in a dark bar in Madrid.

這件事的起始發生在

I encountered my colleague from McGill, Michael Meaney.

馬德里的一間昏暗酒吧裡。

And we were drinking a few beers,

我遇到麥吉爾大學的同事 邁克·梅尼。

and like scientists do,

幾杯啤酒下肚，

he told me about his work.

就像所有科學家一樣，

And he told me that he is interested in how mother rats lick their pups

他跟我聊起了他的工作。

after they were born.

他告訴我他有興趣研究 老鼠媽媽怎麼舔

And I was sitting there and saying,

剛出生的小老鼠。

"This is where my tax dollars are wasted --

然後我吐槽說：

(Laughter)

「我們納稅人的錢就這麼被你們浪費

on this kind of soft science."

（笑聲）

And he started telling me

在這種軟科學上。」

that the rats, like humans,

然後他開始告訴我，

lick their pups in very different ways.

老鼠和人類一樣，

Some mothers do a lot of that,

用各種不同的方法舔牠們的寶寶。

some mothers do very little,

有些媽媽很喜歡舔，

and most are in between.

有些媽媽就不怎麼舔，

But what's interesting about it

大多在中間值。

is when he follows these pups when they become adults --

有趣的是，

like, years in human life, long after their mother died.

在這些小老鼠成年後繼續追蹤牠們，

They are completely different animals.

就像人類成人以後一樣， 在媽媽死了很久以後，

The animals that were licked and groomed heavily,

牠們變成完全不一樣的動物。

the high-licking and grooming,

常常被媽媽又舔又理毛的，

are not stressed.

大量的舔和理毛，

They have different sexual behavior.

壓力會小些。

They have a different way of living

牠們有不同的性行為，

than those that were not treated as intensively by their mothers.

牠們有不同的生活方式，

So then I was thinking to myself:

相較於沒有被母親密集舔過的。

Is this magic?

所以我在想：

How does this work?

有什麼魔力嗎？

As geneticists would like you to think,

為什麼這樣呢？

perhaps the mother had the "bad mother" gene

遺傳學家會讓你這樣想，

that caused her pups to be stressful,

也許母親有「壞媽媽」的基因，

and then it was passed from generation to generation;

使牠的小老鼠變得緊張，

it's all determined by genetics.

然後一代又一代的傳承；

Or is it possible that something else is going on here?

這一切都是由遺傳學決定的。

In rats, we can ask this question and answer it.

或是還有別的東西在做怪？

So what we did is a cross-fostering experiment.

我們可以在老鼠身上 問這個問題並得到答案。

You essentially separate the litter, the babies of this rat, at birth,

所以我們做了交叉寄養實驗。

to two kinds of fostering mothers --

基本上你把一窩剛出生的老鼠分開，

not the real mothers, but mothers that will take care of them:

給兩種寄養母親代養──

high-licking mothers and low-licking mothers.

不是真正的母親，但是會照顧牠們：

And you can do the opposite with the low-licking pups.

密集舔的母親和不太舔的母親。

And the remarkable answer was,

對不太被舔的小老鼠做相反的事情。

it wasn't important what gene you got from your mother.

值得注意的答案是，

It was not the biological mother that defined this property of these rats.

你從母親得到什麼基因不重要。

It is the mother that took care of the pups.

造就成鼠這種特性的 不是親生母親，

So how can this work?

而是寄養母親。

I am an a epigeneticist.

為什麼這麼說呢？

I am interested in how genes are marked

我是表觀遺傳學家。

by a chemical mark

我對基因如何被標記非常感興趣，

during embryogenesis, during the time we're in the womb of our mothers,

這是一種化學標記，

and decide which gene will be expressed

在胚胎形成期間， 在母親的子宮內就有，

in what tissue.

並決定哪種基因會在

Different genes are expressed in the brain than in the liver and the eye.

什麼組織中表現。

And we thought: Is it possible

在大腦表現的基因， 跟在肝臟和眼睛的不一樣。

that the mother is somehow reprogramming the gene of her offspring

我們猜想：是否有可能

through her behavior?

母親通過她的行為

And we spent 10 years,

改寫後代的基因？

and we found that there is a cascade of biochemical events

我們花了 10 年時間，

by which the licking and grooming of the mother, the care of the mother,

發現的確有一系列的生化反應，

is translated to biochemical signals

會被母親的舔和梳理、 母親的照顧所引發，

that go into the nucleus and into the DNA

然後被翻譯成生化信號

and program it differently.

進入細胞核及 DNA，

So now the animal can prepare itself for life:

寫成不一樣的東西。

Is life going to be harsh?

所以現在動物可以為自己做好準備：

Is there going to be a lot of food?

生活會變得艱苦嗎？

Are there going to be a lot of cats and snakes around,

會有很多食物嗎？

or will I live in an upper-class neighborhood

會有很多貓和蛇在附近嗎？

where all I have to do is behave well and proper,

或要是我住在上層階級社區裡，

and that will gain me social acceptance?

我只要表現良好和適當，

And now one can think about how important that process can be

那我就會被社會接受？

for our lives.

我們可以想一下這個過程

We inherit our DNA from our ancestors.

對於生活的重要性。

The DNA is old.

我們從祖先繼承 DNA。

It evolved during evolution.

這些 DNA 很古老。

But it doesn't tell us if you are going to be born in Stockholm,

它在進化過程中演變。

where the days are long in the summer and short in the winter,

但是它不能告訴我們 你是在斯德哥爾摩出生，

or in Ecuador,

那裡的白天在夏天很長，冬天很短；

where there's an equal number of hours for day and night all year round.

那裡一年四季晝夜相當。

And that has such an enormous [effect] on our physiology.

而那對我們的生理學 有非常大的影響。

So what we suggest is, perhaps what happens early in life,

所以我們推斷，生命早期發生的事，

those signals that come through the mother,

即透過母親發出的那些信號，

tell the child what kind of social world you're going to be living in.

會告訴孩子你將要生活 在什麼樣的社會。

It will be harsh, and you'd better be anxious and be stressful,

是嚴苛的世界， 你可能會焦慮和壓力大，

or it's going to be an easy world, and you have to be different.

或是安逸的世界，你最好與眾不同。

Is it going to be a world with a lot of light or little light?

會是有很多陽光 還是很少陽光的世界？

Is it going to be a world with a lot of food or little food?

會是有很多食物 還是很少食物的世界？

If there's no food around,

如果周圍沒有食物，

you'd better develop your brain to binge whenever you see a meal,

你最好訓練你的大腦 每次看到食物就大吃一頓，

or store every piece of food that you have as fat.

或者把每一塊食物都轉成脂肪保存。

So this is good.

這很好。

Evolution has selected this

進化已經選擇了這一點，

to allow our fixed, old DNA to function in a dynamic way

讓我們不變、古老的 DNA

in new environments.

能在新的環境中隨機應變。

But sometimes things can go wrong;

但有時候事情可能會出錯；

for example, if you're born to a poor family

例如，如果你出生在貧窮的家庭，

and the signals are, "You better binge,

信號是，「你最好大吃大喝，

you better eat every piece of food you're going to encounter."

你最好把每一塊 看得到的食物都吞下去。」

But now we humans and our brain have evolved,

但是現在我們人類和大腦都已演化，

have changed evolution even faster.

進化的速度更快了。

Now you can buy McDonald's for one dollar.

現在你可以花一美元買份麥當勞。

And therefore, the preparation that we had by our mothers

變成不適當。

is turning out to be maladaptive.

本來要保護我們 免於飢餓和飢荒的準備，

The same preparation that was supposed to protect us from hunger and famine

將導致肥胖、

is going to cause obesity,

心血管問題和代謝疾病。

cardiovascular problems and metabolic disease.

因此，基因可以透過我們的經驗，

So this concept that genes could be marked by our experience,

特別是早期生活經驗來標記的概念，

and especially the early life experience,

可以為我們提供

can provide us a unifying explanation

對健康和疾病統一的解釋。

of both health and disease.

但是只有老鼠才這樣嗎？

But is true only for rats?

問題是，我們不能拿人類測這個，

The problem is, we cannot test this in humans,

因為在道德上，我們不能 隨機選孩子經歷逆境。

because ethically, we cannot administer child adversity in a random way.

所以如果一個可憐的 小孩養成某種習慣，

So if a poor child develops a certain property,

我們不知道這是由貧困造成的，

we don't know whether this is caused by poverty

還是窮人有壞的基因。

or whether poor people have bad genes.

所以遺傳學家會試圖解釋 窮人之所以窮，

So geneticists will try to tell you that poor people are poor

是因為他們的基因使他們貧窮。

because their genes make them poor.

窮人處於惡劣或貧窮的環境中，

Epigeneticists will tell you

創造出這種表現型，這種特性。

poor people are in a bad environment or an impoverished environment

所以我們調查了我們的表親，猴子。

that creates that phenotype, that property.

我的同事斯蒂芬·蘇米

So we moved to look into our cousins, the monkeys.

以兩種不同的方式飼養猴子：

My colleague, Stephen Suomi, has been rearing monkeys

隨機將被選取的猴子與母親分開，

in two different ways:

找奶媽養育牠，

randomly separated the monkey from the mother

設下代理母親的條件。

and reared her with a nurse

所以這些猴子沒有媽媽； 牠們有奶媽。

and surrogate motherhood conditions.

而其他猴子則由生母養大。

So these monkeys didn't have a mother; they had a nurse.

當牠們老了， 牠們變成完全不同的動物。

And other monkeys were reared with their normal, natural mothers.

由生母撫養的猴子不愛酒精，

And when they were old, they were completely different animals.

牠們沒有性侵略性。

The monkeys that had a mother did not care about alcohol,

沒有母親的猴子 具侵略性、壓力很大，

they were not sexually aggressive.

並且酗酒。

The monkeys that didn't have a mother were aggressive, were stressed

我們在牠們一出生 就檢查 DNA，想看：

and were alcoholics.

媽媽有可能在標記嗎？

So we looked at their DNA early after birth, to see:

在後代的 DNA 中 有母親的「簽名」嗎？

Is it possible that the mother is marking?

這些是 14 天大的猴子，

Is there a signature of the mother in the DNA of the offspring?

這裡你們看到的是我們 研究表觀遺傳學的現代方式。

These are Day-14 monkeys,

我們可以定位這些化學標記， 我們稱做甲基化標記，

and what you see here is the modern way by which we study epigenetics.

解析度為在單核苷酸上 DNA 的情況。

We can now map those chemical marks, which we call methylation marks,

我們可以定位整個基因組。

on DNA at a single nucleotide resolution.

我們現在可以比較 有或沒有母親的猴子。

We can map the entire genome.

這是視覺圖。

We can now compare the monkey that had a mother or not.

你可以看到 有更多甲基化的基因是紅的；

And here's a visual presentation of this.

少甲基化的是基因是綠色的。

What you see is the genes that got more methylated are red.

你們可以看到很多基因在改變，

The genes that got less methylated are green.

因為沒有母親可不是小事一樁，

You can see many genes are changing,

這會影響整體；

because not having a mother is not just one thing --

它會送信號告訴我們

it affects the whole way;

你長大後你的世界是什麼樣子。

it sends signals about the whole way your world is going to look

你們可以看見兩組猴子

when you become an adult.

完全不一樣。

And you can see the two groups of monkeys

這是在多早期就發展出來？

extremely well-separated from each other.

這些猴子早就看不到自己的母親，

How early does this develop?

所以牠們有了某種社會經驗。

These monkeys already didn't see their mothers,

我們在出生時就會感受到 自己的社會地位嗎？

so they had a social experience.

所以在這項實驗中，

Do we sense our social status, even at the moment of birth?

我們從不同社會地位的 猴子身上取出胎盤。

So in this experiment, we took placentas of monkeys

社會階級有趣的地方 就是所有的生物，

that had different social status.

都會把自己分成幾個等級。

What's interesting about social rank is that across all living beings,

猴子一號是老大；

they will structure themselves by hierarchy.

猴子四號是小兵。

Monkey number one is the boss;

你把四隻猴子關在一個籠子裡，

monkey number four is the peon.

一定會產生一隻老大和一隻小兵。

You put four monkeys in a cage,

有趣的是猴子一號

there will always be a boss and always be a peon.

一定比猴子四號更健康。

And what's interesting is that the monkey number one

如果你把牠們關在一個籠子裡，

is much healthier than monkey number four.

猴子一號不會吃太多。

And if you put them in a cage,

猴子四號會吃很多。

monkey number one will not eat as much.

你們在這裡看到的是甲基化定位，

Monkey number four will eat [a lot].

把出生時被迫分離

And what you see here in this methylation mapping,

但社會地位高的動物，

a dramatic separation at birth

與社會地位沒那麼高的動物相比。

of the animals that had a high social status

所以我們出生時 已經對社會訊息略有所知，

versus the animals that did not have a high status.

這種社會訊息沒有什麼好壞，

So we are born already knowing the social information,

只是幫助我們預備好過人生，

and that social information is not bad or good,

因為我們必須針對高或低的社會地位

it just prepares us for life,

編寫不同的生物學程式。

because we have to program our biology differently

但是你要怎麼在人體做這種研究？

if we are in the high or the low social status.

我們不能做實驗， 不能施加厄運給人類。

But how can you study this in humans?

但是神的確在人身上做了實驗，

We can't do experiments, we can't administer adversity to humans.

那就是天災。

But God does experiments with humans,

加拿大史上有一場嚴重天災，

and it's called natural disasters.

就發生在我的省分魁北克，

One of the hardest natural disasters in Canadian history

即 1998 年的冰暴。

happened in my province of Quebec.

我們因這場冰暴 而失去整個輸電網路，

It's the ice storm of 1998.

當時的溫度，在魁北克的隆冬，

We lost our entire electrical grid because of an ice storm

是零下 20、30 度。

when the temperatures were, in the dead of winter in Quebec,

當時有些懷孕的母親。

minus 20 to minus 30.

我的同事金蘇珊持續追蹤

And there were pregnant mothers during that time.

這些母親生下的孩子 15 年。

And my colleague Suzanne King followed the children of these mothers

她發現到，隨著壓力愈來愈高，

for 15 years.

我們有客觀的方法測量壓力：

And what happened was, that as the stress increased --

你有多久無電可用？你在哪裡避難？

and here we had objective measures of stress:

是在婆家的公寓，還是鄉村別墅？

How long were you without power? Where did you spend your time?

把這些加起來得到社會壓力強度，

Was it in your mother-in-law's apartment or in some posh country home?

然後你問：

So all of these added up to a social stress scale,

孩子狀況如何？

and you can ask the question:

顯然隨著壓力增加，

How did the children look?

孩子得到自閉症的情況也增加，

And it appears that as stress increases,

他們更容易得到代謝疾病，

the children develop more autism,

也更容易發展出自體免疫疾病。

they develop more metabolic diseases

我們會定位甲基化程度，

and they develop more autoimmune diseases.

跟之前一樣，綠色的基因 會隨著壓力增加而轉紅，

We would map the methylation state,

紅色的基因會因壓力增加而變綠，

and again, you see the green genes becoming red as stress increases,

基因組會因應壓力而重新排列組合。

the red genes becoming green as stress increases,

所以如果我們可以編寫基因，

an entire rearrangement of the genome in response to stress.

如果我們不受限於基因的來源，

So if we can program genes,

而是能編寫，我們可以抹去 壓力造成的影響嗎？

if we are not just the slaves of the history of our genes,

因為表觀遺傳會造成疾病，如癌症、

that they could be programmed, can we deprogram them?

新陳代謝疾病、

Because epigenetic causes can cause diseases like cancer,

及精神疾病。

metabolic disease

來看一下古柯鹼上癮。

and mental health diseases.

古柯鹼上癮是一種很糟的情況，

Let's talk about cocaine addiction.

會導致死亡，失去生命。

Cocaine addiction is a terrible situation

我們問這個問題：

that can lead to death and to loss of human life.

我們能不能重新改寫上癮的腦部，

We asked the question:

讓成癮的動物完全戒掉？

Can we reprogram the addicted brain

我們使用一種古柯鹼成癮模式，

to make that animal not addicted anymore?

概述一下人類的狀況。

We used a cocaine addiction model

在人類是這樣的，你在高中時

that recapitulates what happens in humans.

一些朋友要你試試古柯鹼，

In humans, you're in high school,

你吸了一點，沒事。

some friends suggest you use some cocaine,

幾個月後，某個契機 讓你回想起第一次的狀況，

you take cocaine, nothing happens.

毒販又給了你一點古柯鹼，

Months pass by, something reminds you of what happened the first time,

然後你就上癮，生命因此改變。

a pusher pushes cocaine,

我們也在老鼠身上做同樣的事。

and you become addicted and your life has changed.

我的同事亞迪德

In rats, we do the same thing.

他訓練動物習慣古柯鹼，

My colleague, Gal Yadid,

然後一個月不給古柯鹼。

he trains the animals to get used to cocaine,

然後他讓牠們想起第一次古柯鹼趴，

then for one month, no cocaine.

就是把牠們關在一樣顏色的籠子裡。