0:00:00.920,0:00:02.604
So it all came to life

0:00:02.628,0:00:04.460
in a dark bar in Madrid.

0:00:05.023,0:00:09.247
I encountered my colleague[br]from McGill, Michael Meaney.

0:00:09.271,0:00:11.576
And we were drinking a few beers,

0:00:11.600,0:00:13.653
and like scientists do,

0:00:13.677,0:00:15.123
he told me about his work.

0:00:16.304,0:00:23.258
And he told me that he is interested[br]in how mother rats lick their pups

0:00:23.282,0:00:24.652
after they were born.

0:00:25.656,0:00:28.075
And I was sitting there and saying,

0:00:28.099,0:00:31.099
"This is where my tax[br]dollars are wasted --

0:00:31.123,0:00:32.157
(Laughter)

0:00:32.181,0:00:34.959
on this kind of soft science."

0:00:35.835,0:00:38.332
And he started telling me

0:00:38.356,0:00:41.756
that the rats, like humans,

0:00:41.780,0:00:44.226
lick their pups in very different ways.

0:00:44.250,0:00:46.985
Some mothers do a lot of that,

0:00:47.009,0:00:49.214
some mothers do very little,

0:00:49.238,0:00:51.208
and most are in between.

0:00:51.867,0:00:53.768
But what's interesting about it

0:00:53.792,0:00:58.710
is when he follows these pups[br]when they become adults --

0:00:58.734,0:01:02.913
like, years in human life,[br]long after their mother died.

0:01:02.937,0:01:05.005
They are completely different animals.

0:01:05.029,0:01:09.402
The animals that were licked[br]and groomed heavily,

0:01:09.426,0:01:11.178
the high licking and grooming,

0:01:12.059,0:01:13.423
are not stressed.

0:01:14.022,0:01:16.271
They have different sexual behavior.

0:01:16.295,0:01:19.250
They have a different way of living

0:01:19.274,0:01:24.754
than those that were not treated[br]as intensively by their mothers.

0:01:25.934,0:01:29.098
So then I was thinking to myself:

0:01:29.122,0:01:30.414
Is this magic?

0:01:31.002,0:01:32.371
How does this work?

0:01:32.395,0:01:34.604
As geneticists would like you to think,

0:01:35.390,0:01:39.362
perhaps the mother had[br]the "bad mother" gene

0:01:39.386,0:01:43.023
that caused her pups to be stressful,

0:01:43.047,0:01:45.594
and then it was passed[br]from generation to generation;

0:01:45.618,0:01:48.318
it's all determined by genetics.

0:01:48.342,0:01:51.836
Or is it possible that something[br]else is going on here?

0:01:51.860,0:01:55.431
In rats, we can ask[br]this question and answer it.

0:01:55.455,0:01:59.060
So what we did is[br]a cross-fostering experiment.

0:01:59.084,0:02:03.839
You essentially separate the litter,[br]the babies of this rat, at birth,

0:02:03.863,0:02:05.730
to two kinds of fostering mothers --

0:02:05.754,0:02:09.082
not the real mothers,[br]but mothers that will take care of them:

0:02:09.106,0:02:11.360
high-licking mothers[br]and low-licking mothers.

0:02:11.384,0:02:15.262
And you can do the opposite[br]with the low-licking pups.

0:02:15.708,0:02:18.081
And the remarkable answer was,

0:02:18.105,0:02:22.144
it wasn't important[br]what gene you got from your mother.

0:02:22.168,0:02:27.916
It was not the biological mother[br]that defined this property of these rats.

0:02:27.940,0:02:31.946
It is the mother that[br]took care of the pups.

0:02:32.771,0:02:35.596
So how can this work?

0:02:36.921,0:02:38.724
I am an a epigeneticist.

0:02:38.748,0:02:42.420
I am interested in how genes are marked

0:02:42.444,0:02:44.160
by a chemical mark

0:02:44.184,0:02:48.989
during embryogenesis, during the time[br]we're in the womb of our mothers,

0:02:49.013,0:02:51.492
and decide which gene will be expressed

0:02:51.516,0:02:52.698
in what tissue.

0:02:52.722,0:02:56.892
Different genes are expressed in the brain[br]than in the liver and the eye.

0:02:57.718,0:03:00.557
And we thought: Is it possible

0:03:00.581,0:03:07.528
that the mother is somehow[br]reprogramming the gene of her offspring

0:03:07.552,0:03:09.101
through her behavior?

0:03:09.125,0:03:10.736
And we spent 10 years,

0:03:10.760,0:03:14.801
and we found that there is a cascade[br]of biochemical events

0:03:14.825,0:03:18.268
by which the licking and grooming[br]of the mother, the care of the mother,

0:03:18.292,0:03:20.775
is translated to biochemical signals

0:03:20.799,0:03:24.110
that go into the nucleus and into the DNA

0:03:24.134,0:03:26.212
and program it differently.

0:03:26.236,0:03:31.132
So now the animal can prepare[br]itself for life:

0:03:31.156,0:03:33.777
Is life going to be harsh?

0:03:33.801,0:03:35.563
Is there going to be a lot of food?

0:03:35.587,0:03:38.112
Are there going to be a lot of cats[br]and snakes around,

0:03:38.136,0:03:40.459
or will I live[br]in an upper-class neighborhood

0:03:40.483,0:03:43.190
where all I have to do[br]is behave well and proper,

0:03:43.214,0:03:46.349
and that will gain me social acceptance?

0:03:46.978,0:03:52.569
And now one can think about[br]how important that process can be

0:03:52.593,0:03:53.768
for our lives.

0:03:53.792,0:03:56.704
We inherit our DNA from our ancestors.

0:03:57.411,0:03:59.340
The DNA is old.

0:03:59.364,0:04:01.432
It evolved during evolution.

0:04:01.938,0:04:06.271
But it doesn't tell us[br]if you are going to be born in Stockholm,

0:04:06.295,0:04:09.681
where the days are long in the summer[br]and short in the winter,

0:04:09.705,0:04:11.010
or in Ecuador,

0:04:11.034,0:04:14.567
where there's an equal number of hours[br]for day and night all year round.

0:04:14.591,0:04:18.386
And that has such an enormous [effect][br]on our physiology.

0:04:19.489,0:04:23.725
So what we suggest is,[br]perhaps what happens early in life,

0:04:23.749,0:04:25.916
those signals that come[br]through the mother,

0:04:25.940,0:04:30.455
tell the child what kind of social world[br]you're going to be living in.

0:04:30.479,0:04:33.879
It will be harsh, and you'd better[br]be anxious and be stressful,

0:04:33.903,0:04:37.026
or it's going to be an easy world,[br]and you have to be different.

0:04:37.050,0:04:40.240
Is it going to be a world[br]with a lot of light or little light?

0:04:40.264,0:04:44.249
Is it going to be a world[br]with a lot of food or little food?

0:04:44.273,0:04:45.797
If there's no food around,

0:04:45.821,0:04:50.437
you'd better develop your brain to binge[br]whenever you see a meal,

0:04:50.461,0:04:55.217
or store every piece of food[br]that you have as fat.

0:04:56.819,0:04:58.249
So this is good.

0:04:58.273,0:05:00.130
Evolution has selected this

0:05:00.154,0:05:05.050
to allow our fixed, old DNA[br]to function in a dynamic way

0:05:05.074,0:05:06.923
in new environments.

0:05:07.377,0:05:09.960
But sometimes things can go wrong;

0:05:10.706,0:05:14.568
for example, if you're born[br]to a poor family

0:05:14.592,0:05:17.521
and the signals are, "You better binge,

0:05:17.545,0:05:20.760
you better eat every piece of food[br]you're going to encounter."

0:05:20.784,0:05:23.036
But now we humans[br]and our brain have evolved,

0:05:23.060,0:05:25.156
have changed evolution even faster.

0:05:25.180,0:05:28.544
Now you can buy McDonald's for one dollar.

0:05:28.568,0:05:34.978
And therefore, the preparation[br]that we had by our mothers

0:05:35.002,0:05:37.594
is turning out to be maladaptive.

0:05:38.351,0:05:42.564
The same preparation that was supposed[br]to protect us from hunger and famine

0:05:42.588,0:05:45.045
is going to cause obesity,

0:05:45.069,0:05:48.039
cardiovascular problems[br]and metabolic disease.

0:05:48.666,0:05:52.138
So this concept that genes[br]could be marked by our experience,

0:05:52.162,0:05:54.463
and especially the early life experience,

0:05:54.487,0:05:57.301
can provide us a unifying explanation

0:05:57.325,0:05:59.668
of both health and disease.

0:06:00.612,0:06:02.970
But is true only for rats?

0:06:02.994,0:06:05.946
The problem is, we cannot[br]test this in humans,

0:06:05.970,0:06:10.082
because ethically, we cannot administer[br]child adversity in a random way.

0:06:10.106,0:06:13.410
So if a poor child develops[br]a certain property,

0:06:13.434,0:06:17.173
we don't know whether[br]this is caused by poverty

0:06:17.197,0:06:20.021
or whether poor people have bad genes.

0:06:20.045,0:06:23.160
So geneticists will try to tell you[br]that poor people are poor

0:06:23.184,0:06:25.240
because their genes make them poor.

0:06:25.264,0:06:27.224
Epigeneticists will tell you

0:06:27.248,0:06:31.358
poor people are in a bad environment[br]or an impoverished environment

0:06:31.382,0:06:34.346
that creates that phenotype,[br]that property.

0:06:35.576,0:06:41.418
So we moved to look[br]into our cousins, the monkeys.

0:06:42.087,0:06:45.781
My colleague, Stephen Suomi,[br]has been rearing monkeys

0:06:45.805,0:06:46.966
in two different ways:

0:06:46.990,0:06:49.891
randomly separated the monkey[br]from the mother

0:06:49.915,0:06:52.507
and reared her with a nurse

0:06:52.531,0:06:55.490
and surrogate motherhood conditions.

0:06:55.514,0:06:58.185
So these monkeys didn't have[br]a mother; they had a nurse.

0:06:58.209,0:07:02.829
And other monkeys were reared[br]with their normal, natural mothers.

0:07:02.853,0:07:07.549
And when they were old,[br]they were completely different animals.

0:07:07.573,0:07:10.666
The monkeys that had a mother[br]did not care about alcohol,

0:07:10.690,0:07:12.369
they were not sexually aggressive.

0:07:12.393,0:07:16.160
The monkeys that didn't have a mother[br]were aggressive, were stressed

0:07:16.184,0:07:17.798
and were alcoholics.

0:07:18.482,0:07:23.964
So we looked at their DNA[br]early after birth, to see:

0:07:23.988,0:07:26.755
Is it possible that the mother is marking?

0:07:26.779,0:07:32.137
Is there a signature of the mother[br]in the DNA of the offspring?

0:07:32.161,0:07:34.413
These are Day-14 monkeys,

0:07:34.437,0:07:38.513
and what you see here is the modern way[br]by which we study epigenetics.

0:07:38.537,0:07:43.200
We can now map those chemical marks,[br]which we call methylation marks,

0:07:43.224,0:07:46.482
on DNA at a single nucleotide resolution.

0:07:46.506,0:07:48.383
We can map the entire genome.

0:07:48.407,0:07:51.474
We can now compare the monkey[br]that had a mother or not.

0:07:51.498,0:07:53.452
And here's a visual presentation of this.

0:07:53.476,0:07:58.213
What you see is the genes[br]that got more methylated are red.

0:07:58.237,0:08:01.251
The genes that got[br]less methylated are green.

0:08:01.275,0:08:03.759
You can see many genes are changing,

0:08:03.783,0:08:06.497
because not having a mother[br]is not just one thing --

0:08:06.521,0:08:08.052
it affects the whole way;

0:08:08.076,0:08:11.584
it sends signals about the whole way[br]your world is going to look

0:08:11.608,0:08:13.367
when you become an adult.

0:08:13.391,0:08:15.812
And you can see the two groups of monkeys

0:08:15.836,0:08:18.556
extremely well-separated from each other.

0:08:19.392,0:08:21.521
How early does this develop?

0:08:22.078,0:08:24.291
These monkeys already[br]didn't see their mothers,

0:08:24.315,0:08:26.014
so they had a social experience.

0:08:26.038,0:08:30.303
Do we sense our social status,[br]even at the moment of birth?

0:08:31.131,0:08:35.180
So in this experiment,[br]we took placentas of monkeys

0:08:35.204,0:08:37.161
that had different social status.

0:08:37.698,0:08:43.072
What's interesting about social rank[br]is that across all living beings,

0:08:43.096,0:08:45.714
they will structure[br]themselves by hierarchy.

0:08:46.345,0:08:48.533
Monkey number one is the boss;

0:08:48.557,0:08:50.895
monkey number four is the peon.

0:08:50.919,0:08:53.358
You put four monkeys in a cage,

0:08:53.382,0:08:56.393
there will always be a boss[br]and always be a peon.

0:08:57.448,0:09:01.296
And what's interesting[br]is that the monkey number one

0:09:01.320,0:09:04.752
is much healthier than monkey number four.

0:09:04.776,0:09:06.580
And if you put them in a cage,

0:09:06.604,0:09:11.301
monkey number one will not eat as much.

0:09:11.325,0:09:13.162
Monkey number four will eat [a lot].

0:09:14.129,0:09:18.402
And what you see here[br]in this methylation mapping,

0:09:18.426,0:09:21.201
a dramatic separation at birth

0:09:21.225,0:09:23.939
of the animals that had[br]a high social status

0:09:23.963,0:09:26.637
versus the animals[br]that did not have a high status.

0:09:27.349,0:09:31.580
So we are born already knowing[br]the social information,

0:09:31.604,0:09:34.657
and that social information[br]is not bad or good,

0:09:34.681,0:09:36.100
it just prepares us for life,

0:09:36.124,0:09:40.365
because we have to program[br]our biology differently

0:09:40.389,0:09:43.470
if we are in the high[br]or the low social status.

0:09:44.326,0:09:46.207
But how can you study this in humans?

0:09:46.710,0:09:50.158
We can't do experiments,[br]we can't administer adversity to humans.

0:09:50.182,0:09:52.775
But God does experiments with humans,

0:09:52.799,0:09:55.087
and it's called natural disasters.

0:09:55.111,0:09:59.371
One of the hardest natural disasters[br]in Canadian history

0:09:59.395,0:10:01.805
happened in my province of Quebec.

0:10:01.829,0:10:04.232
It's the ice storm of 1998.

0:10:04.256,0:10:08.056
We lost our entire electrical grid[br]because of an ice storm

0:10:08.080,0:10:11.077
when the temperatures[br]were, in the dead of winter in Quebec,

0:10:11.101,0:10:13.050
minus 20 to minus 30.

0:10:13.074,0:10:15.606
And there were pregnant[br]mothers during that time.

0:10:16.082,0:10:22.114
And my colleague Suzanne King[br]followed the children of these mothers

0:10:22.138,0:10:23.852
for 15 years.

0:10:24.565,0:10:28.811
And what happened was,[br]that as the stress increased --

0:10:28.835,0:10:31.443
and here we had objective[br]measures of stress:

0:10:31.467,0:10:35.905
How long were you without power?[br]Where did you spend your time?

0:10:35.929,0:10:40.932
Was it in your mother-in-law's apartment[br]or in some posh country home?

0:10:40.956,0:10:43.614
So all of these added up[br]to a social stress scale,

0:10:43.638,0:10:45.020
and you can ask the question:

0:10:45.044,0:10:48.088
How did the children look?

0:10:48.112,0:10:50.746
And it appears that as stress increases,

0:10:50.770,0:10:52.828
the children develop more autism,

0:10:52.852,0:10:55.391
they develop more metabolic diseases

0:10:55.415,0:10:58.247
and they develop more autoimmune diseases.

0:10:58.787,0:11:01.211
We would map the methylation state,

0:11:01.235,0:11:06.773
and again, you see the green genes[br]becoming red as stress increases,

0:11:06.797,0:11:10.289
the red genes becoming green[br]as stress increases,

0:11:10.313,0:11:14.863
an entire rearrangement[br]of the genome in response to stress.

0:11:17.442,0:11:20.651
So if we can program genes,

0:11:20.675,0:11:24.648
if we are not just the slaves[br]of the history of our genes,

0:11:24.672,0:11:27.300
that they could be programmed,[br]can we deprogram them?

0:11:28.093,0:11:32.675
Because epigenetic causes[br]can cause diseases like cancer,

0:11:33.659,0:11:35.462
metabolic disease

0:11:35.486,0:11:37.589
and mental health diseases.

0:11:38.120,0:11:40.813
Let's talk about cocaine addiction.

0:11:41.575,0:11:44.631
Cocaine addiction is a terrible situation

0:11:44.655,0:11:48.422
that can lead to death[br]and to loss of human life.

0:11:49.545,0:11:51.470
We asked the question:

0:11:51.494,0:11:54.733
Can we reprogram the addicted brain

0:11:54.757,0:11:59.681
to make that animal not addicted anymore?

0:12:00.377,0:12:04.657
We used a cocaine addiction model

0:12:04.681,0:12:06.770
that recapitulates what happens in humans.

0:12:06.794,0:12:09.462
In humans, you're in high school,

0:12:09.486,0:12:11.566
some friends suggest you use some cocaine,

0:12:11.590,0:12:13.396
you take cocaine, nothing happens.

0:12:13.420,0:12:17.621
Months pass by, something reminds you[br]of what happened the first time,

0:12:17.645,0:12:19.285
a pusher pushes cocaine,

0:12:19.309,0:12:22.141
and you become addicted[br]and your life has changed.

0:12:22.165,0:12:23.811
In rats, we do the same thing.

0:12:23.835,0:12:25.410
My colleague, Gal Yadid,

0:12:25.434,0:12:28.434
he trains the animals[br]to get used to cocaine,

0:12:28.458,0:12:31.586
then for one month, no cocaine.

0:12:31.610,0:12:35.286
Then he reminds them of the party[br]when they saw the cocaine the first time

0:12:35.310,0:12:38.126
by cue, the colors of the cage[br]when they saw cocaine.

0:12:38.150,0:12:39.802
And they go crazy.

0:12:39.826,0:12:42.273
They will press the lever to get cocaine

0:12:42.297,0:12:43.556
till they die.

0:12:44.047,0:12:48.490
We first determined that the difference[br]between these animals

0:12:48.514,0:12:51.215
is that during that time[br]when nothing happens,

0:12:51.239,0:12:53.011
there's no cocaine around,

0:12:53.035,0:12:54.956
their epigenome is rearranged.

0:12:54.980,0:12:57.869
Their genes are re-marked[br]in a different way,

0:12:57.893,0:13:01.635
and when the cue comes,[br]their genome is ready

0:13:01.659,0:13:03.948
to develop this addictive phenotype.

0:13:04.565,0:13:11.335
So we treated these animals with drugs[br]that either increase DNA methylation,

0:13:11.359,0:13:13.583
which was the epigenetic[br]marker to look at,

0:13:13.607,0:13:17.090
or decrease epigenetic markings.

0:13:17.114,0:13:20.369
And we found that[br]if we increased methylation,

0:13:20.393,0:13:22.276
these animals go even crazier.

0:13:22.300,0:13:24.784
They become more craving for cocaine.

0:13:24.808,0:13:28.234
But if we reduce the DNA methylation,

0:13:28.258,0:13:30.362
the animals are not addicted anymore.

0:13:30.386,0:13:32.005
We have reprogrammed them.

0:13:32.029,0:13:35.335
And a fundamental difference[br]between an epigenetic drug

0:13:35.359,0:13:36.665
and any other drug

0:13:36.689,0:13:38.861
is that with epigenetic drugs,

0:13:38.885,0:13:43.017
we essentially remove[br]the signs of experience,

0:13:43.041,0:13:45.168
and once they're gone,

0:13:45.192,0:13:48.213
they will not come back[br]unless you have the same experience.

0:13:48.237,0:13:49.891
The animal now is reprogrammed.

0:13:49.915,0:13:54.136
So when we visited the animals[br]30 days, 60 days later,

0:13:54.160,0:13:57.079
which is in human terms[br]many years of life,

0:13:57.103,0:14:02.409
they were still not addicted --[br]by a single epigenetic treatment.

0:14:04.472,0:14:07.743
So what did we learn about DNA?

0:14:07.767,0:14:10.892
DNA is not just a sequence of letters;

0:14:10.916,0:14:13.035
it's not just a script.

0:14:13.059,0:14:15.430
DNA is a dynamic movie.

0:14:16.367,0:14:21.278
Our experiences are being written[br]into this movie, which is interactive.

0:14:21.302,0:14:24.855
You're, like, watching a movie[br]of your life, with the DNA,

0:14:24.879,0:14:26.661
with your remote control.

0:14:26.685,0:14:30.074
You can remove an actor and add an actor.

0:14:30.872,0:14:36.767
And so you have, in spite[br]of the deterministic nature of genetics,

0:14:36.791,0:14:40.480
you have control of the way[br]your genes look,

0:14:40.504,0:14:43.774
and this has a tremendous[br]optimistic message

0:14:43.798,0:14:47.306
for the ability to now encounter[br]some of the deadly diseases

0:14:47.330,0:14:50.234
like cancer, mental health,

0:14:50.258,0:14:53.186
with a new approach,

0:14:53.210,0:14:55.744
looking at them as maladaptation.

0:14:55.768,0:14:58.842
And if we can epigenetically intervene,

0:14:58.866,0:15:02.362
[we can] reverse the movie[br]by removing an actor

0:15:02.386,0:15:05.243
and setting up a new narrative.

0:15:06.028,0:15:08.525
So what I told you today is,

0:15:08.549,0:15:13.641
our DNA is really combined[br]of two components,

0:15:13.665,0:15:15.490
two layers of information.

0:15:16.106,0:15:19.781
One layer of information is old,

0:15:19.805,0:15:23.310
evolved from millions[br]of years of evolution.

0:15:23.334,0:15:26.510
It is fixed, and very hard to change.

0:15:27.411,0:15:31.261
The other layer of information[br]is the epigenetic layer,

0:15:31.285,0:15:35.180
which is open and dynamic

0:15:35.204,0:15:39.796
and sets up a narrative[br]that is interactive,

0:15:39.820,0:15:46.608
that allows us to control,[br]to a large extent, our destiny,

0:15:47.695,0:15:51.151
to help the destiny of our children

0:15:51.175,0:15:55.330
and to hopefully conquer disease

0:15:55.354,0:15:59.770
and serious health challenges

0:15:59.794,0:16:03.405
that have plagued humankind[br]for a long time.

0:16:03.429,0:16:06.822
So even though we are determined

0:16:06.846,0:16:08.601
by our genes,

0:16:08.625,0:16:11.692
we have a degree of freedom

0:16:11.716,0:16:15.849
that can set up our life[br]to a life of responsibility.

0:16:15.873,0:16:17.093
Thank you.

0:16:17.117,0:16:22.072
(Applause)