Grégoire Courtine: The paralyzed rat that walked

譯者: Willy Feng 審譯者: Li Li

I am a neuroscientist

我是一位神經科學家

with a mixed background in physics and medicine.

有物理和醫學的背景

My lab at the Swiss Federal Institute of Technology

在蘇黎世聯邦理工學院

focuses on spinal cord injury,

我的實驗室專注在脊椎損傷

which affects more than 50,000 people

每年全球有超過五萬人

around the world every year,

深受其害

with dramatic consequences for affected individuals,

每位受害者遇到的戲劇性後果

whose life literally shatters

確實地粉碎了他們的生活

in a matter of a handful of seconds.

一切都發生在短短幾秒的瞬間

And for me, the Man of Steel,

對我來說, 鋼鐵英雄,

Christopher Reeve,

克里斯多夫．李維

has best raised the awareness

喚起大數人們

on the distress of spinal cord injured people.

對脊椎損傷患者困境的認識

And this is how I started my own personal journey

這是我如何開始我個人的旅程

in this field of research,

在這研究領域中

working with the Christopher and Dana Reeve Foundation.

和李維夫婦基金會一同共事

I still remember this decisive moment.

我仍記得這決定性的時刻

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

那是一個在基金會的平常日子

with the foundation.

工作結束時

Chris addressed us, the scientists and experts,

克里斯多夫對我們這群科學家和專家說

"You have to be more pragmatic.

"你們應該要更務實一點

When leaving your laboratory tomorrow,

明天你們離開實驗時

I want you to stop by the rehabilitation center

我要你們到復健中心來一下

to watch injured people

看看這些傷患

fighting to take a step,

努力的跨出每一個步伐

struggling to maintain their trunk.

艱難的維持他們的身軀

And when you go home,

然後當你們回家後

think of what you are going to change in your research

想想你們要如何改變你們的研究

on the following day to make their lives better."

在將來可以讓他們的生活更好"

These words, they stuck with me.

這段話震驚了我

This was more than 10 years ago,

這是十多年之前的事

but ever since, my laboratory has followed

到今, 我實驗室一直都是

the pragmatic approach to recovery

追求務實的方式

after spinal cord injury.

使脊椎損傷患者復原

And my first step in this direction

而我的第一步

was to develop a new model of spinal cord injury

是發展一個新的模型

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

使脊椎損傷能像其它種類的損傷

while offering well-controlled experimental conditions.

提供一個控制良好的實驗環境

And for this purpose, we placed two hemisections

為了這個目的, 我們安置兩個半切的部位

on opposite sides of the body.

在身軀的兩側

They completely interrupt the communication

他們完全地阻礙

between the brain and the spinal cord,

大腦和脊椎的溝通

thus leading to complete and permanent paralysis

造成腿部全面性及永久性的

of the leg.

癱瘓

But, as observed, after most injuries in humans,

但觀察後發現, 大部分人體的損傷

there is this intervening gap of intact neural tissue

在完好神經組織之間的存在著空隙

through which recovery can occur.

讓復原的現象發生

But how to make it happen?

這是如何發生的呢?

Well, the classical approach

傳統的方法是

consists of applying intervention

施行手術

that would promote the growth of the severed fiber

讓斷裂的神經纖維

to the original target.

生長到你的目標去

And while this certainly remained the key for a cure,

這是目前治療的重要關鍵

this seemed extraordinarily complicated to me.

但對我來說是非常的複雜

To reach clinical fruition rapidly,

要即刻享受臨床的成果

it was obvious:

很明顯地

I had to think about the problem differently.

我必須要用不同的方式思考問題

It turned out that more than 100 years of research

脊椎神經生理學超過一百年的研究

on spinal cord physiology,

脊椎神經生理學超過一百年的研究

starting with the Nobel Prize Sherrington,

諾貝爾獎得主謝靈頓

had shown that

曾指出

the spinal cord, below most injuries,

脊椎神經在未達到重大損傷

contained all the necessary and sufficient neural networks

保有必要及足夠的神經網絡

to coordinate locomotion,

來協調運動

but because input from the brain is interrupted,

但因為從大腦來的訊號被阻礙

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

它們處於無作用狀態, 像是冬眠

My idea: We awaken this network.

我的想法是: 喚醒這神經網絡

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

當我在洛杉機做博士後研究時

after completing my Ph.D. in France,

也是我在法國拿到博士學位之後

where independent thinking

獨立思考的能力

is not necessarily promoted.

還沒有必然地建立起來

(Laughter)

(笑聲)

I was afraid to talk to my new boss,

我很擔心和我的新老闆對談

but decided to muster up my courage.

但我鼓起勇氣

I knocked at the door of my wonderful advisor,

敲了敲我那出色指導教授 Reggie Edgerton 的門

Reggie Edgerton, to share my new idea.

分享我新的想法

He listened to me carefully,

他仔細地聆聽

and responded with a grin.

不時露齒而笑

"Why don't you try?"

"你為何不去試試看呢?"

And I promise to you,

我可以向你保證

this was such an important moment in my career,

這是我生命中一個重要的時刻

when I realized that the great leader

一個出色的領導者

believed in young people and new ideas.

相信一位年輕人和新想法

And this was the idea:

我的新想法是:

I'm going to use a simplistic metaphor

我要使用最簡單的比喻

to explain to you this complicated concept.

向你們解釋這複雜的概念

Imagine that the locomotor system is a car.

想像一台汽車裡的引擎

The engine is the spinal cord.

這引擎就是脊椎神經

The transmission is interrupted. The engine is turned off.

當神經傳導被中斷, 引擎就熄火了

How could we re-engage the engine?

我們要如何讓引擎再次起動呢?

First, we have to provide the fuel;

首先, 我們要提供燃油

second, press the accelerator pedal;

其次, 踩下油門

third, steer the car.

最後, 發動汽車

It turned out that there are known neural pathways

有一個已知的從大腦出來的神經傳導路徑

coming from the brain that play this very function

扮演著運動的關鍵功能

during locomotion.

扮演著運動的關鍵功能

My idea: Replace this missing input

我的想法: 取代遺失的訊號

to provide the spinal cord

提供脊椎神經

with the kind of intervention

一種手術

that the brain would deliver naturally in order to walk.

讓大腦可以自然地傳達走路的訊號

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

我使用了過去二十幾年的神經科學研究成果

first to replace the missing fuel

先是用輔佐藥取代遺失的燃油

with pharmacological agents

先是用輔佐藥取代遺失的燃油

that prepare the neurons in the spinal cord to fire,

讓脊椎中的神經元預備起動

and second, to mimic the accelerator pedal

然後用電極刺激模仿油門

with electrical stimulation.

然後用電極刺激模仿油門

So here imagine an electrode

想像一個電極

implanted on the back of the spinal cord

植入脊椎的後面

to deliver painless stimulation.

以傳導無痛的刺激

It took many years, but eventually we developed

歷經許多年, 最終發展出

an electrochemical neuroprosthesis

電化學神經修補術

that transformed the neural network

可以將脊椎的神經網絡

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

從休眠中喚醒成具高度功能性狀態

Immediately, the paralyzed rat can stand.

緊接著, 癱瘓的老鼠就可以站立了

As soon as the treadmill belt starts moving,

步行機一旦開始移動

the animal shows coordinated movement of the leg,

老鼠腳部可以表現出相對應的動作

but without the brain.

但不需要經過大腦

Here what I call "the spinal brain"

我稱之為 "脊椎腦"

cognitively processes sensory information

它能處理從運動的腿部

arising from the moving leg

傳來的感覺訊息

and makes decisions as to how to activate the muscle

然後決定如何去作動肌肉

in order to stand, to walk, to run,

以便能站立, 行走, 或跑步

and even here, while sprinting,

甚至在衝刺時

instantly stand

能在跑步機停止時

if the treadmill stops moving.

馬上站立住

This was amazing.

這相當地神奇

I was completely fascinated by this locomotion

我完全被這種

without the brain,

不需大腦的運動動作所震攝

but at the same time so frustrated.

但同時也很挫折

This locomotion was completely involuntary.

這種運動是完全非自願性

The animal had virtually no control over the legs.

動物幾乎是無法控制它的腿

Clearly, the steering system was missing.

很明顯地, 缺乏方向盤操控系統

And it then became obvious from me

對我來說

that we had to move away

我們必須改變方式

from the classical rehabilitation paradigm,

從傳統復健的模式

stepping on a treadmill,

踏上這一跑步機

and develop conditions that would encourage

然後發展出一個機制

the brain to begin voluntary control over the leg.

能喚起腦部自發性地控制大腿

With this in mind, we developed a completely new

在這思維下, 我們發展一個全新的機械系統

robotic system to support the rat

在任何方位來幫忙這隻老鼠

in any direction of space.

在任何方位來幫忙這隻老鼠

Imagine, this is really cool.

這很酷的

So imagine the little 200-gram rat

想像一個200公克的小老鼠

attached at the extremity of this 200-kilo robot,

依在一個200公斤的機械上

but the rat does not feel the robot.

但它不會感覺到機械的存在

The robot is transparent,

這機械是透明的

just like you would hold a young child

就像你扶著一個小孩

during the first insecure steps.

讓他踏出他的第一步

Let me summarize: The rat received

簡言之

a paralyzing lesion of the spinal cord.

這老鼠得了脊椎麻痺損傷

The electrochemical neuroprosthesis enabled

電化學神經修補術

a highly functional state of the spinal locomotor networks.

能讓脊椎運動神經網絡再次作用起來

The robot provided the safe environment

這機械提供一個安全的環境

to allow the rat to attempt anything

讓老鼠能自主的觸發

to engage the paralyzed legs.

作動起癱瘓的腿部

And for motivation, we used what I think

就動機而言, 我們使用了

is the most powerful pharmacology of Switzerland:

在瑞典最有影響力的藥理學:

fine Swiss chocolate.

瑞士巧克力

(Laughter)

(笑聲)

Actually, the first results were very, very,

事實上, 第一的結果是非常非常

very disappointing.

非常的令人失望

Here is my best physical therapist

這是我最好的物理治療師

completely failing to encourage the rat

他完全地失敗

to take a single step,

無法讓老鼠踏出一步

whereas the same rat, five minutes earlier,

這是五分鐘前的同一隻老鼠

walked beautifully on the treadmill.

很優雅的在跑步機上行走

We were so frustrated.

我們感到非常的挫折

But you know, one of the most essential qualities

但是你知道的, 科學家最重要特質之一

of a scientist is perseverance.

就是堅持不懈

We insisted. We refined our paradigm,

我們重新改善我們的模型

and after several months of training,

經過數個月的訓練

the otherwise paralyzed rat could stand,

另外癱瘓的老鼠可以站立了

and whenever she decided,

無論何時它想要

initiated full weight-bearing locomotion

可以激起帶動全身重量的運動

to sprint towards the rewards.

衝刺達向終點

This is the first recovery ever observed

這是第一次的大發現

of voluntary leg movement

自主性的腿部運動

after an experimental lesion of the spinal cord

在造成永久癱瘓的脊椎損傷之後

leading to complete and permanent paralysis.

在造成永久癱瘓的脊椎損傷之後

In fact --

事實上...

(Applause)

(掌聲)

Thank you.

謝謝

In fact, not only could the rat initiate

事實上, 這老鼠不單單地

and sustain locomotion on the ground,

激發並維持著運動

they could even adjust leg movement,

也能夠調整腿部的運動

for example, to resist gravity

例如, 抵抗重力

in order to climb a staircase.

以便能爬樓梯

I can promise you this was

我可以向各位保證

such an emotional moment in my laboratory.

這是我實驗室中多麼令人動容的時刻

It took us 10 years of hard work

十年的努力

to reach this goal.

達到這樣的成果

But the remaining question was, how?

但我們仍要問, 這是如何辦到的?

I mean, how is it possible?

我是說, 為什麼可能?

And here, what we found

這裡我們所發現的

was completely unexpected.

是完全在意料之外的

This novel training paradigm

這個全新的訓練模式

encouraged the brain to create new connections,

讓腦部產生新的網絡聯結

some relay circuits

一些轉接的網絡

that relay information from the brain

將來自大腦的訊息

past the injury and restore cortical control

繞過損傷, 恢復皮層的控制

over the locomotor networks below the injury.

在損傷之下重建運動的網絡

And here, you can see one such example,

你可以看到一個例子

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

我們將來自大腦的神輕標成紅色

This blue neuron is connected with the locomotor center,

藍色神經元連接到運動中樞

and what this constellation

這些像星座的

of synaptic contacts means

神經突觸代表著

is that the brain is reconnected with the locomotor center

大腦重新連結到運動中樞

with only one relay neuron.

只經由一個轉接神經元

But the remodeling was not restricted

但這個重建現象不僅限於

to the lesion area.

癱瘓的部位

It occurred throughout the central nervous system,

它也發生在中央神經系統

including in the brain stem,

包含腦幹

where we observed up to 300-percent increase

我們觀察到來自大腦的神經纖維密度

in the density of fibers coming from the brain.

增加了三倍

We did not aim to repair the spinal cord,

我們並沒有想要修復脊椎神經

yet we were able to promote

但我們提供了一個

one of the more extensive remodeling

針對神經突軸

of axonal projections ever observed

非常廣泛的重建技術

in the central nervous system of adult mammal

應用在損傷的成年哺乳類動物的

after an injury.

中央神經統上

And there is a very important message

在這個發現背後

hidden behind this discovery.

有個非常重要的訊息

They are the result of a young team

這些成果來自於

of very talented people:

一個很有才氣的年經團隊:

physical therapists, neurobiologists, neurosurgeons,

包括物理治療師, 神經生物學家, 神經外科家

engineers of all kinds,

各類的工程師

who have achieved together

一同達成的成果

what would have been impossible by single individuals.

這對任何一個單獨的人都是不可能的任務

This is truly a trans-disciplinary team.

這是一個真正的跨領域團隊

They are working so close to each other

他們很密切的合作

that there is horizontal transfer of DNA.

像是DNA的平行轉移

We are creating the next generation

我們創造出下個世代的

of M.D.'s and engineers

醫生和工程師

capable of translating discoveries all the way

有能力將基礎研究

from bench to bedside.

轉到臨床實驗上

And me?

那我呢?

I am only the maestro who orchestrated this beautiful symphony.

我只是一個交響樂團的指揮家

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

現在, 你們一定都很好奇

will this help injured people?

這個真的能幫助受傷的人們嗎?

Me too, every day.

我每天也問這個問題

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

事實上我們還不知道

This is certainly not a cure for spinal cord injury,

這確實不算是脊椎損傷的治療

but I begin to believe that this may lead

但我開始相信

to an intervention to improve recovery

這很有可能是一個開端去改善

and people's quality of life.

人們的復原和生活狀況

I would like you all

我希望各位

to take a moment and dream with me.

和我一起有著這個夢想

Imagine a person just suffered a spinal cord injury.

想像一個受到脊椎損傷的人

After a few weeks of recovery,

在數週之後的復原

we will implant a programmable pump

植入一個可程式化的泵

to deliver a personalized pharmacological cocktail

把個人化的藥物

directly to the spinal cord.

直接送到脊椎裡

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

同時, 也植入一個電極陣列

a sort of second skin

像是第二層的表皮

covering the area of the spinal cord controlling leg movement,

覆蓋控制腿部運動的脊椎神經

and this array is attached to an electrical pulse generator

這些電極陣列連結到一個電脈衝產生器

that delivers stimulations that are tailored

根據個人的需要

to the person's needs.

傳導神經刺激

This defines a personalized electrochemical neuroprosthesis

這是一個個人化的電化學神經修補術

that will enable locomotion

能夠在新設計的支撐機構上復健後

during training with a newly designed supporting system.

進行運動動作

And my hope is that after several months of training,

而我希望在數個月的訓練後

there may be enough remodeling of residual connection

有足夠的網絡能重建起來

to allow locomotion without the robot,

使得不依賴這些機械而能運動

maybe even without pharmacology or stimulation.

甚至是可以不用靠藥物或電流刺激

My hope here is to be able to create

我希望能創造出一個

the personalized condition

個人化的環境

to boost the plasticity of the brain

來加強大腦和脊椎神經的

and the spinal cord.

可塑性

And this is a radically new concept

這是一個全新的概念

that may apply to other neurological disorders,

或許可以應用在其它的神經失調

what I termed "personalized neuroprosthetics,"

我稱之為 "個人化神經修補術"

where by sensing and stimulating neural interfaces,

透過感應和刺激神經介面

I implanted throughout the nervous system,

遍及整個神經系統

in the brain, in the spinal cord,

包含大腦, 脊椎神經

even in peripheral nerves,

甚至在周邊神經系統

based on patient-specific impairments.

根據病患的損傷程度來進行

But not to replace the lost function, no --

這不是取代失去的功能

to help the brain help itself.

而且幫大腦自行重建

And I hope this enticed your imagination,

我期盼這能誘發你的想像力

because I can promise to you

因為我保證

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

這不是關於革新能否成功

but when.

而且在於何時

And remember, we are only as great

記住, 我們因想像而美好

as our imagination, as big as our dream.

因夢想而偉大

Thank you.

謝謝

(Applause)

(掌聲)