Autism — what we know (and what we don't know yet) | Wendy Chung

翻译人员: Yiding(Eden) Wen 校对人员: 杏儀 歐陽

"Why?"

“为什么？”

"Why?" is a question

父母们总是问我

that parents ask me all the time.

“为什么？”这个问题。

"Why did my child develop autism?"

“为什么我的孩子得了自闭症？”

As a pediatrician, as a geneticist, as a researcher,

身为儿科医生、基因专家、学者，

we try and address that question.

我们试着找出答案。

But autism is not a single condition.

但是自闭症的症状不是单一的。

It's actually a spectrum of disorders,

它事实上是一整个谱系发生了失调，

a spectrum that ranges, for instance,

自闭症谱系有很多种表现形式：

from Justin, a 13-year-old boy

比如，13岁的贾斯丁，

who's not verbal, who can't speak,

他不能说话，

who communicates by using an iPad

只能利用 iPad 与人交流，

to touch pictures to communicate

通过触碰图像

his thoughts and his concerns,

来表达他的想法和担忧。

a little boy who, when he gets upset,

另一位得了自闭症的男孩

will start rocking,

在难过时会不断摇摆晃动，

and eventually, when he's disturbed enough,

要是足够心烦了，

will bang his head to the point

他会撞自己的头，

that he can actually cut it open and require stitches.

一直撞到头破血流，需要进行缝线。

That same diagnosis of autism, though,

同样被诊断得了自闭症的，

also applies to Gabriel,

是另一个13岁男孩，

another 13-year-old boy

他叫戈贝尔，

who has quite a different set of challenges.

但他所面对的挑战却截然不同。

He's actually quite remarkably gifted in mathematics.

实际上，他对数学极有天赋。

He can multiple three numbers by three numbers

他可以轻易在脑海中

in his head with ease,

进行3位数间的乘法运算，

yet when it comes to trying to have a conversation,

然而要与人谈话时，

he has great difficulty.

他却无法应对。

He doesn't make eye contact.

他不会进行眼神交流。

He has difficulty starting a conversation,

他不会开启一个话题，

feels awkward,

他会感到尴尬。

and when he gets nervous,

当他感到紧张时

he actually shuts down.

就会缄默不言。

Yet both of these boys

这些男孩

have the same diagnosis of autism spectrum disorder.

都同样被诊断患有自闭症谱系失调。

One of the things that concerns us

不过我们关心的一个问题是

is whether or not there really is

自闭症是否

是一种流行病。

an epidemic of autism.

These days, one in 88 children

如今，每88个孩子中

will be diagnosed with autism,

就有一个被诊断出患有自闭症，

and the question is,

而问题就是

why does this graph look this way?

呈现的数据为什么会是这样？

Has that number been increasing

患者人数是否随着时间推移

dramatically over time?

剧烈地增长呢？

Or is it because we have now started labeling

还是因为我们现在开始会辨认

individuals with autism,

患有自闭症的儿童，

simply giving them a diagnosis

能给他们一个诊断，

when they were still present there before

其实这个群体一直都存在，

yet simply didn't have that label?

只不过一直没人会诊断？

And in fact, in the late 1980s, the early 1990s,

实际上， 在20世纪80年代末、90年代早期，

legislation was passed

议会通过了一个法案，

that actually provided individuals with autism

为患自闭症的人

with resources, with access to educational materials

提供资源，让他们能够同样接受教育，

that would help them.

来帮助他们。

With that increased awareness, more parents,

随着人们对自闭症的认识日益增长，

more pediatricians, more educators

更多的父母、儿科医生、教育者

learned to recognize the features of autism.

了解了如何辨认自闭症的特征。

As a result of that, more individuals were diagnosed

于是，更多人被诊断出了自闭症，

and got access to the resources they needed.

并获得了他们所需的资源。

In addition, we've changed our definition over time,

此外，我们也在不断改变 自闭症的定义，

so in fact we've widened the definition of autism,

实际上，我们拓展了自闭症的定义。

and that accounts for some of

这也成为了患者人数

the increased prevalence that we see.

不断上升的原因之一。

The next question everyone wonders is,

人们想知道的下一个问题是，

what caused autism?

到底是什么引起了自闭症？

And a common misconception

一个普遍的理论误区是

is that vaccines cause autism.

疫苗会引发自闭症。

But let me be very clear:

但请允许我在此澄清：

Vaccines do not cause autism.

疫苗不会引起自闭症。

(Applause)

（掌声）

In fact, the original research study

实际上，最初得出这种

that suggested that was the case

误导性结论的

was completely fraudulent.

是一项彻头彻尾的学术欺诈性研究。

It was actually retracted from the journal Lancet,

它最初刊登在《柳叶刀》医学期刊上，

in which it was published,

但后来被撤稿了，

and that author, a physician,

文章的作者是一名内科医生，

had his medical license taken away from him.

后来也被吊销了执照。

(Applause)

（掌声）

The Institute of Medicine,

药物监管局

The Centers for Disease Control,

以及疾病控制中心

have repeatedly investigated this

已经反复研究过这个结论，

and there is no credible evidence

并指出并无确凿证据

that vaccines cause autism.

证明疫苗会引起自闭症。

Furthermore,

除此之外，

one of the ingredients in vaccines,

疫苗的组成成分之一：

something called thimerosal,

硫柳汞，

was thought to be what the cause of autism was.

被认为是引发自闭症的诱因。

That was actually removed from vaccines

但这一成分早在1992年就被

in the year 1992,

从疫苗中移除，

and you can see that it really did not have an effect

而你们可以看到这一成分的 移除并未能阻止

in what happened with the prevalence of autism.

自闭症大量增加的情况。

So again, there is no evidence

因此我必须再次阐明： 没有证据表明

that this is the answer.

疫苗会导致自闭症。

So the question remains, what does cause autism?

那们问题依然存在： 到底是什么导致了自闭症？

In fact, there's probably not one single answer.

事实上，答案可能不止一个。

Just as autism is a spectrum,

就像自闭症是一个谱系一样，

there's a spectrum of etiologies,

病因也有一个谱系，

a spectrum of causes.

一个诱因的谱系。

Based on epidemiological data,

根据流行病学数据，

we know that one of the causes,

我们知道，诱因之一，

or one of the associations, I should say,

或者说，关联因素之一，

is advanced paternal age,

是较高的父亲年龄，

that is, increasing age of the father

也就是说，在受孕时间

at the time of conception.

父方的年龄较高。

In addition, another vulnerable

自闭症发展阶段中

and critical period in terms of development

另一个易受影响的关键时期是

is when the mother is pregnant.

母亲的怀孕时期。

During that period, while the fetal brain is developing,

在此时期，婴儿的大脑正在发育

we know that exposure to certain agents

我们知道与某些介质的接触

can actually increase the risk of autism.

实际上会增加患自闭症的风险。

In particular, there's a medication, valproic acid,

尤其要指出的是，有一种药物丙戊酸，

which mothers with epilepsy sometimes take,

有些患有癫痫的母亲们有时会服用，

we know can increase that risk of autism.

也会增加新生儿自闭症的风险。

In addition, there can be some infectious agents

不止如此，还有些传染性病原体

that can also cause autism.

也会诱发自闭症。

And one of the things I'm going to spend

而其中一项我会花

a lot of time focusing on

大量时间研究的，

are the genes that can cause autism.

是能诱发自闭症的基因。

I'm focusing on this not because genes

我关注这个不是因为

are the only cause of autism,

基因是自闭症的唯一诱因，

but it's a cause of autism

而是因为这种诱因可以让我们

that we can readily define

更好地对其给出定义，

and be able to better understand the biology

并借此更好地了解生物学，

and understand better how the brain works

更好地理解大脑的运作方式，

so that we can come up with strategies

这样我们才能制定出

to be able to intervene.

干预性策略。

One of the genetic factors that we don't understand,

然而其中一项我们不理解的基因因素，

however, is the difference that we see

是我们在男女患者身上

in terms of males and females.

观察到的差别。

Males are affected four to one compared to females

患上自闭症的男女比例

with autism,

是4:1，

and we really don't understand what that cause is.

我们确实不知道原因是什么。

One of the ways that we can understand

我们了解基因诱因的

that genetics is a factor

方式之一，

is by looking at something called

是观察我们所称的

the concordance rate.

“一致率”。

In other words, if one sibling has autism,

换言之，如果兄弟姐妹中 有一位患有自闭症，

what's the probability

那其他兄弟姐妹

that another sibling in that family will have autism?

患上自闭症的概率是多少？

And we can look in particular

我们特别选取了三类兄弟姐妹

at three types of siblings:

做对照：

identical twins,

同卵双胞胎，

twins that actually share 100 percent

他们共享100%的

of their genetic information

基因信息，

and shared the same intrauterine environment,

与其兄弟姐妹共享同一宫腔环境；

versus fraternal twins,

第二组是异卵双胞胎，

twins that actually share 50 percent

异卵双胞胎共享50%的

of their genetic information,

基因信息，

versus regular siblings,

第三组是一般的兄弟姐妹，

brother-sister, sister-sister,

兄妹，姐弟，或者姐妹，

also sharing 50 percent of their genetic information,

也共享50%基因信息，

yet not sharing the same intrauterine environment.

但经历不同的宫腔环境。

And when you look at those concordance ratios,

在观察这些对照组的一致率时，

one of the striking things that you will see

引人注意的事情之一是，

is that in identical twins,

同卵胞胎

that concordance rate is 77 percent.

一致率为77%。

Remarkably, though,

要指出的是，

it's not 100 percent.

这并不是100%。

It is not that genes account for all of the risk for autism,

基因并不是决定自闭症 风险的全部因素。

but yet they account for a lot of that risk,

但基因还是占了很大比例。

because when you look at fraternal twins,

因为当你看异卵双胞胎时，

that concordance rate is only 31 percent.

一致率只有31%

On the other hand, there is a difference

另外，异卵双胞胎之间的一致率

between those fraternal twins and the siblings,

与普通兄弟姐妹的一致率也不同，

suggesting that there are common exposures

这表明了异卵双胞胎共享的

for those fraternal twins

一些介质

that may not be shared as commonly

是普通的兄弟姐妹

无法共同接触到的。

with siblings alone.

So this provides some of the data

这佐证了一些数据，

that autism is genetic.

表明自闭症是遗传的。

Well, how genetic is it?

那么，遗传的影响到底有多大呢？

When we compare it to other conditions

当我们将它同其他

that we're familiar with,

我们熟悉的疾病进行对比，

things like cancer, heart disease, diabetes,

像癌症，心脏病，厌食症等，

in fact, genetics plays a much larger role in autism

事实上，相比起来，遗传在自闭症中

than it does in any of these other conditions.

扮演了更重要的角色。

But with this, that doesn't tell us what the genes are.

但只有这些， 我们还是不知道哪些是致病基因。

It doesn't even tell us in any one child,

数据甚至也没有告诉我们， 一个孩子患上自闭症

is it one gene

是单一基因，

or potentially a combination of genes?

还是潜在的一组基因造成的结果？

And so in fact, in some individuals with autism,

因此，对一些自闭症个体来说，

it is genetic!

这明显是遗传的！

That is, that it is one single,

也就是说，是由一条单一的

powerful, deterministic gene

强有力的、决定性的基因

that causes the autism.

引起的自闭症。

However, in other individuals,

然而，在其他个体中，

it's genetic, that is,

它基本上是遗传的，也就是说

that it's actually a combination of genes

那实际上是一组基因

in part with the developmental process

以及整个发育过程，

that ultimately determines that risk for autism.

最终决定患上自闭症的风险。

We don't know in any one person, necessarily,

我们并不知道对于任一个体来说

which of those two answers it is

哪个答案才是正确的，

until we start digging deeper.

直到我们深入进行发掘。

So the question becomes,

所以问题变成了

how can we start to identify

我们如何才能鉴别出

what exactly those genes are.

究竟是哪些基因会引发自闭症。

And let me pose something

让我展示一些

that might not be intuitive.

可能与直觉相悖的东西。

In certain individuals,

某些个体

they can have autism

可能因为遗传因素

for a reason that is genetic

患上自闭症，

but yet not because of autism running in the family.

但并不一定因为家族中 多人患有自闭症。

And the reason is because in certain individuals,

原因就在于，对于某些个体而言，

they can actually have genetic changes or mutations

他们实际上会发生基因变化， 或者说变异，

that are not passed down from the mother

而这些并非继承自他们的母亲

or from the father,

或者父亲，

but actually start brand new in them,

而是在他们自己体内才开始的产生，

mutations that are present

也就是说卵子或精子

in the egg or the sperm

受育过程中

at the time of conception

发生的突变，

but have not been passed down

并不是随着家族

generation through generation within the family.

代代相传而导致的。

And we can actually use that strategy

我们也能使用这个策略

to now understand and to identify

来理解并甄别

those genes causing autism in those individuals.

在这些个体中引起自闭症的基因。

So in fact, at the Simons Foundation,

实际上，在西门斯基金会，

we took 2,600 individuals

我们选取了家族史上

that had no family history of autism,

没有自闭症的2600个个体，

and we took that child and their mother and father

同时也选取了这些孩子及他们的父母，

and used them to try and understand

并利用这些样本试着了解

what were those genes

当中引发自闭症的

causing autism in those cases?

基因究竟是哪些？

To do that, we actually had to comprehensively

为达成这一目标，我们实际上不得不

be able to look at all that genetic information

全面回顾所有基因信息，

and determine what those differences were

并找出父母及孩子

between the mother, the father and the child.

之间的不同之处。

In doing so, I apologize,

为了达到这个目的， 我得抱歉的告诉大家，

I'm going to use an outdated analogy

我将使用过时的百科全书做比喻，

of encyclopedias rather than Wikipedia,

而不是利用维基百科。

but I'm going to do so to try and help make the point

但我会试着来让大家更明白，

that as we did this inventory,

当我们进行总结归纳时，

we needed to be able to look at

我们必须能够观察

massive amounts of information.

大量的信息。

Our genetic information is organized

我们的基因信息存在于

into a set of 46 volumes,

46卷百科全书中（影射46条染色体），

and when we did that, we had to be able to account

在我们分析数据时，需要对

for each of those 46 volumes,

这46卷进行逐一计数。

because in some cases with autism,

因为在某些自闭症案列中，

there's actually a single volume that's missing.

实际上是整条单一染色体消失了。

We had to get more granular than that, though,

然而我们必须得到更多数据，

and so we had to start opening those books,

所以，我们不得不打开这些书，

and in some cases, the genetic change

而在某些案例中，基因变化

was more subtle.

要微妙得多，

It might have been a single paragraph that was missing,

可能是单一段落（基因片段）消失了，

or yet, even more subtle than that,

也可能，更微妙地，

a single letter,

单独一个字母（碱基），

one out of three billion letters

30亿字母（碱基）中的一个，

that was changed, that was altered,

被改变了，被替换了，

yet had profound effects

但仍能极大的影响

in terms of how the brain functions

大脑的功能

and affects behavior.

以及患者的行为。

In doing this within these families,

通过对这些家族进行反复对比，

we were able to account for approximately

我们能计算出在这些家族中，

25 percent of the individuals

大约25%的个体

and determine that there was a single

是由单一，强有力的

powerful genetic factor

基因因素

that caused autism within those families.

诱发了自闭症。

On the other hand, there's 75 percent

换句话说，有75%的

that we still haven't figured out.

自闭症原因仍不明。

As we did this, though,

当我们做这个实验时，

it was really quite humbling,

确实很让我们觉得自己很渺小，

because we realized that there was not simply

因为我们意识到自闭症的基因

one gene for autism.

并不是单一的

In fact, the current estimates are

事实上，现在的数据表明

that there are 200 to 400 different genes

有200到400个不同的基因

that can cause autism.

都可以导致自闭症。

And that explains, in part,

这也部分地解释了

why we see such a broad spectrum

为何它的影响形成了

in terms of its effects.

如此宽广的谱系。

Although there are that many genes,

尽管有如此众多的基因，

there is some method to the madness.

确实有通路可以导致发疯。

It's not simply random

这不是随意的

200到400个不同基因，

200, 400 different genes,

but in fact they fit together.

事实上，它们是互补的。

They fit together in a pathway.

它们在通路中结合。

They fit together in a network

它们在神经网中互补，

that's starting to make sense now

这样才会在大脑的

in terms of how the brain functions.

功能中产生意义。

We're starting to have a bottom-up approach

我们开始用自上而下的方法

where we're identifying those genes,

来辨认那些基因，

those proteins, those molecules,

那些蛋白质、分子，

understanding how they interact together

理解它们如何互相作用

to make that neuron work,

使神经元工作，

understanding how those neurons interact together

理解神经元如何相互作用

to make circuits work,

来使神经中枢工作，

and understand how those circuits work

理解神经中枢如何工作

to now control behavior,

来控制行为，

and understand that both in individuals with autism

这些理解既针对自闭症个体，

as well as individuals who have normal cognition.

又针对认知正常的个体。

But early diagnosis is a key for us.

但早期诊断对我们来说至关重要。

Being able to make that diagnosis

能够在某一个时间点

of someone who's susceptible

提早诊断出

at a time in a window

某人可能患有自闭症，

where we have the ability to transform,

并在我们还有能力对正在发育的大脑

to be able to impact

进行改变和影响的时候，

that growing, developing brain is critical.

及时作出诊断是相当重要的。

And so folks like Ami Klin have developed methods

比如Ami Klin这样的团队 已经开发了一些方法

to be able to take infants, small babies,

能够在新生儿，婴儿身上，

and be able to use biomarkers,

借助生物标记物，

in this case eye contact and eye tracking,

这里也就是眼神接触和追踪，

to identify an infant at risk.

来确认婴儿的患病风险。

This particular infant, you can see,

你们可以看到，这个婴儿

making very good eye contact with this woman

和这位女士有很好的眼神交流，

as she's singing "Itsy, Bitsy Spider,"

她在唱“织织织织，小蜘蛛……”，

in fact is not going to develop autism.

事实上它不会患自闭症。

This baby we know is going to be in the clear.

我们知道，这个婴儿没问题。

On the other hand, this other baby

而在另一个例子中，这个婴儿

is going to go on to develop autism.

将会发展成自闭症。

In this particular child, you can see,

你们可以看到，这个孩子

it's not making good eye contact.

没有进行眼神接触。

Instead of the eyes focusing in

它没有进行目光聚焦

and having that social connection,

并形成社交联系，

looking at the mouth, looking at the nose,

而是看着嘴巴、鼻子，

looking off in another direction,

以及其他方向，

but not again socially connecting,

但总是没有社交联系，

and being able to do this on a very large scale,

能够大范围地做这些测试，

screen infants, screen children for autism,

利用强大可靠的方式

through something very robust, very reliable,

对婴儿和儿童进行自闭症筛查，

is going to be very helpful to us in terms of being

将会帮助我们

able to intervene at an early stage

及早发现自闭症

when we can have the greatest impact.

并做出最及时的干预治疗。

How are we going to intervene?

那么我们要如何诊治呢？

It's probably going to be a combination of factors.

这可能是多重因素的结合。

In part, in some individuals,

某些情况下，在一些个体上

we're going to try and use medications.

我们会尝试使用药物。

And so in fact, identifying the genes for autism

事实上，甄别自闭症的基因

is important for us

非常重要，

to identify drug targets,

可以使我们锁定用药目标，

to identify things that we might be able to impact

也可以使我们能找到干预的方法，

and can be certain that that's really

并确认这是对付自闭症

what we need to do in autism.

可以采取的方式。

But that's not going to be the only answer.

但这不会是唯一答案。

Beyond just drugs, we're going to use educational strategies.

除了药物，我们也会使用教育策略。

Individuals with autism,

自闭症个体

some of them are wired a little bit differently.

各自有不同的思维方式。

They learn in a different way.

他们以不同的方式学习。

They absorb their surroundings in a different way,

他们以不同的方式吸收学习环境，

and we need to be able to educate them

而我们需要能够以最适合

in a way that serves them best.

他们的方式来帮助他们。

Beyond that, there are a lot of individuals

此外，在场的还有许多人

in this room who have great ideas

有出色的想法和新技术

in terms of new technologies we can use,

可以供我们借鉴，

everything from devices we can use to train the brain

我们可以运用一些设备用来训练大脑，

to be able to make it more efficient

让它更高效，

and to compensate for areas in which

还可以为一些仍然有技术困难的领域

it has a little bit of trouble,

提供更行之有效的方法，

to even things like Google Glass.

甚至可以使用谷歌眼镜。

You could imagine, for instance, Gabriel,

例如，你们可以想象

with his social awkwardness,

有社交障碍的戈贝尔，

might be able to wear Google Glass

也许能带上谷歌眼镜

with an earpiece in his ear,

再戴上一副耳机，

and have a coach be able to help him,

耳边就可以有一个老师帮助他，

be able to help think about conversations,

帮助他思考对话，

conversation-starters,

能够积极开启对话，

being able to even perhaps one day

也许有一天

invite a girl out on a date.

他甚至能约女孩上街。

All of these new technologies

所有这些新技术

just offer tremendous opportunities

都提供了极大的机会，

for us to be able to impact

帮助我们诊断和干预

the individuals with autism,

自闭症个体的症状。

but yet we have a long way to go.

但我们还有很长一段路要走。

As much as we know,

正如我们所知，

there is so much more that we don't know,

我们不知道的还有如此之多。

and so I invite all of you

所以，我在此邀请你们所有人

to be able to help us think about

帮助我们思考

how to do this better,

如何将它做得更好，

to use as a community our collective wisdom

利用我们的集体智慧，

to be able to make a difference,

来做出改变，

and in particular,

尤其是，

for the individuals in families with autism,

有自闭症家族史的个体，

I invite you to join the interactive autism network,

我诚邀你们加入网络互动自闭症研究，

to be part of the solution to this,

为治疗方案贡献自己的力量，

because it's going to take really a lot of us

因为，这需要我们众人一起

to think about what's important,

来思考什么才是重要的，

what's going to be a meaningful difference.

如何做出有意义的改变。

As we think about something

当我们想到一些

that's potentially a solution,

有潜力的解决方案，

how well does it work?

它到底可以有多大成效？

Is it something that's really going to make a difference

是否会为自闭症患者的个人生活，

in your lives, as an individual,

家庭生活，带来真正

as a family with autism?

积极的影响？

We're going to need individuals of all ages,

我们将会需要各个年龄层的个体，

from the young to the old,

青年到老年，

and with all different shapes and sizes

需要拥有自闭症谱系失调中各种

of the autism spectrum disorder

症状的个体

to make sure that we can have an impact.

来确保我们的影响广泛有力。

So I invite all of you to join the mission

所以我们邀请在座所有人 加入这个项目，

and to help to be able to make the lives

并帮助改善自闭症

of individuals with autism

个体的生活状态，

so much better and so much richer.

让他们的生活越来越美好。

Thank you.

谢谢

(Applause)

（掌声）