0:00:00.761,0:00:02.752
So it all came to life

0:00:02.752,0:00:04.806
in a dark bar in Madrid.

0:00:04.806,0:00:09.453
I encountered my colleague[br]from McGill, Michael Meaney.

0:00:09.453,0:00:11.342
And we were drinking a few beers,

0:00:11.342,0:00:13.677
and like scientists do,

0:00:13.677,0:00:16.147
he told me about his work.

0:00:16.147,0:00:18.615
And he told me that he is interested

0:00:18.615,0:00:21.276
in how mother rats

0:00:21.276,0:00:23.292
lick their pups

0:00:23.292,0:00:25.534
after they were born.

0:00:25.534,0:00:28.033
And I was sitting there and saying,

0:00:28.033,0:00:31.644
this is where my tax dollars are wasted,

0:00:31.644,0:00:34.776
on this kind of soft science.

0:00:35.955,0:00:38.475
And he started telling me

0:00:38.475,0:00:41.780
that when the rats, like humans,

0:00:41.780,0:00:44.508
lick their pups in very different ways.

0:00:44.508,0:00:47.009
Some mothers do a lot of that,

0:00:47.009,0:00:49.424
some mothers do very little,

0:00:49.424,0:00:51.794
and most are in between.

0:00:51.794,0:00:53.982
But what's interesting about it

0:00:53.982,0:00:58.923
is when he follows these pups[br]when they become adults,

0:00:58.923,0:01:01.036
like years in human life,

0:01:01.036,0:01:03.124
long after their mother died,

0:01:03.124,0:01:05.029
they are completely different animals.

0:01:05.029,0:01:09.553
The animals that were licked[br]and groomed heavily,

0:01:09.553,0:01:11.644
the high licking and grooming,

0:01:11.644,0:01:14.125
are not stressed.

0:01:14.125,0:01:16.472
They have different sexual behavior.

0:01:16.472,0:01:19.450
They have a different way of living

0:01:19.450,0:01:22.540
than those that were not treated

0:01:22.540,0:01:26.022
as intensively by their mothers.

0:01:26.022,0:01:29.285
So then I was thinking to myself,

0:01:29.285,0:01:31.002
is this magic?

0:01:31.002,0:01:32.730
How does this work?

0:01:32.730,0:01:35.214
Us geneticists would like you to think

0:01:35.214,0:01:39.299
perhaps the mother had[br]the bad mother gene

0:01:39.299,0:01:43.047
that caused her pups to be stressful,

0:01:43.047,0:01:46.304
and then it was passed[br]from generation to generation.

0:01:46.304,0:01:48.422
It's all determined by genetics.

0:01:48.422,0:01:50.437
Or is it possible that something else

0:01:50.437,0:01:52.016
is going on here?

0:01:52.016,0:01:53.718
So in rats we can ask this question

0:01:53.718,0:01:55.455
and answer it.

0:01:55.455,0:01:59.084
So what we did is[br]a cross-fostering experiment.

0:01:59.084,0:02:01.575
You essentially separate the litter,

0:02:01.575,0:02:03.991
the babies of this rat, at birth,

0:02:03.991,0:02:05.881
to two kinds of fostering mothers,

0:02:05.881,0:02:07.065
not the real mothers,

0:02:07.065,0:02:09.163
but mothers that will take care of them,

0:02:09.163,0:02:11.599
high-licking mothers[br]and low-licking mothers.

0:02:11.599,0:02:15.501
And you can do the opposite[br]with the low-licking pups.

0:02:15.501,0:02:18.105
And the remarkable answer was,

0:02:18.105,0:02:19.713
it wasn't important

0:02:19.713,0:02:22.037
what the gene you got from your mother.

0:02:22.037,0:02:26.449
It was not the biological mother[br]that defined this property

0:02:26.449,0:02:27.767
of these rats.

0:02:27.767,0:02:32.419
It is the mother that[br]took care of the pups.

0:02:32.419,0:02:36.292
So how can this work?

0:02:36.292,0:02:38.889
I am an a epigeneticist.

0:02:38.889,0:02:40.841
I am interested

0:02:40.841,0:02:43.625
in how genes are marked by a chemical mark

0:02:43.625,0:02:49.013
during embryogenesis, during the time[br]we're in the womb of our mothers,

0:02:49.013,0:02:51.516
and decide which gene will be expressed

0:02:51.516,0:02:52.830
in what tissue.

0:02:52.830,0:02:56.881
Different genes are expressed in the brain[br]than in the liver and the eye.

0:02:56.881,0:03:00.367
And we thought, is it possible

0:03:00.367,0:03:03.233
that the mother is somehow

0:03:03.233,0:03:07.270
reprogramming the gene of her offspring

0:03:07.270,0:03:09.423
through her behavior?

0:03:09.423,0:03:12.160
And we spent 10 years,

0:03:12.160,0:03:15.022
and we found that there is[br]a cascade of biochemical events

0:03:15.022,0:03:17.641
by which the licking and grooming[br]of the mother, the care of the mother

0:03:17.641,0:03:20.575
is translated to biochemical signals

0:03:20.575,0:03:24.134
that go into the nucleus and into the DNA

0:03:24.134,0:03:26.236
and program it differently.

0:03:26.236,0:03:31.300
So now the animal can[br]prepare itself for life.

0:03:31.300,0:03:33.801
Is life going to be harsh?

0:03:33.801,0:03:35.784
Is there going to be a lot of food?

0:03:35.784,0:03:38.256
Are there going to be a lot[br]of cats and snakes around,

0:03:38.256,0:03:40.954
or will I live in an upper[br]class neighborhood

0:03:40.954,0:03:44.568
where all I have to do[br]is behave well and proper

0:03:44.568,0:03:47.272
and that will gain me social acceptance?

0:03:47.272,0:03:52.886
And now one can think about[br]how important that process can be

0:03:52.886,0:03:54.351
for our lives.

0:03:54.351,0:03:57.287
We inherit our DNA from our ancestors.

0:03:57.287,0:03:59.634
The DNA is old.

0:03:59.634,0:04:01.854
It evolved during evolution.

0:04:01.854,0:04:06.058
But it doesn't tell us if you are going[br]to be born in Stockholm,

0:04:06.058,0:04:10.036
where the days are long in the summer[br]and short in the winter,

0:04:10.036,0:04:13.870
or in Ecuador, where equal number[br]of hours for day and night

0:04:13.870,0:04:14.846
all year round.

0:04:14.846,0:04:19.192
And that has such an enormous amount[br]on our physiology.

0:04:19.192,0:04:23.977
So what we suggest is perhaps[br]what happens early in life,

0:04:23.977,0:04:25.862
those signals that come through the mother

0:04:25.862,0:04:27.222
tell the child

0:04:27.222,0:04:30.650
what kind of social world[br]you're going to be living in.

0:04:30.650,0:04:34.029
It will be harsh, and you'd better[br]be anxious and be stressful,

0:04:34.029,0:04:37.269
or it's going to be an easy world,[br]and you have to be different.

0:04:37.269,0:04:40.312
Is it going to be a world[br]with a lot of light or little light?

0:04:40.312,0:04:44.420
Is it going to be a world[br]with a lot of food or little food?

0:04:44.420,0:04:46.110
If there's no food around,

0:04:46.110,0:04:50.111
you'd better develop your brain[br]to binge whenever you see a meal,

0:04:50.111,0:04:56.819
or store every piece of food[br]that you have as fat.

0:04:56.819,0:04:58.591
So this is good.

0:04:58.591,0:05:00.256
Evolution has selected this

0:05:00.256,0:05:03.706
to allow our fixed, old DNA

0:05:03.706,0:05:05.268
to function in a dynamic way

0:05:05.268,0:05:07.575
in new environments.

0:05:07.575,0:05:10.366
But sometimes things can go wrong.

0:05:10.366,0:05:14.592
For example, if you're born[br]to a poor family,

0:05:14.592,0:05:17.458
and the signals are, "You'd better binge.

0:05:17.458,0:05:20.784
You'd better eat every piece of food[br]you're going to encounter."

0:05:20.784,0:05:23.209
But now we humans[br]and our brain have evolved,

0:05:23.209,0:05:25.180
have changed evolution even faster.

0:05:25.180,0:05:27.161
Now you can buy a McDonald's

0:05:27.161,0:05:28.707
for one dollar.

0:05:28.707,0:05:31.720
And therefore, the preparation

0:05:31.720,0:05:33.060
that we had

0:05:33.060,0:05:35.212
by our mothers

0:05:35.212,0:05:37.828
is turning to be maladaptive.

0:05:37.828,0:05:40.658
The same preparation that was[br]supposed to protect us

0:05:40.658,0:05:42.588
from hunger and famine

0:05:42.588,0:05:45.069
is going to cause obesity,

0:05:45.069,0:05:48.529
cardiovascular problems,[br]and metabolic disease.

0:05:48.529,0:05:52.353
So this concept that genes[br]could be marked by our experience,

0:05:52.353,0:05:54.677
and especially the early life experience,

0:05:54.677,0:05:57.342
can provide us a unifying explanation

0:05:57.342,0:06:00.827
of both health and disease.

0:06:00.827,0:06:03.050
But is true only for rats?

0:06:03.050,0:06:05.970
The problem is, we cannot[br]test this in humans,

0:06:05.970,0:06:09.065
because ethically, we cannot[br]administer child adversity

0:06:09.065,0:06:10.252
in a random way.

0:06:10.252,0:06:13.434
So if a poor child develops[br]a certain property,

0:06:13.434,0:06:15.803
we don't know whether this is caused

0:06:15.803,0:06:17.014
by poverty

0:06:17.014,0:06:20.045
or whether poor people have bad genes.

0:06:20.045,0:06:23.316
So geneticists will try to tell you[br]that poor people are poor

0:06:23.316,0:06:25.297
because their genes make them poor.

0:06:25.297,0:06:27.138
Epigeneticists will tell you

0:06:27.138,0:06:31.382
poor people are in a bad environment[br]or an impoverished environment

0:06:31.382,0:06:34.846
that creates that phenotype,[br]that property.

0:06:34.846,0:06:38.011
So we moved to look

0:06:38.011,0:06:41.979
into our cousins, the monkeys.

0:06:41.979,0:06:43.976
My colleague Steven Soomey

0:06:43.976,0:06:47.226
has been rearing monkeys[br]in two different ways:

0:06:47.226,0:06:50.074
randomly separated the monkey[br]from the mother

0:06:50.074,0:06:52.689
and reared her with a nurse,

0:06:52.689,0:06:55.818
and a surrogate motherhood conditions.

0:06:55.818,0:06:57.346
So these monkeys didn't have a mother.

0:06:57.346,0:06:58.464
They had a nurse.

0:06:58.464,0:06:59.738
And other monkeys

0:06:59.738,0:07:03.080
were reared with their normal,[br]natural mothers,

0:07:03.080,0:07:04.741
and when they were old,

0:07:04.741,0:07:07.749
they were completely different animals.

0:07:07.749,0:07:09.253
The monkeys that had a mother

0:07:09.253,0:07:10.749
would not care about alcohol,

0:07:10.749,0:07:12.249
they were not sexually aggressive.

0:07:12.249,0:07:14.154
The monkeys that didn't have a mother

0:07:14.154,0:07:16.184
were aggressive, were stressed,

0:07:16.184,0:07:18.546
and were alcoholics.

0:07:18.546,0:07:21.111
So we looked at their DNA

0:07:21.111,0:07:23.496
early after birth

0:07:23.496,0:07:27.043
and see is it possible[br]that the mother is marking.

0:07:27.043,0:07:32.249
There is a signature of the mother[br]in the DNA of the offspring.

0:07:32.249,0:07:34.313
These are Day 14 monkeys,

0:07:34.313,0:07:39.197
and what you see here is the modern way[br]by which we study epigenetics.

0:07:39.197,0:07:43.470
We can now map those chemical marks,[br]which we call methylation marks,

0:07:43.470,0:07:46.751
on DNA at a single nucleotide resolution.

0:07:46.751,0:07:48.651
We can map the entire genome.

0:07:48.651,0:07:51.630
We can now compare the monkey[br]that had a mother and not.

0:07:51.630,0:07:53.559
And here's a visual presentation of this.

0:07:53.559,0:07:58.237
What you see is the genes that[br]got more methylated are red.

0:07:58.237,0:08:01.543
The genes that got less[br]methylated are green.

0:08:01.543,0:08:03.980
You can see many genes are changing,

0:08:03.980,0:08:05.331
because not having a mother

0:08:05.331,0:08:06.656
is not just one thing.

0:08:06.656,0:08:09.126
It affects the whole way, it sends[br]a signals about the whole way

0:08:09.126,0:08:11.516
your world is going to look like

0:08:11.516,0:08:13.449
when you become an adult,

0:08:13.449,0:08:16.325
and you can see the two groups of monkey

0:08:16.325,0:08:19.069
extremely well separated from each other.

0:08:19.069,0:08:21.381
How early does this develop?

0:08:21.381,0:08:24.118
These monkeys already didn't[br]see their mothers,

0:08:24.118,0:08:26.238
so they had a social experience.

0:08:26.238,0:08:28.411
Do we sense our social status

0:08:28.411,0:08:31.131
even at the moment of birth?

0:08:31.131,0:08:33.848
So in this experiment,[br]we took placentas

0:08:33.848,0:08:35.204
of monkeys

0:08:35.204,0:08:37.698
that had different social status.

0:08:37.698,0:08:39.984
What's interesting about social rank

0:08:39.984,0:08:42.843
is that across all living beings,

0:08:42.843,0:08:46.345
they will structure themselves[br]by hierarchy.

0:08:46.345,0:08:48.335
Monkey number one is the boss.

0:08:48.335,0:08:50.919
Monkey number four is the peon.

0:08:50.919,0:08:53.070
And you put four monkeys in a cage,

0:08:53.070,0:08:56.890
there will always be a boss[br]and always be a peon.

0:08:56.890,0:09:01.503
And what's interesting is that[br]the monkey number one

0:09:01.503,0:09:04.776
is much healthier than monkey number four,

0:09:04.776,0:09:06.238
and if you put them in a cage,

0:09:06.238,0:09:11.130
monkey number one will not eat as much.

0:09:11.130,0:09:14.201
Monkey number four will eat as much.

0:09:14.201,0:09:18.497
And what you see here in this[br]methylation mapping,

0:09:18.497,0:09:21.225
a dramatic separation at birth

0:09:21.225,0:09:24.061
of the animals that had[br]a high social status

0:09:24.061,0:09:27.446
versus the animals that did not[br]have a high status.

0:09:27.446,0:09:31.473
So we are born already knowing[br]the social information,

0:09:31.473,0:09:34.773
and that social information[br]is not bad or good.

0:09:34.773,0:09:38.335
It just prepares us for life,[br]because we have to program

0:09:38.335,0:09:40.660
our biology differently

0:09:40.660,0:09:44.326
if we are in the high[br]or the low social status.

0:09:44.326,0:09:46.897
But how can you study this in humans?

0:09:46.897,0:09:48.334
So we can't do experiments,

0:09:48.334,0:09:51.165
we can't administer adversity to humans,

0:09:51.165,0:09:53.022
but God does experiments with humans,

0:09:53.022,0:09:55.333
and it's called natural disasters.

0:09:55.333,0:09:57.002
So one of the natural disasters,

0:09:57.002,0:09:59.898
the hardest natural disaster[br]in Canadian history happened

0:09:59.898,0:10:01.713
in my province of Quebec.

0:10:01.713,0:10:04.256
It's the ice storm of 1998.

0:10:04.256,0:10:08.312
We lost our entire electrical grid[br]because of an ice storm

0:10:08.312,0:10:11.338
when the temperatures were in[br]the dead of winter in Quebec,

0:10:11.338,0:10:13.233
minus 20 to minus 30,

0:10:13.233,0:10:15.936
and there were pregnant[br]mothers during that time.

0:10:15.936,0:10:18.197
And my colleague Suzanne King

0:10:18.197,0:10:22.138
followed the children of these mothers

0:10:22.138,0:10:24.787
for 15 years.

0:10:24.787,0:10:26.548
And what happened was

0:10:26.548,0:10:29.055
that as the stress increased,

0:10:29.055,0:10:31.537
and here we had objective[br]measures of stress --

0:10:31.537,0:10:35.929
how long you were without power,[br]where did you spend your time,

0:10:35.929,0:10:37.955
was it in your mother's in law apartment

0:10:37.955,0:10:41.135
or in some posh country home?

0:10:41.135,0:10:43.789
so all of these added up[br]to a social stress scale,

0:10:43.789,0:10:45.167
and you can ask the question,

0:10:45.167,0:10:48.189
how did the children look like?

0:10:48.189,0:10:50.770
And it appears that as stress increases,

0:10:50.770,0:10:52.694
the children develop more autism,

0:10:52.694,0:10:55.190
they develop more metabolic diseases,

0:10:55.190,0:10:58.170
and they develop more autoimmune diseases.

0:10:58.913,0:11:03.250
And we would map the methylation state,[br]and again you see the green genes

0:11:03.250,0:11:06.923
becoming red as stress increases,

0:11:06.923,0:11:11.123
the red genes becoming green[br]as stress increases,

0:11:11.123,0:11:15.223
an entire rearrangement[br]of the genome in response to stress.

0:11:15.223,0:11:20.796
So if we can program genes,

0:11:20.796,0:11:24.672
if we are not just the slaves[br]of the history of our genes,

0:11:24.672,0:11:26.552
that they could be programmed,[br]can we deprogram them?

0:11:26.552,0:11:32.207
Because epigenetic causes can cause[br]diseases like cancer,

0:11:32.207,0:11:35.153
metabolic disease,

0:11:35.153,0:11:38.371
and mental health disease.

0:11:38.371,0:11:41.365
Let's talk about cocaine addiction.

0:11:41.365,0:11:44.412
Cocaine addiction is a terrible situation

0:11:44.412,0:11:46.280
that can lead to death

0:11:46.280,0:11:49.799
and to loss of human life.

0:11:49.799,0:11:51.747
We asked the question,

0:11:51.747,0:11:54.885
can we reprogram the addicted brain

0:11:54.885,0:11:58.082
to make that animal

0:11:58.082,0:12:00.608
non-addicted anymore?

0:12:00.608,0:12:04.878
We used a cocaine addiction model

0:12:04.878,0:12:07.015
that recapitulates what happens in humans.

0:12:07.015,0:12:09.562
In humans, you're in high school,

0:12:09.562,0:12:11.622
some friends suggest you some cocaine,

0:12:11.622,0:12:13.583
you take cocaine, nothing happens,

0:12:13.583,0:12:17.807
months pass by, something reminds you[br]of what happened the first time,

0:12:17.807,0:12:19.470
a pusher pushes cocaine,

0:12:19.470,0:12:20.696
and you become addicted,

0:12:20.696,0:12:22.321
and your life has changed.

0:12:22.321,0:12:24.142
In rats, we do the same thing.

0:12:24.142,0:12:25.740
My colleague [??] did.

0:12:25.740,0:12:27.362
He trains the animals

0:12:27.362,0:12:28.730
to get used to cocaine,

0:12:28.730,0:12:31.610
then for one month, no cocaine,

0:12:31.610,0:12:35.310
and then he reminds them of the party[br]when they saw the cocaine the first time

0:12:35.310,0:12:37.963
by cues, the colors of the cage[br]when they saw cocaine.

0:12:37.963,0:12:40.079
And they go crazy.

0:12:40.079,0:12:42.380
They will press the lever to get cocaine

0:12:42.380,0:12:43.866
until they die.

0:12:43.866,0:12:45.691
We first determined

0:12:45.691,0:12:48.722
that the difference between these animals

0:12:48.722,0:12:51.427
is that during that time[br]when nothing happens,

0:12:51.427,0:12:53.035
there's no cocaine around,

0:12:53.035,0:12:56.956
their epigenome is rearranged.

0:12:56.956,0:12:58.467
Their genes are remarked[br]in a different way,

0:12:58.467,0:13:00.684
and when the cue comes,

0:13:00.684,0:13:02.596
their genome is ready

0:13:02.596,0:13:04.708
to develop this addictive phenotype.

0:13:04.708,0:13:06.629
So we treated these animals

0:13:06.629,0:13:09.525
with drugs that either increase

0:13:09.525,0:13:13.607
DNA methylation, which was[br]the epigenetic marker to look at,

0:13:13.607,0:13:17.212
or decrease epigenetic markings.

0:13:17.212,0:13:20.268
And we found that if we[br]increased methylation,

0:13:20.268,0:13:22.534
these animals go even crazier.

0:13:22.534,0:13:24.808
They become more craving for cocaine.

0:13:24.808,0:13:28.215
But if we reduce the DNA methylation,

0:13:28.215,0:13:30.682
the animals are not addicted anymore.

0:13:30.682,0:13:32.142
We have reprogrammed them.

0:13:32.142,0:13:35.478
And a fundamental difference[br]between an epigenetic drug

0:13:35.478,0:13:36.689
and any other drug

0:13:36.689,0:13:39.029
is that with epigenetic drugs,[br]we essentially remove

0:13:39.029,0:13:43.130
the signs of experience,

0:13:43.130,0:13:45.352
and once they're gone,

0:13:45.352,0:13:48.237
they will not come back[br]unless you have the same experience.

0:13:48.237,0:13:49.915
So the animal now is reprogrammed.

0:13:49.915,0:13:54.160
So when we visited the animals[br]30 days, 60 days longer,

0:13:54.160,0:13:57.103
which is in human terms[br]many years of life,

0:13:57.103,0:13:59.657
they were still not addicted

0:13:59.657,0:14:03.751
by a single epigenetic treatment.

0:14:03.751,0:14:07.957
So what we learned about DNA?

0:14:07.957,0:14:10.916
The DNA is not just a sequence of letters.

0:14:10.916,0:14:12.779
It's not just a script.

0:14:12.779,0:14:16.550
DNA is a dynamic movie.

0:14:16.550,0:14:19.560
Our experiences are being[br]written into this movie,

0:14:19.560,0:14:21.235
which is interactive.

0:14:21.235,0:14:24.987
You are like watching a movie[br]of your life with the DNA

0:14:24.987,0:14:27.642
with your remote control.

0:14:27.642,0:14:31.055
You can remove an actor and add an actor.

0:14:31.055,0:14:36.973
And so you have, in spite[br]of deterministic nature of genetics,

0:14:36.973,0:14:40.685
you have control of the way[br]your genes look like,

0:14:40.685,0:14:43.798
and this has a tremendous[br]optimistic message

0:14:43.798,0:14:47.501
for ability to now encounter[br]some of the deadly diseases

0:14:47.501,0:14:50.376
like cancer, mental health,

0:14:50.376,0:14:53.468
with new approach

0:14:53.468,0:14:56.096
looking at them as maladaptations

0:14:56.096,0:14:58.866
that if we can epigenetically intervene,

0:14:58.866,0:15:00.371
reverse the movie

0:15:00.371,0:15:02.328
by removing an actor

0:15:02.328,0:15:06.163
and setting up a new narrative.

0:15:06.163,0:15:09.331
So what I told you today is

0:15:09.331,0:15:11.888
that our DNA is really combined

0:15:11.888,0:15:13.548
of two components,

0:15:13.548,0:15:16.352
two layers of information.

0:15:16.352,0:15:23.194
One layer of information is old,[br]evolved from millions of years

0:15:23.194,0:15:25.939
of evolution.

0:15:25.939,0:15:26.975
It is fixed

0:15:26.975,0:15:27.705
and very hard to change.

0:15:27.705,0:15:32.220
The other layer of information[br]is the epigenetic layer

0:15:32.220,0:15:34.556
which is open and dynamic

0:15:34.556,0:15:37.623
and sets up a narrative

0:15:37.623,0:15:39.505
that is interactive,

0:15:39.505,0:15:44.222
that allows us to control,

0:15:44.222,0:15:47.329
to a large extent, our destiny,

0:15:47.329,0:15:51.378
to help the destiny of our children,

0:15:51.378,0:15:55.229
and to hopefully conquer disease

0:15:55.229,0:15:59.960
and serious health challenges

0:15:59.960,0:16:03.429
that have plagued humankind[br]for a long time.

0:16:03.429,0:16:06.846
So even though we are determined

0:16:06.846,0:16:08.819
by our genes,

0:16:08.819,0:16:11.716
we have a degree of freedom

0:16:11.716,0:16:16.129
that can set up our life[br]to a life of responsibility.

0:16:16.129,0:16:17.372
Thank you.

0:16:17.372,0:16:22.072
(Applause)