What we'll learn about the brain in the next century | Sam Rodriques

譯者: Helen Chang 審譯者: Adrienne Lin

I want to tell you guys something about neuroscience.

我想告訴你們一些 關於神經科學的東西。

I'm a physicist by training.

我是一名通過培訓的物理學家。

About three years ago, I left physics

大約三年前，我離開物理學，

to come and try to understand how the brain works.

試圖理解大腦的工作原理。

And this is what I found.

這就是我發現的。

Lots of people are working on depression.

很多人研究抑鬱症。

And that's really good,

這真的很好，

depression is something that we really want to understand.

抑鬱症是我們真正想要了解的東西。

Here's how you do it:

做法是：

you take a jar and you fill it up, about halfway, with water.

拿個罐子，裝大約半滿的水。

And then you take a mouse, and you put the mouse in the jar, OK?

然後抓隻老鼠，放進罐子裡，

And the mouse swims around for a little while

老鼠游了一會兒，

and then at some point, the mouse gets tired

到某個時候，老鼠感到疲倦，

and decides to stop swimming.

決定不游了。

And when it stops swimming, that's depression.

停止游泳時就是得了抑鬱症。

OK?

這樣嗎？

And I'm from theoretical physics,

我學的是理論物理學，

so I'm used to people making very sophisticated mathematical models

所以習慣了人們用非常複雜的數學模型

to precisely describe physical phenomena,

來精確地描述物理現象，

so when I saw that this is the model for depression,

當我看到這是抑鬱症的模型時，

I though to myself, "Oh my God, we have a lot of work to do."

我對自己說：「哦，天啊， 我們還有很多工作要做。」

(Laughter)

（笑聲）

But this is a kind of general problem in neuroscience.

但這是神經科學中的普遍問題。

So for example, take emotion.

舉情感為例。

Lots of people want to understand emotion.

很多人想要了解情感。

But you can't study emotion in mice or monkeys

但你不能研究老鼠或猴子的情感，

because you can't ask them

因為你不能問牠們感覺如何

how they're feeling or what they're experiencing.

或者正經歷些什麼。

因此替代的是，想要了解情感的人

So instead, people who want to understand emotion,

typically end up studying what's called motivated behavior,

通常終會研究所謂的行為動機，

which is code for "what the mouse does when it really, really wants cheese."

是「老鼠在極想要乳酪時 所做的事情」的另一種說法。

OK, I could go on and on.

我的例子可多著呢。

I mean, the point is, the NIH spends about 5.5 billion dollars a year

我的意思是，美國衛生研究院 每年約花費 55 億美元

on neuroscience research.

研究神經科學。

And yet there have been almost no significant improvements in outcomes

然而幾乎沒有顯著的改善結果，

for patients with brain diseases in the past 40 years.

過去 40 年來 腦病患者預後的改善結果不大。

And I think a lot of that is basically due to the fact

我認為其中很大一部分原因

that mice might be OK as a model for cancer or diabetes,

是老鼠雖可當作 癌症或糖尿病的模型，

but the mouse brain is just not sophisticated enough

但鼠腦不夠複雜，

to reproduce human psychology or human brain disease.

不足以複製人類心理學 或人類的腦部疾病。

OK?

明白嗎？

So if the mouse models are so bad, why are we still using them?

如果老鼠的模型很糟糕， 為什麼我們仍用呢？

Well, it basically boils down to this:

基本上可以歸結為：

the brain is made up of neurons

大腦由神經元組成，

which are these little cells that send electrical signals to each other.

神經元是互相發送電訊的小細胞。

If you want to understand how the brain works,

要瞭解大腦的工作方式，

you have to be able to measure the electrical activity of these neurons.

就必須能測量神經元活動的電訊。

But to do that, you have to get really close to the neurons

但為了要做到，就必須用某種

with some kind of electrical recording device or a microscope.

電子記錄設備或顯微鏡 來真正接近神經元。

And so you can do that in mice and you can do it in monkeys,

在老鼠和在猴子身上做得到，

because you can physically put things into their brain

因為能把異物實際放入牠們的腦中；

but for some reason we still can't do that in humans, OK?

但由於某種原因， 我們仍無法在人類身上這麼做。

So instead, we've invented all these proxies.

於是我們發明了這些替代品。

So the most popular one is probably this,

最流行的可能是這個，

functional MRI, fMRI,

功能性核磁共振成像（fMRI），

which allows you to make these pretty pictures like this,

可以讓你做出像這樣的漂亮圖片，

that show which parts of your brain light up

顯示你從事不同的活動時，

when you're engaged in different activities.

腦部的哪些部位會發光。

But this is a proxy.

但這是替代品，

You're not actually measuring neural activity here.

並未實際測量腦的神經活動，

What you're doing is you're measuring, essentially,

基本上測量的是腦中的血流。

like, blood flow in the brain.

Where there's more blood.

實際上血流多的地方含氧量就高，

It's actually where there's more oxygen, but you get the idea, OK?

明白了吧？

另一樣是能驗「腦電圖」：

The other thing that you can do is you can do this --

electroencephalography -- you can put these electrodes on your head, OK?

把電極放在頭上，測量腦波。

And then you can measure your brain waves.

And here, you're actually measuring electrical activity.

這裡實際測量的是電子的活動，

But you're not measuring the activity of neurons.

不是測量神經元的活動。

You're measuring these electrical currents,

測量這些電流

sloshing back and forth in your brain.

在腦中流來流去。

So the point is just that these technologies that we have

重點是我們擁有的這些技術

are really measuring the wrong thing.

是在量錯誤的東西。

Because, for most of the diseases that we want to understand --

因為大多數我們想要了解的疾病──

like, Parkinson's is the classic example.

帕金森氏症就是個典型例子──

In Parkinson's, there's one particular kind of neuron deep in your brain

帕金森氏症患者的大腦深處 有種特定類型的神經元

that is responsible for the disease,

是造成這病的原因，

and these technologies just don't have the resolution that you need

而這些技術根本沒有 你需要的解析度。

to get at that.

And so that's why we're still stuck with the animals.

這就是為什麼我們仍使用動物實驗。

Not that anyone wants to be studying depression

不是每個人都想透過 把老鼠裝罐來研究抑鬱症吧？

by putting mice into jars, right?

It's just that there's this pervasive sense that it's not possible

只是大家普遍意識到

監看健康人士的神經元活動 是不可能的。

to look at the activity of neurons in healthy humans.

So here's what I want to do.

因此我想要做的是這個：

I want to take you into the future.

我想帶你走進未來，

To have a look at one way in which I think it could potentially be possible.

看看我認為一種未來可能實現的方式。

And I want to preface this by saying, I don't have all the details.

先聲明，我沒有所有的細節，

So I'm just going to provide you with a kind of outline.

我只會提供一個大致樣貌。

But we're going to go the year 2100.

我們來到 2100 年。

Now what does the year 2100 look like?

2100 年是什麼樣子？

Well, to start with, the climate is a bit warmer that what you're used to.

首先，氣候比你習慣的還熱些。 （麻薩諸塞州的波士頓市）

(Laughter)

（笑聲）

And that robotic vacuum cleaner that you know and love

那個你熟悉且喜愛的掃地機器人

went through a few generations,

經歷了幾代，

and the improvements were not always so good.

而改進並不總是盡如人意。

(Laughter)

（笑聲）

It was not always for the better.

未必總是改得更好。

But actually, in the year 2100 most things are surprisingly recognizable.

但實際上在 2100 年， 出乎意料地，大多事情仍可辨識出來。

It's just the brain is totally different.

只是大腦完全不同。

For example, in the year 2100,

例如，在 2100 年，

we understand the root causes of Alzheimer's.

我們了解阿茲海默症的根本原因，

So we can deliver targeted genetic therapies or drugs

因此，能提供標靶基因療法或藥物，

to stop the degenerative process before it begins.

在病發前就先阻止它惡化。

So how did we do it?

我們如何辦到的？

Well, there were essentially three steps.

基本上有三個步驟。

The first step was that we had to figure out

第一是我們必須找出

some way to get electrical connections through the skull

某種通過顱骨的接電方式

so we could measure the electrical activity of neurons.

來測量神經元的電訊活動。

And not only that, it had to be easy and risk-free.

不僅如此，它必須簡單且無風險，

Something that basically anyone would be OK with,

是基本上人人可行的方法，

like getting a piercing.

就像穿耳洞一樣。

Because back in 2017,

回溯到 2017 年，

the only way that we knew of to get through the skull

我們唯一知道進入頭骨的方法

was to drill these holes the size of quarters.

是鑽出 25 分錢幣大小的洞。

You would never let someone do that to you.

你絕不會允許有人 在你頭上鑽那樣的洞。

So in the 2020s,

所以到了 2020 年代，

people began to experiment -- rather than drilling these gigantic holes,

人們開始試驗不鑽大的洞，

drilling microscopic holes, no thicker than a piece of hair.

而是鑽細細的孔，不比一根頭髮粗。

And the idea here was really for diagnosis --

這想法主要是用於診斷。

there are lots of times in the diagnosis of brain disorders

為了經常要診斷異常的腦神經活動

when you would like to be able to look at the neural activity beneath the skull

而鑽這些觸及顱下的小洞，

使得重複多次為病人診斷腦障礙

and being able to drill these microscopic holes

would make that much easier for the patient.

變得更容易。

In the end, it would be like getting a shot.

最終會像是打一針而已，

You just go in and you sit down

你只要進去，坐下來，

and there's a thing that comes down on your head,

一樣東西落在你頭上，

瞬間感到刺痛，就結束了，

and a momentary sting and then it's done,

and you can go back about your day.

你可以回去做你原先做的事。

So we're eventually able to do it

我們最終能用雷射光鑽孔。

using lasers to drill the holes.

And with the lasers, it was fast and extremely reliable,

雷射光的速度非常快且非常可靠，

you couldn't even tell the holes were there,

你甚至看不出那裡有個洞，

any more than you could tell that one of your hairs was missing.

就像看不出那裡掉了根頭髮一樣。

And I know it might sound crazy, using lasers to drill holes in your skull,

用雷射光在頭骨上打洞 聽起來可能很瘋狂，

but back in 2017,

但是在 2017 年，

people were OK with surgeons shooting lasers into their eyes

外科醫生將雷射光射入眼睛

進行矯正視力是可被人接受的，

for corrective surgery

So when you're already here, it's not that big of a step.

雷射已被使用了， 所以這不算是多大的進步。

OK?

明白嗎？

So the next step, that happened in the 2030s,

2030 年代發生的下一步

was that it's not just about getting through the skull.

不止於穿過顱骨，

To measure the activity of neurons,

為了測量神經元的活動，

you have to actually make it into the brain tissue itself.

必須實際上穿透進腦組織本身。

And the risk, whenever you put something into the brain tissue,

無論何時，把異物放入腦組織的風險

基本上都是中風。

is essentially that of stroke.

That you would hit a blood vessel and burst it,

你會碰破血管，

導致中風。

and that causes a stroke.

So, by the mid 2030s, we had invented these flexible probes

因此，我們在 2030 年代中期 發明了靈活的探針，

that were capable of going around blood vessels,

能夠隨著血管繞行，

rather than through them.

不會刺穿血管。

And thus, we could put huge batteries of these probes

如此，我們可以將大量的探針電池

into the brains of patients

放入患者腦中，

and record from thousands of their neurons without any risk to them.

記錄成千上萬個神經元， 且不會造成任何風險。

And what we discovered, sort of to our surprise,

我們驚奇地發現

is that the neurons that we could identify

可辨識的神經元

were not responding to things like ideas or emotion,

對想法或情緒等事物沒反應，

which was what we had expected.

不如我們原先的預期。

They were mostly responding to things like Jennifer Aniston

神經元主要回應珍妮佛安妮斯頓、

or Halle Berry

荷莉貝瑞

or Justin Trudeau.

或加拿大總理賈斯汀杜魯道之類。

I mean --

我的意思是……

(Laughter)

（笑聲）

In hindsight, we shouldn't have been that surprised.

事後看來，我們不該感到訝異。

I mean, what do your neurons spend most of their time thinking about?

不然你的神經元 大部分時間在想什麼？

(Laughter)

（笑聲）

But really, the point is that

但說真的，重點是

this technology enabled us to begin studying neuroscience in individuals.

這項技術使我們能 開始研究個體的神經科學。

So much like the transition to genetics, at the single cell level,

就像遺傳學轉到單細胞層次那樣，

we started to study neuroscience, at the single human level.

我們開始在個人身上研究神經科學。

But we weren't quite there yet.

但我們尚未到那兒。

Because these technologies

因為這些技術

were still restricted to medical applications,

仍然侷限於醫療應用，

which meant that we were studying sick brains, not healthy brains.

這意味著我們研究生病的腦，

不是健康的腦。

Because no matter how safe your technology is,

因為不管你的技術有多安全，

you can't stick something into someone's brain

你都不能為了研究的目的

for research purposes.

而將異物插入某人的腦裡。

They have to want it.

必須經過他們同意才行。

And why would they want it?

他們為什麼會同意？

Because as soon as you have an electrical connection to the brain,

因為一旦腦有了電的接頭，

you can use it to hook the brain up to a computer.

就可以用它來接上電腦。

Oh, well, you know, the general public was very skeptical at first.

哦，你是知道的，一開始 公眾對此一直持懷疑態度。

I mean, who wants to hook their brain up to their computers?

畢竟有誰會想要把大腦連上電腦？

Well just imagine being able to send an email with a thought.

想像你腦筋一動， 就能夠發送電子郵件。

(Laughter)

（笑聲）

Imagine being able to take a picture with your eyes, OK?

想像能夠用你的眼睛拍照。

(Laughter)

（笑聲）

Imagine never forgetting anything anymore,

想像再也不會忘記任何東西了，

because anything that you choose to remember

因為你選擇記住的任何東西

will be stored permanently on a hard drive somewhere,

都會永久儲存在某個硬碟上，

able to be recalled at will.

可以隨時召回。

(Laughter)

（笑聲）

The line here between crazy and visionary

瘋狂和夢想之間的界線

was never quite clear.

從來就不是很清楚。

But the systems were safe.

但系統是安全的。

So when the FDA decided to deregulate these laser-drilling systems, in 2043,

因此，當美國食品藥品監督管理局

在 2043 年決定放寬 對雷射光鑽孔系統的管制時，

commercial demand just exploded.

商業需求就爆增了。

People started signing their emails,

人們開始在電子郵件寫著：

"Please excuse any typos.

「錯別字請見諒。

Sent from my brain."

由我的腦送出。」

(Laughter)

（笑聲）

Commercial systems popped up left and right,

到處冒出的商業系統

offering the latest and greatest in neural interfacing technology.

提供最新和最好的神經接口技術。

There were 100 electrodes.

有一百個電極。

A thousand electrodes.

一千個電極。

High bandwidth for only 99.99 a month.

寬頻每月只要 99.99 美元。

(Laughter)

（笑聲）

Soon, everyone had them.

很快，每個人都有了。

And that was the key.

那就是關鍵。

Because, in the 2050s, if you were a neuroscientist,

因為在 2050 年代， 如果你是個神經科學家，

you could have someone come into your lab essentially from off the street.

可從街上找個人進你的實驗室，

And you could have them engaged in some emotional task

讓他們參與一些情緒上的任務、

or social behavior or abstract reasoning,

社會行為或抽象推理，

things you could never study in mice.

這些永遠無法 在老鼠身上學到的東西。

And you could record the activity of their neurons

你可以用他們現成的接口

using the interfaces that they already had.

記錄他們的神經元活動。

And then you could also ask them about what they were experiencing.

也可以問他們正經歷什麼。

因此，你永遠無法在動物身上做出的

So this link between psychology and neuroscience

that you could never make in the animals, was suddenly there.

這種心理學和神經科學之間的聯繫 突然間就出現了。

So perhaps the classic example of this

也許這個典型的例子

was the discovery of the neural basis for insight.

是發現洞察力的神經基礎。

That "Aha!" moment, the moment it all comes together, it clicks.

那個激出「啊哈！」 靈光乍現時刻的當下，

And this was discovered by two scientists in 2055,

在 2055 年，被兩位科學家 貝瑞和雷特發現了。

Barry and Late,

who observed, in the dorsal prefrontal cortex,

他們觀察背外側前額葉 （Dorsolateral Prefrontal Cortex）

how in the brain of someone trying to understand an idea,

試圖了解某個想法的人腦內部，

how different populations of neurons would reorganize themselves --

不同的神經元群如何重組自己──

you're looking at neural activity here in orange --

神經活動在這裡以橙色顯示──

until finally their activity aligns in a way that leads to positive feedback.

直到最後活動以一種 導致正面反饋的方式對齊。

Right there.

在那裡。

That is understanding.

那就是理解。

So finally, we were able to get at the things that make us human.

我們終於能了解 使我們成為人類的東西。

And that's what really opened the way to major insights from medicine.

這才能真正打開 通向主要醫學見解的道路。

Because, starting in the 2060s,

因為從 2060 年代開始，

with the ability to record the neural activity

我們能夠開始記錄這些

in the brains of patients with these different mental diseases,

不同精神病患者的腦神經活動，

rather than defining the diseases on the basis of their symptoms,

而不是根據他們的症狀來定義疾病，

as we had at the beginning of the century,

就像本世紀初時那樣，

we started to define them

根據我們在神經水平觀察到的

on the basis of the actual pathology that we observed at the neural level.

實際病理來定義它們。

So for example, in the case of ADHD,

例如，對注意力不足過動症 （ADHD）而言，

we discovered that there are dozens of different diseases,

我們發現有幾十種不同的疾病，

all of which had been called ADHD at the start of the century,

在本世紀初全被稱為 ADHD，

that actually had nothing to do with each other,

但實際上它們之間沒有任何關聯，

except that they had similar symptoms.

只是症狀類似，

And they needed to be treated in different ways.

應該要用不同的治療方式。

So it was kind of incredible, in retrospect,

這有點令人難以置信，

that at the beginning of the century,

回想本世紀初，

we had been treating all those different diseases

我們一直在用同樣的藥物 治療這些不同的疾病，

with the same drug,

just by giving people amphetamine, basically is what we were doing.

基本上就是只是給人服用安非他命。

精神分裂症和抑鬱症也是如此。

And schizophrenia and depression are the same way.

So rather than prescribing drugs to people essentially at random,

因此，我們不像以前那樣隨意開藥，

as we had,

we learned how to predict which drugs would be most effective

而是學會瞭解如何預測

哪種藥物對哪些患者最有效，

in which patients,

and that just led to this huge improvement in outcomes.

因而導致巨大的改善結果。

OK, I want to bring you back now to the year 2017.

我現在帶你回 2017 年。

Some of this may sound satirical or even far fetched.

其中一些聽起來很諷刺， 甚至牽強附會。

And some of it is.

有些的確是。

I mean, I can't actually see into the future.

意思是，實際上我看不到未來，

I don't actually know

實際上我並不知道

if we're going to be drilling hundreds or thousands of microscopic holes

我們是否會在 30 年內 在頭部鑽幾百或幾千個微小洞。

in our heads in 30 years.

But what I can tell you

但我能告訴你，

is that we're not going to make any progress

我們無法在理解人類大腦

towards understanding the human brain or human diseases

或人類疾病方面取得任何進展，

until we figure out how to get at the electrical activity of neurons

除非我們先弄清楚如何取得

健康人的神經元電訊活動才能夠做到。

in healthy humans.

And almost no one is working on figuring out how to do that today.

而現今幾乎沒有人在研究如何做。

That is the future of neuroscience.

那是神經科學的未來。

And I think it's time for neuroscientists to put down the mouse brain

我認為現在是神經科學家放下鼠腦，

and to dedicate the thought and investment necessary

專心投入必要的腦力和金錢

to understand the human brain and human disease.

來了解人腦和人類疾病的時候了。

Thank you.

謝謝。

(Applause)

（掌聲）