TED2011
Ed Boyden: A light switch for neurons
Ed Boyden: 為神經元安裝發光的配備
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Ed Boyden 告訴我們通過轉錄光敏感的蛋白基因進入腦細胞，以及植入的光纖，他可以選擇性地活化或去活化特定的神經元細胞。利用這突破性的大腦精控制技術，他成功地在老鼠身上，治癒類似創傷症候群和某些失明現象，以期不久的未來發展神經修復術、神經性義肢。會議的主持人Juan Enriquez 在演講結束後引導簡短的"問與答"談話單元。
Ed Boyden - Neuroengineer
Ed Boyden is a professor of biological engineering and brain and cognitive sciences at the MIT Media Lab and the MIT McGovern Institute. Full bio
Ed Boyden is a professor of biological engineering and brain and cognitive sciences at the MIT Media Lab and the MIT McGovern Institute. Full bio
Double-click the English transcript below to play the video.
00:15
Think about your day for a second.
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花一點時間想想你的一天
00:17
You woke up, felt fresh air on your face as you walked out the door,
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早上你醒來,走出家門口,感覺清新空氣輕拂過你的臉龐.
00:20
encountered new colleagues and had great discussions,
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巧遇你的一些新同事並和他們相談甚歡、
00:22
and felt in awe when you found something new.
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也為新奇的事物目瞪口呆.
00:24
But I bet there's something you didn't think about today --
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但我敢打賭,有一些東西你今天絕對沒想到-
00:26
something so close to home
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有些東西是如此貼近您,
00:28
that you probably don't think about it very often at all.
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以至於很多時候你根本忽略它的存在.
00:30
And that's that all the sensations, feelings,
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那就是你所有的一切喜怒哀樂,一切感覺,
00:32
decisions and actions
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所有的決定和行動
00:34
are mediated by the computer in your head
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都是被你腦袋裡的電腦所控制.
00:36
called the brain.
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也就是你的大腦.
00:38
Now the brain may not look like much from the outside --
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大腦看起來和它的外表大不同--
00:40
a couple pounds of pinkish-gray flesh,
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是幾英磅粉紅偏灰色的肉，
00:42
amorphous --
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無特定形狀--
00:44
but the last hundred years of neuroscience
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但近百年來神經科學的研究
00:46
have allowed us to zoom in on the brain,
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使我們能夠放大細究大腦，
00:48
and to see the intricacy of what lies within.
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看到大腦內的複雜構造.
00:50
And they've told us that this brain
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過往的研究告訴我們,
00:52
is an incredibly complicated circuit
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大腦是由數千億的神經元細胞
00:54
made out of hundreds of billions of cells called neurons.
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組造成一個令人難以置信的複雜電路.
00:58
Now unlike a human-designed computer,
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不同於人為設計的電腦,
01:01
where there's a fairly small number of different parts --
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只由相當少數的零件組成、
01:03
we know how they work, because we humans designed them --
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知道它們是如何運作,因為那是我們人類所設計的
01:06
the brain is made out of thousands of different kinds of cells,
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而大腦是由數千種不同種類的細胞架構的，
01:09
maybe tens of thousands.
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或許有數萬種吧。
01:11
They come in different shapes; they're made out of different molecules.
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它們各有不同的形狀,是由不同的分子組成，
01:13
And they project and connect to different brain regions,
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各自連結到大腦不同的區域。
01:16
and they also change different ways in different disease states.
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會隨著不同疾病狀態而呈現不同的改變.
01:19
Let's make it concrete.
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讓我更進一步解釋.
01:21
There's a class of cells,
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有一類細胞,是一種相當小的、
01:23
a fairly small cell, an inhibitory cell, that quiets its neighbors.
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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.
01:26
It's one of the cells that seems to be atrophied in disorders like schizophrenia.
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在精神分裂症患者腦部被發現萎縮的細胞種類之一.
01:30
It's called the basket cell.
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也就是所謂的籃狀細胞。
01:32
And this cell is one of the thousands of kinds of cell
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是我們正在學習瞭解中的
01:34
that we are learning about.
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數千種細胞其中之一.
01:36
New ones are being discovered everyday.
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還有更多新種類的細胞每天不斷地被發掘。
01:38
As just a second example:
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這是第二個例子：
01:40
these pyramidal cells, large cells,
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這些是錐體細胞,很大的細胞，
01:42
they can span a significant fraction of the brain.
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它們覆蓋大腦很大一部分.
01:44
They're excitatory.
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它們具有興奮性.
01:46
And these are some of the cells
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當癲癇患者發病時,
01:48
that might be overactive in disorders such as epilepsy.
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這類細胞都可能有些過度活躍.
01:51
Every one of these cells
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每一個腦神經細胞都像是
01:53
is an incredible electrical device.
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一種巧奪天工的電子器材。
01:56
They receive input from thousands of upstream partners
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它們接收上千個上游腦神經細胞傳來的訊息
01:58
and compute their own electrical outputs,
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規劃整理出自己的電子訊號,
02:01
which then, if they pass a certain threshold,
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然後等到訊號強過臨界點後,
02:03
will go to thousands of downstream partners.
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就會把訊號傳送給成千上萬的下游細胞.
02:05
And this process, which takes just a millisecond or so,
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而這個過程,只需要一毫秒左右，
02:08
happens thousands of times a minute
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而且每分鐘發生幾千次,
02:10
in every one of your 100 billion cells,
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同部在腦中1千億個腦細胞之間進行.
02:12
as long as you live
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只要你還活著,
02:14
and think and feel.
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有思想、有感覺都是如此.
02:17
So how are we going to figure out what this circuit does?
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那麼我們如何能確認這個電路各扮演什麼角色呢?
02:20
Ideally, we could go through the circuit
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理想的情況下,我們可以通過電路,
02:22
and turn these different kinds of cell on and off
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開啟或關閉這些不同類型的細胞
02:25
and see whether we could figure out
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看看我們能否找出
02:27
which ones contribute to certain functions
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它們各自特殊的功能,
02:29
and which ones go wrong in certain pathologies.
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或是當它們表現不正常時,所產生的那些病癥.
02:31
If we could activate cells, we could see what powers they can unleash,
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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、
02:34
what they can initiate and sustain.
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什麼功能是它們可以啟動或維持的.
02:36
If we could turn them off,
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如果我們可以將它們關閉，
02:38
then we could try and figure out what they're necessary for.
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我們就可以試著弄清楚他們對我們的必要性是什麼。
02:40
And that's a story I'm going to tell you about today.
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這就是今天我要告訴你的故事.
02:43
And honestly, where we've gone through over the last 11 years,
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真的,超過11年的研究經歷中,
02:46
through an attempt to find ways
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我們企圖尋找方法
02:48
of turning circuits and cells and parts and pathways of the brain
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去開關腦中的電路、細胞、任何小部份
02:50
on and off,
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和它們傳導的途徑.
02:52
both to understand the science
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不僅是為了滿足對科學的好奇心
02:54
and also to confront some of the issues
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也為了正視、解決人類現在
02:57
that face us all as humans.
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所面臨的一些問題.
03:00
Now before I tell you about the technology,
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現在，在我開始告訴你有關的科技之前,
03:03
the bad news is that a significant fraction of us in this room,
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我要告訴您一個壞消息,在這房間裡的不少人
03:06
if we live long enough,
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如果活的夠久
03:08
will encounter, perhaps, a brain disorder.
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他們的大腦就會有機會紊亂,不聽指揮.
03:10
Already, a billion people
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目前,約有十億人
03:12
have had some kind of brain disorder
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已經得了大腦病變，
03:14
that incapacitates them,
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以至他們癱瘓殘障。
03:16
and the numbers don't do it justice though.
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而數字無法真切代表出疾病的嚴重性.
03:18
These disorders -- schizophrenia, Alzheimer's,
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這些疾病-精神分裂症，阿茲海默老年癡呆症、
03:20
depression, addiction --
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憂鬱症，癮癖-
03:22
they not only steal our time to live, they change who we are.
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疾病不僅偷走我們的生命,還改變我們的人格
03:25
They take our identity and change our emotions
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不僅剽竊走我們的自我認知，還改變我們的情緒--
03:27
and change who we are as people.
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讓我們變成另一個人。
03:30
Now in the 20th century,
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20世紀的今天,
03:33
there was some hope that was generated
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由於治療腦部疾病的新藥品
03:36
through the development of pharmaceuticals for treating brain disorders,
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不斷被研發出來,為我們帶來一絲希望。
03:39
and while many drugs have been developed
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縱使已有許多藥物能
03:42
that can alleviate symptoms of brain disorders,
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緩解腦部疾病的的症狀，
03:44
practically none of them can be considered to be cured.
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幾乎沒有任何一種能被認為可以完全治癒腦部病變。
03:47
And part of that's because we're bathing the brain in the chemical.
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部分的原因是因為，服藥就好似把大腦浸泡在化學藥劑中
03:50
This elaborate circuit
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但是腦部內精心設計的電路是由
03:52
made out of thousands of different kinds of cell
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數千種不同的細胞組成
03:54
is being bathed in a substance.
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卻都被浸泡在同一種液體中.
03:56
That's also why, perhaps, most of the drugs, and not all, on the market
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這也是為什麼,市場上的許多藥物，並不是所有的，
03:58
can present some kind of serious side effect too.
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都會引起一些嚴重的副作用
04:01
Now some people have gotten some solace
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現在有些人把電極植入大腦中
04:04
from electrical stimulators that are implanted in the brain.
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刺激腦細胞來改善某些疾病的症狀.
04:07
And for Parkinson's disease,
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的確對於像帕金森氏症病患，
04:09
Cochlear implants,
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由耳蝸植入電極
04:11
these have indeed been able
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確實能夠帶來
04:13
to bring some kind of remedy
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某種程度的緩解,
04:15
to people with certain kinds of disorder.
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降低病人的身體殘礙的程度.
04:17
But electricity also will go in all directions --
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但是電流波會導向各個方向-
04:19
the path of least resistance,
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而且"專撿軟柿子捏"，傳向阻礙力最小的通路
04:21
which is where that phrase, in part, comes from.
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想來這也可能是這句名言的起源.
04:23
And it also will affect normal circuits as well as the abnormal ones that you want to fix.
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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.
04:26
So again, we're sent back to the idea
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所以問題回到
04:28
of ultra-precise control.
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極精密的控制上.
04:30
Could we dial-in information precisely where we want it to go?
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我們可不可能只把訊息傳送到標靶區呢?
04:34
So when I started in neuroscience 11 years ago,
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11年前,當我開始投入神經科學研究時，
04:38
I had trained as an electrical engineer and a physicist,
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我已受過電氣工程師和物理學家的訓練，
04:41
and the first thing I thought about was,
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所以首先我想到是，
04:43
if these neurons are electrical devices,
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如果這些神經元都是電氣設備的話，
04:45
all we need to do is to find some way
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我們須要做的只是找到某種方式,
04:47
of driving those electrical changes at a distance.
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在一定距離中傳送電流的變化到目的地.
04:49
If we could turn on the electricity in one cell,
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如果我們能使某一個細胞的電路被打開,
04:51
but not its neighbors,
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而不要干擾到它的鄰居們.
04:53
that would give us the tool we need to activate and shut down these different cells,
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這將讓我們有能力去活化或催眠不同的各種細胞,
04:56
figure out what they do and how they contribute
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進而瞭解它們的功能和對
04:58
to the networks in which they're embedded.
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整體腦神經系統的貢獻.
05:00
And also it would allow us to have the ultra-precise control we need
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同時也允許我們去執行極精密的控制,
05:02
in order to fix the circuit computations
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以修改腦中出了錯的
05:05
that have gone awry.
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電路運算.
05:07
Now how are we going to do that?
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那我們該怎麼做呢？
05:09
Well there are many molecules that exist in nature,
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自然界中存有很多小分子，
05:11
which are able to convert light into electricity.
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能夠將光能轉化成電能.
05:14
You can think of them as little proteins
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你可以把它們想像成類太陽能電池
05:16
that are like solar cells.
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的微小蛋白質。
05:18
If we can install these molecules in neurons somehow,
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如果我們將這些分子安裝在神經元內
05:21
then these neurons would become electrically drivable with light.
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那麼這些神經元將可以被光驅動
05:24
And their neighbors, which don't have the molecule, would not.
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而相鄰的神經細胞因為不具有這些轉化分子不會被活化.
05:27
There's one other magic trick you need to make this all happen,
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但是還需要一個神奇的技術配合一切才能成功.
05:29
and that's the ability to get light into the brain.
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那就是怎麼讓光進入腦中啊!
05:32
And to do that -- the brain doesn't feel pain -- you can put --
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並且要做到這-把光導入大腦而不引起疼痛--
05:35
taking advantage of all the effort
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我們運用腦中本有的
05:37
that's gone into the Internet and communications and so on --
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互聯網和其溝通能力等等功能-
05:39
optical fibers connected to lasers
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將光纖連接到雷射光
05:41
that you can use to activate, in animal models for example,
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使我們能夠精準的利用光束來啟動細胞
05:43
in pre-clinical studies,
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讓我們從臨床實驗前期的動物研究中
05:45
these neurons and to see what they do.
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知道各神經元扮演的角色.
05:47
So how do we do this?
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那麼,如何才能做到這一點？
05:49
Around 2004,
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大約在2004年,
05:51
in collaboration with Gerhard Nagel and Karl Deisseroth,
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在與吉爾 納格(Gerhard Nagel),和卡爾 得許窪多(Karl Deisseroth) 的合作中
05:53
this vision came to fruition.
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一切的構想終於開花結果
05:55
There's a certain alga that swims in the wild,
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我們發現一種野生的藻類
05:58
and it needs to navigate towards light
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它們會自動導航向光源游去,
06:00
in order to photosynthesize optimally.
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好讓自身的光合作用發揮到最佳狀態。
06:02
And it senses light with a little eye-spot,
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它感光系統是一個光感眼點,
06:04
which works not unlike how our eye works.
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跟我們的眼睛運作方法不同.
06:07
In its membrane, or its boundary,
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在眼點的外膜,或者其周圍，
06:09
it contains little proteins
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含有這些小蛋白質
06:12
that indeed can convert light into electricity.
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可以將光能轉化成電能。
06:15
So these molecules are called channelrhodopsins.
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這些分子被稱為:視紫質管道(channelrhodospins).
06:18
And each of these proteins acts just like that solar cell that I told you about.
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這些蛋白質就像我之前說的跟太陽能電池的功能一樣。
06:21
When blue light hits it, it opens up a little hole
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當藍光照射到它,它會開一個小洞，
06:24
and allows charged particles to enter the eye-spot,
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讓帶電粒子進入眼點。
06:26
and that allows this eye-spot to have an electrical signal
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然後眼點就能產生電子信號，
06:28
just like a solar cell charging up a battery.
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就像太陽能電池充電的道理一樣。
06:31
So what we need to do is to take these molecules
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因此,我們需要做的就是把這些分子，
06:33
and somehow install them in neurons.
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想辦法安裝在神經元中。
06:35
And because it's a protein,
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而且因為它是一種蛋白質，
06:37
it's encoded for in the DNA of this organism.
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而有關的DNA可以從藻類中被拆解出
06:40
So all we've got to do is take that DNA,
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所以我們要做的就是採取這段DNA，
06:42
put it into a gene therapy vector, like a virus,
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利用基因治療的運輸工具,像是病毒,
06:45
and put it into neurons.
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攜帶進腦神經元中.
06:48
So it turned out that this was a very productive time in gene therapy,
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剛巧那幾年基因治療正蓬葧發展，
06:51
and lots of viruses were coming along.
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多種不同的病毒都可被利用.
06:53
So this turned out to be very simple to do.
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我們發現原來這非常簡單容易
06:55
And early in the morning one day in the summer of 2004,
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在2004年夏天的一個早上,
06:58
we gave it a try, and it worked on the first try.
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是我們第一次嘗試這個實驗,而且一舉成功。
07:00
You take this DNA and you put it into a neuron.
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我們把DNA送進神經元中,
07:03
The neuron uses its natural protein-making machinery
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神經元則利用它自己本有的蛋白質製造裝置
07:06
to fabricate these little light-sensitive proteins
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編造出許多小感光蛋白質,
07:08
and install them all over the cell,
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很快的整個神經元細胞都佈滿了這種蛋白質,
07:10
like putting solar panels on a roof,
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就像在屋頂上安裝太陽能電池板一樣。
07:12
and the next thing you know,
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不用多久,
07:14
you have a neuron which can be activated with light.
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我們就有個能被光活化的神經元.
07:16
So this is very powerful.
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這是非常有價值的發現.
07:18
One of the tricks you have to do
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其中一個關鍵的技巧是必須要準確地
07:20
is to figure out how to deliver these genes to the cells that you want
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將感光DNA傳送到某些特定腦神經元中的，
07:22
and not all the other neighbors.
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而不是它們的左鄰右舍們。
07:24
And you can do that; you can tweak the viruses
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而我們可以這樣做:我們可以調整變換病毒
07:26
so they hit just some cells and not others.
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讓病毒只去襲擊某些特定的神經元。
07:28
And there's other genetic tricks you can play
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當然也可以利用其他生物基因工程的技術
07:30
in order to get light-activated cells.
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來獲得可被光活化細胞。
07:33
This field has now come to be known as optogenetics.
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這個領域現在被稱為光電遺傳學(optogenetics)。
07:37
And just as one example of the kind of thing you can do,
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舉個例子來說,你可以這樣做,
07:39
you can take a complex network,
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你可以在一個複雜的網絡系統中，
07:41
use one of these viruses to deliver the gene
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使用一種病毒去輸送基因到特定的一類細胞內
07:43
just to one kind of cell in this dense network.
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即使是在高密度的細胞社區裡也能達成.
07:46
And then when you shine light on the entire network,
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然後用光去照射整個細胞社區,
07:48
just that cell type will be activated.
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而只有那種具感光蛋白質的細胞會被活化.
07:50
So for example, lets sort of consider that basket cell I told you about earlier --
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好!讓我們用之前所提過的籃狀細胞為例子--
07:53
the one that's atrophied in schizophrenia
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就是那種具有抑制作用、精神分裂症者身上
07:55
and the one that is inhibitory.
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萎縮的細胞。
07:57
If we can deliver that gene to these cells --
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如果我們能夠將感光基因送到籃狀細胞內--
07:59
and they're not going to be altered by the expression of the gene, of course --
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當然前提是它們不會因感光基因而突變--
08:02
and then flash blue light over the entire brain network,
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-然後當我們用藍光照射所有腦細胞時,
08:05
just these cells are going to be driven.
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只有籃狀細胞會被驅動活化.
08:07
And when the light turns off, these cells go back to normal,
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把光線關閉後,籃狀細胞則會恢復正常，
08:09
so they don't seem to be averse against that.
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不會產生不良的副作用。
08:12
Not only can you use this to study what these cells do,
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我們不僅可利用這技術去研究這些細胞在做什麼，
08:14
what their power is in computing in the brain,
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它們在大腦內如何跟別種細胞協調互動，
08:16
but you can also use this to try to figure out --
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而且也可以試著利用這技術去找到如何:
08:18
well maybe we could jazz up the activity of these cells,
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讓已經萎縮的細胞興奮起來、
08:20
if indeed they're atrophied.
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手舞足蹈。
08:22
Now I want to tell you a couple of short stories
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現在我想告訴你一兩個有關於我們如何利用
08:24
about how we're using this,
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這項技術的故事,
08:26
both at the scientific, clinical and pre-clinical levels.
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都是應用在科學,臨床和臨床前的試驗.
08:29
One of the questions we've confronted
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我們所面臨的其中一個問題是:
08:31
is, what are the signals in the brain that mediate the sensation of reward?
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在腦中的什麼信號會挑起被嘉獎的感覺?
08:34
Because if you could find those,
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因為如果我們知道就可以利用
08:36
those would be some of the signals that could drive learning.
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這種信號去驅動細胞學習.
08:38
The brain will do more of whatever got that reward.
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讓大腦會竭盡所能去得到獎勵。
08:40
And also these are signals that go awry in disorders such as addiction.
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正因為這些信號出差錯,才導致如癮癖性疾病，。
08:43
So if we could figure out what cells they are,
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因此,如果我們能弄清楚這是哪些細胞,
08:45
we could maybe find new targets
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我們也許能找到新的標靶細胞，
08:47
for which drugs could be designed or screened against,
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以設計出或篩選出適合的藥物,去對抗這類疾病，
08:49
or maybe places where electrodes could be put in
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或者也可以為有非常嚴重殘疾的病患
08:51
for people who have very severe disability.
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在標靶細胞植入電極。
08:54
So to do that, we came up with a very simple paradigm
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要做到這一點,我們設計出一個非常簡單的模型，
08:56
in collaboration with the Fiorella group,
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並得到菲兒瑞拉(Fiorella)公司的贊助.
08:58
where one side of this little box,
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在這個小盒子的一邊,
09:00
if the animal goes there, the animal gets a pulse of light
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如果動物跑到那兒,會被一道光照到,
09:02
in order to make different cells in the brain sensitive to light.
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用來刺激各種不同對光敏感的腦部細胞.
09:04
So if these cells can mediate reward,
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所以如果這些細胞可以產生被獎勵的感覺,
09:06
the animal should go there more and more.
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那動物會越做越樂意.
09:08
And so that's what happens.
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事情就是這樣.
09:10
This animal's going to go to the right-hand side and poke his nose there,
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這隻動物跑到盒子的右手邊,然後用他的鼻子戳那地方
09:12
and he gets a flash of blue light every time he does that.
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每次它這樣做,藍光就會閃動照耀它一次.
09:14
And he'll do that hundreds and hundreds of times.
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他會一做再做,做上千百次.
09:16
These are the dopamine neurons,
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這是多巴胺神經元，
09:18
which some of you may have heard about, in some of the pleasure centers in the brain.
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在座的一些人可能已知道那是大腦的愉悅中樞之一.
09:20
Now we've shown that a brief activation of these
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您現在已看到我們這簡短的實驗
09:22
is enough, indeed, to drive learning.
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已可以鼓勵學習行為.
09:24
Now we can generalize the idea.
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現在我們再進一步,
09:26
Instead of one point in the brain,
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不是只影響大腦的一點,
09:28
we can devise devices that span the brain,
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我們可以設計一些儀器把這實驗應用到整個大腦,
09:30
that can deliver light into three-dimensional patterns --
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由這一組組的光纖傳送
09:32
arrays of optical fibers,
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三度空間(立體)的光束
09:34
each coupled to its own independent miniature light source.
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每個光纖都只連結到自己獨立的微型光源。
09:36
And then we can try to do things in vivo
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然後我們可以嘗試活體實驗,
09:38
that have only been done to-date in a dish --
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試驗一些目前為止只能在培養皿中的實驗--
09:41
like high-throughput screening throughout the entire brain
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像是對於整個大腦做全面高效率的篩選,
09:43
for the signals that can cause certain things to happen.
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瞭解到這某些腦波信號會導致哪些事情發生。
09:45
Or that could be good clinical targets
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或哪些可被應用到臨床治療上,
09:47
for treating brain disorders.
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來治療腦部疾病。
09:49
And one story I want to tell you about
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另一個我想告訴你的故事是，
09:51
is how can we find targets for treating post-traumatic stress disorder --
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我們如何找到治療創傷症候群的標靶細胞
09:54
a form of uncontrolled anxiety and fear.
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那一種無法控制的焦慮和恐懼的症候群。
09:57
And one of the things that we did
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首先我們採用一個被學術界接受的恐懼模式
09:59
was to adopt a very classical model of fear.
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﹣經典的恐懼制約(Classical fear conditioning).
10:02
This goes back to the Pavlovian days.
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那就要回到俄國帕弗洛夫(Pavlovian )時代.
10:05
It's called Pavlovian fear conditioning --
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所以也被稱做:帕弗洛夫的恐懼制約(Pavlovian fear conditioning)-
10:07
where a tone ends with a brief shock.
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在一陣聲響後,接著出現短暫電擊.
10:09
The shock isn't painful, but it's a little annoying.
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電擊並不會很疼痛但有點惱人。
10:11
And over time -- in this case, a mouse,
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然後一次又一次--在這個實驗中我們使用老鼠。
10:13
which is a good animal model, commonly used in such experiments --
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老鼠是一個很好的動物模型,常被用在此類實驗中。-
10:15
the animal learns to fear the tone.
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最後動物一聽到那種聲音就怕。
10:17
The animal will react by freezing,
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動物會作出呆僵的反應，
10:19
sort of like a deer in the headlights.
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像鹿在夜晚被車頭燈照到一樣--呆僵在那兒.
10:21
Now the question is, what targets in the brain can we find
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那現在的問題是:在腦中的那部份
10:24
that allow us to overcome this fear?
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能夠讓動物克服這種恐懼？
10:26
So what we do is we play that tone again
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我們於是放了這些跟恐懼有關的
10:28
after it's been associated with fear.
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聲音給聽了會害怕的動物聽,
10:30
But we activate targets in the brain, different ones,
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然後我們活化大腦中的標靶位,每次都不同,
10:32
using that optical fiber array I told you about in the previous slide,
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用我前面展示的幻燈片一樣的光纖儀器
10:35
in order to try and figure out which targets
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去試圖找出哪些標靶細胞
10:37
can cause the brain to overcome that memory of fear.
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希望能夠克服恐懼的記憶。
10:40
And so this brief video
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這個簡短的片段
10:42
shows you one of these targets that we're working on now.
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展示了我們現在所試探過的其中一個標靶位，
10:44
This is an area in the prefrontal cortex,
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這區是在額葉前部皮質，
10:46
a region where we can use cognition to try to overcome aversive emotional states.
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這個區域讓我們可以用認知努力克服厭惡的情感。
10:49
And the animal's going to hear a tone -- and a flash of light occurred there.
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動物將聽到聲音,然後看見閃光.
10:51
There's no audio on this, but you can see the animal's freezing.
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這閃光並沒有聲音,但你可以看到動物僵立凍結在那兒,
10:53
This tone used to mean bad news.
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這聲音以前是用來警告老鼠壞消息的信號。
10:55
And there's a little clock in the lower left-hand corner,
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在左下方的角落有一個小時鐘，
10:57
so you can see the animal is about two minutes into this.
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所以我們可知動物大約僵立兩分鐘。
11:00
And now this next clip
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下一個片段是在
11:02
is just eight minutes later.
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八分鐘後,
11:04
And the same tone is going to play, and the light is going to flash again.
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相同聲音和緊接的的閃光
11:07
Okay, there it goes. Right now.
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好,開始了。現在。
11:10
And now you can see, just 10 minutes into the experiment,
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看!才只有10分鐘後的實驗，
11:13
that we've equipped the brain by photoactivating this area
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我們已經用光源活化這部份的腦細胞
11:16
to overcome the expression
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幫助動物克服這種
11:18
of this fear memory.
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恐懼的記憶。
11:20
Now over the last couple of years, we've gone back to the tree of life
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在過去的幾年裡,我們一再檢驗大自然的生命樹，
11:23
because we wanted to find ways to turn circuits in the brain off.
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因為我們想要找出把大腦中的電路關掉的方法。
11:26
If we could do that, this could be extremely powerful.
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如果我們能做到這一點,這作用可大了。
11:29
If you can delete cells just for a few milliseconds or seconds,
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如果你能讓細胞停擺即使只要幾毫秒或幾秒，
11:32
you can figure out what necessary role they play
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你就可以找出他它們在大腦電路中
11:34
in the circuits in which they're embedded.
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是承擔什麼必要的作用，
11:36
And we've now surveyed organisms from all over the tree of life --
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我們仔細調查生命樹上的物種-除了動物之外的
11:38
every kingdom of life except for animals, we see slightly differently.
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每一個生物,只要我們發現它們有一點任何差異。
11:41
And we found all sorts of molecules, they're called halorhodopsins or archaerhodopsins,
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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)
11:44
that respond to green and yellow light.
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能對綠色和黃色光有反應。
11:46
And they do the opposite thing of the molecule I told you about before
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它們跟我剛剛跟你提起的會感藍光的分子,
11:48
with the blue light activator channelrhodopsin.
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單胞藻感光紫紅質蛋白質(channelrhodopsin)的作用相反。
11:52
Let's give an example of where we think this is going to go.
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讓我舉一個例子來告訴你們,我們如何應用這技術。
11:55
Consider, for example, a condition like epilepsy,
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比如說癲癇這個例子,
11:58
where the brain is overactive.
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癲癇是因大腦某部份過度活躍。
12:00
Now if drugs fail in epileptic treatment,
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如果癲癇藥物治療的策略失敗,
12:02
one of the strategies is to remove part of the brain.
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那其他治療選舉方案之一是:切除一部份的大腦。
12:04
But that's obviously irreversible, and there could be side effects.
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但是這顯然不可逆的，而且有可能有副作用。
12:06
What if we could just turn off that brain for a brief amount of time,
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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,
12:09
until the seizure dies away,
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直到癲癇症狀消失殆盡為止，
12:12
and cause the brain to be restored to its initial state --
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並讓大腦恢復到初始狀態-
12:15
sort of like a dynamical system that's being coaxed down into a stable state.
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有點像把一個將暴動的系統哄騙推回穩定的狀態一樣。
12:18
So this animation just tries to explain this concept
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這個動畫只是試圖解釋
12:21
where we made these cells sensitive to being turned off with light,
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我們利用光源來關閉催眠腦細胞的概念。
12:23
and we beam light in,
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當我們把光源射出,
12:25
and just for the time it takes to shut down a seizure,
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時間僅僅是足夠終止癲癇發作。
12:27
we're hoping to be able to turn it off.
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我們希望實驗能夠成功。
12:29
And so we don't have data to show you on this front,
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現在我們還沒有這個方面數據可以展示給大眾，
12:31
but we're very excited about this.
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但我們對此感到非常興奮。
12:33
Now I want to close on one story,
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現在我要用一個故事來結束我的演講，
12:35
which we think is another possibility --
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那就是我們認為這技術還有其他用途--
12:37
which is that maybe these molecules, if you can do ultra-precise control,
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如果能做到超精確的控制,這些感光蛋白質
12:39
can be used in the brain itself
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可用於腦中使腦本身
12:41
to make a new kind of prosthetic, an optical prosthetic.
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形成的一種新型義肢,光學義肢。
12:44
I already told you that electrical stimulators are not uncommon.
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就像我已經告訴過你們的,電極刺激器並不是很普遍。
12:47
Seventy-five thousand people have Parkinson's deep-brain stimulators implanted.
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只有75000個帕金森病患植入深腦刺激器，
12:50
Maybe 100,000 people have Cochlear implants,
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也許有100,000人在耳蝸中植入刺激器
12:52
which allow them to hear.
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好讓他們能聽到聲音。
12:54
There's another thing, which is you've got to get these genes into cells.
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另一件事是，就是你得讓這些基因移植進細胞內。
12:57
And new hope in gene therapy has been developed
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而這基因治療的新希望已被開發出，
13:00
because viruses like the adeno-associated virus,
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一些病毒像是腺病毒家族（adeno-associated virus),
13:02
which probably most of us around this room have,
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在這個房間裡大多數人可能都感染過,
13:04
and it doesn't have any symptoms,
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但沒有任何症狀，
13:06
which have been used in hundreds of patients
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這種病毒已被用來傳送基因
13:08
to deliver genes into the brain or the body.
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到數百個病人的大腦或身體內。
13:10
And so far, there have not been serious adverse events
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到目前為止,沒有發現任何有關該病毒
13:12
associated with the virus.
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的嚴重不良反應。
13:14
There's one last elephant in the room, the proteins themselves,
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沒錯!這技術有一個不能忽視的大隱憂,有關蛋白質本身,
13:17
which come from algae and bacteria and fungi,
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感光蛋白質是從藻類、細菌、真菌
13:19
and all over the tree of life.
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或生命樹上其他不同的物種上取出的,
13:21
Most of us don't have fungi or algae in our brains,
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大多數人沒有真菌或藻類(的DNA)在我們的大腦中，
13:23
so what is our brain going to do if we put that in?
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如果移植蛋白質進入大腦中,那究竟大腦會有什麼反應?
13:25
Are the cells going to tolerate it? Will the immune system react?
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腦細胞會容忍它們嗎？免疫系統會有什麼反應呢？
13:27
In its early days -- these have not been done on humans yet --
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在這渾沌的初始階段--還未有人體實驗過--
13:29
but we're working on a variety of studies
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但是，我們正努力做各種研究,
13:31
to try and examine this,
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試圖評估這可能的副作用。
13:33
and so far we haven't seen overt reactions of any severity
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目前為止,我們還沒有明顯看到因為這些分子
13:36
to these molecules
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所引起的任何嚴重不良反應
13:38
or to the illumination of the brain with light.
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而對腦照光也一樣沒有任何嚴重的的不良反應。
13:41
So it's early days, to be upfront, but we're excited about it.
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當然這只是初期的研究,但即使是如此,我們還是很興奮。
13:44
I wanted to close with one story,
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我想用一個故事來結束演講，
13:46
which we think could potentially
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我們認為這技術具有
13:48
be a clinical application.
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臨床應用的價值。
13:50
Now there are many forms of blindness
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我們知道失明有很多種原因.
13:52
where the photoreceptors,
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像是眼內的感光細胞消失，
13:54
our light sensors that are in the back of our eye, are gone.
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也就是在我們的眼球後面的光接受器不見了。
13:57
And the retina, of course, is a complex structure.
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我們的視網膜當然是一個複雜的結構。
13:59
Now let's zoom in on it here, so we can see it in more detail.
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讓我們放大它的結構圖,仔細研究一下。
14:01
The photoreceptor cells are shown here at the top,
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照片中感光細胞在頂部，
14:04
and then the signals that are detected by the photoreceptors
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感光細胞接收到光線,然後一層一層
14:06
are transformed by various computations
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轉變成各種不同信號直到
14:08
until finally that layer of cells at the bottom, the ganglion cells,
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到達視網膜的最後一層底部的細胞:神經節細胞，
14:11
relay the information to the brain,
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然後將信息轉遞給大腦，
14:13
where we see that as perception.
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轉換成視覺認知。
14:15
In many forms of blindness, like retinitis pigmentosa,
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有很多原因導致失明,如視網膜色素變性，
14:18
or macular degeneration,
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或黃斑變性，
14:20
the photoreceptor cells have atrophied or been destroyed.
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感光細胞萎縮或者根本破壞殆盡。
14:23
Now how could you repair this?
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那我們怎麼才能改善修復呢？
14:25
It's not even clear that a drug could cause this to be restored,
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沒有明確證據指出藥物可以治療修復這些症狀，
14:28
because there's nothing for the drug to bind to.
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因為藥物很難停留在那兒(沒特效藥)。
14:30
On the other hand, light can still get into the eye.
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但是,光線仍然可以射入眼睛。
14:32
The eye is still transparent and you can get light in.
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光線仍然經由眼睛透入接觸視網膜。
14:35
So what if we could just take these channelrhodopsins and other molecules
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所以如果我們能將單胞藻感光紫紅質蛋白質
14:38
and install them on some of these other spare cells
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或其他感光分子安裝在其他健康的細胞上,
14:40
and convert them into little cameras.
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把它們轉換成一台台小相機。
14:42
And because there's so many of these cells in the eye,
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而且因為眼部有很多的這種細胞存在,
14:44
potentially, they could be very high-resolution cameras.
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理論上,它們可以成為高清晰度攝像機。
14:47
So this is some work that we're doing.
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這就是我們正在進行的工作之一。
14:49
It's being led by one of our collaborators,
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我們的合夥人之一,艾倫 (Alan Horsager)
14:51
Alan Horsager at USC,
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在南加州大學正領導這個計劃，
14:53
and being sought to be commercialized by a start-up company Eos Neuroscience,
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也正在一家由美國國立衛生研究院提供經費的
14:56
which is funded by the NIH.
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創投公司(Eos Neuroscience）的協助下將其技術產業化
14:58
And what you see here is a mouse trying to solve a maze.
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現在你可以看見這隻老鼠試圖在迷宮裡找出口。
15:00
It's a six-arm maze. And there's a bit of water in the maze
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在這六臂迷宮裡被倒入一些流動的水
15:02
to motivate the mouse to move, or he'll just sit there.
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來激勵老鼠移動，否則牠就停在某處不動。
15:04
And the goal, of course, of this maze
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這迷宮設計的目的
15:06
is to get out of the water and go to a little platform
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是讓水會從出口處流出到一個
15:08
that's under the lit top port.
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安裝光源的平臺.
15:10
Now mice are smart, so this mouse solves the maze eventually,
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老鼠是很聰明的,這隻老鼠最終找到出口了,
15:13
but he does a brute-force search.
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但牠可是努力搜索才達成的.
15:15
He's swimming down every avenue until he finally gets to the platform.
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他試過每一條途徑最後才到達有點燈的平臺。
15:18
So he's not using vision to do it.
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由此可知,它不是用視力來游出迷宮。
15:20
These different mice are different mutations
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這些不同的老鼠經由不同的突變而失明,
15:22
that recapitulate different kinds of blindness that affect humans.
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每隻老鼠各代表人類失明的不同種原因.
15:25
And so we're being careful in trying to look at these different models
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所以我們小心試圖尋找在這些不同的失明模型中
15:28
so we come up with a generalized approach.
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一個通用的方法去解決失明問題。
15:30
So how are we going to solve this?
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那麼我們該如何去執行呢？
15:32
We're going to do exactly what we outlined in the previous slide.
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我們要照著前一張幻燈片所展示的藍圖一樣去做。
15:34
We're going to take these blue light photosensors
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我們要將這些對藍光感光的蛋白質
15:36
and install them on a layer of cells
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安裝在眼球最後面的視網膜
15:38
in the middle of the retina in the back of the eye
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的其中一層細胞上面，
15:41
and convert them into a camera --
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並將其轉換成一台照相機。
15:43
just like installing solar cells all over those neurons
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就像將太陽能電池佈滿在這些神經元上，
15:45
to make them light sensitive.
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使它們對光敏感。
15:47
Light is converted to electricity on them.
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讓這些細胞將光能轉換為電能。
15:49
So this mouse was blind a couple weeks before this experiment
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所以即使這隻老鼠在此實驗前幾個星期就瞎了,
15:52
and received one dose of this photosensitive molecule in a virus.
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只接受過一次病毒攜帶的感光分子的治療。
15:55
And now you can see, the animal can indeed avoid walls
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現在你可以看到，老鼠能避過牆
15:57
and go to this little platform
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找到有亮光的小平臺，
15:59
and make cognitive use of its eyes again.
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再一次的使用牠的視覺訊息。
16:02
And to point out the power of this:
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為了顯現出這實驗的功力:
16:04
these animals are able to get to that platform
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這些動物游出迷宮的速度還跟
16:06
just as fast as animals that have seen their entire lives.
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沒瞎的動物一樣快。
16:08
So this pre-clinical study, I think,
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雖然這是臨床前研究，
16:10
bodes hope for the kinds of things
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但我相信這是個好預兆
16:12
we're hoping to do in the future.
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我們希望未來能成功應用到人體上。
16:14
To close, I want to point out that we're also exploring
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最後,我要指出的是我們正發展的一種
16:17
new business models for this new field of neurotechnology.
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新的商業模式,雖然這神經科學的技術
16:19
We're developing these tools,
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是我們研發的,
16:21
but we share them freely with hundreds of groups all over the world,
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但我們願意讓世界各地的不同組織自由分享這技術,
16:23
so people can study and try to treat different disorders.
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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。
16:25
And our hope is that, by figuring out brain circuits
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我們的希望是:經由瞭解大腦的電路系統,再借助
16:28
at a level of abstraction that lets us repair them and engineer them,
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精簡化來修復和建構神經網絡,
16:31
we can take some of these intractable disorders that I told you about earlier,
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讓那些我先前提到的一些棘手的疑難雜症，
16:34
practically none of which are cured,
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這些在21世紀幾乎無法治愈的疾病，
16:36
and in the 21st century make them history.
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從此被存封在歷史印記中。
16:38
Thank you.
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謝謝。
16:40
(Applause)
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（鼓掌）
16:53
Juan Enriquez: So some of the stuff is a little dense.
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Juan Enriquez:您的演講有些部份有一點深奧。
16:56
(Laughter)
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（眾笑）
16:58
But the implications
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但重點是
17:00
of being able to control seizures or epilepsy
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能夠利用光來控制痙癵或癲癇發作,
17:03
with light instead of drugs,
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而不是用傳統的藥物控制,
17:05
and being able to target those specifically
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並且能夠精確找到標靶位(對症下光)
17:08
is a first step.
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是第一步
17:10
The second thing that I think I heard you say
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第二件事是我想我聽到您說
17:12
is you can now control the brain in two colors,
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您現在已經可以用兩種顏色的光來控制大腦
17:15
like an on/off switch.
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像電燈開關一樣。
17:17
Ed Boyden: That's right.
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Ed Boyden:沒錯!
17:19
JE: Which makes every impulse going through the brain a binary code.
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JE:也就是刺激大腦的訊號已進階至二進制代碼。
17:22
EB: Right, yeah.
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EB:對，沒錯。
17:24
So with blue light, we can drive information, and it's in the form of a one.
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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"。
17:27
And by turning things off, it's more or less a zero.
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如果燈光黯淡時,大致可把它歸類為"0"。
17:29
So our hope is to eventually build brain coprocessors
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我們最終的希望是想建立大腦輔助處理器
17:31
that work with the brain
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來幫大腦工作,
17:33
so we can augment functions in people with disabilities.
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所以我們可以增加其功能來幫助殘疾人士。
17:36
JE: And in theory, that means that,
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JE:這意味著在理論上,
17:38
as a mouse feels, smells,
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不管是任何有關老鼠的的感覺,嗅覺，
17:40
hears, touches,
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聽覺,觸覺，
17:42
you can model it out as a string of ones and zeros.
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你可以模擬出來一連串的"1"和 "0"。
17:45
EB: Sure, yeah. We're hoping to use this as a way of testing
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EB:當然,是的。我們希望借此方式,
17:47
what neural codes can drive certain behaviors
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去測試瞭解是什麼神經代碼可以驅動某些行為,
17:49
and certain thoughts and certain feelings,
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某些想法和某些感受，
17:51
and use that to understand more about the brain.
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並利用它進一步來瞭解大腦。
17:54
JE: Does that mean that some day you could download memories
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JE:這是否意味著有一天,你可以下載回憶,
17:57
and maybe upload them?
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也許也可再上傳回去大腦嗎？
17:59
EB: Well that's something we're starting to work on very hard.
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EB:這件事情我們已經開始了,
18:01
We're now working on some work
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目前正朝幾個方面努力中,
18:03
where we're trying to tile the brain with recording elements too.
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我們也正在嘗試在大腦每個角落安置記錄器。
18:05
So we can record information and then drive information back in --
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因此,我們可以收錄大腦信息,然後驅動信息返回大腦-
18:08
sort of computing what the brain needs
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來計算什麼是大腦所須要的,
18:10
in order to augment its information processing.
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以便來增強其信息處理。
18:12
JE: Well, that might change a couple things. Thank you. (EB: Thank you.)
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JE:嗯,這可能會對我們的世界有所改變或影響。謝謝。 (EB:謝謝。)
18:15
(Applause)
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（鼓掌）
ABOUT THE SPEAKER
Ed Boyden - NeuroengineerEd Boyden is a professor of biological engineering and brain and cognitive sciences at the MIT Media Lab and the MIT McGovern Institute.
Why you should listen
Ed Boyden leads the Synthetic Neurobiology Group, which develops tools for analyzing and repairing complex biological systems such as the brain. His group applies these tools in a systematic way in order to reveal ground truth scientific understandings of biological systems, which in turn reveal radical new approaches for curing diseases and repairing disabilities. These technologies include expansion microscopy, which enables complex biological systems to be imaged with nanoscale precision, and optogenetic tools, which enable the activation and silencing of neural activity with light (TED Talk: A light switch for neurons). Boyden also co-directs the MIT Center for Neurobiological Engineering, which aims to develop new tools to accelerate neuroscience progress.
Amongst other recognitions, Boyden has received the Breakthrough Prize in Life Sciences (2016), the BBVA Foundation Frontiers of Knowledge Award (2015), the Carnegie Prize in Mind and Brain Sciences (2015), the Jacob Heskel Gabbay Award (2013), the Grete Lundbeck Brain Prize (2013) and the NIH Director's Pioneer Award (2013). He was also named to the World Economic Forum Young Scientist list (2013) and the Technology Review World's "Top 35 Innovators under Age 35" list (2006). His group has hosted hundreds of visitors to learn how to use new biotechnologies and spun out several companies to bring inventions out of his lab and into the world. Boyden received his Ph.D. in neurosciences from Stanford University as a Hertz Fellow, where he discovered that the molecular mechanisms used to store a memory are determined by the content to be learned. Before that, he received three degrees in electrical engineering, computer science and physics from MIT. He has contributed to over 300 peer-reviewed papers, current or pending patents and articles, and he has given over 300 invited talks on his group's work.
Ed Boyden | Speaker | TED.com