So I'm a neurosurgeon. And like most of my colleagues, I have to deal, every day, with human tragedies. I realize how your life can change from one second to the other after a major stroke or after a car accident. And what is very frustrating for us neurosurgeons is to realize that unlike other organs of the body, the brain has very little ability for self-repair. And after a major injury of your central nervous system, the patients often remain with a severe handicap. And that's probably the reason why I've chosen to be a functional neurosurgeon.
我是一名神经外科医生。 跟我的大多数同事一样, 我每天都要面对各种人世间的悲剧。 我认识到一次严重的中风 或者一次车祸, 就足以在下一秒改变一个人的命运。 对我们这些神经外科医生来说, 最难过的事情就是意识到 与其他身体器官不同, 大脑几乎不能进行自我修复。 在中枢神经系统受到一次严重损伤后, 患者将会终身面对严重的残疾。 这可能也是我想要成为一名 功能性神经外科医生的原因。
What is a functional neurosurgeon? It's a doctor who is trying to improve a neurological function through different surgical strategies. You've certainly heard of one of the famous ones called deep brain stimulation, where you implant an electrode in the depths of the brain in order to modulate a circuit of neurons to improve a neurological function. It's really an amazing technology in that it has improved the destiny of patients with Parkinson's disease, with severe tremor, with severe pain. However, neuromodulation does not mean neuro-repair. And the dream of functional neurosurgeons is to repair the brain. I think that we are approaching this dream.
功能性神经外科医生是做什么的? 他们主要通过各种不同的手术方法 来改善神经功能。 你们一定听说过 很多主流方法中的一个, 叫做深度脑电刺激, 通常是把一个电极植入大脑深处, 通过调控神经元电流 来改善神经功能。 这项技术不可思议地 扭转了患有帕金森, 和被颤抖及疼痛困扰的 患者的命运。 但是,神经调控并不意味着 神经元的修复。 而功能性神经外科医生希望有朝一日 能够修复受损的大脑。 我认为 我们正在一步步接近这个目标。
And I would like to show you that we are very close to this. And that with a little bit of help, the brain is able to help itself.
我想让大家看看 我们离成功已经近在咫尺了。 只需要一点点的人工辅助, 大脑就可以进行自我修复。
So the story started 15 years ago. At that time, I was a chief resident working days and nights in the emergency room. I often had to take care of patients with head trauma. You have to imagine that when a patient comes in with a severe head trauma, his brain is swelling and he's increasing his intracranial pressure. And in order to save his life, you have to decrease this intracranial pressure. And to do that, you sometimes have to remove a piece of swollen brain. So instead of throwing away these pieces of swollen brain, we decided with Jean-François Brunet, who is a colleague of mine, a biologist, to study them.
事情还要从15年前说起。 那时候我还是一名住院总医师, 夜以继日地在急诊室忙碌。 我经常要护理有大脑损伤的病患。 你们可以想象一下, 带有严重脑外伤的患者被推进来, 他的大脑不断肿胀, 颅内压越来越高。 要挽救他的生命, 就必须要降低颅内压。 要做到这一点, 有时候就需要移除一部分肿胀的脑组织。 不过我们并没有把这一部分 肿胀的大脑直接丢弃, 而是在与生物学家 , 也是我的一位同事 Jean-François Brunet商量之后, 决定对这部分组织进行进一步研究。
What do I mean by that? We wanted to grow cells from these pieces of tissue. It's not an easy task. Growing cells from a piece of tissue is a bit the same as growing very small children out from their family. So you need to find the right nutrients, the warmth, the humidity and all the nice environments to make them thrive. So that's exactly what we had to do with these cells. And after many attempts, Jean-François did it. And that's what he saw under his microscope.
具体要怎么研究呢? 我们想让这一部分组织长出细胞来。 这可不是件容易的事儿。 让组织生长出细胞, 就好比一个家庭开始 养育一个小宝宝。 需要找到合适的营养成分, 合适的温度和湿度, 保证它们能够在适宜的环境下存活。 我们就是要在这样的条件下 培养这些细胞。 尝试过很多次之后, Jean-François成功了。 这就是他在显微镜下看到的一幕。
And that was, for us, a major surprise. Why? Because this looks exactly the same as a stem cell culture, with large green cells surrounding small, immature cells. And you may remember from biology class that stem cells are immature cells, able to turn into any type of cell of the body. The adult brain has stem cells, but they're very rare and they're located in deep and small niches in the depths of the brain. So it was surprising to get this kind of stem cell culture from the superficial part of swollen brain we had in the operating theater.
对我们来说,这是个天大的惊喜。 为什么呢? 因为这看起来跟干细胞群落 几乎一模一样, 小的,尚未成熟的细胞被一大群 绿色,较大的细胞包围着。 你们可能还记得生物课上讲过, 干细胞是未发育成熟的细胞, 可以演变成人体的任何一种细胞。 成人的大脑也有干细胞, 但是数量很少, 而且分布于大脑深处 隐蔽的角落里。 所以能够在操作室里从肿胀的 大脑表面获得这种干细胞群落, 真是太让人意外了。
And there was another intriguing observation: Regular stem cells are very active cells -- cells that divide, divide, divide very quickly. And they never die, they're immortal cells. But these cells behave differently. They divide slowly, and after a few weeks of culture, they even died. So we were in front of a strange new cell population that looked like stem cells but behaved differently.
而我们还观察到了 另外一个有趣的现象: 正常的干细胞非常活跃—— 它们可以不断地进行快速分裂。 它们也不会凋亡,能够一直存活。 但是这些细胞却有着不同的行为。 它们分裂得很慢, 而且仅仅过了几个星期, 就会慢慢死掉。 于是我们面前就出现了 一个奇怪的新的细胞群落, 看起来像干细胞, 但其行为却又跟干细胞有着天壤之别。
And it took us a long time to understand where they came from. They come from these cells. These blue and red cells are called doublecortin-positive cells. All of you have them in your brain. They represent four percent of your cortical brain cells. They have a very important role during the development stage. When you were fetuses, they helped your brain to fold itself. But why do they stay in your head? This, we don't know. We think that they may participate in brain repair because we find them in higher concentration close to brain lesions. But it's not so sure. But there is one clear thing -- that from these cells, we got our stem cell culture. And we were in front of a potential new source of cells to repair the brain. And we had to prove this.
我们花了好长时间 才搞清楚它们是从哪儿来的。 它们来自于这些细胞。 这些蓝色和红色的细胞称为 DCX(doublecortin-positive)阳性细胞。 它们存在于我们每个人的大脑中, 组成了我们4%的大脑皮层细胞。 在大脑发育过程中, 这些细胞起着至关重要的作用。 在婴儿时期, 它们能帮助大脑产生褶皱。 但它们为什么会一直留在大脑中呢? 这一点我们还不清楚。 我们认为它们可能参与了大脑修复, 是因为我们发现在大脑损伤的部位 它们的浓度比较高。 但我们还不是非常确定。 但有一点已经很清楚了—— 也就是从这些细胞中, 我们得到了干细胞群落。 我们面前正是一群有可能修复大脑的 细胞的新来源。 我们需要证明这一点。
So to prove it, we decided to design an experimental paradigm. The idea was to biopsy a piece of brain in a non-eloquent area of the brain, and then to culture the cells exactly the way Jean-François did it in his lab. And then label them, to put color in them in order to be able to track them in the brain. And the last step was to re-implant them in the same individual. We call these autologous grafts -- autografts.
那么想要证明, 我们决定设计一组对照试实验。 基本概念就是在大脑中一块 功能尚不明确的区域进行活组织提取, 然后用Jean-François在实验室 尝试过的同样的方法培养细胞。 然后给它们做标记,染色, 这样就可以在大脑中追踪它们的活动。 最后一步就是把它们重新移植入 相同的个体中。 我们把这叫做 自体同源嫁接——自嫁接。
So the first question we had, "What will happen if we re-implant these cells in a normal brain, and what will happen if we re-implant the same cells in a lesioned brain?" Thanks to the help of professor Eric Rouiller, we worked with monkeys.
我们的第一个问题就是, “如果我们把这些细胞 重新植入一个正常的大脑, 或者一个受过损伤的大脑, 会有什么区别呢?” 很幸运,在Eric Rouiller教授的帮助下, 我们得以在猴子身上进行试验。
So in the first-case scenario, we re-implanted the cells in the normal brain and what we saw is that they completely disappeared after a few weeks, as if they were taken from the brain, they go back home, the space is already busy, they are not needed there, so they disappear.
在第一种情况中, 我们把这些细胞移植入了正常大脑中, 发现它们在 仅仅几周后就完全消失了, 就好像被从大脑中清除了一样, 它们被驱赶出了这一区域, 这里没有多余的空间了, 它们发挥不了任何作用,于是就消失了。
In the second-case scenario, we performed the lesion, we re-implanted exactly the same cells, and in this case, the cells remained -- and they became mature neurons. And that's the image of what we could observe under the microscope. Those are the cells that were re-implanted. And the proof they carry, these little spots, those are the cells that we've labeled in vitro, when they were in culture.
在第二种情况中, 我们用了受损的大脑, 把一模一样的细胞移植了进去, 而这一次,细胞存活了下来—— 它们发育成了成熟的神经细胞。 这就是我们在显微镜下看到的图像。 这些是重新移植过的细胞。 证据表明, 这些小点就是我们在体外标记过的 还处在群落状态下的细胞。
But we could not stop here, of course. Do these cells also help a monkey to recover after a lesion? So for that, we trained monkeys to perform a manual dexterity task. They had to retrieve food pellets from a tray. They were very good at it. And when they had reached a plateau of performance, we did a lesion in the motor cortex corresponding to the hand motion. So the monkeys were plegic, they could not move their hand anymore. And exactly the same as humans would do, they spontaneously recovered to a certain extent, exactly the same as after a stroke. Patients are completely plegic, and then they try to recover due to a brain plasticity mechanism, they recover to a certain extent, exactly the same for the monkey.
但这肯定还远远不够。 那么这些细胞到底会不会 修复猴子的脑损伤呢? 为了证明这一点,我们训练猴子 完成一些有关肢体敏捷性的任务。 它们需要从盘子里取出食物。 它们一向很擅长这种事儿。 当它们的表现稳定后, 我们在大脑的运动皮层管理手部动作的 区域人为制造了一些损伤。 于是猴子们失去了手部行动能力, 手再也不停使唤了。 跟人类一样, 它们自动恢复到了某种水平, 跟中风后的情形相同。 中风患者完全不具备行动能力, 他们会试图利用大脑的弹性机制, 恢复到某种程度, 猴子也是一样。
So when we were sure that the monkey had reached his plateau of spontaneous recovery, we implanted his own cells. So on the left side, you see the monkey that has spontaneously recovered. He's at about 40 to 50 percent of his previous performance before the lesion. He's not so accurate, not so quick. And look now when we re-implant the cells: Two months after re-implantation, the same individual.
于是当我们很确定猴子的自我恢复能力 已经到达极限时, 我们移植了它自身的细胞。 在左边,你们可以看到 猴子自行恢复的状况。 与大脑受到损伤之前的状况相比, 它大概恢复了 40-50%的行动能力。 它的动作不是很精准,也比较慢。 再看看现在,我们重新移植了细胞之后: 同样的个体,移植两个月后的状况。
(Applause)
(掌声)
It was also very exciting results for us, I tell you. Since that time, we've understood much more about these cells. We know that we can cryopreserve them, we can use them later on. We know that we can apply them in other neuropathological models, like Parkinson's disease, for example. But our dream is still to implant them in humans. And I really hope that I'll be able to show you soon that the human brain is giving us the tools to repair itself.
说实话,这样的结果 就连我们也感到很意外。 从那时起, 我们对这些细胞就更加了解了。 我们知道我们能对 它们进行加密保存, 以后也能用得到。 我们也知道我们可以把它们应用到 其他神经病理学模型中, 比如帕金森。 但我们始终梦想有一天 能把它们移植入人体中。 我真的希望很快就能让你们看到 人类大脑为我们提供了 让它进行自我修复的工具。
Thank you.
谢谢大家。
(Applause)
(掌声)
Bruno Giussani: Jocelyne, this is amazing, and I'm sure that right now, there are several dozen people in the audience, possibly even a majority, who are thinking, "I know somebody who can use this." I do, in any case. And of course the question is, what are the biggest obstacles before you can go into human clinical trials?
Bruno Giussaini(BG): Jocelyne,这太精彩了, 现在我很确定,在座的很多人, 甚至可能是大部分人, 都在想,“我知道什么人会需要这项技术。” 总之我很确信。 当然我还有个问题, 在你们能够进行人体临床试验之前, 你们面临的最大障碍都有哪些呢?
Jocelyne Bloch: The biggest obstacles are regulations. (Laughs) So, from these exciting results, you need to fill out about two kilograms of papers and forms to be able to go through these kind of trials.
Jocelyne Bloch (JB): 最大的障碍就是监管制度。(笑声) 就是说,有了这些不可思议的结果, 你就得开始处理 大约两公斤的各种文件和表格, 然后才能开始临床试验。
BG: Which is understandable, the brain is delicate, etc.
BG:这还算合理吧,毕竟大脑太复杂了, 还有其他种种需要考虑的问题。
JB: Yes, it is, but it takes a long time and a lot of patience and almost a professional team to do it, you know?
JB:的确,但是这个过程太漫长了, 需要极度的耐心,还有一个专业团队 来做这个事儿,对吧?
BG: If you project yourself -- having done the research and having tried to get permission to start the trials, if you project yourself out in time, how many years before somebody gets into a hospital and this therapy is available?
BG:如果你们自己立项—— 自己做研究, 然后试着拿到临床试验的许可, 如果能够按时完成这一系列过程, 一个普通人要去医院做这种治疗 还要等上几年呢?
JB: So, it's very difficult to say. It depends, first, on the approval of the trial. Will the regulation allow us to do it soon? And then, you have to perform this kind of study in a small group of patients. So it takes, already, a long time to select the patients, do the treatment and evaluate if it's useful to do this kind of treatment. And then you have to deploy this to a multicentric trial. You have to really prove first that it's useful before offering this treatment up for everybody.
JB:这很难说。 首先取决于临床试验的批准日期。 监管机构会让我们尽快开始吗? 其次我们还得先在一小部分患者中间 进行预试验。 光是挑选合适的患者就要花上一阵子, 还得进行治疗, 再评估这种治疗是否有效。 之后还要进行多中心治疗。 我们必须在把这种治疗推广到 普通大众身上之前确认它是有效的。
BG: And safe, of course. JB: Of course.
BG:当然还要安全。 JB:肯定的。
BG: Jocelyne, thank you for coming to TED and sharing this. BG: Thank you.
BG:Jocelyne, 感谢你来TED分享这项研究。 BG:谢谢。 (掌声)
(Applause)