0:00:00.555,0:00:02.288 I am a neuroscientist 0:00:02.288,0:00:06.056 with a mixed background in physics and medicine. 0:00:06.056,0:00:10.600 My lab at Swiss Federal Institute of Technology 0:00:10.600,0:00:14.036 focuses on spinal cord injury, 0:00:14.036,0:00:16.816 which affect more than 50,000 people 0:00:16.816,0:00:19.612 around the world every year, 0:00:19.612,0:00:22.987 with dramatic consequences for affected individuals, 0:00:22.987,0:00:25.605 whose life literally shatters 0:00:25.605,0:00:28.762 in a matter of a handful of seconds. 0:00:28.762,0:00:32.437 And for me, the man of steel, 0:00:32.437,0:00:34.178 Christopher Reeve, 0:00:34.178,0:00:36.114 had best raised the awareness 0:00:36.114,0:00:38.922 on the distress of spinal cord injured people. 0:00:38.922,0:00:42.122 And this is how I started my own personal journey 0:00:42.122,0:00:43.838 in this field of research, 0:00:43.838,0:00:46.874 working with the Christopher and Dana Reeve Foundation. 0:00:46.874,0:00:49.019 I still remember 0:00:49.019,0:00:51.762 this decisive moment. 0:00:51.762,0:00:53.730 It was just at the end of a regular day of work 0:00:53.730,0:00:55.317 with the foundation. 0:00:55.317,0:00:59.739 Chris addressed to us, the scientists and experts, 0:00:59.739,0:01:03.362 "You have to be more pragmatic. 0:01:03.362,0:01:05.791 When leaving your laboratory tomorrow, 0:01:05.791,0:01:08.603 I want you to stop by the rehabilitation center 0:01:08.603,0:01:10.428 to watch injured people 0:01:10.428,0:01:12.283 fighting to take a step, 0:01:12.283,0:01:15.031 struggling to maintain their [??]. 0:01:15.031,0:01:16.723 And when you go home, 0:01:16.723,0:01:18.778 think about what you are going to change in your research 0:01:18.778,0:01:22.146 on the following day to make their lives better." 0:01:22.146,0:01:25.785 These words, they stuck with me. 0:01:25.785,0:01:28.790 This was more than 10 years ago, 0:01:28.790,0:01:31.499 but ever since, my laboratory has followed 0:01:31.499,0:01:33.614 the pragmatic approach to recovery 0:01:33.614,0:01:36.030 after spinal cord injury. 0:01:36.030,0:01:38.157 And my first step in this direction 0:01:38.157,0:01:41.199 was to develop a new model of spinal cord injury 0:01:41.199,0:01:44.877 that would more closely mimic some of the key features of human injury 0:01:44.877,0:01:48.251 while offering well-controlled experimental conditions. 0:01:48.251,0:01:50.816 And for this purpose, we placed two [??] 0:01:50.816,0:01:52.693 on opposite sides of the body. 0:01:52.693,0:01:54.669 They completely interrupt the communication 0:01:54.669,0:01:56.789 between the brain and the spinal cord, 0:01:56.789,0:01:59.485 thus leaving to complete and permanent paralysis 0:01:59.485,0:02:01.590 of the leg. 0:02:01.590,0:02:05.418 But, as observed, after most injuries in humans, 0:02:05.418,0:02:08.247 there is this intervening gap of intact neural tissue 0:02:08.247,0:02:11.018 through which recovery can occur. 0:02:11.018,0:02:13.482 But how to make it happen? 0:02:13.482,0:02:17.458 Well, the classical approach 0:02:17.458,0:02:20.071 consists of applying intervention 0:02:20.071,0:02:22.974 that would promote the growth of the severed fiber 0:02:22.974,0:02:25.022 to the original target. 0:02:25.022,0:02:28.295 And while this certainly remained the key for a cure, 0:02:28.295,0:02:32.393 this seemed extraordinarily complicated to me. 0:02:32.393,0:02:35.046 To reach clinical fruition rapidly, 0:02:35.046,0:02:36.818 it was obvious: 0:02:36.818,0:02:40.552 I had to think about the problem differently. 0:02:40.552,0:02:43.034 It turned out that more than 100 years of research 0:02:43.034,0:02:45.210 on spinal cord physiology, 0:02:45.210,0:02:47.703 starting with the Nobel Prize Sherrington, 0:02:47.703,0:02:49.526 had shown that 0:02:49.526,0:02:51.638 the spinal cord below most injuries 0:02:51.638,0:02:54.862 contained all the necessary and sufficient neural networks 0:02:54.862,0:02:57.273 to coordinate locomotion, 0:02:57.273,0:03:00.071 but because input from the brain are interrupted, 0:03:00.071,0:03:02.154 they are in a non-functional state, 0:03:02.154,0:03:03.886 like kind of dormant. 0:03:03.886,0:03:07.777 My idea: we awaken this network. 0:03:07.777,0:03:11.958 And at the time, I was a post-doctoral fellow in Los Angeles, 0:03:11.958,0:03:14.584 after completing my Ph.D in France, 0:03:14.584,0:03:16.478 where independent thinking 0:03:16.478,0:03:19.415 is not necessarily promoted. 0:03:19.415,0:03:21.491 (Laughter) 0:03:21.491,0:03:24.903 I was afraid to talk to my new boss, 0:03:24.903,0:03:27.512 but decided to muster up my courage. 0:03:27.512,0:03:30.122 I knock at the door, my wonderful advisor, 0:03:30.122,0:03:34.175 Reggie Edgerton, to share my new idea. 0:03:34.175,0:03:36.703 He listened to me carefully, 0:03:36.703,0:03:39.412 and responded with a grin. 0:03:39.412,0:03:42.487 "Why don't you try?" 0:03:42.487,0:03:43.950 And I promise to you, 0:03:43.950,0:03:46.966 this was such an important moment in my career, 0:03:46.966,0:03:49.293 when I realized that the great leader 0:03:49.293,0:03:52.686 believed in young people and new ideas. 0:03:52.686,0:03:53.971 And this was the idea: 0:03:53.971,0:03:56.499 I'm going to use a simplistic metaphor 0:03:56.499,0:03:58.763 to explain you this complicated concept. 0:03:58.763,0:04:04.192 Imagine that the locomotor system is a car. 0:04:04.192,0:04:05.853 The engine is the spinal cord. 0:04:05.853,0:04:09.157 The transmission is interrupted. The engine is turned off. 0:04:09.157,0:04:11.902 How could we re-engage the engine? 0:04:11.902,0:04:14.997 First, we have to provide the fuel; 0:04:14.997,0:04:17.340 second, press the accelerator pedal; 0:04:17.340,0:04:19.463 third, steer the car. 0:04:19.463,0:04:21.349 It turned out that there are known neural pathways 0:04:21.349,0:04:24.149 coming from the brain that play this very function 0:04:24.149,0:04:25.823 during locomotion. 0:04:25.823,0:04:27.939 My idea: replace this missing input 0:04:27.939,0:04:29.602 to provide the spinal cord 0:04:29.602,0:04:31.244 with the kind of intervention 0:04:31.244,0:04:35.619 that the brain would deliver naturally in order to walk. 0:04:35.619,0:04:40.105 For this, I leveraged 20 years of past research in neuroscience, 0:04:40.105,0:04:42.746 first to replace the missing fuel 0:04:42.746,0:04:45.023 with pharmacological agents 0:04:45.023,0:04:48.370 that prepare the neural and in the spinal cord to fire, 0:04:48.370,0:04:52.425 and second, to mim the accelerator pedal 0:04:52.425,0:04:54.352 with electrical stimulation. 0:04:54.352,0:04:56.321 So here imagine an electrode 0:04:56.321,0:04:58.665 implanted on the back of the spinal cord 0:04:58.665,0:05:00.897 to deliver painless stimulation. 0:05:00.897,0:05:03.360 It took many years, but eventually we developed 0:05:03.360,0:05:06.193 an electrochemical neuroprosthesis 0:05:06.193,0:05:08.176 that transformed the neural network 0:05:08.176,0:05:12.827 in the spinal cord from dormant to highly functional state. 0:05:12.827,0:05:19.214 Immediately, the paralyzed rat can stand. 0:05:19.214,0:05:21.526 As soon as the treadmill starts moving, 0:05:21.526,0:05:25.471 the animals show coordinated movement of the leg, 0:05:25.471,0:05:27.448 but without the brain. 0:05:27.448,0:05:29.454 Here what I call "the spinal brain" 0:05:29.454,0:05:32.191 cognitively processes sensory information 0:05:32.191,0:05:34.333 arising from the moving leg 0:05:34.333,0:05:38.227 and takes decisions as to how to activate the muscle 0:05:38.227,0:05:41.386 in order to stand, to walk, to run, 0:05:41.386,0:05:43.498 and even here, while sprinting, 0:05:43.498,0:05:45.795 instantly stand 0:05:45.795,0:05:48.458 if the treadmill stops moving. 0:05:48.458,0:05:49.857 This was amazing. 0:05:49.857,0:05:53.121 I was completed fascinated by this locomotion 0:05:53.121,0:05:55.601 without the brain, 0:05:55.601,0:05:59.256 but at the same time so frustrated. 0:05:59.256,0:06:01.695 This locomotion was completely involuntary. 0:06:01.695,0:06:04.952 The animal had virtually no control over the legs. 0:06:04.952,0:06:09.257 Clearly, the steering system was missing. 0:06:09.257,0:06:11.133 And it then became obvious from me 0:06:11.133,0:06:12.729 that we had to move away 0:06:12.729,0:06:15.561 from the classical rehabilitation paradigm, 0:06:15.561,0:06:17.529 stepping on a treadmill, 0:06:17.529,0:06:20.289 and develop conditions that would encourage 0:06:20.289,0:06:25.721 the brain to begin a voluntary control over the leg. 0:06:25.721,0:06:29.006 With this in mind, we developed a completely new 0:06:29.006,0:06:32.089 robotic system to support the rat 0:06:32.089,0:06:35.097 in any direction of space. 0:06:35.097,0:06:37.113 Imagine, this is really cool. 0:06:37.113,0:06:41.114 So imagine the little 200 gram rat 0:06:41.114,0:06:44.707 attached at the extremity of this 200 kilo robot, 0:06:44.707,0:06:47.217 but the rat does not feel the robot. 0:06:47.217,0:06:49.289 The robot is transparent, 0:06:49.289,0:06:51.467 just how you would hold a young child 0:06:51.467,0:06:54.187 during the first insecure steps. 0:06:54.187,0:06:57.569 Let me summarize: the rat received 0:06:57.569,0:07:00.083 a paralyzing lesion of the spinal cord. 0:07:00.083,0:07:02.666 The electrochemical neuroprostheses enable 0:07:02.666,0:07:06.858 highly functional state of the spinal locomotor networks. 0:07:06.858,0:07:10.593 The robot provides the safe environment 0:07:10.593,0:07:12.587 to allow the rat to attempt anything 0:07:12.587,0:07:15.361 to engage the paralyzed legs. 0:07:15.361,0:07:17.663 And for motivation, we used what I think 0:07:17.663,0:07:21.928 is the more powerful pharmacology of Switzerland: 0:07:21.928,0:07:24.188 fine Swiss chocolate. 0:07:24.188,0:07:27.312 (Laughter) 0:07:27.312,0:07:31.673 Actually, the first results were very, very, 0:07:31.673,0:07:33.758 very disappointing. 0:07:33.758,0:07:37.610 Here is my best physical therapist 0:07:44.841,0:07:47.569 completely failing to encourage the rat 0:07:47.569,0:07:49.569 to take a single step, 0:07:49.569,0:07:52.553 whereas the same rat, five minutes earlier, 0:07:52.553,0:07:54.890 walked beautifully on the treadmill. 0:07:54.890,0:07:56.925 We were so frustrated. 0:07:56.925,0:07:59.653 But you know, one of the most essential qualities 0:07:59.653,0:08:02.209 of a scientist is perseverance. 0:08:02.209,0:08:05.853 We insisted. We refined our paradigm, 0:08:05.853,0:08:08.024 and after several months of training, 0:08:08.024,0:08:11.799 the otherwise paralyzed rat could stand, 0:08:11.799,0:08:13.708 and whenever she decided, 0:08:13.708,0:08:15.943 initiated full weight-bearing locomotion 0:08:15.943,0:08:19.256 to sprint towards the rewards. 0:08:19.256,0:08:22.475 This is the first recovery ever observed 0:08:22.475,0:08:24.432 of voluntary leg movement 0:08:24.432,0:08:27.027 after an experimental lesion of the spinal cord 0:08:27.027,0:08:30.412 leading to complete and permanent paralysis. 0:08:30.412,0:08:32.209 In fact -- 0:08:32.209,0:08:34.361 (Applause) 0:08:34.361,0:08:38.556 Thank you. 0:08:38.556,0:08:41.402 In fact, not only the rat could initiate 0:08:41.402,0:08:44.141 and sustain locomotion on the ground, 0:08:44.141,0:08:46.545 they could even adjust leg movement, 0:08:46.545,0:08:48.932 for example, to resist gravity 0:08:48.932,0:08:52.172 in order to climb a staircase. 0:08:52.172,0:08:53.877 I can promise you this was 0:08:53.877,0:08:56.476 such an emotional moment in my laboratory. 0:08:56.476,0:08:59.142 It took us 10 years of hard work 0:08:59.142,0:09:01.732 to reach this goal. 0:09:01.732,0:09:04.437 But the remaining question was, how? 0:09:04.437,0:09:06.391 I mean, how is it possible? 0:09:06.391,0:09:08.021 And here, what we found 0:09:08.021,0:09:11.252 was completely unexpected. 0:09:11.252,0:09:15.103 This novel training paradigm 0:09:15.103,0:09:19.127 encouraged the brain to create new connections, 0:09:19.127,0:09:21.754 some relay circuits 0:09:21.754,0:09:25.002 that relay information from the brain 0:09:25.002,0:09:28.372 past the injury and restore cortical control 0:09:28.372,0:09:31.674 over the locomotor networks below the injury. 0:09:31.674,0:09:34.719 And here, you can see one such example, 0:09:34.719,0:09:38.039 where we label the fibers coming from the brain in red. 0:09:38.039,0:09:41.210 This blue neuron is connected with the locomotor center, 0:09:41.210,0:09:43.419 and what this constellation 0:09:43.419,0:09:45.970 of synaptive contacts means 0:09:45.970,0:09:50.057 is that the brain is reconnected with locomotor center 0:09:50.057,0:09:53.922 with only one relay neuron. 0:09:53.922,0:09:55.898 But the remodeling was not restricted 0:09:55.898,0:09:57.051 to the lesion area. 0:09:57.051,0:09:59.875 It occurred throughout the central nervous system, 0:09:59.875,0:10:02.611 including in the brain stem, 0:10:02.611,0:10:05.731 where we observed up to 300 percent increase 0:10:05.731,0:10:09.459 in the density of fibers coming from the brain. 0:10:09.459,0:10:13.074 We did not aim to repair the spinal cord, 0:10:13.074,0:10:15.722 yet we were able to promote 0:10:15.722,0:10:17.786 one of the more extensive remodeling 0:10:17.786,0:10:20.178 of external projection ever observed 0:10:20.178,0:10:22.410 in the central nervous system of adult mammal 0:10:22.410,0:10:25.008 after an injury. 0:10:25.008,0:10:30.001 And, you know, there is a very important message 0:10:30.001,0:10:34.604 hidden behind this discovery. 0:10:34.604,0:10:37.811 They are the result of a young team 0:10:37.811,0:10:40.249 of very talented people: 0:10:40.249,0:10:44.785 physical therapist, neurobiologist, neurosurgeon, 0:10:44.785,0:10:47.183 engineers of all kinds. 0:10:47.183,0:10:48.943 We have achieved together 0:10:48.943,0:10:52.201 what would have been impossible by single individuals. 0:10:52.201,0:10:55.284 This is truly a trans-disciplinary team. 0:10:55.284,0:10:57.472 They are work so close to each other 0:10:57.472,0:11:00.833 that there is almost like a transfer of DNA. 0:11:00.833,0:11:02.579 We are creating the next generation 0:11:02.579,0:11:04.635 of MDs and engineers, 0:11:04.635,0:11:07.171 get a bit of translating discoveries all the way 0:11:07.171,0:11:09.782 from bench to bedside. 0:11:09.782,0:11:11.820 And me? 0:11:11.820,0:11:16.427 I am only the maestro who orchestrated this beautiful symphony. 0:11:16.427,0:11:22.523 Now, I am sure you are all wondering, aren't you, 0:11:22.523,0:11:27.259 will this help injured people? 0:11:27.259,0:11:30.655 Me too, every day. 0:11:30.655,0:11:34.269 The truth is that we don't know enough yet. 0:11:34.269,0:11:38.893 This is certainly not a cure for spinal cord injury, 0:11:38.893,0:11:41.103 but I begin to believe that this may lead 0:11:41.103,0:11:43.640 to an intervention to improve recovery 0:11:43.640,0:11:46.965 and people's quality of life. 0:11:46.965,0:11:49.346 I would like you all 0:11:49.346,0:11:53.045 to take a moment and dream with me. 0:11:53.045,0:11:58.931 Imagine a person just suffered spinal cord injury. 0:11:58.931,0:12:02.070 After a few weeks of recovery, 0:12:02.070,0:12:04.522 we will implant a programmable [??] 0:12:04.522,0:12:07.449 to deliver a personalized pharmacological cocktail 0:12:07.449,0:12:09.966 directly into the spinal cord. 0:12:09.966,0:12:13.046 At the same time, we will implant an electrode array, 0:12:13.046,0:12:15.338 a sort of second skin 0:12:15.338,0:12:18.958 covering the area of the spinal cord controlling leg movement, 0:12:18.958,0:12:22.193 and this array is attached to an electrical pulse generator 0:12:22.193,0:12:24.193 that delivers stimulations that are tailored 0:12:24.193,0:12:26.841 to the person's needs. 0:12:26.841,0:12:31.730 This defines a personalized electrochemical neuroprosthesis 0:12:31.730,0:12:33.835 that will enable locomotion 0:12:33.835,0:12:38.529 during training with a newly designed supporting system. 0:12:38.529,0:12:41.674 And my hope is that after several months of training, 0:12:41.674,0:12:44.143 there may be enough remodeling of residual connection 0:12:44.143,0:12:47.613 to allow locomotion without the robot, 0:12:47.613,0:12:51.298 maybe even without pharmacology or stimulation. 0:12:51.298,0:12:53.817 My hope here is to be able to create 0:12:53.817,0:12:56.297 the personalized condition 0:12:56.297,0:12:58.960 to boost the plasticity of the brain 0:12:58.960,0:13:00.706 and the spinal cord. 0:13:00.706,0:13:02.906 And this is a radically new concept 0:13:02.906,0:13:06.292 that may apply to other neurological disorders. 0:13:06.292,0:13:10.737 What I termed "personalized neuroprosthetics," 0:13:10.737,0:13:13.823 where by sensing and stimulating neural interfaces, 0:13:13.823,0:13:17.722 I implanted throughout the nervous system, 0:13:17.722,0:13:20.893 in the brain, in the spinal cord, 0:13:20.893,0:13:23.572 even in peripheral nerves, 0:13:23.572,0:13:26.924 based on patient-specific impairments. 0:13:26.924,0:13:31.532 But not to replace the lost function, no: 0:13:31.532,0:13:34.647 to help the brain help itself. 0:13:34.647,0:13:37.502 And I hope this enticed your imagination, 0:13:37.502,0:13:39.321 because I can promise to you 0:13:39.321,0:13:42.535 this is not a matter of whether this revolution will occur, 0:13:42.535,0:13:44.294 but when. 0:13:44.294,0:13:46.543 And remember, we are only as great 0:13:46.543,0:13:50.062 as our imagination, as big as our dream. 0:13:50.062,0:13:51.934 Thank you. 0:13:51.934,0:13:55.934 (Applause)