有一个很明显、无法否认的事实，最好的说法就是，睡眠不足的时候，每个人都会有眼袋，看起来状态很差。

One thing that's just striking like that is undeniable is probably the best way to put it is, everybody has bags under their eyes and looks like shit when they are sleep deprived.

好好睡一两个晚上，眼袋就消失了。

They sleep for a night or two, and it goes away.

这明显是淋巴液堆积的结果。

That's clearly accumulation of lymph.

这一点我们其实是知道的。

We actually know that.

那只是没被清除的淋巴液，甚至可能跟大脑的类淋巴清除系统没关系。

That's just lymph fluid that's not being cleared, and it might not even be the brain's glymphatic clearance system.

对。

Right.

就是一堆淋巴液积在眼睛下面。

It's just, there's a bunch of lymph pooling under your eyes.

所以你看起来才那么憔悴。

That's why you look like shit.

是的。

Yeah.

然后你好好睡两晚，就又恢复精神了。

And then you sleep for two nights, well, and then you look better again.

眼睛还会变得无神。

And the eyes get glassy.

我们知道睡眠不足时眼睛会变得无神。

We know that the eyes get glassy when we're sleep deprived.

那也是个淋巴清除的问题。

That's also a lymphatic clearance issue.

这已经是很明确的结论了。

This is well established.

所以有些东西就像管道系统一样，我们睡觉再起来的时候，它工作得更好。

So there's some things that are just like plumbing works better when we sleep and get up again.

躺下和起来这个动作本身就有影响。

There's something literally about lying down and getting up.

但对我来说，这并不能完全解释免疫方面的问题，因为淋巴系统除了其他功能外，还负责免疫监视。但我的意思是，只要一晚没睡好，房间对面有人咳嗽，你就很容易被传染。

But that to me can't explain the immune thing entirely, because like the lymphatic system is like, among other things, immune surveillance, but I mean, one night lousy sleep and the person coughing across the room gets you sick often.

但当你休息好的时候，你会感觉到那种抵抗力，就像，好吧，我洗个手，或者躲开他们一点，就没事了。

But when you're well rested, you actually feel this robustness like, man, like, okay, might wash my hands or just kind of avoid them and you're good.

对。

Yeah.

所以，不管怎么说，这个影响真的很大。

So it's, I mean, it's an incredible effect one way or the other.

不过，我们很难确切地说清楚，发生的这些事情里，哪些部分对应的是哪个环节。

Again, don't know the degree to which we can nail down, you know, which part of things that are happening is which.

我一直很喜欢那个说法，就是眼睛里有巨噬细胞这种免疫细胞，它们基本上是在清理晶状体。

I always liked the story that there's macrophages immune cells in your eye that are basically clearing lens.

所以，身体各处都有这种小清理工作在进行。你可以想象，如果它要清除的是那种颗粒状的东西，那你就需要睡觉，因为睡觉的时候你不会再制造更多颗粒，这样它才能彻底清理干净，就像洗车挡风玻璃一样，一次性搞定。

So there's all these places where it's doing little cleanup that you can imagine that if the thing it's trying to get rid of is granularity, that you need to have sleep where you just aren't making more granularity so that it can, know, sort of like when you wash your car windshield, you do it completely at that point.

但你总不能一边开车一边有虫子撞上来吧？

But you can't be driving with flies hitting it, right?

那样永远也清理不干净。

You'll never clear it.

这个比喻很贴切。

That's a great analogy.

所以我觉得，某些清理过程在你不制造脏东西的时候效果最好。而且，我们讨论的很多东西，其实都是能量代谢的副产品，会留下一些损伤。

You know, so I think there's certain elements of some of these cleanup processes that happen best when you're not getting things dirty or again, I think a lot of what we're talking about is byproducts of our energetics that leave some damage behind it.

我们消耗了大量的ATP，身体在睡眠时间也做了很多事。这时候你不能再继续制造那些副产品，才能稍微领先一步，把东西清理干净，就像把车开进加油站，顺便把挡风玻璃擦干净一样。

And I think we just use a lot of ATP and we do a lot of stuff as our body's in the sleep business time where you cannot be producing more of that and get ahead of the curve on cleaning things up a bit, like pulling into a gas station, cleaning off your windshield.

我想快速插播一下，感谢我们的赞助商AG1。

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

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I'm excited to share that AG1 has just launched their newest formulation, AG1 Pro.

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Calcium HMB to support muscle recovery and reduce muscle breakdown and zinc carnosine to support and improve the lining of your gut.

这三种成分都有充分的科学依据支持。

All three of these ingredients have compelling science to support them.

所以我很高兴看到它们被加入到现有的AG1配方中。

And therefore I love seeing them added to the existing AG1 formula.

你们大多数人都知道，我每天服用AG1已经将近十四年了。

As most of you know, I've been taking AG1 every day for nearly fourteen years now.

我早在知道播客是什么之前就开始喝了。

I started taking it long before I even knew what a podcast was.

这款产品本身就很棒，现在新的AG1 Pro配方让它更出色了。

It's a great product and it's now made even better with the new AG1 Pro formula.

如果你想试试AG1 Pro，可以访问drinkag1.com/huberman，获取特别优惠。

If you would like to try AG1 Pro, you can go to drinkag1.com/huberman to get a special offer.

AG1会赠送一瓶Omega-3辅酶Q10，作为你首次订阅的赠品。

AG1 is giving away a free bottle of omega-three coenzyme Q10 with your first subscription.

再说一次，去drinkag1.com/huberman，首次订阅AG1就能免费获得一瓶Omega-3辅酶Q10。

Again, go to drinkag1.com/huberman to get a free bottle of omega-three coenzyme Q10 with your first AG1 subscription.

这个胸腺的话题真的很有意思。

This thymus thing is really intriguing.

我知道很多人选择储存孩子的脐带，希望脐带里的干细胞将来能派上用场。

And I know a lot of people who opted to bank their child's umbilical cord in the hopes that the stem cells from the umbilical cord will someday be useful.

是的。

Yeah.

这个操作有多大的侵入性？或者说，我们是不是应该把胸腺细胞也存起来？

How invasive is it and or should we be banking thymic cells?

因为这些细胞似乎非常有价值，它们能够进行免疫监视，并且利用我们自身的内源性T细胞来对抗感染，创造出一种近乎理想的状态。

Because these seem like incredibly valuable cells for their ability to immune surveil and create kind of the perfect situation using our own endogenous T cells to battle infections.

我真希望自己有一小块胸腺组织，放在零下80度的冰柜里存着，这样等我85岁的时候，也许还能派上用场。

I mean, I kind of wish I had a little chunk of my thymus in a minus 80 freezer someplace, so that when I'm 85 years old, might be able to exploit that.

对。

Yeah.

嗯，我得说，脐带血储存这件事其实挺简单的。

Well, I'll say that the umbilical cord one is pretty straightforward.

脐带本身基本上就是被丢弃的东西，但它含有大量的骨髓干细胞，这你也知道。

The umbilical cord is being essentially discarded anyway, and it contains a lot of, as you know, bone marrow stem cells.

这些细胞的用途和胸腺细胞有点不一样。

The utility of those is a little different than the thymus.

储存这些材料——所谓储存，就是把它放进一个小瓶子里，加上合适的培养基，然后放在一个非常非常冷的环境里，以备将来可能需要——它的用处在于，如果你需要做骨髓移植，比如你得了骨髓系统的肿瘤，你可以接受放射治疗，把所有肿瘤细胞都清除掉，但同时也会把所有的干细胞都清除掉。

Utility of banking that material, and banking just means you put it into a vial, small little vial with the right media, and you set it in a very, very cold environment for whenever you might need it, is that if you need to have a bone marrow transplant, so for example, if you have a tumor of the bone marrow system, you can subject yourself to radiation and wipe out all that tumor cells, but you'll wipe out all the stem cells.

但如果你有这个样本，你就有个替代品。

But if you get this vial here, you've got a little replacement.

这个有成功案例吗？

Has that ever been done successfully?

对，对，可以给孩子做自体移植。

Yeah, yeah, you can do autologous kids.

现在有没有孩子或成年人因为储存了脐带血而活下来的？但

Are there kids or adults that are alive today because they banked their umbilical But

当然有公司在卖这种服务。

certainly companies sell access to that.

嗯，总得有人付钱维持冰箱的备用电源什么的。

Well, somebody has to pay to keep the freezers on backup generators and things like that.

所以大家投入时间和金钱在这个想法上。

So people invest time and money into this idea.

是的。

Yeah.

有没有一个活生生的人，本来会死掉，抱歉，本来会死掉，就因为他们花钱存了脐带血？

Is there a walking, talking, breathing human who would be otherwise dead, would otherwise be dead, excuse me, because they paid money to bank their umbilical cord.

这个问题问得非常好。

It's a really good question.

我不知道这个问题的答案。

I don't know the answer to that question.

我想，那些父母

I guess the I parents

可以告诉你，这就像，我要说的就是，你描述的那种深度，就像我往老鼠体内注射东西一样，在小鼠身上，这是真的。

can tell you, and this will be just like, this is the depths of to which you're describing a dayfelt that I'm injecting a, you know, like mouse, is that in mice, this is true.

如果你取骨髓干细胞，就能重建一只患有血癌的小鼠的血液系统，这是可以做到的。

That if you take, you know, bone marrow stem cells, you can reconstitute a mouse with a blood blood cancer, and you can do that.

我相信在人类身上也能做到。

I'm sure you can do it in humans too.

我对此毫不怀疑，它同样有效。

Have zero doubt that it also works.

我不知道那些公司有没有做过这种事。

I don't know whether those companies have done that.

这其实只是某种情况，

That's just actually something where

现在这种脐带血储存服务已经大规模推广了。

I This pull them is offered in mass now.

对。

Yeah.

也许问题不只是你想不想保存脐带？

Maybe it's more than do you wanna keep the umbilical cord?

说实话，我会选择存，因为如果费用不太高的话……不过我也不确定，这得看你有多少钱可以花，因为

Honestly, I would do it because it's one of those situations where if it's not too ex well, I don't know if it you know, it depends on your your how much money you have to spend because the

但假设费用在可承受范围内。

But assuming it's within within the noise.

是的。

Yeah.

对。

Yeah.

这就是那种情况，特别是如果你有孩子，你会想保护他们免受任何可能发生的伤害。

It's it's one of those so it's one of those ones where you particularly, you have kids, there's this whole aspect of, like, I would like to protect them from anything that could come their way.

而且我觉得，如果他们不幸得了儿童白血病，这个技术就能治好它。

And I think this would if if they happen to have a a childhood leukemia, this would this would cure it.

想想看，这真是个了不起的说法。

Which is an incredible statement if you think about it.

即使目前还没成功过，你也没说这项新技术可能有助于找到治疗方法。

Even if it hasn't been done successfully yet, You didn't say it might be able to lead to a cure by virtue of a new technology.

你直接说它能治好。

You said it would cure it.

是的。

Yeah.

我是说，这话说得挺大的。

I mean, that's a big statement.

对。

Yeah.

你看，我正从睡眠领域逐步升级，现在开始研究胸腺和脐带血了。

You can tell I'm ratcheting up from like sleep to banking thymus and umbilical cord.

接下来我要进入下一个层次，这就不只是湾区的事了。

Now I'm gonna go to the sort of next level, which is not just in the Bay Area.

不过，现在很多人开始琢磨：也许我可以从自己的皮肤细胞里提取成纤维细胞，用山中因子诱导成多能干细胞，让它恢复干细胞特性，然后说不定能培育出一个新的胰腺，或者研究自己的各种器官，就是那些所谓的类器官之类的。

A lot of people, however, are starting to think about, oh, maybe I make some induced pluripotent stem cells from a fibroblast from one of my skin cells, put the so called Yamanaka factors on, revert that to stemness, and then I might be able to grow a new pancreas or study my, you know, whatever organs in these so called organoids or whatever they refer to.

是的。

Yep.

但今天从你这里学到，如果我把那个成纤维细胞拿来用，它可能并不完全是基因意义上的安德鲁·休伯曼，实际上它可能带有一些突变，所以跟标准细胞做对比似乎很重要。

But I learned today from you that if I take that fibroblast now, that fibroblast might not be completely Andrew Huberman as I know him to be genetically, it's actually could have some mutations that seems important to compare against a sort of standard cell.

我可不想从带有突变的诱导多能干细胞环境里培育类器官。

I don't want to grow organoids from an IPS environment that carries mutations.

那听起来可不是个好主意。

That that seems like a bad idea.

对。

Yeah.

因为那样的话，我不是说要把那些类器官移植进去。

Because then anything I would I'm not talking about transplanting in those organoids.

我是说研究它们，以为能从中获取信息。

I'm talking about studying them, thinking I'm getting information about them.

人们正在这么做。

People are doing this.

明白。

Mhmm.

我在想，看看哪些药物对治疗肝病或心脏病有效。

I'm thinking, oh, seeing what drugs are effective in treating, you know, a liver disease or a heart disease.

但如果那些是突变细胞，那实验就没什么意义了。

But if those are mutant cells, that's a lousy experiment.

是的。

Yeah.

我不会说，出于这个原因，它们就应该是突变细胞。

I wouldn't I wouldn't say there would like to be mutant cells for that reason.

我觉得最大的问题是，你诱导它们变成你想要的器官，即使成功了，它是否真的复制了真实器官本身。

I think the biggest question would be whether your induction of them to become the organ that you, you know, once was successful, was replicating the actual organ itself.

所以你提到的这些类器官，就是从人体中提取的细胞集合，通过多种不同因子诱导生长，使其类似于某个器官，比如特定器官。

So you're you're referencing these things called organoids, which are collections of cells from a body, human for example, that are induced with various different factors to grow to resemble maybe an organ, a particular organ.

我想我们大家都不怀疑，根据加州再生医学研究所的说法，制造能变成特定器官的干细胞总有一天会实现。

I think all of us have little doubt, this is the source of the California Institute for Regenerative Medicine, that making stem cells that can become particular organs will at someday happen.

我们最终会解决所有这些问题。

We will figure all these things out.

而且我相信科学。

And and I believe in science.

我相信我们有能力不断测试、学习、再测试、再学习。

I believe in our ability to sort of like test, learn, test, learn, test, learn.

至于这些成果多久能派上用场，那就是更大的问题了。

How soon, you know, that becomes useful is a bigger question.

如果你今天提取你的成纤维细胞，那可能要到未来某一天才能治好你。

If you take out your fibroblast today, that might only cure you someday in the future.

而与此同时，你可能因为那个你希望有干细胞治疗的病而死去，因为技术还没准备好。

And meanwhile, you may die of that thing that you wish you had the stem cells, because it's not yet ready.

技术和认知都还没准备好。

The technology and the understanding isn't yet ready.

但另一个问题是，你很可能死于别的原因，比如被车撞了。

But the other problem with those is you probably will die of something else, you're be hit by a car.

你存了那些东西也帮不上忙。

It won't help you that you've got those things banged.

所以我觉得在某些情况下，过度强调这一点——可能就是你关于储存脐带血的观点——就是，在什么情况下，你的孩子需要它并且你正好存了它的概率很高，相比之下，其他各种可能降临在我们人类身上的命运，跟骨髓干细胞毫无关系。

So I think in some of these cases, overemphasizing, this might be your point about the storage of umbilical cords, is like at what point is that a high odds situation where you your kid needs it and you have it stored away versus all the other things, fates that can befall us as humans that have nothing to do with, you know, stem cells from the bone marrow.

而对我来说，这就是一个点：你可以花一辈子担心自己怎么死。

And and to me, that's that's a point where you could spend your life worrying about how you're gonna die.

但也许那不是一种好的活法。

And and maybe that's not a good way to live.

那当然不是我的生活方式。

Well, certainly not how I live.

现在，所谓的‘长寿’话题引起了很大的兴奋和关注。

Right now, there's a lot of kind of excitement and attention around so called longevity.

对。

Yeah.

极端情况下，比如永远不死或者活到120岁——这似乎是目前基因上的极限。

At at the extremes of never dying or living to be 120, which seems to be the perhaps the genetic limit currently.

是的。

Yeah.

但这并不是我热衷的方向。

It's it's not my fascination.

我更关心的是如何过好我拥有的这些年。

I'm more interested in living in the years I've got Yeah.

看来你也是这么想的，对吧？

As it seems you are Yeah.

没错。

Exactly.

充满活力、身体健康，能活动、有感知、能思考，还有记忆力，这些才是关键。

Vital, healthy, you know, being able to move, sense, and and think seems like and remember, you know, those seem like the critical ones.

你刚才提到了切除一部分胸腺的想法。

You know, you know, a moment ago, you mentioned the concept of, like, removing a bit of thymus.

对我来说，问题在于这是一种侵入性手术。

And I I think that the issues with for me with that are are, you know, it's an invasive surgery.

而且，如果切除胸腺，我不确定你需要的到底是不是胸腺本身。

And, if you were to take out thymus, it would it's not clear to me that it's the thymus that you need.

实际上，你可以制造胸腺组织。胸腺既包含从骨髓来的细胞，作为一个器官，它有内容物，但它的结构是由胸腺上皮细胞构成的，这种细胞形成基质，让所有细胞在其中生活并接受教育。

You might be able to I mean, in fact, you can make thymic So the thymus is both the cells that come into it from the bone marrow, so as an organ, it has contents, But its structure are some thymic epithelial cells, a kind of cell that make a matrix that all those cells live in and they get educated in.

确实有相当有力的研究表明，你可以制造一种胸腺上皮组织，它能完成部分工作。

And there's definitely pretty strong work that says that you can create sort of a thymic epithelium that will do some of this work.

但一个普通人能否保存胸腺细胞，并在我们有生之年用它来做一些对长寿重要的事情，我不知道。

But whether a guy at home could hold onto the thymic cells and we would be in a position to do something important for longevity in our lifetime, I don't know.

说实话，我真的不知道。

I honestly don't know.

在我的职业生涯中，有些事情发展得非常快，快到你几乎都没意识到自己在做。

Some things, in my career, I've seen things happen really fast, so fast that almost like you didn't realize that you were doing it.

你会想，天哪，我们找到治愈癌症的方法了。

You're like, oh my god, we've got a cure for cancer.

那太好了。

That's great.

好，那我们继续做下一件事吧。

Okay, let's go on do the next thing.

有两件事，比如加州再生医学研究所，我们原本以为在那笔债券的七八年窗口期内就能推出一些干细胞疗法，结果后来又发行了第二笔债券。

Two things that you're like, you know the California Institute for Regenerative Medicine, we thought that we would have some stem cell therapies within the seven or eight year window of that bond, first bond, and then there was a second bond.

但实际上我们并没有从中得到多少成果。

We didn't really get very many out of that.

我们学到了很多，这就是风险所在。

We learned a lot, and that is the risk

关于干细胞生物学。

About stem cell biology.

关于干细胞生物学。

About stem cell biology.

这就是我们做研究时要承担的风险。

And that is the risk we take when we do research.

刚才我们还在说，你在实验室里可能花了几百个小时，却什么也没搞明白。

We're talking a moment ago about how many times you might be in a lab, spending hundreds of hours and not getting anything that you understand.

然后突然有一个小时，你什么都明白了，因为之前所有的失败突然都有了意义。

And then one hour and you understand everything because, so all of a sudden all those failures make sense.

我觉得当我们深入研究干细胞生物学时，凭直觉几乎可以肯定，我们会有一些这样的成果。

I think when we get into some of this stem cell biology, it's intuitive and it's almost certainly true that we will have some of these things.

至于这些成果能不能及时惠及你或我，我不知道。

Whether we will have them in time for like you or me, I don't know.

我真的不知道。

I just don't know.

我觉得很多事都是这样。

And I think that's true of a lot of these things.

比如说，现在好像就快要突破了。

Say, oh, seem to be right on the cusp right now.

就拿癌症治疗来说，我们谈CAR-T疗法已经谈了十到十五年了，一直说快要有突破了。

For example, in cancer therapy, we've been on the cusp for ten or fifteen years of these things called CAR Ts.

亚历克斯应该跟你提过这个，就是改造你的T细胞，给它们装上特殊的受体，让它们去消灭肿瘤。

Alex will have told you about these, where you engineer your T cells and you give them special receptors that can get them to go into to eliminate tumors.

但不知什么原因，在病人身上就是没效果。

But for whatever reason, they haven't worked in patients.

一直没效果，一直没效果，一直没效果。

They haven't worked, they haven't worked, they haven't worked.

然后T细胞，免疫系统就被关闭了。

And T cell, the immune system gets turned off.

这些细胞根本活不下来。

These cells don't make it.

它们没能消灭肿瘤。

They fail to eliminate the tumor.

我们迟早会搞明白的。

We will figure that out.

但过去五到十年里，我们一直觉得自己差不多已经搞明白了。

But we've been thinking that we've figured it out sort of for five or ten years.

这确实让人沮丧。

And that gets frustrating.

而且我觉得，那些在外面等着的人也会觉得沮丧，他们会想，为什么你们就解决不了这个问题呢？

And I think it gets frustrating for people that are waiting for it to, on the outside, like, why can't you solve this?

而你的回答只能是，因为宇宙的运作方式并不总是我们想的那样，而这正是科学发现的过程。

And you're like, well, because the universe isn't always configured how we think it is, and that's discovery.

这就是科学发现的难点所在。

That's the problem of discovery.

如果我们知道该怎么做，直接设计出来就行了，问题也就解决了。

If we knew what we needed to do, we would engineer it, it would work.

但我们现在还没有。这是一个很重要的讨论，我们在播客里花的时间还不够，我觉得这对听众来说非常重要。

But we don't This is an important discussion that we haven't spent enough time on in this podcast that I think is very important for people to hear.

我对此有一些想法，但我很乐意听到不同的意见。

And I have some thoughts about it, but I'd I'd love for any disagreements.

我不是只想听赞同的声音，不过，是的。

I'm not looking for just agreements, but Yeah.

所以，根据我从事科学研究二十多年、后来主要转向做播客的观察——这就是我现在做的事。

So my observation from a couple decades or more doing science and then mainly shifting to podcasting, but this is what I do.

我和顶尖科学家交流。

I talk with great scientists.

这就是播客的内容。

So that's the podcast.

所以，我非常了解前沿领域正在发生的事情，这多亏了像您这样优秀的嘉宾。

So I'm very immersed in like what's happening right at the cutting edge and because of great guests like you.

我的感觉是，在每个领域，都有一种持续的压力，就像水对岩石的压力一样——比如，我们想了解蝾螈是如何再生的，如果我们也能做到，那该多好啊？

My sense is that in every field, there's been like this kind of steady pressure, like water on rock pressure, like, okay, we're gonna understand, like salamanders regenerate, wouldn't it be great if we could do that too?

砍掉一条肢体，它还能长回来。

Cut off a limb, it could grow back.

对，太神奇了。

Okay, amazing.

我觉得伊莱·田中（Eli Tanaka）的研究已经证明了这一点。

I think it's like Eli Tanaka's work has just shown that.

你会想，哇，这对截肢者和大脑再生来说太不可思议了。

You're like, wow, this would be incredible for amputees and brain regeneration.

但就是没法真正转化到实际应用。

But then it never really transfers.

或者像，哦，我们要想办法把基因送进细胞里。

Or like, oh, we're gonna figure out ways to get genes into cells.

我们要用电穿孔法处理脂质体。

We're gonna electroporate liposomes.

我们要用磷酸钙。

We're gonna use a calcium phosphate.

就像很棒的研究工具，能催生出大量成果。

Like great research tools, tons of things happen.

然后就是，我们要修改基因，锌指蛋白、细胞核，所有这些，好，CRISPR，一下子爆发了。

And it's like, we're gonna modify genes, zinc finger, nucleus, all this, okay, CRISPR, boom.

而其中一项技术就突破了重围，走得更远。

And one thing just breaks through and goes so much further.

尽管伦理问题备受争议，但确实有婴儿通过CRISPR被故意诱导基因改变，还有镰状细胞贫血的治疗，这是一个更仁慈的例子，不过也有那个在中国擅自对人类进行实验的疯狂科学家。

And even though the ethics are questionable, there are babies that have deliberately induced gene alterations with CRISPR, sickle cell anemia treatments as well, it's a more benevolent example, but then the person who went rogue and just kind of did this in humans in China.

但CRISPR就是突破了所有障碍。

But CRISPR just kind of broke through it all.

对干细胞的热情引发了很多事情，是的，我的意思是，甚至立法层面的倡议，还有所有那些实验室都在研究相关课题。

The excitement about stem cells led to like, yeah, I mean, even initiatives at the legislative level and like all these labs working on things.

然后，就像你说的，它似乎遇到了瓶颈。

And then, as you said, it's kind of like run up against the dam.

是的。

Yeah.

但我觉得十年后，这些信息中的一部分或全部会变得极其重要，因为突然之间，某个东西就会从细菌或蚱蜢里跳出来——当然，我不是故意拿蚱蜢开玩笑。

But I feel like in ten years, some or all of that information will be extremely relevant when boom, one thing will just like leap out of bacteria or like grasshoppers, no pun intended with the grasshoppers.

但最后一个例子是，多年来，人们一直在说这个国家越来越胖，肥胖问题越来越严重。

But the last example would be, for years, it was like the country's getting fatter, the country's getting obese.

我们该怎么办？

What are we gonna do?

卡路里重要吗？

Do calories matter?

当然，卡路里很重要，热力学定律依然适用。

Of course, calories matter, this kind of thing, laws of thermodynamics still apply.

然后突然之间，那个研究吉拉怪兽的生物学家

And then all of a sudden, this freaking Gila monster biologists

对，对。

Yeah, yeah.

告诉了人们他们早就知道的事情，因为GLP类药物早就被用作药物了，只是剂量不够高而已。

Tells people what they already knew because the GLPs were already being used as a drug, just not at significantly high levels.

对。

Yeah.

然后突然之间，我们就有了一种虽然不完美但非常重要的、可以说是肥胖症的疗法。

And all of a sudden, we have a imperfect, but very important, more or less, dare I say cure for obesity.

是的。

Yeah.

它也有问题，比如肌肉流失，可能还有其他问题，像情绪淡漠等等。

It's got problems, there's muscle wasting, there could be other issues, apathy, etcetera.

我不是要否定这些，但我觉得科学就是这样运作的。

I'm not trying to discount any of that, but I feel like that's the way science works.

就像持续的压力、持续的压力、持续的压力、挫折，然后突然冒出点什么来。

It's like steady pressure, steady pressure, steady pressure, frustration, and something comes out of nowhere.

而且似乎那些年积累的挫折和失败是必不可少的。

And it almost seems prerequisite to have all those years of frustration and failure.

对。

Yeah.

然后你会说，难道我们不能先搞出CRISPR或者GLP类药物吗？

And then, and you say, well, couldn't we have just gotten CRISPR first or the GLPs first?

为什么我们要经历所有这些，你知道的，数十亿美元的投入、时间和精力？

Like, why did we go through all these, you know, billions of dollars of expenditures, time, energy?

对。

Yeah.

我不知道。

I don't know.

我觉得这里面有某种自然规律，我只是想听听你的看法。

I feel like there's some natural order to this, and I just would like your thoughts on it.

我觉得大量的失败是必要的，但光有失败还不够。

I feel like it's necessary, but not sufficient to have lots and lots and lots of failures.

对。

Yeah.

而且我认为，研究那些在某个阶段纯粹只是出于好奇的东西，是必要的，绝对必要的。

And I think it's necessary and necessary, absolutely necessary, to study things that are just, at some point, curiosities.

听起来科学好像是在研究琐碎的东西，但你刚才举了个例子。

And that sounds like science is about trivia, but, you know, you you gave an example clip.

比如有人好奇为什么吉拉毒蜥能休眠十个月不吃东西，然后还能活过来。

One, somebody was just curious as to why Gila monsters it was the the feature was that Gila monsters can go into, you know, dormancy for, like, ten months, not eat, and then and then come out.

它们是怎么做到的呢？

And, like, how do they manage that?

所以当时就是纯粹想知道，那到底是什么？

And so that's that was just like, what is that?

是什么原因导致的呢？

What is it what what causes that?

CRISPR也是，人们当时在研究细菌怎么防御其他细菌。

CRISPR, you know, that was, people were studying like how do bacteria defend against other bacteria?

结果发现，细菌里有一种酶，它能记住之前入侵过的细菌的基因序列，然后修改基因组，把入侵者干掉。

Well, use this, it turns out, well, there's this enzyme in it, and it remembers the sequence of this one bacteria that has come and invaded you before, and then can like modify the genome and get rid of it and like kill it.

而我们现在用来做人类基因编辑的，正是同一种酶——它最初就是从基础研究里来的，研究的就是细菌怎么自我保护。

Well, that same enzyme that we now use for all this human engineering came out of a basic, like, how do bacteria defend themselves?

这跟治疗镰状细胞贫血症毫无关系，它只是想弄清楚这个世界是怎么运作的。

It's not anything about modifying sickle cell anemia, it was about how does the world work?

我的职业生涯正好和癌症免疫疗法这个领域的历史一样长。

My career is exactly as long as the lifespan of this field we call cancer immunotherapy.

我做了第一个免疫疗法的实验。

I did the first immunotherapy experiment.

我给一只老鼠注射了我自己制作的一种抗体。

I injected a mouse with an antibody that I had made.

这种抗体是针对T细胞上的分子的，而且我早就在实验室里证明了，当你阻断那个分子时，T细胞会被激活得更厉害。

It was against molecules on T cells, And I'd shown already in the lab that that molecule caused the T cells to get more activated when you blocked it.

然后我们用老鼠做了一系列其他疾病的实验，结果发现它一直在不停地激活T细胞。

And we did a series of like other mouse experiments of like all kinds of diseases and it kept jamming up the T cells.

后来，我的心理医生吉姆说，冰箱里还有一些肿瘤样本。

Then Jim, my psychiatrist, I said we got some tumors in the fridge.

于是我们就设计了那个实验，他注射了那种抗体，结果肿瘤就消失了。

And so we set up that experiment and, you know, he injected this antibody and the tumor's melted.

嗯，那就是癌症免疫疗法的开端。

Well, that was the start of cancer immunotherapy.

非常棒。

Really good.

这就是起源。

That's the origin

这个实验，咱们直说吧，就是让你的导师拿了诺贝尔奖的那个实验。

This is the experiment for which, let's just be direct, that your adviser won the Nobel Prize.

对。

Correct.

对。

Correct.

你至少去参加了颁奖典礼吧？

Did you at least get to attend the ceremony?

是的。

Yeah.