TED2011
Ed Boyden: A light switch for neurons
艾德·博伊登：神经的光控开关
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艾德·博伊登展示了他如何用植入性光纤选择性地激活或冻结某一部分神经，那就是将感光性蛋白质基因植入脑细胞。通过这种史无前例的控制技术，他用来治疗患有创伤后应激障碍和某些程度失明的老鼠。相信在不久的将来，就会出现人造神经。会议主持人Juan Enriquez将开展简短的提问与回答。
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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花点时间回想你的一天
00:17
You woke up, felt fresh air on your face as you walked out the door,
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你清晨醒来，走出房门的时候感受到清风拂过你的脸颊
00:20
encountered new colleagues and had great discussions,
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巧遇新的同事，与其谈天说地
00:22
and felt in awe when you found something new.
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当你发现新事物时则心怀敬畏
00:24
But I bet there's something you didn't think about today --
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但我确定今天会有些你没有想到的事情--
00:26
something so close to home
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一些如此贴近生活的
00:28
that you probably don't think about it very often at all.
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但你可能完全忽略的事情。
00:30
And that's that all the sensations, feelings,
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其中包含的所有的感知能力，感情
00:32
decisions and actions
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决策和行动
00:34
are mediated by the computer in your head
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都直接受控于在你头部的电脑
00:36
called the brain.
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叫做大脑的部分。
00:38
Now the brain may not look like much from the outside --
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大脑看可不像外表看起来那样--
00:40
a couple pounds of pinkish-gray flesh,
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只是几磅桃灰色的肉块，
00:42
amorphous --
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非结晶的固体--
00:44
but the last hundred years of neuroscience
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但是经过上百年积淀的神经学
00:46
have allowed us to zoom in on the brain,
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让我们能进一步的研究大脑，
00:48
and to see the intricacy of what lies within.
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并了解大脑的错综复杂。
00:50
And they've told us that this brain
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研究告诉我们大脑
00:52
is an incredibly complicated circuit
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是由上千亿个神经元细胞
00:54
made out of hundreds of billions of cells called neurons.
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组成的难以想象的复杂电路
00:58
Now unlike a human-designed computer,
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不同于人类设计的电脑
01:01
where there's a fairly small number of different parts --
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那种由较少的不同元件组成的--
01:03
we know how they work, because we humans designed them --
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我们了解它们如何工作，因为是我们人类设计出了它们--
01:06
the brain is made out of thousands of different kinds of cells,
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大脑由上千种不同的细胞组成
01:09
maybe tens of thousands.
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也许是上万种
01:11
They come in different shapes; they're made out of different molecules.
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它们分化成不同的形状；它们分泌出不同分子；
01:13
And they project and connect to different brain regions,
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它们延伸并连接大脑的不同地区。
01:16
and they also change different ways in different disease states.
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它们对于不同的疾病也表现出不同的方式。
01:19
Let's make it concrete.
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说的具体一点
01:21
There's a class of cells,
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有一种细胞，
01:23
a fairly small cell, an inhibitory cell, that quiets its neighbors.
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一种较小的，抑制性细胞，能够抑制周围细胞。
01:26
It's one of the cells that seems to be atrophied in disorders like schizophrenia.
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这是一种其萎缩能导致类似神经分裂症状的细胞
01:30
It's called the basket cell.
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这叫做篮细胞
01:32
And this cell is one of the thousands of kinds of cell
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它是我们正在研究的成千上万种细胞
01:34
that we are learning about.
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中的一种
01:36
New ones are being discovered everyday.
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每天都会有发现新型的细胞。
01:38
As just a second example:
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第二个例子：
01:40
these pyramidal cells, large cells,
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这些锥体细胞，大型的细胞
01:42
they can span a significant fraction of the brain.
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他们分布在大脑的很多部位
01:44
They're excitatory.
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它们易受刺激。
01:46
And these are some of the cells
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其中的一部分细胞
01:48
that might be overactive in disorders such as epilepsy.
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可能会因过度的活动而导致疾病类似癫症。
01:51
Every one of these cells
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这些细胞中每一个
01:53
is an incredible electrical device.
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都是一个神奇的电子元件
01:56
They receive input from thousands of upstream partners
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它们从上游细胞接收信息
01:58
and compute their own electrical outputs,
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然后编辑出它们自己的输出信息，
02:01
which then, if they pass a certain threshold,
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然后，如果这些信息通过了特定的界限，
02:03
will go to thousands of downstream partners.
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就会传递到下游上千个细胞那里。
02:05
And this process, which takes just a millisecond or so,
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这个仅仅会花费一毫秒左右的时间的过程
02:08
happens thousands of times a minute
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在你身上的每个1万亿个细胞中
02:10
in every one of your 100 billion cells,
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每分钟发生上千次，
02:12
as long as you live
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只要你活着
02:14
and think and feel.
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思考着感受着。
02:17
So how are we going to figure out what this circuit does?
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我们将如何解释这些回路的运作呢？
02:20
Ideally, we could go through the circuit
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主观上，我们能刺激这些回路
02:22
and turn these different kinds of cell on and off
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把不同种细胞反复刺激
02:25
and see whether we could figure out
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看我们是否能了解
02:27
which ones contribute to certain functions
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哪种细胞作用于特定的功用
02:29
and which ones go wrong in certain pathologies.
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哪种细胞出错会引起特定的病理
02:31
If we could activate cells, we could see what powers they can unleash,
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如果我们能激活细胞，我们就能了解它们能释放哪种能量
02:34
what they can initiate and sustain.
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他们是如何启动和维持的.
02:36
If we could turn them off,
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如果我们能把它们全部切断
02:38
then we could try and figure out what they're necessary for.
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我们就可能弄清楚它们的必要性。
02:40
And that's a story I'm going to tell you about today.
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这就是今天我要告诉大家的故事。
02:43
And honestly, where we've gone through over the last 11 years,
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老实说，
02:46
through an attempt to find ways
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我们试图寻找方法
02:48
of turning circuits and cells and parts and pathways of the brain
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来控制大脑中的回路，细胞，部分的组织还有
02:50
on and off,
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它的传输途径
02:52
both to understand the science
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这不仅是对科学的探索，
02:54
and also to confront some of the issues
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也是直面人类所面临的
02:57
that face us all as humans.
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一些问题。
03:00
Now before I tell you about the technology,
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在我告诉大家这项技术之前
03:03
the bad news is that a significant fraction of us in this room,
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坏消息是我们之间的绝大数人
03:06
if we live long enough,
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如果你们活的够久远的话
03:08
will encounter, perhaps, a brain disorder.
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将会面临，也许，脑部疾病
03:10
Already, a billion people
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如今，10亿人
03:12
have had some kind of brain disorder
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已经患有某些脑部疾病
03:14
that incapacitates them,
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阻碍它们生活
03:16
and the numbers don't do it justice though.
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虽然这数字无法准确的表现出其严重性
03:18
These disorders -- schizophrenia, Alzheimer's,
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这些疾病--精神分裂症，老年痴呆症
03:20
depression, addiction --
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抑郁症，成瘾症--
03:22
they not only steal our time to live, they change who we are.
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它们不仅榨取我们的生命，而且篡改我们生存的意义
03:25
They take our identity and change our emotions
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它剥夺了我们的性格也改变了我们的情感--
03:27
and change who we are as people.
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更改变了我们做人的本质
03:30
Now in the 20th century,
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如今在20世纪，
03:33
there was some hope that was generated
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通过治疗脑部疾病的
03:36
through the development of pharmaceuticals for treating brain disorders,
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制药业的发展浮现出的一些希望
03:39
and while many drugs have been developed
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同时很多药物被研发出
03:42
that can alleviate symptoms of brain disorders,
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能减缓脑部疾病的症状
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practically none of them can be considered to be cured.
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实际上没有那种病被认为是能被治愈的
03:47
And part of that's because we're bathing the brain in the chemical.
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其中一部分是因为，我们大脑浸泡在化学物质当中
03:50
This elaborate circuit
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这复杂的回路
03:52
made out of thousands of different kinds of cell
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由上千种不同类型的细胞组成
03:54
is being bathed in a substance.
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正浸泡在液体当中
03:56
That's also why, perhaps, most of the drugs, and not all, on the market
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这也是为什么，市面上大部分的药物，不全都
03:58
can present some kind of serious side effect too.
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会引起某些严重的副作用。
04:01
Now some people have gotten some solace
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如今有些人通过在大脑植入电击器
04:04
from electrical stimulators that are implanted in the brain.
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来改善某些疾病。
04:07
And for Parkinson's disease,
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对于帕金森症
04:09
Cochlear implants,
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耳蜗移植电击器
04:11
these have indeed been able
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的确能够
04:13
to bring some kind of remedy
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带给患有一些特殊疾病的患者
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to people with certain kinds of disorder.
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一些治疗效果
04:17
But electricity also will go in all directions --
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但是电流还是会往四散开去--
04:19
the path of least resistance,
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找软柿子捏（从阻碍最小的地方通过）
04:21
which is where that phrase, in part, comes from.
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这也是这句谚语的，部分的，出处
04:23
And it also will affect normal circuits as well as the abnormal ones that you want to fix.
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电流不仅作用在我们需要修复的细胞还会影响到那些正常的回路
04:26
So again, we're sent back to the idea
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再一次，我们绕回到了
04:28
of ultra-precise control.
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超精确控制的问题上
04:30
Could we dial-in information precisely where we want it to go?
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我们是否能把信息精确的传输到我们想要地方？
04:34
So when I started in neuroscience 11 years ago,
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当11年前我开始研究神经科学
04:38
I had trained as an electrical engineer and a physicist,
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我受训成为一个电学工程师和物理学家
04:41
and the first thing I thought about was,
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而且第一件我想到的事
04:43
if these neurons are electrical devices,
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如果这些神经元是电子元件
04:45
all we need to do is to find some way
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所有我们要做的是找到某些方法
04:47
of driving those electrical changes at a distance.
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在一定距离控制电流的变化
04:49
If we could turn on the electricity in one cell,
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如果我们能刺激单独一个细胞
04:51
but not its neighbors,
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而不牵涉它周边
04:53
that would give us the tool we need to activate and shut down these different cells,
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那就我们就有了能激活和关闭各种不同细胞的工具
04:56
figure out what they do and how they contribute
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了解它们的作用和他们如何作用
04:58
to the networks in which they're embedded.
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在它们位于的脑部网络
05:00
And also it would allow us to have the ultra-precise control we need
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同样这给了我们需要的超精确控制
05:02
in order to fix the circuit computations
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来修复出错
05:05
that have gone awry.
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的回路
05:07
Now how are we going to do that?
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如今我们将怎么做呢？
05:09
Well there are many molecules that exist in nature,
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自然中有很多分子
05:11
which are able to convert light into electricity.
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能够把光转化为电流
05:14
You can think of them as little proteins
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你可以把它们看做小蛋白质
05:16
that are like solar cells.
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像太阳能细胞
05:18
If we can install these molecules in neurons somehow,
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如果我们能用某种方法把这些分子注入到神经元中
05:21
then these neurons would become electrically drivable with light.
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这些神经元就能转型成光控的电子元件
05:24
And their neighbors, which don't have the molecule, would not.
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那些周边的细胞，那些没有接受分子的，就不会转型
05:27
There's one other magic trick you need to make this all happen,
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另外还有一个你需要知道的小窍门，
05:29
and that's the ability to get light into the brain.
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就是把光注入脑中。
05:32
And to do that -- the brain doesn't feel pain -- you can put --
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这么做--大脑不会感知到痛苦--你能--
05:35
taking advantage of all the effort
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充分利用脑中
05:37
that's gone into the Internet and communications and so on --
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类似互联网和沟通的功能--
05:39
optical fibers connected to lasers
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把光纤连接到激光束中
05:41
that you can use to activate, in animal models for example,
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以此来激活，比如说动物的细胞
05:43
in pre-clinical studies,
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在潜伏期的研究中
05:45
these neurons and to see what they do.
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要了解这些神经元的功用
05:47
So how do we do this?
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那我们应该怎么做呢？
05:49
Around 2004,
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大概在2004年
05:51
in collaboration with Gerhard Nagel and Karl Deisseroth,
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在与格哈德·内格尔和卡尔·戴斯洛合作的时候
05:53
this vision came to fruition.
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假想得到了最终的成功
05:55
There's a certain alga that swims in the wild,
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自然界中有一种特定的海藻
05:58
and it needs to navigate towards light
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它就有趋光性
06:00
in order to photosynthesize optimally.
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来达到最理想的光合效果
06:02
And it senses light with a little eye-spot,
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它用一个小眼点来感知光线
06:04
which works not unlike how our eye works.
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但其工作原理和人眼大相径庭
06:07
In its membrane, or its boundary,
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在它的细胞膜，或者它的边界
06:09
it contains little proteins
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含有少量的蛋白质
06:12
that indeed can convert light into electricity.
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能把光转化为电流
06:15
So these molecules are called channelrhodopsins.
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这些分子被叫做槽型视紫质（TRB）
06:18
And each of these proteins acts just like that solar cell that I told you about.
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这种蛋白质就像我告诉过你们的太阳能细胞那样运作
06:21
When blue light hits it, it opens up a little hole
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当蓝光照射时，它会打开一个小口
06:24
and allows charged particles to enter the eye-spot,
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允许带点的微粒进入眼点中
06:26
and that allows this eye-spot to have an electrical signal
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这样眼点就有了电信号
06:28
just like a solar cell charging up a battery.
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就像是用太阳能细胞给电池充电一般
06:31
So what we need to do is to take these molecules
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我们需要做的就是提取这些分子
06:33
and somehow install them in neurons.
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然后用某种方法注入到神经元中
06:35
And because it's a protein,
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同时因为这是蛋白质
06:37
it's encoded for in the DNA of this organism.
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由生物的DNA编码而成
06:40
So all we've got to do is take that DNA,
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所以我们所要做的就是提取DNA
06:42
put it into a gene therapy vector, like a virus,
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注入到基因载体上，比如病毒
06:45
and put it into neurons.
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然后把病毒注入到神经元中
06:48
So it turned out that this was a very productive time in gene therapy,
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结果证明基因载体是一个很直接的方法
06:51
and lots of viruses were coming along.
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病毒长驱直入
06:53
So this turned out to be very simple to do.
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证实了操作的简易性
06:55
And early in the morning one day in the summer of 2004,
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在2004年夏天的一个早晨
06:58
we gave it a try, and it worked on the first try.
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我们实物操作了一番，第一次尝试有了起效
07:00
You take this DNA and you put it into a neuron.
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你提取出DNA并注入到神经元中
07:03
The neuron uses its natural protein-making machinery
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神经元用它自身的蛋白质合成器
07:06
to fabricate these little light-sensitive proteins
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来组装出这些小型的光敏蛋白质
07:08
and install them all over the cell,
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并使其分不到细胞各处
07:10
like putting solar panels on a roof,
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就像在顶层架设太阳能板
07:12
and the next thing you know,
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接下去
07:14
you have a neuron which can be activated with light.
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你就有了个光敏的神经元
07:16
So this is very powerful.
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这是个很有效的工具
07:18
One of the tricks you have to do
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你要做的步骤
07:20
is to figure out how to deliver these genes to the cells that you want
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就是设法把这些基因注入到你需要的细胞内
07:22
and not all the other neighbors.
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而不是其他周边的细胞
07:24
And you can do that; you can tweak the viruses
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你可以完成；你能转变这些病毒
07:26
so they hit just some cells and not others.
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让它们只针对一些细胞而涉及到其他细胞
07:28
And there's other genetic tricks you can play
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还有其他基因方式能
07:30
in order to get light-activated cells.
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得到这种光敏细胞
07:33
This field has now come to be known as optogenetics.
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如今这领域叫做光遗传学
07:37
And just as one example of the kind of thing you can do,
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举个例子来说明你要做的，
07:39
you can take a complex network,
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你可以在一个复杂的网络系统
07:41
use one of these viruses to deliver the gene
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利用一种病毒来传递这种基因
07:43
just to one kind of cell in this dense network.
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在密集的细胞区域只针对一种细胞
07:46
And then when you shine light on the entire network,
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接着当你照射整个区域的时候
07:48
just that cell type will be activated.
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只有那些特定的细胞被激活
07:50
So for example, lets sort of consider that basket cell I told you about earlier --
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比如说，用篮细胞来做例子会更简单一点
07:53
the one that's atrophied in schizophrenia
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就是那种萎缩导致精神分裂
07:55
and the one that is inhibitory.
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有抑制作用的细胞
07:57
If we can deliver that gene to these cells --
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如果我们能把基因注入到这些细胞中--
07:59
and they're not going to be altered by the expression of the gene, of course --
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而且他们不会引起基因的表现型有所改变--
08:02
and then flash blue light over the entire brain network,
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接着用蓝光照射整个脑组织
08:05
just these cells are going to be driven.
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只有蓝细胞会被激活
08:07
And when the light turns off, these cells go back to normal,
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而当无光线的时候，这些细胞就变回普通的细胞
08:09
so they don't seem to be averse against that.
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没有产生不良的后果
08:12
Not only can you use this to study what these cells do,
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不仅你能了解到这些细胞的功用
08:14
what their power is in computing in the brain,
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在大脑运作中它们的能效
08:16
but you can also use this to try to figure out --
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而且你也能尝试解决--
08:18
well maybe we could jazz up the activity of these cells,
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也许我们可以激活这些细胞的活性，
08:20
if indeed they're atrophied.
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如果它们真的萎缩的话。
08:22
Now I want to tell you a couple of short stories
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现在我想告诉你一些小故事
08:24
about how we're using this,
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关于我们怎么利用这技术的,
08:26
both at the scientific, clinical and pre-clinical levels.
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在科学，临床阶段和临床前阶段的研究。
08:29
One of the questions we've confronted
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在我们遭遇到的问题中有一个
08:31
is, what are the signals in the brain that mediate the sensation of reward?
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是，大脑用什么样的信号来代表奖励的感觉呢？
08:34
Because if you could find those,
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因为如果我们找到的话
08:36
those would be some of the signals that could drive learning.
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那能够驱使细胞学习的信号
08:38
The brain will do more of whatever got that reward.
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大脑就会为了奖励竭尽全力
08:40
And also these are signals that go awry in disorders such as addiction.
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同时也是这些出错的信号引起疾病类似成瘾症
08:43
So if we could figure out what cells they are,
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如果我们能够知道是哪些细胞的话
08:45
we could maybe find new targets
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我们可能就有新的靶细胞
08:47
for which drugs could be designed or screened against,
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来专门设计或者挑选药物来对抗疾病
08:49
or maybe places where electrodes could be put in
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或者找到植入电击器的位置
08:51
for people who have very severe disability.
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来帮助那些有着严重残疾的病人
08:54
So to do that, we came up with a very simple paradigm
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为了做到这些，我们想出了一个简单的例子
08:56
in collaboration with the Fiorella group,
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在菲奥雷拉集团的协助下
08:58
where one side of this little box,
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在盒子的一边
09:00
if the animal goes there, the animal gets a pulse of light
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如果动物经过这里，就会被光波照射到
09:02
in order to make different cells in the brain sensitive to light.
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来区别不同细胞对光的感应能力.
09:04
So if these cells can mediate reward,
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那如果这些细胞是识别为被奖励的
09:06
the animal should go there more and more.
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那动物就会多次的经过那里
09:08
And so that's what happens.
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这就是大致的经过
09:10
This animal's going to go to the right-hand side and poke his nose there,
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动物会向右转并用鼻子顶那块地方
09:12
and he gets a flash of blue light every time he does that.
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每次它做这个动作就会有一道蓝光照射
09:14
And he'll do that hundreds and hundreds of times.
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那它就会为此重复千上百次
09:16
These are the dopamine neurons,
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这些是多巴胺神经元
09:18
which some of you may have heard about, in some of the pleasure centers in the brain.
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你们中的一些可能可能听说过它在大脑的快感中枢某处
09:20
Now we've shown that a brief activation of these
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现在我们所展示的简短的步骤
09:22
is enough, indeed, to drive learning.
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就足够，确定的，来诱导学习行为
09:24
Now we can generalize the idea.
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如今我们概括出大致的观点
09:26
Instead of one point in the brain,
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不是大脑中的某一点
09:28
we can devise devices that span the brain,
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我们可以发明一些能够桥接大脑的设备
09:30
that can deliver light into three-dimensional patterns --
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来把光照射成三维的模式--
09:32
arrays of optical fibers,
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利用光纤的巧妙排列
09:34
each coupled to its own independent miniature light source.
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每个光纤都有自身独立的微型光源.
09:36
And then we can try to do things in vivo
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接着我们在生物体上试验
09:38
that have only been done to-date in a dish --
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测试那些已经在培养皿中完成的实验--
09:41
like high-throughput screening throughout the entire brain
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就像是给整个大脑做了高速的扫描一般
09:43
for the signals that can cause certain things to happen.
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来确定特定的信号会触发哪些特定的事情
09:45
Or that could be good clinical targets
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或者它们会成为临床上很好的
09:47
for treating brain disorders.
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治疗脑部疾病的新目标
09:49
And one story I want to tell you about
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另外一件我想说的事是
09:51
is how can we find targets for treating post-traumatic stress disorder --
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我们如何寻找靶细胞来治疗创伤后应激障碍--
09:54
a form of uncontrolled anxiety and fear.
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这是一种不受控制的焦虑恐慌的症候群
09:57
And one of the things that we did
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我们要做的一件事
09:59
was to adopt a very classical model of fear.
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接受一个经典的恐怖模式
10:02
This goes back to the Pavlovian days.
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那就回到了巴甫洛夫的时代
10:05
It's called Pavlovian fear conditioning --
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也被称作巴甫洛夫恐惧条件反射
10:07
where a tone ends with a brief shock.
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在响声后的短暂电击
10:09
The shock isn't painful, but it's a little annoying.
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电极并不疼痛，但是有点烦人
10:11
And over time -- in this case, a mouse,
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久而久之--这里的例子，老鼠
10:13
which is a good animal model, commonly used in such experiments --
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是一个很好的动物典型，在试验中广泛使用--
10:15
the animal learns to fear the tone.
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动物学会去害怕响声
10:17
The animal will react by freezing,
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会表现出呆滞的反应
10:19
sort of like a deer in the headlights.
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有点像鹿被车灯照射后的反应一样
10:21
Now the question is, what targets in the brain can we find
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如今的问题是，大脑中哪些目标位置
10:24
that allow us to overcome this fear?
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能让我们克服这种恐惧？
10:26
So what we do is we play that tone again
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我们所做的就是再一次播放那
10:28
after it's been associated with fear.
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当已经和恐惧联系起来的响声
10:30
But we activate targets in the brain, different ones,
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但是我们激活大脑中的靶细胞，每次不同的位置
10:32
using that optical fiber array I told you about in the previous slide,
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利用光纤阵列来演示出之前那样的图片
10:35
in order to try and figure out which targets
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来尝试找出能让大脑克服
10:37
can cause the brain to overcome that memory of fear.
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恐惧记忆的靶细胞
10:40
And so this brief video
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这简短的录像
10:42
shows you one of these targets that we're working on now.
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展示给大家一些我们正在研究的几个靶细胞
10:44
This is an area in the prefrontal cortex,
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这是前额皮层的一部分
10:46
a region where we can use cognition to try to overcome aversive emotional states.
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一块能让我们用感知来尝试克服厌恶情绪的区域
10:49
And the animal's going to hear a tone -- and a flash of light occurred there.
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动物将听到同样的响声--以及一束光线
10:51
There's no audio on this, but you can see the animal's freezing.
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光线不伴随声音，但是你也能看到动物呆滞的反应
10:53
This tone used to mean bad news.
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这声响意味着坏的消息
10:55
And there's a little clock in the lower left-hand corner,
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在左下角有个小型的闹钟
10:57
so you can see the animal is about two minutes into this.
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你能看到老鼠用了大约两分钟僵立在那里
11:00
And now this next clip
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下一个片段
11:02
is just eight minutes later.
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是八分钟之后
11:04
And the same tone is going to play, and the light is going to flash again.
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同样的响声，和相同的光线再一次的出现
11:07
Okay, there it goes. Right now.
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好，开始了，就现在
11:10
And now you can see, just 10 minutes into the experiment,
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正如你所见，只用了10分钟的实验
11:13
that we've equipped the brain by photoactivating this area
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我们就用光激活了大脑的这部分区域
11:16
to overcome the expression
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来克服恐惧记忆
11:18
of this fear memory.
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的表现行为
11:20
Now over the last couple of years, we've gone back to the tree of life
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近几年里，我们正回溯本源
11:23
because we wanted to find ways to turn circuits in the brain off.
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因为我们想找到控制大脑的方法
11:26
If we could do that, this could be extremely powerful.
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如果我们能够控制的话，那就可能是极具影响的
11:29
If you can delete cells just for a few milliseconds or seconds,
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如果让细胞失效就算几毫秒或者几秒的话
11:32
you can figure out what necessary role they play
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就能了解到它们所在位置的脑电路
11:34
in the circuits in which they're embedded.
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所扮演的本质的角色
11:36
And we've now surveyed organisms from all over the tree of life --
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如今我们已经调查了生物界所有的生物--
11:38
every kingdom of life except for animals, we see slightly differently.
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所有生物除了动物，我们并没有发现太大的差异。
11:41
And we found all sorts of molecules, they're called halorhodopsins or archaerhodopsins,
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我们发现了各种各样的分子，被命名为感光紫红蛋白或者远古感光蛋白
11:44
that respond to green and yellow light.
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会对绿色和黄色光线作出反应
11:46
And they do the opposite thing of the molecule I told you about before
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它们的反应是与之前我所提到的蓝光
11:48
with the blue light activator channelrhodopsin.
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活性槽型视紫质的反应恰恰相反
11:52
Let's give an example of where we think this is going to go.
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举个例子来说明具体的情况
11:55
Consider, for example, a condition like epilepsy,
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比如说癫痫这个症状
11:58
where the brain is overactive.
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起因是大脑过度活跃
12:00
Now if drugs fail in epileptic treatment,
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如果癫痫药物治疗失败
12:02
one of the strategies is to remove part of the brain.
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其他一种方法就是移除那部分大脑
12:04
But that's obviously irreversible, and there could be side effects.
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但是这显然是不可逆的过程，而且会引起副作用
12:06
What if we could just turn off that brain for a brief amount of time,
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那如果我们让那部分大脑休眠一会儿
12:09
until the seizure dies away,
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知道症状全部消失
12:12
and cause the brain to be restored to its initial state --
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再让大脑恢复到原来的阶段--
12:15
sort of like a dynamical system that's being coaxed down into a stable state.
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就好像把一个活跃的系统诱骗到一个稳定的系统一样
12:18
So this animation just tries to explain this concept
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这动画只是为了解释
12:21
where we made these cells sensitive to being turned off with light,
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我们能利用光源来控制脑细胞这个概念
12:23
and we beam light in,
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当我们用光照射时
12:25
and just for the time it takes to shut down a seizure,
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照射的时间也仅仅是能够刚好让症状消除
12:27
we're hoping to be able to turn it off.
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我们希望实验能够成功
12:29
And so we don't have data to show you on this front,
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暂时我们还没有这方面的实验数据展示给大家
12:31
but we're very excited about this.
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但是我们对此充满期待
12:33
Now I want to close on one story,
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现在我想用一个故事来结束我的演讲
12:35
which we think is another possibility --
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我们认为此技术能有其他用途---
12:37
which is that maybe these molecules, if you can do ultra-precise control,
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如果能超精确控制这些感光蛋白
12:39
can be used in the brain itself
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能够在脑中
12:41
to make a new kind of prosthetic, an optical prosthetic.
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形成一个新型的假肢，光学的价值
12:44
I already told you that electrical stimulators are not uncommon.
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我曾说过，电击器并不普遍
12:47
Seventy-five thousand people have Parkinson's deep-brain stimulators implanted.
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如今只有75000位帕金森病人植入了脑部电击器
12:50
Maybe 100,000 people have Cochlear implants,
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大约10万人在耳蜗中植入电击器
12:52
which allow them to hear.
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通过这样来恢复他们的听觉
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，就是你要让这些基因细胞移植入细胞中
12:57
And new hope in gene therapy has been developed
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基因治疗的新希望也就此诞生了
13:00
because viruses like the adeno-associated virus,
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因为像腺类病毒这类病毒
13:02
which probably most of us around this room have,
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可能我们大多数都有携带
13:04
and it doesn't have any symptoms,
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但它不会引发任何症状
13:06
which have been used in hundreds of patients
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它已经在上百名病人体内应用治疗
13:08
to deliver genes into the brain or the body.
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来转送基因进入大脑或者身体内
13:10
And so far, there have not been serious adverse events
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目前为止，还有没有因为此病毒
13:12
associated with the virus.
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而引起任何严重不良反应的报告
13:14
There's one last elephant in the room, the proteins themselves,
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还有最后一点要重视的大隐患，就是蛋白质其本身
13:17
which come from algae and bacteria and fungi,
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那些来自于藻类，细菌以及真菌
13:19
and all over the tree of life.
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以及来自生物界的各种蛋白质
13:21
Most of us don't have fungi or algae in our brains,
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我们大多数脑子没有真菌或者藻类的存在
13:23
so what is our brain going to do if we put that in?
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那如果我们把它们放入脑中会怎么样呢？
13:25
Are the cells going to tolerate it? Will the immune system react?
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我们大脑是否会排斥它？免疫系统是否会反应？
13:27
In its early days -- these have not been done on humans yet --
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早期的时候--我们并没有在人体里做实验--
13:29
but we're working on a variety of studies
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但是我们做了其他各种研究
13:31
to try and examine this,
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来评估这方法
13:33
and so far we haven't seen overt reactions of any severity
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目前为止，我们还没有因这些分子或者
13:36
to these molecules
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因光照大脑
13:38
or to the illumination of the brain with light.
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而产生的严重不良反应
13:41
So it's early days, to be upfront, but we're excited about it.
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这还是初步的研究，就算如此，我们很激动
13:44
I wanted to close with one story,
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我想用一个故事来结束我的演讲
13:46
which we think could potentially
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我们认为这有可能
13:48
be a clinical application.
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成为一种临床的疗法
13:50
Now there are many forms of blindness
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失明有很多种类
13:52
where the photoreceptors,
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大多关于
13:54
our light sensors that are in the back of our eye, are gone.
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我们的眼球内部的光受体的损害。
13:57
And the retina, of course, is a complex structure.
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我们的视网膜是个很复杂的结构
13:59
Now let's zoom in on it here, so we can see it in more detail.
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我们来放大，仔细研究一下
14:01
The photoreceptor cells are shown here at the top,
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照片中的感光受体在顶部
14:04
and then the signals that are detected by the photoreceptors
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被感光受体接收到的光信号
14:06
are transformed by various computations
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经过各种转化
14:08
until finally that layer of cells at the bottom, the ganglion cells,
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最终从上而下，从神经节细胞
14:11
relay the information to the brain,
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传输信息到大脑出
14:13
where we see that as perception.
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以此来获得视觉
14:15
In many forms of blindness, like retinitis pigmentosa,
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很多种类的失明，比如色素性视网膜炎
14:18
or macular degeneration,
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或者黄斑部变性
14:20
the photoreceptor cells have atrophied or been destroyed.
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感光细胞是萎缩或者有损伤的
14:23
Now how could you repair this?
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那我们如何才能修复呢？
14:25
It's not even clear that a drug could cause this to be restored,
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还没有证据证明药物可以对治疗这些疾病
14:28
because there's nothing for the drug to bind to.
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因为还没有针对的特效药
14:30
On the other hand, light can still get into the eye.
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但是，光还是能进入眼球的
14:32
The eye is still transparent and you can get light in.
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眼球还是通透的，你也能看到光线能够进入
14:35
So what if we could just take these channelrhodopsins and other molecules
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所以，如果我们能把这些单细胞感光紫红质蛋白和其他分子
14:38
and install them on some of these other spare cells
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注入到那些正常的细胞中
14:40
and convert them into little cameras.
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把它们转化为一台台小的摄像机
14:42
And because there's so many of these cells in the eye,
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因为眼球内部有很多细胞
14:44
potentially, they could be very high-resolution cameras.
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有可能，他们会成为高清的相机
14:47
So this is some work that we're doing.
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这就是我们所在做的
14:49
It's being led by one of our collaborators,
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我们合作人之一
14:51
Alan Horsager at USC,
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艾伦·霍斯葛
14:53
and being sought to be commercialized by a start-up company Eos Neuroscience,
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也正在美国卫生研究所的资助下将其技术
14:56
which is funded by the NIH.
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商业化运作
14:58
And what you see here is a mouse trying to solve a maze.
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现在你所看到的是一个走迷宫的老鼠
15:00
It's a six-arm maze. And there's a bit of water in the maze
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这是六臂的迷宫，迷宫中有些许水
15:02
to motivate the mouse to move, or he'll just sit there.
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来刺激老鼠移动，否则它只会呆在某处
15:04
And the goal, of course, of this maze
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当然，这迷宫的目的
15:06
is to get out of the water and go to a little platform
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是为了让水流入一个
15:08
that's under the lit top port.
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顶光源的平台
15:10
Now mice are smart, so this mouse solves the maze eventually,
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老鼠很聪明，最终走出了这迷宫
15:13
but he does a brute-force search.
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但是这是靠蛮力解决的
15:15
He's swimming down every avenue until he finally gets to the platform.
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它游过了每条分支最终才找到了平台
15:18
So he's not using vision to do it.
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所以它没有利用视觉来解决这问题
15:20
These different mice are different mutations
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这些老鼠有着不一样的突变基因
15:22
that recapitulate different kinds of blindness that affect humans.
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各自代表着人类不用种类的失明症状
15:25
And so we're being careful in trying to look at these different models
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所以我们有很小心的探索不同种类的失明情况下
15:28
so we come up with a generalized approach.
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找出一个普遍的解决方法
15:30
So how are we going to solve this?
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那我们如何解决呢？
15:32
We're going to do exactly what we outlined in the previous slide.
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我们就完全按照之前片子里讲的那样
15:34
We're going to take these blue light photosensors
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把蓝光感光蛋白
15:36
and install them on a layer of cells
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注入到眼球最后方的视网膜的
15:38
in the middle of the retina in the back of the eye
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一层细胞上
15:41
and convert them into a camera --
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把它们转化为一台台相机
15:43
just like installing solar cells all over those neurons
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就好像这些神经元上布满了太阳能细胞一样
15:45
to make them light sensitive.
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让它们接受光信号
15:47
Light is converted to electricity on them.
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并把光信号转化为电信号
15:49
So this mouse was blind a couple weeks before this experiment
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这老鼠实验前几周就瞎了
15:52
and received one dose of this photosensitive molecule in a virus.
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只接受过一次携带有感光受体分子的病毒注射
15:55
And now you can see, the animal can indeed avoid walls
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你现在可以看到，老鼠能够避开墙壁
15:57
and go to this little platform
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找到有亮光的平台
15:59
and make cognitive use of its eyes again.
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视觉得到了恢复
16:02
And to point out the power of this:
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为了指出其中的意义：
16:04
these animals are able to get to that platform
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这些动物走到平台的时间
16:06
just as fast as animals that have seen their entire lives.
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和那些没有瞎的东西用时是一样的
16:08
So this pre-clinical study, I think,
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虽然还处于临床前阶段
16:10
bodes hope for the kinds of things
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但是我认为这是个好兆头
16:12
we're hoping to do in the future.
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未来我们希望我们能够成功
16:14
To close, I want to point out that we're also exploring
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最后，我想指出我们正研究的一种
16:17
new business models for this new field of neurotechnology.
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针对神经科学这新领域的商业模式
16:19
We're developing these tools,
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我们发明了这些工具
16:21
but we share them freely with hundreds of groups all over the world,
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但是我们愿意和全世界的人共同分享
16:23
so people can study and try to treat different disorders.
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这样人们才能进一步研究并尝试治疗其他各种疾病
16:25
And our hope is that, by figuring out brain circuits
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我们希望，通过了解大脑的神经网络
16:28
at a level of abstraction that lets us repair them and engineer them,
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通过某种程度的手术，能让我们修复并设计神经网络
16:31
we can take some of these intractable disorders that I told you about earlier,
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我们会继续研究我之前讲过的几种疾病
16:34
practically none of which are cured,
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特别是那几种从未被治愈过的
16:36
and in the 21st century make them history.
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他们在21世纪将会成为历史
16:38
Thank you.
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谢谢
16:40
(Applause)
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（掌声）
16:53
Juan Enriquez: So some of the stuff is a little dense.
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Juan Enriquez(JE)：您的演讲有些深奥啊。
16:56
(Laughter)
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（笑声）
16:58
But the implications
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但是利用光
17:00
of being able to control seizures or epilepsy
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来控制癫痫或者抽搐
17:03
with light instead of drugs,
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而不是用药物
17:05
and being able to target those specifically
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还要能够精确地控制靶细胞
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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据我所听到的，第二步
17:12
is you can now control the brain in two colors,
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是用两种色彩的光来控制大脑
17:15
like an on/off switch.
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就好像开关一样
17:17
Ed Boyden: That's right.
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艾德·博伊登(EB):没错.
17:19
JE: Which makes every impulse going through the brain a binary code.
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JE：这让每个大脑中的神经冲动变成二进制的代码
17:22
EB: Right, yeah.
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EB：是的
17:24
So with blue light, we can drive information, and it's in the form of a one.
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当蓝灯亮起时，我们能传输信息。就类似于代码1
17:27
And by turning things off, it's more or less a zero.
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等光关闭了，就类似代码0
17:29
So our hope is to eventually build brain coprocessors
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我们的希望是最终建造一个大脑协同处理器
17:31
that work with the brain
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来和大脑一起运作
17:33
so we can augment functions in people with disabilities.
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以此来帮助那些有残疾的人
17:36
JE: And in theory, that means that,
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那就是理论上，这代表着
17:38
as a mouse feels, smells,
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老鼠的感觉，嗅觉
17:40
hears, touches,
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听觉和触觉
17:42
you can model it out as a string of ones and zeros.
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你都能把它整合到一串0和1
17:45
EB: Sure, yeah. We're hoping to use this as a way of testing
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EB：的确是这样的。我们希望通过这种测试
17:47
what neural codes can drive certain behaviors
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来确定哪种神经代码代表着哪种行为举止
17:49
and certain thoughts and certain feelings,
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或者是想法或者感受
17:51
and use that to understand more about the brain.
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通过这样来更多的了解大脑
17:54
JE: Does that mean that some day you could download memories
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JE：这是不是意味着某天你能下载记忆
17:57
and maybe upload them?
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或者上传记忆呢？
17:59
EB: Well that's something we're starting to work on very hard.
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EB：我们着手的某些工作是很复杂的
18:01
We're now working on some work
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我们还在继续的研究
18:03
where we're trying to tile the brain with recording elements too.
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我们也在尝试去标记下这个大脑记录数据
18:05
So we can record information and then drive information back in --
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我们就能记录信息，并把信息传输回大脑--
18:08
sort of computing what the brain needs
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类似于了解什么是大脑所需的
18:10
in order to augment its information processing.
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来增强它的信息处理效率.
18:12
JE: Well, that might change a couple things. Thank you. (EB: Thank you.)
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JE: 嗯，这会改变我的世界的。谢谢! (EB: 谢谢.)
18:15
(Applause)
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（掌声）
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