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.
我是一位神經㚈科醫生。 就像我的大部分同事一樣, 我每天要面對很多人間悲剧。 使我明白到人可能因為一次 嚴重中風或車禍, 而瞬間改變一生的命運。 最令我們這些神經學家苦惱的, 就是知道腦部不似其他器官, 很難自我修復。 病人的中央神經系統 受到嚴重受創後, 最後常常變成嚴重殘障。 可能因為這樣, 我決定成為功能性神經㚈科醫生。
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.
功能性神經㚈科醫生 做什麼工作呢? 這些醫生採用不同的㚈科方法, 致力改善神經功能。 各位一定聽過其中一個著名的方法 叫做腦部深層刺激手術。 就是植入一種電極在腦部深層, 改變神經元的迴路, 繼而改善神經系統的功能。 這種科技實在神奇, 因為它已經改變一些病人的命運, 例如柏金遜症、 嚴重腦震盪和痛症。 但是神經調節並不是修復神經。 功能性㚈科醫生的夢想 就是修復腦部。 我想 我們正朝著這個夢想前進。
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.
而且我想告訴大家 我們很快實現夢想。 只需要一點的幫忙, 腦部就能自我修復。
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.
這件事源自15年前, 那時我是駐院總醫師, 在急診室日夜不停工作。 常常要照顧腦創傷病人。 可以想像當一個病人頭部 受到重創入院, 他的腦部不斷腫脹, 顱內壓增加, 為了拯救他的生命, 一定要降低顱內壓。 因此 有時需要替病人移除一塊 腫脹的腦組織。 我們沒有把那塊腦組織丟棄, 反而決定跟我的一位同事, 那是生物學家Jean-Francois Brunet 一同硏究。
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.
我那樣說是什麼意思呢? 那時我們想從這些腦組織 培育細胞。 但這是並非容易的事。 從一塊腦組織培育細胞 就像把一個幼童跟家人分開, 由我們養育一樣。 所以一定要找到適合的營養食物、 溫暖和濕度的環境, 和所有良好的外圍 使他們茁壯成長。 這正是我們培養 這些細胞的想法。 經過多次嘗試, Jean-Francois 終於成功。 這是他在顯微鏡下看到的東西。
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.
我們知道結果後,感到很驚訝。 為什麼? 因為這個情況就跟培養 幹細胞一樣, 有大的綠色細胞包圍著 未長成的小細胞。 或許你會記得上生物課, 學過幹細胞是未成熟的細胞, 可以變成身體任何一種細胞。 成人的腦部也有幹細胞, 但十分稀少。 這些細胞存在於腦部低層 深處小小的位置。 所以能夠從手術室病人 腫脹的腦部表面, 得到這些幹細胞培養組織, 實在令人感到意外。
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.
還有另一個有趣的觀測結果: 正常的幹細胞非常活躍- 它們不停分裂,非常迅速。 永遠不會死亡,是一種不死細胞。 但是這些細胞行為不一樣。 它們緩慢地分裂, 經過數星期的培養, 它們甚至死亡。 所以我們面對了一群 奇怪的新細胞, 它們貌似幹細胞,但行為有分別。
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.
我們花了很長時間, 才知道它們從那𥚃來。 就是來自這些細胞, 這些藍色、紅色細胞叫做 微管相關蛋白正向細胞。 在座各位的腦部都有這些細胞。 它們佔了腦部皮質細胞的4%。 對人類的成長期很重要。 在胚胎期, 它們幫助腦部摺疊起來。 但為什麼它們仍然留在 大家的腦部呢? 這個我們不知道。 或許它們要參與腦部的修復, 因為我們發現它們 在腦損傷的附近 比較高度聚集。 但我們仍然不能確定。 但是有一件事實很清楚- 我們從這些細胞, 可以培養幹細胞。 這些具有潛力的新細胞 就在我們面前, 它們能夠修復腦部。 我們一定要證實這個論點。
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.
為了證實它, 我們決定設計一個實驗範例。 方法是在腦部不重要的區域 做活體組織切片, 然後培殖這些細胞, 就跟Jean-Francois在實驗室 試驗的方法一樣。 然後把它標籤再染上顏色, 方便追踨它在腦部的位置。 最後把它再次植入在 同一個病人。 我們稱這些是 自體移植物。
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.
我們首先有一個疑問, 「如果我們再次植入這些細胞 在正常腦部,會有什麼事; 又或者再次植入有創傷的腦部, 又會發生什麼事情呢? 很多謝Eric Rouiller 教授的幫忙, 我們一同利用猴子做研究,
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.
第一個的方案, 我們再次植入細胞 在正常的腦部, 數星期後,我們發現 這些細胞完全消失, 就如它們從腦部帶走, 後來回到從前腦部的家, 由於地方實在太擠擁, 所以沒需要再逗留, 唯有自行消失。
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.
第二個方案, 我們替𤠣腦做一個傷口, 跟著再次植入完全一樣的細胞, 這一次細胞繼續留下來- 而且變成成熟的神經元。 這是我們在顯微鏡下 觀察到的影像。 這是再次植入的細胞。 它們帶了實證, 這些小點就是我們培養細胞時, 在試管𥚃標籤而成的。
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.
當然我們不會就此停下來。 這些細胞是否可以幫助 有腦創傷的猴子恢復呢? 因此我們訓練猴子做一些 手指靈巧的動作。 牠們要從托盤拿起食物粒。 猴子做得勝任有餘。 當訓練牠們到了穩定期時, 我們替牠們手部動作相應的腦部 皮質做了一個傷口。 於是猴子癱瘓了, 雙手不能移動, 就跟人類的情況一樣, 猴子中風後, 身體自行恢復到某個程度。 病人完全癱瘓, 病人希望康復,由於腦部的 可塑性機制, 病人能夠恢復到某一程度, 就跟猴子的情況完全一樣。
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.
當我們確定猴子已經完成 身體自行恢復的階段, 我們便植入牠自己的細胞。 在左方,你可以見到猴子 已經自行恢復。 牠跟未有腦損傷時的表現, 大概做到4至5成。 牠的動作並不那麼準確和敏捷。 再看看,我們再次植入這些細胞: 兩個月後,同一隻猴子。
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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.
那是令人非常興奮的結果。 從此我們更加了解這些細胞。 也知道可以把細胞超低溫冷凍, 留待日後再用。 我們可以應用在其他 神經病理模式。 例如柏金遜症。 但是我們的夢想仍是 把細胞植入人腦。 我真的希望很快顯示各位面前, 我們可以利用人腦成為 人體自我修復的功具。
Thank you.
謝謝。
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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 Glussani: Jocelyne, 真是令人驚嘆呢, 我肯定在座有很多觀眾, 甚至可能大部分人 都在想:「我知道某人可以 接受這個治療。」 無論如何我也認同。 但問題是 什麼是你進行人體臨床試驗時, 最大的阻力呢?
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: 最大的阻力 就是規條。(笑聲) 雖然有這些令人興奮的結果, 但要填寫大約2公斤的表格, 才能獲准去做這些試驗。
BG: Which is understandable, the brain is delicate, etc.
BG:這是可以理解,因為腦部是那麼纖細脆弱等等。
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: 對的,但是需要很長的時間, 需要耐力和一个專業的團隊。
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: 如果你自己預測 完成研究 和獲准開始試驗後, 假如妳可以預計需要多少時間, 病人要入院接受這種治療, 需要等多少年呢?
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 : 這樣很難說。 首先要看做實驗可否獲批。 那些規條會否讓我們 盡快做試驗呢? 然後要替一小撮病人 進行硏究。 那又要花長時間挑選病人 接受治療, 然後評估這類治療是否有效。 繼而要展開多核心試驗。 一定先要證實那是對病人有作用, 才能給大眾接受治療。
BG: And safe, of course. JB: Of course.
BG:當然要安全可靠。 JB:一定。
BG: Jocelyne, thank you for coming to TED and sharing this. BG: Thank you.
BG:Jocelyne,謝謝妳來到Ted 跟我們分享這些見解。 BG:謝謝。
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