TEDxBratislava
Moshe Szyf: How early life experience is written into DNA
Filmed:
Readability: 4.2
1,469,368 views
Moshe Szyf is a pioneer in the field of epigenetics, the study of how living things reprogram their genome in response to social factors like stress and lack of food. His research suggests that biochemical signals passed from mothers to offspring tell the child what kind of world they're going to live in, changing the expression of genes. "DNA isn't just a sequence of letters; it's not just a script." Szyf says. "DNA is a dynamic movie in which our experiences are being written."
Moshe Szyf - Epigeneticist
Moshe Szyf's research is focused on understanding the broad implications of epigenetic mechanisms in human behavior, health and disease. Full bio
Moshe Szyf's research is focused on understanding the broad implications of epigenetic mechanisms in human behavior, health and disease. Full bio
Double-click the English transcript below to play the video.
00:12
So it all came to life
0
920
1684
00:14
in a dark bar in Madrid.
1
2628
1832
00:17
I encountered my colleague
from McGill, Michael Meaney.
from McGill, Michael Meaney.
2
5023
4224
00:21
And we were drinking a few beers,
3
9271
2305
00:23
and like scientists do,
4
11600
2053
00:25
he told me about his work.
5
13677
1446
00:28
And he told me that he is interested
in how mother rats lick their pups
in how mother rats lick their pups
6
16304
6954
00:35
after they were born.
7
23282
1370
00:37
And I was sitting there and saying,
8
25656
2419
00:40
"This is where my tax
dollars are wasted --
dollars are wasted --
9
28099
3000
00:43
(Laughter)
10
31123
1034
00:44
on this kind of soft science."
11
32181
2778
00:47
And he started telling me
12
35835
2497
00:50
that the rats, like humans,
13
38356
3400
00:53
lick their pups in very different ways.
14
41780
2446
00:56
Some mothers do a lot of that,
15
44250
2735
00:59
some mothers do very little,
16
47009
2205
01:01
and most are in between.
17
49238
1970
01:03
But what's interesting about it
18
51867
1901
01:05
is when he follows these pups
when they become adults --
when they become adults --
19
53792
4918
01:10
like, years in human life,
long after their mother died.
long after their mother died.
20
58734
4179
01:14
They are completely different animals.
21
62937
2068
01:17
The animals that were licked
and groomed heavily,
and groomed heavily,
22
65029
4373
01:21
the high-licking and grooming,
23
69426
1752
01:24
are not stressed.
24
72059
1364
01:26
They have different sexual behavior.
25
74022
2249
01:28
They have a different way of living
26
76295
2955
01:31
than those that were not treated
as intensively by their mothers.
as intensively by their mothers.
27
79274
5480
01:37
So then I was thinking to myself:
28
85934
3164
01:41
Is this magic?
29
89122
1292
01:43
How does this work?
30
91002
1369
01:44
As geneticists would like you to think,
31
92395
2209
01:47
perhaps the mother had
the "bad mother" gene
the "bad mother" gene
32
95390
3972
01:51
that caused her pups to be stressful,
33
99386
3637
01:55
and then it was passed
from generation to generation;
from generation to generation;
34
103047
2547
01:57
it's all determined by genetics.
35
105618
2700
02:00
Or is it possible that something
else is going on here?
else is going on here?
36
108342
3494
02:03
In rats, we can ask
this question and answer it.
this question and answer it.
37
111860
3571
02:07
So what we did is
a cross-fostering experiment.
a cross-fostering experiment.
38
115455
3605
02:11
You essentially separate the litter,
the babies of this rat, at birth,
the babies of this rat, at birth,
39
119084
4755
02:15
to two kinds of fostering mothers --
40
123863
1867
02:17
not the real mothers,
but mothers that will take care of them:
but mothers that will take care of them:
41
125754
3328
02:21
high-licking mothers
and low-licking mothers.
and low-licking mothers.
42
129106
2254
02:23
And you can do the opposite
with the low-licking pups.
with the low-licking pups.
43
131384
3878
02:27
And the remarkable answer was,
44
135708
2373
02:30
it wasn't important
what gene you got from your mother.
what gene you got from your mother.
45
138105
4039
02:34
It was not the biological mother
that defined this property of these rats.
that defined this property of these rats.
46
142168
5748
02:39
It is the mother that
took care of the pups.
took care of the pups.
47
147940
4006
02:44
So how can this work?
48
152771
2825
02:48
I am an a epigeneticist.
49
156921
1803
02:50
I am interested in how genes are marked
50
158748
3672
02:54
by a chemical mark
51
162444
1716
02:56
during embryogenesis, during the time
we're in the womb of our mothers,
we're in the womb of our mothers,
52
164184
4805
03:01
and decide which gene will be expressed
53
169013
2479
03:03
in what tissue.
54
171516
1182
03:04
Different genes are expressed in the brain
than in the liver and the eye.
than in the liver and the eye.
55
172722
4170
03:09
And we thought: Is it possible
56
177718
2839
03:12
that the mother is somehow
reprogramming the gene of her offspring
reprogramming the gene of her offspring
57
180581
6947
03:19
through her behavior?
58
187552
1549
03:21
And we spent 10 years,
59
189125
1611
03:22
and we found that there is a cascade
of biochemical events
of biochemical events
60
190760
4041
03:26
by which the licking and grooming
of the mother, the care of the mother,
of the mother, the care of the mother,
61
194825
3443
03:30
is translated to biochemical signals
62
198292
2483
03:32
that go into the nucleus and into the DNA
63
200799
3311
03:36
and program it differently.
64
204134
2078
03:38
So now the animal can prepare
itself for life:
itself for life:
65
206236
4896
03:43
Is life going to be harsh?
66
211156
2621
03:45
Is there going to be a lot of food?
67
213801
1762
03:47
Are there going to be a lot of cats
and snakes around,
and snakes around,
68
215587
2525
03:50
or will I live
in an upper-class neighborhood
in an upper-class neighborhood
69
218136
2323
03:52
where all I have to do
is behave well and proper,
is behave well and proper,
70
220483
2707
03:55
and that will gain me social acceptance?
71
223214
3135
03:58
And now one can think about
how important that process can be
how important that process can be
72
226978
5591
04:04
for our lives.
73
232593
1175
04:05
We inherit our DNA from our ancestors.
74
233792
2912
04:09
The DNA is old.
75
237411
1929
04:11
It evolved during evolution.
76
239364
2068
04:13
But it doesn't tell us
if you are going to be born in Stockholm,
if you are going to be born in Stockholm,
77
241938
4333
04:18
where the days are long in the summer
and short in the winter,
and short in the winter,
78
246295
3386
04:21
or in Ecuador,
79
249705
1305
04:23
where there's an equal number of hours
for day and night all year round.
for day and night all year round.
80
251034
3533
04:26
And that has such an enormous [effect]
on our physiology.
on our physiology.
81
254591
3795
04:31
So what we suggest is,
perhaps what happens early in life,
perhaps what happens early in life,
82
259489
4236
04:35
those signals that come
through the mother,
through the mother,
83
263749
2167
04:37
tell the child what kind of social world
you're going to be living in.
you're going to be living in.
84
265940
4515
04:42
It will be harsh, and you'd better
be anxious and be stressful,
be anxious and be stressful,
85
270479
3400
04:45
or it's going to be an easy world,
and you have to be different.
and you have to be different.
86
273903
3123
04:49
Is it going to be a world
with a lot of light or little light?
with a lot of light or little light?
87
277050
3190
04:52
Is it going to be a world
with a lot of food or little food?
with a lot of food or little food?
88
280264
3985
04:56
If there's no food around,
89
284273
1524
04:57
you'd better develop your brain to binge
whenever you see a meal,
whenever you see a meal,
90
285821
4616
05:02
or store every piece of food
that you have as fat.
that you have as fat.
91
290461
4756
05:08
So this is good.
92
296819
1430
05:10
Evolution has selected this
93
298273
1857
05:12
to allow our fixed, old DNA
to function in a dynamic way
to function in a dynamic way
94
300154
4896
05:17
in new environments.
95
305074
1849
05:19
But sometimes things can go wrong;
96
307377
2583
05:22
for example, if you're born
to a poor family
to a poor family
97
310706
3862
05:26
and the signals are, "You better binge,
98
314592
2929
05:29
you better eat every piece of food
you're going to encounter."
you're going to encounter."
99
317545
3215
05:32
But now we humans
and our brain have evolved,
and our brain have evolved,
100
320784
2252
05:35
have changed evolution even faster.
101
323060
2096
05:37
Now you can buy McDonald's for one dollar.
102
325180
3364
05:40
And therefore, the preparation
that we had by our mothers
that we had by our mothers
103
328568
6410
05:47
is turning out to be maladaptive.
104
335002
2592
05:50
The same preparation that was supposed
to protect us from hunger and famine
to protect us from hunger and famine
105
338351
4213
05:54
is going to cause obesity,
106
342588
2457
05:57
cardiovascular problems
and metabolic disease.
and metabolic disease.
107
345069
2970
06:00
So this concept that genes
could be marked by our experience,
could be marked by our experience,
108
348666
3472
06:04
and especially the early life experience,
109
352162
2301
06:06
can provide us a unifying explanation
110
354487
2814
06:09
of both health and disease.
111
357325
2343
06:12
But is true only for rats?
112
360612
2358
06:14
The problem is, we cannot
test this in humans,
test this in humans,
113
362994
2952
06:17
because ethically, we cannot administer
child adversity in a random way.
child adversity in a random way.
114
365970
4112
06:22
So if a poor child develops
a certain property,
a certain property,
115
370106
3304
06:25
we don't know whether
this is caused by poverty
this is caused by poverty
116
373434
3739
06:29
or whether poor people have bad genes.
117
377197
2824
06:32
So geneticists will try to tell you
that poor people are poor
that poor people are poor
118
380045
3115
06:35
because their genes make them poor.
119
383184
2056
06:37
Epigeneticists will tell you
120
385264
1960
06:39
poor people are in a bad environment
or an impoverished environment
or an impoverished environment
121
387248
4110
06:43
that creates that phenotype,
that property.
that property.
122
391382
2964
06:47
So we moved to look
into our cousins, the monkeys.
into our cousins, the monkeys.
123
395576
5842
06:54
My colleague, Stephen Suomi,
has been rearing monkeys
has been rearing monkeys
124
402087
3694
06:57
in two different ways:
125
405805
1161
06:58
randomly separated the monkey
from the mother
from the mother
126
406990
2901
07:01
and reared her with a nurse
127
409915
2592
07:04
and surrogate motherhood conditions.
128
412531
2959
07:07
So these monkeys didn't have
a mother; they had a nurse.
a mother; they had a nurse.
129
415514
2671
07:10
And other monkeys were reared
with their normal, natural mothers.
with their normal, natural mothers.
130
418209
4620
07:14
And when they were old,
they were completely different animals.
they were completely different animals.
131
422853
4696
07:19
The monkeys that had a mother
did not care about alcohol,
did not care about alcohol,
132
427573
3093
07:22
they were not sexually aggressive.
133
430690
1679
07:24
The monkeys that didn't have a mother
were aggressive, were stressed
were aggressive, were stressed
134
432393
3767
07:28
and were alcoholics.
135
436184
1614
07:30
So we looked at their DNA
early after birth, to see:
early after birth, to see:
136
438482
5482
07:35
Is it possible that the mother is marking?
137
443988
2767
07:38
Is there a signature of the mother
in the DNA of the offspring?
in the DNA of the offspring?
138
446779
5358
07:44
These are Day-14 monkeys,
139
452161
2252
07:46
and what you see here is the modern way
by which we study epigenetics.
by which we study epigenetics.
140
454437
4076
07:50
We can now map those chemical marks,
which we call methylation marks,
which we call methylation marks,
141
458537
4663
07:55
on DNA at a single nucleotide resolution.
142
463224
3258
07:58
We can map the entire genome.
143
466506
1877
08:00
We can now compare the monkey
that had a mother or not.
that had a mother or not.
144
468407
3067
08:03
And here's a visual presentation of this.
145
471498
1954
08:05
What you see is the genes
that got more methylated are red.
that got more methylated are red.
146
473476
4737
08:10
The genes that got
less methylated are green.
less methylated are green.
147
478237
3014
08:13
You can see many genes are changing,
148
481275
2484
08:15
because not having a mother
is not just one thing --
is not just one thing --
149
483783
2714
08:18
it affects the whole way;
150
486521
1531
08:20
it sends signals about the whole way
your world is going to look
your world is going to look
151
488076
3508
08:23
when you become an adult.
152
491608
1759
08:25
And you can see the two groups of monkeys
153
493391
2421
08:27
extremely well-separated from each other.
154
495836
2720
08:31
How early does this develop?
155
499392
2129
08:34
These monkeys already
didn't see their mothers,
didn't see their mothers,
156
502078
2213
08:36
so they had a social experience.
157
504315
1699
08:38
Do we sense our social status,
even at the moment of birth?
even at the moment of birth?
158
506038
4265
08:43
So in this experiment,
we took placentas of monkeys
we took placentas of monkeys
159
511131
4049
08:47
that had different social status.
160
515204
1957
08:49
What's interesting about social rank
is that across all living beings,
is that across all living beings,
161
517698
5374
08:55
they will structure
themselves by hierarchy.
themselves by hierarchy.
162
523096
2618
08:58
Monkey number one is the boss;
163
526345
2188
09:00
monkey number four is the peon.
164
528557
2338
09:02
You put four monkeys in a cage,
165
530919
2439
09:05
there will always be a boss
and always be a peon.
and always be a peon.
166
533382
3011
09:09
And what's interesting
is that the monkey number one
is that the monkey number one
167
537448
3848
09:13
is much healthier than monkey number four.
168
541320
3432
09:16
And if you put them in a cage,
169
544776
1804
09:18
monkey number one will not eat as much.
170
546604
4697
09:23
Monkey number four will eat [a lot].
171
551325
1837
09:26
And what you see here
in this methylation mapping,
in this methylation mapping,
172
554129
4273
09:30
a dramatic separation at birth
173
558426
2775
09:33
of the animals that had
a high social status
a high social status
174
561225
2714
09:35
versus the animals
that did not have a high status.
that did not have a high status.
175
563963
2674
09:39
So we are born already knowing
the social information,
the social information,
176
567349
4231
09:43
and that social information
is not bad or good,
is not bad or good,
177
571604
3053
09:46
it just prepares us for life,
178
574681
1419
09:48
because we have to program
our biology differently
our biology differently
179
576124
4241
09:52
if we are in the high
or the low social status.
or the low social status.
180
580389
3081
09:56
But how can you study this in humans?
181
584326
1881
09:58
We can't do experiments,
we can't administer adversity to humans.
we can't administer adversity to humans.
182
586710
3448
10:02
But God does experiments with humans,
183
590182
2593
10:04
and it's called natural disasters.
184
592799
2288
10:07
One of the hardest natural disasters
in Canadian history
in Canadian history
185
595111
4260
10:11
happened in my province of Quebec.
186
599395
2410
10:13
It's the ice storm of 1998.
187
601829
2403
10:16
We lost our entire electrical grid
because of an ice storm
because of an ice storm
188
604256
3800
10:20
when the temperatures
were, in the dead of winter in Quebec,
were, in the dead of winter in Quebec,
189
608080
2997
10:23
minus 20 to minus 30.
190
611101
1949
10:25
And there were pregnant
mothers during that time.
mothers during that time.
191
613074
2532
10:28
And my colleague Suzanne King
followed the children of these mothers
followed the children of these mothers
192
616082
6032
10:34
for 15 years.
193
622138
1714
10:36
And what happened was,
that as the stress increased --
that as the stress increased --
194
624565
4246
10:40
and here we had objective
measures of stress:
measures of stress:
195
628835
2608
10:43
How long were you without power?
Where did you spend your time?
Where did you spend your time?
196
631467
4438
10:47
Was it in your mother-in-law's apartment
or in some posh country home?
or in some posh country home?
197
635929
5003
10:52
So all of these added up
to a social stress scale,
to a social stress scale,
198
640956
2658
10:55
and you can ask the question:
199
643638
1382
10:57
How did the children look?
200
645044
3044
11:00
And it appears that as stress increases,
201
648112
2634
11:02
the children develop more autism,
202
650770
2058
11:04
they develop more metabolic diseases
203
652852
2539
11:07
and they develop more autoimmune diseases.
204
655415
2832
11:10
We would map the methylation state,
205
658787
2424
11:13
and again, you see the green genes
becoming red as stress increases,
becoming red as stress increases,
206
661235
5538
11:18
the red genes becoming green
as stress increases,
as stress increases,
207
666797
3492
11:22
an entire rearrangement
of the genome in response to stress.
of the genome in response to stress.
208
670313
4550
11:29
So if we can program genes,
209
677442
3209
11:32
if we are not just the slaves
of the history of our genes,
of the history of our genes,
210
680675
3973
11:36
that they could be programmed,
can we deprogram them?
can we deprogram them?
211
684672
2628
11:40
Because epigenetic causes
can cause diseases like cancer,
can cause diseases like cancer,
212
688093
4582
11:45
metabolic disease
213
693659
1803
11:47
and mental health diseases.
214
695486
2103
11:50
Let's talk about cocaine addiction.
215
698120
2693
11:53
Cocaine addiction is a terrible situation
216
701575
3056
11:56
that can lead to death
and to loss of human life.
and to loss of human life.
217
704655
3767
12:01
We asked the question:
218
709545
1925
12:03
Can we reprogram the addicted brain
219
711494
3239
12:06
to make that animal not addicted anymore?
220
714757
4924
12:12
We used a cocaine addiction model
221
720377
4280
12:16
that recapitulates what happens in humans.
222
724681
2089
12:18
In humans, you're in high school,
223
726794
2668
12:21
some friends suggest you use some cocaine,
224
729486
2080
12:23
you take cocaine, nothing happens.
225
731590
1806
12:25
Months pass by, something reminds you
of what happened the first time,
of what happened the first time,
226
733420
4201
12:29
a pusher pushes cocaine,
227
737645
1640
12:31
and you become addicted
and your life has changed.
and your life has changed.
228
739309
2832
12:34
In rats, we do the same thing.
229
742165
1646
12:35
My colleague, Gal Yadid,
230
743835
1575
12:37
he trains the animals
to get used to cocaine,
to get used to cocaine,
231
745434
3000
12:40
then for one month, no cocaine.
232
748458
3128
12:43
Then he reminds them of the party
when they saw the cocaine the first time
when they saw the cocaine the first time
233
751610
3676
12:47
by cue, the colors of the cage
when they saw cocaine.
when they saw cocaine.
234
755310
2816
12:50
And they go crazy.
235
758150
1652
12:51
They will press the lever to get cocaine
236
759826
2447
12:54
until they die.
237
762297
1259
12:56
We first determined that the difference
between these animals
between these animals
238
764047
4443
13:00
is that during that time
when nothing happens,
when nothing happens,
239
768514
2701
13:03
there's no cocaine around,
240
771239
1772
13:05
their epigenome is rearranged.
241
773035
1921
13:06
Their genes are re-marked
in a different way,
in a different way,
242
774980
2889
13:09
and when the cue comes,
their genome is ready
their genome is ready
243
777893
3742
13:13
to develop this addictive phenotype.
244
781659
2289
13:16
So we treated these animals with drugs
that either increase DNA methylation,
that either increase DNA methylation,
245
784565
6770
13:23
which was the epigenetic
marker to look at,
marker to look at,
246
791359
2224
13:25
or decrease epigenetic markings.
247
793607
3483
13:29
And we found that
if we increased methylation,
if we increased methylation,
248
797114
3255
13:32
these animals go even crazier.
249
800393
1883
13:34
They become more craving for cocaine.
250
802300
2484
13:36
But if we reduce the DNA methylation,
251
804808
3426
13:40
the animals are not addicted anymore.
252
808258
2104
13:42
We have reprogrammed them.
253
810386
1619
13:44
And a fundamental difference
between an epigenetic drug
between an epigenetic drug
254
812029
3306
13:47
and any other drug
255
815359
1306
13:48
is that with epigenetic drugs,
256
816689
2172
13:50
we essentially remove
the signs of experience,
the signs of experience,
257
818885
4132
13:55
and once they're gone,
258
823041
2127
13:57
they will not come back
unless you have the same experience.
unless you have the same experience.
259
825192
3021
14:00
The animal now is reprogrammed.
260
828237
1654
14:01
So when we visited the animals
30 days, 60 days later,
30 days, 60 days later,
261
829915
4221
14:06
which is in human terms
many years of life,
many years of life,
262
834160
2919
14:09
they were still not addicted --
by a single epigenetic treatment.
by a single epigenetic treatment.
263
837103
5306
14:16
So what did we learn about DNA?
264
844472
3271
14:19
DNA is not just a sequence of letters;
265
847767
3125
14:22
it's not just a script.
266
850916
2119
14:25
DNA is a dynamic movie.
267
853059
2371
14:28
Our experiences are being written
into this movie, which is interactive.
into this movie, which is interactive.
268
856367
4911
14:33
You're, like, watching a movie
of your life, with the DNA,
of your life, with the DNA,
269
861302
3553
14:36
with your remote control.
270
864879
1782
14:38
You can remove an actor and add an actor.
271
866685
3389
14:42
And so you have, in spite
of the deterministic nature of genetics,
of the deterministic nature of genetics,
272
870872
5895
14:48
you have control of the way
your genes look,
your genes look,
273
876791
3689
14:52
and this has a tremendous
optimistic message
optimistic message
274
880504
3270
14:55
for the ability to now encounter
some of the deadly diseases
some of the deadly diseases
275
883798
3508
14:59
like cancer, mental health,
276
887330
2904
15:02
with a new approach,
277
890258
2928
15:05
looking at them as maladaptation.
278
893210
2534
15:07
And if we can epigenetically intervene,
279
895768
3074
15:10
[we can] reverse the movie
by removing an actor
by removing an actor
280
898866
3496
15:14
and setting up a new narrative.
281
902386
2857
15:18
So what I told you today is,
282
906028
2497
15:20
our DNA is really combined
of two components,
of two components,
283
908549
5092
15:25
two layers of information.
284
913665
1825
15:28
One layer of information is old,
285
916106
3675
15:31
evolved from millions
of years of evolution.
of years of evolution.
286
919805
3505
15:35
It is fixed and very hard to change.
287
923334
3176
15:39
The other layer of information
is the epigenetic layer,
is the epigenetic layer,
288
927411
3850
15:43
which is open and dynamic
289
931285
3895
15:47
and sets up a narrative
that is interactive,
that is interactive,
290
935204
4592
15:51
that allows us to control,
to a large extent, our destiny,
to a large extent, our destiny,
291
939820
6788
15:59
to help the destiny of our children
292
947695
3456
16:03
and to hopefully conquer disease
293
951175
4155
16:07
and serious health challenges
294
955354
4416
16:11
that have plagued humankind
for a long time.
for a long time.
295
959794
3611
16:15
So even though we are determined
296
963429
3393
16:18
by our genes,
297
966846
1755
16:20
we have a degree of freedom
298
968625
3067
16:23
that can set up our life
to a life of responsibility.
to a life of responsibility.
299
971716
4133
16:27
Thank you.
300
975873
1220
16:29
(Applause)
301
977117
4955
ABOUT THE SPEAKER
Moshe Szyf - EpigeneticistMoshe Szyf's research is focused on understanding the broad implications of epigenetic mechanisms in human behavior, health and disease.
Why you should listen
Moshe Szyf is one of the pioneers in the field of epigenetics. Szyf's lab has 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."
Szyf received his PhD from the Hebrew University and did his postdoctoral fellowship in Genetics at Harvard Medical School, joined the department in 1989 and currently holds a James McGill Professorship and GlaxoSmithKline-CIHR Chair in Pharmacology. He is the founding co-director of the Sackler Institute for Epigenetics and Psychobiology at McGill and is a Fellow of the Canadian Institute for Advanced Research Experience-based Brain and Biological Development program.
Moshe Szyf | Speaker | TED.com