Grégoire Courtine: The paralyzed rat that walked

翻译人员: Wei Wu 校对人员: Tingting Zhao

I am a neuroscientist

我是一名神经学家

with a mixed background in physics and medicine.

同时有着医学和物理学背景

My lab at the Swiss Federal Institute of Technology

我的实验室隶属于瑞士联邦理工学院

focuses on spinal cord injury,

专攻脊椎损伤研究

which affects more than 50,000 people

全球每天有超过5万的人

around the world every year,

受到该伤病的影响

with dramatic consequences for affected individuals,

对于那些脊椎损伤的人来说

whose life literally shatters

生活, 往往就在那么短短几秒钟

in a matter of a handful of seconds.

被完全摧毁

And for me, the Man of Steel,

对于我而言, 是"钢铁英雄"

Christopher Reeve,

克里斯托弗·里夫

has best raised the awareness

尽自己的努力唤醒人们

on the distress of spinal cord injured people.

开始关注那些脊椎受伤的人

And this is how I started my own personal journey

而我进入这个研究领域的缘起

in this field of research,

第一次的接触

working with the Christopher and Dana Reeve Foundation.

就源于与里夫夫妇基金的合作

I still remember this decisive moment.

我到现在都还记得那个决定性的时刻

It was just at the end of a regular day of work

那是一个再普通不过的一天的结尾

with the foundation.

我在帮基金会工作

Chris addressed us, the scientists and experts,

克里斯托弗对我们, 一群学者和技术专家说

"You have to be more pragmatic.

"你们一定要专注实用价值"

When leaving your laboratory tomorrow,

"明天, 当你离开实验室的时候"

I want you to stop by the rehabilitation center

"我希望你们能去康复中心"

to watch injured people

"看看那些伤者"

fighting to take a step,

"如何费尽全力迈出一小步"

struggling to maintain their trunk.

"如何努力保持自己的平衡"

And when you go home,

"在你到家之后"

think of what you are going to change in your research

"仔细想想是否需要改变自己的研究方向"

on the following day to make their lives better."

"能够让他们的生活变得更美好一些"

These words, they stuck with me.

这段话, 刻到我心里去了

This was more than 10 years ago,

十多年过去了

but ever since, my laboratory has followed

直到今天, 我的实验室还都在

the pragmatic approach to recovery

坚持尝试用实用的方法

after spinal cord injury.

帮助脊椎损伤后恢复

And my first step in this direction

我在这研究方向上

was to develop a new model of spinal cord injury

需要做的第一件事情就是建立一个新的模型

that would more closely mimic some of the key features of human injury

一个新的脊椎损伤模型, 能够很好的模拟出人类的损伤

while offering well-controlled experimental conditions.

同时也能够提供很好的实验控制环境

And for this purpose, we placed two hemisections

基于这个目标, 我们首先在身体的两侧

on opposite sides of the body.

进行了两次半切操作

They completely interrupt the communication

半切完全阻断了

between the brain and the spinal cord,

大脑和脊髓的通信

thus leading to complete and permanent paralysis

导致了下肢永久性的

of the leg.

完全瘫痪

But, as observed, after most injuries in humans,

但是, 正如你们看到的, 对于大多数损伤

there is this intervening gap of intact neural tissue

在神经需要进行修复的位置

through which recovery can occur.

周边的神经组织都是完好的

But how to make it happen?

那么如何利用这一点?

Well, the classical approach

经典的方法是

consists of applying intervention

通过介入疗法

that would promote the growth of the severed fiber

刺激被切断的神经纤维重新生长

to the original target.

拼接到切断前的位置

And while this certainly remained the key for a cure,

这依然是治疗的关键步骤

this seemed extraordinarily complicated to me.

但对我而言实在是太复杂了

To reach clinical fruition rapidly,

如果要尽早实现临床应用

it was obvious:

那么很明显的

I had to think about the problem differently.

我需要换个角度来思考这个问题

It turned out that more than 100 years of research

脊髓外科的研究起始于谢林顿

on spinal cord physiology,

一位诺贝尔奖得主

starting with the Nobel Prize Sherrington,

至今已经有一百多年的研究史

had shown that

许多研究都证实

the spinal cord, below most injuries,

大多数受伤后的脊髓

contained all the necessary and sufficient neural networks

包含了协调运动所需的

to coordinate locomotion,

所有的神经网络

but because input from the brain is interrupted,

但是由于来自大脑的输入被切断了

they are in a nonfunctional state, like kind of dormant.

这些神经网络进入了类似休眠的状态

My idea: We awaken this network.

我的想法是: 激活这些网络

And at the time, I was a post-doctoral fellow in Los Angeles,

当时我还只是加州大学洛杉矶分校的小小博士后

after completing my Ph.D. in France,

刚刚从法国博士毕业

where independent thinking

这个身份其实并不是

is not necessarily promoted.

太需要独立思考精神的

(Laughter)

(笑声)

I was afraid to talk to my new boss,

我一开始不敢跟我的新老板提这个想法

but decided to muster up my courage.

但是后来终于鼓足了勇气

I knocked at the door of my wonderful advisor,

我敲开了我导师的门, 说出了我的想法

Reggie Edgerton, to share my new idea.

我的导师, Reggie Edgerton, 他太好了

He listened to me carefully,

他仔细的听了我的想法

and responded with a grin.

然后咧嘴一笑

"Why don't you try?"

"干嘛不试试？"

And I promise to you,

我要再三强调

this was such an important moment in my career,

这一刻在我职业生涯中有多重要

when I realized that the great leader

这一刻我意识到伟大的领导者

believed in young people and new ideas.

信任年轻人, 以及他们的新想法

And this was the idea:

这是我的想法:

I'm going to use a simplistic metaphor

我要用一个简单的比喻

to explain to you this complicated concept.

来向你解释这个复杂的概念

Imagine that the locomotor system is a car.

假设运动神经系统是一辆汽车

The engine is the spinal cord.

引擎就是脊髓

The transmission is interrupted. The engine is turned off.

变速箱坏了, 引擎熄火了

How could we re-engage the engine?

我们怎么把引擎重新打着？

First, we have to provide the fuel;

首先, 我们要加好油

second, press the accelerator pedal;

第二, 我们要踩油门

third, steer the car.

第三, 我们把握方向盘

It turned out that there are known neural pathways

研究人员已经发现了一些大脑发出的神经

coming from the brain that play this very function

在人的运动过程中承担着非常重要的

during locomotion.

控制作用

My idea: Replace this missing input

我的想法: 代替联系不上的大脑

to provide the spinal cord

向脊髓发送神经信号

with the kind of intervention

模拟大脑通过神经网络发出的信号

that the brain would deliver naturally in order to walk.

干预脊髓, 让下肢可以行走

For this, I leveraged 20 years of past research in neuroscience,

我借助过去20年神经科学的研究成果实现这一点

first to replace the missing fuel

首先是替换汽油

with pharmacological agents

使用药理学方法

that prepare the neurons in the spinal cord to fire,

刺激脊椎神经细胞, 做好发送神经信号的准备

and second, to mimic the accelerator pedal

然后, 用电刺激来模拟

with electrical stimulation.

汽车的油门

So here imagine an electrode

你可以想象成

implanted on the back of the spinal cord

在脊髓后面植入两个电极

to deliver painless stimulation.

用于发送无痛的电刺激

It took many years, but eventually we developed

虽然花了很多年, 但是最终我们还是

an electrochemical neuroprosthesis

成功开发了一套电化学神经康复疗法

that transformed the neural network

让受伤的脊髓中

in the spinal cord from dormant to a highly functional state.

已经冬眠的神经网络重新焕发生机

Immediately, the paralyzed rat can stand.

立竿见影的, 瘫痪的老鼠立刻站了起来

As soon as the treadmill belt starts moving,

脚底下的跑步机一启动

the animal shows coordinated movement of the leg,

老鼠的双腿就开始协调的运动起来

but without the brain.

完全没有大脑参与

Here what I call "the spinal brain"

我将相关的神经命名为"脊髓脑"

cognitively processes sensory information

它负责认知双腿传送上来的

arising from the moving leg

各种运动相关的感觉

and makes decisions as to how to activate the muscle

并且就肌肉如何运动做出决策

in order to stand, to walk, to run,

使老鼠能够站立, 行走和奔跑

and even here, while sprinting,

甚至在冲刺的时候

instantly stand

能够做到

if the treadmill stops moving.

跑步机一停老鼠就停下来

This was amazing.

这很神奇

I was completely fascinated by this locomotion

当我看到这种没有大脑参与的运动时

without the brain,

我非常的开心

but at the same time so frustrated.

但是也感到非常的沮丧

This locomotion was completely involuntary.

这种运动完全是非自主的

The animal had virtually no control over the legs.

小白鼠实际上并不能控制自己的腿

Clearly, the steering system was missing.

很显然, 还缺个方向盘

And it then became obvious from me

之后我就很清楚的认定

that we had to move away

我们需要抛开过去的方式

from the classical rehabilitation paradigm,

创建一种新的康复治疗过程

stepping on a treadmill,

将小白鼠放在跑步机上

and develop conditions that would encourage

同时创造一个环境, 这个环境能够激励

the brain to begin voluntary control over the leg.

大脑去自发的控制下肢

With this in mind, we developed a completely new

基于这个想法, 我们开发了一个全新的装备

robotic system to support the rat

一个机械臂, 能够帮助老鼠

in any direction of space.

向任何一个方向运动

Imagine, this is really cool.

想象一下, 很棒的设计

So imagine the little 200-gram rat

想象一下这个不到两百克的小老鼠

attached at the extremity of this 200-kilo robot,

被固定在将近200公斤的机械臂上

but the rat does not feel the robot.

但是小老鼠完全感觉不到机械臂的存在

The robot is transparent,

机械臂是感知不到的

just like you would hold a young child

就像是你撑着一个

during the first insecure steps.

蹒跚学步的婴儿一般

Let me summarize: The rat received

让我小结一下之前的内容

a paralyzing lesion of the spinal cord.

一个老鼠的脊髓被切断了

The electrochemical neuroprosthesis enabled

我们利用电化学神经康复疗法

a highly functional state of the spinal locomotor networks.

将老鼠的脊髓运动神经网络激活

The robot provided the safe environment

改进的机械臂提供一个安全的环境

to allow the rat to attempt anything

使得老鼠瘫痪的双腿

to engage the paralyzed legs.

可以做任何尝试

And for motivation, we used what I think

为了激励老鼠走起来, 我们使用了

is the most powerful pharmacology of Switzerland:

我认为是瑞士最强有力的刺激药物——

fine Swiss chocolate.

优质的瑞士巧克力

(Laughter)

(笑声)

Actually, the first results were very, very,

但是, 初步的实验结果非常, 非常, 非常地

very disappointing.

叫人失望

Here is my best physical therapist

视频中是我们最好的理疗师

completely failing to encourage the rat

他也完全没有办法诱使老鼠

to take a single step,

迈出一小步

whereas the same rat, five minutes earlier,

而同样是这只老鼠, 5分钟前

walked beautifully on the treadmill.

还在跑步机上优雅的迈着步子

We were so frustrated.

我们深受挫败

But you know, one of the most essential qualities

但是你也知道, 我们搞科学研究的, 最基本的素质

of a scientist is perseverance.

就是坚持不懈的精神

We insisted. We refined our paradigm,

我们继续努力, 继续完善我们的方法

and after several months of training,

经过几个月的不断训练

the otherwise paralyzed rat could stand,

一些瘫痪的老鼠能够自己站起来了

and whenever she decided,

并且它可以按照自己的意愿

initiated full weight-bearing locomotion

开始一种全速冲刺的姿态

to sprint towards the rewards.

冲向作为奖励的巧克力

This is the first recovery ever observed

这是迄今为止第一次

of voluntary leg movement

在实施了脊髓切断手术

after an experimental lesion of the spinal cord

导致完全和永久性的下肢瘫痪之后

leading to complete and permanent paralysis.

第一次成功实现下肢的自主运动

In fact --

事实上

(Applause)

(掌声)

Thank you.

谢谢

In fact, not only could the rat initiate

事实上, 这只老鼠不仅可以

and sustain locomotion on the ground,

在平地上启动并保持运动的状态

they could even adjust leg movement,

它们甚至可以调整自己的下肢运动

for example, to resist gravity

例如, 它们能够克服重力因素

in order to climb a staircase.

在楼梯上爬上爬下

I can promise you this was

可以说, 当这一刻发生时

such an emotional moment in my laboratory.

我们整个实验室的人都激动不已

It took us 10 years of hard work

我们花费了10年的辛苦努力

to reach this goal.

才做到这一点

But the remaining question was, how?

接下来的问题是, "怎么做到的?"

I mean, how is it possible?

我是说, 这怎么可能？

And here, what we found

而这个问题的答案

was completely unexpected.

完全出乎我们的意料

This novel training paradigm

这个新的康复训练方式

encouraged the brain to create new connections,

刺激了大脑去生成新的神经连接

some relay circuits

也就是一些传播网络

that relay information from the brain

将大脑的神经信号

past the injury and restore cortical control

穿过受损的脊髓部分, 连接上新恢复的脊髓神经

over the locomotor networks below the injury.

最终连接上了受损脊髓下部的神经网络

And here, you can see one such example,

你现在看到的这个例子中

where we label the fibers coming from the brain in red.

红色的纤维就是从大脑发出的神经

This blue neuron is connected with the locomotor center,

蓝色的神经能够连接到运动中枢

and what this constellation

看起来像是星座图

of synaptic contacts means

图中的连接表示的意思是

is that the brain is reconnected with the locomotor center

大脑与运动中枢通过这一个神经细胞

with only one relay neuron.

重新连接了起来

But the remodeling was not restricted

但是这种神经网络的改变

to the lesion area.

并不局限于此

It occurred throughout the central nervous system,

在中枢神经系统中, 这种改变也在发生着

including in the brain stem,

包括大脑内部的神经束

where we observed up to 300-percent increase

我们观察到大脑中相关的区域

in the density of fibers coming from the brain.

运动纤维的密度增长了300%

We did not aim to repair the spinal cord,

我们并不是要将脊髓恢复原状

yet we were able to promote

但是我们或许可以

one of the more extensive remodeling

在一个成年哺乳动物瘫痪之后

of axonal projections ever observed

通过这种神经网络重构的方式

in the central nervous system of adult mammal

重建中枢神经系统中

after an injury.

的神经连接

And there is a very important message

这项发现的背后, 隐藏着一个

hidden behind this discovery.

非常重要的事实

They are the result of a young team

这是由许多有才华的人组成的年轻团队

of very talented people:

合作努力的结果

physical therapists, neurobiologists, neurosurgeons,

理疗师, 神经生物学家, 神经外科医生

engineers of all kinds,

各种专业的工程师

who have achieved together

他们一起工作

what would have been impossible by single individuals.

做出了个人无法做到的成果

This is truly a trans-disciplinary team.

这是一个真正的跨学科团队

They are working so close to each other

我们工作中是如此的紧密

that there is horizontal transfer of DNA.

就像是我们之间发生了基因水平转移一样 (译注: 指生物将遗传物质传递给其他细胞而非其子代的过程)

We are creating the next generation

我们正在培养下一代的

of M.D.'s and engineers

医学博士和工程师

capable of translating discoveries all the way

他们有能力将自己的发现及成果

from bench to bedside.

从实验室转化到病房中

And me?

我呢？

I am only the maestro who orchestrated this beautiful symphony.

我只是这首美妙协奏乐章的指挥而已

Now, I am sure you are all wondering, aren't you,

现在, 我确定你们一定都在问

will this help injured people?

"这项技术能帮助人类么？"

Me too, every day.

其实我每天也都在问自己

The truth is that we don't know enough yet.

而事实上，现在我们还都不那么清楚

This is certainly not a cure for spinal cord injury,

这很显然并不能让断开的脊髓恢复如初

but I begin to believe that this may lead

但是我逐渐相信, 或许我们

to an intervention to improve recovery

能够帮助受伤的人提高伤后恢复的效果

and people's quality of life.

改善他们的生活质量

I would like you all

我邀请你们

to take a moment and dream with me.

花一点时间, 与我一起畅想一下

Imagine a person just suffered a spinal cord injury.

想象一个人刚刚经历了脊髓损伤

After a few weeks of recovery,

数周的恢复期之后

we will implant a programmable pump

我们植入一个可编程的药泵

to deliver a personalized pharmacological cocktail

能够直接向脊椎注入药物, 药物的选择和配比

directly to the spinal cord.

都是基于个人的情况定制的

At the same time, we will implant an electrode array,

同时, 我们会植入一个电极阵列

a sort of second skin

就像皮肤一样薄

covering the area of the spinal cord controlling leg movement,

覆盖控制下肢运动的脊髓位置

and this array is attached to an electrical pulse generator

这个电极阵列连接到一个电脉冲发生器上

that delivers stimulations that are tailored

电脉冲发生器发出的刺激频率和模式

to the person's needs.

可以因人而异

This defines a personalized electrochemical neuroprosthesis

这就构成了一个个性化的电化学神经康复治疗过程

that will enable locomotion

能够在康复训练中, 借助一个

during training with a newly designed supporting system.

新的运动支持系统, 进行下肢的运动

And my hope is that after several months of training,

我希望的是经过几个月的训练之后

there may be enough remodeling of residual connection

大脑和脊髓中的神经网络重建能够

to allow locomotion without the robot,

让人可以不借助辅助机械臂自由运动

maybe even without pharmacology or stimulation.

甚至可能不再需要药物泵和电脉冲发生器

My hope here is to be able to create

我的愿望是能够开发出

the personalized condition

个性化的治疗手段

to boost the plasticity of the brain

提高大脑和脊髓之间的

and the spinal cord.

神经网络的可塑性

And this is a radically new concept

这是一个全新的概念

that may apply to other neurological disorders,

或许也可以应用到其它的神经障碍性疾病中

what I termed "personalized neuroprosthetics,"

我提出了一种"个性化的神经假肢技术"

where by sensing and stimulating neural interfaces,

即根据病人自己的受损情况

I implanted throughout the nervous system,

在整个神经系统不同的位置植入电极

in the brain, in the spinal cord,

大脑中, 脊髓中

even in peripheral nerves,

甚至周围神经中

based on patient-specific impairments.

感知并模拟神经刺激

But not to replace the lost function, no --

我并不是要替换受损的功能, 不是的--

to help the brain help itself.

我是帮助大脑自我修复

And I hope this enticed your imagination,

我希望能够激发你们的想象

because I can promise to you

因为我敢保证

this is not a matter of whether this revolution will occur,

这场革命的问题, 不是能否发生

but when.

而是何时到来

And remember, we are only as great

请记住, 心有多大, 世界就有多大

as our imagination, as big as our dream.

思想有多远, 就能走多远

Thank you.

谢谢

(Applause)

(掌声)