WEBVTT 00:00:00.920 --> 00:00:02.604 So it all came to life 00:00:02.628 --> 00:00:04.460 in a dark bar in Madrid. 00:00:05.023 --> 00:00:09.247 I encountered my colleague from McGill, Michael Meaney. 00:00:09.271 --> 00:00:11.576 And we were drinking a few beers, 00:00:11.600 --> 00:00:13.653 and like scientists do, 00:00:13.677 --> 00:00:15.123 he told me about his work. 00:00:16.304 --> 00:00:23.258 And he told me that he is interested in how mother rats lick their pups 00:00:23.282 --> 00:00:24.652 after they were born. 00:00:25.656 --> 00:00:28.075 And I was sitting there and saying, 00:00:28.099 --> 00:00:31.099 "This is where my tax dollars are wasted -- 00:00:31.123 --> 00:00:32.157 (Laughter) 00:00:32.181 --> 00:00:34.959 on this kind of soft science." 00:00:35.835 --> 00:00:38.332 And he started telling me 00:00:38.356 --> 00:00:41.756 that the rats, like humans, 00:00:41.780 --> 00:00:44.226 lick their pups in very different ways. 00:00:44.250 --> 00:00:46.985 Some mothers do a lot of that, 00:00:47.009 --> 00:00:49.214 some mothers do very little, 00:00:49.238 --> 00:00:51.208 and most are in between. 00:00:51.867 --> 00:00:53.768 But what's interesting about it 00:00:53.792 --> 00:00:58.710 is when he follows these pups when they become adults -- 00:00:58.734 --> 00:01:02.913 like, years in human life, long after their mother died. 00:01:02.937 --> 00:01:05.005 They are completely different animals. 00:01:05.029 --> 00:01:09.402 The animals that were licked and groomed heavily, 00:01:09.426 --> 00:01:11.178 the high licking and grooming, 00:01:12.059 --> 00:01:13.423 are not stressed. 00:01:14.022 --> 00:01:16.271 They have different sexual behavior. 00:01:16.295 --> 00:01:19.250 They have a different way of living 00:01:19.274 --> 00:01:24.754 than those that were not treated as intensively by their mothers. NOTE Paragraph 00:01:25.934 --> 00:01:29.098 So then I was thinking to myself: 00:01:29.122 --> 00:01:30.414 Is this magic? 00:01:31.002 --> 00:01:32.371 How does this work? 00:01:32.395 --> 00:01:34.604 As geneticists would like you to think, 00:01:35.390 --> 00:01:39.362 perhaps the mother had the "bad mother" gene 00:01:39.386 --> 00:01:43.023 that caused her pups to be stressful, 00:01:43.047 --> 00:01:45.594 and then it was passed from generation to generation; 00:01:45.618 --> 00:01:48.318 it's all determined by genetics. 00:01:48.342 --> 00:01:51.836 Or is it possible that something else is going on here? NOTE Paragraph 00:01:51.860 --> 00:01:55.431 In rats, we can ask this question and answer it. 00:01:55.455 --> 00:01:59.060 So what we did is a cross-fostering experiment. 00:01:59.084 --> 00:02:03.839 You essentially separate the litter, the babies of this rat, at birth, 00:02:03.863 --> 00:02:05.730 to two kinds of fostering mothers -- 00:02:05.754 --> 00:02:09.082 not the real mothers, but mothers that will take care of them: 00:02:09.106 --> 00:02:11.360 high-licking mothers and low-licking mothers. 00:02:11.384 --> 00:02:15.262 And you can do the opposite with the low-licking pups. 00:02:15.708 --> 00:02:18.081 And the remarkable answer was, 00:02:18.105 --> 00:02:22.144 it wasn't important what gene you got from your mother. 00:02:22.168 --> 00:02:27.916 It was not the biological mother that defined this property of these rats. 00:02:27.940 --> 00:02:31.946 It is the mother that took care of the pups. 00:02:32.771 --> 00:02:35.596 So how can this work? NOTE Paragraph 00:02:36.921 --> 00:02:38.724 I am an a epigeneticist. 00:02:38.748 --> 00:02:42.420 I am interested in how genes are marked 00:02:42.444 --> 00:02:44.160 by a chemical mark 00:02:44.184 --> 00:02:48.989 during embryogenesis, during the time we're in the womb of our mothers, 00:02:49.013 --> 00:02:51.492 and decide which gene will be expressed 00:02:51.516 --> 00:02:52.698 in what tissue. 00:02:52.722 --> 00:02:56.892 Different genes are expressed in the brain than in the liver and the eye. 00:02:57.718 --> 00:03:00.557 And we thought: Is it possible 00:03:00.581 --> 00:03:07.528 that the mother is somehow reprogramming the gene of her offspring 00:03:07.552 --> 00:03:09.101 through her behavior? 00:03:09.125 --> 00:03:10.736 And we spent 10 years, 00:03:10.760 --> 00:03:14.801 and we found that there is a cascade of biochemical events 00:03:14.825 --> 00:03:18.268 by which the licking and grooming of the mother, the care of the mother, 00:03:18.292 --> 00:03:20.775 is translated to biochemical signals 00:03:20.799 --> 00:03:24.110 that go into the nucleus and into the DNA 00:03:24.134 --> 00:03:26.212 and program it differently. 00:03:26.236 --> 00:03:31.132 So now the animal can prepare itself for life: 00:03:31.156 --> 00:03:33.777 Is life going to be harsh? 00:03:33.801 --> 00:03:35.563 Is there going to be a lot of food? 00:03:35.587 --> 00:03:38.112 Are there going to be a lot of cats and snakes around, 00:03:38.136 --> 00:03:40.459 or will I live in an upper-class neighborhood 00:03:40.483 --> 00:03:43.190 where all I have to do is behave well and proper, 00:03:43.214 --> 00:03:46.349 and that will gain me social acceptance? 00:03:46.978 --> 00:03:52.569 And now one can think about how important that process can be 00:03:52.593 --> 00:03:53.768 for our lives. 00:03:53.792 --> 00:03:56.704 We inherit our DNA from our ancestors. 00:03:57.411 --> 00:03:59.340 The DNA is old. 00:03:59.364 --> 00:04:01.432 It evolved during evolution. 00:04:01.938 --> 00:04:06.271 But it doesn't tell us if you are going to be born in Stockholm, 00:04:06.295 --> 00:04:09.681 where the days are long in the summer and short in the winter, 00:04:09.705 --> 00:04:11.010 or in Ecuador, 00:04:11.034 --> 00:04:14.567 where there's an equal number of hours for day and night all year round. 00:04:14.591 --> 00:04:18.386 And that has such an enormous [effect] on our physiology. 00:04:19.489 --> 00:04:23.725 So what we suggest is, perhaps what happens early in life, 00:04:23.749 --> 00:04:25.916 those signals that come through the mother, 00:04:25.940 --> 00:04:30.455 tell the child what kind of social world you're going to be living in. 00:04:30.479 --> 00:04:33.879 It will be harsh, and you'd better be anxious and be stressful, 00:04:33.903 --> 00:04:37.026 or it's going to be an easy world, and you have to be different. 00:04:37.050 --> 00:04:40.240 Is it going to be a world with a lot of light or little light? 00:04:40.264 --> 00:04:44.249 Is it going to be a world with a lot of food or little food? 00:04:44.273 --> 00:04:45.797 If there's no food around, 00:04:45.821 --> 00:04:50.437 you'd better develop your brain to binge whenever you see a meal, 00:04:50.461 --> 00:04:55.217 or store every piece of food that you have as fat. NOTE Paragraph 00:04:56.819 --> 00:04:58.249 So this is good. 00:04:58.273 --> 00:05:00.130 Evolution has selected this 00:05:00.154 --> 00:05:05.050 to allow our fixed, old DNA to function in a dynamic way 00:05:05.074 --> 00:05:06.923 in new environments. 00:05:07.377 --> 00:05:09.960 But sometimes things can go wrong; 00:05:10.706 --> 00:05:14.568 for example, if you're born to a poor family 00:05:14.592 --> 00:05:17.521 and the signals are, "You better binge, 00:05:17.545 --> 00:05:20.760 you better eat every piece of food you're going to encounter." 00:05:20.784 --> 00:05:23.036 But now we humans and our brain have evolved, 00:05:23.060 --> 00:05:25.156 have changed evolution even faster. 00:05:25.180 --> 00:05:28.544 Now you can buy McDonald's for one dollar. 00:05:28.568 --> 00:05:34.978 And therefore, the preparation that we had by our mothers 00:05:35.002 --> 00:05:37.594 is turning out to be maladaptive. 00:05:38.351 --> 00:05:42.564 The same preparation that was supposed to protect us from hunger and famine 00:05:42.588 --> 00:05:45.045 is going to cause obesity, 00:05:45.069 --> 00:05:48.039 cardiovascular problems and metabolic disease. 00:05:48.666 --> 00:05:52.138 So this concept that genes could be marked by our experience, 00:05:52.162 --> 00:05:54.463 and especially the early life experience, 00:05:54.487 --> 00:05:57.301 can provide us a unifying explanation 00:05:57.325 --> 00:05:59.668 of both health and disease. NOTE Paragraph 00:06:00.612 --> 00:06:02.970 But is true only for rats? 00:06:02.994 --> 00:06:05.946 The problem is, we cannot test this in humans, 00:06:05.970 --> 00:06:10.082 because ethically, we cannot administer child adversity in a random way. 00:06:10.106 --> 00:06:13.410 So if a poor child develops a certain property, 00:06:13.434 --> 00:06:17.173 we don't know whether this is caused by poverty 00:06:17.197 --> 00:06:20.021 or whether poor people have bad genes. 00:06:20.045 --> 00:06:23.160 So geneticists will try to tell you that poor people are poor 00:06:23.184 --> 00:06:25.240 because their genes make them poor. 00:06:25.264 --> 00:06:27.224 Epigeneticists will tell you 00:06:27.248 --> 00:06:31.358 poor people are in a bad environment or an impoverished environment 00:06:31.382 --> 00:06:34.346 that creates that phenotype, that property. NOTE Paragraph 00:06:35.576 --> 00:06:41.418 So we moved to look into our cousins, the monkeys. 00:06:42.087 --> 00:06:45.781 My colleague, Stephen Suomi, has been rearing monkeys 00:06:45.805 --> 00:06:46.966 in two different ways: 00:06:46.990 --> 00:06:49.891 randomly separated the monkey from the mother 00:06:49.915 --> 00:06:52.507 and reared her with a nurse 00:06:52.531 --> 00:06:55.490 and surrogate motherhood conditions. 00:06:55.514 --> 00:06:58.185 So these monkeys didn't have a mother; they had a nurse. 00:06:58.209 --> 00:07:02.829 And other monkeys were reared with their normal, natural mothers. 00:07:02.853 --> 00:07:07.549 And when they were old, they were completely different animals. 00:07:07.573 --> 00:07:10.666 The monkeys that had a mother did not care about alcohol, 00:07:10.690 --> 00:07:12.369 they were not sexually aggressive. 00:07:12.393 --> 00:07:16.160 The monkeys that didn't have a mother were aggressive, were stressed 00:07:16.184 --> 00:07:17.798 and were alcoholics. 00:07:18.482 --> 00:07:23.964 So we looked at their DNA early after birth, to see: 00:07:23.988 --> 00:07:26.755 Is it possible that the mother is marking? 00:07:26.779 --> 00:07:32.137 Is there a signature of the mother in the DNA of the offspring? NOTE Paragraph 00:07:32.161 --> 00:07:34.413 These are Day-14 monkeys, 00:07:34.437 --> 00:07:38.513 and what you see here is the modern way by which we study epigenetics. 00:07:38.537 --> 00:07:43.200 We can now map those chemical marks, which we call methylation marks, 00:07:43.224 --> 00:07:46.482 on DNA at a single nucleotide resolution. 00:07:46.506 --> 00:07:48.383 We can map the entire genome. 00:07:48.407 --> 00:07:51.474 We can now compare the monkey that had a mother or not. 00:07:51.498 --> 00:07:53.452 And here's a visual presentation of this. 00:07:53.476 --> 00:07:58.213 What you see is the genes that got more methylated are red. 00:07:58.237 --> 00:08:01.251 The genes that got less methylated are green. 00:08:01.275 --> 00:08:03.759 You can see many genes are changing, 00:08:03.783 --> 00:08:06.497 because not having a mother is not just one thing -- 00:08:06.521 --> 00:08:08.052 it affects the whole way; 00:08:08.076 --> 00:08:11.584 it sends signals about the whole way your world is going to look 00:08:11.608 --> 00:08:13.367 when you become an adult. 00:08:13.391 --> 00:08:15.812 And you can see the two groups of monkeys 00:08:15.836 --> 00:08:18.556 extremely well-separated from each other. 00:08:19.392 --> 00:08:21.521 How early does this develop? 00:08:22.078 --> 00:08:24.291 These monkeys already didn't see their mothers, 00:08:24.315 --> 00:08:26.014 so they had a social experience. 00:08:26.038 --> 00:08:30.303 Do we sense our social status, even at the moment of birth? NOTE Paragraph 00:08:31.131 --> 00:08:35.180 So in this experiment, we took placentas of monkeys 00:08:35.204 --> 00:08:37.161 that had different social status. 00:08:37.698 --> 00:08:43.072 What's interesting about social rank is that across all living beings, 00:08:43.096 --> 00:08:45.714 they will structure themselves by hierarchy. 00:08:46.345 --> 00:08:48.533 Monkey number one is the boss; 00:08:48.557 --> 00:08:50.895 monkey number four is the peon. 00:08:50.919 --> 00:08:53.358 You put four monkeys in a cage, 00:08:53.382 --> 00:08:56.393 there will always be a boss and always be a peon. 00:08:57.448 --> 00:09:01.296 And what's interesting is that the monkey number one 00:09:01.320 --> 00:09:04.752 is much healthier than monkey number four. 00:09:04.776 --> 00:09:06.580 And if you put them in a cage, 00:09:06.604 --> 00:09:11.301 monkey number one will not eat as much. 00:09:11.325 --> 00:09:13.162 Monkey number four will eat [a lot]. 00:09:14.129 --> 00:09:18.402 And what you see here in this methylation mapping, 00:09:18.426 --> 00:09:21.201 a dramatic separation at birth 00:09:21.225 --> 00:09:23.939 of the animals that had a high social status 00:09:23.963 --> 00:09:26.637 versus the animals that did not have a high status. 00:09:27.349 --> 00:09:31.580 So we are born already knowing the social information, 00:09:31.604 --> 00:09:34.657 and that social information is not bad or good, 00:09:34.681 --> 00:09:36.100 it just prepares us for life, 00:09:36.124 --> 00:09:40.365 because we have to program our biology differently 00:09:40.389 --> 00:09:43.470 if we are in the high or the low social status. NOTE Paragraph 00:09:44.326 --> 00:09:46.207 But how can you study this in humans? 00:09:46.710 --> 00:09:50.158 We can't do experiments, we can't administer adversity to humans. 00:09:50.182 --> 00:09:52.775 But God does experiments with humans, 00:09:52.799 --> 00:09:55.087 and it's called natural disasters. NOTE Paragraph 00:09:55.111 --> 00:09:59.371 One of the hardest natural disasters in Canadian history 00:09:59.395 --> 00:10:01.805 happened in my province of Quebec. 00:10:01.829 --> 00:10:04.232 It's the ice storm of 1998. 00:10:04.256 --> 00:10:08.056 We lost our entire electrical grid because of an ice storm 00:10:08.080 --> 00:10:11.077 when the temperatures were, in the dead of winter in Quebec, 00:10:11.101 --> 00:10:13.050 minus 20 to minus 30. 00:10:13.074 --> 00:10:15.606 And there were pregnant mothers during that time. 00:10:16.082 --> 00:10:22.114 And my colleague Suzanne King followed the children of these mothers 00:10:22.138 --> 00:10:23.852 for 15 years. 00:10:24.565 --> 00:10:28.811 And what happened was, that as the stress increased -- 00:10:28.835 --> 00:10:31.443 and here we had objective measures of stress: 00:10:31.467 --> 00:10:35.905 How long were you without power? Where did you spend your time? 00:10:35.929 --> 00:10:40.932 Was it in your mother-in-law's apartment or in some posh country home? 00:10:40.956 --> 00:10:43.614 So all of these added up to a social stress scale, 00:10:43.638 --> 00:10:45.020 and you can ask the question: 00:10:45.044 --> 00:10:48.088 How did the children look? 00:10:48.112 --> 00:10:50.746 And it appears that as stress increases, 00:10:50.770 --> 00:10:52.828 the children develop more autism, 00:10:52.852 --> 00:10:55.391 they develop more metabolic diseases 00:10:55.415 --> 00:10:58.247 and they develop more autoimmune diseases. 00:10:58.787 --> 00:11:01.211 We would map the methylation state, 00:11:01.235 --> 00:11:06.773 and again, you see the green genes becoming red as stress increases, 00:11:06.797 --> 00:11:10.289 the red genes becoming green as stress increases, 00:11:10.313 --> 00:11:14.863 an entire rearrangement of the genome in response to stress. NOTE Paragraph 00:11:17.442 --> 00:11:20.651 So if we can program genes, 00:11:20.675 --> 00:11:24.648 if we are not just the slaves of the history of our genes, 00:11:24.672 --> 00:11:27.300 that they could be programmed, can we deprogram them? 00:11:28.093 --> 00:11:32.675 Because epigenetic causes can cause diseases like cancer, 00:11:33.659 --> 00:11:35.462 metabolic disease 00:11:35.486 --> 00:11:37.589 and mental health diseases. NOTE Paragraph 00:11:38.120 --> 00:11:40.813 Let's talk about cocaine addiction. 00:11:41.575 --> 00:11:44.631 Cocaine addiction is a terrible situation 00:11:44.655 --> 00:11:48.422 that can lead to death and to loss of human life. 00:11:49.545 --> 00:11:51.470 We asked the question: 00:11:51.494 --> 00:11:54.733 Can we reprogram the addicted brain 00:11:54.757 --> 00:11:59.681 to make that animal not addicted anymore? 00:12:00.377 --> 00:12:04.657 We used a cocaine addiction model 00:12:04.681 --> 00:12:06.770 that recapitulates what happens in humans. 00:12:06.794 --> 00:12:09.462 In humans, you're in high school, 00:12:09.486 --> 00:12:11.566 some friends suggest you use some cocaine, 00:12:11.590 --> 00:12:13.396 you take cocaine, nothing happens. 00:12:13.420 --> 00:12:17.621 Months pass by, something reminds you of what happened the first time, 00:12:17.645 --> 00:12:19.285 a pusher pushes cocaine, 00:12:19.309 --> 00:12:22.141 and you become addicted and your life has changed. 00:12:22.165 --> 00:12:23.811 In rats, we do the same thing. 00:12:23.835 --> 00:12:25.410 My colleague, Gal Yadid, 00:12:25.434 --> 00:12:28.434 he trains the animals to get used to cocaine, 00:12:28.458 --> 00:12:31.586 then for one month, no cocaine. 00:12:31.610 --> 00:12:35.286 Then he reminds them of the party when they saw the cocaine the first time 00:12:35.310 --> 00:12:38.126 by cue, the colors of the cage when they saw cocaine. 00:12:38.150 --> 00:12:39.802 And they go crazy. 00:12:39.826 --> 00:12:42.273 They will press the lever to get cocaine 00:12:42.297 --> 00:12:43.556 till they die. 00:12:44.047 --> 00:12:48.490 We first determined that the difference between these animals 00:12:48.514 --> 00:12:51.215 is that during that time when nothing happens, 00:12:51.239 --> 00:12:53.011 there's no cocaine around, 00:12:53.035 --> 00:12:54.956 their epigenome is rearranged. 00:12:54.980 --> 00:12:57.869 Their genes are re-marked in a different way, 00:12:57.893 --> 00:13:01.635 and when the cue comes, their genome is ready 00:13:01.659 --> 00:13:03.948 to develop this addictive phenotype. 00:13:04.565 --> 00:13:11.335 So we treated these animals with drugs that either increase DNA methylation, 00:13:11.359 --> 00:13:13.583 which was the epigenetic marker to look at, 00:13:13.607 --> 00:13:17.090 or decrease epigenetic markings. 00:13:17.114 --> 00:13:20.369 And we found that if we increased methylation, 00:13:20.393 --> 00:13:22.276 these animals go even crazier. 00:13:22.300 --> 00:13:24.784 They become more craving for cocaine. 00:13:24.808 --> 00:13:28.234 But if we reduce the DNA methylation, 00:13:28.258 --> 00:13:30.362 the animals are not addicted anymore. 00:13:30.386 --> 00:13:32.005 We have reprogrammed them. 00:13:32.029 --> 00:13:35.335 And a fundamental difference between an epigenetic drug 00:13:35.359 --> 00:13:36.665 and any other drug 00:13:36.689 --> 00:13:38.861 is that with epigenetic drugs, 00:13:38.885 --> 00:13:43.017 we essentially remove the signs of experience, 00:13:43.041 --> 00:13:45.168 and once they're gone, 00:13:45.192 --> 00:13:48.213 they will not come back unless you have the same experience. 00:13:48.237 --> 00:13:49.891 The animal now is reprogrammed. 00:13:49.915 --> 00:13:54.136 So when we visited the animals 30 days, 60 days later, 00:13:54.160 --> 00:13:57.079 which is in human terms many years of life, 00:13:57.103 --> 00:14:02.409 they were still not addicted -- by a single epigenetic treatment. NOTE Paragraph 00:14:04.472 --> 00:14:07.743 So what did we learn about DNA? 00:14:07.767 --> 00:14:10.892 DNA is not just a sequence of letters; 00:14:10.916 --> 00:14:13.035 it's not just a script. 00:14:13.059 --> 00:14:15.430 DNA is a dynamic movie. 00:14:16.367 --> 00:14:21.278 Our experiences are being written into this movie, which is interactive. 00:14:21.302 --> 00:14:24.855 You're, like, watching a movie of your life, with the DNA, 00:14:24.879 --> 00:14:26.661 with your remote control. 00:14:26.685 --> 00:14:30.074 You can remove an actor and add an actor. 00:14:30.872 --> 00:14:36.767 And so you have, in spite of the deterministic nature of genetics, 00:14:36.791 --> 00:14:40.480 you have control of the way your genes look, 00:14:40.504 --> 00:14:43.774 and this has a tremendous optimistic message 00:14:43.798 --> 00:14:47.306 for the ability to now encounter some of the deadly diseases 00:14:47.330 --> 00:14:50.234 like cancer, mental health, 00:14:50.258 --> 00:14:53.186 with a new approach, 00:14:53.210 --> 00:14:55.744 looking at them as maladaptation. 00:14:55.768 --> 00:14:58.842 And if we can epigenetically intervene, 00:14:58.866 --> 00:15:02.362 [we can] reverse the movie by removing an actor 00:15:02.386 --> 00:15:05.243 and setting up a new narrative. NOTE Paragraph 00:15:06.028 --> 00:15:08.525 So what I told you today is, 00:15:08.549 --> 00:15:13.641 our DNA is really combined of two components, 00:15:13.665 --> 00:15:15.490 two layers of information. 00:15:16.106 --> 00:15:19.781 One layer of information is old, 00:15:19.805 --> 00:15:23.310 evolved from millions of years of evolution. 00:15:23.334 --> 00:15:26.510 It is fixed, and very hard to change. 00:15:27.411 --> 00:15:31.261 The other layer of information is the epigenetic layer, 00:15:31.285 --> 00:15:35.180 which is open and dynamic 00:15:35.204 --> 00:15:39.796 and sets up a narrative that is interactive, 00:15:39.820 --> 00:15:46.608 that allows us to control, to a large extent, our destiny, 00:15:47.695 --> 00:15:51.151 to help the destiny of our children 00:15:51.175 --> 00:15:55.330 and to hopefully conquer disease 00:15:55.354 --> 00:15:59.770 and serious health challenges 00:15:59.794 --> 00:16:03.405 that have plagued humankind for a long time. NOTE Paragraph 00:16:03.429 --> 00:16:06.822 So even though we are determined 00:16:06.846 --> 00:16:08.601 by our genes, 00:16:08.625 --> 00:16:11.692 we have a degree of freedom 00:16:11.716 --> 00:16:15.849 that can set up our life to a life of responsibility. NOTE Paragraph 00:16:15.873 --> 00:16:17.093 Thank you. NOTE Paragraph 00:16:17.117 --> 00:16:22.072 (Applause)