How early life experience is written into DNA

So it all came to life

in a dark bar in Madrid.

I encountered my colleague
from McGill, Michael Meaney.

And we were drinking a few beers,

and like scientists do,

he told me about his work.

And he told me that he is interested

in how mother rats

lick their pups

after they were born.

And I was sitting there and saying,

this is where my tax dollars are wasted,

on this kind of soft science.

And he started telling me

that when the rats, like humans,

lick their pups in very different ways.

Some mothers do a lot of that,

some mothers do very little,

and most are in between.

But what's interesting about it

is when he follows these pups
when they become adults,

like years in human life,

long after their mother died,

they are completely different animals.

The animals that were licked
and groomed heavily,

the high licking and grooming,

are not stressed.

They have different sexual behavior.

They have a different way of living

than those that were not treated

as intensively by their mothers.

So then I was thinking to myself,

is this magic?

How does this work?

Us geneticists would like you to think

perhaps the mother had
the bad mother gene

that caused her pups to be stressful,

and then it was passed
from generation to generation.

It's all determined by genetics.

Or is it possible that something else

is going on here?

So in rats we can ask this question

and answer it.

So what we did is
a cross-fostering experiment.

You essentially separate the litter,

the babies of this rat, at birth,

to two kinds of fostering mothers,

not the real mothers,

but mothers that will take care of them,

high-licking mothers
and low-licking mothers.

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

And the remarkable answer was,

it wasn't important

what the gene you got from your mother.

It was not the biological mother
that defined this property

of these rats.

It is the mother that
took care of the pups.

So how can this work?

I am an a epigeneticist.

I am interested

in how genes are marked by a chemical mark

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

and decide which gene will be expressed

in what tissue.

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

And we thought, is it possible

that the mother is somehow

reprogramming the gene of her offspring

through her behavior?

And we spent 10 years,

and we found that there is
a cascade of biochemical events

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

is translated to biochemical signals

that go into the nucleus and into the DNA

and program it differently.

So now the animal can
prepare itself for life.

Is life going to be harsh?

Is there going to be a lot of food?

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

or will I live in an upper
class neighborhood

where all I have to do
is behave well and proper

and that will gain me social acceptance?

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

for our lives.

We inherit our DNA from our ancestors.

The DNA is old.

It evolved during evolution.

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

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

or in Ecuador, where equal number
of hours for day and night

all year round.

And that has such an enormous amount
on our physiology.

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

those signals that come through the mother

tell the child

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

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

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

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

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

If there's no food around,

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

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

So this is good.

Evolution has selected this

to allow our fixed, old DNA

to function in a dynamic way

in new environments.

But sometimes things can go wrong.

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

and the signals are, "You'd better binge.

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

But now we humans
and our brain have evolved,

have changed evolution even faster.

Now you can buy a McDonald's

for one dollar.

And therefore, the preparation

that we had

by our mothers

is turning to be maladaptive.

The same preparation that was
supposed to protect us

from hunger and famine

is going to cause obesity,

cardiovascular problems,
and metabolic disease.

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

and especially the early life experience,

can provide us a unifying explanation

of both health and disease.

But is true only for rats?

The problem is, we cannot
test this in humans,

because ethically, we cannot
administer child adversity

in a random way.

So if a poor child develops
a certain property,

we don't know whether this is caused

by poverty

or whether poor people have bad genes.

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

because their genes make them poor.

Epigeneticists will tell you

poor people are in a bad environment
or an impoverished environment

that creates that phenotype,
that property.

So we moved to look

into our cousins, the monkeys.

My colleague Steven Soomey

has been rearing monkeys
in two different ways:

randomly separated the monkey
from the mother

and reared her with a nurse,

and a surrogate motherhood conditions.

So these monkeys didn't have a mother.

They had a nurse.

And other monkeys

were reared with their normal,
natural mothers,

and when they were old,

they were completely different animals.

The monkeys that had a mother

would not care about alcohol,

they were not sexually aggressive.

The monkeys that didn't have a mother

were aggressive, were stressed,

and were alcoholics.

So we looked at their DNA

early after birth

and see is it possible
that the mother is marking.

There is a signature of the mother
in the DNA of the offspring.

These are Day 14 monkeys,

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

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

on DNA at a single nucleotide resolution.

We can map the entire genome.

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

And here's a visual presentation of this.

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

The genes that got less
methylated are green.

You can see many genes are changing,

because not having a mother

is not just one thing.

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

your world is going to look like

when you become an adult,

and you can see the two groups of monkey

extremely well separated from each other.

How early does this develop?

These monkeys already didn't
see their mothers,

so they had a social experience.

Do we sense our social status

even at the moment of birth?

So in this experiment,
we took placentas

of monkeys

that had different social status.

What's interesting about social rank

is that across all living beings,

they will structure themselves
by hierarchy.

Monkey number one is the boss.

Monkey number four is the peon.

And you put four monkeys in a cage,

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

And what's interesting is that
the monkey number one

is much healthier than monkey number four,

and if you put them in a cage,

monkey number one will not eat as much.

Monkey number four will eat as much.

And what you see here in this
methylation mapping,

a dramatic separation at birth

of the animals that had
a high social status

versus the animals that did not
have a high status.

So we are born already knowing
the social information,

and that social information
is not bad or good.

It just prepares us for life,
because we have to program

our biology differently

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

But how can you study this in humans?

So we can't do experiments,

we can't administer adversity to humans,

but God does experiments with humans,

and it's called natural disasters.

So one of the natural disasters,

the hardest natural disaster
in Canadian history happened

in my province of Quebec.

It's the ice storm of 1998.

We lost our entire electrical grid
because of an ice storm

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

minus 20 to minus 30,

and there were pregnant
mothers during that time.

And my colleague Suzanne King

followed the children of these mothers

for 15 years.

And what happened was

that as the stress increased,

and here we had objective
measures of stress --

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

was it in your mother's in law apartment

or in some posh country home?

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

and you can ask the question,

how did the children look like?

And it appears that as stress increases,

the children develop more autism,

they develop more metabolic diseases,

and they develop more autoimmune diseases.

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

becoming red as stress increases,

the red genes becoming green
as stress increases,

an entire rearrangement
of the genome in response to stress.

So if we can program genes,

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

that they could be programmed,
can we deprogram them?

Because epigenetic causes can cause
diseases like cancer,

metabolic disease,

and mental health disease.

Let's talk about cocaine addiction.

Cocaine addiction is a terrible situation

that can lead to death

and to loss of human life.

We asked the question,

can we reprogram the addicted brain

to make that animal

non-addicted anymore?

We used a cocaine addiction model

that recapitulates what happens in humans.

In humans, you're in high school,

some friends suggest you some cocaine,

you take cocaine, nothing happens,

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

a pusher pushes cocaine,

and you become addicted,

and your life has changed.

In rats, we do the same thing.

My colleague [??] did.

He trains the animals

to get used to cocaine,

then for one month, no cocaine,

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

by cues, the colors of the cage
when they saw cocaine.

And they go crazy.

They will press the lever to get cocaine

until they die.

We first determined

that the difference between these animals

is that during that time
when nothing happens,

there's no cocaine around,

their epigenome is rearranged.

Their genes are remarked
in a different way,

and when the cue comes,

their genome is ready

to develop this addictive phenotype.

So we treated these animals

with drugs that either increase

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

or decrease epigenetic markings.

And we found that if we
increased methylation,

these animals go even crazier.

They become more craving for cocaine.

But if we reduce the DNA methylation,

the animals are not addicted anymore.

We have reprogrammed them.

And a fundamental difference
between an epigenetic drug

and any other drug

is that with epigenetic drugs,
we essentially remove

the signs of experience,

and once they're gone,

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

So the animal now is reprogrammed.

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

which is in human terms
many years of life,

they were still not addicted

by a single epigenetic treatment.

So what we learned about DNA?

The DNA is not just a sequence of letters.

It's not just a script.

DNA is a dynamic movie.

Our experiences are being
written into this movie,

which is interactive.

You are like watching a movie
of your life with the DNA

with your remote control.

You can remove an actor and add an actor.

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

you have control of the way
your genes look like,

and this has a tremendous
optimistic message

for ability to now encounter
some of the deadly diseases

like cancer, mental health,

with new approach

looking at them as maladaptations

that if we can epigenetically intervene,

reverse the movie

by removing an actor

and setting up a new narrative.

So what I told you today is

that our DNA is really combined

of two components,

two layers of information.

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

of evolution.

It is fixed

and very hard to change.

The other layer of information
is the epigenetic layer

which is open and dynamic

and sets up a narrative

that is interactive,

that allows us to control,

to a large extent, our destiny,

to help the destiny of our children,

and to hopefully conquer disease

and serious health challenges

that have plagued humankind
for a long time.

So even though we are determined

by our genes,

we have a degree of freedom

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

Thank you.

(Applause)