I have a doppelganger. (Laughter) Dr. Gero is a brilliant but slightly mad scientist in the "Dragonball Z: Android Saga." If you look very carefully, you see that his skull has been replaced with a transparent Plexiglas dome so that the workings of his brain can be observed and also controlled with light. That's exactly what I do -- optical mind control.
我有一個分身 (笑聲) 基洛(台:蓋洛/可羅)博士是一個天才 但也是一個有少許瘋狂的科學家 在《龍珠.人造人傳說》中 如果你細心留意 你可以發現他的頭蓋骨被換掉了 並以一個玻璃罩蓋著 因此,他的腦部運作可被看見 亦可以光學控制 這實在就是我所做的 -- 光學操控思想
(Laughter)
(笑聲)
But in contrast to my evil twin who lusts after world domination, my motives are not sinister. I control the brain in order to understand how it works. Now wait a minute, you may say, how can you go straight to controlling the brain without understanding it first? Isn't that putting the cart before the horse? Many neuroscientists agree with this view and think that understanding will come from more detailed observation and analysis. They say, "If we could record the activity of our neurons, we would understand the brain." But think for a moment what that means. Even if we could measure what every cell is doing at all times, we would still have to make sense of the recorded activity patterns, and that's so difficult, chances are we'll understand these patterns just as little as the brains that produce them.
但與我的攣生兄弟不同 他貪戀操控世界 我的動機並不邪惡 我控制腦部 是希望可以了解它的運作 現在,你或許會說 你怎可以直接操控腦部的運作 而沒有先了解它的運作呢? 這不是本末倒置嗎? 很多腦神經科學家會同意這個懷疑 但也相信從精細的觀察和分析中 他們將會更了解腦部的運作 他們說:如果我們可以記錄腦神經的活動 我們即可了解腦部的運作 但是,請試想他們的理據 即使我們可以量度 每一個細胞、每一刻的活動 我們也需要解釋 所記錄的神經細胞活動規律 這是很困難的 我們了解這些規律的機會不大 就像我們不知道為何腦部會製造它們
Take a look at what brain activity might look like. In this simulation, each black dot is one nerve cell. The dot is visible whenever a cell fires an electrical impulse. There's 10,000 neurons here. So you're looking at roughly one percent of the brain of a cockroach. Your brains are about 100 million times more complicated. Somewhere, in a pattern like this, is you, your perceptions, your emotions, your memories, your plans for the future. But we don't know where, since we don't know how to read the pattern. We don't understand the code used by the brain. To make progress, we need to break the code. But how? An experienced code-breaker will tell you that in order to figure out what the symbols in a code mean, it's essential to be able to play with them, to rearrange them at will. So in this situation too, to decode the information contained in patterns like this, watching alone won't do. We need to rearrange the pattern. In other words, instead of recording the activity of neurons, we need to control it. It's not essential that we can control the activity of all neurons in the brain, just some. The more targeted our interventions, the better. And I'll show you in a moment how we can achieve the necessary precision.
看一看這腦部的活動 在這個模擬中,每一個黑點 是一個神經細胞 那些點是可見的 每當一個細胞發出一個電子脈衝 這裏有一萬個神經細胞 你現在看到的是 蟑螂腦部的百分之一 你們的腦部有大概有一億倍 的複雜 在這個的圖案中,有一部分 代表你 你的感知 你的情緒,你的記億 你對將來的計劃 但是我們無法得知哪裏 因為我們不懂得去為這些圖案解碼 我們不了解大腦所用的編碼 要有進展 我們需要解碼 但怎樣解碼呢? 一個富有經驗的密碼破譯員會告訴你 要解開符號的真正意義 我們必須能夠使用它們 以我們的意願重新組合它們 所以,在這個情況下 要獲取蘊含在這個圖案 當中的信息 光是觀察是不能實現的 我們需要重新組合這些圖案 換句話說 單單記錄神經細胞的活動並不可取 我們需要控制這些圖案 我們無須控制 腦中所有神經細胞的活動,一些就足夠 對神經細胞的活動干預愈多,效果愈佳 我將在往後的時間為你展示 我們怎樣達到所需的精確度
And since I'm realistic, rather than grandiose, I don't claim that the ability to control the function of the nervous system will at once unravel all its mysteries. But we'll certainly learn a lot. Now, I'm by no means the first person to realize how powerful a tool intervention is. The history of attempts to tinker with the function of the nervous system is long and illustrious. It dates back at least 200 years, to Galvani's famous experiments in the late 18th century and beyond. Galvani showed that a frog's legs twitched when he connected the lumbar nerve to a source of electrical current. This experiment revealed the first, and perhaps most fundamental, nugget of the neural code: that information is written in the form of electrical impulses. Galvani's approach of probing the nervous system with electrodes has remained state-of-the-art until today, despite a number of drawbacks. Sticking wires into the brain is obviously rather crude. It's hard to do in animals that run around, and there is a physical limit to the number of wires that can be inserted simultaneously.
因為我個人比較現實,而非華而不實 我不會宣稱能夠操控神經細胞的功能 會一次揭開所有關於神經細胞的奧秘 但是我們的確會從中學到很多 現在,我絕不是 世上第一個發現 干預神經細胞運作的後果多麼強大的人 歷史上,嘗試 去改變神經系統的機能 有長久且卓越的效果 在至少二百年前就有這樣的例子 從伽伐尼(Galvani)著名的實驗 十八世紀開始,一直就出現 伽伐尼證明,只要他把青蛙的腰神經 接上電流 青蛙的腳會抽搐 這個實驗首次,並從根本顯示 一個神經訊號的事實: 這些訊號是以 電子脈衝的方式編寫的 伽伐尼嘗試 以電極探究神經系統 即使以今天的科技來說,都是最先進領前的 雖然當中有相當的缺陷 將電線接到腦部上,顯然是相當殘忍的 這樣的設計也難實踐於走動的動物上 當中亦有物理上的限制 只有少量的電線 能夠同時安插在腦部
So around the turn of the last century, I started to think, "Wouldn't it be wonderful if one could take this logic and turn it upside down?" So instead of inserting a wire into one spot of the brain, re-engineer the brain itself so that some of its neural elements become responsive to diffusely broadcast signals such as a flash of light. Such an approach would literally, in a flash of light, overcome many of the obstacles to discovery. First, it's clearly a non-invasive, wireless form of communication. And second, just as in a radio broadcast, you can communicate with many receivers at once. You don't need to know where these receivers are, and it doesn't matter if these receivers move -- just think of the stereo in your car. It gets even better, for it turns out that we can fabricate the receivers out of materials that are encoded in DNA. So each nerve cell with the right genetic makeup will spontaneously produce a receiver that allows us to control its function. I hope you'll appreciate the beautiful simplicity of this concept. There's no high-tech gizmos here, just biology revealed through biology.
因此,在上世紀末 我開始思考 如果這樣的邏輯能得到認同,並反過來思考 那就好了 我們沒有把電線 接到腦部的某一點 反而是以生物工程改造腦部 令某些神經系統的組件 能夠感應擴散的廣播訊號 好像一束的閃光 這樣的方式會確實地,很迅速地 解決很多科學發現的障礙 第一,明顯地這是無創傷性的、 無線的傳輸方法 第二,就像無線電廣播 你可以跟很多訊號接收者同時溝通 但是你並不需要知道那些接收器所在的地點 再者,訊號接收者的活動也不會妨礙接收 情況就像車子中的收音機 我們的情況更理想 我們可以用 DNA 編碼的物料 裝配這些接收器 以致每一個神經細胞 都有正確的基因構造 它們會自然產生出一個接收器 讓我們能夠控制這些功能 我希望你會欣賞 這概念的 美麗樸實 這裏沒有高科技的小玩意 只有生物理論推展出的生物理論
Now let's take a look at these miraculous receivers up close. As we zoom in on one of these purple neurons, we see that its outer membrane is studded with microscopic pores. Pores like these conduct electrical current and are responsible for all the communication in the nervous system. But these pores here are special. They are coupled to light receptors similar to the ones in your eyes. Whenever a flash of light hits the receptor, the pore opens, an electrical current is switched on, and the neuron fires electrical impulses. Because the light-activated pore is encoded in DNA, we can achieve incredible precision. This is because, although each cell in our bodies contains the same set of genes, different mixes of genes get turned on and off in different cells. You can exploit this to make sure that only some neurons contain our light-activated pore and others don't. So in this cartoon, the bluish white cell in the upper-left corner does not respond to light because it lacks the light-activated pore. The approach works so well that we can write purely artificial messages directly to the brain. In this example, each electrical impulse, each deflection on the trace, is caused by a brief pulse of light. And the approach, of course, also works in moving, behaving animals.
現在,我們不妨一看這些不可思議的接收器 我們把鏡頭拉近到一個紫色的神經細胞 我們可以看到它的細胞外膜 佈滿著微細的氣孔 這些氣孔能夠讓電流通過 以及負責 為神經系統傳遞信息 但是你看到的是一些特別的氣孔 他們結合光感應受體 這些光感應受體跟你眼裏的很相似 只要一束閃光射在這些光感應受體 那些氣孔便會打開,電流亦會隨之而開啟 那神經細胞便會發出電子脈衝 因為那些光驅動氣孔是以編寫在 DNA 裏 我們可以達到無比的精確性 這是因為 雖然我們身體裏的每一個細胞 都藏有同樣的基因 在不同細胞裡,不同組合的基因 能被開啟或關掉 你可以利用這個原理去令 只有部分的神經細胞 藏有我們設計的光驅動氣孔,而其他沒有 在這個卡通中,藍白色的細胞 在左上角的那些 並不會對光有反應 因為它們缺少了光驅動氣孔 這個方法運作得非常好 我們可以用光把純淨的人工訊息 直接編寫到腦部 在這個例子中,每一個電子脈衝 每一個痕跡的偏差 都是起源於一束短暫的光脈衝 同時,這個方法也 適用於行走的動物身上
This is the first ever such experiment, sort of the optical equivalent of Galvani's. It was done six or seven years ago by my then graduate student, Susana Lima. Susana had engineered the fruit fly on the left so that just two out of the 200,000 cells in its brain expressed the light-activated pore. You're familiar with these cells because they are the ones that frustrate you when you try to swat the fly. They trained the escape reflex that makes the fly jump into the air and fly away whenever you move your hand in position. And you can see here that the flash of light has exactly the same effect. The animal jumps, it spreads its wings, it vibrates them, but it can't actually take off because the fly is sandwiched between two glass plates. Now to make sure that this was no reaction of the fly to a flash it could see, Susana did a simple but brutally effective experiment. She cut the heads off of her flies. These headless bodies can live for about a day, but they don't do much. They just stand around and groom excessively. So it seems that the only trait that survives decapitation is vanity. (Laughter) Anyway, as you'll see in a moment, Susana was able to turn on the flight motor of what's the equivalent of the spinal cord of these flies and get some of the headless bodies to actually take off and fly away. They didn't get very far, obviously. Since we took these first steps, the field of optogenetics has exploded. And there are now hundreds of labs using these approaches.
這是同類實驗中的第一個 可說是光學版本的伽伐尼實驗 這是六至七年前的事 我當時的研究生蘇珊娜.利馬負責這實驗 蘇珊娜改變左邊那果蠅的基因 令二十萬神經細胞中的其中兩個 出現光驅動氣孔 你相當熟悉這些神經細胞 因為它們就是那些煩擾你的神經細胞 在你嘗試拍打它的時候 它們刺激逃跑反射作用 繼而令果蠅飛上空中和飛走 你可以看到,一陣閃光跟拍打的動作有著同樣的效果 那動物跳起,伸展翅膀,震動它們 但它們不能飛離地面 因為這果蠅被夾在兩片玻璃的中間 要保證令果蠅展翅的 並非因為果蠅見到那道閃光 蘇珊娜做了一個簡單 但直截了當的實驗 她把果蠅的頭切掉 這些無頭的身體可以生存約一天 但它們並不會有太多活動 它們會站著 並替自己梳理 因此,斷頭之後,能夠保存下來好像只有虛榮心 (笑聲) 無論如何,等會你將會看到 蘇珊娜能夠啟動果蠅的逃走運動神經 這相等於果蠅的脊椎 以及令一些無頭的身體 離地及飛走 明顯地,它們不能走多遠 自我們開始嘗試後 光遺傳學這個領域就一觸即發 現時,數以百計的實驗室 正使用這個方法
And we've come a long way since Galvani's and Susana's first successes in making animals twitch or jump. We can now actually interfere with their psychology in rather profound ways, as I'll show you in my last example, which is directed at a familiar question. Life is a string of choices creating a constant pressure to decide what to do next. We cope with this pressure by having brains, and within our brains, decision-making centers that I've called here the "Actor." The Actor implements a policy that takes into account the state of the environment and the context in which we operate. Our actions change the environment, or context, and these changes are then fed back into the decision loop.
這些年來,我們取得了進展 從伽伐尼及蘇珊娜第一步 令動物抽搐或跳動 現在我們能夠 徹底地干擾它們的心理 在我最後的例子中,我將會為你展示 一個老生常談的問題 生命就是一連串的決擇 常存的壓力,迫使我們下一步的行動 我們以頭腦去處理這些壓力 以及在我們頭腦中的決策中心 我會形容這個決策中心為「行者」 這個行者執行一個政策 政策會考慮到周遭環境的因素 和我們生活的背景 我們的行為改變環境,或情景 而這些改變會反饋到我們的決策迴路
Now to put some neurobiological meat on this abstract model, we constructed a simple one-dimensional world for our favorite subject, fruit flies. Each chamber in these two vertical stacks contains one fly. The left and the right halves of the chamber are filled with two different odors, and a security camera watches as the flies pace up and down between them. Here's some such CCTV footage. Whenever a fly reaches the midpoint of the chamber where the two odor streams meet, it has to make a decision. It has to decide whether to turn around and stay in the same odor, or whether to cross the midline and try something new. These decisions are clearly a reflection of the Actor's policy. Now for an intelligent being like our fly, this policy is not written in stone but rather changes as the animal learns from experience. We can incorporate such an element of adaptive intelligence into our model by assuming that the fly's brain contains not only an Actor, but a different group of cells, a "Critic," that provides a running commentary on the Actor's choices. You can think of this nagging inner voice as sort of the brain's equivalent of the Catholic Church, if you're an Austrian like me, or the super-ego, if you're Freudian, or your mother, if you're Jewish.
現在我把神經生物的物質 加插到這個模型中 我們建造了一個一維的空間 把我們心愛的實驗對象,果蠅,放進去 兩幢玻璃管中的每一個室裏 都放有一隻果蠅 左右兩邊室中 瀰漫著兩種不同的氣味 監視器會一直監察著 看著果蠅來回踱步 這裏有一些錄到的片段 當一隻果蠅到達室的中間 兩種氣味會交錯 果蠅必須作出決定 它要決定回頭 留在同一種氣味中 又或者跨過中線 嘗試新事物 這顯然是一個 「行者」政策的反映 以我們的果蠅,這樣有智慧的生物來說 這個政策並非刻在石板上永遠不變的 它會根據生物的經驗而轉變 我們可以將這一個 有關適應的智能元素加進我們的模型裏 我們要假設果蠅的腦裏 不只有「行者」 也有不同組合的細胞 包括一個「批評家」,不斷地 為「行者」的決定提出意見 你可以想像成是種嘮叨的內在聲音 就把它當成是腦裏的 天主教教會吧 如果你跟我一樣是奧地利人 或可以把它當成佛洛依德所說的「超我」 或你是猶太人,可以把它當成「母親大人」
(Laughter)
(笑聲)
Now obviously, the Critic is a key ingredient in what makes us intelligent. So we set out to identify the cells in the fly's brain that played the role of the Critic. And the logic of our experiment was simple. We thought if we could use our optical remote control to activate the cells of the Critic, we should be able, artificially, to nag the Actor into changing its policy. In other words, the fly should learn from mistakes that it thought it had made but, in reality, it had not made. So we bred flies whose brains were more or less randomly peppered with cells that were light addressable. And then we took these flies and allowed them to make choices. And whenever they made one of the two choices, chose one odor, in this case the blue one over the orange one, we switched on the lights. If the Critic was among the optically activated cells, the result of this intervention should be a change in policy. The fly should learn to avoid the optically reinforced odor.
現在,明顯的 「批評家」在我們的智力系統中 是一個重要的組成部分 所以,我們希望可以確認 這些細胞在果蠅的腦部 扮演著「批評家」的角色 我們實驗的邏輯不太花巧 我們的假設是: 若我們能夠無線遙控 驅動「批評家」的細胞 我們應該可以,人工地,不斷煩擾「行者」 使它改變它的政策 換句話說 那這飛蠅應該能夠從錯誤中學習 它們會認為自己做錯了決定 即使它們其實沒有 我們培植了一些果蠅 它們的腦部被隨機地安置了 一些可以光驅動的細胞 我們拿出這些果蠅 給予它們決策的機會 每當它們作出兩選一的決定時 選到一種氣味 在這個情況中,它選了藍色而非橙色的那種 我們就亮燈 如果「批評家」在光驅動細胞中 這種干擾的結果是 果蠅會改變它的政策 這果蠅會學習避免 那種受光學加強的氣味
Here's what happened in two instances: We're comparing two strains of flies, each of them having about 100 light-addressable cells in their brains, shown here in green on the left and on the right. What's common among these groups of cells is that they all produce the neurotransmitter dopamine. But the identities of the individual dopamine-producing neurons are clearly largely different on the left and on the right. Optically activating these hundred or so cells into two strains of flies has dramatically different consequences. If you look first at the behavior of the fly on the right, you can see that whenever it reaches the midpoint of the chamber where the two odors meet, it marches straight through, as it did before. Its behavior is completely unchanged. But the behavior of the fly on the left is very different. Whenever it comes up to the midpoint, it pauses, it carefully scans the odor interface as if it was sniffing out its environment, and then it turns around. This means that the policy that the Actor implements now includes an instruction to avoid the odor that's in the right half of the chamber. This means that the Critic must have spoken in that animal, and that the Critic must be contained among the dopamine-producing neurons on the left, but not among the dopamine producing neurons on the right.
這裏有兩個不同情況 我們比較兩個品種的果蠅 它們的腦部分別擁有 大概一百個可光驅動的細胞 在這裏以綠色來顯示 兩組細胞的相同之處 在於它們都會製造神經遞質多巴胺 但是製造多巴胺細胞 的分佈 在左右兩邊的腦部中,顯然在不同的位置 光學驅動的 大概一百多個細胞 在兩個不同品種的果蠅裏 發揮著戲劇性的不同效果 如果你先看它們的行為 右邊的果蠅 你可以看到,當它到達室的中心點 兩種氣味的交匯處 它會一直走過去,就像從前一樣 它的行為完全沒有受光學驅動的細胞影響 但是另一邊廂的果蠅,情況就大不同了 每當它來到中心點 它會停下 謹慎地審視氣味的接合點 就好像要打探周遭的環境 然後它會回頭 這證明「行者」實施的那種政策 包括躲開另一端的氣味 該種氣味是從右邊室散發過來的 這說明「批評家」 對果蠅說: 不要跨過去 這說明在左邊的果蠅中,「批評家」 藏身在那些能夠製造多巴胺的細胞裏 但不存在於(能製造多巴胺的細胞)右邊的果蠅中
Through many such experiments, we were able to narrow down the identity of the Critic to just 12 cells. These 12 cells, as shown here in green, send the output to a brain structure called the "mushroom body," which is shown here in gray. We know from our formal model that the brain structure at the receiving end of the Critic's commentary is the Actor. So this anatomy suggests that the mushroom bodies have something to do with action choice. Based on everything we know about the mushroom bodies, this makes perfect sense. In fact, it makes so much sense that we can construct an electronic toy circuit that simulates the behavior of the fly. In this electronic toy circuit, the mushroom body neurons are symbolized by the vertical bank of blue LEDs in the center of the board. These LED's are wired to sensors that detect the presence of odorous molecules in the air. Each odor activates a different combination of sensors, which in turn activates a different odor detector in the mushroom body. So the pilot in the cockpit of the fly, the Actor, can tell which odor is present simply by looking at which of the blue LEDs lights up.
透過很多這樣的實驗 我們能夠縮窄 「批評家」的位置及身分 到只有十二個細胞 這十二個細胞,綠色部分 它們對一個腦結構發出訊號 它叫做「蘑菇體」 在這裏我以灰色呈現出來 我們從模型中知道 那個在「批評家」末端 接收著批評的腦結構,就是「行者」 這個結構提出 蘑菇體對於「行者」的決策 起著一定的作用 對於我們對蘑菇體的了解 這是完全能夠想像的 事實上,這非常合理 令我們能夠建構一個電子玩具線路 用以模擬果蠅的行為 這個電子玩具線路中 蘑菇體的細胞以 排成直線的藍色LED(發光二極體)來表示 於線路的正中心 這些LED有接上感應器 用以探測空氣中的氣味分子 不同的氣味都會驅動不同組合的感應器 再驅動 蘑菇體中不同的氣味檢測器 所以在果蠅駕駛室中的飛行員 「行者」 可以知道哪一種氣味存在 只要看看哪顆藍色LED燈亮起來就行了
What the Actor does with this information depends on its policy, which is stored in the strengths of the connection, between the odor detectors and the motors that power the fly's evasive actions. If the connection is weak, the motors will stay off and the fly will continue straight on its course. If the connection is strong, the motors will turn on and the fly will initiate a turn. Now consider a situation in which the motors stay off, the fly continues on its path and it suffers some painful consequence such as getting zapped. In a situation like this, we would expect the Critic to speak up and to tell the Actor to change its policy. We have created such a situation, artificially, by turning on the critic with a flash of light. That caused a strengthening of the connections between the currently active odor detector and the motors. So the next time the fly finds itself facing the same odor again, the connection is strong enough to turn on the motors and to trigger an evasive maneuver.
「行者」得到這個訊息後 視乎它的政策 這些政策都以關聯的強度來儲存 於氣味檢測器 與運動神經之間 這驅動了果蠅的逃亡行為 如果關聯性弱,運動神經會保持關上 那果蠅會繼續往那氣味進發 如果關聯性強,運動神經會啟動 那果蠅會轉身 現在有一個情況 就是當運動神經保持關上 那果蠅繼續前行 接著,它遭受一些痛苦的後果 例如遭電擊 在這樣的情況下 我們可以預期「批評家」會發聲 並告訴「行者」 要改變它的政策 我們人工地製造這樣的一個情境 以一束光啟動「批評家」 這樣就可以加強 正在起作用的氣味檢測細胞 與運動神經之間的關聯 所以,下一次 當果蠅再面對同樣的氣味時 關聯性將會有足夠的強度去啟動運動神經 以及引發一個迴避策略
I don't know about you, but I find it exhilarating to see how vague psychological notions evaporate and give rise to a physical, mechanistic understanding of the mind, even if it's the mind of the fly. This is one piece of good news. The other piece of good news, for a scientist at least, is that much remains to be discovered. In the experiments I told you about, we have lifted the identity of the Critic, but we still have no idea how the Critic does its job. Come to think of it, knowing when you're wrong without a teacher, or your mother, telling you, is a very hard problem. There are some ideas in computer science and in artificial intelligence as to how this might be done, but we still haven't solved a single example of how intelligent behavior springs from the physical interactions in living matter. I think we'll get there in the not too distant future.
不知道各位覺得如何 但我覺得這樣的實驗很令人興奮 虛無的心理學概念 揮發並引出 一個對思維方式在物理學上、機能上的理解 雖然這只是發生在果蠅的腦部 這是一個好消息 另一個好消息 至少是對於一個科學家來說 就是世界上還有很多尚待發掘的東西 在我告訴你的實驗裏 我們發掘出「批評家」的真正身分 但是我們還不知道 「批評家」怎樣完成它的工作 試想,在沒有老師或母親告訴你的情況下 要知道你自己犯錯 是一件不容易的事 電腦科學以及 人工智能的領域上有一些想法 就是要想出這件事怎樣可以發生 但是我們還沒有解決 任何這樣的一個難題 為甚麼在生物中 智慧會在物理層面的 互動中形成 我想,在不久的將來我們會找到答案
Thank you.
謝謝
(Applause)
(掌聲)