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

翻译人员: Yan Gao 校对人员: Yolanda Zhang

I want to tell you guys something about neuroscience.

我想跟各位聊一聊神经科学。

I'm a physicist by training.

我是物理学家，科班出身。

About three years ago, I left physics

大约三年前，我离开了物理学领域，

to come and try to understand how the brain works.

转行到神经科学，试图了解 大脑是如何工作的。

And this is what I found.

我发现，

Lots of people are working on depression.

很多人都在研究抑郁症。

And that's really good,

这非常好，

depression is something that we really want to understand.

我们的确特别想了解抑郁症。

但研究是这样进行的：

Here's how you do it:

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

拿个罐子，装上大约半罐的水。

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

然后找一只老鼠，把它放进罐子里。

And the mouse swims around for a little while

老鼠四处游了一会儿，

and then at some point, the mouse gets tired

到某一时刻，老鼠累了，

and decides to stop swimming.

决定不游了。

And when it stops swimming, that's depression.

它一旦不游了，就是得了抑郁症。

OK?

对吗？

And I'm from theoretical physics,

我以前是学理论物理的，

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

所以我习惯了 用非常复杂的数学模型

to precisely describe physical phenomena,

来精确描述物理现象，

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

所以当我看到抑郁症的 模型是这个样子时，

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

我心想，“天呐， 要做的工作还多着呢。”

(Laughter)

（笑声）

But this is a kind of general problem in neuroscience.

但这问题在神经科学中 几乎普遍存在。

So for example, take emotion.

比如说，以情绪为例。

Lots of people want to understand emotion.

很多人想理解情绪。

But you can't study emotion in mice or monkeys

但是，在老鼠或猴子身上 没法研究情绪，

because you can't ask them

因为你不能问它们

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

感觉如何或正在经历什么。

所以，想要理解情绪的人

So instead, people who want to understand emotion,

typically end up studying what's called motivated behavior,

通常变成研究所谓的行为激励法，

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

这个术语的意思是“老鼠 特别特别想要奶酪时会做什么”。

OK, I could go on and on.

我可以没完没了地说下去。

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

我的意思是，关键在于， NIH每年花费大约55亿美元

on neuroscience research.

用于神经科学研究。

And yet there have been almost no significant improvements in outcomes

然而，在过去40年中， 对脑病患者的治疗效果

for patients with brain diseases in the past 40 years.

几乎没有获得任何显著的进步。

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

我认为，这在很大程度上是由于

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

老鼠也许能做癌症 或糖尿病的模型，

but the mouse brain is just not sophisticated enough

但是老鼠的大脑却不够复杂，

to reproduce human psychology or human brain disease.

无法复制人类的心理 或人类的脑部疾病。

OK?

对吧？

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

那么，既然老鼠模型那么差， 为什么我们还在用它？

Well, it basically boils down to this:

原因大致是这样的：

the brain is made up of neurons

大脑是由神经元组成的，

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

这些神经元是相互发送 电信号的小细胞。

If you want to understand how the brain works,

如果你想了解大脑是如何工作的，

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

就必须能够测量 这些神经元的电活动。

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

但要做到这一点，你必须

with some kind of electrical recording device or a microscope.

用某种电记录设备或显微镜 来真正接近神经元。

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

这个可以在老鼠身上做， 也可以在猴子身上做，

because you can physically put things into their brain

因为你可以真正地把 设备放进它们的大脑，

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

但是由于某些原因，我们 还不能在人类身上这样做，对吧？

So instead, we've invented all these proxies.

所以，我们发明了各种替代工具。

So the most popular one is probably this,

最流行的应该是这个，

functional MRI, fMRI,

功能性磁共振成像，fMRI，

which allows you to make these pretty pictures like this,

它可以做出这样的美丽图片，

that show which parts of your brain light up

显示当你从事不同的活动时，

when you're engaged in different activities.

大脑的哪个部分会发光。

But this is a proxy.

但这只是一个替代工具。

You're not actually measuring neural activity here.

你实际上并不是在测量神经活动。

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

你是在测量大脑中的

like, blood flow in the brain.

血液流动。

Where there's more blood.

看哪里的含血量更高。

其实是看哪里氧气多， 但你懂我意思了，对吧？

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

另一种方法是这个——

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

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

脑电图——可以把 这些电极放在你的头上，

And then you can measure your brain waves.

然后可以测量你的脑电波。

And here, you're actually measuring electrical activity.

而这实际上是在测量电活动。

But you're not measuring the activity of neurons.

而不是在测量神经元的活动。

You're measuring these electrical currents,

你测量的是这些电流，

sloshing back and forth in your brain.

在你的大脑中来回流动的电流。

So the point is just that these technologies that we have

所以问题是，我们所拥有的这些技术

are really measuring the wrong thing.

实际上是在测量错误的东西。

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

因为，对于我们想了解的 大多数疾病——

like, Parkinson's is the classic example.

比如帕金森症就是典型的例子。

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

对于帕金森症，大脑深处 有一种特殊的神经元

that is responsible for the disease,

对这种疾病负责，

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

而现有的这些技术还没有办法

检测这些神经元。

to get at that.

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

所以这就是为什么 我们仍然在用动物。

Not that anyone wants to be studying depression

谁也不是真的想

用罐子里的老鼠 来研究抑郁症，对吧？

by putting mice into jars, right?

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

只是有一种共识告诉我们，

to look at the activity of neurons in healthy humans.

不可能观察到 健康人的神经元活动。

So here's what I want to do.

那么，接下来，

I want to take you into the future.

我想带你们进入未来。

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

看一看我认为有可能的一种方式。

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

首先我想说，我没有完善的细节。

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

所以我只提供大概的介绍。

But we're going to go the year 2100.

我们要去的是2100年。

Now what does the year 2100 look like?

2100年是什么样子呢？

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

首先，气候比你习惯的暖和一点。

(Laughter)

（笑声）

And that robotic vacuum cleaner that you know and love

你了解并喜爱的机器人真空吸尘器

went through a few generations,

进化了好几代，

and the improvements were not always so good.

但进化的结果不怎么样。

(Laughter)

（笑声）

It was not always for the better.

并不总是越来越好。

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

但实际上，在2100年， 我们居然还能认出大部分的事物，

It's just the brain is totally different.

只是大脑完全不同了。

For example, in the year 2100,

例如，在2100年，

we understand the root causes of Alzheimer's.

我们了解了阿尔茨海默症的病源。

So we can deliver targeted genetic therapies or drugs

所以我们可以在 大脑功能退化开始之前，

提供有针对性的基因治疗 或药物来阻止退化。

to stop the degenerative process before it begins.

So how did we do it?

那是怎么做到的呢？

Well, there were essentially three steps.

基本上有三个步骤。

The first step was that we had to figure out

第一步，我们必须想办法

some way to get electrical connections through the skull

让电信号的连接穿过头骨，

so we could measure the electrical activity of neurons.

这样我们就可以测量 神经元的电活动。

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

不仅如此，这一过程还必须 容易操作且无风险。

Something that basically anyone would be OK with,

它必须是人人都能接受的，

like getting a piercing.

就像穿个耳洞。

Because back in 2017,

因为早在2017年，

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

人们知道的穿过头骨的唯一方法

was to drill these holes the size of quarters.

就是钻出硬币大小的洞。

You would never let someone do that to you.

谁都不会接受的。

So in the 2020s,

所以在21世纪20年代，

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

人们开始实验—— 不是钻这些巨大的孔，

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

而是钻出不到一根头发丝 那么厚的微型孔。

And the idea here was really for diagnosis --

这个方法实际是用于诊断——

there are lots of times in the diagnosis of brain disorders

在脑部疾病的诊断中，有很多时候，

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

你希望能够看到 颅骨底下的神经活动，

and being able to drill these microscopic holes

而能够钻这些微小的孔，

would make that much easier for the patient.

会让病人更容易 接受这种诊断方法。

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

最终，它就像打针。

You just go in and you sit down

你只要到医院，坐下来，

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

有个设备降到你的头上，

短暂的一下刺痛，就完事了，

and a momentary sting and then it's done,

and you can go back about your day.

你可以回去继续忙你的了。

So we're eventually able to do it

最终，我们能够用激光钻孔

using lasers to drill the holes.

来实现这种方法。

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

激光又快又非常可靠，

you couldn't even tell the holes were there,

你甚至感觉不到有孔，

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

就像感觉不到掉了一根头发一样。

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

我知道用激光在颅骨上钻孔 听起来可能很疯狂，

but back in 2017,

但早在2017年，

people were OK with surgeons shooting lasers into their eyes

人们就已经接受外科医生向 他们的眼睛里发射激光了，

就为了做矫正手术，

for corrective surgery

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

所以，有了这个基础， 跨度也就不显得那么大了。

OK?

对吧？

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

下一步，发生在2030年代的，

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

就不仅仅是穿过头骨了。

To measure the activity of neurons,

为了测量神经元的活动，

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

你必须真正进入大脑组织本身。

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

而风险是，只要往脑组织里放东西，

那基本上就等于在引发中风。

is essentially that of stroke.

That you would hit a blood vessel and burst it,

你会碰到血管并使其破裂，

从而导致中风。

and that causes a stroke.

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

所以，到2030年代中期， 我们发明了柔性探针，

that were capable of going around blood vessels,

它能围绕血管安置，

rather than through them.

而不用穿过血管。

And thus, we could put huge batteries of these probes

因此，我们可以将 这些探针的巨大电池

into the brains of patients

放入病人的大脑中，

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

对成千上万个神经元 进行记录，而不带来风险。

And what we discovered, sort of to our surprise,

令人惊讶的是，我们发现，

is that the neurons that we could identify

我们能识别的神经元

were not responding to things like ideas or emotion,

对想法或情绪之类的东西 并没有做出反应，

which was what we had expected.

这就与我们所期望的不一样。

They were mostly responding to things like Jennifer Aniston

让它们有反应的是 珍妮弗 · 安妮斯顿、

or Halle Berry

哈里 · 贝瑞、

or Justin Trudeau.

或贾斯汀 · 特鲁多。

I mean --

我的意思是——

(Laughter)

（笑声）

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

事后看来，也不用太惊讶。

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

再说，你的神经元 大部分时间想的是什么呢？

(Laughter)

（笑声）

But really, the point is that

但说真的，关键是，

this technology enabled us to begin studying neuroscience in individuals.

这项技术使我们能够开始 以个体为单位研究神经科学。

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

就像遗传学转化到 单细胞水平的研究，

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

我们开始在单个人类水平上 研究神经科学。

But we weren't quite there yet.

但这一步也还不够。

Because these technologies

因为这些技术

were still restricted to medical applications,

仍然局限于医学应用，

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

意味着我们研究的是病态大脑， 而不是健康的大脑。

Because no matter how safe your technology is,

因为不管技术有多安全，

你都不能为了研究目的把东西塞进

you can't stick something into someone's brain

for research purposes.

别人的大脑。

They have to want it.

人们必须自己想要这么做。

And why would they want it?

那人们为什么想这么做呢？

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

因为一旦大脑通了电，

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

就可以把人脑连接到电脑上。

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

你知道，公众一开始很怀疑。

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

谁想把自己的大脑连到电脑上呢？

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

那想象一下，你可以 用你的想法来发电邮。

(Laughter)

（笑声）

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

想象一下能用眼睛拍照。

(Laughter)

（笑声）

Imagine never forgetting anything anymore,

想象永远不会忘记任何东西，

because anything that you choose to remember

因为你选择记住的所有事

will be stored permanently on a hard drive somewhere,

都将永久存储在某个硬盘上，

able to be recalled at will.

可以随意回忆。

(Laughter)

（笑声）

The line here between crazy and visionary

疯狂与眼界之间的界限

was never quite clear.

一直不太清晰。

But the systems were safe.

但这些系统是安全的。

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

因此，当FDA在2043年决定 解除对激光钻孔系统的管制时，

commercial demand just exploded.

商业需求爆发了。

People started signing their emails,

人们的电邮签名变成，

"Please excuse any typos.

“请原谅我的错别字。

Sent from my brain."

本文来自我的大脑。”

(Laughter)

（笑声）

Commercial systems popped up left and right,

商业系统左右逢源，

offering the latest and greatest in neural interfacing technology.

开始提供最新最大的 神经接口技术。

There were 100 electrodes.

有百电极规格。

A thousand electrodes.

千电极规格。

High bandwidth for only 99.99 a month.

高速带宽，每月仅99.99。

（笑声）

(Laughter)

Soon, everyone had them.

很快，大家都有了。

And that was the key.

那才是关键。

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

因为，到2050年代， 如果你是神经科学家，

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

你可以到大街上 随便找个人来实验室。

And you could have them engaged in some emotional task

让他们做一些情绪任务、

or social behavior or abstract reasoning,

社交行为或抽象推理，

things you could never study in mice.

这些不能用老鼠研究的东西。

And you could record the activity of their neurons

你可以用他们已经有的接口

using the interfaces that they already had.

记录他们神经元的活动。

然后问他们的感受。

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

So this link between psychology and neuroscience

所以在动物身上永远无法建立的 心理学和神经科学

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

之间的这种联系，就这么出现了。

So perhaps the classic example of this

这方面的典型例子可能是

was the discovery of the neural basis for insight.

发现了洞察力的神经基础。

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

那种“原来如此！”的瞬间， 恍然大悟的时刻到来了。

And this was discovered by two scientists in 2055,

这是两位科学家巴里和雷特

Barry and Late,

在2055年发现的，

who observed, in the dorsal prefrontal cortex,

他们在背侧前额叶皮层观察到

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

人的大脑如何理解一个想法，

不同的神经元群体 如何重新组织自己——

how different populations of neurons would reorganize themselves --

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

你现在看到的橙色是神经活动——

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

直到它们的活动最终以一种 导向正反馈的方式匹配。

Right there.

就这一下。

That is understanding.

这就是理解。

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

终于，我们能够找到 让我们成为人类的东西。

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

它真正为医学的 深入研究开辟了道路。

Because, starting in the 2060s,

因为从2060年代开始，

with the ability to record the neural activity

我们将有能力记录 这些不同精神疾病的

in the brains of patients with these different mental diseases,

患者大脑中的神经活动，

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

而不是像本世纪初那样，

as we had at the beginning of the century,

根据症状来定义疾病，

we started to define them

我们开始根据

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

在神经层面观察到的 实际病理来定义疾病。

So for example, in the case of ADHD,

例如，在多动症（ADHD）的例子中，

we discovered that there are dozens of different diseases,

我们发现有数十种不同的疾病，

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

所有这些疾病在本世纪初 都被称为ADHD，

that actually had nothing to do with each other,

但它们除了症状相似之外，

except that they had similar symptoms.

实际上彼此无关。

And they needed to be treated in different ways.

并且需要以不同的方式治疗。

So it was kind of incredible, in retrospect,

回想起来，令人难以置信的是，

that at the beginning of the century,

在本世纪初，

we had been treating all those different diseases

我们一直用同一种药物

治疗所有这些不同的疾病，

with the same drug,

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

基本上我们所做的就是 给患者服用安非他明。

治疗精神分裂症和抑郁症也一样。

And schizophrenia and depression are the same way.

So rather than prescribing drugs to people essentially at random,

因此，我们不再像以前那样， 几乎是随机地

as we had,

给人们开药，

we learned how to predict which drugs would be most effective

而是学会了如何预测 哪些药物对哪些患者

in which patients,

最有效，

and that just led to this huge improvement in outcomes.

这将带来治疗结果的巨大改善。

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

好的，现在我们回到2017年。

Some of this may sound satirical or even far fetched.

有些内容可能听起来很讽刺， 甚至有些牵强。

And some of it is.

有些的确是。

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

我的意思是，我不能真的看到未来。

I don't actually know

我也不知道

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

30年后我们是否 会在头上钻上成百上千个

in our heads in 30 years.

微小的孔。

But what I can tell you

但我可以告诉你的是，

is that we're not going to make any progress

如果要在了解人脑或

towards understanding the human brain or human diseases

人类疾病方面取得任何进步，

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

就必须先知道如何获得

健康人大脑神经元的电活动。

in healthy humans.

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

今天几乎没有人在研究 要如何做到这一点。

That is the future of neuroscience.

而这才是神经科学的未来。

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

我认为是时候让 神经科学家放弃鼠脑，

and to dedicate the thought and investment necessary

投入必要的人力和资金

to understand the human brain and human disease.

去理解人脑和人类疾病了。

Thank you.

谢谢。

(Applause)

（掌声）