"Why?" is a question

父母們總是問我這個問題。 （Wendy Chung 溫蒂.張）

that parents ask me all the time.

“為什麼我的孩子會有自閉症？” （2014年3月 溫哥華卑詩省）

"Why did my child develop autism?"

作為一名兒科醫生、遺傳學家、研究員，

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

我們想要找到這個問題的答案。

we try and address that question.

自閉症的病狀體現不是單一的，

But autism is not a single condition.

(自閉症譜系） 它可以是一系列的病狀。

It's actually a spectrum of disorders,

自閉症的表現多樣，舉個例子：

a spectrum that ranges, for instance,

13歲少年：Justin，

from Justin, a 13-year-old boy

他不太會表達、不能講話，

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

他通過iPad和人溝通，

who communicates by using an iPad

他用碰觸圖片 來表達他的想法和意見。

to touch pictures to communicate

當這個男孩子不高興時，

his thoughts and his concerns,

他會開始前後搖擺，

a little boy who, when he gets upset,

如果他受到更大的刺激，

will start rocking,

他會開始用頭撞東西，

and eventually, when he's disturbed enough,

甚至頭破血流，嚴重到需要縫針。

will bang his head to the point

同樣的，Gabriel也被判定為自閉症患者。

that he can actually cut it open and require stitches.

他也是13歲，

That same diagnosis of autism, though,

不過他的問題和Justin截然不同。

also applies to Gabriel,

他是一位數學神童，

another 13-year-old boy

他可以輕而易舉地 心算三位數的乘法

who has quite a different set of challenges.

不過，當他與人聊天時，

He's actually quite remarkably gifted in mathematics.

他就一團糟了。

He can multiple three numbers by three numbers

他不會和人有目光接觸，

in his head with ease,

他很難開啟話匣子，

yet when it comes to trying to have a conversation,

感覺不自在，

he has great difficulty.

當他緊張時，

He doesn't make eye contact.

他就開始封閉自己了。

He has difficulty starting a conversation,

不過這兩個男孩子 都被診斷為自閉症譜系障礙。

feels awkward,

（自閉症譜系障礙）

and when he gets nervous,

我們非常擔心的是：

he actually shuts down.

自閉症到底是不是一種流行病？

Yet both of these boys

現今，每88個兒童裡 就會有一個被診斷有自閉症。

have the same diagnosis of autism spectrum disorder.

我們想知道的是：為什麼 我們的圖表有這樣的趨勢？

One of the things that concerns us

是因為得了自閉症的孩子 在近年急劇增長？

is whether or not there really is

(自閉症實際上沒有圖表所顯示的巨大增加） 還是因為我們的診斷方式包括了更多人？

an epidemic of autism.

(紅線：殘障教育法案） 我們現在把一種症狀歸類為自閉症，

These days, one in 88 children

不過之前卻沒有把這種症狀視為自閉症。

will be diagnosed with autism,

在80年代末，90年代初期，

and the question is,

立法通過讓患有自閉症的人群

why does this graph look this way?

有足夠的資源、有條件接受教育，

Has that number been increasing

從中得益。

dramatically over time?

社會對自閉症更多的重視，讓父母、

Or is it because we have now started labeling

兒科醫師、教學人員

individuals with autism,

熟悉如何識別自閉症的特征。

simply giving them a diagnosis

因此，更多的人被診斷有自閉症

when they were still present there before

並得到他們所需要的幫助。

yet simply didn't have that label?

另外，我們對自閉症的定義 也隨著時間改變，

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

事實上，我們拓寬了對自閉症的定義，

legislation was passed

主要是因為我們看到 某種病狀日趨增加。

that actually provided individuals with autism

那麼下一個人人都關注的問題就是：

with resources, with access to educational materials

什麼導致自閉症？

that would help them.

以及最大的誤區：

With that increased awareness, more parents,

疫苗會造成自閉症。

more pediatricians, more educators

讓我清楚地告訴各位：

learned to recognize the features of autism.

疫苗不會造成自閉症。

As a result of that, more individuals were diagnosed

（鼓掌）

and got access to the resources they needed.

事實上，最初聲稱疫苗造成自閉症的報告

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

完全是假的。

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

這個報告被其發表的科刊《Lancet》收回

and that accounts for some of

它的作者被吊銷了他的行醫執照。

the increased prevalence that we see.

（鼓掌）

The next question everyone wonders is,

美國醫學研究院、

what caused autism?

疾病控制中心

And a common misconception

已經做過重複的調查，

is that vaccines cause autism.

都沒有發現任何可靠的證據表明

But let me be very clear:

疫苗會造成自閉症。

Vaccines do not cause autism.

（疫苗不會導致自閉症） 此外，

(Applause)

疫苗的成份之一：

In fact, the original research study

硫柳汞

that suggested that was the case

曾被認為會造成自閉症，

was completely fraudulent.

但在1992年已經從疫苗中移除。

It was actually retracted from the journal Lancet,

你可以發現，它和自閉症之後的發展

in which it was published,

沒有任何關聯。

and that author, a physician,

因此，沒有任何證據表明 疫苗和自閉症有個。

had his medical license taken away from him.

所以問題來了：是什麼造成自閉症？

(Applause)

事實上，我們沒有一個單一的答案。

The Institute of Medicine,

自閉症包括一系列的病情

The Centers for Disease Control,

它的病原也不是單一的。

have repeatedly investigated this

流行病學的數據顯示 （什麼造成自閉症）

and there is no credible evidence

我們知道其中一個原因

that vaccines cause autism.

或者應該說關聯

Furthermore,

和父親的高齡有關。

one of the ingredients in vaccines,

就是說，在孩子受精時，

something called thimerosal,

父親的年齡越高，越會出現自閉症。

was thought to be what the cause of autism was.

另外一個易受傷害

That was actually removed from vaccines

而格外重要的時間段：

in the year 1992,

母親懷孕期間。

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

在這段時期，嬰兒的大腦不斷發育。

in what happened with the prevalence of autism.

我們知道此時如受外界影響，

So again, there is no evidence

孩子將會更容易患上自閉症。

that this is the answer.

特別是一種叫做丙戊酸的藥物，

So the question remains, what does cause autism?

患有癲癇的孕婦有時會服用的，

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

我們知道這個藥物 會增加患上自閉症的機率。

Just as autism is a spectrum,

另外，還有一些傳染病的導因，

there's a spectrum of etiologies,

也會造成自閉症。

a spectrum of causes.

我會用很多時間跟大家講一講

Based on epidemiological data,

基因如何造成自閉症。

we know that one of the causes,

我的意思不是只有基因

or one of the associations, I should say,

會造成自閉症。

is advanced paternal age,

但是這個病因是我們可以完全界定的。

that is, increasing age of the father

我們可以更好的從生物學

at the time of conception.

從大腦運作的方式明白病因。

In addition, another vulnerable

因此我們可以找到方法

and critical period in terms of development

得以應對。

is when the mother is pregnant.

（性別之謎） 一個我們還不理解的遺傳因素

During that period, while the fetal brain is developing,

是男女之間的區別。

we know that exposure to certain agents

男性和女性患有自閉症的比例是4:1

can actually increase the risk of autism.

我們不知道是什麼原因。

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

我們可以確認自閉症

which mothers with epilepsy sometimes take,

和遺傳有關的一個方式是

we know can increase that risk of autism.

統計“和合率”

In addition, there can be some infectious agents

換句話說：如果有兄弟姊妹得了自閉症，

that can also cause autism.

家中其他成員患上 自閉症的可能是多少?

And one of the things I'm going to spend

我們會看三種弟兄姊妹的情況：

a lot of time focusing on

同卵雙胞胎，

are the genes that can cause autism.

雙胞胎有100%一樣的遺傳信息。

I'm focusing on this not because genes

並有一樣的子宮環境。

are the only cause of autism,

對比異卵雙胞胎

but it's a cause of autism

異卵雙胞胎有50%一樣的遺傳信息。

that we can readily define

再對比一般的弟兄姊妹：

and be able to better understand the biology

有50%的遺傳信息，

and understand better how the brain works

但是沒有一樣的子宮環境。

so that we can come up with strategies

當我們看“和合率“時，

to be able to intervene.

我們驚奇地發現， 在同卵雙胞胎的情況下

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

如果其中一個患有自閉症， 另外一個得自閉症的概率是77%。

however, is the difference that we see

要留意的是，這不是100%。

in terms of males and females.

遺傳不是唯一造成自閉症的因素。

Males are affected four to one compared to females

但是我們知道它佔了很大的比例。

with autism,

如果我們看異卵雙胞胎，

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

相對的比例只有31%。

One of the ways that we can understand

另外一方面，異卵雙胞胎和兄弟姊妹也有不同

that genetics is a factor

讓我們推測，異卵雙胞胎 所受所到的相同的影響

is by looking at something called

比普通兄弟姊妹受到的要多。

the concordance rate.

所以這些研究給讓我們可以推論

In other words, if one sibling has autism,

自閉症是和遺傳有關的。

what's the probability

那么它和遺傳的關系有多大呢？

that another sibling in that family will have autism?

當我們那其他熟悉的病情做比較時，

And we can look in particular

比如腫瘤、心臟病、糖尿病，

at three types of siblings:

基因對自閉症的引導作用

identical twins,

超過這些其他的疾病。

twins that actually share 100 percent

即便如此，我們不知道是哪些特別的基因。

of their genetic information

我們甚至不知道是孩子的一個基因，

and shared the same intrauterine environment,

還是一組基因造成自閉症。

versus fraternal twins,

所以，某些患有自閉症的人

twins that actually share 50 percent

來自遺傳！！！

of their genetic information,

就是一個很強大、很頑固的基因

versus regular siblings,

造成的自閉症。

brother-sister, sister-sister,

不過，對於其他的人，

also sharing 50 percent of their genetic information,

自閉症來自遺傳。

yet not sharing the same intrauterine environment.

它可以是一組基因、

And when you look at those concordance ratios,

在嬰兒發育過程中，

one of the striking things that you will see

多種因素最終造成自閉症的風險。

is that in identical twins,

我們不能確定某個患有自閉症的人

that concordance rate is 77 percent.

是屬於以上哪一種情況，

Remarkably, though,

直到我們更深入的了解研究。

it's not 100 percent.

所以我們的問題成了：

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

我們如何識別造成自閉症的基因？

but yet they account for a lot of that risk,

讓我提出一個不是那麼明顯的說法：

because when you look at fraternal twins,

對於某些人來說，

that concordance rate is only 31 percent.

他們可以因為遺傳而患上自閉症，

On the other hand, there is a difference

但他們沒有任何自閉症的家族史。

between those fraternal twins and the siblings,

為什麼呢？因為某些人的基因

suggesting that there are common exposures

出現改變或者突變，

for those fraternal twins

這些突變不是從父母那裡遺傳過來的，

that may not be shared as commonly

卻是從孩子本身開始的：

with siblings alone.

卵子或精子所發生的突變，

So this provides some of the data

這不是在家族中一代一代傳下來。

that autism is genetic.

我們就可以用這發現

Well, how genetic is it?

去解讀和識別

When we compare it to other conditions

哪些基因造成這些人患上自閉症。

that we're familiar with,

所以，在Simons基金會，

things like cancer, heart disease, diabetes,

我們找到2600位

in fact, genetics plays a much larger role in autism

沒有自閉症家族史的實驗對象。

than it does in any of these other conditions.

我們找到孩子和他們父母的基因，

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

用這些基因嘗試明白哪些基因

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

造成自閉症。

is it one gene

要達到這個目標，我們要全面地

or potentially a combination of genes?

了解他們的整個基因信息，

And so in fact, in some individuals with autism,

看看孩子和父母的基因 在什麼地方出現偏差。

it is genetic!

先抱歉一下，要這樣做呢， 我用的方法比較老套。

That is, that it is one single,

我會用百科全書的比喻，不是維基百科。

powerful, deterministic gene

我會嘗試用這個表達我的意思，

that causes the autism.

當我們開始做他們的基因記錄時，

However, in other individuals,

我們需要處理巨量的信息。

it's genetic, that is,

我們的基因信息被整理成46卷書，

that it's actually a combination of genes

當我們整理時，我們需要知道 每一卷書的具體位置，

in part with the developmental process

因為有些情況下，

that ultimately determines that risk for autism.

可能丟失一卷書造成自閉症。

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

當然我們需要更細緻一些，

which of those two answers it is

所以我們需要打開這些書，

until we start digging deeper.

在一些情況下，基因的改變是微妙的。

So the question becomes,

可能是某頁的一段話不見了，

how can we start to identify

甚至更細微，

what exactly those genes are.

一個字母！

And let me pose something

30億個字母中的一個改變了，

that might not be intuitive.

造成對大腦、對行為的深遠影響。

In certain individuals,

（Simons 單一取樣發現 25%自閉症是由全新的變異造成的） 通過和這些家庭的基因做對比，

they can have autism

我們發現大約有

for a reason that is genetic

25%的患者是因為單一的，重要的

but yet not because of autism running in the family.

基因因素而造成他們的自閉症。

And the reason is because in certain individuals,

另外一方面，我們還不知道 其他75%是什麼具體情況。

they can actually have genetic changes or mutations

整個研究過程，

that are not passed down from the mother

真的叫我們謙卑自抑，

or from the father,

我們明白並非是一個基因導致自閉症。

but actually start brand new in them,

事實上，我們現在的推測表明：

mutations that are present

至少有200-400個基因 會造成自閉症。

in the egg or the sperm

這樣間接解釋了為什麼

at the time of conception

自閉症可以有一系列的病狀。

but have not been passed down

雖然有很多的基因，

generation through generation within the family.

其實還是有跡可循的。

And we can actually use that strategy

這200-400個基因並非胡亂孤立的。

to now understand and to identify

它們是互相關聯的。

those genes causing autism in those individuals.

它們是一條道上的，

So in fact, at the Simons Foundation,

它們有組織，

we took 2,600 individuals

讓我們明白原因，

that had no family history of autism,

找到大腦是如何運作的。

and we took that child and their mother and father

我們開始追根尋源，識別這些基因，

and used them to try and understand

這些蛋白質、這些分子，

what were those genes

了解它們如何互動，

causing autism in those cases?

讓神經元正常運作，

To do that, we actually had to comprehensively

然後瞭解神經元如何合作，

be able to look at all that genetic information

影響某些大腦連接，

and determine what those differences were

而大腦的神經連接是如何被影響

between the mother, the father and the child.

人的行為舉止：

In doing so, I apologize,

患有自閉症的人是什麼樣的，

I'm going to use an outdated analogy

有正常的認知的人是什麼樣的。

of encyclopedias rather than Wikipedia,

前期診斷對我們來說至關重要，

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

如果可以提早診斷 有患上自閉症風險的人，

that as we did this inventory,

我們就有時間幫助他們改變，

we needed to be able to look at

能夠改變他們正在發育的大腦 起著決定性作用。

massive amounts of information.

像Ami Klin這樣的研究員開發出一些方法

Our genetic information is organized

用在嬰兒和幼童上，

into a set of 46 volumes,

通過生物標誌，

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

比如這個是用了 目光接觸和眼球追蹤，

for each of those 46 volumes,

看看嬰兒是否有患有自閉症的風險。

because in some cases with autism,

你看到的這個嬰兒

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

和這位女士有很好的目光接觸

We had to get more granular than that, though,

她在唱兒歌：小小蜘蛛

and so we had to start opening those books,

這個嬰兒不會患上自閉症。

and in some cases, the genetic change

這個嬰兒我們知道是沒問題的。

was more subtle.

不過，另外的這個孩子，

It might have been a single paragraph that was missing,

將會患上自閉症。

or yet, even more subtle than that,

你可以發現這個孩子

a single letter,

不能保持很好的目光接觸，

one out of three billion letters

嬰兒沒有注視， 沒有在女士的眼神上進行交流，

that was changed, that was altered,

而是看看嘴巴，看看鼻子

yet had profound effects

看別的方向，

in terms of how the brain functions

不能保持社交交流。

and affects behavior.

通過這樣的方法，

In doing this within these families,

我們能夠檢查大批的嬰兒， 檢定他們自閉症的風險，

we were able to account for approximately

這些方法很有效也很可靠。

25 percent of the individuals

它們將幫助

and determine that there was a single

在自閉症剛開始的時期介入，

powerful genetic factor

這個階段是最容易看到成效的。

that caused autism within those families.

我們如何介入呢？

On the other hand, there's 75 percent

這應該會是綜合不同方式的。

that we still haven't figured out.

對於一些人，

As we did this, though,

我們會使用藥物，

it was really quite humbling,

所以找到影響自閉症的基因 是至關重要的，

because we realized that there was not simply