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

譯者: Helen Chang 審譯者: Wilde Luo

Hello, everybody.

大家好。

I brought with me today a baby diaper.

今天我帶來了嬰兒紙尿布。

You'll see why in a second.

過一會兒，你就知道為什麼了。

Baby diapers have interesting properties.

嬰兒紙尿布有個有趣的特性。

They can swell enormously when you add water to them,

加了水，它們會脹得極大，

an experiment done by millions of kids every day.

每天有數百萬計的小孩子親身實驗。

(Laughter)

（笑聲）

But the reason why

膨脹的原因

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

是它們的巧妙設計。

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

它們是用可膨脹的材料做出來的。

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

若你把水加到這種特殊材料中，

it will swell up enormously,

它會脹的碩大，

maybe a thousand times in volume.

體積約脹大 1000 倍。

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

這是個非常有用的工業類型聚合物。

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

我在麻省理工學院的研究團隊

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

正嘗試要類似地把腦脹大。

Can we make it bigger,

我們能否把腦脹大，

big enough that you can peer inside

大到能夠往內面窺視，

and see all the tiny building blocks, the biomolecules,

看裡頭的小組件、生物分子，

how they're organized in three dimensions,

看它們在三度空間的組合方式，

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

腦的結構，裡面的實況？

If we could get that,

如果辦得到，

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

也許我們能更理解腦的組織，

to yield thoughts and emotions

它是如何產生思想、情感、

and actions and sensations.

行動和感覺。

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

或許我們能嘗試準確地查明

那些導致疾病的大腦變化；

that result in diseases,

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

像是阿滋海默症、癲癇， 和帕金森氏症這些疾病，

for which there are few treatments, much less cures,

只有少數療法，談不上治癒；

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

我們往往不知道 那些疾病的原因、起源，

and what's really causing them to occur.

以及是什麼引發了疾病。

Now, our group at MIT

我們在麻省理工學院的研究小組

is trying to take a different point of view

正嘗試採取不同的觀點，

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

有別於過往百年研究 神經科學的方法。

We're designers. We're inventors.

我們設計。我們發明。

We're trying to figure out how to build technologies

我們正嘗試找出和開發技術

that let us look at and repair the brain.

讓我們能審視和修復大腦。

And the reason is,

原因是

the brain is incredibly, incredibly complicated.

大腦令人難以置信地複雜。

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

回望腦神經科學研究的 第一個百年，我們得知了

大腦是個很複雜的網路，

is that the brain is a very complicated network,

made out of very specialized cells called neurons

由稱做神經元的專門細胞

with very complex geometries,

以複雜的幾何形狀連結而成；

and electrical currents will flow through these complexly shaped neurons.

電流通過這些形狀複雜的神經元。

Furthermore, neurons are connected in networks.

此外，神經元被連接在網絡中。

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

它們通過被稱為突觸的小小連接口

交換化學物質， 讓神經元彼此間交流訊息。

and allow the neurons to talk to each other.

The density of the brain is incredible.

大腦有著不可思議的高密度。

In a cubic millimeter of your brain,

在每一立方毫米的大腦中

there are about 100,000 of these neurons

約有十萬個神經元，

and maybe a billion of those connections.

可能有十億個連接。

But it's worse.

十億個還不止。

So, if you could zoom in to a neuron,

如果你能拉近神經元放大看，

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

當然，這僅僅是藝術家的描繪，

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

你會看到成千上萬種的生物分子，

little nanoscale machines organized in complex, 3D patterns,

這些三度空間、奈米級的小結構，

and together they mediate those electrical pulses,

合起來斡旋調停電脈衝 和交換化學物質，

those chemical exchanges that allow neurons to work together

使得神經元一起

to generate things like thoughts and feelings and so forth.

產生思想、感覺等等。

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

我們不知道大腦中的神經元

如何組織成網路，

to form networks,

and we don't know how the biomolecules are organized

我們也不知道生物分子

within neurons

如何在神經元中

to form these complex, organized machines.

形成這複雜、有秩序的機制。

If we really want to understand this,

若我們真想了解，

we're going to need new technologies.

就必須有新的技術。

But if we could get such maps,

若我們有這圖譜，

if we could look at the organization of molecules and neurons

若我們看得到分子和神經元的構造，

and neurons and networks,

看得到神經元和網路，

maybe we could really understand how the brain conducts information

也許我們能真正了解 大腦如何傳送來自感官區的信號，

from sensory regions,

mixes it with emotion and feeling,

混合情緒和情感，

and generates our decisions and actions.

以及產生決策和行動。

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

也許我們可以確切查明 腦病變中發生的分子改變。

in a brain disorder.

And once we know how those molecules have changed,

一旦我們察覺分子如何改變，

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

不論是數目增加或是型態改變，

we could use those as targets for new drugs,

我們可以把這些 當作病灶來開發新藥，

for new ways of delivering energy into the brain

以新的方式把能量送到大腦，

in order to repair the brain computations that are afflicted

修復受腦疾折磨的患者的腦。

in patients who suffer from brain disorders.

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

上個世紀有許多技術

to try to confront this.

嘗試面對這個問題。

I think we've all seen brain scans

我們都見過核磁共振成像儀 被用來掃描腦部。

taken using MRI machines.

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

它們適用於研究活生生的人體，

they can be used on living human subjects.

不具有侵入性。

But also, they're spatially crude.

但同時，它們的成像粗糙。

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

這些斑點，或者稱為立體像素，

can contain millions and millions of neurons.

可能含有數以百萬計的神經元。

So it's not at the level of resolution

這樣的解析度

where it can pinpoint the molecular changes that occur

不足以查明是哪些分子的改變

or the changes in the wiring of these networks

或哪些網路連結的變動，

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

這些網絡連接使我們 身為有意識的強大生物。

At the other extreme, you have microscopes.

在另一端，有顯微鏡。

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

顯微鏡以射入光來看微小的東西。

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

數百年來被用以觀察 像細菌這樣的小東西。

For neuroscience,

就神經科學來說，

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

約 130 年前用顯微鏡 首次發現了神經元。

about 130 years ago.

But light is fundamentally limited.

但是光本身有限制。

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

用普通的舊式光學顯微鏡 無法看到單個分子。

You can't look at these tiny connections.

看不到這些微小的連接。

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

因此，如果要踏踏實實、 更加強而有力地觀察大腦和其結構，

to get down to the ground truth structure,

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

我們需有更好的技術。

My group, a couple years ago, started thinking:

數年前，我的研究小組開始思考：

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,

如果要近看大腦是這麼複雜，

why can't we make the brain bigger?

難道我們不能把腦變大嗎？

It initially started

起頭的是我組裡的兩個研究生， 陳飛和保羅·提博格。

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

現在我組裡的許多人都幫著做。

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

我們嘗試聚合物──

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

like the stuff in the baby diaper,

像是嬰兒尿布中的東西──

and install it physically within the brain.

把它放在大腦中。

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

如果做得恰到好處，加入水，

you can potentially blow the brain up

就可能把腦放大到這種地步：

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

足以把小生物分子個別地分辨出來。

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

可以看到那些連結而得到腦的圖譜。

This could potentially be quite dramatic.

這可能相當戲劇化，

We brought a little demo here.

所以我們準備了小小的示範。

We got some purified baby diaper material.

我們取得一些嬰兒尿布的純化原料。

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

購買它比從紙尿布內 取出幾粒原料來要容易得多。

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

I'm going to put just one teaspoon here

我只放入一茶匙純化的聚合物。

of this purified polymer.

And here we have some water.

然後加入一些水。

What we're going to do

接下來，

is see if this teaspoon of the baby diaper material

這一茶匙的尿布材料

can increase in size.

體積膨脹了。

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

在你眼前，它的體積變成約千倍大。

before your very eyes.

I could pour much more of this in there,

雖然我可以倒入更多的水，

but I think you've got the idea

但你們都已明白

that this is a very, very interesting molecule,

這是一種非常有意思的分子，

and if can use it in the right way,

如果適當地使用，

we might be able to really zoom in on the brain

或許我們真能以 前所未能的技術來近觀大腦，

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

OK. So a little bit of chemistry now.

好。說明一點點化學原理。

What's going on in the baby diaper polymer?

嬰兒尿布的聚合物裡是怎麼回事？

If you could zoom in,

如果你能拉近放大，

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

可能就如同你在螢幕上看到的。

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

聚合物是原子排成的細、長鏈。

The chains are very tiny,

該鏈非常微小，

about the width of a biomolecule,

大約是生物分子的寬度，

and these polymers are really dense.

這些聚合物非常密集。

They're separated by distances

它們之間的距離

that are around the size of a biomolecule.

大約是生物分子的大小。

This is very good

這非常好，

because we could potentially move everything apart in the brain.

因有足夠的空間可以把大腦中 每一樣東西的距離拉遠。

If we add water, what will happen is,

如果我們加入水，

this swellable material is going to absorb the water,

這可膨脹的物質吸了水，

the polymer chains will move apart from each other,

聚合物鏈彼此間的距離就拉遠了，

and the entire material is going to become bigger.

整個體積變得更大。

And because these chains are so tiny

由於這些鏈是如此的渺小，

and spaced by biomolecular distances,

而且原本的間距 只有生物分子那麼一丁點大，

we could potentially blow up the brain

所以我們能讓大腦脹大，

and make it big enough to see.

大到足以被觀察。

Here's the mystery, then:

奧秘在於：

How do we actually make these polymer chains inside the brain

我們怎樣把聚合物鏈置入大腦中，

so we can move all the biomolecules apart?

讓我們得以拉開生物分子的間距呢？

If we could do that,

如果做得到，

maybe we could get ground truth maps of the brain.

或許我們就能得到腦圖的實況，

We could look at the wiring.

可以窺視大腦迴路，

We can peer inside and see the molecules within.

可以窺見裡頭的分子。

To explain this, we made some animations

我們準備了動畫來解釋，

where we actually look at, in these artist renderings,

此處看到的是藝術家所詮釋

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

生物分子的概貌和可能的分開程序。

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

步驟一：首先要在

is attach every biomolecule, shown in brown here,

每一個以棕色示意的生物分子上

to a little anchor, a little handle.

黏上一個小錨，小把手。

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

為了把腦中分子彼此的距離拉遠，

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

我們需要小把手

that allows those polymers to bind to them

以讓聚合物結合分子，

and to exert their force.

讓它可以施力。

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

如果你只把嬰兒尿布的聚合物

傾倒在腦上，

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

很顯然，它就只會堆在腦上而已。

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

因此，我們需要找個方法 讓聚合物進到腦裡面去。

And this is where we're really lucky.

這正是我們幸運之處。

It turns out, you can get the building blocks,

事實上，若把被稱為單體的基本組件

monomers, as they're called,

and if you let them go into the brain

放到腦裡面，

and then trigger the chemical reactions,

它們就會觸發化學反應，

you can get them to form those long chains,

然後在腦組織裡形成這些長鏈。

right there inside the brain tissue.

They're going to wind their way around biomolecules

它們會纏繞生物分子

and between biomolecules,

也會佔住生物分子間的空隙，

forming those complex webs

形成複雜的網

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

讓你終於能把這些分子拉開。

from each other.

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

聚合物會黏住這些把手，

成為拉開分子的施力點。

in order to pull the molecules apart from each other.

All right, the moment of truth.

好吧，來到關鍵時刻。

We have to treat this specimen

我們得先用化學物質 處理樣本以鬆開分子，

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

and then, when we add water,

然後加水，

that swellable material is going to start absorbing the water,

這個會膨脹的材料開始吸水，

the polymer chains will move apart,

聚合鏈移動開來，

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

生物分子隨著一起移動。

And much like drawing a picture on a balloon,

就像在氣球上繪圖，

and then you blow up the balloon,

然後將氣吹入氣球，

the image is the same,

圖案相同，

but the ink particles have moved away from each other.

但是墨水粒子的間距拉遠了，

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

這就是我們所做的， 不過是在三度空間裡。

There's one last trick.

還有最後一技巧。

As you can see here,

如你所見，

we've color-coded all the biomolecules brown.

我們把所有的生物分子都標成褐色。

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

這是因為他們看起來是一樣的。

Biomolecules are made out of the same atoms,

雖然生物分子的組成原子相同，

but just in different orders.

但順序卻可有差異。

So we need one last thing

最後，我們還要使不同的生物分子 能用視覺辨別出來。

in order to make them visible.

We have to bring in little tags,

用發光的染料 作為區分他們的小標籤。

with glowing dyes that will distinguish them.

So one kind of biomolecule might get a blue color.

將某一種生物分子染成藍色，

Another kind of biomolecule might get a red color.

而另一種會染成紅色，等等。

And so forth.

And that's the final step.

這就是最後一步。

Now we can look at something like a brain

如此，我們就可以看到腦

and look at the individual molecules,

和各個分子，

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

因為我們把分子拉得很開，

that we can tell them apart.

所以可以分辨彼此。

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

成功的希望繫於 我們把不可見的變成可見的。

We can turn things that might seem small and obscure

我們把小而模糊的東西放大，

and blow them up

until they're like constellations of information about life.

大到它們看起來 像是生命信息的星座圖。

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

這是大概模樣的真正影片。

We have here a little brain in a dish --

碟裡放著小小的一個腦──

a little piece of a brain, actually.

其實是一小片腦。

We've infused the polymer in,

我們已在裡頭注入聚合物，

and now we're adding water.

現在要加水。

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

你眼前將看到的是──

this video is sped up about sixtyfold --

以 60 倍速放映的影片──

this little piece of brain tissue is going to grow.

這小片腦組織將會脹大。

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

它的體積將會脹成百倍或更大。

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

酷的是，因為聚合物是如此渺小，

we're separating biomolecules evenly from each other.

我們將能均勻地分開生物分子。

It's a smooth expansion.

是平整的擴張，

We're not losing the configuration of the information.

資訊信息的組態不會失真，

We're just making it easier to see.

只是變成更容易被看得到。

So now we can take actual brain circuitry --

取一實際的大腦神經組織──

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

例如與記憶有關的這一部分──

and we can zoom in.

拉近放大。

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

我們開始能看到實際的 神經電路構造。

Maybe someday we could read out a memory.

也許有一天我們也能 讀出記憶的內容。

Maybe we could actually look at how circuits are configured

也許我們能真切地看到 處理情緒的神經電路組織，

to process emotions,

how the actual wiring of our brain is organized

腦內的神經怎樣連結，

in order to make us who we are.

使我們成為我們。

And of course, we can pinpoint, hopefully,

當然我們也希望

the actual problems in the brain at a molecular level.

能精準到分子層次地 查明腦病的問題。

What if we could actually look into cells in the brain

試想，若我們真的深入到腦細胞裡，

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

哇，並且查出是腦組織中的 這 17 個分子病變

in this brain tissue that has been undergoing epilepsy

而產生如癲癇、

or changing in Parkinson's disease

帕金森氏症，

or otherwise being altered?

或其他種類的異常？

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

如果我們有系統地把變異列表，

those become our therapeutic targets.

就可以當作治療的靶點。

We can build drugs that bind those.

我們可以針對那些標靶製藥。

We can maybe aim energy at different parts of the brain

或許我們能集中精力 研究不一樣的大腦部位，

in order to help people with Parkinson's or epilepsy

以幫助世界各地罹患帕金森、癲癇 或其他病症的十億人口。

or other conditions that affect over a billion people

around the world.

Now, something interesting has been happening.

一些有趣的事已經發生了。

It turns out that throughout biomedicine,

在整個生物醫​​藥界還存在著

there are other problems that expansion might help with.

這個擴張大腦的方法 可以助益的其他問題。

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

這是個實際來自 乳腺癌患者的活體組織切片。

It turns out that if you look at cancers,

若你檢視癌症、

if you look at the immune system,

免疫系統、

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

老化、

發育──

all these processes are involving large-scale biological systems.

這些過程都與 大規模的生物系統有關。

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

當然，問題始於奈米級的分子，

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

和細胞、身體器官規律運行的機制。

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

我們正試圖釐清

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

是否真能用這技術描繪出

各式各樣疾病中 基礎生命結構組成的脈絡。

in a wide variety of diseases.

Can we actually pinpoint the molecular changes in a tumor

我們能否精確地定位 腫瘤的分子變化，

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

以巧妙的方法追尋並發展出

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

能殲滅我們要殺死的 惡細胞的藥品呢？

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

要知道，很多藥的風險非常高。

Sometimes, it's even guesswork.

有時候，使用它只能聽天由命。

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

我希望把大膽、高風險的藥品開發

into something that's more reliable.

轉成更可靠的方式。

If you think about the original moon shot,

如果仔細想想原先的登月，

where they actually landed on the moon,

真正地登陸月球，

乃基於紮實的科學基礎。

it was based on solid science.

We understood gravity;

我們明瞭重力；

we understood aerodynamics.

我們了解空氣動力學。

We knew how to build rockets.

我們知道如何建造火箭。

The science risk was under control.

科學的風險得到控制。

It was still a great, great feat of engineering.

至今登月仍是個偉大的工程壯舉。

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

但在醫學上， 我們未必了解所有的定律。

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

我們有類似重力，

that are analogous to aerodynamics?

類似空氣動力學的所有定律嗎？

I would argue that with technologies

我認為，以我今天所談論的技術。

like the kinds I'm talking about today,

maybe we can actually derive those.

也許某天我們真的能夠 導出那些定律來。

We can map the patterns that occur in living systems,

我們能描繪、測繪生命系統的模型，

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

找出克服疫病的方法。

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

内人和我有兩個年幼的孩子，

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

身為生物工程學家，我有個心願，

than it currently is for us.

希望孩子的生命能比我們的更美好。

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

我希望我們能把生物學和醫學

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

由偶然和運氣支配的高風險努力，

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

轉向為技藝和辛勤工作的贏面，

then that would be a great advance.

那麼這將是一個巨大的進步。

Thank you very much.

非常感謝。

(Applause)

（掌聲）