你体内的鲨鱼

哦，等等。你在听。好的。

Oh, wait. You're listen Okay.

好的。明白了。好的。你在听 听着

Alright. Okay. Alright. You are listening Listening

Radiolab Radiolab。来自

Radiolab Radiolab. From

WNY 看？是的。

WNY See? Yep.

我必须道歉的一件事是我还有点鼻塞，所以你们会频繁听到擤鼻涕的声音，但我会在麦克风外进行。

My the one thing I have to apologize for is I'm still kind of stuffed up, so you're gonna hear noses being blown frequently, but I will do it off mic.

哦，没关系。我对擤鼻涕的声音不太敏感。所以

Oh, that's okay. I I'm not particularly sensitive to nose blowing. So

这里是Radiolab。我是Lulu Miller。今天是我们鲨鱼周的第三天。你感觉好吗？进入状态了吗？

This is Radiolab. I'm Lulu Miller. And today is day three of our week of sharks. Do you feel good? You in a zone?

你觉得我

You feel I'm

进入状态了。

in a zone.

今天的故事由制作人Becca Bressler带给我们。

And today's story comes to us from producer, Becca Bressler.

是的。不过，我确实认为这可能是我参与过最有趣的故事了。

Yeah. Well, I do think that this is maybe the most interesting story I've ever worked on.

哦。

Oh.

而且你现在生病了，说起来还挺诡异的应景。

And it's actually kinda weirdly fitting that you're sick right now.

好吧。

Okay.

不过言归正传。前几期节目里，我们游弋在鲨鱼肆虐的澳大利亚海域。今天我要带你们去个不同的地方。太好了。我们要去哪儿？

But okay. So first couple of episodes, we were swimming in the shark infested waters of Australia. Today, I'm gonna take you somewhere different. Great. Where are we going?

系好安全带。系好了。我们要去威斯康星州。

Buckle up. Buckled. We are going to Wisconsin.

祝你愉快。

Have a nice day.

好吧。中西部内陆？这地方可不像会遇到鲨鱼的样子。

Okay. Midwest Landlocked? This is not where I'm thinking you're gonna encounter a shark.

没错。我也没想到，但我要去拜访这位科学家。嘿，亚伦。他叫亚伦·马修·拉博。最近怎么样？

No. As I wasn't expecting it either, but I was going to see this scientist. Hey, Aaron. His name's Aaron Matthew Laboe. How's it going?

挺好的。你呢？

Good. How are you?

而他

And he

我认识的人里就属我最不懂科学。

I'm the least science y person I know.

以一种有趣的方式进入了这个领域。

Has a kind of funny way into this.

我本科最初去亚利桑那大学是为了打橄榄球、找乐子和参加派对。

I originally went to University of Arizona as an undergrad to play football, have fun, and party.

选了一门化学课。

Took a chemistry class.

彻底爱上了化学。从那以后，我就成为了一名科学家。

Absolutely fell in love with chemistry. And then from there on, I just became a scientist.

但你也参加派对了对吧？重要问题。

But did you party too? Important question.

我参加过很多派对。没错。我喝下的龙舌兰酒量都够填满自己身体好几回了。

I partied a whole lot. Yes. I've I've consumed my body volume in tequila many times.

总之他拿到了博士学位。拉博博士。拉博博士。最后在麦迪逊的威斯康星大学有了自己的实验室。所以你能说说我们现在要去哪儿吗？

Anyway, he gets his PhD. Doctor Laboe. Doctor Laboe. Ends up at the University of Wisconsin in Madison where he has his own lab. So can you say where we're headed right now?

我们要去我的实验室在...哦，这个我不能说。

We're headed to my laboratory on the sub oh, I can't say that.

一个秘密实验室。哦。哦，我们现在要登上穿梭车了。

A secret lab. Oh. Oh, we're we're gonna hop on the shuttle now.

是的。

Yes.

好的。我们坐了大约五到十分钟的巴士穿过校园。

Okay. So we took a bus about five to ten minutes across campus.

这里有一站吗？

Is there a stop right here?

下车后走到一个不起眼的地方。

Got off and walked over to a nondescript location.

我不能告诉你它在哪。

I can't tell you where it is.

我不会再问了。

I won't ask again.

发誓。这边是黑的。

Swear. Black this side.

进入这栋建筑，下一段楼梯——如果我能告诉你的话——来到地下室。我们现在所在的房间看起来有点空，像是进入了一个废弃的大实验室。

Went into this building and down a flight of stairs If I can tell you into the basement. The room we're in right now looks kind of empty. It's into this big abandoned lab.

我想这里最后一次使用大约是十五、二十年前。

It was, I think, last used about fifteen, twenty years ago.

空荡荡的橱柜，积满灰尘的黑色柜台。

Empty cabinets, dusty black counters.

从那以后就被废弃了。

It's been abandoned since.

然后我们拐过一个角落进入另一个房间，哇哦。就在房间中央。你能描述一下我现在看到的是什么吗？

And then we turned around a corner into this other room where Oh, woah. In the middle of it. Can you just describe to me what I'm looking at right now?

是的。你看到的是一个最先进的7000加仑海水缸。

Yeah. You're looking at a state of the art 7,000 gallon saltwater tank.

这里有

There is

基本上就是一个巨大、巨大、巨大的鱼缸。

A huge, huge, huge fish tank, basically.

一个地面上的泳池，哇哦。鲨鱼。天啊。这里面有多少条鲨鱼？

An above ground pool of Woah. Sharks. Oh my god. So how many sharks are in here?

五条。

Five.

五条鲨鱼。

Five sharks.

所以你们是在一个无标识的地堡里，里面有个装满...

So you're in, like, an unmarked bunker with a pool full

关于鲨鱼吗？是的，具体来说是护士鲨。

of sharks? Yes. Specifically nurse sharks.

护士鲨。

Nurse sharks.

所以它们是

So they are

它们是体型较小的那种吗？

They're the littler ones?

这些大概只有两英尺长左右。

So these ones were only about, like, two feet long.

但这些家伙也还没完全长大。在野外，护士鲨可以长到八、九、十英尺长。

But these guys are also not full grown yet. In the wild, you have nurse sharks that are, you know, eight, nine, 10 feet long. The

真的吗？好吧。

heck? Okay.

它们看起来像鲨鱼，但可能和你想的不完全一样。

And they look shark like, but maybe not exactly what you're thinking.

它们没有像大白鲨那样的大颌。

They don't have the large jaws like a a great white do.

它们长着这样的小嘴巴

They've got these tiny little mouths that

吸食食物。

Suck up food.

那是吸吮的声音。没错。它们还有胡须，所以有些人称它们为猫鲨。好吧。但也许最重要的是，这些鲨鱼。

That's the sound of the suction. Yeah. They also have whiskers, so some people call them cat sharks. Okay. But maybe most importantly, these sharks.

这些就像游动的化石。

These are like swimming fossils.

它们很古老。哦。它们属于一个可以追溯到

They're ancient. Oh. They come from a line of sharks that date back

4亿年前的鲨鱼家族。哦。

400,000,000 years ago. Oh.

科学家如亚伦认为，在它们体内隐藏着一个非常古老的钥匙，这把钥匙可能解锁我们抵御地球上一些最致命威胁的能力。而这实际上就是这个。这正是我想讲述的故事。

And hidden inside of them, scientists like Aaron believe there is this very ancient key, a key that could unlock our ability to fight off some of the deadliest threats we face on Earth. And that's that's actually this. That's really the story that I wanna tell.

是的。好的。继续说吧。

Yeah. Okay. Keep us going.

好的。首先，要去艾琳的实验室，我们必须从鲨鱼

Okay. First, to get to Erin's lab, we have to go from sharks

戴着耳机说话时感觉有点奇怪。

Sounds kind of strange when you've got the headphones on actually talking.

回到我们的话题。

Back to us.

我现在听不见她说话。

I can't hear her now.

喂？哦，好了。嗨。嘿，卡罗琳。嗨，贝卡。

Hello? Oh, there we go. Hi. Hey, Caroline. Hi, Becca.

因为要找到这把钥匙，科学家们首先必须弄清楚关于人类的一些非常深刻而神秘的事情。所以我想先开始，卡罗琳，你能告诉我一些关于你是谁以及你做什么的事情吗？

Because to find this key, scientists first had to figure out something very deep and mysterious about humans. So I guess to just start this off, Caroline, can you tell me a little bit about who you are and what you do?

好的，当然，贝卡。是的，我是卡罗琳·伯勒尔。我一直对生命科学充满热情，大学时学习生物化学开启了我的职业生涯，然后继续攻读博士学位。

Yeah, sure, Becca. So yes, so I'm Caroline Burrell. I've always been passionate about life sciences, kind of set off my career at university studying biochemistry, then moved on to a Ph. D.

她现在经营一家生物技术公司。是的。她花了大量时间研究和学习免疫系统。在

She runs a biotech company now. Yeah. And she's spent a ton of time researching and studying the immune system. In

特别是抗体。哦，它们非常强大。

particular Antibodies. Oh, they're formidable.

这是我们免疫系统中最不可思议的部分之一。

One of the most incredible parts of our immune system.

它们无时无刻不在保护我们，免受日常生活中各种侵袭的伤害。

That are protecting us nonstop 20 fourseven from the onslaught of what's going on in our daily lives.

假设你在外面，比如在公园之类的地方，

So let's say you're out in the world, like at a park or something,

然后

and

有人直接对着你的脸咳嗽。假设他携带的一点感冒病毒进入了你的身体。接下来会发生的是

some guy coughs right in your face. And let's say a little bit of that cold virus he has goes into your body. And what happens is

简直是魔法。

Just wizardry.

这些免疫细胞会出现，每一个都开始大量分泌

These immune cells show up, and each one of them starts pumping out

成千上万的这些抗体。

Hundreds of thousands of these antibodies.

于是很快

So that quickly

你的体内就充满了这支大军

Your body is full of this army

由数十亿专门设计的抗体组成

Of billions and billions of antibodies that are specifically designed

它们的靶标。病毒。而一个抗体

Their target. Virus. And an antibody

看起来像个大写的Y。

that looks like a big Y.

于是这支由Y形组成的军队包围了这个病毒。

So this army of Ys surround this virus.

那个Y字形的两个分支

And the two arms of that Y

会伸出去并抓住病毒。

reach out and latch onto the virus.

就像是紧紧抓住它。

Just kind of hold onto it.

非常紧密地抓着，直到其他细胞过来消灭它。

Really tightly. Until other cells can come in and kill it.

这简直让人难以置信，真的。

It's just it blows your mind. It really does.

因为卡罗琳指出，你的免疫细胞不仅仅是对病毒这样反应。

Because Caroline points out, it's not just that your immune cells are doing this for a virus. It can be something

可能是真菌，细菌，

like a fungus, like a bacteria,

也可能是寄生虫，毒素。

maybe a parasite, a toxin.

你可能只是划了个小口子，眼睛里进了灰尘，或者发生了其他状况。

You you may get a small cut, you may get dust in your eyes, you may get something going on.

无论是什么，

Whatever it is,

你可以针对几乎任何外界物质制造抗体。

you can make antibodies against almost anything that's out there.

泰勒能为任何物质定制专属抗体。

Taylor made bespoke antibodies for anything.

任何物质，即使是我们环境中从未存在过的。

Anything, even if it's never existed in our environment before.

等等，什么？

Wait. What?

是的。即使是对不存在的物质，你的免疫细胞也能制造相应抗体。

Yes. Even for things that don't exist, your immune cells can make antibodies for it.

这太酷了。

That is so cool.

实际上这很神奇。抱歉，我...这听起来几乎有点宗教意味。教皇刚去世，我不知道...

It's amazing, actually. Sorry. I I it's it's almost sounds religious. The pope just died and I don't know.

所以你听到的这两个新声音

So these two new voices you hear

是啊。

Yeah.

我是海伦·杜利。

I'm Helen Dooley.

一位是海伦·杜利。另一位

One is Helen Dooley. The other

马丁·弗兰诺克。

Martin Flannock.

马丁·弗兰诺克。

Martin Flannock.

我在马里兰大学巴尔的摩分校的医学院工作。

I work for the medical school here at University of Maryland, Baltimore.

马丁也是。

So does Martin.

在马里兰大学工作了近三十年。

Almost thirty years at Maryland.

他们两人研究免疫系统的进化。

And the two of them, they study the evolution of immune systems.

试图理解我们所拥有的免疫系统是如何进化而来的。

To try and understand how the immune system that we have evolved.

所以故事从这里真正展开。好吧。因为艺术界的海伦解释说，当我们首次发现抗体时，它们如何可能存在是一个真正的谜。免疫细胞如何能做到它所做的事情。它如何能

So this is where the story really picks up. Okay. Because Helen of Art explained, when we first discovered antibodies, there was this real puzzle as to how they could even exist. How an immune cell can even do what it does. How it can

产生数十亿种不同的抗体。

Generate billions of different antibodies.

就像这是细胞本不该具备的能力。

Like that's something a cell shouldn't be able to do.

这说不通。

It didn't make sense.

因为以毛细胞为例，它内部的DNA会指导它如何生成毛发。

Because if you think about, say, a hair cell, it has DNA in it that tells it how to make hair.

我们原以为抗体也是如此，但后来发现，如果要制造针对所有不同物质的抗体，细胞需要携带的DNA量会让整个系统崩溃。

And we thought that was the same with antibodies, but then it turns out if you can make antibodies against all these different things, you would need so much DNA in your cells that the whole system just wouldn't work.

你的细胞根本容纳不了那么多信息。

Your cells literally can't contain that much information.

没错。于是在上世纪七十年代，有个团队开始研究抗体基因——那些编码抗体或抗体片段的基因。

Yeah. So then in the nineteen seventies, a group was looking at antibody genes, the genes that encode antibodies or part of antibodies.

当他们观察这种免疫细胞的基因时

And while they were looking at the genes in this immune cell

他们意识到

What they realized

在其中

was that in it

存在着非常特殊的东西。

There was something really special.

那里似乎存在一种基因，它会四处游走并剪切DNA，然后将这些片段重新洗牌并缝合起来。

There seemed to be a gene in there that was going around and snipping up DNA, and then shuffling those bits and then stitching them back together.

这意味着细胞可以进行混搭组合吗？

And what that meant was the cell could mix and match?

不同的DNA片段。

Different pieces of DNA.

正因如此

And by virtue of that

免疫细胞能够创造数十亿种不同组合，从而生成

The immune cell could create billions of different combinations in order to create

数十亿种不同的抗体。这简直不可思议。虽然极其复杂，但也令人惊叹。

billions of different antibodies. It just is incredible. It's incredibly complicated, but it's just amazing.

这就像一种魔法。

It's a sort of magic.

这部分基因操作堪称巫术。

That bit is genetically just wizardry.

我们体内其他细胞都无法做到，只有免疫细胞可以。

That no other cell in our body can do, just our immune cells.

但当他们发现这一点时，心想：好吧，这很有趣。当然，学术研究的美妙之处就在于他们会深入挖掘，开始提出更多问题，试图解答更多疑问，展开深入研究。而这整件事的序幕正是由此拉开。

But when they saw that, they thought, Okay, that's interesting. And of course the beauty of academia is that they will then dive down and they will start asking more questions, trying to answer more questions, researching it. And that really was the start of the whole thing.

因为科学家们现在想知道的是，这一切是何时发生的？就像这个免疫细胞是何时突然获得这种超能力的？多年来，像迈阿密这支团队一样的科学家小组一直在研究。

Because what scientists wanted to know now was when did this happen? Like when did this one cell, the immune cell suddenly get this superpower? So for years, what you had were groups of scientists like this team down in Miami.

基本上就是观察佛罗里达附近水域中的动物，并采集血液样本。

Basically looking at the animals that were there in the waters off Florida and taking blood samples.

寻找

Looking for

抗体。

Antibodies.

这种超能力的证据，以及它首次出现的时间。

Evidence of this superpower, and when it first showed up.

所以他们基本上是在回溯其他生物，看看这些抗体在当时是否存在。

So they were basically going back to other creatures to see if these antibodies were present or not at that point in time.

所以他们的想法是，从这些动物身上采集血液样本，仔细分析其中发现的任何东西

So the idea being they would take blood samples from these animals, comb through whatever it is they find in there

看看是否有任何抗体具有与人类抗体相似的重量或特征。

And see if any of them kind of had the same, like, weight or characteristics as a human antibody.

典型的Y形。

Classic y.

对，Y形。首先，鸟类。鸟类在大约3亿年前的进化树上分化出来。

Right. The y shape. So First up. Birds. Birds split off on the evolutionary tree about 300,000,000 years ago.

好的。事实证明研究人员早已知道，鸟类体内含有微小的Y抗体。没错。所以

Okay. Turns out researchers already knew this, but birds have the little y antibody. Yes. And so

下一步。

Next step.

他们回溯到了

They went back

爬行动物。

To reptiles.

3.2亿年前。

320,000,000 years ago.

它们也有抗体。继续往前追溯。两栖动物。

They have antibodies. So Back further. Amphibians.

约3.6亿年前。存在抗体。再往前。

About 360,000,000 years ago. Antibodies. Even further back.

鱼类。

To fish.

4.3亿年前。再次发现抗体。4.5亿年前。

430,000,000 years ago. Antibodies again. 450,000,000 years ago.

鲨鱼。

Sharks.

它们也有这些。然后它就停止了。

They have them too. And then it stopped.

所以无脊椎动物中，海胆是众所周知的。

So animals without backbones, everybody would know the sea urchin.

它们大约有5亿年的历史。

Which is about 500,000,000 years old.

当你观察这些生物时，它们体内没有抗体。

When you look at those creatures, there there are no antibodies.

它们拥有的是更简单的免疫细胞，能抵御的威胁种类少得多。

What they have are much simpler immune cells that can defend against far fewer things.

没错。

That's right.

所以鲨鱼其实是...等等。

And so sharks are really Wait.

稍等，真的抱歉。我得停下说话去擤鼻子，因为我...

Hold on. Literally, sorry. I have to stop talking. I have to blow my nose because I can't

听不见你。

hear you.

哦，好的。当然。

Oh, yeah. Sure.

好吧。比如，那些鼻涕里有抗体吗？

Okay. Like, are there antibodies in that snot?

我我想是的。我我是说，那其实不太... 好吧，继续。总之，鲨鱼是地球上现存最古老的拥有类似我们免疫系统的生物。

I I think so. I I mean, I that's not really Okay. Keep going. Okay. Anyways, so sharks are the oldest living things on earth that have an immune system like ours.

几乎可以说我们的免疫系统就是从那里起源的。有人知道原因吗？为什么鲨鱼会成为这种免疫系统首次出现的地方？

It's like pretty much where our immune system began. Does anyone know why? Like, why were sharks the place where this immune system first showed up?

对。大约在那个时期

Yeah. So around that time

四亿五千万到五亿年前发生了一些有趣的事情。

There were some interesting things that happened four hundred and fifty to five hundred million years ago.

在进化的随机性中，拥有海胆的分支突然分化。于是开始出现了具有

Through the randomness of evolution, the branch that had sea urchins suddenly split. And now you started to have animals with

脊椎的动物。

A backbone.

尾巴。鳍。头部。

A tail. Fins. A head.

颌骨。

A jaw.

还有牙齿。发达的大脑。

And teeth. A large brain.

复杂的神经元回路。

Complex neuronal circuits.

从小鱼开始，逐渐发展成更大的鱼，最终

You get fish that lead to bigger fish and eventually

鲨鱼。

The shark.

一个世界前所未见的掠食者。一旦有了掠食者，几乎其他所有生物都会沦为猎物。

A predator that the world has never seen before. And once you have a predator, pretty much everything else becomes prey.

而且你必须维持一定的比例。

And there is going to be a ratio that you have to maintain.

就像，必须保持某种平衡。

Like, there has to be some sort of balance.

没错。掠食者与猎物的数量不能失衡。

Yes. You can't have too many predators with prey.

如果失衡，掠食者会吃光所有猎物。最后将无物可食。正如马丁所说，自然界中常见的情况是

If you did, all the predators would eat all the prey. There would be nothing left to eat. And so what you see, Martin says, often in nature

掠食者通常繁殖率较低。

Is predators in general don't have very many offspring.

它们后代较少，从而维持这种平衡。现在

They have fewer babies, so it maintains this balance. Now

这是非常大胆的推测。明白吗？

This is heavy speculation. Okay?

明白。但马丁的理论是，如果后代数量减少，那么这些后代就需要竭尽所能获取所有防御手段。

Okay. But Martin's theory is if you have fewer offspring, then those offspring will need every defense they can get.

比如？

Such as

那些带两个分叉臂的Y形小分子——抗体。科学家们拼凑出的结论是：就在这个进化分水岭时期，当有颌掠食者长出牙齿时，海胆体内那种简单的免疫细胞...

Little y shaped molecules with two arms. Antibodies. And what scientists piece together is that right here, around that split, when you have jawed predators with teeth, that simple immune cell in sea urchins.

理论认为这是个幸运的偶然事件。

The idea is it was this lucky event.

那段在所有动物体内都能找到的游离DNA片段，恰好嵌入了那个简单免疫细胞，并改写了它的某个基因。

Where this little rogue piece of DNA that you can find in all animals just so happened to make its way into that simple immune cell and tweak one of its genes.

从而赋予它这种能够混合搭配不同DNA片段的新特性。

And give it this property where now it can mix and match different pieces of DNA.

生成数十亿种不同抗体的能力。

The ability to generate billions of different antibodies.

简直像MJ附体，听着——就像咬了彼得·帕克的那只蜘蛛，咬了这个免疫细胞，这个原始抗体，突然间你就得到了能抵御任何威胁的超级英雄免疫细胞。

It's almost like MJ, let's go. The way that I think about it is the spider that bit Peter Parker, like, bit this immune cell, this, like, proto antibody, and suddenly you have this superhero immune cell that can defend against anything.

那些来自外界的威胁。

That has come in from the outside.

这是一种理论。你在电话里提到还有其他理论，并且非常风趣地暗示它们都是错的。但你知道具体有哪些吗？目前还存在其他重要理论吗？

That's one theory. On the phone, you said there there are others, and you very funnily suggested they're all wrong. But do you know what they are? Are there any other any other big theories out there?

我可以告诉你一个。听着，这个叫做'颌骨假说'。

I can tell you one. I can tell you Okay. So this one's called the jaws hypothesis.

颌骨。一旦进化出颌骨，就出现了能啃食骨头的物种，它们可以嚼碎猎物的骨骼。

Jaws. So once jaws emerge, you have these species that can eat things with bones. They can munch on their bones.

而这些骨头在消化过程中可能导致消化道损伤，从而引发潜在感染。

And the bones during digestion could cause scarring of the digestive tract and therefore, you know, potential infections.

所以有人认为免疫系统进化是因为现在接触到的病原体更多，需要抵御可能出现的各类感染。

So some people think it evolved because you are now exposed to so many more things and you need to fight off those different infections that could arise.

明白了。确实合理。就像，遭遇致命威胁的机会越多，战胜这些威胁的能力就越重要。

Okay. Right. That makes sense. Like, the more opportunities there are to be exposed to things that kill you, therefore, defeating things that kill you must be better.

没错。但有趣的是，有位科学家开始全面研究我们免疫系统的演化历程时，他们在鲨鱼体内发现类似机制后，反应却很平淡。

Right. Exactly. But the but the funny thing is is that one scientist started to really put this whole puzzle together of how we got this immune system. When they found it in sharks, they were just like, meh. Okay.

当时主流观点认为鲨鱼的免疫系统是我们免疫系统的简陋版，差不多像是法拉利跑车对比T型福特车。

The prevailing thought was that sharks had a very simplistic version of our immune system, almost like the, you know, the model t Ford of our Ferrari immune system.

比如我们三四天就能产生抗体，而鲨鱼...

Like, we can make antibodies in three to four days. Sharks

需要三四个月时间。

We're looking at three to four months.

他们认为这效率不高。

They thought it's not that efficient.

它的免疫反应非常缓慢。

Its immune responses are very slow.

它已经有4亿年历史了。当然比不上我们的系统。是的。但这个想法会...抱歉。没关系。

It's like 400,000,000 years old. Of course, it's not as good as ours. Yeah. But that idea would Sorry. It's okay.

这个想法将被证明是大错特错的。完全错误。我们稍后回来。

That idea would be proven to be very, very wrong. Dead wrong. We'll be right back.

别走开，伙伴们。大家好，我是露露，这是BetterHelp的广告。每天似乎都有新说法宣称能带来心理健康与和谐——冷水浴、瑜伽、感恩日记、心理咨询、宠物，听起来都不错，但如何确定什么真正适合你呢？

Stick with us, partner. Hi. This is Lulu, and this is an ad by BetterHelp. It can feel like every day, there's a new claim about what will finally bring you mental wellness and harmony. Cold plunges, yoga, gratitude journals, therapy, pets, all sound great, but how do you actually know what works for you?

借助可信资源至关重要。而你知道什么是最可靠的心理健康资源吗？就是真实存在、会呼吸会思考的专属心理咨询师。他们能帮你找到专属的前进道路。我个人既热爱冷水浴，也热爱心理咨询。

Using trusted resources is so important. And you know what is the most trusted resource for your mental health? Your own real living and breathing and thinking therapist. Someone who can help you find your specific path forward. I, for one, am a lover of cold plunges and a lover of therapy.

心理咨询无数次帮助我建立更好的界限，成为更善于沟通的人。心理咨询适合所有人。作为全球最大在线心理咨询平台，BetterHelp提供涵盖多元专业领域的心理健康服务。与BetterHelp畅谈心声，操作也很便捷。

It has helped me countless times with setting better boundaries, becoming a better communicator. Therapy is for anyone. As the largest online therapy provider in the world, BetterHelp can provide access to mental health professionals with a diverse variety of expertise. Talk it out with BetterHelp. It's convenient too.

点击按钮即可开启心理咨询，轻松融入忙碌生活，并可随时更换咨询师。Radialab听众专享首月九折优惠，访问betterhelp.com/radiolab。网址是betterhelp.com/radiolab。

You can join a session with a therapist at the click of a button, helping you fit therapy into your busy life, and you can switch therapists at any time. Radialab listeners get 10% off their first month at betterhelp.com/radiolab. That's better,help,.com/radiolab.

美国之音和自由欧洲电台正面临政府资金断供风险。一位曾因在该机构工作而入狱的记者正在应对后续影响。

Voice of America and Radio Free Europe are at risk of losing government funding. A journalist who spent time in a Russian prison for her work with it grapples with the fallout.

这几天我要与被囚记者的家属通话。我该怎么告诉他们？他们的亲人只是无辜被囚禁？

I'll be talking to the families of our imprisoned journalists these days. What am I gonna tell them? That their loved ones are imprisoned for nothing?

这里是WNYC本周的《媒体内外》节目。

On this week's On the Media from WNYC.

露露，Radiolab节目回来了，这次有贝卡·布雷斯勒、鲨鱼，以及它们体内让它们不生病的奥秘。

Lulu, Radiolab back with Becca Bressler, sharks, and the things inside them that keep them from getting sick.

免疫系统简直太神奇了。我是说，我们居然能对自然界中不存在的东西产生抗体。

Immune systems are just insane. I mean, just the fact that we can create antibodies against things that don't even exist in nature

不然呢？太酷了。对啊。好吧，等等。

or what? So cool. Yeah. Okay. Wait.

让我们把镜头拉远一点。

So let's zoom way out.

好的，简单回顾一下。继续说吧。

Okay. So just a recap. Go ahead.

我们遇到一个叫亚伦的人。他带你们去了一个地堡。他对免疫反应很感兴趣。我们了解到，大概在五亿年前发生过一次大爆发，这与复杂性的出现密切相关。而现在，是的。

We meet a guy named Aaron. He takes you to a bunker. He's curious in immune responses. We're learning about, like, you know, probably there was this big bang around five hundred million years ago that goes hand in hand with complexity. And now yes.

我们接下来要去哪里？

Where are we going next?

对。上次我们说到，科学家发现鲨鱼有免疫系统，但认为它比我们的简单得多。就像海伦说的，它们的像是福特，我们的是法拉利。但这一切在八十年代末马丁出现后开始改变。

Yeah. So where we left off, scientists had discovered sharks have an immune system, but thought it was pretty simple compared to ours. Right. You know, the Ford to our Ferrari, as Helen put it. But that all started to change in the late eighties, when Martin showed up.

1987年我在迈阿密大学找到了第一份工作。

Got my first job in 1987 at the University of Miami.

在一家免疫学实验室里。

In an immunology lab.

然后在那里研究鲨鱼，这很明显。

And there, worked on sharks, obviously.

观察它们制造抗体的免疫细胞。

Looking at their immune cells that make their antibodies.

我们想从鲨鱼体内分离出这些细胞，然后研究它们的功能。

We wanted to isolate the cells from the shark and then study their functions.

所以当他们开始摆弄这些细胞时，他们当然看到了鲨鱼制造的抗体。

So when they started playing around with these cells, they saw of course, they made shark antibodies.

没错。

Right.

显然如此。但后来他还发现了另一个东西

Obviously. That's right. But then he also saw this other thing

那是鲨鱼制造的。

That the shark was making.

看起来有点像抗体

That sort of looked like an antibody

但略有不同。

But a little different.

它有着相同的Y形结构，两个臂状部分，但体积更小。

It had the same y shape, the two arms, but it was smaller.

这确实很奇怪。

And that was weird.

以前从未见过这种情况。于是他取了些微型Y形物，放在显微镜下观察。

Hadn't seen that before. No. So he grabs some of these itty bitty y's, puts them under microscope.

这叫电子显微镜技术。

It's called electron microscopy.

而他观察到这些物体的臂状部分

And what he sees is that the arms on these things

具有高度流动性。

highly mobile.

对，就像橡皮筋一样灵活。

Like, really flexible.

它们能从零度旋转到180度，就像啦啦队员张开双臂那样。

They move from zero degrees to a 180 degrees, like a, you know, a cheerleader with her arms out.

这完全是新发现。在鲨鱼体内、人类体内，任何免疫系统中都前所未见。

And this was something completely new. We've never seen it before in a shark, in us, in any immune system.

没错。直觉告诉我这将是重大发现。

Yeah. It just smelled to me like this was something interesting.

我想那大概就是我最初介入的地方。

I think that's kind of where I think that's kind of where I came in.

于是在接下来的几年里，海伦和马丁做了这些实验：他们把不属于鲨鱼体内的东西放进去，观察这些小小的附属物如何包围住这个异物。它们用灵活的手臂探入其中，紧紧地、死死地抓住它。

So over the next few years, Helen and Martin, they would do these experiments where they would take something that didn't belong in a shark, put it inside of it, and watch these little wives surround this thing in the shark. And with their flexible arms, they would get into it, and they would hold it super, super tightly.

简直令人惊叹。

Just amazed by it.

他们两人当时的反应就像是

And the two of them were like

太神奇了。哦，

It's amazing. Oh,

这些是抗体。这就像是一种全新的抗体类型。

these are antibodies. These are like a whole new type of antibody.

那太棒了。

That was fantastic.

所以当你发现这个时，你理解它的意义吗？

So when you discovered this, did you understand the implications of it?

不，我本该理解的。我本该理解的。但是，你知道...

No, I probably should have. I probably should have. But, you know

所以马丁，他只是发现了新事物。基础科学。

So Martin, he's just seeing something new. Basic science.

他刚刚看到了一样东西。

He just saw a thing.

他刚刚看到了一样东西。然而，由于这些抗体如此微小、灵活且具有粘性，科学家们现在实际上认为它们可能是——我在找哪个词来着？不是解决，而是像治愈癌症的关键。在人类身上吗？在人类身上。

He just saw a thing. However, because these antibodies are so tiny and so flexible and so sticky, scientists today actually think that they might be the key to what's the word I'm looking for? Not solving, but like the key to curing cancer. In humans? In humans.

什么？是的。等等。什么？怎么做到的？

What? Yes. Wait. What? How?

好吧，听我说。那我能拍照吗？还是不行？不行。绝对不行。

Okay. Stick with me. So can I take photos or is that a no no? No. Absolutely.

好的。其实这里我想带大家回到亚伦的实验室。

Okay. This is actually where I wanna take us back to Aaron's lab.

在麦迪逊的一个地下室里。

In a basement in Madison.

在麦迪逊的一个地下室里。

In a basement in Madison.

那边的大块头是斯坦珀先生。

The big boy there is Mr. Stamper.

因为亚伦是少数几位正在研发这些抗体以尝试治愈癌症的人之一。所以我们撒出了网，你们正在用这些网来

Because Aaron is one of the few people who is developing these antibodies to try to cure cancer. So we've got nets out and you're using the nets to

把鲨鱼围到一个地方，这样我们就能用这边的大网抓住它们。

To corral the sharks in a place so we can catch them with a big net here.

所以运作原理是这样的

And so how this works is

好了。

There we go.

他们捕获了一条鲨鱼。现在我们有一条鲨鱼。哦，我是不是该

They catch a shark. So we got a shark. Oh, should

移动一下？

I move?

我应该挪开。他们把鲨鱼倒进这个装满麻醉剂的桶里让它昏迷。如果你不按住桶盖，它会从桶里飞出来吗？

I should move. They dump them in this bucket full of anesthesia to put them to If you weren't putting pressure on the top, would it, like, fly out of the bin?

对，会从桶里飞出来。没错。

Yeah. It would fly out of the bin. Yes.

一旦它出来

And once it's out

它就出来了。

He's out.

好。我们有一条昏睡的鲨鱼。他们往鲨鱼体内注射了一小块癌细胞表面的物质。

Okay. We got a sleepy shark. They inject a little piece of the surface of a cancer cell into that shark.

这是针对任何癌症的吗？

Is this any kind of cancer?

这是某种特定的癌细胞吗？前列腺癌。

Is this a particular kind of cancer cell? Prostate cancer.

这是对当前所有化疗形式都产生耐药性的前列腺癌。

This is prostate cancer that is resistant to all forms of current chemotherapy.

好的。那么你们要把这个注射剂注射到哪个部位？

Okay. And where are you where are you putting this injection?

上次我们注射的是左鳍，所以这次是右鳍。

Last time we did the left fin, so this time we're doing the right fin.

一旦鲨鱼体内有了这点癌细胞，你们就——

And once they have this little bit of a cancer cell in the shark You

会引发强烈的免疫反应。

have a huge immune response.

鲨鱼开始产生数百万抗体。接着

The shark starts producing millions of antibodies. Then

你们会重复注射这些加强针

You deliver repeat booster shots of these

他们反复进行。让这些鲨鱼不断制造这些抗体。

They do it again and again. Getting these sharks to make these antibodies over and over.

这有点像打篮球。练习越多，投篮越准。免疫系统也是同样的道理。

It's kind of like playing basketball. So if you practice more, you're a better shot. Same with the immune system.

这是免疫疗法，训练抗体使其擅长锁定目标。因为一旦你训练它去锁定癌细胞，你就可以在抗体上附加一个小型放射性炸弹。

This is immunotherapy, training antibodies to be really good at latching onto a target. Because once you've trained it to say latch onto a cancer cell, you can attach a little, like, radioactive bomb to the antibody.

我们基本上是将抗体作为一种递送系统，高效地输送

We basically use the antibody as a delivery system to efficiently deliver

这个小炸弹。

This little bomb.

到癌细胞上。

To the cancer cell.

以杀死它。

To kill it.

是的。

Yes.

没错。这也是我们用人类抗体做的事情，甚至针对某些类型的癌症。但有时人类抗体不太擅长附着在癌细胞上。

Correct. And this is also something we do with human antibodies, even for, like, certain types of cancers. But sometimes human antibodies are not very good at sticking to cancer cells.

但鲨鱼抗体

But shark antibodies

凭借那些小巧、灵活、能扭动的臂

With those small, flexible, wiggly arms

它们本质上能进行分子层面的瑜伽，呈现多种不同形态。通过这种多形态变化，它们能深入人类抗体无法触及的目标缝隙中。

They can essentially do molecular yoga and adopt many different shapes. And by adopting many different shapes, they can get into nooks and crannies of targets that human antibodies can't access.

就像癌细胞某些特定部分那样。

Like certain parts of cancer cells.

是的。

Yes.

所以亚伦说过，训练这些抗体大约需要两个月时间。他们第一次去测试其中一种抗体时

So Aaron said that it takes about two months to train these antibodies. And that the first time they went to test one of these things

哦，这大概是两年前的事了。

Oh, this is about two years ago.

他们取出鲨鱼抗体，注射到带肿瘤的小鼠体内

They took the shark antibody, injected it into a mouse with a tumor

通过小鼠的尾静脉注射。

Through the tail vein of the mouse.

做了些高级成像。

Did some fancy imaging.

我当时想，这景象我可从没见过。不到一天时间，我们就看到抗体向肿瘤归巢并聚集在那里。

And I thought, well, I've never seen this before. Within a day, we saw the antibody homing to the tumor and just collecting there.

它们只附着在这些肿瘤细胞上，其他部位完全没有。在体内其他地方都找不到。简直像激光制导般精准锁定肿瘤。

They were just latching onto these tumor cells and nowhere else. They didn't find it anywhere else in the body. Stop. It, like, laser focused right to the tumor.

它的行动方式就像我们印象中的鲨鱼，就像...它们能侦测到隐形目标似的。对，侦测到一滴血然后就——砰。什么？

It moved like we think sharks move, like, where they, like, detect Stealth. Yeah. Detect a drop of blood and then, boom. What?

你对这个结果感到惊讶还是早有预料？

Were you surprised by this or were you expecting these results?

我从事小鼠放射学研究二十年，这结果简直让我震惊。真的？老实说，是的。我从未见过任何抗体效果如此出色。

I've been doing mouse radiology for twenty years and it it knocked my socks off. Really? Honestly, yeah. I've never seen anything I've never seen an antibody work that well.

他们后续又做了项研究，给抗体装上微型炸弹居然也奏效了。哇。他们彻底清除了癌细胞。哇。你观察到抗体引发免疫反应了吗？

And they would follow-up that study with another where they attached a little bomb to the antibody and it worked. Wow. They eradicated the cancer. Wow. Do you see any immune response to the antibody?

因为我猜鲨鱼抗体对小鼠来说就像外来入侵者，小鼠应该会产生对抗它的抗体才对。

Because I guess I would just expect that a shark antibody for a mouse is like a foreign invader that the mouse would then, you know, produce antibodies against.

没错。但不知为何我们没观察到免疫反应。具体原因尚不明确。我们在小鼠和其他啮齿类动物身上做过实验，全球也有其他团队在研究鲨鱼抗体。这是我们所有人都在讨论的未解之谜。

Yeah. So for some reason, we do not see an immune response. And we don't really know the concrete reason why. We've done studies in mice and other rodents, and there are a few other people working on shark antibodies in the world. And that's one thing that we all talk about is how we don't see an immune response against them.

这太不可思议了——就算对人类而言，怀着一个基因半异己的胎儿，身体都会发动免疫攻击。这就是胎盘存在的意义，也是妊娠的艰难所在。我实在无法理解鲨鱼抗体竟不会触发免疫反应。

I mean, I think that's so fascinating because like even for a human, if you're growing a fetus that's half genetically yours, your body will launch an immune response. Like that's the, you know, the purpose of the placenta and the sort of struggle of pregnancy. I just can't even grasp that a shark antibody would not trigger an immune response.

是啊。这种事非得亲眼所见才能相信，而我们已多次验证。我们准备开展灵长类研究，用影像学观察抗体在非人灵长类体内的分布。还会多次给药，看是否产生免疫应答。

Yeah. It's, it's one of those things that you have to, see to believe, and we've seen it many times. And, we're gonna do a primate study. We're gonna do an imaging study to see where this antibody goes in the body of a nonhuman primate. And then we're gonna also repeatedly dose the primate with the antibody to see if we do generate an immune response against it.

我的直觉是：我们不会检测到任何对抗鲨鱼抗体的抗体。

And my hunch is we won't see any antibodies against our shark antibody.

哇。确实。我是说，我不知道...

Wow. Yeah. I mean, I don't know if

或许不该过度解读，但能让我说说吗？我们在鲨鱼周前两天学到的核心就是：怪物通过保持未知、隐形和异质性来维持恐惧。而在分子层面，如果我们能接纳这些元素作为自身的一部分，就会产生深刻的分子纠缠——它们比我想象的亲近得多。

we should do any meaning making here, but can I just like Yeah, go for it? I mean, I think so much of what we learned in the first couple days of our week of shark is like that a monster, it maintains its fear by being unknown, unseen, sort of other. And there's something like if at the molecular level we can embrace these things as us, there is like profound molecular entanglement. Like, they are so much closer than I ever thought.