David Anderson: Your brain is more than a bag of chemicals

Translator: Joseph Geni Reviewer: Morton Bast

翻译人员: Celine Kan 校对人员: xuan wang

So raise your hand if you know someone

如果你知道

in your immediate family or circle of friends

你的亲人或者朋友中

who suffers from some form of mental illness.

有人正遭受某种精神疾病折磨的请举手。

Yeah. I thought so. Not surprised.

和我想的一样，没什么好惊讶的。

And raise your hand if you think that

如果你觉得对果蝇的基础研究

basic research on fruit flies has anything to do

对人类精神疾病的了解

with understanding mental illness in humans.

有任何作用的话，请举手。

Yeah. I thought so. I'm also not surprised.

和我想的一样，这也没什么好惊讶的。

I can see I've got my work cut out for me here.

看来我的任务艰巨了。

As we heard from Dr. Insel this morning,

像我们今早从Insel博士那里听到的那样，

psychiatric disorders like autism, depression and schizophrenia

像自闭症、 抑郁症、 精神分裂症等精神障碍

take a terrible toll on human suffering.

让人类遭受着可怕的痛苦。

We know much less about their treatment

我们对（精神疾病）的治疗

and the understanding of their basic mechanisms

和它们基本机理的了解

than we do about diseases of the body.

比我们对身体上疾病的了解少的多。

Think about it: In 2013,

想想看： 在 2013 年，

the second decade of the millennium,

千禧年的第二个十年，

if you're concerned about a cancer diagnosis

如果你对罹患癌症感到担心

and you go to your doctor, you get bone scans,

你可以去看医生， 你可以进行骨扫描，

biopsies and blood tests.

切片检查以及血液测试。

In 2013, if you're concerned about a depression diagnosis,

在 2013 年，如果你担心得了抑郁症，

you go to your doctor, and what do you get?

你去看医生，你能得到些什么呢？

A questionnaire.

一份调查问卷。

Now, part of the reason for this is that we have

现在，这种情况发生的部分原因是

an oversimplified and increasingly outmoded view

对于精神障碍的生物学基础

of the biological basis of psychiatric disorders.

我们有一个过分简化和过时的观点，

We tend to view them --

我们倾向于认为他们 －－

and the popular press aids and abets this view --

同时大众媒体也教唆给大家同样的观点 －－

as chemical imbalances in the brain,

（精神疾病）即是大脑中化学物质的失衡，

as if the brain were some kind of bag of chemical soup

好像大脑就是某种袋子，

full of dopamine, serotonin and norepinephrine.

里面装满了由多巴胺，5 - 羟色胺和去甲肾上腺素混合的化学物质。

This view is conditioned by the fact

以下例子可以印证上述观点

that many of the drugs that are prescribed to treat these disorders,

即很多被开出来治疗这些疾病的处方药，

like Prozac, act by globally changing brain chemistry,

如百忧解，都是通过全局性的改变大脑化学构成来起效果的，

as if the brain were indeed a bag of chemical soup.

好像大脑真是一袋子化学物质。

But that can't be the answer,

但那肯定不是正确的解释，

because these drugs actually don't work all that well.

实际上这些药并不都会带来显著疗效。

A lot of people won't take them, or stop taking them,

因为这些药有不好的副作用，

because of their unpleasant side effects.

很多人不会吃这些药，或者干脆停药。

These drugs have so many side effects

这些药有很多副作用

because using them to treat a complex psychiatric disorder

因为用他们去治疗一例复杂的精神障碍

is a bit like trying to change your engine oil

就好像你为了去换一下发动机的机油

by opening a can and pouring it all over the engine block.

却打开了机油罐然后倒的引擎上到处都是。

Some of it will dribble into the right place,

有些药效会直接作用于正确的病处，

but a lot of it will do more harm than good.

但大多数对人体造成的伤害多于好处。

Now, an emerging view

现在，一个今天早上

that you also heard about from Dr. Insel this morning,

你也从Insel博士那里听说的全新的观点

is that psychiatric disorders are actually

即精神障碍实际上就是

disturbances of neural circuits that mediate

一种对那些谐调表情、情绪以及情感

emotion, mood and affect.

的神经回路的干扰。

When we think about cognition,

当我们想着去认知它的时候，

we analogize the brain to a computer. That's no problem.

我们把大脑比作电脑是没问题的。

Well it turns out that the computer analogy

那么结果显示把大脑比作电脑的比喻

is just as valid for emotion.

对处理情感也是有效的。

It's just that we don't tend to think about it that way.

只是我们通常不倾向于用这种方式去思考。

But we know much less about the circuit basis

但是因为这种化学不平衡假说

of psychiatric disorders

具有压倒性的优势

because of the overwhelming dominance

所以我们对精神障碍回路

of this chemical imbalance hypothesis.

的基础知识知之甚少。

Now, it's not that chemicals are not important

现在，我们不是说化学物质

in psychiatric disorders.

在精神障碍中不重要。

It's just that they don't bathe the brain like soup.

只是大脑不是简单混沌的(由化学物质组成的)混合液体，

Rather, they're released in very specific locations

而是，他们(化学物质)被释放在非常精确的位置

and they act on specific synapses

并作用于某个确定的神经突触

to change the flow of information in the brain.

来改变大脑中的信息流。

So if we ever really want to understand

因此如果我们真正想懂得精神障碍

the biological basis of psychiatric disorders,

相关的生物基础知识，

we need to pinpoint these locations in the brain

我们得搞清楚这些化学物质

where these chemicals act.

具体起作用于大脑中的哪些位置。

Otherwise, we're going to keep pouring oil all over our mental engines

否则，我们将要继续把油弄的满是我们的精神引擎

and suffering the consequences.

并且承受各种痛苦。

Now to begin to overcome our ignorance

现在为了克服我们对大脑化学物质

of the role of brain chemistry in brain circuitry,

在大脑回路中的作用的无知，

it's helpful to work on what we biologists call

在我们生物学家称作的

"model organisms,"

“模式生物”，

animals like fruit flies and laboratory mice,

比如果蝇和试验鼠等动物身上做试验是有帮助的。

in which we can apply powerful genetic techniques

这样我们可以应用强大的基因技术来

to molecularly identify and pinpoint

分子识别以及

specific classes of neurons,

确定具体的神经元的种类，

as you heard about in Allan Jones's talk this morning.

就如大家今天早上听到 Allan Jones的讲话内容一样。

Moreover, once we can do that,

而且，一旦我们可以那么做了，

we can actually activate specific neurons

实际上我们就可以激活特定的神经元

or we can destroy or inhibit the activity of those neurons.

或者可以毁坏或者抑制那些神经元的活性。

So if we inhibit a particular type of neuron,

因此一旦我们抑制了某种特定的神经元，

and we find that a behavior is blocked,

并且发现某种行为被阻止了的时候，

we can conclude that those neurons

我们就可以得出

are necessary for that behavior.

那些神经元是负责相应的行为的结论。

On the other hand, if we activate a group of neurons

从另一方面来讲，如果我们激活了一组神经元

and we find that that produces the behavior,

并且发现他们激发了某种行为，

we can conclude that those neurons are sufficient for the behavior.

我们就可以得到这组神经元是对特定行为负责的结论。

So in this way, by doing this kind of test,

因此，通过做这种试验，

we can draw cause and effect relationships

我们可以理清楚

between the activity of specific neurons

特定神经元在某种回路上的活动

in particular circuits and particular behaviors,

与相应行为的因果关系，

something that is extremely difficult, if not impossible,

而在人类身上做这些实验

to do right now in humans.

是极其困难的。

But can an organism like a fruit fly, which is --

但是有机体如果蝇--

it's a great model organism

就是很好的试验对象

because it's got a small brain,

因为它有一个小的大脑，

it's capable of complex and sophisticated behaviors,

一个能完成复杂的行为的脑袋，

it breeds quickly, and it's cheap.

而且它培育起来很快，费用也不高。

But can an organism like this

但像果蝇这样的有机体

teach us anything about emotion-like states?

是否可以给我们展示任何情感状态呢？

Do these organisms even have emotion-like states,

这些有机体是否拥有情感状态，

or are they just little digital robots?

或者他们只是像小型数字机器人(无情感状态)？

Charles Darwin believed that insects have emotion

查尔斯·达尔文认为昆虫是有情感的

and express them in their behaviors, as he wrote

并且有它们的情感表现方式

in his 1872 monograph on the expression of the emotions in man and animals.

就像他在1872年出版的著作中关于人类与动物情感的表达方式的描写。

And my eponymous colleague, Seymour Benzer, believed it as well.

与我齐名的同事，Seymour Benzer，同样认为昆虫是有情感的。

Seymour is the man that introduced the use of drosophila

在60年代的加州理工学院，

here at CalTech in the '60s as a model organism

Seymour引进了用果蝇作为有机体

to study the connection between genes and behavior.

来研究基因与行为之间的关系。

Seymour recruited me to CalTech in the late 1980s.

Seymour在80年代末聘请我到加州理工学院。

He was my Jedi and my rabbi while he was here,

当他在那儿的时候，他是我的启发者与导师，

and Seymour taught me both to love flies

Seymour也教会了我们俩爱上果蝇

and also to play with science.

用果蝇去试验科学原理。

So how do we ask this question?

我们怎么提这个问题呢？

It's one thing to believe that flies have emotion-like states,

一方面我们相信果蝇有情感状态，

but how do we actually find out whether that's true or not?

但又如何求证这个假设是真是假？

Now, in humans we often infer emotional states,

现在，在人类中我们经常通过面部表情推断情感状态，

as you'll hear later today, from facial expressions.

这个大家稍后会了解更多。

However, it's a little difficult to do that in fruit flies.

然而，在果蝇身上，这个可有点困难。

(Laughter)

（笑声）

It's kind of like landing on Mars

这有点像你降落在火星上

and looking out the window of your spaceship

然后从飞船往窗外看外面的小绿人

at all the little green men who are surrounding it

并且试着找出

and trying to figure out, "How do I find out

“我如何知道他们是否有情感”

if they have emotions or not?"

这个问题的答案。

What can we do? It's not so easy.

我们能做什么？显然不容易。

Well, one of the ways that we can start

好了，其中一个方法是我们可以从

is to try to come up with some general characteristics

试着提炼出一些情感状态的

or properties of emotion-like states

一般特性或属性

such as arousal, and see if we can identify

比如刺激，然后看看我们是否可以分别出

any fly behaviors that might exhibit some of those properties.

任何可能展现果蝇的那些（情感）属性的行为。

So three important ones that I can think of

因此我能想到的三个要点就是

are persistence, gradations in intensity, and valence.

持久性，渐层的强度以及效价。

Persistence means long-lasting.

持久性意味着(情感的)长效持久。

We all know that the stimulus that triggers an emotion

我们都知道当刺激触发了某一种情感，

causes that emotion to last long after the stimulus is gone.

这种情感会在这种刺激消失后继续持续。

Gradations of intensity means what it sounds like.

渐层的强度（情感表现强度）就是其字面意思。

You can dial up the intensity or dial down the intensity of an emotion.

你可以调高或者调低情感的强烈程度。

If you're a little bit unhappy, the corners of your mouth

如果你有点不开心，那么你的嘴角会向下

turn down and you sniffle,

并且会抽泣，

and if you're very unhappy, tears pour down your face

如果你很不开心，泪水就会流出来

and you might sob.

并且会呜咽。

Valence means good or bad, positive or negative.

效价表示(情绪中)好的或者坏的，积极的或者消极的。

So we decided to see if flies could be provoked into showing

所以我们决定看看果蝇会不会做出

the kind of behavior that you see

跟人在野餐桌上

by the proverbial wasp at the picnic table,

被那只黄蜂骚扰后相似的行为。

you know, the one that keeps coming back to your hamburger

众所周知，它越是一直试图接近你的汉堡，

the more vigorously you try to swat it away,

你就越想猛的把它赶走，

and it seems to keep getting irritated.

而且这种情况会让人很恼火。

So we built a device, which we call a puff-o-mat,

因此，我们制作了一种装置，叫做 puff-o-mat，

in which we could deliver little brief air puffs to fruit flies

在我们的实验室工作台上

in these plastic tubes in our laboratory bench

这种装置可通过塑料管向果蝇喷出极少的空气

and blow them away.

并把它们吹走。

And what we found is that if we gave these flies

我们发现如果给这些在装置里的果蝇

in the puff-o-mat several puffs in a row,

不断的喷一阵子空气，

they became somewhat hyperactive

他们会变的有点亢奋

and continued to run around for some time after the air puffs actually stopped

并且直到空气供给停止后都会保持到处乱跑的状态

and took a while to calm down.

而且需要一小会儿才会冷静下来。

So we quantified this behavior

为了量化这个行为

using custom locomotor tracking software

我们用我跟一个在加州理工学院电气工程部门

developed with my collaborator Pietro Perona,

的合作者Pietro Perona一起开发的

who's in the electrical engineering division here at CalTech.

自主跟踪软件来实现(这个目的)。

And what this quantification showed us is that,

这个量化数据给我们展示的是，

upon experiencing a train of these air puffs,

在被这些空气流喷了一段时间之后，

the flies appear to enter a kind of state of hyperactivity

这些果蝇好像进入了一种亢奋的状态

which is persistent, long-lasting,

而这种状态是持久有效的，

and also appears to be graded.

并且可以(按持久性)被分级。

More puffs, or more intense puffs,

更多的空气供给，或者更激烈的空气喷射量

make the state last for a longer period of time.

会让这种状态持续更长的一段时间。

So now we wanted to try to understand something

现在我们想了解一下

about what controls the duration of this state.

是什么因素控制这种状态持续的时间长短。

So we decided to use our puff-o-mat

我们决定通过我们的装置

and our automated tracking software

以及自动跟踪软件

to screen through hundreds of lines of mutant fruit flies

去监测数百批突变的果蝇

to see if we could find any that showed abnormal responses to the air puffs.

来看看能否发现它们对空气供给会否有任何不正常的反应。

And this is one of the great things about fruit flies.

这就是果蝇的一个非常大的好处。

There are repositories where you can just pick up the phone

你可以拿起电话跟仓库预定

and order hundreds of vials of flies of different mutants

数百瓶的不同类型的变异的果蝇

and screen them in your assay and then find out

并且在试验中监测它们来找出

what gene is affected in the mutation.

什么基因在突变中起了变化。

So doing the screen, we discovered one mutant

通过监测，我们发现了一种突变的果蝇

that took much longer than normal to calm down

在空气供给之后，比在正常情况下

after the air puffs,

要花更长的时间去冷静下来，

and when we examined the gene that was affected in this mutation,

当我们检查了这种在突变中受到影响的基因之后，

it turned out to encode a dopamine receptor.

发现它是用来编译一种多巴胺受体的。

That's right -- flies, like people, have dopamine,

对--果蝇，就像人一样，有多巴胺，

and it acts on their brains and on their synapses

而且它通过跟你我一样都有的

through the same dopamine receptor molecules

多巴胺受体分子直接作用到

that you and I have.

它们的脑部和神经突触。

Dopamine plays a number of important functions in the brain,

多巴胺负责大脑里一些重要的功能，

including in attention, arousal, reward,

包括注意力，觉醒，激励，

and disorders of the dopamine system have been linked

并且多巴胺系统的紊乱已经被联系到

to a number of mental disorders including drug abuse,

一些精神方面的紊乱，包括药物滥用，

Parkinson's disease, and ADHD.

帕金森氏症和多动症。

Now, in genetics, it's a little counterintuitive.

现在从遗传学上来说，这有点有悖常理。

We tend to infer the normal function of something

通过把某种因素剔除然后观察什么没有发生，

by what doesn't happen when we take it away,

我们推断出这个被移除的因素的正常功能是什么。

by the opposite of what we see when we take it away.

也就是与我们看到正在发生的截然相反。

So when we take away the dopamine receptor

因此当我们移除多巴胺受体后

and the flies take longer to calm down,

果蝇需要更长的时间冷静下来，

from that we infer that the normal function of this receptor and dopamine

因此我们推测受体和多巴胺的正常功能

is to cause the flies to calm down faster after the puff.

是保证果蝇在接触更多空气后更快冷静下来的原因。

And that's a bit reminiscent of ADHD,

这有点让人想起了多动症，

which has been linked to disorders of the dopamine system in humans.

人们把它和人体中的多巴胺系统紊乱联系起来。

Indeed, if we increase the levels of dopamine in normal flies

确实，在获得DEA的许可证之后， 如果我们

by feeding them cocaine

通过给正常的果蝇喂食可卡因

after getting the appropriate DEA license

来增加其体内的多巴胺的水平

— oh my God -- (Laughter) —

哦，天哪(大笑)

we find indeed that these cocaine-fed flies

我们会发现这些喂食了可卡因的果蝇

calm down faster than normal flies do,

会比正常的果蝇更快的冷静下来，

and that's also reminiscent of ADHD,

这也让我们想起了多动症，

which is often treated with drugs like Ritalin

它通常都是用利他林来治疗的

that act similarly to cocaine.

这种药物的作用类似于可卡因(所起的作用)。

So slowly I began to realize that what started out

因此慢慢的我开始意识到

as a rather playful attempt to try to annoy fruit flies

一个开始只是试图激怒果蝇的有趣尝试

might actually have some relevance to a human psychiatric disorder.

也许跟人类精神障碍有一定的相关性。

Now, how far does this analogy go?

现在，这个类比能站住脚吗？

As many of you know, individuals afflicted with ADHD

像你们大多数人都知道的一样，

also have learning disabilities.

患有多动症的人同时也患有学习障碍。

Is that true of our dopamine receptor mutant flies?

多巴胺受体突变的果蝇也可以印证上述观点吗？

Remarkably, the answer is yes.

可喜的是，答案是肯定的。

As Seymour showed back in the 1970s,

就像Seymour在70年代展示的那样，

flies, like songbirds, as you just heard,

果蝇，像鸣鸟一样，正如刚才你们都听过的，

are capable of learning.

它们是有学习能力的。

You can train a fly to avoid an odor, shown here in blue,

如果你把一种气味和一次空气冲击结合起来，

if you pair that odor with a shock.

你就可以训练果蝇去回避这种气味（如这里蓝色部分展示的一样）

Then when you give those trained flies the chance to choose

然后当你给这些已经完成训练的果蝇在

between a tube with the shock-paired odor and another odor,

充有这种气味的管子与另外一种气味中选择

it avoids the tube containing the blue odor that was paired with shock.

它会回避这种充有（曾跟冲击气流同时释放的）蓝色气体的管子。

Well, if you do this test on dopamine receptor mutant flies,

如果你在多巴胺受体变异的果蝇身上做这个试验，

they don't learn. Their learning score is zero.

它们是不会学习的。他们的学习能力为零。

They flunk out of CalTech.

它们可考不上加州理工学院。

So that means that these flies have two abnormalities,

因此那表明了这些果蝇有两种异常或者表现，

or phenotypes, as we geneticists call them,

就如我们遗传学家认为的多动症的表现：

that one finds in ADHD: hyperactivity and learning disability.

过度活跃以及学习障碍。

Now what's the causal relationship, if anything, between these phenotypes?

现在，如果有(关系的话)，在这些表型之中到底有什么因果关系？

In ADHD, it's often assumed that the hyperactivity

多动症中，一般认为

causes the learning disability.

学习障碍是由过度活跃引起的。

The kids can't sit still long enough to focus, so they don't learn.

孩子们无法静坐足够长的时间去集中精神，所以他们学不进去。

But it could equally be the case that it's the learning disabilities

但同样的，它也可以解释为

that cause the hyperactivity.

是因为有学习障碍才会引起过度活跃的。

Because the kids can't learn, they look for other things to distract their attention.

因为孩子们学不进去，他们就会寻找其他的东西去分散他们的注意力。

And a final possibility is that there's no relationship at all

最后一个可能就是

between learning disabilities and hyperactivity,

学习障碍与过度活跃是没有任何联系的，

but that they are caused by a common underlying mechanism in ADHD.

它们是被一种在多动症中的共同的底层机制所引发的。

Now people have been wondering about this for a long time

现在人们对这个问题已经困惑很久了，

in humans, but in flies we can actually test this.

但我们可以在果蝇身上做这个试验。

And the way that we do this is to delve deeply into the mind

我们试验的方式是利用遗传学深入挖掘果蝇的意识

of the fly and begin to untangle its circuitry using genetics.

并且利用遗传学来理清楚它的(神经)回路。

We take our dopamine receptor mutant flies

我们先选出多巴胺受体变异的果蝇们

and we genetically restore, or cure, the dopamine receptor

然后通过在它们的大脑中

by putting a good copy of the dopamine receptor gene

放置一份正常的多巴胺受体基因

back into the fly brain.

来进行基因还原或者治愈。

But in each fly, we put it back only into certain neurons

但在每只果蝇身上，我们仅仅(把正常的多巴胺受体基因)放回到

and not in others, and then we test each of these flies

固定的神经元(并非所有神经元都放置)，然后我们测试

for their ability to learn and for hyperactivity.

每一只果蝇的学习能力以及过度活跃现象。

Remarkably, we find we can completely dissociate these two abnormalities.

可喜的是，我们发现可以完全分离出这两种异常现象。

If we put a good copy of the dopamine receptor back

假如我们在果蝇的椭圆形结构(中央处理器集群)

in this elliptical structure called the central complex,

放置一份正常的多巴胺受体，

the flies are no longer hyperactive, but they still can't learn.

果蝇就不会再过度活跃，但依旧没有学习能力。

On the other hand, if we put the receptor back in a different structure

另一方面，如果我们在果蝇大脑别的结构，称作磨菇体的地方

called the mushroom body,

放置正常的多巴胺受体，

the learning deficit is rescued, the flies learn well,

学习能力就得到修复，果蝇就有很好的学习能力，

but they're still hyperactive.

但它们依旧过度活跃。

What that tells us is that dopamine

这些事实告诉我们，

is not bathing the brain of these flies like soup.

多巴胺并不会让大脑乱成一锅粥。

Rather, it's acting to control two different functions

相反，它是在两个不同的神经回路中

on two different circuits,

控制两种不同的功能的。

so the reason there are two things wrong with our dopamine receptor flies

因此，多巴胺受体(变异)的果蝇有两种功能不正常的原因是

is that the same receptor is controlling two different functions

同样一份受体控制了

in two different regions of the brain.

大脑两个的不同区域上的两种不同的功能。

Whether the same thing is true in ADHD in humans

是否这个结论也在人类的多动症中适用，

we don't know, but these kinds of results

我们还不知道，但这些结论至少给了

should at least cause us to consider that possibility.

我们去考虑这种可能性的启发。

So these results make me and my colleagues more convinced than ever

因此这些结论让我跟我同事比以往都更加确信一点，

that the brain is not a bag of chemical soup,

就是大脑它不是一袋子化学物质，

and it's a mistake to try to treat complex psychiatric disorders

并且想通过仅仅改变化学物质的“味道”

just by changing the flavor of the soup.

去治愈复杂的精神障碍是错误的。

What we need to do is to use our ingenuity and our scientific knowledge

我们需要做的是运用我们的创造力以及科学知识

to try to design a new generation of treatments

去开发一系列新的治疗方式

that are targeted to specific neurons and specific regions of the brain

一种可以在特定的精神障碍疾病中

that are affected in particular psychiatric disorders.

作用于精确的神经元以及大脑特定区域的方法。

If we can do that, we may be able to cure these disorders

如果可以做到的话，我们就可以

without the unpleasant side effects,

在没有不好的副作用的情况下治愈这些疾病了，

putting the oil back in our mental engines,

就如只把"机油“倒在我们精神引擎上真正需要的地方。

just where it's needed. Thank you very much.

非常感谢。