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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)

Hello, everybody.

大家好。

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B1 中級 中文 TED 分子 聚合物 大腦 生物 神經元

TED】艾德-博伊登:研究大腦看不見的祕密的新方法(A new way to study the brain's invisible secrets | Ed Boyden)。 (【TED】Ed Boyden: A new way to study the brain's invisible secrets (A new way to study the brain's invisible secrets | Ed Boyden))

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