Ed Boyden: A light switch for neurons

譯者: Inder Peng(彭) 審譯者: Shirley Hsieh

花一點時間想想你的一天

Think about your day for a second.

You woke up, felt fresh air on your face as you walked out the door,

早上你醒來,走出家門口,感覺清新空氣輕拂過你的臉龐.

encountered new colleagues and had great discussions

巧遇你的一些新同事並和他們相談甚歡、

也為新奇的事物目瞪口呆.

and felt in awe when you found something new.

但我敢打賭,有一些東西你今天絕對沒想到-

But I bet there's something you didn't think about today,

有些東西是如此貼近您,

something so close to home,

以至於很多時候你根本忽略它的存在.

you probably don't think about it very often at all.

那就是你所有的一切喜怒哀樂,一切感覺,

And that's that all those sensations, feelings, decisions and actions

所有的決定和行動

都是被你腦袋裡的電腦所控制.

are mediated by the computer in your head

也就是你的大腦.

called your brain.

Now, the brain may not look like much from the outside --

大腦看起來和它的外表大不同--

是幾英磅粉紅偏灰色的肉，

a couple pounds of pinkish-gray flesh,

無特定形狀--

amorphous.

But the last 100 years of neuroscience have allowed us to zoom in on the brain

但近百年來神經科學的研究

使我們能夠放大細究大腦，

and to see the intricacy of what lies within.

看到大腦內的複雜構造.

And they've told us that this brain is an incredibly complicated circuit

過往的研究告訴我們,

大腦是由數千億的神經元細胞

made out of hundreds of billions of cells called neurons.

組造成一個令人難以置信的複雜電路.

Now, unlike a human-designed computer,

不同於人為設計的電腦,

where there's a fairly small number of different parts,

只由相當少數的零件組成、

知道它們是如何運作,因為那是我們人類所設計的

and we know how they work because we humans designed them,

the brain is made out of thousands of different kinds of cells,

而大腦是由數千種不同種類的細胞架構的，

或許有數萬種吧。

maybe tens of thousands.

They come in different shapes; they're made out of different molecules;

它們各有不同的形狀,是由不同的分子組成，

各自連結到大腦不同的區域。

they project and connect to different brain regions.

會隨著不同疾病狀態而呈現不同的改變.

They also change in different ways in different disease states.

讓我更進一步解釋.

Let's make it concrete.

There's a class of cells,

有一類細胞,是一種相當小的、

a fairly small cell, an inhibitory cell, that quiets its neighbors.

具抑制作用的細胞,專門控制它的鄰居,使大家安靜下來守紀律.

在精神分裂症患者腦部被發現萎縮的細胞種類之一.

It's one of the cells that seems to be atrophied

in disorders like schizophrenia.

It's called the basket cell.

也就是所謂的籃狀細胞。

And this cell is one of the thousands of kinds of cell

是我們正在學習瞭解中的

數千種細胞其中之一.

that we're learning about.

New ones are being discovered every day.

還有更多新種類的細胞每天不斷地被發掘。

這是第二個例子：

As just a second example:

these pyramidal cells, large cells, can span a significant fraction

這些是錐體細胞,很大的細胞，

它們覆蓋大腦很大一部分.

of the brain.

它們具有興奮性.

They're excitatory.

當癲癇患者發病時,

And these are some of the cells that might be overactive

這類細胞都可能有些過度活躍.

in disorders such as epilepsy.

每一個腦神經細胞都像是

Every one of these cells is an incredible electrical device.

一種巧奪天工的電子器材。

They receive inputs from thousands of upstream partners

它們接收上千個上游腦神經細胞傳來的訊息

規劃整理出自己的電子訊號,

and compute their own electrical outputs,

which then, if they pass a certain threshold,

然後等到訊號強過臨界點後,

就會把訊號傳送給成千上萬的下游細胞.

will go to thousands of downstream partners.

而這個過程,只需要一毫秒左右，

And this process, which takes just a millisecond or so,

happens thousands of times a minute in every one of your 100 billion cells,

而且每分鐘發生幾千次,

同部在腦中1千億個腦細胞之間進行.

as long as you live and think and feel.

只要你還活著,

有思想、有感覺都是如此.

So how are we going to figure out what this circuit does?

那麼我們如何能確認這個電路各扮演什麼角色呢?

理想的情況下,我們可以通過電路,

Ideally, we could go through this circuit

開啟或關閉這些不同類型的細胞

and turn these different kinds of cell on and off

and see whether we could figure out

看看我們能否找出

which ones contribute to certain functions

它們各自特殊的功能,

and which ones go wrong in certain pathologies.

或是當它們表現不正常時,所產生的那些病癥.

如果我們可以啟動某些細胞,我們就知道它們可以發揮什麼能力、

If we could activate cells, we could see what powers they can unleash,

什麼功能是它們可以啟動或維持的.

what they can initiate and sustain.

如果我們可以將它們關閉，

If we could turn them off,

then we could try and figure out what they're necessary for.

我們就可以試著弄清楚他們對我們的必要性是什麼。

這就是今天我要告訴你的故事.

And that's the story I'm going to tell you about today.

真的,超過11年的研究經歷中,

And honestly, where we've gone through over the last 11 years,

我們企圖尋找方法

through an attempt to find ways

of turning circuits and cells and parts and pathways of the brain

去開關腦中的電路、細胞、任何小部份

和它們傳導的途徑.

on and off,

不僅是為了滿足對科學的好奇心

both to understand the science

and also to confront some of the issues that face us all as humans.

也為了正視、解決人類現在

所面臨的一些問題.

Now, before I tell you about the technology,

現在，在我開始告訴你有關的科技之前,

the bad news is that a significant fraction of us in this room,

我要告訴您一個壞消息,在這房間裡的不少人

如果活的夠久

if we live long enough,

will encounter, perhaps, a brain disorder.

他們的大腦就會有機會紊亂,不聽指揮.

目前,約有十億人

Already, a billion people have had some kind of brain disorder

已經得了大腦病變，

以至他們癱瘓殘障。

that incapacitates them.

The numbers don't do it justice, though.

而數字無法真切代表出疾病的嚴重性.

These disorders -- schizophrenia, Alzheimer's,

這些疾病-精神分裂症，阿茲海默老年癡呆症、

憂鬱症，癮癖-

depression, addiction --

they not only steal away our time to live,

疾病不僅偷走我們的生命,還改變我們的人格

they change who we are.

They take our identity and change our emotions

不僅剽竊走我們的自我認知，還改變我們的情緒--

and change who we are as people.

讓我們變成另一個人。

Now, in the 20th century,

20世紀的今天,

由於治療腦部疾病的新藥品

there was some hope that was generated

through the development of pharmaceuticals for treating brain disorders.

不斷被研發出來,為我們帶來一絲希望。

縱使已有許多藥物能

And while many drugs have been developed

that can alleviate symptoms of brain disorders,

緩解腦部疾病的的症狀，

幾乎沒有任何一種能被認為可以完全治癒腦部病變。

practically none of them can be considered to be cured.

In part, that's because, if you think about it,

部分的原因是因為，服藥就好似把大腦浸泡在化學藥劑中

we're bathing the brain in a chemical --

但是腦部內精心設計的電路是由

this elaborate circuit, made of thousands of different kinds of cell --

數千種不同的細胞組成

卻都被浸泡在同一種液體中.

is being bathed in a substance.

That's also why most of the drugs, not all, on the market

這也是為什麼,市場上的許多藥物，並不是所有的，

都會引起一些嚴重的副作用

can present some kind of serious side effect too.

現在有些人把電極植入大腦中

Now some people have gotten some solace from electrical stimulators

刺激腦細胞來改善某些疾病的症狀.

that are implanted in the brain,

for Parkinson's disease or cochlear implants.

的確對於像帕金森氏症病患，

由耳蝸植入電極

These have indeed been able to bring some kind of remedy

確實能夠帶來

某種程度的緩解,

to people with certain kinds of disorders.

降低病人的身體殘礙的程度.

But electricity also will go in all directions --

但是電流波會導向各個方向-

the path of least resistance --

而且"專撿軟柿子捏"，傳向阻礙力最小的通路

which is where that phrase, in part, comes from,

想來這也可能是這句名言的起源.

and will also affect normal circuits,

電流也有可能影響到正常的電路,不只在我們想修復的不正常處.

as well as the abnormal ones you want to fix.

所以問題回到

So again, we're sent back to the idea of ultraprecise control:

極精密的控制上.

Could we dial in information precisely where we want it to go?

我們可不可能只把訊息傳送到標靶區呢?

11年前,當我開始投入神經科學研究時，

So, when I started in neuroscience 11 years ago --

I had trained as an electrical engineer and a physicist --

我已受過電氣工程師和物理學家的訓練，

the first thing I thought about was,

所以首先我想到是，

if these neurons are electrical devices,

如果這些神經元都是電氣設備的話，

all we need to do is to find some way of driving those electrical changes

我們須要做的只是找到某種方式,

在一定距離中傳送電流的變化到目的地.

at a distance.

如果我們能使某一個細胞的電路被打開,

If we could turn on the electricity in one cell but not its neighbors,

而不要干擾到它的鄰居們.

that'd give us the tool to activate and shut down these different cells

這將讓我們有能力去活化或催眠不同的各種細胞,

進而瞭解它們的功能和對

to figure out what they do

and how they contribute to the networks in which they're embedded.

整體腦神經系統的貢獻.

同時也允許我們去執行極精密的控制,

It would also allow us to have the ultraprecise control we need

以修改腦中出了錯的

to fix the circuit computations that have gone awry.

電路運算.

Now, how are we going to do that?

那我們該怎麼做呢？

Well, there are many molecules that exist in nature

自然界中存有很多小分子，

能夠將光能轉化成電能.

which are able to convert light into electricity.

你可以把它們想像成類太陽能電池

You can think of them as little proteins that are like solar cells.

的微小蛋白質。

If we install these molecules in neurons somehow,

如果我們將這些分子安裝在神經元內

then these neurons would become electrically drivable with light,

那麼這些神經元將可以被光驅動

and their neighbors, which don't have this molecule, would not.

而相鄰的神經細胞因為不具有這些轉化分子不會被活化.

There's one other magic trick you need to make this happen:

但是還需要一個神奇的技術配合一切才能成功.

那就是怎麼讓光進入腦中啊!

the ability to get light into the brain.

The brain doesn't feel pain.

並且要做到這-把光導入大腦而不引起疼痛--

Taking advantage of all the effort

我們運用腦中本有的

that's gone into the internet, telecommunications, etc.,

互聯網和其溝通能力等等功能-

you can put optical fibers connected to lasers

將光纖連接到雷射光

to activate -- in animal models, for example, in preclinical studies --

使我們能夠精準的利用光束來啟動細胞

讓我們從臨床實驗前期的動物研究中

these neurons and see what they do.

知道各神經元扮演的角色.

那麼,如何才能做到這一點？

So how do we do this?

Around 2004, in collaboration with Georg Nagel and Karl Deisseroth,

大約在2004年,

在與吉爾 納格(Gerhard Nagel),和卡爾 得許窪多(Karl Deisseroth) 的合作中

this vision came to fruition.

一切的構想終於開花結果

There's a certain alga that swims in the wild,

我們發現一種野生的藻類

and it needs to navigate towards light in order to photosynthesize optimally.

它們會自動導航向光源游去,

好讓自身的光合作用發揮到最佳狀態。

And it senses light with a little eyespot,

它感光系統是一個光感眼點,

which works not unlike how our eye works.

跟我們的眼睛運作方法不同.

In its membrane, or its boundary,

在眼點的外膜,或者其周圍，

it contains little proteins

含有這些小蛋白質

可以將光能轉化成電能。

that indeed can convert light into electricity.

這些分子被稱為:視紫質管道(channelrhodospins).

These molecules are called channelrhodopsins.

And each of these proteins acts just like that solar cell

這些蛋白質就像我之前說的跟太陽能電池的功能一樣。

that I told you about.

當藍光照射到它,它會開一個小洞，

When blue light hits it,

it opens a little hole and allows charged particles to enter the eyespot;

讓帶電粒子進入眼點。

然後眼點就能產生電子信號，

that allows this eyespot to have an electrical signal,

就像太陽能電池充電的道理一樣。

just like a solar cell charging a battery.

So what we need to do is take these molecules

因此,我們需要做的就是把這些分子，

想辦法安裝在神經元中。

and somehow install them in neurons.

And because it's a protein,

而且因為它是一種蛋白質，

it's encoded for in the DNA of this organism.

而有關的DNA可以從藻類中被拆解出

So all we've got to do is take that DNA,

所以我們要做的就是採取這段DNA，

put it into a gene therapy vector, like a virus,

利用基因治療的運輸工具,像是病毒,

and put it into neurons.

攜帶進腦神經元中.

And this was a very productive time in gene therapy,

剛巧那幾年基因治療正蓬葧發展，

and lots of viruses were coming along,

多種不同的病毒都可被利用.

so this turned out to be fairly simple.

我們發現原來這非常簡單容易

Early in the morning one day in the summer of 2004,

在2004年夏天的一個早上,

we gave it a try, and it worked on the first try.

是我們第一次嘗試這個實驗,而且一舉成功。

我們把DNA送進神經元中,

You take this DNA and put it into the neuron.

The neuron uses its natural protein-making machinery

神經元則利用它自己本有的蛋白質製造裝置

to fabricate these little light-sensitive proteins

編造出許多小感光蛋白質,

很快的整個神經元細胞都佈滿了這種蛋白質,

and install them all over the cell, like putting solar panels on a roof.

就像在屋頂上安裝太陽能電池板一樣。

And the next thing you know,

不用多久,

you have a neuron which can be activated with light.

我們就有個能被光活化的神經元.

這是非常有價值的發現.

So this is very powerful.

One of the tricks you have to do is figure out how to deliver these genes

其中一個關鍵的技巧是必須要準確地

將感光DNA傳送到某些特定腦神經元中的，

to the cells you want and not all the other neighbors.

而不是它們的左鄰右舍們。

而我們可以這樣做:我們可以調整變換病毒

And you can do that;

you can tweak the viruses so they hit some cells and not others.

讓病毒只去襲擊某些特定的神經元。

當然也可以利用其他生物基因工程的技術

And there's other genetic tricks you can play

來獲得可被光活化細胞。

in order to get light-activated cells.

這個領域現在被稱為光電遺傳學(optogenetics)。

This field has now come to be known as "optogenetics."

And just as one example of the kind of thing you can do,

舉個例子來說,你可以這樣做,

你可以在一個複雜的網絡系統中，

you can take a complex network,

use one of these viruses to deliver the gene

使用一種病毒去輸送基因到特定的一類細胞內

即使是在高密度的細胞社區裡也能達成.

just to one kind of cell in this dense network.

And then when you shine light on the entire network,

然後用光去照射整個細胞社區,

just that cell type will be activated.

而只有那種具感光蛋白質的細胞會被活化.

For example, let's consider that basket cell I told you about earlier,

好!讓我們用之前所提過的籃狀細胞為例子--

就是那種具有抑制作用、精神分裂症者身上

the one that's atrophied in schizophrenia

萎縮的細胞。

and the one that is inhibitory.

如果我們能夠將感光基因送到籃狀細胞內--

If we can deliver that gene to these cells --

當然前提是它們不會因感光基因而突變--

they won't be altered by the expression of the gene, of course --

-然後當我們用藍光照射所有腦細胞時,

then flash blue light over the entire brain network,

just these cells are going to be driven.

只有籃狀細胞會被驅動活化.

把光線關閉後,籃狀細胞則會恢復正常，

And when the light turns off, these cells go back to normal;

不會產生不良的副作用。

there don't seem to be adverse events.

Not only can you study what these cells do,

我們不僅可利用這技術去研究這些細胞在做什麼，

what their power is in computing in the brain,

它們在大腦內如何跟別種細胞協調互動，

而且也可以試著利用這技術去找到如何:

you can also use this to try to figure out

讓已經萎縮的細胞興奮起來、

if we could jazz up the activity of these cells

手舞足蹈。

if indeed, they're atrophied.

I want to tell you some short stories about how we're using this

現在我想告訴你一兩個有關於我們如何利用

這項技術的故事,

both at the scientific clinical and preclinical levels.

都是應用在科學,臨床和臨床前的試驗.

One of the questions that we've confronted is:

我們所面臨的其中一個問題是:

What signals in the brain mediate the sensation of reward?

在腦中的什麼信號會挑起被嘉獎的感覺?

Because if you could find those,

因為如果我們知道就可以利用

those would be some of the signals that could drive learning;

這種信號去驅動細胞學習.

讓大腦會竭盡所能去得到獎勵。

the brain will do more of what got that reward.

正因為這些信號出差錯,才導致如癮癖性疾病，。

These are also signals that go awry in disorders such as addiction.

因此,如果我們能弄清楚這是哪些細胞,

So if we could figure out what cells they are, we could maybe find new targets

我們也許能找到新的標靶細胞，

以設計出或篩選出適合的藥物,去對抗這類疾病，

for which drugs can be designed or screened against

或者也可以為有非常嚴重殘疾的病患

or maybe places where electrodes could be put in

在標靶細胞植入電極。

for people who have severe disability.

To do that, we came up with a very simple paradigm

要做到這一點,我們設計出一個非常簡單的模型，

並得到菲兒瑞拉(Fiorella)公司的贊助.

in collaboration with the Fiorillo group,

在這個小盒子的一邊,

where, if the animal goes to one side of this little box,

如果動物跑到那兒,會被一道光照到,

it gets a pulse of light.

用來刺激各種不同對光敏感的腦部細胞.

And we'll make different cells in the brain sensitive to light.

所以如果這些細胞可以產生被獎勵的感覺,

If these cells can mediate reward, the animal should go there more and more.

那動物會越做越樂意.

事情就是這樣.

And that's what happens.

The animal goes to the right-hand side and pokes his nose there

這隻動物跑到盒子的右手邊,然後用他的鼻子戳那地方

每次它這樣做,藍光就會閃動照耀它一次.

and gets a flash of blue light every time he does it.

他會一做再做,做上千百次.

He'll do that hundreds of times.

這是多巴胺神經元，

These are the dopamine neurons,

在座的一些人可能已知道那是大腦的愉悅中樞之一.

in some of the pleasure centers in the brain.

您現在已看到我們這簡短的實驗

We've shown that a brief activation of these is enough to drive learning.

已可以鼓勵學習行為.

現在我們再進一步,

Now we can generalize the idea.

不是只影響大腦的一點,

Instead of one point in the brain, we can devise devices that span the brain,

我們可以設計一些儀器把這實驗應用到整個大腦,

由這一組組的光纖傳送

that can deliver light into three-dimensional patterns --

三度空間(立體)的光束

arrays of optical fibers,

每個光纖都只連結到自己獨立的微型光源。

each coupled to its own independent miniature light source.

然後我們可以嘗試活體實驗,

Then we can try to do things in vivo

試驗一些目前為止只能在培養皿中的實驗--

that have only been done to date in a dish,

like high-throughput screening throughout the entire brain

像是對於整個大腦做全面高效率的篩選,

瞭解到這某些腦波信號會導致哪些事情發生。

for the signals that can cause certain things to happen

或哪些可被應用到臨床治療上,

or that could be good clinical targets for treating brain disorders.

來治療腦部疾病。

另一個我想告訴你的故事是，

One story I want to tell you about is:

我們如何找到治療創傷症候群的標靶細胞

How can we find targets for treating post-traumatic stress disorder,

那一種無法控制的焦慮和恐懼的症候群。

a form of uncontrolled anxiety and fear?

首先我們採用一個被學術界接受的恐懼模式

One of the things that we did was to adopt a very classical model of fear.

﹣經典的恐懼制約(Classical fear conditioning).

This goes back to the Pavlovian days.

那就要回到俄國帕弗洛夫(Pavlovian )時代.

It's called Pavlovian fear conditioning, where a tone ends with a brief shock.

所以也被稱做:帕弗洛夫的恐懼制約(Pavlovian fear conditioning)-

在一陣聲響後,接著出現短暫電擊.

The shock isn't painful, but it's a little annoying.

電擊並不會很疼痛但有點惱人。

然後一次又一次--在這個實驗中我們使用老鼠。

And over time -- in this case, a mouse,

老鼠是一個很好的動物模型,常被用在此類實驗中。-

which is a good animal model, commonly used in such experiments --

最後動物一聽到那種聲音就怕。

the animal learns to fear the tone.

動物會作出呆僵的反應，

It will react by freezing, sort of like a deer in the headlights.

像鹿在夜晚被車頭燈照到一樣--呆僵在那兒.

Now the question is: What targets in the brain can we find

那現在的問題是:在腦中的那部份

that allow us to overcome this fear?

能夠讓動物克服這種恐懼？

我們於是放了這些跟恐懼有關的

So we play that tone again, after it's been associated with fear.

聲音給聽了會害怕的動物聽,

然後我們活化大腦中的標靶位,每次都不同,

But we activate different targets in the brain,

用我前面展示的幻燈片一樣的光纖儀器

using that optical fiber array I showed on the previous slide,

去試圖找出哪些標靶細胞

in order to try and figure out

which targets can cause the brain to overcome that memory of fear.

希望能夠克服恐懼的記憶。

這個簡短的片段

This brief video shows you one of these targets

展示了我們現在所試探過的其中一個標靶位，

that we're working on now.

This is an area in the prefrontal cortex, a region where we can use cognition

這區是在額葉前部皮質，

這個區域讓我們可以用認知努力克服厭惡的情感。

to try to overcome aversive emotional states.

動物將聽到聲音,然後看見閃光.

The animal hears a tone. A flash of light occurs.

這閃光並沒有聲音,但你可以看到動物僵立凍結在那兒,

There's no audio, but you see that the animal freezes --

這聲音以前是用來警告老鼠壞消息的信號。

the tone used to mean bad news.

在左下方的角落有一個小時鐘，

There's a little clock in the lower left-hand corner.

所以我們可知動物大約僵立兩分鐘。

You can see the animal is about two minutes into this.

下一個片段是在

This next clip is just eight minutes later.

八分鐘後,

And the same tone is going to play, and the light is going to flash again.

相同聲音和緊接的的閃光

好,開始了。現在。

OK, there it goes. Right ... now.

看!才只有10分鐘後的實驗，

And now you can see, just 10 minutes into the experiment,

我們已經用光源活化這部份的腦細胞

that we've equipped the brain, by photoactivating this area,

幫助動物克服這種

to overcome the expression of this fear memory.

恐懼的記憶。

在過去的幾年裡,我們一再檢驗大自然的生命樹，

Over the last couple years, we've gone back to the tree of life,

因為我們想要找出把大腦中的電路關掉的方法。

because we wanted to find ways to turn circuits in the brain off.

如果我們能做到這一點,這作用可大了。

If we could do that, this could be extremely powerful.

If you can delete cells for a few milliseconds or seconds,

如果你能讓細胞停擺即使只要幾毫秒或幾秒，

you can figure out what role they play in the circuits in which they're embedded.

你就可以找出他它們在大腦電路中

是承擔什麼必要的作用，

We surveyed organisms from all over the tree of life --

我們仔細調查生命樹上的物種-除了動物之外的

每一個生物,只要我們發現它們有一點任何差異。

every kingdom of life but animals; we see slightly differently.

我們發現多種不同的分子，所謂感光紫紅質蛋白質(halorhodopsins)或一種古細胞感光蛋白質(archaerhodopsins)

We found molecules called halorhodopsins or archaerhodopsins,

能對綠色和黃色光有反應。

that respond to green and yellow light.

And they do the opposite of the molecule I told you about before,

它們跟我剛剛跟你提起的會感藍光的分子,

單胞藻感光紫紅質蛋白質(channelrhodopsin)的作用相反。

with the blue light activator, channelrhodopsin.

Let's give an example of where we think this is going to go.

讓我舉一個例子來告訴你們,我們如何應用這技術。

Consider, for example, a condition like epilepsy,

比如說癲癇這個例子,

where the brain is overactive.

癲癇是因大腦某部份過度活躍。

Now, if drugs fail in epileptic treatment,

如果癲癇藥物治療的策略失敗,

one of the strategies is to remove part of the brain,

那其他治療選舉方案之一是:切除一部份的大腦。

但是這顯然不可逆的，而且有可能有副作用。

but that's irreversible, and there could be side effects.

如果我們可以只關閉大腦不正常那部份一會兒,很短暫的時間,

What if we could just turn off that brain for the brief amount of time

直到癲癇症狀消失殆盡為止，

until the seizure dies away,

and cause the brain to be restored to its initial state,

並讓大腦恢復到初始狀態-

like a dynamical system that's being coaxed down into a stable state?

有點像把一個將暴動的系統哄騙推回穩定的狀態一樣。

這個動畫只是試圖解釋

This animation tries to explain this concept

where we made these cells sensitive to being turned off with light,

我們利用光源來關閉催眠腦細胞的概念。

當我們把光源射出,

and we beam light in,

and just for the time it takes to shut down a seizure,

時間僅僅是足夠終止癲癇發作。

我們希望實驗能夠成功。

we're hoping to be able to turn it off.

現在我們還沒有這個方面數據可以展示給大眾，

We don't have data to show you on this front,

但我們對此感到非常興奮。

but we're very excited about this.

I want to close on one story, which we think is another possibility,

現在我要用一個故事來結束我的演講，

那就是我們認為這技術還有其他用途--

which is that maybe these molecules, if you can do ultraprecise control,

如果能做到超精確的控制,這些感光蛋白質

可用於腦中使腦本身

can be used in the brain itself to make a new kind of prosthetic,

形成的一種新型義肢,光學義肢。

an optical prosthetic.

就像我已經告訴過你們的,電極刺激器並不是很普遍。

I already told you that electrical stimulators are not uncommon.

只有75000個帕金森病患植入深腦刺激器，

Seventy-five thousand people

have Parkinson's deep-brain stimulators implanted,

也許有100,000人在耳蝸中植入刺激器

maybe 100,000 people have cochlear implants, which allow them to hear.

好讓他們能聽到聲音。

另一件事是，就是你得讓這些基因移植進細胞內。

Another thing -- you've got to get these genes into cells.

而這基因治療的新希望已被開發出，

A new hope in gene therapy has been developed,

because viruses like the adeno-associated virus --

一些病毒像是腺病毒家族（adeno-associated virus),

在這個房間裡大多數人可能都感染過,

which probably most of us around this room have;

但沒有任何症狀，

it doesn't have any symptoms --

這種病毒已被用來傳送基因

have been used in hundreds of patients

to deliver genes into the brain or the body.

到數百個病人的大腦或身體內。

And so far, there have not been serious adverse events

到目前為止,沒有發現任何有關該病毒

的嚴重不良反應。

associated with the virus.

There's one last elephant in the room: the proteins themselves,

沒錯!這技術有一個不能忽視的大隱憂,有關蛋白質本身,

which come from algae, bacteria and funguses

感光蛋白質是從藻類、細菌、真菌

and all over the tree of life.

或生命樹上其他不同的物種上取出的,

Most of us don't have funguses or algae in our brains,

大多數人沒有真菌或藻類(的DNA)在我們的大腦中，

如果移植蛋白質進入大腦中,那究竟大腦會有什麼反應?

so what will our brain do if we put that in?

腦細胞會容忍它們嗎？免疫系統會有什麼反應呢？

Will the cells tolerate it? Will the immune system react?

在這渾沌的初始階段--還未有人體實驗過--

It's early -- these haven't been done in humans yet --

但是，我們正努力做各種研究,

but we're working on a variety of studies to examine this.

試圖評估這可能的副作用。

目前為止,我們還沒有明顯看到因為這些分子

So far, we haven't seen overt reactions of any severity

所引起的任何嚴重不良反應

to these molecules

or to the illumination of the brain with light.

而對腦照光也一樣沒有任何嚴重的的不良反應。

當然這只是初期的研究,但即使是如此,我們還是很興奮。

So it's early days, to be upfront, but we're excited about it.

我想用一個故事來結束演講，

I wanted to close with one story,

which we think could potentially be a clinical application.

我們認為這技術具有

臨床應用的價值。

Now, there are many forms of blindness

我們知道失明有很多種原因.

像是眼內的感光細胞消失，

where the photoreceptors -- light sensors in the back of our eye --

也就是在我們的眼球後面的光接受器不見了。

are gone.

And the retina is a complex structure.

我們的視網膜當然是一個複雜的結構。

Let's zoom in on it so we can see it in more detail.

讓我們放大它的結構圖,仔細研究一下。

照片中感光細胞在頂部，

The photoreceptor cells are shown here at the top.

The signals that are detected by the photoreceptors are transformed

感光細胞接收到光線,然後一層一層

轉變成各種不同信號直到

via various computations

到達視網膜的最後一層底部的細胞:神經節細胞，

until finally, the layer of cells at the bottom, the ganglion cells,

然後將信息轉遞給大腦，

relay the information to the brain,

轉換成視覺認知。

where we see that as perception.

有很多原因導致失明,如視網膜色素變性，

In many forms of blindness, like retinitis pigmentosa

or macular degeneration,

或黃斑變性，

the photoreceptor cells have atrophied or been destroyed.

感光細胞萎縮或者根本破壞殆盡。

Now, how could you repair this?

那我們怎麼才能改善修復呢？

It's not even clear that a drug could cause this to be restored,

沒有明確證據指出藥物可以治療修復這些症狀，

since there's nothing for the drug to bind to.

因為藥物很難停留在那兒(沒特效藥)。

On the other hand, light can still get into the eye.

但是,光線仍然可以射入眼睛。

光線仍然經由眼睛透入接觸視網膜。

The eye is still transparent and you can get light in.

所以如果我們能將單胞藻感光紫紅質蛋白質

So what if we could take these channelrhodopsins and other molecules

或其他感光分子安裝在其他健康的細胞上,

and install them on some of these other spared cells

把它們轉換成一台台小相機。

and convert them into little cameras?

而且因為眼部有很多的這種細胞存在,

And because there are so many of these cells in the eye,

理論上,它們可以成為高清晰度攝像機。

potentially, they could be very high-resolution cameras.

這就是我們正在進行的工作之一。

This is some work that we're doing,

我們的合夥人之一,艾倫 (Alan Horsager)

led by one of our collaborators, Alan Horsager at USC,

在南加州大學正領導這個計劃，

and being sought to be commercialized by a start-up company, Eos Neuroscience,

也正在一家由美國國立衛生研究院提供經費的

創投公司(Eos Neuroscience）的協助下將其技術產業化

which is funded by the NIH.

What you see here is a mouse trying to solve a six-arm maze.

現在你可以看見這隻老鼠試圖在迷宮裡找出口。

在這六臂迷宮裡被倒入一些流動的水

There's a bit of water to motivate the mouse to move or he'll just sit there.

來激勵老鼠移動，否則牠就停在某處不動。

這迷宮設計的目的

The goal of this maze is to get out of the water

是讓水會從出口處流出到一個

and go to a little platform that's under the lit top port.

安裝光源的平臺.

老鼠是很聰明的,這隻老鼠最終找到出口了,

Mice are smart, so this one solves the maze eventually,

but he does a brute-force search.

但牠可是努力搜索才達成的.

He's swimming down every avenue until he finally gets to the platform.

他試過每一條途徑最後才到達有點燈的平臺。

He's not using vision to do it.

由此可知,它不是用視力來游出迷宮。

These different mice are different mutations

這些不同的老鼠經由不同的突變而失明,

每隻老鼠各代表人類失明的不同種原因.

that recapitulate different kinds of blindness that affect humans.

所以我們小心試圖尋找在這些不同的失明模型中

So we're being careful in trying to look at these different models

一個通用的方法去解決失明問題。

so we come up with a generalized approach.

那麼我們該如何去執行呢？

So how can we solve this?

我們要照著前一張幻燈片所展示的藍圖一樣去做。

We'll do exactly what we outlined in the previous slide.

我們要將這些對藍光感光的蛋白質

We'll take these blue light photo sensors

安裝在眼球最後面的視網膜

and install them onto a layer of cells

的其中一層細胞上面，

in the middle of the retina in the back of the eye

and convert them into a camera --

並將其轉換成一台照相機。

just like installing solar cells all over those neurons

就像將太陽能電池佈滿在這些神經元上，

使它們對光敏感。

to make them light-sensitive.

Light is converted to electricity on them.

讓這些細胞將光能轉換為電能。

So this mouse was blind a couple weeks before this experiment

所以即使這隻老鼠在此實驗前幾個星期就瞎了,

and received one dose of this photosensitive molecule on a virus.

只接受過一次病毒攜帶的感光分子的治療。

現在你可以看到，老鼠能避過牆

And now you can see, the animal can indeed avoid walls

找到有亮光的小平臺，

and go to this little platform

再一次的使用牠的視覺訊息。

and make cognitive use of its eyes again.

為了顯現出這實驗的功力:

And to point out the power of this:

這些動物游出迷宮的速度還跟

these animals can get to that platform

just as fast as animals that have seen their entire lives.

沒瞎的動物一樣快。

雖然這是臨床前研究，

So this preclinical study, I think, bodes hope

但我相信這是個好預兆

for the kinds of things we're hoping to do in the future.

我們希望未來能成功應用到人體上。

最後,我要指出的是我們正發展的一種

We're also exploring new business models for this new field of neurotechnology.

新的商業模式,雖然這神經科學的技術

是我們研發的,

We're developing tools and sharing them freely

但我們願意讓世界各地的不同組織自由分享這技術,

with hundreds of groups all over the world

這樣更多人可以深入研究並有機會造福治療各種不同疾病。

for them to study and try to treat different disorders.

我們的希望是:經由瞭解大腦的電路系統,再借助

Our hope is that by figuring out brain circuits

精簡化來修復和建構神經網絡,

at a level of abstraction that lets us repair them and engineer them,

讓那些我先前提到的一些棘手的疑難雜症，

we can take some of these intractable disorders I mentioned earlier,

這些在21世紀幾乎無法治愈的疾病，

practically none of which are cured,

從此被存封在歷史印記中。

and in the 21st century, make them history.

謝謝。

Thank you.

(Applause)

（鼓掌）

Juan Enriquez: So some of this stuff is a little dense.

Juan Enriquez:您的演講有些部份有一點深奧。

(Laughter)

（眾笑）

但重點是

But the implications of being able to control seizures or epilepsy

能夠利用光來控制痙癵或癲癇發作,

with light instead of drugs

而不是用傳統的藥物控制,

and being able to target those specifically

並且能夠精確找到標靶位(對症下光)

is a first step.

是第一步

The second thing that I think I heard you say

第二件事是我想我聽到您說

is you can now control the brain in two colors,

您現在已經可以用兩種顏色的光來控制大腦

像電燈開關一樣。

like an on-off switch.

Ed Boyden:沒錯!

Ed Boyden: That's right.

JE:也就是刺激大腦的訊號已進階至二進制代碼。

JE: Which makes every impulse going through the brain a binary code.

EB:對，沒錯。

EB: Right.

With blue light, we can drive information, and it's in the form of a one.

當藍光亮時,我們可以驅動神經元傳播信號,所以可被認為是"1"。

如果燈光黯淡時,大致可把它歸類為"0"。

And by turning things off, it's more or less a zero.

我們最終的希望是想建立大腦輔助處理器

Our hope is to eventually build brain coprocessors that work with the brain

來幫大腦工作,

所以我們可以增加其功能來幫助殘疾人士。

so we can augment functions in people with disabilities.

JE: And in theory, that means that, as a mouse feels, smells, hears, touches,

JE:這意味著在理論上,

不管是任何有關老鼠的的感覺,嗅覺，

聽覺,觸覺，

you can model it out as a string of ones and zeros.

你可以模擬出來一連串的"1"和 "0"。

EB: Yeah. We're hoping to use this as a way of testing

EB:當然,是的。我們希望借此方式,

去測試瞭解是什麼神經代碼可以驅動某些行為,

what neural codes can drive certain behaviors

某些想法和某些感受，

and certain thoughts and certain feelings

並利用它進一步來瞭解大腦。

and use that to understand more about the brain.

JE: Does that mean that someday you could download memories

JE:這是否意味著有一天,你可以下載回憶,

and maybe upload them?

也許也可再上傳回去大腦嗎？

EB: That's something we're starting to work on very hard.

EB:這件事情我們已經開始了,

目前正朝幾個方面努力中,

We're now working on trying to tile the brain with recording elements, too,

我們也正在嘗試在大腦每個角落安置記錄器。

so we can record information and then drive information back in --

因此,我們可以收錄大腦信息,然後驅動信息返回大腦-

sort of computing what the brain needs

來計算什麼是大腦所須要的,

in order to augment its information processing.

以便來增強其信息處理。

JE: Well, that might change a couple things. Thank you.

JE:嗯,這可能會對我們的世界有所改變或影響。謝謝。 (EB:謝謝。)

EB: Thank you.

（鼓掌）

(Applause)