Epigenetics - our bodies' way to change the destiny written in our DNA | Moshe Szyf | TEDxBratislava

What we thought of as something fixed, DNA is actually very cleverly modified according to current environmental needs. Even before a baby is born, it already knows what world to prepare itself for. In this talk, Moshe sheds light on his groundbreaking findings.

Moshe Szyf is one of the pioneers in the field of epigenetics. Szyf’s lab 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.” The Szyf lab is interested in understanding basic epigenetic mechanisms and their broad implications in human behavior, health and disease, as well as in developing epigenetics-based therapeutics and diagnostics.

This talk was given at a TEDx event using the TED conference format but independently organized by a local community. Learn more at http://ted.com/tedx

So, it all came to life
in a dark bar in Madrid,

and as I was stepping into the bar,
I encountered my colleague from McGill,

Michael Meaney.

And we're drinking a few beers,

and like scientists do,
he told me about his work.

He told me that he is interested
in how mother rats

lick their pups after they are born.

And I was sitting there and saying,
"This is where my tax dollars are wasted,

(Laughter)

on this kind of soft science."

But as the beer got more intense
and the alcohol gets into the brain,

you become more receptive,
and he started telling me

that 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 that when he follows these pups
when they become adults,

like years in human life,
long after their mother has 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 her mother.

So, then I was thinking to myself,

Is this magic?

How does this work?

I'm a biochemist.

I believe that there are chemical
explanations to nature.

I was working in a field
called 'epigenetics,'

but before I jumped into that conclusion,
we had to do another experiment.

"Is this genetic?" a geneticist
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?

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 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?

And as I told you, I am an 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?

We spent ten 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 summer
and short in the winter,

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

all year around, and that has such
an enormous [impact] 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 are going to be living in.

Is it going to be harsh and you better
be anxious and be stressful?

Or is it 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 a little light?

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

If there's no food around,

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

But now we humans,
in our brain, have evolved,

have changed evolution even faster.

Now you can buy
a McDonald's [hamburger] for $1.00.

And therefore, the preparation
that we had by our mothers

is turning out 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,

especially the early life experience,

can provide us a unifying explanation
of both health and disease.

But is it true only for rats?

The problem is, we cannot
test this in humans,

because ethically, we cannot administer
childhood 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 made them poor.

Epigeneticists will tell you
poor people are in a bad environment,

or impoverished environment

that creates that phenotype,
that property.

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

My colleague Stephen Suomi has been
rearing monkeys in two different ways.

Randomly separated
the monkey from the mother

and reared her with a nurse
in 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,

to 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 is 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,

if affects the whole way.

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

when you become an adult,

and you can see the two groups of monkeys
extremely well separated from each other.

How early does this develop?

These monkeys already
didn't see their mother

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 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,

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're in a high or low social status.

But how can you study this in humans?

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

But God does experiments with humans,
and it's called natural disasters.

One of the hardest natural disasters
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,

-20 to -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 mothers-in-law apartment
or in some posh country home?

All these added up
to a social stress scale

and you can ask the question,
how did the children look?

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,

but they can be programmed,
can we deprogram them?

Because epigenetic causes
can cause diseases like cancer,

metabolic disease
and mental health diseases.

Let's talk about cocaine addiction.

Cocaine addiction is a terrible situation,

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

We ask 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 use 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 Gal Yadid, 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 cocaine the first time

via cue - the colors of the cage
when they saw cocaine,

and they go crazy.

They will press the lever
to get cocaine till 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 re-marked
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 mark to look at,

or decrease epigenetic markings.

And we found that
if we increase methylation,

these animals go even crazier,
they have even more craving for cocaine.

But if we reduce the DNA methylation,
the animals are not addicted anymore,

we have reprogrammed them.

And the fundamental difference between
an epigenetic drug and any other drug

is that with epigenetic drugs

we essentially remove
the science 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 that movie, which is interactive.

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

You can remove an actor, and add an actor.

So, in spite of the deterministic
nature of genetics,

you have control
of the way your genes look.

And this has a tremendous
optimistic message.

For the ability to now encounter
some of the deadly diseases

like cancer, mental health,
with a new approach,

looking at them as maladaptation,

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 a combination 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.

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)