A new way to study the brain's invisible secrets | Ed Boyden

翻译人员: Jin Wu 校对人员: Tianyu Qiao

Hello, everybody.

大家好

I brought with me today a baby diaper.

今天我带来了婴儿纸尿布

You'll see why in a second.

等一下，你们就知道为什么了

Baby diapers have interesting properties.

婴儿纸尿布有些很有趣的特性

They can swell enormously when you add water to them,

比如加水会膨胀

an experiment done by millions of kids every day.

每天有数百万的小孩在做这个实验

(Laughter)

（笑声）

But the reason why

但尿布会膨胀的原因

is that they're designed in a very clever way.

是源于它们的巧妙设计

They're made out of a thing called a swellable material.

它们是用可膨胀的材料制成

It's a special kind of material that, when you add water,

如果把水加到这种特殊材料中

it will swell up enormously,

它就会疯狂地膨胀

体积约胀到1000倍

maybe a thousand times in volume.

And this is a very useful, industrial kind of polymer.

这是个非常有用的工业类聚合物

But what we're trying to do in my group at MIT

我在麻省理工学院的研究团队

is to figure out if we can do something similar to the brain.

想要尝试用类似的方法让大脑膨胀

Can we make it bigger,

试试我们能否把人脑胀大

big enough that you can peer inside

大到可以让人窥视它的内部

and see all the tiny building blocks, the biomolecules,

看里面的小组件和生物分子

看它们在三度空间的组合方式

how they're organized in three dimensions,

the structure, the ground truth structure of the brain, if you will?

看大脑的结构和里面的实况

If we could get that,

如果办得到

maybe we could have a better understanding of how the brain is organized

也许我们能更理解人脑的组织

to yield thoughts and emotions

理解它如何产生思想和情感

and actions and sensations.

行动和感觉

Maybe we could try to pinpoint the exact changes in the brain

或许我们可以知道究竟是什么产生了变化

that result in diseases,

导致大脑发生病变

diseases like Alzheimer's and epilepsy and Parkinson's,

像是老年痴呆症、癫痫和帕金森氏症这些疾病

for which there are few treatments, much less cures,

这些疾病只有少数相应疗法，极少人可以被治愈

我们往往不知道这些疾病的原因或者起源

and for which, very often, we don't know the cause or the origins

and what's really causing them to occur.

以及是什么引发了疾病

Now, our group at MIT

我们在麻省理工学院的研究小组

is trying to take a different point of view

正尝试采取不同的观点

这些观点有别于过往百年研究神经科学的方法

from the way neuroscience has been done over the last hundred years.

We're designers. We're inventors.

我们既是设计师，又是发明家

We're trying to figure out how to build technologies

我们正在尝试怎样发明出新的科技

that let us look at and repair the brain.

能让我们审视和修复大脑

And the reason is,

这么做的原因是

大脑的复杂程度令人难以置信

the brain is incredibly, incredibly complicated.

So what we've learned over the first century of neuroscience

回望脑神经科学研究的第一个百年,我们得知了

is that the brain is a very complicated network,

大脑是个很复杂的网络

made out of very specialized cells called neurons

由称做神经元的特殊细胞

with very complex geometries,

以复杂的几何形状连结而成

and electrical currents will flow through these complexly shaped neurons.

电流可以通过这些形状复杂的神经元

Furthermore, neurons are connected in networks.

此外，神经元被连接在网络中

They're connected by little junctions called synapses that exchange chemicals

它们通过被称为突触的微小连接口来交换化学物质

and allow the neurons to talk to each other.

让神经元彼此间交流讯息

The density of the brain is incredible.

大脑有着不可思议的高密度

In a cubic millimeter of your brain,

在每一立方毫米的大脑中

there are about 100,000 of these neurons

约有十万个神经元

and maybe a billion of those connections.

可能有十亿个连接

But it's worse.

怎么可能进行研究

So, if you could zoom in to a neuron,

如果你能拉近神经元放大看

and, of course, this is just our artist's rendition of it.

当然，你们看到的这个只是我们的艺术家做的图像

What you would see are thousands and thousands of kinds of biomolecules,

你会看到成千上万种的生物分子

little nanoscale machines organized in complex, 3D patterns,

这些立体3D、纳米级的结构共同作用

产生电脉冲

and together they mediate those electrical pulses,

those chemical exchanges that allow neurons to work together

并交换化学物质，使神经元相互作用

to generate things like thoughts and feelings and so forth.

以产生想法、感觉等等

Now, we don't know how the neurons in the brain are organized

我们不知道大脑中的神经元

是如何形成网络系统的

to form networks,

and we don't know how the biomolecules are organized

我们也不知道生物分子

within neurons

是如何在神经元中

形成这复杂有序的机制的

to form these complex, organized machines.

If we really want to understand this,

如果我们真想理解这些问题

we're going to need new technologies.

就必须有新的技术

But if we could get such maps,

如果我们可以做出图像

if we could look at the organization of molecules and neurons

让我们看得到分子和神经元的构造

and neurons and networks,

和神经元网络系统

maybe we could really understand how the brain conducts information

也许我们能真正了解大脑是如何传送

from sensory regions,

来自感官区的信号

mixes it with emotion and feeling,

从而混合入情绪和情感

and generates our decisions and actions.

以产生决策和行动

也许我们可以确切查明

Maybe we could pinpoint the exact set of molecular changes that occur

in a brain disorder.

病变大脑中产生变化的分子

一旦我们弄清楚分子如何改变

And once we know how those molecules have changed,

不论是数目增加或是型态改变

whether they've increased in number or changed in pattern,

we could use those as targets for new drugs,

我们可以把这些分子用来开发新药

for new ways of delivering energy into the brain

用来发明新的把能量传送到大脑的方式

帮助受脑疾折磨的患者

in order to repair the brain computations that are afflicted

in patients who suffer from brain disorders.

修复它们脑中受损的地方

We've all seen lots of different technologies over the last century

我们已经见证到，上个世纪有许多技术

都尝试要解決这个问题

to try to confront this.

I think we've all seen brain scans

我们都见过核磁共振成像仪

被用来扫描脑部

taken using MRI machines.

These, of course, have the great power that they are noninvasive,

当然，这些仪器有不具侵入性

they can be used on living human subjects.

所以可用于活体研究

But also, they're spatially crude.

但是它们的成像却很粗糙

Each of these blobs that you see, or voxels, as they're called,

你可以看到的这些黄色块状物，或者立体像素

can contain millions and millions of neurons.

可能包含有数以百万计的神经元

So it's not at the level of resolution

这样的分辨率

where it can pinpoint the molecular changes that occur

仍不足以查明是哪些分子发生了变化

or the changes in the wiring of these networks

或哪些连接有了变化

正是这些使我们成为有意识的强大的生物

that contributes to our ability to be conscious and powerful beings.

At the other extreme, you have microscopes.

另一个极端的仪器是显微镜

显微镜利用光源来观察微小的东西

Microscopes, of course, will use light to look at little tiny things.

For centuries, they've been used to look at things like bacteria.

数百年来被用以观察像细菌这样的小东西

For neuroscience,

就神经科学来说

microscopes are actually how neurons were discovered in the first place,

我们首次使用显微镜发现神经元

大约是在130年前

about 130 years ago.

But light is fundamentally limited.

但"光"有极大的局限性

You can't see individual molecules with a regular old microscope.

用普通的旧式光学显微镜人们无法看到单个分子

看不到这些微小的连接

You can't look at these tiny connections.

So if we want to make our ability to see the brain more powerful,

所以，如果我们要用更强而有力的方法

来观察大脑的结构

to get down to the ground truth structure,

we're going to need to have even better technologies.

我们需有更好的技术

My group, a couple years ago, started thinking:

几年前，我的研究小组开始思考

Why don't we do the opposite?

何不反向操作呢

If it's so darn complicated to zoom in to the brain,

如果想试着拉近距离去观察大脑这么费劲

why can't we make the brain bigger?

我们为什么不把大脑变大呢

开始这个项目的是我组里的两个研究生

It initially started

with two grad students in my group, Fei Chen and Paul Tillberg.

Fei Chen和Paul Tillberg

Now many others in my group are helping with this process.

现在有更多人加入进来帮着做

我们决定要找出方法，尝试利用聚合物

We decided to try to figure out if we could take polymers,

like the stuff in the baby diaper,

就是婴儿纸尿裤中的那个材料

and install it physically within the brain.

把它放在大脑中

If we could do it just right, and you add water,

如果做得恰到好处，再加入水

you can potentially blow the brain up

就可能把大脑放大到

to where you could distinguish those tiny biomolecules from each other.

足以把小分子个别地分辨出来的程度

这样你就可以看到脑中那些(神经元)连结的图像

You would see those connections and get maps of the brain.

This could potentially be quite dramatic.

这相当激励人心

我今天准备向各位演示一下

We brought a little demo here.

We got some purified baby diaper material.

这有一些婴儿纸尿裤的原料

在网上直接买这个

It's much easier just to buy it off the Internet

than to extract the few grains that actually occur in these diapers.

比从纸尿布里提取少数原料要容易得多

I'm going to put just one teaspoon here

我只放入一茶匙的

of this purified polymer.

精致聚合物

And here we have some water.

然后加入一些水

What we're going to do

接下来要做的

is see if this teaspoon of the baby diaper material

是看看这一茶匙的聚合物会不会

can increase in size.

膨胀开来

You're going to see it increase in volume by about a thousandfold

现在，各位可以亲眼看到

before your very eyes.

它大约会膨胀一千倍

I could pour much more of this in there,

我可以继续加水

but I think you've got the idea

但大家肯定已经知道会发生什么了

这是一种非常有意思的分子

that this is a very, very interesting molecule,

and if can use it in the right way,

如果使用得当

we might be able to really zoom in on the brain

我们就可以观察到

in a way that you can't do with past technologies.

以前无法观察到的大脑细节

OK. So a little bit of chemistry now.

好了，讲化学时间到

What's going on in the baby diaper polymer?

纸尿裤里的聚合物发生了什么呢

If you could zoom in,

如果你能拉近放大来看

it might look something like what you see on the screen.

可能就像你现在在屏幕上看到的

这个聚合物正是由原子排成的众多细长的链条组成

Polymers are chains of atoms arranged in long, thin lines.

The chains are very tiny,

这些链条非常微小

大约是一个生物分子的宽度

about the width of a biomolecule,

and these polymers are really dense.

而且这些聚合物非常密集

They're separated by distances

它们之间的距离

that are around the size of a biomolecule.

大约是一个生物分子的大小

This is very good

这非常好

because we could potentially move everything apart in the brain.

因为我们就可能把大脑每一部分都分解开

If we add water, what will happen is,

如果再加入水

this swellable material is going to absorb the water,

这个会膨胀的物质会吸收水分

the polymer chains will move apart from each other,

聚合物链条彼此间的距离就会拉远

and the entire material is going to become bigger.

整个体积就会变得更大

And because these chains are so tiny

由于这些链条是如此的渺小

and spaced by biomolecular distances,

而且原本的间距只有一个生物分子那么一丁点大

we could potentially blow up the brain

所以我们可能令让大脑膨胀

and make it big enough to see.

大到足以被观察

需要解决的一点是

Here's the mystery, then:

How do we actually make these polymer chains inside the brain

我们要如何把聚合物链置入大脑中

so we can move all the biomolecules apart?

让我们得以拉开生物分子的间距呢

If we could do that,

如果做得到

maybe we could get ground truth maps of the brain.

或许我们就能得到大脑图的实况

We could look at the wiring.

观察到大脑的连接系统

We can peer inside and see the molecules within.

及里面的分子状况

To explain this, we made some animations

我们准备了一个动画视频来解释这一点

where we actually look at, in these artist renderings,

在这个艺术家的作品中，我们可以看到

生物分子的样貌和我们如何把它们分开的情况

what biomolecules might look like and how we might separate them.

Step one: what we'd have to do, first of all,

步骤一：首先我们要做的是

is attach every biomolecule, shown in brown here,

在每一个棕色的生物分子上

to a little anchor, a little handle.

粘上一个小锚，小把手

We need to pull the molecules of the brain apart from each other,

想要把大脑中分子之间的距离拉远

and to do that, we need to have a little handle

我们需要利用这些小把手

that allows those polymers to bind to them

让聚合物和分子连接起来

and to exert their force.

因此让聚合物产生效应

Now, if you just take baby diaper polymer and dump it on the brain,

如果只把尿布中的聚合物直接倒在大脑上

obviously, it's going to sit there on top.

很显然，它们就只会堆在上面而已

So we need to find a way to make the polymers inside.

因此，我们需要找个方法让聚合物进到大脑里面去

在研究过程中我们特别幸运

And this is where we're really lucky.

It turns out, you can get the building blocks,

发现我们可以利用一些建筑块

一种被叫做"单体"的东西

monomers, as they're called,

and if you let them go into the brain

如果把它们放到大脑里面

and then trigger the chemical reactions,

它们就会触发化学反应

you can get them to form those long chains,

然后在大脑组织里

形成细长的链条

right there inside the brain tissue.

They're going to wind their way around biomolecules

这些链条会缠绕住生物分子

and between biomolecules,

也会占住生物分子间的空隙

forming those complex webs

形成复杂的网络

that will allow you, eventually, to pull apart the molecules

最终，这可以使

from each other.

大脑中的分子被拉开

And every time one of those little handles is around,

在有小把手的地方

the polymer will bind to the handle, and that's exactly what we need

聚合物就会粘住这些把手

正好可以成为拉开分子的施力点

in order to pull the molecules apart from each other.

All right, the moment of truth.

好吧，讲到关键时刻

We have to treat this specimen

我们得先用化学物质处理样本

with a chemical to kind of loosen up all the molecules from each other,

让分子彼此分散开

然后加水

and then, when we add water,

that swellable material is going to start absorbing the water,

这个会膨胀的材料开始吸收水分

the polymer chains will move apart,

聚合物链条会移动开来

but now, the biomolecules will come along for the ride.

这一次，生物分子也会跟随着一起移动

And much like drawing a picture on a balloon,

就像一个被画了图画的气球

and then you blow up the balloon,

如果被吹大

the image is the same,

气球上的画还是同一幅画

but the ink particles have moved away from each other.

但是上面的颜色分子间的距离被拉大了

这正是我们所做的，不过是在三维空间里

And that's what we've been able to do now, but in three dimensions.

There's one last trick.

还有最后一个点

As you can see here,

如你所见

we've color-coded all the biomolecules brown.

我们把所有的生物分子都标成棕色

That's because they all kind of look the same.

这是因为他们看起来都差不多是一样的

生物分子由相同的原子组成

Biomolecules are made out of the same atoms,

but just in different orders.

只是顺序有差异

So we need one last thing

最后，我们还要做一件事

来把他们辨别出来

in order to make them visible.

We have to bring in little tags,

我们需要利用发光的染料

with glowing dyes that will distinguish them.

作为区分他们的标示

So one kind of biomolecule might get a blue color.

所以某一种生物分子可能会被标成蓝色

而另一种会被标成红色

Another kind of biomolecule might get a red color.

And so forth.

等等

And that's the final step.

这就是最后一步

Now we can look at something like a brain

如此，我们就可以观察到大脑

and look at the individual molecules,

和一个个不同的分子

because we've moved them far apart enough from each other

因为我们已经把分子拉得足够开

that we can tell them apart.

可以对它们进行分辨

So the hope here is that we can make the invisible visible.

我们愿望是把不可见的变成可见的

We can turn things that might seem small and obscure

把小而模糊的东西放大

and blow them up

并且不停地放大

until they're like constellations of information about life.

直到它们看起来像是生命信息的星座图

Here's an actual video of what it might look like.

这个视频正可以展现这个过程

We have here a little brain in a dish --

碟里放着一個小小的脑

a little piece of a brain, actually.

实际上是一片脑标本的切片

We've infused the polymer in,

我们已在里面注入聚合物

and now we're adding water.

现在要加水

What you'll see is that, right before your eyes --

你们现在看到的

this video is sped up about sixtyfold --

是以加快了60倍速度放映的视频

this little piece of brain tissue is going to grow.

这小片脑组织将会胀大

It can increase by a hundredfold or even more in volume.

它的体积将会胀成百倍或更大

And the cool part is, because those polymers are so tiny,

最牛的是，因为聚合物是如此渺小

we're separating biomolecules evenly from each other.

我们能均匀地分开这些生物分子

It's a smooth expansion.

这个过程会缓慢有序地进行

We're not losing the configuration of the information.

而且信息的型态不会失真

We're just making it easier to see.

我们只是把它变得更容易被观察

So now we can take actual brain circuitry --

现在我们可以取一个真实的大脑神经组织

here's a piece of the brain involved with, for example, memory --

例如这片与记忆有关的部分

and we can zoom in.

拉近放大后

We can start to actually look at how circuits are configured.

就可以看到实际的神经电路构造

Maybe someday we could read out a memory.

也许有一天我们能读出一段记忆

Maybe we could actually look at how circuits are configured

也许我们能看到大脑在处理情绪的过程中

to process emotions,

脑神经的回路状态

how the actual wiring of our brain is organized

以及脑内的神经是如何连结的

in order to make us who we are.

正是这些决定了人与人思想之间的区别

And of course, we can pinpoint, hopefully,

当然我们也更希望

the actual problems in the brain at a molecular level.

能在脑分子层面上分析出脑部病变的原因

What if we could actually look into cells in the brain

试想，假如我们真的深入到大脑细胞里

and figure out, wow, here are the 17 molecules that have altered

发现原来大脑组织中的有17个分子发生了病变

in this brain tissue that has been undergoing epilepsy

所以病人患了癫痫

or changing in Parkinson's disease

或者帕金森氏综合症

or otherwise being altered?

以及其它疾病，那就太好了

如果我们能有系统地把这些变异列表

If we get that systematic list of things that are going wrong,

这就会变成我们治疗的目标

those become our therapeutic targets.

We can build drugs that bind those.

我们可以针对那些目标来制药

或许我们能集中精力研究不同的大脑部位

We can maybe aim energy at different parts of the brain

in order to help people with Parkinson's or epilepsy

以帮助世界各地

or other conditions that affect over a billion people

患有帕金森症、癫痫病

around the world.

或其他病症的十亿人口

Now, something interesting has been happening.

有一种有意思的现象正在发生

It turns out that throughout biomedicine,

原来，这个方法对整个生物医药界的研究

there are other problems that expansion might help with.

也许都能帮得上忙

This is an actual biopsy from a human breast cancer patient.

这是来自一个乳腺癌患者的活体标本

It turns out that if you look at cancers,

实际上，癌症

if you look at the immune system,

免疫系统

if you look at aging, if you look at development --

老化，生长

all these processes are involving large-scale biological systems.

所有这些过程都与大规模的生物系统有关

But of course, the problems begin with those little nanoscale molecules,

当然，问题是从纳米级的分子开始的

the machines that make the cells and the organs in our body tick.

这些分子正是引发细胞和器官活动的机器

So what we're trying to do now is to figure out

我们目前正在试着理清

if we can actually use this technology to map the building blocks of life

是否真的能用这个技术描绘出

各式各样疾病中基础生命结构组成的脉络

in a wide variety of diseases.

Can we actually pinpoint the molecular changes in a tumor

我们能否精确地看到肿瘤的分子变化

so that we can actually go after it in a smart way

从而更有效地应对

并将药物直接传送到我们想要的位置内呢

and deliver drugs that might wipe out exactly the cells that we want to?

要知道，很多药物的风险非常高

You know, a lot of medicine is very high risk.

Sometimes, it's even guesswork.

有的药物并未被确定真正有效

My hope is we can actually turn what might be a high-risk moon shot

我希望我们不只以高风险的登月思维做事

into something that's more reliable.

而是发现更可靠的方式

If you think about the original moon shot,

如果仔细想想我们的登月计划

where they actually landed on the moon,

宇航员登陆月球的壮举

it was based on solid science.

是基于扎实的科学研究的

We understood gravity;

我们通晓重力

we understood aerodynamics.

通晓空气动力学

We knew how to build rockets.

知道如何建造火箭

The science risk was under control.

科学的风险在我们的掌控之中

It was still a great, great feat of engineering.

至今，登月仍是个伟大的工程壮举

But in medicine, we don't necessarily have all the laws.

但在医学上，我们未必有定律可循

我们未必能研究出类似重力

Do we have all the laws that are analogous to gravity,

that are analogous to aerodynamics?

和类似空气动力学的所有定律

I would argue that with technologies

我认为，以我今天所谈论的技术

like the kinds I'm talking about today,

也许某天我们真的能够

maybe we can actually derive those.

导出那些定律来

我们能描绘和测绘生命系统的模型

We can map the patterns that occur in living systems,

and figure out how to overcome the diseases that plague us.

找出方法来克服困扰我们的疾病

You know, my wife and I have two young kids,

我妻子和我有两个年幼的孩子

and one of my hopes as a bioengineer is to make life better for them

身为一个生物工程学家，我有个心愿是

than it currently is for us.

希望孩子们未来的生活能比目前我们的更美好

And my hope is, if we can turn biology and medicine

我希望我们能把生物学和医学的研究

from these high-risk endeavors that are governed by chance and luck,

从偶然和运气支配又高风险的努力

and make them things that we win by skill and hard work,

转向以技艺和勤奋支配却真正有效的工作

then that would be a great advance.

那么这将是一个巨大的进步

Thank you very much.

非常感谢

(Applause)

（掌声）