TEDxBratislava
Moshe Szyf: How early life experience is written into DNA
摩西·西夫: 早期生活经历如何写入DNA
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摩西·西夫是表观遗传学领域的先驱，他研究生物如何对其基因组重新编码，以应对压力和缺乏食物等社会因素。 他的研究表明，从母体传递到后代的生化信号告诉孩子他们将要生活在什么样的世界，这改变了基因的表达。 “DNA不仅仅是一系列字母，它不只是一个脚本。” 西夫说。 “DNA是动态的电影，我们的经历正在被写入DNA”。
Moshe Szyf - Epigeneticist
Moshe Szyf's research is focused on understanding the broad implications of epigenetic mechanisms in human behavior, health and disease. Full bio
Moshe Szyf's research is focused on understanding the broad implications of epigenetic mechanisms in human behavior, health and disease. Full bio
Double-click the English transcript below to play the video.
00:12
So it all came to life
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这一切都是
在马德里的一个黑暗的酒吧里发生的。
00:14
in a dark bar in Madrid.
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我遇到了麦吉尔大学的同事，迈克尔·梅尼。
00:17
I encountered my colleague
from McGill, Michael Meaney.
from McGill, Michael Meaney.
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我们喝着几杯啤酒，
00:21
And we were drinking a few beers,
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像所有科学家一样，
00:23
and like scientists do,
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他跟我聊他的工作。
00:25
he told me about his work.
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00:28
And he told me that he is interested
in how mother rats lick their pups
in how mother rats lick their pups
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他告诉我，他感兴趣的是
小鼠出生后，母鼠如何舔它们的婴儿。
00:35
after they were born.
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我呆住了，说：
00:37
And I was sitting there and saying,
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“我交的税就浪费在这儿了啊，——
00:40
"This is where my tax
dollars are wasted --
dollars are wasted --
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（笑声）
00:43
(Laughter)
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就是这种软科学。”
00:44
on this kind of soft science."
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他开始给我讲，
00:47
And he started telling me
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老鼠和人类一样，
00:50
that the rats, like humans,
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用不同的方式舔抚她们的孩子。
00:53
lick their pups in very different ways.
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00:56
Some mothers do a lot of that,
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一些母亲做的很多，
一些母亲做的很少，
00:59
some mothers do very little,
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大多数介于两者之间。
01:01
and most are in between.
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但是有趣的是，
01:03
But what's interesting about it
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当他跟踪这些小鼠直到成年——
01:05
is when he follows these pups
when they become adults --
when they become adults --
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相当于人类的很多年后，
母亲去世后的很长时间。
母亲去世后的很长时间。
01:10
like, years in human life,
long after their mother died.
long after their mother died.
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它们变成了完全不同的动物。
01:14
They are completely different animals.
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那些受到大量舔舐和梳毛的动物，
01:17
The animals that were licked
and groomed heavily,
and groomed heavily,
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即高舔舐和梳毛的动物，
01:21
the high-licking and grooming,
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不会紧张不安。
01:24
are not stressed.
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它们的性行为不同。
01:26
They have different sexual behavior.
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它们的生活方式
01:28
They have a different way of living
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与没有被妈妈密切照顾的小鼠不同。
01:31
than those that were not treated
as intensively by their mothers.
as intensively by their mothers.
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01:37
So then I was thinking to myself:
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那么我问自己：
这是魔法吗？
01:41
Is this magic?
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怎么会这样的？
01:43
How does this work?
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遗传学家希望你这样想：
01:44
As geneticists would like you to think,
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也许那些妈妈拥有“坏妈妈”基因，
01:47
perhaps the mother had
the "bad mother" gene
the "bad mother" gene
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导致她的婴儿紧张不安，
01:51
that caused her pups to be stressful,
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然后这种基因代代相传；
01:55
and then it was passed
from generation to generation;
from generation to generation;
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全部是遗传决定的。
01:57
it's all determined by genetics.
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有没有别的可能？
02:00
Or is it possible that something
else is going on here?
else is going on here?
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在老鼠身上，我们可以
提出这个问题并解答它。
提出这个问题并解答它。
02:03
In rats, we can ask
this question and answer it.
this question and answer it.
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所以我们做了交叉养育实验。
02:07
So what we did is
a cross-fostering experiment.
a cross-fostering experiment.
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基本上在一窝小鼠出生时
把它们分开，
把它们分开，
02:11
You essentially separate the litter,
the babies of this rat, at birth,
the babies of this rat, at birth,
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分给两种不同类型的养母——
02:15
to two kinds of fostering mothers --
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不是生母，而是照顾小鼠的母鼠：
02:17
not the real mothers,
but mothers that will take care of them:
but mothers that will take care of them:
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高舔舐母鼠和低舔舐母鼠。
02:21
high-licking mothers
and low-licking mothers.
and low-licking mothers.
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另外一边是低舔舐小鼠。
02:23
And you can do the opposite
with the low-licking pups.
with the low-licking pups.
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令人惊奇的答案是，
02:27
And the remarkable answer was,
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从母亲那里得到什么基因并不重要。
02:30
it wasn't important
what gene you got from your mother.
what gene you got from your mother.
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定义这些老鼠的这种特征的不是生母，
02:34
It was not the biological mother
that defined this property of these rats.
that defined this property of these rats.
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而是照顾小鼠的母鼠。
02:39
It is the mother that
took care of the pups.
took care of the pups.
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那么，这是怎么实现的？
02:44
So how can this work?
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02:48
I am an a epigeneticist.
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我是一个表观遗传学家。
我的兴趣是在胚胎期间，
02:50
I am interested in how genes are marked
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我们在母体子宫里时，
02:54
by a chemical mark
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如何用化学记号标记基因，
02:56
during embryogenesis, during the time
we're in the womb of our mothers,
we're in the womb of our mothers,
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并决定
03:01
and decide which gene will be expressed
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哪个基因在哪个组织中表达。
03:03
in what tissue.
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大脑中表达的基因与肝脏和眼睛中的不同。
03:04
Different genes are expressed in the brain
than in the liver and the eye.
than in the liver and the eye.
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03:09
And we thought: Is it possible
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我们怀疑：有没有可能
妈妈通过自己的行为
03:12
that the mother is somehow
reprogramming the gene of her offspring
reprogramming the gene of her offspring
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改写她后代的基因编码？
03:19
through her behavior?
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我们花了10年，
03:21
And we spent 10 years,
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发现有一系列的生物化学事件，
03:22
and we found that there is a cascade
of biochemical events
of biochemical events
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母鼠的舔舐和梳毛，妈妈的照顾
03:26
by which the licking and grooming
of the mother, the care of the mother,
of the mother, the care of the mother,
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被转化成生物化学信号，
03:30
is translated to biochemical signals
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这信号进入细胞核并进入DNA，
03:32
that go into the nucleus and into the DNA
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改写了编码。
03:36
and program it differently.
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所以现在这个动物能
为生活做更好的准备：
为生活做更好的准备：
03:38
So now the animal can prepare
itself for life:
itself for life:
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生活会很艰难吗？
03:43
Is life going to be harsh?
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会有很多食物吗？
03:45
Is there going to be a lot of food?
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周围会有很多猫和蛇吗？
03:47
Are there going to be a lot of cats
and snakes around,
and snakes around,
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还是会住在上层社区，
03:50
or will I live
in an upper-class neighborhood
in an upper-class neighborhood
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只要行为端正举止适当
03:52
where all I have to do
is behave well and proper,
is behave well and proper,
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就会赢得社会认可？
03:55
and that will gain me social acceptance?
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现在可以想想这个过程
03:58
And now one can think about
how important that process can be
how important that process can be
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对我们的生命有多重要了。
04:04
for our lives.
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我们从祖先继承了DNA。
04:05
We inherit our DNA from our ancestors.
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04:09
The DNA is old.
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DNA历史悠久。
它在进化过程中演变。
04:11
It evolved during evolution.
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但它并不告诉我们，
04:13
But it doesn't tell us
if you are going to be born in Stockholm,
if you are going to be born in Stockholm,
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你会出生在夏季白天长、
冬季白天短的斯德哥尔摩，
冬季白天短的斯德哥尔摩，
04:18
where the days are long in the summer
and short in the winter,
and short in the winter,
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还是出生在
04:21
or in Ecuador,
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整年都白天黑夜一样长的厄瓜多尔。
04:23
where there's an equal number of hours
for day and night all year round.
for day and night all year round.
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这对我们的生理有巨大的影响。
04:26
And that has such an enormous [effect]
on our physiology.
on our physiology.
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04:31
So what we suggest is,
perhaps what happens early in life,
perhaps what happens early in life,
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所以我们认为，
也许是在生命早期发生的事，
也许是在生命早期发生的事，
通过母亲传递的那些信号，
04:35
those signals that come
through the mother,
through the mother,
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告诉子女将要在怎样的社会环境中生存。
04:37
tell the child what kind of social world
you're going to be living in.
you're going to be living in.
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如果环境艰难，你最好焦虑紧张，
04:42
It will be harsh, and you'd better
be anxious and be stressful,
be anxious and be stressful,
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或者如果环境轻松，你必定也不同。
04:45
or it's going to be an easy world,
and you have to be different.
and you have to be different.
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那世界会有很多光线还是很少光线？
04:49
Is it going to be a world
with a lot of light or little light?
with a lot of light or little light?
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那世界会有很多食物还是很少食物？
04:52
Is it going to be a world
with a lot of food or little food?
with a lot of food or little food?
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如果周围没有食物，
04:56
If there's no food around,
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你最好让大脑发育成
一旦看到食物马上大吃一顿，
一旦看到食物马上大吃一顿，
04:57
you'd better develop your brain to binge
whenever you see a meal,
whenever you see a meal,
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或者把拥有的每一块食物都
储存成脂肪。
储存成脂肪。
05:02
or store every piece of food
that you have as fat.
that you have as fat.
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05:08
So this is good.
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所以，这很好。
进化已经这样选择，
05:10
Evolution has selected this
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让我们固有的、陈旧的DNA
05:12
to allow our fixed, old DNA
to function in a dynamic way
to function in a dynamic way
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在新的环境中不断变化地发挥作用。
05:17
in new environments.
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但有些事可能会出错：
05:19
But sometimes things can go wrong;
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05:22
for example, if you're born
to a poor family
to a poor family
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例如，如果你出生在一个贫穷的家庭，
信号是，“你最好快吃，
05:26
and the signals are, "You better binge,
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你最好把遇到的每一块食物都吃掉。”
05:29
you better eat every piece of food
you're going to encounter."
you're going to encounter."
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但是现在我们人类和人脑已经进化了，
05:32
But now we humans
and our brain have evolved,
and our brain have evolved,
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已经进化得更快。
05:35
have changed evolution even faster.
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现在你用一块钱就可以买麦当劳。
05:37
Now you can buy McDonald's for one dollar.
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因此，母亲为我们所做的准备
05:40
And therefore, the preparation
that we had by our mothers
that we had by our mothers
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变得不适用了。
05:47
is turning out to be maladaptive.
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05:50
The same preparation that was supposed
to protect us from hunger and famine
to protect us from hunger and famine
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本应保护我们免受饥苦的
同样的准备工作
同样的准备工作
却会导致肥胖症、
05:54
is going to cause obesity,
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心血管问题和代谢疾病。
05:57
cardiovascular problems
and metabolic disease.
and metabolic disease.
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所以，这个可以通过经历、
尤其是早期生活经历
尤其是早期生活经历
06:00
So this concept that genes
could be marked by our experience,
could be marked by our experience,
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来标记基因的概念
06:04
and especially the early life experience,
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可以为我们提供
06:06
can provide us a unifying explanation
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对健康和疾病的统一解释。
06:09
of both health and disease.
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06:12
But is true only for rats?
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但这只在老鼠身上才正确吗？
问题是，我们不能用人类做测试，
06:14
The problem is, we cannot
test this in humans,
test this in humans,
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因为从道德上，我们不能
随机地为儿童设置逆境。
随机地为儿童设置逆境。
06:17
because ethically, we cannot administer
child adversity in a random way.
child adversity in a random way.
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所以，如果穷孩子养成某种特征，
06:22
So if a poor child develops
a certain property,
a certain property,
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我们不知道它是由贫穷引起的
06:25
we don't know whether
this is caused by poverty
this is caused by poverty
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还是因为穷人有不良的基因。
06:29
or whether poor people have bad genes.
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所以，遗传学家试图告诉你
06:32
So geneticists will try to tell you
that poor people are poor
that poor people are poor
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穷人之所以穷是因为基因让他们穷。
06:35
because their genes make them poor.
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表观遗传学家会告诉你
06:37
Epigeneticists will tell you
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穷人所在的不良环境或贫穷环境
06:39
poor people are in a bad environment
or an impoverished environment
or an impoverished environment
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环境创造了那些表型，那种贫穷。
06:43
that creates that phenotype,
that property.
that property.
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06:47
So we moved to look
into our cousins, the monkeys.
into our cousins, the monkeys.
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所以我们转而观察我们的表亲：猴子。
我的同事斯蒂芬·苏米
06:54
My colleague, Stephen Suomi,
has been rearing monkeys
has been rearing monkeys
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以两种不同的方式饲养猴子：
06:57
in two different ways:
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随机地将猴子与母亲分离，
06:58
randomly separated the monkey
from the mother
from the mother
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通过护理员和代养条件
07:01
and reared her with a nurse
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来培养她。
07:04
and surrogate motherhood conditions.
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所以这些猴子没有妈妈，
只有护理员。
只有护理员。
07:07
So these monkeys didn't have
a mother; they had a nurse.
a mother; they had a nurse.
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07:10
And other monkeys were reared
with their normal, natural mothers.
with their normal, natural mothers.
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而其他猴子是正常的亲生妈妈养育的。
当他们年老时，他们变成了完全不同的动物。
07:14
And when they were old,
they were completely different animals.
they were completely different animals.
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有妈妈的猴子不嗜酒，
07:19
The monkeys that had a mother
did not care about alcohol,
did not care about alcohol,
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他们没有性暴力倾向。
07:22
they were not sexually aggressive.
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没有妈妈的猴子有攻击性，紧张，
07:24
The monkeys that didn't have a mother
were aggressive, were stressed
were aggressive, were stressed
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还是酒鬼。
07:28
and were alcoholics.
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07:30
So we looked at their DNA
early after birth, to see:
early after birth, to see:
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我们在出生后的早期观察他们的DNA：
看看有没有可能是妈妈在标记？
07:35
Is it possible that the mother is marking?
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后代的DNA里有没有妈妈的签名？
07:38
Is there a signature of the mother
in the DNA of the offspring?
in the DNA of the offspring?
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这些是14天的猴子，
07:44
These are Day-14 monkeys,
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这里看到的是我们研究
表观遗传学的现代方式。
表观遗传学的现代方式。
07:46
and what you see here is the modern way
by which we study epigenetics.
by which we study epigenetics.
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我们能把这些化学标记——
称为甲基化标记，
称为甲基化标记，
07:50
We can now map those chemical marks,
which we call methylation marks,
which we call methylation marks,
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以单核苷酸分辨率绘制到DNA上。
07:55
on DNA at a single nucleotide resolution.
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我们能够绘制整个基因组。
07:58
We can map the entire genome.
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现在我们可以比较
有妈妈或没有妈妈的猴子了。
有妈妈或没有妈妈的猴子了。
08:00
We can now compare the monkey
that had a mother or not.
that had a mother or not.
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这里是直观展示。
08:03
And here's a visual presentation of this.
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你看到的是
较多甲基化的基因呈现红色。
较多甲基化的基因呈现红色。
08:05
What you see is the genes
that got more methylated are red.
that got more methylated are red.
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较少甲基化的基因呈现绿色。
08:10
The genes that got
less methylated are green.
less methylated are green.
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你能看到很多基因在改变，
08:13
You can see many genes are changing,
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因为没有妈妈不只是简单一件事——
08:15
because not having a mother
is not just one thing --
is not just one thing --
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它影响所有的一切；
08:18
it affects the whole way;
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它传递着关于你
08:20
it sends signals about the whole way
your world is going to look
your world is going to look
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成年后的世界
是什么样子的全部信号。
是什么样子的全部信号。
08:23
when you become an adult.
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你可以看到两组猴子
08:25
And you can see the two groups of monkeys
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它们极其明显的大不相同。
08:27
extremely well-separated from each other.
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这种发育从多早开始？
08:31
How early does this develop?
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这些猴子已经没见过妈妈，
08:34
These monkeys already
didn't see their mothers,
didn't see their mothers,
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所以它们有社交经历。
08:36
so they had a social experience.
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我们在出生的时刻也能
感受自己的社会地位吗？
感受自己的社会地位吗？
08:38
Do we sense our social status,
even at the moment of birth?
even at the moment of birth?
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所以在这个实验中，
08:43
So in this experiment,
we took placentas of monkeys
we took placentas of monkeys
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我们采用具有不同
社会地位的猴子的胎盘。
社会地位的猴子的胎盘。
08:47
that had different social status.
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关于社会秩序，有趣的是
在所有的生物中，
在所有的生物中，
08:49
What's interesting about social rank
is that across all living beings,
is that across all living beings,
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他们都用等级制度构建社会。
08:55
they will structure
themselves by hierarchy.
themselves by hierarchy.
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一号猴子是老板；
08:58
Monkey number one is the boss;
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四号猴子是苦力。
09:00
monkey number four is the peon.
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在一个笼子里放四只猴子，
09:02
You put four monkeys in a cage,
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总是有一个老板，一个苦力。
09:05
there will always be a boss
and always be a peon.
and always be a peon.
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09:09
And what's interesting
is that the monkey number one
is that the monkey number one
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并且，有趣的是，一号猴子
比四号猴子健康得多。
09:13
is much healthier than monkey number four.
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如果把它们放在一个笼子里，
09:16
And if you put them in a cage,
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一号猴子吃得不多。
09:18
monkey number one will not eat as much.
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四号猴子能吃（很多）。
09:23
Monkey number four will eat [a lot].
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在这个甲基绘制图中可以看到，
09:26
And what you see here
in this methylation mapping,
in this methylation mapping,
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社会地位高的动物与社会地位低的动物
09:30
a dramatic separation at birth
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09:33
of the animals that had
a high social status
a high social status
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在刚出生时的明显不同
09:35
versus the animals
that did not have a high status.
that did not have a high status.
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的对比图。
所以我们出生时已经知道社会信息，
09:39
So we are born already knowing
the social information,
the social information,
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该社会信息并无好坏之分，
09:43
and that social information
is not bad or good,
is not bad or good,
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它只是帮我们为生活做准备，
09:46
it just prepares us for life,
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09:48
because we have to program
our biology differently
our biology differently
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因为我们要根据所处的
高社会地位或低社会地位，
高社会地位或低社会地位，
用不同方式给自己进行生物编码。
09:52
if we are in the high
or the low social status.
or the low social status.
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但如何在人类中研究这种现象？
09:56
But how can you study this in humans?
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我们不能做实验，
不能给人类制造逆境。
不能给人类制造逆境。
09:58
We can't do experiments,
we can't administer adversity to humans.
we can't administer adversity to humans.
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但上帝在用人类做实验，
10:02
But God does experiments with humans,
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它叫做自然灾害。
10:04
and it's called natural disasters.
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加拿大历史上最严重的自然灾害之一
10:07
One of the hardest natural disasters
in Canadian history
in Canadian history
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发生在我来自的魁北克省。
10:11
happened in my province of Quebec.
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是1998年的冰暴。
10:13
It's the ice storm of 1998.
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因为冰暴，我们整个电网坏掉，
10:16
We lost our entire electrical grid
because of an ice storm
because of an ice storm
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当时是魁北克最冷的冬天，
10:20
when the temperatures
were, in the dead of winter in Quebec,
were, in the dead of winter in Quebec,
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温度在零下20至零下30。
10:23
minus 20 to minus 30.
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在那段时间有怀孕的妈妈们。
10:25
And there were pregnant
mothers during that time.
mothers during that time.
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我同事苏珊娜·金对这些妈妈们的孩子
10:28
And my colleague Suzanne King
followed the children of these mothers
followed the children of these mothers
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跟踪调查了15年。
10:34
for 15 years.
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事实是，随着压力增大——
10:36
And what happened was,
that as the stress increased --
that as the stress increased --
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我们这里有对压力的客观度量：
10:40
and here we had objective
measures of stress:
measures of stress:
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你停电多长时间？在哪里度日？
10:43
How long were you without power?
Where did you spend your time?
Where did you spend your time?
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在婆婆的小公寓还是
奢侈的乡间别墅？
奢侈的乡间别墅？
10:47
Was it in your mother-in-law's apartment
or in some posh country home?
or in some posh country home?
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所有这些加起来得出社会压力评级，
10:52
So all of these added up
to a social stress scale,
to a social stress scale,
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你可以问的是：
10:55
and you can ask the question:
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孩子们看上去如何？
10:57
How did the children look?
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显然，随着压力增大，
11:00
And it appears that as stress increases,
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孩子们的自闭症更多，
11:02
the children develop more autism,
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他们的代谢疾病更多，
11:04
they develop more metabolic diseases
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自身免疫性疾病也更多。
11:07
and they develop more autoimmune diseases.
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我们绘制甲基化状态，
11:10
We would map the methylation state,
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再一次看到，随着压力增大
绿色基因变成红色，
绿色基因变成红色，
11:13
and again, you see the green genes
becoming red as stress increases,
becoming red as stress increases,
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随着压力增大，红色基因变成绿色，
11:18
the red genes becoming green
as stress increases,
as stress increases,
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基因组响应于压力进行完全重排。
11:22
an entire rearrangement
of the genome in response to stress.
of the genome in response to stress.
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11:29
So if we can program genes,
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所以，如果我们能编写基因，
如果我们不仅仅做我们基因历史的奴隶，
11:32
if we are not just the slaves
of the history of our genes,
of the history of our genes,
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如果基因可以编写，
那我们能抹掉对基因的编写吗？
那我们能抹掉对基因的编写吗？
11:36
that they could be programmed,
can we deprogram them?
can we deprogram them?
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因为表观遗传因素会导致癌症、
11:40
Because epigenetic causes
can cause diseases like cancer,
can cause diseases like cancer,
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代谢疾病
11:45
metabolic disease
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和精神健康疾病等。
11:47
and mental health diseases.
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我们来谈谈可卡因成瘾。
11:50
Let's talk about cocaine addiction.
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可卡因成瘾是一种可怕的状态
11:53
Cocaine addiction is a terrible situation
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会导致死亡和丧命。
11:56
that can lead to death
and to loss of human life.
and to loss of human life.
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我们问了一个问题：
12:01
We asked the question:
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我们可以重新编写上瘾的大脑，
12:03
Can we reprogram the addicted brain
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让上瘾的动物不再有瘾吗？
12:06
to make that animal not addicted anymore?
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12:12
We used a cocaine addiction model
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我们使用可卡因成瘾模型，
该模型概括了人类成瘾的情况。
12:16
that recapitulates what happens in humans.
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对于人类，你上高中时，
12:18
In humans, you're in high school,
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某些朋友建议你用点可卡因，
12:21
some friends suggest you use some cocaine,
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你用了可卡因，没发生什么事。
12:23
you take cocaine, nothing happens.
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几个月后，突然想起第一次的事，
12:25
Months pass by, something reminds you
of what happened the first time,
of what happened the first time,
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毒贩子在卖可卡因，
12:29
a pusher pushes cocaine,
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然后你上瘾了，然后生活彻底改变。
12:31
and you become addicted
and your life has changed.
and your life has changed.
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我们用老鼠做同样的事。
12:34
In rats, we do the same thing.
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我同事加尔·雅迪
12:35
My colleague, Gal Yadid,
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他训练这些动物习惯可卡因，
12:37
he trains the animals
to get used to cocaine,
to get used to cocaine,
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然后一个月没有可卡因。
12:40
then for one month, no cocaine.
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然后他提醒动物们
第一次看到可卡因的场景，
第一次看到可卡因的场景，
12:43
Then he reminds them of the party
when they saw the cocaine the first time
when they saw the cocaine the first time
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提示方法是
看到可卡因时笼子的颜色。
看到可卡因时笼子的颜色。
12:47
by cue, the colors of the cage
when they saw cocaine.
when they saw cocaine.
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动物们疯了。
12:50
And they go crazy.
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它们一直按动会提供可卡因的杠杆，
12:51
They will press the lever to get cocaine
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直到死亡。
12:54
until they die.
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我们首先确定的是，
这些动物之间的区别
这些动物之间的区别
12:56
We first determined that the difference
between these animals
between these animals
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是在什么都没发生的那段时间里
13:00
is that during that time
when nothing happens,
when nothing happens,
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周围没有可卡因时，
13:03
there's no cocaine around,
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它们的表观基因组重新排列。
13:05
their epigenome is rearranged.
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它们的基因以不同的方式重新标记，
13:06
Their genes are re-marked
in a different way,
in a different way,
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当提示出现时，
13:09
and when the cue comes,
their genome is ready
their genome is ready
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它们的基因组已经准备好
发展出成瘾表型。
发展出成瘾表型。
13:13
to develop this addictive phenotype.
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然后我们用药治疗这些动物，
13:16
So we treated these animals with drugs
that either increase DNA methylation,
that either increase DNA methylation,
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药物要么增加DNA甲基化——
对象是表观基因标记物，
对象是表观基因标记物，
13:23
which was the epigenetic
marker to look at,
marker to look at,
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要么减少表观基因标记。
13:25
or decrease epigenetic markings.
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我们发现，如果增加甲基化，
13:29
And we found that
if we increased methylation,
if we increased methylation,
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这些动物会更疯狂。
13:32
these animals go even crazier.
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它们对可卡因更渴望。
13:34
They become more craving for cocaine.
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但如果减少DNA甲基化，
13:36
But if we reduce the DNA methylation,
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动物不再有瘾。
13:40
the animals are not addicted anymore.
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我们把这些动物重新编码了。
13:42
We have reprogrammed them.
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表观基因药物与其他药物
13:44
And a fundamental difference
between an epigenetic drug
between an epigenetic drug
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的基本区别是，
13:47
and any other drug
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通过表观基因药物，
13:48
is that with epigenetic drugs,
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我们在根本上去除了经历的印记，
13:50
we essentially remove
the signs of experience,
the signs of experience,
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一旦去除印记，
13:55
and once they're gone,
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它不会回来，除非再经历一遍。
13:57
they will not come back
unless you have the same experience.
unless you have the same experience.
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现在动物被重新编码。
14:00
The animal now is reprogrammed.
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14:01
So when we visited the animals
30 days, 60 days later,
30 days, 60 days later,
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所以在30天、60天后——
等于人类的很多年，
等于人类的很多年，
再造访这些动物时，
14:06
which is in human terms
many years of life,
many years of life,
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它们仍然没有瘾——
只通过单一的表观基因治疗。
只通过单一的表观基因治疗。
14:09
they were still not addicted --
by a single epigenetic treatment.
by a single epigenetic treatment.
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14:16
So what did we learn about DNA?
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那么关于DNA，我们学到了什么？
DNA不仅仅是一系列的字母;
14:19
DNA is not just a sequence of letters;
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它不只是一个脚本。
14:22
it's not just a script.
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DNA是一部动态电影。
14:25
DNA is a dynamic movie.
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我们的经历正在写入这部电影中，
它是互动的。
它是互动的。
14:28
Our experiences are being written
into this movie, which is interactive.
into this movie, which is interactive.
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就像用遥控器看电影一样，
14:33
You're, like, watching a movie
of your life, with the DNA,
of your life, with the DNA,
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你在用DNA来观看你的人生。
14:36
with your remote control.
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你可以去掉一个演员、增加一个演员。
14:38
You can remove an actor and add an actor.
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因此，尽管遗传学具有确定性，
14:42
And so you have, in spite
of the deterministic nature of genetics,
of the deterministic nature of genetics,
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你仍可以控制基因的表达方式，
14:48
you have control of the way
your genes look,
your genes look,
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这为我们面对某些致命疾病的能力
14:52
and this has a tremendous
optimistic message
optimistic message
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14:55
for the ability to now encounter
some of the deadly diseases
some of the deadly diseases
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例如癌症、心理疾病等
提供了非常乐观的信息，
14:59
like cancer, mental health,
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提供了新的方法，
15:02
with a new approach,
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可以把这些疾病看作适应不良。
15:05
looking at them as maladaptation.
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15:07
And if we can epigenetically intervene,
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如果我们能进行表观基因干预，
我们就可以去掉一个演员，让电影倒退
15:10
[we can] reverse the movie
by removing an actor
by removing an actor
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并设置新的故事线。
15:14
and setting up a new narrative.
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所以我今天告诉你的是，
15:18
So what I told you today is,
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我们的DNA实际由两个部分组成，
15:20
our DNA is really combined
of two components,
of two components,
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两层信息。
15:25
two layers of information.
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一层信息是古老的，
15:28
One layer of information is old,
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3675
从数百万年的进化演变而来。
15:31
evolved from millions
of years of evolution.
of years of evolution.
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它是固定的，很难改变。
15:35
It is fixed and very hard to change.
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另一层信息是表观遗传层，
15:39
The other layer of information
is the epigenetic layer,
is the epigenetic layer,
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3850
它是开放和动态的，
15:43
which is open and dynamic
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并设置了一个可以互动的故事线，
15:47
and sets up a narrative
that is interactive,
that is interactive,
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4592
让我们能够在很大程度上
控制自己的命运，
控制自己的命运，
15:51
that allows us to control,
to a large extent, our destiny,
to a large extent, our destiny,
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6788
15:59
to help the destiny of our children
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3456
帮助改变我们下一代的命运，
并且有希望征服那些
16:03
and to hopefully conquer disease
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长期困扰人类的
16:07
and serious health challenges
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疾病和严峻的健康挑战。
16:11
that have plagued humankind
for a long time.
for a long time.
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所以即使我们
16:15
So even though we are determined
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已经被我们的基因决定，
16:18
by our genes,
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我们还是有一定程度的自由，
16:20
we have a degree of freedom
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能够把自己的生命设置成
有责任担当的生命。
有责任担当的生命。
16:23
that can set up our life
to a life of responsibility.
to a life of responsibility.
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16:27
Thank you.
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谢谢。
16:29
(Applause)
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（掌声）
ABOUT THE SPEAKER
Moshe Szyf - EpigeneticistMoshe Szyf's research is focused on understanding the broad implications of epigenetic mechanisms in human behavior, health and disease.
Why you should listen
Moshe Szyf is one of the pioneers in the field of epigenetics. Szyf's lab has proposed three decades ago that DNA methylation is a prime therapeutic target in cancer and other diseases and has postulated and provided the first set of evidence that the "social environment" early in life can alter DNA methylation launching the emerging field of "social epigenetics."
Szyf received his PhD from the Hebrew University and did his postdoctoral fellowship in Genetics at Harvard Medical School, joined the department in 1989 and currently holds a James McGill Professorship and GlaxoSmithKline-CIHR Chair in Pharmacology. He is the founding co-director of the Sackler Institute for Epigenetics and Psychobiology at McGill and is a Fellow of the Canadian Institute for Advanced Research Experience-based Brain and Biological Development program.
Moshe Szyf | Speaker | TED.com