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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

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in how mother rats

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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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on this kind of soft science.

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And started telling me

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that when 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,

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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

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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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Us 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

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is going on?

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So in rats we can ask this question

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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,

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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,

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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

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what the gene you got from your mother.

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It was not the biological mother
that defined this property

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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

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in how genes are marked 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

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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, where equal number
of hours for day and night

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all year round.

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And that has such an enormous amount
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

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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

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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'd better binge.

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You'd 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 a McDonald's

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for one dollar.

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And therefore, the preparation

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that we had

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by our mothers

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is turning to be maladaptive.

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The same preparation that was
supposed to protect us

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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

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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

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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

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into our cousins, the monkeys.

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My colleague Steven Soomey

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has been rearing monkeys
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 a surrogate motherhood conditions.

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So these monkeys didn't have a mother.

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They had a nurse.

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And other monkeys

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were reared with their normal,
natural mothers,

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and when they were old,

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they were completely different animals.

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The monkeys that had a mother

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would 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

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were aggressive, were stressed,

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and were alcoholics.

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So we looked at their DNA

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early after birth

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and see is it possible
that the mother is marking.

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There is 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 and 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

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is not just one thing.

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It affects the whole way, it sends
a signals about the whole way

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your world is going to look like

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when you become an adult,

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and you can see the two groups of monkey

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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

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even at the moment of birth?

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So in this experiment,
we took placentas

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of monkeys

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that had different social status.

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What's interesting about social rank

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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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And 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 as much.

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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,
because we have to program

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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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So we can't do experiments,

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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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So one of the natural disasters,

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the hardest natural disaster
in Canadian history happened

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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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And my colleague Suzanne King

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followed the children of these mothers

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for 15 years.

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And what happened was

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that as the stress increased,

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and here we had objective
measures of stress --

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how long you were without power,
where did you spend your time,

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was it in your mother's in law apartment

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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 like?

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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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and they develop more autoimmune diseases.

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And we would map the methylation state,
and again you see the green genes

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becoming red as stress increases,

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the red genes becoming green
as stress increases,

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an entire rearrangement
of the genome in response to stress.

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So if we can program genes,

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

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that they could be programmed,
can we deprogram them?

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Because epigenetic causes can cause
diseases like cancer,

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metabolic disease,

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and mental health disease.

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Let's talk about cocaine addiction.

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Cocaine addiction is a terrible situation

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that can lead to death

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and to loss of human life.

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We asked the question,

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can we reprogram the addicted brain

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to make that animal

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non-addicted anymore?

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We used a cocaine addiction model

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that recapitulates what happens in humans.

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In humans, you're in high school,

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some friends suggest you some cocaine,

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you take cocaine, nothing happens,

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

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a pusher pushes cocaine,

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and you become addicted,

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and your life has changed.

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In rats, we do the same thing.

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My colleague [??] did.

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He trains the animals

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to get used to cocaine,

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then for one month, no cocaine,

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and then he reminds them of the party
when they saw the cocaine the first time

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by the colors of the cage
when they saw cocaine.

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And they go crazy.

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They will press the lever to get cocaine

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until they die.

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We first determined

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that the difference between these animals

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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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Their genes are remarked
in a different way,

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and when the cue comes,

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their genome is ready

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to develop this addictive phenotype.

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So we treated these animals

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with drugs that either increase

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DNA methylation, which was
the epigenetic marker to look at,

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or decrease epigenetic markings.

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And we found that if we
increased methylation,

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these animals go even crazier.

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They become more craving for cocaine.

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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,
we essentially remove

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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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So the animal now is reprogrammed.

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

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which is in human terms
many years of life,

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they were still not addicted

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by a single epigenetic treatment.

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So what we learned about DNA?

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The 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,

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which is interactive.

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You are 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 deterministic nature of genetics,

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you have control of the way
your genes look like,

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and this has a tremendous
optimistic message

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for ability to now encounter
some of the deadly diseases

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like cancer, mental health,

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with new approach

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looking at them as maladaptations

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that if we can epigenetically intervene,

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reverse the movie

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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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that our DNA is really combined

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of two components,

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two layers of information.

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One layer of information is old,
evolved from millions of years

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of evolution.

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It is fixed

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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

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that is interactive,

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that allows us to control,

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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)