WEBVTT

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I am a neuroscientist

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with a mixed background in physics and medicine.

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My lab at the Swiss Federal Institute of Technology

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focuses on spinal cord injury,

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which affects more than 50,000 people

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around the world every year,

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with dramatic consequences for affected individuals,

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whose life literally shatters

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in a matter of a handful of seconds.

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And for me, the Man of Steel,

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Christopher Reeve,

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has best raised the awareness

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on the distress of spinal cord injured people.

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And this is how I started my own personal journey

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in this field of research,

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working with the Christopher and Dana Reeve Foundation.

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I still remember this decisive moment.

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

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with the foundation.

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Chris addressed us, the scientists and experts,

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"You have to be more pragmatic.

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When leaving your laboratory tomorrow,

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I want you to stop by the rehabilitation center

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to watch injured people

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fighting to take a step,

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struggling to maintain their trunk.

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And when you go home,

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think of what you are going to change in your research

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on the following day to make their lives better."

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These words, they stuck with me.

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This was more than 10 years ago,

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but ever since, my laboratory has followed

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the pragmatic approach to recovery

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after spinal cord injury.

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And my first step in this direction

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was to develop a new model of spinal cord injury

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

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while offering well-controlled experimental conditions.

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And for this purpose, we placed two hemisections

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on opposite sides of the body.

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They completely interrupt the communication

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between the brain and the spinal cord,

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thus leading to complete and permanent paralysis

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of the leg.

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But, as observed, after most injuries in humans,

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there is this intervening gap of intact neural tissue

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through which recovery can occur.

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But how to make it happen?

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Well, the classical approach

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consists of applying intervention

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that would promote the growth of the severed fiber

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to the original target.

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And while this certainly remained the key for a cure,

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this seemed extraordinarily complicated to me.

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To reach clinical fruition rapidly,

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it was obvious:

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I had to think about the problem differently.

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It turned out that more than 100 years of research

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on spinal cord physiology,

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starting with the Nobel Prize Sherrington,

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had shown that

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the spinal cord, below most injuries,

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contained all the necessary and sufficient neural networks

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to coordinate locomotion,

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but because input from the brain is interrupted,

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

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My idea: We awaken this network.

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

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after completing my Ph.D. in France,

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where independent thinking

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is not necessarily promoted.

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(Laughter)

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I was afraid to talk to my new boss,

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but decided to muster up my courage.

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I knocked at the door of my wonderful advisor,

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Reggie Edgerton, to share my new idea.

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He listened to me carefully,

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and responded with a grin.

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"Why don't you try?"

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And I promise to you,

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this was such an important moment in my career,

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when I realized that the great leader

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believed in young people and new ideas.

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And this was the idea:

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I'm going to use a simplistic metaphor

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to explain to you this complicated concept.

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Imagine that the locomotor system is a car.

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The engine is the spinal cord.

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The transmission is interrupted. The engine is turned off.

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How could we re-engage the engine?

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First, we have to provide the fuel;

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second, press the accelerator pedal;

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third, steer the car.

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It turned out that there are known neural pathways

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coming from the brain that play this very function

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during locomotion.

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My idea: Replace this missing input

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to provide the spinal cord

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with the kind of intervention

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that the brain would deliver naturally in order to walk.

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

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first to replace the missing fuel

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with pharmacological agents

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that prepare the neurons in the spinal cord to fire,

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and second, to mimic the accelerator pedal

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with electrical stimulation.

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So here imagine an electrode

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implanted on the back of the spinal cord

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to deliver painless stimulation.

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It took many years, but eventually we developed

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an electrochemical neuroprosthesis

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that transformed the neural network

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

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Immediately, the paralyzed rat can stand.

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As soon as the treadmill belt starts moving,

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the animal shows coordinated movement of the leg,

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but without the brain.

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Here what I call "the spinal brain"

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cognitively processes sensory information

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arising from the moving leg

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and makes decisions as to how to activate the muscle

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in order to stand, to walk, to run,

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and even here, while sprinting,

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instantly stand

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if the treadmill stops moving.

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This was amazing.

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I was completely fascinated by this locomotion

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without the brain,

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but at the same time so frustrated.

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This locomotion was completely involuntary.

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The animal had virtually no control over the legs.

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Clearly, the steering system was missing.

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And it then became obvious from me

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that we had to move away

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from the classical rehabilitation paradigm,

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stepping on a treadmill,

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and develop conditions that would encourage

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the brain to begin voluntary control over the leg.

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With this in mind, we developed a completely new

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robotic system to support the rat

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in any direction of space.

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Imagine, this is really cool.

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So imagine the little 200-gram rat

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attached at the extremity of this 200-kilo robot,

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but the rat does not feel the robot.

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The robot is transparent,

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just like you would hold a young child

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during the first insecure steps.

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Let me summarize: The rat received

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a paralyzing lesion of the spinal cord.

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The electrochemical neuroprosthesis enabled

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a highly functional state of the spinal locomotor networks.

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The robot provided the safe environment

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to allow the rat to attempt anything

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to engage the paralyzed legs.

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And for motivation, we used what I think

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is the most powerful pharmacology of Switzerland:

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fine Swiss chocolate.

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(Laughter)

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Actually, the first results were very, very,

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very disappointing.

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Here is my best physical therapist

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completely failing to encourage the rat

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to take a single step,

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whereas the same rat, five minutes earlier,

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walked beautifully on the treadmill.

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We were so frustrated.

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But you know, one of the most essential qualities

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of a scientist is perseverance.

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We insisted. We refined our paradigm,

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and after several months of training,

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the otherwise paralyzed rat could stand,

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and whenever she decided,

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initiated full weight-bearing locomotion

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to sprint towards the rewards.

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This is the first recovery ever observed

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of voluntary leg movement

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after an experimental lesion of the spinal cord

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leading to complete and permanent paralysis.

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In fact --

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(Applause)

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Thank you.

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In fact, not only could the rat initiate

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and sustain locomotion on the ground,

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they could even adjust leg movement,

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for example, to resist gravity

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in order to climb a staircase.

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I can promise you this was

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such an emotional moment in my laboratory.

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It took us 10 years of hard work

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to reach this goal.

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But the remaining question was, how?

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I mean, how is it possible?

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And here, what we found

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was completely unexpected.

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This novel training paradigm

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encouraged the brain to create new connections,

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some relay circuits

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that relay information from the brain

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past the injury and restore cortical control

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over the locomotor networks below the injury.

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And here, you can see one such example,

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

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This blue neuron is connected with the locomotor center,

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and what this constellation

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of synaptic contacts means

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is that the brain is reconnected with the locomotor center

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with only one relay neuron.

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But the remodeling was not restricted

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to the lesion area.

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It occurred throughout the central nervous system,

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including in the brain stem,

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where we observed up to 300-percent increase

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in the density of fibers coming from the brain.

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We did not aim to repair the spinal cord,

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yet we were able to promote

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one of the more extensive remodeling

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of axonal projections ever observed

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in the central nervous system of adult mammal

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after an injury.

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And there is a very important message

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hidden behind this discovery.

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They are the result of a young team

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of very talented people:

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physical therapists, neurobiologists, neurosurgeons,

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engineers of all kinds,

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who have achieved together

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what would have been impossible by single individuals.

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This is truly a trans-disciplinary team.

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They are working so close to each other

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that there is horizontal transfer of DNA.

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We are creating the next generation

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of M.D.'s and engineers

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capable of translating discoveries all the way

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from bench to bedside.

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And me?

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I am only the maestro who orchestrated this beautiful symphony.

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

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will this help injured people?

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Me too, every day.

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

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This is certainly not a cure for spinal cord injury,

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but I begin to believe that this may lead

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to an intervention to improve recovery

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and people's quality of life.

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I would like you all

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to take a moment and dream with me.

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Imagine a person just suffered a spinal cord injury.

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After a few weeks of recovery,

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we will implant a programmable pump

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to deliver a personalized pharmacological cocktail

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directly to the spinal cord.

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

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a sort of second skin

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covering the area of the spinal cord controlling leg movement,

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and this array is attached to an electrical pulse generator

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that delivers stimulations that are tailored

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to the person's needs.

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This defines a personalized electrochemical neuroprosthesis

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that will enable locomotion

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during training with a newly designed supporting system.

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And my hope is that after several months of training,

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there may be enough remodeling of residual connection

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to allow locomotion without the robot,

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maybe even without pharmacology or stimulation.

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My hope here is to be able to create

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the personalized condition

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to boost the plasticity of the brain

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and the spinal cord.

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And this is a radically new concept

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that may apply to other neurological disorders,

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what I termed "personalized neuroprosthetics,"

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where by sensing and stimulating neural interfaces,

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I implanted throughout the nervous system,

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in the brain, in the spinal cord,

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even in peripheral nerves,

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based on patient-specific impairments.

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But not to replace the lost function, no --

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to help the brain help itself.

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And I hope this enticed your imagination,

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because I can promise to you

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

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but when.

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And remember, we are only as great

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as our imagination, as big as our dream.

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Thank you.

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(Applause)