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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
that result in diseases,
那些導致疾病的大腦變化;
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
is that the brain is a very complicated network,
大腦是個很複雜的網路,
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,
and allow the neurons to talk to each other.
讓神經元彼此間交流訊息。
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
to form networks,
如何組織成網路,
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,
混合情緒和情感,
mixes it with emotion and feeling,
以及產生決策和行動。
and generates our decisions and actions.
也許我們可以確切查明 腦病變中發生的分子改變。
Maybe we could pinpoint the exact set of molecular changes that occur
一旦我們察覺分子如何改變-
in a brain disorder.
不論是數目增加或是型態改變-
And once we know how those molecules have changed,
我們可以把這些當作病灶來開發新藥,
whether they've increased in number or changed in pattern,
以新的方式把能量送到大腦,
we could use those as targets for new drugs,
修復受腦疾折磨的患者的腦。
for new ways of delivering energy into the brain
上個世紀有許多技術
in order to repair the brain computations that are afflicted
嘗試面對這個問題。
in patients who suffer from brain disorders.
我們都見過核磁共振成像儀 被用來掃描腦部。
We've all seen lots of different technologies over the last century
它們適用於研究活生生的人體, 不具有侵入性。
to try to confront this.
但同時,它們的成像粗糙。
I think we've all seen brain scans
這些斑點,或者稱為立體像素,
taken using MRI machines.
可能含有數以百萬計的神經元。
These, of course, have the great power that they are noninvasive,
這樣的解析度
they can be used on living human subjects.
不足以查明是哪些分子的改變
But also, they're spatially crude.
或哪些網路連結的變動,
Each of these blobs that you see, or voxels, as they're called,
這些網絡連接使我們 身為有意識的強大生物。
can contain millions and millions of neurons.
在另一端,有顯微鏡。
So it's not at the level of resolution
顯微鏡以射入光來看微小的東西。
where it can pinpoint the molecular changes that occur
數百年來被用以觀察 像細菌這樣的小東西。
or the changes in the wiring of these networks
就神經科學來說,
that contributes to our ability to be conscious and powerful beings.
約130年前用顯微鏡 首次發現了神經元。
At the other extreme, you have microscopes.
但是光本身有限制。
Microscopes, of course, will use light to look at little tiny things.
用普通的舊式光學顯微鏡 無法看到單個分子。
For centuries, they've been used to look at things like bacteria.
看不到這些微小的連接。
For neuroscience,
因此,如果要踏踏實實、 更加強而有力地觀察大腦和其結構,
microscopes are actually how neurons were discovered in the first place,
我們需有更好的技術。
about 130 years ago.
數年前,我的研究小組開始思考:
But light is fundamentally limited.
何不反向操作呢?
You can't see individual molecules with a regular old microscope.
如果要近看大腦是這麼複雜,
You can't look at these tiny connections.
難道我們不能把腦變大嗎?
So if we want to make our ability to see the brain more powerful,
起頭的是我組裡的兩個研究生, 陳飛和保羅·湊博格。
to get down to the ground truth structure,
起頭的是我組裡的兩個研究生, 陳飛和保羅·湊博格。
we're going to need to have even better technologies.
現在我組裡的許多人都幫著做。
My group, a couple years ago, started thinking:
我們嘗試聚合物-
Why don't we do the opposite?
像是嬰兒尿布中的東西-
If it's so darn complicated to zoom in to the brain,
把它放在大腦中。
why can't we make the brain bigger?
如果做得恰到好處,加入水,
It initially started
就可能把腦放大到這種地步:
with two grad students in my group, Fei Chen and Paul Tillberg.
足以把小生物分子個別地分辨出來。
Now many others in my group are helping with this process.
可以看到那些連結而得到腦的圖譜。
We decided to try to figure out if we could take polymers,
這可能相當戲劇化,
like the stuff in the baby diaper,
所以我們準備了小小的示範。
and install it physically within the brain.
我們取得一些嬰兒尿布的純粹原料。
If we could do it just right, and you add water,
購買它比從紙尿布內取出幾粒原料來 要容易得多。
you can potentially blow the brain up
我只放入一茶匙精製的聚合物。
to where you could distinguish those tiny biomolecules from each other.
然後加入一些水。
You would see those connections and get maps of the brain.
接下來,
This could potentially be quite dramatic.
這一茶匙的尿布材料
We brought a little demo here.
體積膨脹了。
We got some purified baby diaper material.
在你眼前,它的體積變成約千倍大。
It's much easier just to buy it off the Internet
雖然我可以倒入更多的水,
than to extract the few grains that actually occur in these diapers.
但你們都已明白
I'm going to put just one teaspoon here
這是一種非常有意思的分子,
of this purified polymer.
如果適當地使用,
And here we have some water.
或許我們真能以 前所未能的技術來近觀大腦,
What we're going to do
好。說明一點點化學原理。
is see if this teaspoon of the baby diaper material
嬰兒尿布的聚合物裡是怎麼回事?
can increase in size.
如果你能拉近放大,
You're going to see it increase in volume by about a thousandfold
可能就如同你在屏幕上看到的。
before your very eyes.
聚合物是原子排成的細、長鏈。
I could pour much more of this in there,
該鏈非常微小,
but I think you've got the idea
大約是生物分子的寬度,
that this is a very, very interesting molecule,
這些聚合物非常密集。
and if can use it in the right way,
它們之間的距離
we might be able to really zoom in on the brain
大約是生物分子的大小。
in a way that you can't do with past technologies.
這非常好,
OK. So a little bit of chemistry now.
因有足夠的空間可以把大腦中 每一樣東西的距離拉遠。
What's going on in the baby diaper polymer?
如果我們加入水,
If you could zoom in,
這可膨脹的物質吸了水,
it might look something like what you see on the screen.
聚合物鏈彼此間的距離就拉遠了,
Polymers are chains of atoms arranged in long, thin lines.
整個體積變得更大。
The chains are very tiny,
由於這些鏈是如此的渺小,
about the width of a biomolecule,
而且原本的間距 只有生物分子那麼一丁點大,
and these polymers are really dense.
所以我們能讓大腦脹大,
They're separated by distances
大到足以被觀察。
that are around the size of a biomolecule.
奧秘在於:
This is very good
我們怎樣把聚合物鏈置入大腦中,
because we could potentially move everything apart in the brain.
讓我們得以拉開生物分子的間距呢?
If we add water, what will happen is,
如果做得到,
this swellable material is going to absorb the water,
或許我們就能得到腦圖的實況,
the polymer chains will move apart from each other,
可以窺視大腦迴路,
and the entire material is going to become bigger.
可以窺見裡頭的分子。
And because these chains are so tiny
我們準備了動畫來解釋,
and spaced by biomolecular distances,
此處看到的是藝術家所詮釋
we could potentially blow up the brain
生物分子的概貌和可能的分開程序。
and make it big enough to see.
步驟一:首先要在
Here's the mystery, then:
每一個以棕色示意的生物分子上
How do we actually make these polymer chains inside the brain
黏上一個小錨,小把手。
so we can move all the biomolecules apart?
為了把腦中分子彼此的距離拉遠,
If we could do that,
我們需要小把手
maybe we could get ground truth maps of the brain.
以讓聚合物結合分子,
We could look at the wiring.
讓它可以施力。
We can peer inside and see the molecules within.
如果你只把嬰兒尿布的聚合物 傾倒在腦上,
To explain this, we made some animations
很顯然,它就只會堆在腦上而已。
where we actually look at, in these artist renderings,
因此,我們需要找個方法 讓聚合物進到腦裡面去。
what biomolecules might look like and how we might separate them.
這正是我們幸運之處。
Step one: what we'd have to do, first of all,
事實上,若把被稱為單體的基本組件
is attach every biomolecule, shown in brown here,
放到腦裡面,
to a little anchor, a little handle.
它們就會觸發化學反應,
We need to pull the molecules of the brain apart from each other,
然後在腦組織裡形成這些長鏈。
and to do that, we need to have a little handle
它們會纏繞生物分子
that allows those polymers to bind to them
也會佔住生物分子間的空隙,
and to exert their force.
形成複雜的網
Now, if you just take baby diaper polymer and dump it on the brain,
讓你終於能把這些分子拉開。
obviously, it's going to sit there on top.
在有小把手的地方,
So we need to find a way to make the polymers inside.
聚合物會黏住這些把手,
And this is where we're really lucky.
成為拉開分子的施力點。
It turns out, you can get the building blocks,
好吧,來到關鍵時刻。
monomers, as they're called,
我們得先用化學物質處理樣本 以鬆開分子,
and if you let them go into the brain
然後加水,
and then trigger the chemical reactions,
這個會膨脹的材料開始吸水,
you can get them to form those long chains,
聚合鏈移動開來,
right there inside the brain tissue.
生物分子隨著一起移動。
They're going to wind their way around biomolecules
就像在氣球上繪圖,
and between biomolecules,
然後將氣吹入氣球,
forming those complex webs
圖案相同,
that will allow you, eventually, to pull apart the molecules
但是墨水粒子的間距拉遠了,
from each other.
這就是我們所做的,不過是在三度空間裡。
And every time one of those little handles is around,
還有最後一技巧。
the polymer will bind to the handle, and that's exactly what we need
如你所見,
in order to pull the molecules apart from each other.
我們把所有的生物分子都標成褐色。
All right, the moment of truth.
這是因為他們看起來是一樣的。
We have to treat this specimen
雖然生物分子的組成原子相同,
with a chemical to kind of loosen up all the molecules from each other,
但順序卻可有差異。
and then, when we add water,
最後,我們還要使不同的生物分子 能用視覺辨別出來。
that swellable material is going to start absorbing the water,
用發光的染料 作為區分他們的小標籤。
the polymer chains will move apart,
將某一種生物分子染成藍色,
but now, the biomolecules will come along for the ride.
而另一種會染成紅色,等等。
And much like drawing a picture on a balloon,
這就是最後一步。
and then you blow up the balloon,
如此,我們就可以看到腦
the image is the same,
和各個分子,
but the ink particles have moved away from each other.
因為我們把分子拉得很開,
And that's what we've been able to do now, but in three dimensions.
所以可以分辨彼此。
There's one last trick.
成功的希望繫於 我們把不可見的變成可見的。
As you can see here,
我們把小而模糊的東西放大,
we've color-coded all the biomolecules brown.
大到它们看起来像是生命信息的星座圖。
That's because they all kind of look the same.
這是大概模樣的真正視頻。
Biomolecules are made out of the same atoms,
碟裡放著小小的一個腦-
but just in different orders.
其實是一小片腦。
So we need one last thing
我們已在裡頭注入聚合物,
in order to make them visible.
現在要加水。
We have to bring in little tags,
你眼前將看到的是-
with glowing dyes that will distinguish them.
以60倍速放映的視頻-
So one kind of biomolecule might get a blue color.
這小片腦組織將會脹大。
Another kind of biomolecule might get a red color.
它的體積將會脹成百倍或更大。
And so forth.
酷的是,因為聚合物是如此渺小,
And that's the final step.
我們將能均勻地分開生物分子。
Now we can look at something like a brain
是平整的擴張,
and look at the individual molecules,
資訊信息的組態不會失真,
because we've moved them far apart enough from each other
只是變成更容易被看得到。
that we can tell them apart.
取一實際的大腦神經組織-
So the hope here is that we can make the invisible visible.
例如與記憶有關的這一部分-
We can turn things that might seem small and obscure
拉近放大。
and blow them up
我們開始能看到實際的神經電路構造。
until they're like constellations of information about life.
也許有一天 我們也能讀出記憶的內容。
Here's an actual video of what it might look like.
也許我們能真切地看到 處理情緒的神經電路組織,
We have here a little brain in a dish --
腦內的神經怎樣連結,
a little piece of a brain, actually.
使我們成為我們。
We've infused the polymer in,
當然我們也希望
and now we're adding water.
能精準到分子層次地 查明腦病的問題。
What you'll see is that, right before your eyes --
試想,若我們真的深入到腦細胞裡,
this video is sped up about sixtyfold --
哇,並且查出是腦組織中 的這17個分子病變
this little piece of brain tissue is going to grow.
而產生如癲癇、
It can increase by a hundredfold or even more in volume.
帕金森氏症,
And the cool part is, because those polymers are so tiny,
或其他種類的異常?
we're separating biomolecules evenly from each other.
如果我們有系統地把變異列表,
It's a smooth expansion.
就可以當作治療的靶點。
We're not losing the configuration of the information.
我們可以針對那些標靶製藥。
We're just making it easier to see.
或許我們能集中精力 研究不一樣的大腦部位,
So now we can take actual brain circuitry --
以幫助世界各地罹患帕金森、癲癇 或其他病症的十億人口。
here's a piece of the brain involved with, for example, memory --
以幫助世界各地罹患帕金森、癲癇 或其他病症的十億人口。
and we can zoom in.
一些有趣的事已經發生了。
We can start to actually look at how circuits are configured.
在整個生物醫藥界還存在著
Maybe someday we could read out a memory.
這個擴張大腦的方法 可以助益的其他問題。
Maybe we could actually look at how circuits are configured
這是個實際來自 乳腺癌患者的活體檢視。
to process emotions,
若你檢視癌症、
how the actual wiring of our brain is organized
免疫系統、
in order to make us who we are.
老化、
And of course, we can pinpoint, hopefully,
發育 -
the actual problems in the brain at a molecular level.
這些過程都與 大規模的生物系統有關。
What if we could actually look into cells in the brain
當然,問題始於奈米級的分子,
and figure out, wow, here are the 17 molecules that have altered
和細胞、身體器官規律運行的機制。
in this brain tissue that has been undergoing epilepsy
我們正試圖釐清
or changing in Parkinson's disease
是否真能用這技術描繪出
or otherwise being altered?
各式各樣疾病中 基礎生命結構組成的脈絡。
If we get that systematic list of things that are going wrong,
我們能否精確地定位 腫瘤的分子變化,
those become our therapeutic targets.
以巧妙的方法追尋並發展出
We can build drugs that bind those.
能殲滅我們要殺死的惡細胞的藥品呢?
We can maybe aim energy at different parts of the brain
要知道,很多藥的風險非常高。
in order to help people with Parkinson's or epilepsy
有時候,使用它只能聽天由命。
or other conditions that affect over a billion people
我希望把大膽、高風險的藥品開發
around the world.
轉成更可靠的方式。
Now, something interesting has been happening.
如果仔細想想原先的登月,
It turns out that throughout biomedicine,
真正地登陸月球,
there are other problems that expansion might help with.
乃基於紮實的科學基礎。
This is an actual biopsy from a human breast cancer patient.
我們明瞭重力;
It turns out that if you look at cancers,
我們了解空氣動力學。
if you look at the immune system,
我們知道如何建造火箭。
if you look at aging, if you look at development --
科學的風險得到控制。
all these processes are involving large-scale biological systems.
至今登月仍是個偉大的工程壯舉。
But of course, the problems begin with those little nanoscale molecules,
但在醫學上, 我們未必了解所有的定律。
the machines that make the cells and the organs in our body tick.
我們有類似重力,
So what we're trying to do now is to figure out
類似空氣動力學的所有定律嗎?
if we can actually use this technology to map the building blocks of life
我認為,以我今天所談論的技術。
in a wide variety of diseases.
也許某天我們真的能夠 導出那些定律來。
Can we actually pinpoint the molecular changes in a tumor
我們能描繪、測繪生命系統的模型,
so that we can actually go after it in a smart way
找出克服疫病的方法。
and deliver drugs that might wipe out exactly the cells that we want to?
内人和我有兩個年幼的孩子,
You know, a lot of medicine is very high risk.
身為生物工程學家,我有個心願,
Sometimes, it's even guesswork.
希望孩子的生命能比我們的更美好。
My hope is we can actually turn what might be a high-risk moon shot
我希望我們能把生物學和醫學
into something that's more reliable.
由偶然和運氣支配的高風險努力,
If you think about the original moon shot,
轉向為技藝和辛勤工作的贏面,
where they actually landed on the moon,
那麼這將是一個巨大的進步。
it was based on solid science.
非常感謝。
We understood gravity;
(掌聲)
we understood aerodynamics.
We knew how to build rockets.
The science risk was under control.
It was still a great, great feat of engineering.
But in medicine, we don't necessarily have all the laws.
Do we have all the laws that are analogous to gravity,
that are analogous to aerodynamics?
I would argue that with technologies
like the kinds I'm talking about today,
maybe we can actually derive those.
We can map the patterns that occur in living systems,
and figure out how to overcome the diseases that plague us.
You know, my wife and I have two young kids,
and one of my hopes as a bioengineer is to make life better for them
than it currently is for us.
And my hope is, if we can turn biology and medicine
from these high-risk endeavors that are governed by chance and luck,
and make them things that we win by skill and hard work,
then that would be a great advance.
Thank you very much.
(Applause)