0:00:15.117,0:00:18.959
So, it all came to life[br]in a dark bar in Madrid,

0:00:19.289,0:00:24.911
and as I was stepping into the bar,[br]I encountered my colleague from McGill,

0:00:24.911,0:00:26.271
Michael Meaney.

0:00:27.282,0:00:29.272
And we're drinking a few beers,

0:00:29.692,0:00:33.501
and like scientists do,[br]he told me about his work.

0:00:34.317,0:00:39.333
He told me that he is interested[br]in how mother rats

0:00:39.333,0:00:42.581
lick their pups after they are born.

0:00:43.632,0:00:49.351
And I was sitting there and saying,[br]"This is where my tax dollars are wasted,

0:00:49.351,0:00:50.432
(Laughter)

0:00:50.432,0:00:53.302
on this kind of soft science."

0:00:53.823,0:00:57.725
But as the beer got more intense[br]and the alcohol gets into the brain,

0:00:57.725,0:01:02.385
you become more receptive,[br]and he started telling me

0:01:02.385,0:01:08.374
that the rats, like humans,[br]lick their pups in very different ways.

0:01:08.374,0:01:11.096
Some mothers do a lot of that,

0:01:11.096,0:01:13.344
some mothers do very little,

0:01:13.344,0:01:15.546
and most are in-between.

0:01:15.926,0:01:17.777
But what's interesting about it

0:01:17.777,0:01:22.779
is that when he follows these pups[br]when they become adults,

0:01:22.779,0:01:26.948
like years in human life,[br]long after their mother has died,

0:01:26.948,0:01:29.090
they are completely different animals.

0:01:29.090,0:01:33.069
The animals that were licked[br]and groomed heavily -

0:01:33.409,0:01:37.509
the high licking and grooming -[br]are not stressed,

0:01:38.129,0:01:43.389
they have different sexual behavior,[br]they have a different way of living,

0:01:43.389,0:01:48.930
than those that were not treated[br]as intensively by her mother.

0:01:49.910,0:01:52.380
So, then I was thinking to myself,

0:01:53.070,0:01:54.400
Is this magic?

0:01:55.090,0:01:56.463
How does this work?

0:01:56.463,0:01:57.859
I'm a biochemist.

0:01:58.058,0:02:02.149
I believe that there are chemical[br]explanations to nature.

0:02:03.038,0:02:07.370
I was working in a field[br]called 'epigenetics,'

0:02:08.401,0:02:14.268
but before I jumped into that conclusion,[br]we had to do another experiment.

0:02:14.268,0:02:18.639
"Is this genetic?" a geneticist[br]would like you to think.

0:02:19.269,0:02:23.300
Perhaps the mother[br]had the 'bad mother' gene

0:02:23.300,0:02:27.053
that caused her pups to be stressful,

0:02:27.053,0:02:29.550
and then it was passed[br]from generation to generation;

0:02:29.550,0:02:31.671
it's all determined by genetics.

0:02:32.241,0:02:35.610
Or is it possible that something else[br]is going on here?

0:02:35.979,0:02:39.071
In rats, we can ask[br]this question and answer it.

0:02:39.422,0:02:42.762
So, what we did[br]is a cross-fostering experiment.

0:02:43.002,0:02:47.783
You essentially separate the litter,[br]the babies of this rat, at birth,

0:02:47.783,0:02:49.764
to two kinds of fostering mothers,

0:02:49.764,0:02:52.924
not the real mothers,[br]but mothers that will take care of them:

0:02:52.924,0:02:55.225
high-licking mothers[br]and low-licking mothers.

0:02:55.225,0:02:59.255
And you can do the opposite[br]with the low-licking pups.

0:02:59.615,0:03:01.965
And the remarkable answer was,

0:03:01.965,0:03:06.135
it wasn't important what gene[br]you got from your mother.

0:03:06.135,0:03:11.886
It was not the biological mother[br]that defined this property of these rats,

0:03:11.886,0:03:16.156
it is the mother[br]that took care of the pups.

0:03:16.726,0:03:19.718
So, how can this work?

0:03:20.430,0:03:23.048
And as I told you, I am an epigeneticist.

0:03:23.048,0:03:26.830
I am interested in how genes are marked

0:03:26.830,0:03:30.410
by a chemical mark during embryogenesis,

0:03:30.410,0:03:33.239
during the time we're in[br]the womb of our mothers,

0:03:33.239,0:03:37.011
and decide which gene[br]will be expressed in what tissue.

0:03:37.011,0:03:40.621
Different genes are expressed in the brain[br]than in the liver and the eye.

0:03:41.991,0:03:43.093
And we thought,

0:03:43.093,0:03:49.183
is it possible that the mother[br]is somehow reprogramming

0:03:49.183,0:03:53.444
the gene of her offspring[br]through her behavior?

0:03:53.444,0:03:55.027
We spent ten years,

0:03:55.027,0:03:59.035
and we found that there[br]is a cascade of biochemical events

0:03:59.035,0:04:02.414
by which the licking and grooming[br]of the mother, the care of the mother,

0:04:02.414,0:04:08.434
is translated to biochemical signals[br]that go into the nucleus and into the DNA,

0:04:08.434,0:04:10.405
and program it differently.

0:04:10.405,0:04:15.476
So now the animal[br]can prepare itself for life.

0:04:15.476,0:04:17.862
Is life going to be harsh?

0:04:18.103,0:04:19.928
Is there going to be a lot of food?

0:04:19.928,0:04:22.466
Are there going to be[br]a lot of cats and snakes around?

0:04:22.466,0:04:24.786
Or will I live in[br]an upper class neighborhood

0:04:24.786,0:04:27.511
where all I have to do[br]is behave well and proper,

0:04:27.511,0:04:30.728
and that will gain me social acceptance?

0:04:31.328,0:04:37.710
And now, one can think about how important[br]that process can be for our lives.

0:04:37.710,0:04:41.249
We inherit our DNA from our ancestors.

0:04:41.689,0:04:45.849
The DNA is old;[br]it evolved during evolution.

0:04:46.270,0:04:50.610
But it doesn't tell us if you[br]are going to be born in Stockholm,

0:04:50.610,0:04:54.038
where the days are long in summer[br]and short in the winter,

0:04:54.038,0:04:57.511
or in Ecuador, where there are an equal[br]number of hours for day and night

0:04:57.511,0:05:02.612
all year around, and that has such[br]an enormous [impact] on our physiology.

0:05:03.721,0:05:08.130
So, what we suggest is perhaps[br]what happens early in life,

0:05:08.130,0:05:11.501
those signals that come[br]through the mother tell the child

0:05:11.501,0:05:14.690
what kind of social world[br]you are going to be living in.

0:05:14.690,0:05:18.131
Is it going to be harsh and you better[br]be anxious and be stressful?

0:05:18.131,0:05:21.140
Or is it going to be an easy world[br]and you have to be different?

0:05:21.140,0:05:24.283
Is it going to be a world[br]with a lot of light or a little light?

0:05:24.588,0:05:28.301
Is it going to be a world[br]with a lot of food or a little food?

0:05:28.601,0:05:30.152
If there's no food around,

0:05:30.152,0:05:34.212
you better develop your brain[br]to binge whenever you see a meal,

0:05:34.802,0:05:39.691
or store every piece of food[br]that you have as fat.

0:05:41.123,0:05:44.452
So, this is good;[br]evolution has selected this

0:05:44.452,0:05:51.414
to allow our fixed old DNA to function[br]in a dynamic way in new environments.

0:05:51.694,0:05:54.408
But sometimes things can go wrong.

0:05:54.994,0:06:00.474
For example, if you're born[br]to a poor family and the signals are

0:06:00.474,0:06:04.702
'You better binge, you better eat every[br]piece of food you're going to encounter.'

0:06:05.013,0:06:07.334
But now we humans,[br]in our brain, have evolved,

0:06:07.334,0:06:09.484
have changed evolution even faster.

0:06:09.484,0:06:12.618
Now you can buy[br]a McDonald's [hamburger] for $1.00.

0:06:12.861,0:06:19.287
And therefore, the preparation[br]that we had by our mothers

0:06:19.287,0:06:21.953
is turning out to be maladaptive.

0:06:22.737,0:06:27.688
The same preparation that was supposed to[br]protect us from hunger and famine

0:06:27.688,0:06:31.887
is going to cause obesity,[br]cardiovascular problems,

0:06:31.887,0:06:33.577
and metabolic disease.

0:06:33.798,0:06:37.378
So, this concept that genes[br]could be marked by our experience,

0:06:37.378,0:06:39.599
especially the early life experience,

0:06:39.599,0:06:44.830
can provide us a unifying explanation[br]of both health and disease.

0:06:45.781,0:06:47.671
But is it true only for rats?

0:06:48.161,0:06:50.961
The problem is, we cannot[br]test this in humans,

0:06:51.185,0:06:55.035
because ethically, we cannot administer[br]childhood adversity in a random way.

0:06:55.298,0:06:58.613
So, if a poor child[br]develops a certain property,

0:06:58.613,0:07:02.401
we don't know whether[br]this is caused by poverty,

0:07:02.401,0:07:04.783
or whether poor people have bad genes.

0:07:05.272,0:07:07.021
So, geneticists will try to tell you

0:07:07.021,0:07:10.282
that poor people are poor[br]because their genes made them poor.

0:07:10.512,0:07:14.492
Epigeneticists will tell you[br]poor people are in a bad environment,

0:07:14.492,0:07:16.512
or impoverished environment

0:07:16.512,0:07:19.830
that creates that phenotype,[br]that property.

0:07:20.772,0:07:26.851
So, we moved to look[br]into our cousins, the monkeys.

0:07:27.242,0:07:32.063
My colleague Stephen Suomi has been[br]rearing monkeys in two different ways.

0:07:32.063,0:07:35.034
Randomly separated[br]the monkey from the mother

0:07:35.034,0:07:40.614
and reared her with a nurse[br]in surrogate motherhood conditions.

0:07:40.614,0:07:43.333
So, these monkeys didn't have a mother,[br]they had a nurse.

0:07:43.333,0:07:48.073
And other monkeys were reared[br]with their normal, natural mothers.

0:07:48.073,0:07:52.518
And when they were old,[br]they were completely different animals.

0:07:52.740,0:07:55.854
The monkeys that had a mother[br]would not care about alcohol,

0:07:55.854,0:07:57.494
they were not sexually aggressive.

0:07:57.494,0:08:01.373
The monkeys that didn't have a mother[br]were aggressive, were stressed,

0:08:01.373,0:08:03.178
and were alcoholics.

0:08:03.692,0:08:08.374
So, we looked at their DNA[br]early after birth,

0:08:08.374,0:08:11.944
to see, is it possible[br]that the mother is marking?

0:08:11.944,0:08:17.124
There is a signature of the mother[br]in the DNA of the offspring.

0:08:17.288,0:08:19.587
These are, today, 14 monkeys,

0:08:19.587,0:08:23.523
and what you see here is the modern way[br]by which we study epigenetics.

0:08:23.523,0:08:28.374
We can now map those chemical marks,[br]which we call methylation marks,

0:08:28.374,0:08:33.534
on DNA at a single nucleotide resolution,[br]we can map the entire genome.

0:08:33.534,0:08:36.664
We can now compare the monkey[br]that had a mother and not.

0:08:36.664,0:08:38.664
And here is a visual presentation of this.

0:08:38.664,0:08:42.993
What you see is the genes[br]that got more methylated are red;

0:08:42.993,0:08:46.060
the genes that got[br]less methylated are green.

0:08:46.060,0:08:48.606
You can see many genes are changing.

0:08:48.606,0:08:51.344
Because not having a mother[br]is not just one thing,

0:08:51.344,0:08:52.770
if affects the whole way.

0:08:52.770,0:08:56.369
It sends us signals about the whole way[br]your world is going to look

0:08:56.369,0:08:58.149
when you become an adult,

0:08:58.149,0:09:03.300
and you can see the two groups of monkeys[br]extremely well separated from each other.

0:09:03.300,0:09:06.510
How early does this develop?

0:09:06.736,0:09:08.830
These monkeys already[br]didn't see their mother

0:09:08.830,0:09:10.712
so they had a social experience.

0:09:10.712,0:09:15.151
Do we sense our social status[br]even at the moment of birth?

0:09:15.731,0:09:16.841
So, in this experiment,

0:09:16.841,0:09:22.122
we took placentas of monkeys[br]that had different social status.

0:09:22.310,0:09:27.724
What's interesting about social rank,[br]is that across all living beings,

0:09:27.724,0:09:30.643
they will structure[br]themselves by hierarchy.

0:09:30.973,0:09:32.925
Monkey number one is the boss.

0:09:33.305,0:09:35.261
Monkey number four is the peon.

0:09:35.502,0:09:39.597
And you put four monkeys in a cage,[br]there will always be a boss,

0:09:39.597,0:09:41.234
and always be a peon.

0:09:42.084,0:09:45.926
And, what's interesting,[br]is that monkey number one

0:09:45.926,0:09:49.117
is much healthier than monkey number four.

0:09:49.338,0:09:55.473
And if you put them in a cage,[br]monkey number one will not eat as much,

0:09:55.843,0:09:58.304
monkey number four will eat as much.

0:09:58.806,0:10:02.875
And what you see here[br]in this methylation mapping,

0:10:02.875,0:10:05.615
the animals that had a high social status,

0:10:05.615,0:10:08.926
versus the animals[br]that did not have a high status.

0:10:08.926,0:10:13.335
So, we are born already knowing[br]the social information,

0:10:13.335,0:10:16.289
and that social information[br]is not bad or good,

0:10:16.289,0:10:17.637
it just prepares us for life

0:10:17.637,0:10:22.087
because we have to program[br]our biology differently

0:10:22.087,0:10:25.368
if we're in a high or low social status.

0:10:26.087,0:10:28.068
But how can you study this in humans?

0:10:28.608,0:10:31.879
We can't do experiments;[br]we can't administer adversity to humans.

0:10:31.879,0:10:36.659
But God does experiments with humans,[br]and it's called natural disasters.

0:10:36.973,0:10:42.318
One of the hardest natural disasters[br]in Canadian history

0:10:42.318,0:10:44.669
happened in my province of Quebec.

0:10:44.898,0:10:47.149
It's the ice storm of 1998.

0:10:47.349,0:10:51.239
We lost our entire electrical grid[br]because of an ice storm

0:10:51.239,0:10:54.049
when the temperatures were[br]in the dead of winter in Quebec,

0:10:54.049,0:10:58.812
-20 to -30, and there were[br]pregnant mothers during that time.

0:10:59.142,0:11:05.191
And my colleague, Suzanne King,[br]followed the children of these mothers

0:11:05.191,0:11:07.172
for 15 years.

0:11:07.621,0:11:11.923
And what happened was[br]that as the stress increased,

0:11:11.923,0:11:14.642
and here we had objective[br]measures of stress:

0:11:14.642,0:11:16.691
How long you were without power;

0:11:16.691,0:11:18.991
where did you spend your time?

0:11:18.991,0:11:24.231
Was it in your mothers-in-law apartment[br]or in some posh country home?

0:11:24.231,0:11:26.592
All these added up[br]to a social stress scale

0:11:26.592,0:11:31.303
and you can ask the question,[br]how did the children look?

0:11:31.303,0:11:35.931
It appears that as stress increases,[br]the children develop more autism,

0:11:35.931,0:11:41.642
they develop more metabolic diseases,[br]and they develop more autoimmune diseases.

0:11:41.921,0:11:44.135
And we would map the methylation state

0:11:44.135,0:11:49.922
and again, you see the green genes[br]becoming red as stress increases.

0:11:49.922,0:11:53.342
The red genes becoming green[br]as stress increases,

0:11:53.342,0:11:58.303
an entire rearrangement of the genome[br]in response to stress.

0:11:58.694,0:12:01.923
So, if we can program genes,

0:12:01.923,0:12:06.253
if we are not just the slaves[br]of the history of our genes,

0:12:06.253,0:12:09.265
but they can be programmed,[br]can we deprogram them?

0:12:09.783,0:12:13.905
Because epigenetic causes[br]can cause diseases like cancer,

0:12:13.905,0:12:18.076
metabolic disease[br]and mental health diseases.

0:12:18.326,0:12:21.276
Let's talk about cocaine addiction.

0:12:21.846,0:12:24.845
Cocaine addiction is a terrible situation,

0:12:24.845,0:12:28.855
that can lead to death[br]and to loss of human life.

0:12:29.847,0:12:35.077
We ask the question,[br]can we reprogram the addicted brain

0:12:35.077,0:12:40.390
to make that animal non-addicted anymore?

0:12:40.609,0:12:46.938
We used a cocaine addiction model[br]that recapitulates what happens in humans.

0:12:46.938,0:12:51.579
In humans, you're in high school,[br]some friends suggest you use some cocaine,

0:12:51.579,0:12:53.669
you take cocaine, nothing happens.

0:12:53.669,0:12:57.800
Months pass by; something reminds you[br]of what happened the first time,

0:12:57.800,0:13:00.690
a pusher pushes cocaine,[br]and you become addicted,

0:13:00.690,0:13:02.548
and your life has changed.

0:13:02.548,0:13:03.988
In rats, we do the same thing.

0:13:03.988,0:13:08.637
My colleague Gal Yadid, he trains[br]the animals to get used to cocaine,

0:13:08.637,0:13:11.849
then for one month, no cocaine.

0:13:11.849,0:13:15.358
And then he reminds them of the party[br]when they saw cocaine the first time

0:13:15.358,0:13:18.411
via cue - the colors of the cage[br]when they saw cocaine,

0:13:18.411,0:13:20.071
and they go crazy.

0:13:20.071,0:13:23.768
They will press the lever[br]to get cocaine till they die.

0:13:24.308,0:13:28.788
We first determined that the difference[br]between these animals

0:13:28.788,0:13:31.409
is that during that time,[br]when nothing happens,

0:13:31.409,0:13:34.980
there's no cocaine around,[br]their epigenome is rearranged,

0:13:34.980,0:13:38.099
their genes are re-marked[br]in a different way,

0:13:38.099,0:13:39.610
and when the cue comes,

0:13:39.610,0:13:44.875
their genome is ready[br]to develop this addictive phenotype.

0:13:44.875,0:13:51.661
So, we treated these animals with drugs[br]that either increase DNA methylation,

0:13:51.661,0:13:53.682
which was the epigenetic mark to look at,

0:13:53.682,0:13:57.373
or decrease epigenetic markings.

0:13:57.373,0:14:00.652
And we found that[br]if we increase methylation,

0:14:00.652,0:14:05.025
these animals go even crazier,[br]they have even more craving for cocaine.

0:14:05.025,0:14:10.634
But if we reduce the DNA methylation,[br]the animals are not addicted anymore,

0:14:10.634,0:14:12.280
we have reprogrammed them.

0:14:12.280,0:14:16.923
And the fundamental difference between[br]an epigenetic drug and any other drug

0:14:16.923,0:14:19.055
is that with epigenetic drugs

0:14:19.055,0:14:23.435
we essentially remove[br]the science of experience,

0:14:23.435,0:14:25.451
and once they're gone,

0:14:25.451,0:14:28.434
they will not come back[br]unless you have the same experience,

0:14:28.434,0:14:30.096
so the animal now is reprogrammed.

0:14:30.096,0:14:34.246
So, when we visited the animals[br]30 days, 60 days longer,

0:14:34.246,0:14:37.324
which is, in human terms,[br]many years of life,

0:14:37.324,0:14:43.098
they were still not addicted[br]by a single epigenetic treatment.

0:14:44.693,0:14:51.153
So, what we learned about DNA:[br]the DNA is not just a sequence of letters,

0:14:51.153,0:14:52.903
it's not just a script.

0:14:53.343,0:14:56.104
DNA is a dynamic movie.

0:14:56.556,0:15:01.525
Our experiences are being written[br]into that movie, which is interactive.

0:15:01.525,0:15:06.664
You're like watching a movie of your life,[br]with the DNA, with your remote control.

0:15:06.877,0:15:10.642
You can remove an actor, and add an actor.

0:15:11.376,0:15:17.005
So, in spite of the deterministic[br]nature of genetics,

0:15:17.005,0:15:20.165
you have control[br]of the way your genes look.

0:15:20.786,0:15:23.985
And this has a tremendous[br]optimistic message.

0:15:23.985,0:15:27.527
For the ability to now encounter[br]some of the deadly diseases

0:15:27.527,0:15:33.388
like cancer, mental health,[br]with a new approach,

0:15:33.388,0:15:35.980
looking at them as maladaptation,

0:15:35.980,0:15:42.240
that if we can epigenetically intervene,[br]reverse the movie by removing an actor

0:15:42.670,0:15:45.710
and setting up a new narrative.

0:15:46.321,0:15:50.261
So, what I told you today is that our DNA

0:15:50.261,0:15:56.081
is really a combination of two components,[br]two layers of information.

0:15:56.351,0:16:00.069
One layer of information is old,

0:16:00.069,0:16:03.059
evolved from millions[br]of years of evolution;

0:16:03.531,0:16:07.164
it is fixed and very hard to change.

0:16:07.692,0:16:11.562
The other layer of information[br]is the epigenetic layer,

0:16:11.562,0:16:14.683
which is open and dynamic,

0:16:15.403,0:16:19.211
and sets up a narrative[br]that is interactive.

0:16:19.870,0:16:24.612
So, even though[br]we are determined by our genes,

0:16:25.142,0:16:27.904
we have a degree of freedom

0:16:28.174,0:16:32.392
that can set up our life[br]to a life of responsibility.

0:16:32.392,0:16:33.864
Thank you.

0:16:33.864,0:16:35.713
(Applause)