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I want to tell you guys something about neuroscience. I'm a physicist by training.
我想跟各位聊一聊神经科学。我是物理学家，科班出身。
About three years ago, I left physics to come and try to understand how the brain works.
大约三年前，我离开了物理学领域，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. Lots of people are working on depression.
我发现，很多人都在研究抑郁症。
And that's really good, depression is something that we really want to understand.
这非常好，我们的确特别想了解抑郁症。
Here's how you do it: you take a jar and you fill it up, about halfway, with water.
但研究是这样进行的：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 and then at some point, the mouse gets tired and decides to stop swimming.
老鼠四处游了一会儿，到某一时刻，老鼠累了，决定不游了。
And when it stops swimming, that's depression. OK?
它一旦不游了，就是得了抑郁症。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 to precisely describe physical phenomena,
所以我习惯了用非常复杂的数学模型来精确描述物理现象，
so when I saw that this is the model for depression, I though to myself, "Oh my God, we have a lot of work to do."
所以当我看到抑郁症的模型是这个样子时，我心想，“天呐，要做的工作还多着呢。”
But this is a kind of general problem in neuroscience. So for example, take emotion.
但这问题在神经科学中几乎普遍存在。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 because you can't ask them how they're feeling or what they're experiencing.
但是，在老鼠或猴子身上没法研究情绪，因为你不能问它们感觉如何或正在经历什么。
So instead, people who want to understand emotion, typically end up studying what's called motivated behavior,
所以，想要理解情绪的人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. I mean, the point is, the NIH spends about 5.5 billion dollars a year on neuroscience research.
我可以没完没了地说下去。我的意思是，关键在于，NIH每年花费大约55亿美元用于神经科学研究。
And yet there have been almost no significant improvements in outcomes for patients with brain diseases in the past 40 years.
然而，在过去40年中，对脑病患者的治疗效果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 that mice might be OK as a model for cancer or diabetes,
我认为，这在很大程度上是由于老鼠也许能做癌症或糖尿病的模型，
but the mouse brain is just not sophisticated enough to reproduce human psychology or human brain disease. OK?
但是老鼠的大脑却不够复杂，无法复制人类的心理或人类的脑部疾病。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 which are these little cells that send electrical signals to each other.
大脑是由神经元组成的，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, you have to be able to measure the electrical activity of these neurons.
如果你想了解大脑是如何工作的，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 with some kind of electrical recording device or a microscope.
但要做到这一点，你必须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 but for some reason we still can't do that in humans, OK?
因为你可以真正地把设备放进它们的大脑，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, functional MRI, fMRI,
最流行的应该是这个，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 when you're engaged in different activities.
显示当你从事不同的活动时，大脑的哪个部分会发光。
But this is a proxy. You're not actually measuring neural activity here.
但这只是一个替代工具。你实际上并不是在测量神经活动。
What you're doing is you're measuring, essentially, like, blood flow in the brain.
你是在测量大脑中的血液流动。
Where there's more blood. It's actually where there's more oxygen, but you get the idea, OK?
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？
The other thing that you can do is you can do this -- electroencephalography -- you can put these electrodes on your head, OK?
另一种方法是这个--脑电图--可以把这些电极放在你的头上。
And then you can measure your brain waves. And here, you're actually measuring electrical activity.
然后可以测量你的脑电波。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, sloshing back and forth in your brain.
你测量的是这些电流，在你的大脑中来回流动的电流。
So the point is just that these technologies that we have are really measuring the wrong thing.
所以问题是，我们所拥有的这些技术实际上是在测量错误的东西。
Because, for most of the diseases that we want to understand -- like, Parkinson's is the classic example.
因为，对于我们想了解的大多数疾病--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 that is responsible for the disease,
对于帕金森症，大脑深处有一种特殊的神经元对这种疾病负责，
and these technologies just don't have the resolution that you need to get at that.
而现有的这些技术还没有办法检测这些神经元。
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 by putting mice into jars, right?
谁也不是真的想用罐子里的老鼠来研究抑郁症，对吧？
It's just that there's this pervasive sense that it's not possible to look at the activity of neurons in healthy humans.
只是有一种共识告诉我们，不可能观察到健康人的神经元活动。
So here's what I want to do. I want to take you into the future.
那么，接下来，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. Now what does the year 2100 look like?
我们要去的是2100年。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。
And that robotic vacuum cleaner that you know and love went through a few generations,
你了解并喜爱的机器人真空吸尘器进化了好几代，
and the improvements were not always so good. It was not always for the better.
但进化的结果不怎么样。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. For example, in the year 2100, we understand the root causes of Alzheimer's.
只是大脑完全不同了。例如，在2100年，我们了解了阿尔茨海默症的病源。
So we can deliver targeted genetic therapies or drugs to stop the degenerative process before it begins.
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。
So how did we do it? Well, there were essentially three steps.
那是怎么做到的呢？基本上有三个步骤。
The first step was that we had to figure out some way to get electrical connections through the skull
第一步，我们必须想办法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, like getting a piercing.
它必须是人人都能接受的，就像穿个耳洞。
Because back in 2017, the only way that we knew of to get through the skull was to drill these holes the size of quarters.
因为早在2017年，人们知道的穿过头骨的唯一方法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, people began to experiment -- rather than drilling these gigantic holes,
所以在21世纪20年代，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 -- there are lots of times in the diagnosis of brain disorders
这个方法实际是用于诊断--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 would make that much easier for the patient.
而能够钻这些微小的孔，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 and there's a thing that comes down on your head,
你只要到医院，坐下来，有个设备降到你的头上，
and a momentary sting and then it's done, and you can go back about your day.
短暂的一下刺痛，就完事了，你可以回去继续忙你的了。
So we're eventually able to do it using lasers to drill the holes.
最终，我们能够用激光钻孔来实现这种方法。
And with the lasers, it was fast and extremely reliable, you couldn't even tell the holes were there,
激光又快又非常可靠，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, people were OK with surgeons shooting lasers into their eyes for corrective surgery.
但早在2017年，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。
So when you're already here, it's not that big of a step. OK?
所以，有了这个基础，跨度也就不显得那么大了。对吧？
So the next step, that happened in the 2030s, was that it's not just about getting through the skull.
下一步，发生在21世纪30年代的，就不仅仅是穿过头骨了。
To measure the activity of neurons, you have to actually make it into the brain tissue itself.
为了测量神经元的活动，你必须真正进入大脑组织本身。
And the risk, whenever you put something into the brain tissue, is essentially that of stroke.
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。
That you would hit a blood vessel and burst it, and that causes a stroke.
你会碰到血管并使其破裂，从而导致中风。
So, by the mid 2030s, we had invented these flexible probes that were capable of going around blood vessels, rather than through them.
所以，到21世纪30年代中期，我们发明了柔性探针，它能围绕血管安置，而不用穿过血管。
And thus, we could put huge batteries of these probes into the brains of patients
因此，我们可以将这些探针的巨大电池放入病人的大脑中，
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 were not responding to things like ideas or emotion, which was what we had expected.
我们能识别的神经元对想法或情绪之类的东西并没有做出反应，这就与我们所期望的不一样。
They were mostly responding to things like Jennifer Aniston or Halle Berry or Justin Trudeau.
让它们有反应的是珍妮弗·安妮斯顿、哈里·贝瑞或贾斯汀·特鲁多。
I mean -- In hindsight, we shouldn't have been that surprised.
我的意思是--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？
But really, the point is that this technology enabled us to begin studying neuroscience in individuals.
但说真的，关键是，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, we started to study neuroscience, at the single human level.
就像遗传学转化到单细胞水平的研究，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. Because these technologies were still restricted to medical applications,
但这一步也还不够。因为这些技术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, you can't stick something into someone's brain for research purposes.
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别人的大脑。
They have to want it. And why would they want it?
人们必须自己想要这么做。那人们为什么想这么做呢？
Because as soon as you have an electrical connection to the brain, you can use it to hook the brain up to a computer.
因为一旦大脑通了电，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子邮件。
Imagine being able to take a picture with your eyes, OK?
想象一下能用眼睛拍照。
Imagine never forgetting anything anymore,
想象永远不会忘记任何东西，
because anything that you choose to remember will be stored permanently on a hard drive somewhere, able to be recalled at will.
因为你选择记住的所有事，都将永久存储在某个硬盘上，可以随意回忆。
The line here between crazy and visionary was never quite clear. But the systems were safe.
疯狂与眼界之间的界限一直不太清晰。但这些系统是安全的。
So when the FDA decided to deregulate these laser-drilling systems, in 2043, commercial demand just exploded.
因此，当FDA在2043年决定解除对激光钻孔系统的管制时，商业需求爆发了。
People started signing their emails, "Please excuse any typos. Sent from my brain."
人们的电邮签名变成，“请原谅我的错别字。本文来自我的大脑。”
Commercial systems popped up left and right, offering the latest and greatest in neural interfacing technology.
商业系统左右逢源，开始提供最新最大的神经接口技术。
There were 100 electrodes. A thousand electrodes. High bandwidth for only 99.99 a month.
有百电极规格。千电极规格。高速带宽，每月仅99.99。
Soon, everyone had them. And that was the key.
很快，大家都有了。那才是关键。
Because, in the 2050s, if you were a neuroscientist, you could have someone come into your lab essentially from off the street.
因为，到21世纪50年代，如果你是神经科学家，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 or social behavior or abstract reasoning,
让他们做一些情绪任务、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 using the interfaces that they already had.
你可以用他们已经有的接口记录他们神经元的活动。
And then you could also ask them about what they were experiencing.
然后你还可以问问他们的感受。
So this link between psychology and neuroscience that you could never make in the animals, was suddenly there.
所以在动物身上永远无法建立的心理学和神经科学之间的这种联系，就这么出现了。
So perhaps the classic example of this was the discovery of the neural basis for insight.
这方面的典型例子可能是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, Barry and Late,
这是两位科学家，巴里和雷特，在2055年发现的，
who observed, in the dorsal prefrontal cortex, how in the brain of someone trying to understand an idea,
他们在背侧前额叶皮层观察到人的大脑如何理解一个想法，
how different populations of neurons would reorganize themselves -- you're looking at neural activity here in orange
不同的神经元群体如何重新组织自己--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. Right there. That is understanding.
直到它们的活动最终以一种导向正反馈的方式匹配。就这一下。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21世纪60年代开始，
with the ability to record the neural activity in the brains of patients with these different mental diseases,
我们将有能力记录这些不同精神疾病的患者大脑中的神经活动，
rather than defining the diseases on the basis of their symptoms, as we had at the beginning of the century,
而不是像本世纪初那样，根据症状来定义疾病，
we started to define them on the basis of the actual pathology that we observed at the neural level.
我们开始根据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, we discovered that there are dozens of different diseases,
例如，在多动症（ADHD）的例子中，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, except that they had similar symptoms.
但它们除了症状相似之外，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, that at the beginning of the century,
回想起来，令人难以置信的是，在本世纪初，
we had been treating all those different diseases with the same drug,
我们一直用同一种药物治疗所有这些不同的疾病，
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。
And schizophrenia and depression are the same way.
治疗精神分裂症和抑郁症也一样。
So rather than prescribing drugs to people essentially at random, as we had,
因此，我们不再像以前那样，几乎是随机地给人们开药，
we learned how to predict which drugs would be most effective in which patients,
而是学会了如何预测哪些药物对哪些患者最有效，
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. I mean, I can't actually see into the future.
有些的确是。我的意思是，我不能真的看到未来。
I don't actually know if we're going to be drilling hundreds or thousands of microscopic holes in our heads in 30 years.
我也不知道30年后我们是否会在头上钻上成百上千个微小的孔。
But what I can tell you is that we're not going to make any progress towards understanding the human brain or human diseases
但我可以告诉你的是，如果要在了解人脑或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 in healthy humans.
就必须先知道如何获得健康人大脑神经元的电活动。
And almost no one is working on figuring out how to do that today. That is the future of neuroscience.
今天几乎没有人在研究要如何做到这一点。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 to understand the human brain and human disease. Thank you.
投入必要的人力和资金去理解人脑和人类疾病了。谢谢。
