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So it all came to life

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in a dark bar in Madrid.

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I encountered my colleague
from McGill, Michael Meaney.

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And we were drinking a few beers,

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and like scientists do,

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he told me about his work.

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

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after they were born.

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And I was sitting there and saying,

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"This is where my tax
dollars are wasted --

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(Laughter)

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on this kind of soft science."

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And he started telling me

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that the rats, like humans,

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lick their pups in very different ways.

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Some mothers do a lot of that,

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some mothers do very little,

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and most are in between.

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But what's interesting about it

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

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

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They are completely different animals.

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The animals that were licked
and groomed heavily,

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the high licking and grooming,

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are not stressed.

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They have different sexual behavior.

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They have a different way of living

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

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So then I was thinking to myself:

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Is this magic?

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How does this work?

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As geneticists would like you to think,

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perhaps the mother had
the "bad mother" gene

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that caused her pups to be stressful,

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and then it was passed
from generation to generation;

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it's all determined by genetics.

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

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

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So what we did is
a cross-fostering experiment.

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

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to two kinds of fostering mothers --

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

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high-licking mothers
and low-licking mothers.

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

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And the remarkable answer was,

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

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

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It is the mother that
took care of the pups.

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So how can this work?

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I am an a epigeneticist.

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I am interested in how genes are marked

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by a chemical mark

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

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and decide which gene will be expressed

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in what tissue.

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

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And we thought: Is it possible

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that the mother is somehow
reprogramming the gene of her offspring

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through her behavior?

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And we spent 10 years,

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and we found that there is a cascade
of biochemical events

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

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is translated to biochemical signals

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that go into the nucleus and into the DNA

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and program it differently.

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So now the animal can prepare
itself for life:

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Is life going to be harsh?

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Is there going to be a lot of food?

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

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or will I live
in an upper-class neighborhood

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

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and that will gain me social acceptance?

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

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for our lives.

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We inherit our DNA from our ancestors.

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The DNA is old.

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It evolved during evolution.

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

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

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or in Ecuador,

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

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

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

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those signals that come
through the mother,

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

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

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

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

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

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If there's no food around,

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

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

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So this is good.

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Evolution has selected this

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

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in new environments.

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But sometimes things can go wrong;

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

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and the signals are, "You better binge,

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

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But now we humans
and our brain have evolved,

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have changed evolution even faster.

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Now you can buy McDonald's for one dollar.

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And therefore, the preparation
that we had by our mothers

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is turning out to be maladaptive.

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

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is going to cause obesity,

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cardiovascular problems
and metabolic disease.

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

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and especially the early life experience,

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can provide us a unifying explanation

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of both health and disease.

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But is true only for rats?

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The problem is, we cannot
test this in humans,

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

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So if a poor child develops
a certain property,

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we don't know whether
this is caused by poverty

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or whether poor people have bad genes.

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

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because their genes make them poor.

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Epigeneticists will tell you

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poor people are in a bad environment
or an impoverished environment

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that creates that phenotype,
that property.

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

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My colleague, Stephen Suomi,
has been rearing monkeys

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in two different ways:

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randomly separated the monkey
from the mother

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and reared her with a nurse

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and surrogate motherhood conditions.

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

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

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

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

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they were not sexually aggressive.

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

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and were alcoholics.

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

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Is it possible that the mother is marking?

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

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These are Day-14 monkeys,

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

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

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on DNA at a single nucleotide resolution.

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We can map the entire genome.

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

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And here's a visual presentation of this.

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

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The genes that got
less methylated are green.

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You can see many genes are changing,

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

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it affects the whole way;

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

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when you become an adult.

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And you can see the two groups of monkeys

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extremely well-separated from each other.

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How early does this develop?

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These monkeys already
didn't see their mothers,

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so they had a social experience.

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

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So in this experiment,
we took placentas of monkeys

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that had different social status.

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

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they will structure
themselves by hierarchy.

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Monkey number one is the boss;

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monkey number four is the peon.

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You put four monkeys in a cage,

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

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And what's interesting
is that the monkey number one

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is much healthier than monkey number four.

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And if you put them in a cage,

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monkey number one will not eat as much.

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Monkey number four will eat [a lot].

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And what you see here
in this methylation mapping,

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a dramatic separation at birth

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of the animals that had
a high social status

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versus the animals
that did not have a high status.

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So we are born already knowing
the social information,

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and that social information
is not bad or good,

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it just prepares us for life,

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because we have to program
our biology differently

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

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But how can you study this in humans?

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

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But God does experiments with humans,

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and it's called natural disasters.

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One of the hardest natural disasters
in Canadian history

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happened in my province of Quebec.

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It's the ice storm of 1998.

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We lost our entire electrical grid
because of an ice storm

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

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minus 20 to minus 30.

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And there were pregnant
mothers during that time.

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00:10:16,082 --> 00:10:22,114
And my colleague Suzanne King
followed the children of these mothers

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for 15 years.

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

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and here we had objective
measures of stress:

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

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

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

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and you can ask the question:

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How did the children look?

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And it appears that as stress increases,

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the children develop more autism,

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they develop more metabolic diseases

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00:10:55,415 --> 00:10:58,247
and they develop more autoimmune diseases.

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We would map the methylation state,

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00:11:01,235 --> 00:11:06,773
and again, you see the green genes
becoming red as stress increases,

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00:11:06,797 --> 00:11:10,289
the red genes becoming green
as stress increases,

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00:11:10,313 --> 00:11:14,863
an entire rearrangement
of the genome in response to stress.

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00:11:17,442 --> 00:11:20,651
So if we can program genes,

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00:11:20,675 --> 00:11:24,648
if we are not just the slaves
of the history of our genes,

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00:11:24,672 --> 00:11:27,300
that they could be programmed,
can we deprogram them?

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00:11:28,093 --> 00:11:32,675
Because epigenetic causes
can cause diseases like cancer,

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00:11:33,659 --> 00:11:35,462
metabolic disease

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00:11:35,486 --> 00:11:37,589
and mental health diseases.

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00:11:38,120 --> 00:11:40,813
Let's talk about cocaine addiction.

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00:11:41,575 --> 00:11:44,631
Cocaine addiction is a terrible situation

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00:11:44,655 --> 00:11:48,422
that can lead to death
and to loss of human life.

219
00:11:49,545 --> 00:11:51,470
We asked the question:

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00:11:51,494 --> 00:11:54,733
Can we reprogram the addicted brain

221
00:11:54,757 --> 00:11:59,681
to make that animal not addicted anymore?

222
00:12:00,377 --> 00:12:04,657
We used a cocaine addiction model

223
00:12:04,681 --> 00:12:06,770
that recapitulates what happens in humans.

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00:12:06,794 --> 00:12:09,462
In humans, you're in high school,

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00:12:09,486 --> 00:12:11,566
some friends suggest you use some cocaine,

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00:12:11,590 --> 00:12:13,396
you take cocaine, nothing happens.

227
00:12:13,420 --> 00:12:17,621
Months pass by, something reminds you
of what happened the first time,

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00:12:17,645 --> 00:12:19,285
a pusher pushes cocaine,

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00:12:19,309 --> 00:12:22,141
and you become addicted
and your life has changed.

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00:12:22,165 --> 00:12:23,811
In rats, we do the same thing.

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00:12:23,835 --> 00:12:25,410
My colleague, Gal Yadid,

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00:12:25,434 --> 00:12:28,434
he trains the animals
to get used to cocaine,

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then for one month, no cocaine.

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00:12:31,610 --> 00:12:35,286
Then he reminds them of the party
when they saw the cocaine the first time

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00:12:35,310 --> 00:12:38,126
by cue, the colors of the cage
when they saw cocaine.

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00:12:38,150 --> 00:12:39,802
And they go crazy.

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00:12:39,826 --> 00:12:42,273
They will press the lever to get cocaine

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till they die.

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00:12:44,047 --> 00:12:48,490
We first determined that the difference
between these animals

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00:12:48,514 --> 00:12:51,215
is that during that time
when nothing happens,

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there's no cocaine around,

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their epigenome is rearranged.

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00:12:54,980 --> 00:12:57,869
Their genes are re-marked
in a different way,

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00:12:57,893 --> 00:13:01,635
and when the cue comes,
their genome is ready

245
00:13:01,659 --> 00:13:03,948
to develop this addictive phenotype.

246
00:13:04,565 --> 00:13:11,335
So we treated these animals with drugs
that either increase DNA methylation,

247
00:13:11,359 --> 00:13:13,583
which was the epigenetic
marker to look at,

248
00:13:13,607 --> 00:13:17,090
or decrease epigenetic markings.

249
00:13:17,114 --> 00:13:20,369
And we found that
if we increased methylation,

250
00:13:20,393 --> 00:13:22,276
these animals go even crazier.

251
00:13:22,300 --> 00:13:24,784
They become more craving for cocaine.

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00:13:24,808 --> 00:13:28,234
But if we reduce the DNA methylation,

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the animals are not addicted anymore.

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We have reprogrammed them.

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And a fundamental difference
between an epigenetic drug

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and any other drug

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is that with epigenetic drugs,

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we essentially remove
the signs of experience,

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and once they're gone,

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they will not come back
unless you have the same experience.

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The animal now is reprogrammed.

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So when we visited the animals
30 days, 60 days later,

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which is in human terms
many years of life,

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they were still not addicted --
by a single epigenetic treatment.

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So what did we learn about DNA?

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DNA is not just a sequence of letters;

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it's not just a script.

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DNA is a dynamic movie.

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Our experiences are being written
into this movie, which is interactive.

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You're, like, watching a movie
of your life, with the DNA,

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with your remote control.

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You can remove an actor and add an actor.

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And so you have, in spite
of the deterministic nature of genetics,

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you have control of the way
your genes look,

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and this has a tremendous
optimistic message

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for the ability to now encounter
some of the deadly diseases

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like cancer, mental health,

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with a new approach,

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looking at them as maladaptation.

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And if we can epigenetically intervene,

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[we can] reverse the movie
by removing an actor

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and setting up a new narrative.

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So what I told you today is,

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our DNA is really combined
of two components,

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two layers of information.

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One layer of information is old,

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evolved from millions
of years of evolution.

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It is fixed, and very hard to change.

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The other layer of information
is the epigenetic layer,

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which is open and dynamic

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and sets up a narrative
that is interactive,

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that allows us to control,
to a large extent, our destiny,

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to help the destiny of our children

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and to hopefully conquer disease

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and serious health challenges

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that have plagued humankind
for a long time.

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So even though we are determined

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by our genes,

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we have a degree of freedom

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that can set up our life
to a life of responsibility.

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Thank you.

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(Applause)