9:59:59.000,9:59:59.000 So it all came to life 9:59:59.000,9:59:59.000 in a dark bar in Madrid. 9:59:59.000,9:59:59.000 I encountered my colleague[br]from McGill, Michael Meaney. 9:59:59.000,9:59:59.000 And we were drinking a few beers, 9:59:59.000,9:59:59.000 and like scientists do, 9:59:59.000,9:59:59.000 he told me about his work. 9:59:59.000,9:59:59.000 And he told me that he is interested 9:59:59.000,9:59:59.000 in how mother rats 9:59:59.000,9:59:59.000 lick their pups 9:59:59.000,9:59:59.000 after they were born. 9:59:59.000,9:59:59.000 And I was sitting there and saying, 9:59:59.000,9:59:59.000 this is where my tax dollars are wasted, 9:59:59.000,9:59:59.000 on this kind of soft science. 9:59:59.000,9:59:59.000 And started telling me 9:59:59.000,9:59:59.000 that when the rats, like humans, 9:59:59.000,9:59:59.000 lick their pups in very different ways. 9:59:59.000,9:59:59.000 Some mothers do a lot of that, 9:59:59.000,9:59:59.000 some mothers do very little, 9:59:59.000,9:59:59.000 and most are in between. 9:59:59.000,9:59:59.000 But what's interesting about it 9:59:59.000,9:59:59.000 is when he follows these pups[br]when they become adults, 9:59:59.000,9:59:59.000 like years in human life, 9:59:59.000,9:59:59.000 long after their mother died, 9:59:59.000,9:59:59.000 they are completely different animals. 9:59:59.000,9:59:59.000 The animals that were licked[br]and groomed heavily, 9:59:59.000,9:59:59.000 the high licking and grooming, 9:59:59.000,9:59:59.000 are not stressed. 9:59:59.000,9:59:59.000 They have different sexual behavior. 9:59:59.000,9:59:59.000 They have a different way of living 9:59:59.000,9:59:59.000 than those that were not treated 9:59:59.000,9:59:59.000 as intensively by their mothers. 9:59:59.000,9:59:59.000 So then I was thinking to myself, 9:59:59.000,9:59:59.000 is this magic? 9:59:59.000,9:59:59.000 How does this work? 9:59:59.000,9:59:59.000 Us geneticists would like you to think 9:59:59.000,9:59:59.000 perhaps the mother had[br]the bad mother gene 9:59:59.000,9:59:59.000 that caused her pups to be stressful, 9:59:59.000,9:59:59.000 and then it was passed[br]from generation to generation. 9:59:59.000,9:59:59.000 It's all determined by genetics. 9:59:59.000,9:59:59.000 Or is it possible that something else 9:59:59.000,9:59:59.000 is going on? 9:59:59.000,9:59:59.000 So in rats we can ask this question 9:59:59.000,9:59:59.000 and answer it. 9:59:59.000,9:59:59.000 So what we did is[br]a cross-fostering experiment. 9:59:59.000,9:59:59.000 You essentially separate the litter, 9:59:59.000,9:59:59.000 the babies of this rat, at birth, 9:59:59.000,9:59:59.000 to two kinds of fostering mothers, 9:59:59.000,9:59:59.000 not the real mothers, 9:59:59.000,9:59:59.000 but mothers that will take care of them, 9:59:59.000,9:59:59.000 high-licking mothers[br]and low-licking mothers. 9:59:59.000,9:59:59.000 And you can do the opposite[br]with the low-licking pups. 9:59:59.000,9:59:59.000 And the remarkable answer was, 9:59:59.000,9:59:59.000 it wasn't important 9:59:59.000,9:59:59.000 what the gene you got from your mother. 9:59:59.000,9:59:59.000 It was not the biological mother[br]that defined this property 9:59:59.000,9:59:59.000 of these rats. 9:59:59.000,9:59:59.000 It is the mother that[br]took care of the pups. 9:59:59.000,9:59:59.000 So how can this work? 9:59:59.000,9:59:59.000 I am an a epigeneticist. 9:59:59.000,9:59:59.000 I am interested 9:59:59.000,9:59:59.000 in how genes are marked by a chemical mark 9:59:59.000,9:59:59.000 during embryogenesis, during the time[br]we're in the womb of our mothers, 9:59:59.000,9:59:59.000 and decide which gene will be expressed 9:59:59.000,9:59:59.000 in what tissue. 9:59:59.000,9:59:59.000 Different genes are expressed in the brain[br]than in the liver and the eye. 9:59:59.000,9:59:59.000 And we thought, is it possible 9:59:59.000,9:59:59.000 that the mother is somehow 9:59:59.000,9:59:59.000 reprogramming the gene of her offspring 9:59:59.000,9:59:59.000 through her behavior? 9:59:59.000,9:59:59.000 And we spent 10 years, 9:59:59.000,9:59:59.000 and we found that there is[br]a cascade of biochemical events 9:59:59.000,9:59:59.000 by which the licking and grooming[br]of the mother, the care of the mother 9:59:59.000,9:59:59.000 is translated to biochemical signals 9:59:59.000,9:59:59.000 that go into the nucleus and into the DNA 9:59:59.000,9:59:59.000 and program it differently. 9:59:59.000,9:59:59.000 So now the animal can[br]prepare itself for life. 9:59:59.000,9:59:59.000 Is life going to be harsh? 9:59:59.000,9:59:59.000 Is there going to be a lot of food? 9:59:59.000,9:59:59.000 Are there going to be a lot[br]of cats and snakes around, 9:59:59.000,9:59:59.000 or will I live in an upper[br]class neighborhood 9:59:59.000,9:59:59.000 where all I have to do[br]is behave well and proper 9:59:59.000,9:59:59.000 and that will gain me social acceptance? 9:59:59.000,9:59:59.000 And now one can think about[br]how important that process can be 9:59:59.000,9:59:59.000 for our lives. 9:59:59.000,9:59:59.000 We inherit our DNA from our ancestors. 9:59:59.000,9:59:59.000 The DNA is old. 9:59:59.000,9:59:59.000 It evolved during evolution. 9:59:59.000,9:59:59.000 But it doesn't tell us if you are going[br]to be born in Stockholm, 9:59:59.000,9:59:59.000 where the days are long in the summer[br]and short in the winter, 9:59:59.000,9:59:59.000 or in Ecuador, where equal number[br]of hours for day and night 9:59:59.000,9:59:59.000 all year round. 9:59:59.000,9:59:59.000 And that has such an enormous amount[br]on our physiology. 9:59:59.000,9:59:59.000 So what we suggest is perhaps[br]what happens early in life, 9:59:59.000,9:59:59.000 those signals that come through the mother 9:59:59.000,9:59:59.000 tell the child 9:59:59.000,9:59:59.000 what kind of social world[br]you're going to be living in. 9:59:59.000,9:59:59.000 It will be harsh, and you'd better[br]be anxious and be stressful, 9:59:59.000,9:59:59.000 or it's going to be an easy world,[br]and you have to be different. 9:59:59.000,9:59:59.000 Is it going to be a world[br]with a lot of light or little light? 9:59:59.000,9:59:59.000 Is it going to be a world[br]with a lot of food or little food? 9:59:59.000,9:59:59.000 If there's no food around, 9:59:59.000,9:59:59.000 you'd better develop your brain[br]to binge whenever you see a meal, 9:59:59.000,9:59:59.000 or store every piece of food[br]that you have as fat. 9:59:59.000,9:59:59.000 So this is good. 9:59:59.000,9:59:59.000 Evolution has selected this 9:59:59.000,9:59:59.000 to allow our fixed, old DNA 9:59:59.000,9:59:59.000 to function in a dynamic way 9:59:59.000,9:59:59.000 in new environments. 9:59:59.000,9:59:59.000 But sometimes things can go wrong. 9:59:59.000,9:59:59.000 For example, if you're born[br]to a poor family, 9:59:59.000,9:59:59.000 and the signals are, "You'd better binge. 9:59:59.000,9:59:59.000 You'd better eat every piece of food[br]you're going to encounter." 9:59:59.000,9:59:59.000 But now we humans[br]and our brain have evolved, 9:59:59.000,9:59:59.000 have changed evolution even faster. 9:59:59.000,9:59:59.000 Now you can buy a McDonald's 9:59:59.000,9:59:59.000 for one dollar. 9:59:59.000,9:59:59.000 And therefore, the preparation 9:59:59.000,9:59:59.000 that we had 9:59:59.000,9:59:59.000 by our mothers 9:59:59.000,9:59:59.000 is turning to be maladaptive. 9:59:59.000,9:59:59.000 The same preparation that was[br]supposed to protect us 9:59:59.000,9:59:59.000 from hunger and famine 9:59:59.000,9:59:59.000 is going to cause obesity, 9:59:59.000,9:59:59.000 cardiovascular problems,[br]and metabolic disease. 9:59:59.000,9:59:59.000 So this concept that genes[br]could be marked by our experience, 9:59:59.000,9:59:59.000 and especially the early life experience, 9:59:59.000,9:59:59.000 can provide us a unifying explanation 9:59:59.000,9:59:59.000 of both health and disease. 9:59:59.000,9:59:59.000 But is true only for rats? 9:59:59.000,9:59:59.000 The problem is, we cannot[br]test this in humans, 9:59:59.000,9:59:59.000 because ethically, we cannot[br]administer child adversity 9:59:59.000,9:59:59.000 in a random way. 9:59:59.000,9:59:59.000 So if a poor child develops[br]a certain property, 9:59:59.000,9:59:59.000 we don't know whether this is caused 9:59:59.000,9:59:59.000 by poverty 9:59:59.000,9:59:59.000 or whether poor people have bad genes. 9:59:59.000,9:59:59.000 So geneticists will try to tell you[br]that poor people are poor 9:59:59.000,9:59:59.000 because their genes make them poor. 9:59:59.000,9:59:59.000 Epigeneticists will tell you 9:59:59.000,9:59:59.000 poor people are in a bad environment[br]or an impoverished environment 9:59:59.000,9:59:59.000 that creates that phenotype,[br]that property. 9:59:59.000,9:59:59.000 So we moved to look 9:59:59.000,9:59:59.000 into our cousins, the monkeys. 9:59:59.000,9:59:59.000 My colleague Steven Soomey 9:59:59.000,9:59:59.000 has been rearing monkeys[br]in two different ways: 9:59:59.000,9:59:59.000 randomly separated the monkey[br]from the mother 9:59:59.000,9:59:59.000 and reared her with a nurse, 9:59:59.000,9:59:59.000 and a surrogate motherhood conditions. 9:59:59.000,9:59:59.000 So these monkeys didn't have a mother. 9:59:59.000,9:59:59.000 They had a nurse. 9:59:59.000,9:59:59.000 And other monkeys 9:59:59.000,9:59:59.000 were reared with their normal,[br]natural mothers, 9:59:59.000,9:59:59.000 and when they were old, 9:59:59.000,9:59:59.000 they were completely different animals. 9:59:59.000,9:59:59.000 The monkeys that had a mother 9:59:59.000,9:59:59.000 would not care about alcohol, 9:59:59.000,9:59:59.000 they were not sexually aggressive. 9:59:59.000,9:59:59.000 The monkeys that didn't have a mother 9:59:59.000,9:59:59.000 were aggressive, were stressed, 9:59:59.000,9:59:59.000 and were alcoholics. 9:59:59.000,9:59:59.000 So we looked at their DNA 9:59:59.000,9:59:59.000 early after birth 9:59:59.000,9:59:59.000 and see is it possible[br]that the mother is marking. 9:59:59.000,9:59:59.000 There is a signature of the mother[br]in the DNA of the offspring. 9:59:59.000,9:59:59.000 These are Day 14 monkeys, 9:59:59.000,9:59:59.000 and what you see here is the modern way[br]by which we study epigenetics. 9:59:59.000,9:59:59.000 We can now map those chemical marks,[br]which we call methylation marks, 9:59:59.000,9:59:59.000 on DNA at a single nucleotide resolution. 9:59:59.000,9:59:59.000 We can map the entire genome. 9:59:59.000,9:59:59.000 We can now compare the monkey[br]that had a mother and not. 9:59:59.000,9:59:59.000 And here's a visual presentation of this. 9:59:59.000,9:59:59.000 What you see is the genes that[br]got more methylated are red. 9:59:59.000,9:59:59.000 The genes that got less[br]methylated are green. 9:59:59.000,9:59:59.000 You can see many genes are changing, 9:59:59.000,9:59:59.000 because not having a mother 9:59:59.000,9:59:59.000 is not just one thing. 9:59:59.000,9:59:59.000 It affects the whole way, it sends[br]a signals about the whole way 9:59:59.000,9:59:59.000 your world is going to look like 9:59:59.000,9:59:59.000 when you become an adult, 9:59:59.000,9:59:59.000 and you can see the two groups of monkey 9:59:59.000,9:59:59.000 extremely well separated from each other. 9:59:59.000,9:59:59.000 How early does this develop? 9:59:59.000,9:59:59.000 These monkeys already didn't[br]see their mothers, 9:59:59.000,9:59:59.000 so they had a social experience. 9:59:59.000,9:59:59.000 Do we sense our social status 9:59:59.000,9:59:59.000 even at the moment of birth? 9:59:59.000,9:59:59.000 So in this experiment,[br]we took placentas 9:59:59.000,9:59:59.000 of monkeys 9:59:59.000,9:59:59.000 that had different social status. 9:59:59.000,9:59:59.000 What's interesting about social rank 9:59:59.000,9:59:59.000 is that across all living beings, 9:59:59.000,9:59:59.000 they will structure themselves[br]by hierarchy. 9:59:59.000,9:59:59.000 Monkey number one is the boss. 9:59:59.000,9:59:59.000 Monkey number four is the peon. 9:59:59.000,9:59:59.000 And you put four monkeys in a cage, 9:59:59.000,9:59:59.000 there will always be a boss[br]and always be a peon. 9:59:59.000,9:59:59.000 And what's interesting is that[br]the monkey number one 9:59:59.000,9:59:59.000 is much healthier than monkey number four, 9:59:59.000,9:59:59.000 and if you put them in a cage, 9:59:59.000,9:59:59.000 monkey number one will not eat as much. 9:59:59.000,9:59:59.000 Monkey number four will eat as much. 9:59:59.000,9:59:59.000 And what you see here in this[br]methylation mapping, 9:59:59.000,9:59:59.000 a dramatic separation at birth 9:59:59.000,9:59:59.000 of the animals that had[br]a high social status 9:59:59.000,9:59:59.000 versus the animals that did not[br]have a high status. 9:59:59.000,9:59:59.000 So we are born already knowing[br]the social information, 9:59:59.000,9:59:59.000 and that social information[br]is not bad or good. 9:59:59.000,9:59:59.000 It just prepares us for life,[br]because we have to program 9:59:59.000,9:59:59.000 our biology differently 9:59:59.000,9:59:59.000 if we are in the high[br]or the low social status. 9:59:59.000,9:59:59.000 But how can you study this in humans? 9:59:59.000,9:59:59.000 So we can't do experiments, 9:59:59.000,9:59:59.000 we can't administer adversity to humans, 9:59:59.000,9:59:59.000 but God does experiments with humans, 9:59:59.000,9:59:59.000 and it's called natural disasters. 9:59:59.000,9:59:59.000 So one of the natural disasters, 9:59:59.000,9:59:59.000 the hardest natural disaster[br]in Canadian history happened 9:59:59.000,9:59:59.000 in my province of Quebec. 9:59:59.000,9:59:59.000 It's the ice storm of 1998. 9:59:59.000,9:59:59.000 We lost our entire electrical grid[br]because of an ice storm 9:59:59.000,9:59:59.000 when the temperatures were in[br]the dead of winter in Quebec, 9:59:59.000,9:59:59.000 minus 20 to minus 30, 9:59:59.000,9:59:59.000 and there were pregnant[br]mothers during that time. 9:59:59.000,9:59:59.000 And my colleague Suzanne King 9:59:59.000,9:59:59.000 followed the children of these mothers 9:59:59.000,9:59:59.000 for 15 years. 9:59:59.000,9:59:59.000 And what happened was 9:59:59.000,9:59:59.000 that as the stress increased, 9:59:59.000,9:59:59.000 and here we had objective[br]measures of stress -- 9:59:59.000,9:59:59.000 how long you were without power,[br]where did you spend your time, 9:59:59.000,9:59:59.000 was it in your mother's in law apartment 9:59:59.000,9:59:59.000 or in some posh country home? 9:59:59.000,9:59:59.000 so all of these added up[br]to a social stress scale, 9:59:59.000,9:59:59.000 and you can ask the question, 9:59:59.000,9:59:59.000 how did the children look like? 9:59:59.000,9:59:59.000 And it appears that as stress increases, 9:59:59.000,9:59:59.000 the children develop more autism, 9:59:59.000,9:59:59.000 they develop more metabolic diseases, 9:59:59.000,9:59:59.000 and they develop more autoimmune diseases. 9:59:59.000,9:59:59.000 And we would map the methylation state,[br]and again you see the green genes 9:59:59.000,9:59:59.000 becoming red as stress increases, 9:59:59.000,9:59:59.000 the red genes becoming green[br]as stress increases, 9:59:59.000,9:59:59.000 an entire rearrangement[br]of the genome in response to stress. 9:59:59.000,9:59:59.000 So if we can program genes, 9:59:59.000,9:59:59.000 if we are not just the slaves[br]of the history of our genes, 9:59:59.000,9:59:59.000 that they could be programmed,[br]can we deprogram them? 9:59:59.000,9:59:59.000 Because epigenetic causes can cause[br]diseases like cancer, 9:59:59.000,9:59:59.000 metabolic disease, 9:59:59.000,9:59:59.000 and mental health disease. 9:59:59.000,9:59:59.000 Let's talk about cocaine addiction. 9:59:59.000,9:59:59.000 Cocaine addiction is a terrible situation 9:59:59.000,9:59:59.000 that can lead to death 9:59:59.000,9:59:59.000 and to loss of human life. 9:59:59.000,9:59:59.000 We asked the question, 9:59:59.000,9:59:59.000 can we reprogram the addicted brain 9:59:59.000,9:59:59.000 to make that animal 9:59:59.000,9:59:59.000 non-addicted anymore? 9:59:59.000,9:59:59.000 We used a cocaine addiction model 9:59:59.000,9:59:59.000 that recapitulates what happens in humans. 9:59:59.000,9:59:59.000 In humans, you're in high school, 9:59:59.000,9:59:59.000 some friends suggest you some cocaine, 9:59:59.000,9:59:59.000 you take cocaine, nothing happens, 9:59:59.000,9:59:59.000 months pass by, something reminds you[br]of what happened the first time, 9:59:59.000,9:59:59.000 a pusher pushes cocaine, 9:59:59.000,9:59:59.000 and you become addicted, 9:59:59.000,9:59:59.000 and your life has changed. 9:59:59.000,9:59:59.000 In rats, we do the same thing. 9:59:59.000,9:59:59.000 My colleague [??] did. 9:59:59.000,9:59:59.000 He trains the animals 9:59:59.000,9:59:59.000 to get used to cocaine, 9:59:59.000,9:59:59.000 then for one month, no cocaine, 9:59:59.000,9:59:59.000 and then he reminds them of the party[br]when they saw the cocaine the first time 9:59:59.000,9:59:59.000 by the colors of the cage[br]when they saw cocaine. 9:59:59.000,9:59:59.000 And they go crazy. 9:59:59.000,9:59:59.000 They will press the lever to get cocaine 9:59:59.000,9:59:59.000 until they die. 9:59:59.000,9:59:59.000 We first determined 9:59:59.000,9:59:59.000 that the difference between these animals 9:59:59.000,9:59:59.000 is that during that time[br]when nothing happens, 9:59:59.000,9:59:59.000 there's no cocaine around, 9:59:59.000,9:59:59.000 their epigenome is rearranged. 9:59:59.000,9:59:59.000 Their genes are remarked[br]in a different way, 9:59:59.000,9:59:59.000 and when the cue comes, 9:59:59.000,9:59:59.000 their genome is ready 9:59:59.000,9:59:59.000 to develop this addictive phenotype. 9:59:59.000,9:59:59.000 So we treated these animals 9:59:59.000,9:59:59.000 with drugs that either increase 9:59:59.000,9:59:59.000 DNA methylation, which was[br]the epigenetic marker to look at, 9:59:59.000,9:59:59.000 or decrease epigenetic markings. 9:59:59.000,9:59:59.000 And we found that if we[br]increased methylation, 9:59:59.000,9:59:59.000 these animals go even crazier. 9:59:59.000,9:59:59.000 They become more craving for cocaine. 9:59:59.000,9:59:59.000 But if we reduce the DNA methylation, 9:59:59.000,9:59:59.000 the animals are not addicted anymore. 9:59:59.000,9:59:59.000 We have reprogrammed them. 9:59:59.000,9:59:59.000 And a fundamental difference[br]between an epigenetic drug 9:59:59.000,9:59:59.000 and any other drug 9:59:59.000,9:59:59.000 is that with epigenetic drugs,[br]we essentially remove 9:59:59.000,9:59:59.000 the signs of experience, 9:59:59.000,9:59:59.000 and once they're gone, 9:59:59.000,9:59:59.000 they will not come back[br]unless you have the same experience. 9:59:59.000,9:59:59.000 So the animal now is reprogrammed. 9:59:59.000,9:59:59.000 So when we visited the animals[br]30 days, 60 days longer, 9:59:59.000,9:59:59.000 which is in human terms[br]many years of life, 9:59:59.000,9:59:59.000 they were still not addicted 9:59:59.000,9:59:59.000 by a single epigenetic treatment. 9:59:59.000,9:59:59.000 So what we learned about DNA? 9:59:59.000,9:59:59.000 The DNA is not just a sequence of letters. 9:59:59.000,9:59:59.000 It's not just a script. 9:59:59.000,9:59:59.000 DNA is a dynamic movie. 9:59:59.000,9:59:59.000 Our experiences are being[br]written into this movie, 9:59:59.000,9:59:59.000 which is interactive. 9:59:59.000,9:59:59.000 You are like watching a movie[br]of your life with the DNA 9:59:59.000,9:59:59.000 with your remote control. 9:59:59.000,9:59:59.000 You can remove an actor and add an actor. 9:59:59.000,9:59:59.000 And so you have, in spite[br]of deterministic nature of genetics, 9:59:59.000,9:59:59.000 you have control of the way[br]your genes look like, 9:59:59.000,9:59:59.000 and this has a tremendous[br]optimistic message 9:59:59.000,9:59:59.000 for ability to now encounter[br]some of the deadly diseases 9:59:59.000,9:59:59.000 like cancer, mental health, 9:59:59.000,9:59:59.000 with new approach 9:59:59.000,9:59:59.000 looking at them as maladaptations 9:59:59.000,9:59:59.000 that if we can epigenetically intervene, 9:59:59.000,9:59:59.000 reverse the movie 9:59:59.000,9:59:59.000 by removing an actor 9:59:59.000,9:59:59.000 and setting up a new narrative. 9:59:59.000,9:59:59.000 So what I told you today is 9:59:59.000,9:59:59.000 that our DNA is really combined 9:59:59.000,9:59:59.000 of two components, 9:59:59.000,9:59:59.000 two layers of information. 9:59:59.000,9:59:59.000 One layer of information is old,[br]evolved from millions of years 9:59:59.000,9:59:59.000 of evolution. 9:59:59.000,9:59:59.000 It is fixed 9:59:59.000,9:59:59.000 and very hard to change. 9:59:59.000,9:59:59.000 The other layer of information[br]is the epigenetic layer 9:59:59.000,9:59:59.000 which is open and dynamic 9:59:59.000,9:59:59.000 and sets up a narrative 9:59:59.000,9:59:59.000 that is interactive, 9:59:59.000,9:59:59.000 that allows us to control, 9:59:59.000,9:59:59.000 to a large extent, our destiny, 9:59:59.000,9:59:59.000 to help the destiny of our children, 9:59:59.000,9:59:59.000 and to hopefully conquer disease 9:59:59.000,9:59:59.000 and serious health challenges 9:59:59.000,9:59:59.000 that have plagued humankind[br]for a long time. 9:59:59.000,9:59:59.000 So even though we are determined 9:59:59.000,9:59:59.000 by our genes, 9:59:59.000,9:59:59.000 we have a degree of freedom 9:59:59.000,9:59:59.000 that can set up our life[br]to a life of responsibility. 9:59:59.000,9:59:59.000 Thank you. 9:59:59.000,9:59:59.000 (Applause)