>> rose: welcome to our program. tonight a special edition the charliee rose brain series year two, in our sixth episode we consider autism. >> we learn an enormous amount about the normal human brain from studying disorders of brain function. in the agnosia selective defect of consciousness we've learned about normal consciousness in. thing pro face recognition how we recognize faces so in autism we're learning an enormous amount about the social brain, how individuals interact with each other as a result of stud oeeing this disorder. >> rose: episode six of the charlie rose brain series 2 underwritten by the simons foundation coming up. >> the charlie rose brain series is the most exciting scientific series of our time. understanding the brain. the series is made possible by a grant from the sigh months foundation. their mission is to-- simons

foundation to advance the research in the basic sciences and mathematics. funding for charlie rose was provided by the following: additional funding provided by these funders:

captioning sponsored by rose communications from our studios in new york city, this is charlie rose. >> rose: tonight we continue our exploration of the human brain with a look at one of the most per plexing disorders, autism. oughtism is a development disorder that presents itself in the first three years of life. symptoms vary widely but most autistic individuals generally have problems in three areas of development, social interaction, language and behavior. autism crosses all racial, ethnic and socioeconomic levels. but we do know that boys are four times more likely to be affected than girls. o donald triply was the first child ever sdiing knowsed with autism, in 1938 at the age of five, he was examined by austrian

psychiatrist leo can wore was puzzled by his symptom os. photograph years later kanner cited him as the initial subject in the journal article announce og the discovery of a condition unlike anything reported so far o today approximately one in 110 children in the united states are dpiing knowsed with some form of autism. no one is sure whether this increase is due to better awareness and diagnostics o or a substantive rise in the disorder. autism's exact cause is not clear. today researchers view it as a neurological condition, most likely resulting from one or more genetic abnormallallities in combination with environmental triggers. the diagnosis has a devastating impact on individuals and their families. alison singer knows this difficulty firsthand. she is the parent of an autistic daughter, jodi, also co-founder and president of the autism science foundation. she joins me this evening to talk about her experience. also joining me tonight a remarkable group of scientist gerald fischbach

is the scientific director of the simons foundation, uta frith of cognitive development at the university of college, london institute's cognitive neuroscience. matthew state is the donald j cohen professor of child psychiatry, psychiatry and genetics at the yale school of medicine. and once again my cohost is dr. erl kdean, a nobel laureate, professor at columbia university and howard hughes medical investigator. >> autism is a developmental disorder that manifests itself as a disturbance in social interaction. people with autism don't o appreciate that other people have minds of their own. so they find it very difficult to put themselves in another person's position to realize they have their own aspirations, their own ambitions, their own ideas about the world. the underlying cause for this is a failure of optimal development of a biological function called theory of mind. you and i have a theory of

mind. when you and i have a conversation, i have got a pretty good idea where you are going in the conversation. and you've got a very good idea where i'm going in the conversation so we're in some ways predicting each other's actions. in autistic person not being able to put themselves in your position can't predict where you're going to go. and you're thinking and your desires, everything else. and this as you can see is a very serious handi cap. as we've often pointed out, and you've emphasized in this series of programs, we learn an he nor o house amount about the normal human brain from studying disorders of brain function. in the agnosia selective defective consciousness we've learned about normal consciousness. in the prosagnosia defect in face recognition, we learn how he recognize faces so in autism we're learning an enormous amount about the

social brain, how individuals interact with each other as a result of studying this disorder. now the mere discovery of this is a fantastickically interesting story. to begin with, it was not recognized until 1940. until then, all of these children were misdiagnosed. they were called intellectually retarded all kinds of other diagnostic categories because one didn't really understand this is a special syndrome, number one number two remarkably this disorder which had not been described until the 1940s was spultly described in 42ee and 43 by two people working in pleatly different countries that had absolutely no contact with one another. the arcana and underberger. this is just absolutely amazing. not only that but both can are and asperger call it the same name, they called it autism. autism is a term that

broiler, the kai the guy who found the term schizophrenia to describe the social isolation that schizophrenic people could feel. kanner wrote a classic paper in 1942 in which he described what he saw as the three defining features of the syndrome. an unbelievable aloneness, of wanting to be alone and not wanting o social interaction is number one. number two, a stereotype, wanting to do the same thing o over and over again and getting terribly up set if you make the slightest change at all. and three, despite the fact that there are areas of suboptimal function, there are is lets of rather satisfactory function so kanner stud oi a group of 11 kids and they were characterized, many of them, by having rather severe language problem, asperger

made the contribution of making one realize that this is a spectrum. that among the four children that he studied, almost all of them had good language, and some of them are very bright. he called them my little professors. if you got them going they could talk unendingly about their stamp collection, about mozart and beethoven, deabout vene ease modernist artists, get them going and ey could talk forever. in fact, one of these, who came to his clinic went on to win the nobel prize in literature. she was so talented. so people with autism can have a wide spectrum of capabilities. some from having language disordersing some from being able to use language in a very creative way. for a number of years people thought that asperger's disease, that these highly well functioning individuals formed a very special

category. it was called the asperger syndrome. but the general feeling now and we'll have more of a discussion of that as we go on, is that this is part of a spectrum. and you can't really subdivide it at any particular point this is all an autism spectrum disorder. and this is what we are going to take up. gerry fischbach was really a profound student of the biology of autism and also the social implication, is going to describe what we understand about the syndrome and also its biological underpinnings. alison sing certificate going to give us an inside view of autism. she has a beautiful daughter that suffers from autism. and she has a brother who suffers from autism. so she knows what it's like to have autism. but also she mo knows what it's like to be a caretaker of a person with autism so we're going to get a double perspective of her. uta frith is a wonderful person and one of the most profound students in autism.

she was one of the pioneers in developing the theory of mind, and pointing out how this is really the defining feature of it. she not only characterized it in psychological terms but she also began to study the biology of it and she's going to describe the difference between the social network in normal kids and kids with theory of mind, and the genetics of the disease which matthew state is going to describe, is really quite fascinating. because several new insights into human genetics emerged just as the genetics of autism was being explored. and they reinforced each other. and we're going to learn a lot about normal human genetics as a result of the study of autism. >> rose: gerald, tell me more about defining, having to understand the biology and the incident of autism. >> charlie, i actual oly have just a very little bit to add to eric's wonderful introduction. this syndrome, the core of

it i believe is, and many people would agree, is the sense of aloneness, of living in isolation, a o boy in a bubble is the way kanner described it. and the other is this insistence on sameness and repetitive behavior. it's really an isolation from the world. and the theory of mind is a very important concept which i know we'll talk about in great detail. but there's a great deal of heterogenaity in the syndrome and there are many other aspects. some people call them integral parts of autism. some say they are copore morbiditis. the language deficit is very interesting. and there's a big spectrum of language disabilities in autism. some children use the same words over and over again. something called, and they repeat what they hear, ecolalia. some children are mute, don't speak at all so there is a wide range of

disability in this regard. some other comorbidities, many children with autism have seizures. many children have intellectual disability. ranging from very mild in the asperger case to severe intellectual disabilities, bordering on mental retardation. the points is that this spectrum blends into the normal population at one end and into the severely disabled population at the other. there is always some arbitrary dividing o line when you say this is something that needs therapy or not. but the comorbidities aside, you have to realize also this is an extreme oly prevalent disorder. largely because it blends into normal behavior on the one hand, and severe disabilities on the other. it's estimated that one in 100, the cdc these days,

estimates that one in a hundred children are on the autism spectrum. that's a big increase from the 1980s. >> rose: and do they also show that there is a higher incidence of autistic children from parents who are older? >> yes, that's been demonstrated. the prevalence of autistic offspring goes up several fold with each decade of paternal and in some evidence maternal life as well. so someone in their 40s having their first children has a 3 to 4 times greater risk of having an autistic child than an individual in their 20s. by the way, i don't think it counts for the really dramatic increase in prevalence. >> rose: so what do you think accounts for the dramatic increase. >> well, i hope we're going to talk about that. >> rose: all right, we'll get to that let me get a sense because alison understands it, give me a sense of what it is, the living experience of autism. >> well, it's really about

each day trying to find a balance between loving your child for exactly who she is, but constantly pushing for more. and by more i mean more language, more social interaction, more restaurants or other places in the community where she can go without having a meltdown. i think o my daughter jodi exhibited a lot of the typical early warning signs of autism. when she was a baby she never babbled. she never had social gestures. she never waved bye-bye. she never shook her head yes or no. she really struggled to make eye contact when i would take her to the playground or to play groups, she never showed any interest in the other children. she did have some words but all of those words were as gerry said earlier, words she had heard from books or videos. she played with toys in very unusual ways. she would organize them, sort them by color, line them up by size, she never

really played with them in the way that the toy manufacturers intended them to be played with. and she had tantrums that were off the charts. she needed everything to be in exactly the same order every day or she really couldn't-- she couldn't deal with thal. and as she's gotten older, now she is 14 and a half. some of these symptoms have become more engrained, more entrenched. she has certain schedules that she needs to follow. and if there is any deviation from those schedules, she really melts down and becomes aggressive, self-injurious. she has certain people that she will be with, certain places that she can go to. but it's really a challenge and a struggle every day for families. it's financially exhausting. it's emotionally exhausting. it's 24/7 taking care of someone who can't really communicate with whom i

can't really communicate. i have to surmise most of the time what shets's trying to say. our families are in crisis. and we really need more research to help us understand how we can find treatments that will help our family members to improve. >> rose: tell me the sense of what we more understand. o how are they not only like other children and o how are they like, unlike what don't they have in common. >> i should say that we are shouldn't only be talking about children because they all grow up to be adults. there are many more adults with autism then there are children. and that is one of the reasons why we have such a great variety, you know, we have to take into account the age of the person. and we do also take into the account the development usual oly brings some improvement so that we find often much milder symptoms

than, for example, in the case of allison described. and i really hope that her daughter will really continue to improve and it will be much easier to interact with her. and she will learn. because we know they learn. so the big difference and the things that's really in common across this huge spectrum of all this hetero again aity are these social communication difficulties. and that's not so easy to define because we really need to dell of quite deep. we need experimental psychology to tell us what's going on. we can't just look at the surface so let's start with a really common rhped sap and perhaps we canee swe a picture here that tells us that people withis autm, and i mean adults a in this case, this was taken fom t adults, n't look other people in the eyes. and there is true for children.

>> there are actual tracings m eyeovement. you can measure i e very precisely. they look at the mouth, as you can see. and you o look at the contrast, here is a neurotypical person, nonautistic person who really concentrates very much at the centre of the face to be able to take into account the eyes. and the question is why, why do we normally pay so much attention to the eyes. and there you have to remember, the eyes are the window to the soul. and it is as if they tell us something about what a person intends, desires, believes. and these words are interesting. they describe invisible mental states, desire, belief, intent. and it seems that most of us, but not the autistic people, behave as if they can observe them directly. of course they are invisible. but this is, this sort of

like makes understand the psychology of people, why they do things. that's how we explain behavior. that is how we predict behavior. and we are born with this ability. let me show you an example o using a painting. now perhaps you are attracted to look at the eyes of this lady sitting in the middle and the lady standing, they are clearly communicate with each other. there is something strange going on. you see the man on the left is holding behind his back the ace of clubs. he is a cheat. and the two ladies are in cole use with him. we can already predict there is something going on. they will defraud this very rich young man on the right side, you see he has a stack of gold coins in front of him. he doesn't knows what's going on. so how can we understand this kind of scene, complex scene that a painter has

presented centuries ago. i think the painter can rely on us to make sense using the cues that he has given. the language of the eyes, the situation that they are sitting with each other. and of course we can translate that into every day life. it's something we do all the time, we predict and explain what other people do and people with autism have tremendous difficulty doing this. so they're much more like that naive young man who doesn't understand that other people can really manipulate him and actually cheat him. so autistic people tend to be very straight, very honest and they are certainly not subject to certain social pressures that we are otherwise subject to. but it's not just sort of talking about words like serious mind or mentallizing. it's a new word that we

coined in order to explain this amazing ability to immediately take into account people's mental states. but we do know something about the brain basis of this amazing capacity which i believe we are born with. so i would just like it illustrate bid one of our experiments. and perhaps you would just rtagine yourself as a ipicpat, as a person, lying in the snner, being vexe relad. they are just littlere triangles, the big one,th e ittle one, they seem to be playing. oside, one is going comi back. and the little one is sort of pulling as if the little one didn't want to go out. it's being pushed out o and indeed the big triangle is blocking the door. so here they are, playing happily outside. >> a lot of social interaction. >> so this is something that we can do very, very easily. it's using our mentallizing ability even though they are

just little line drawings, it is the movements, it's the patterns. that triggered this. it's not all movements and all patterns that trigger. wsoe so we see another little movie. imagine yourself in a scanner. you just to watch this one. just after a few secondsan you begin to get very bored because there is nothing happening. they are just these triangles float oing,ti ifdrng. doing nothing at all of interest. now because we have that contrast, we can look at the activity in the brain when you do this spontaneous mentallizing, as in the first case. and when you don't. and if you subtract the activity one from the other, we can show this in the brain. we can see these artificially blue coloured dots. this shows us where in the brain there is extra activity. and we show the spontaneous

mentallizing, spontaneous attribution of mental states. you can see that there is a whole system, it's very active, and very importantly all the components are incredibly well connected with each o other. now you look at the image that has been obtained for an average, of an autistic group there are adults by the way, and you can see here much reduced activity in this mentallizing system and very o importantly, much weaker connections between the different components. and it's this weakness in connections in brain systems that many researchers have noticed and have commented on. and it's indeed some something that points towards the basic mechanism in building connections to the brain. the synapse. >> rose: if you try to understand why they can't engage in that theory of mind, mentalizing it is probably something to do with the synapse and the absence of a connection. >> that is at the moment one

of the major theories. >> rose: it's a theory, just a theory or -- >> my theory doesn't go on to the level of the synapse. i'm just making a connection. i'm reaching out of hand, the bridge has to be built very carefully. i'm looking 59 millions of -- >> i think what's interesting in uta's findings is that the basic areas that are involved in theory of mind, in the social brain are there. but what is weakened is the interactions between them, is weakened. and one way to explain that is a defect in the way cells communicate in synapses. some of the genetic evidence, some of the physiology that emerges supports that. >> matthew, tell us the genetic component. i think i understand that 99% of our genes are all alike but the one percent is crucial. >> exactly. so we have known for a long

time that a gene's play an important role in autism but it's really only been in the last several years that we've had the tools available to really make progress and get a good picture of the genetic landscape. and really a lot of that is because the advances in genomic technology have allowed to us look at that one percent. the part of the genome that varies between people in a way we have never been able to before so in doing that we found that there are different types of variation that we either didn't know about or didn't pay attention to that turn out to be very important for autism. >> and what are they? >> so we've known for a long time that if you look at twoif people and examine their genomes that there will be changes or there will be differences in the letter code of dna, say one particular position. and we've known that for a long time. but what we've now found out to through very high resolution genomic stud oees that actually the fine structure of chromosomes also varies between people. so in every cell we have 23

pairs of chromosomes. one from mom, one from dad. and that carries ourenome. and because we have one from mom and one from dad, up until recently the thinking was that that meant that we had two copies of every section of the genome in every gene. so would you have one from mom, and one from dad. that was the dogma. and again as we then develop the ability to look very carefully at the dna what we found is that that was not the case at all. so you can take a look at the verynefofi structure of a chromosome and when you real o hone in what you will find is that there may be a section of dna that would typically be present in a single copy on one chromosome but sometimes that duplicates. you'll have two copies on one chromosome and one copy on another chromosome. so many people will be walking around with only two copies of that section and other people will be walking around with three copies of that section. and now conversely you can also lose sections of dna. this is not just a single new kleeotide, a single dna

level but a relatively large but submicroscopic section of dna that may contain many genes so this idea that the structure of chromosomes were not invieable. >> is a revolution. >> the implications were so profound. before we were all thinking in terms of the fact that mutations involve a single gene. and that that is going to account for the various psychiatric, neurological, et cetera, cancer genetic wes have. but it now turns out that you can have significant portions of a chromosome, lots of genes either duplicated or missing. it's a complete oly new concept of a major mutation in the genome. >> exactly. and we've only really been able to see that over the last few years. now that's part of the normal spectrum of human genetic variation. we're all sitting at this table. we all have these things called copy number variations, variations in the number of copies.

>> a completely new insight that emerged within the last five years. >> yes, pfeiffer or six years. >> now what we have found. once we were able to see that that was an important source of genetic variation, then we found regons of the genome that were highly vulnerable so if you have a copy number variation, sometimes either a gain or a loss in a given regon that are you at tremendously increased risk for autism. and in fact for other neareau psychiatric disorders and other developmental disorders so that was really a fundamental change. we also found out that as we were able to look very carefully at the sequence of the dna that spontaneous mutations actually play a very important role in autism so again when o most people think about genetic disorders they think about genetic factors being transmitted from one generation to the next. we think about familiarity and often use that as a sin no of genetics. >> all of the schizophrenia studies were based upon family history. and this has completely

given us a new perspective that another mechanism is possible. fi so in this case, so in iaar c vontifaan variation can be transmitted from generation to generation but it also arises spontaneously so if it arises in a sperm or egg, spontaneously, just prior to conception, then what you willave a is i situation in which the mutation will be carried in the sperm or the egg if it is a female. and the subsequently the child in every cell in their body will have that mutation. but when you look at the parents, the parentses will not have any mutation at all this used to be very difficult for us to discern. very difficult to detect and now with new genomic tools we're able to detect it and we found the novo variation turns out to be tremendously important particularly in families when there is only a single affected child with autism. >> what is the williams syndrome? >> interesting question. so williams syndrome is a

neurodevelopmental disorder. and what is so interesting about it is so work from our laboratory looking at copy number variations po found that in one region op on chromosome 7 that if you have an extra copy on one chromosome so you have a total of three copies, you are at very, very high risk to have autism spectrum disorder. as soon as we found that we recognize that that was exactly the same region of the genome that when lost leads to this other condition called william syndrome. the dichbs between the two in terms of the social reciprocity, the interest, there is just extraordinarily interesting. remember what we are looking at is one spot, 26 genes out of 21,000 in the genome where if you have too much of them, are you at risk for ought im, if you have too little. >> nice to meet you, boss. >> nice to meet you. >> hi. >> hello, how are you. >> i haven't seen you. >> thank you. >> wow. >> what is your favorite color and what's your favorite tv show.

>> kids o love to ask questions. but not as much as these kids. >> my favorite color is blue. >> i have met barney the dinosaur. >> yay. >> where do you live? >> i live in new york city. >> do you have any -- >> i do. >> i have two daughters and a son. >> wow. >> and kids love to make friends but not like these kids. >> what nationality are you. >> i'm italian. >> how are you, buddy? >> so 39 seconds of, you can see this intense interest in social interaction. in fact, what you would think of as the opposite of the kinds of things that we've been talking about here today. >> i think just the notion that one section of the genome can have such a powerful impact in regulating social behavior really points to the power of genetic discovery in autism. because once you get down to the level of the molecule, you can then begin to see how you might be able to move forward to begin to tease apart at the cellular

level these tremendously complex biological and neuroprocesses. >> also the beauty of the biology that is emerging, this has all emerged it in the last few years of the novo mutations, just two things about it that i find fascinating. what is known periodically without understanding it, the families can be perfectly well functioning. all the children can be perfectly well functioning but one child has a disorder. how does that arise? we didn't understand that. we now realize that this is a d nova mutation. the parents don't have it, none of the other children have it because the sperm and the egg didn't have it except for that one conception. >> yes. that's number one. number two is known for elderly fathers is probably known for elderly mothers that this more likely occurs in elderly sperm and elderly ovo. so one possibility is that as the population ages

people have children later. this one of the contributing factors to the increased incidence of autism there are probably many including increased sensitivity to the order and better diagnostic procedures. >> i was going to make the same point. i think that it's very important to make this disphinx-- distinction that a mutation in the sperm or the egg does not affect the person bearing that sperm or egg. his or her brains have developed without any of that mutation. but something has happened in the cells which then will unite to form an offspring. and that is the new revelation and insight. and the sdinteds of de informo-- novo mutations is high it may explain up to 20, 30% of all cases of ideo pathic autism at present. we don't know it may be even higher than that. we're just now turning up the number of these genetic variants. and it's an extremely

exciting time. as eric has emphasized, i think the first really profound paper in this area, well there were two, was in 2007. >> rose: so five years ago. >> five years ago. for example there have been historically, i guess, since the 1940s genetic stud oees of schizophrenia. all of them familiar. and now we know there are denovoo mutations in schizophrenia as well. so there is revolutionizing psychiatric genetics. >> let me go back to talking about cog in difficult psychological explanations that might be there and ask the question obviously that, you know, can an autistic child develop increased ability. >> indeed, i have talked about this struckle that autistic people have in using this capacity to mentalize. but it is certainly possible for them to learn about mental states. and many of them do, many of

them have the ability to get a really good understanding, come to grips about what it means, you know, to have different beliefs, different desires from other people. but if this the same as the normal ability to mentalize? and i doubt that very much. for various reasons for saying this. first of all, it takes them a very long time to learn it. so we get these developal delays in understanding and different mental states. being able to take a different perspective and so on. it takes a very long time. and once it is achieved, it does tend to remain rather fragile so in the very fast every day communication, it really doesn't work very well. where it works extreme oly well is in remote or off-line or when you use

e-mail or when you write about something. when you are, when you use written communication with autistic people who have this understanding of mental states, you can get an enormous amount of insight from them that they can give you. but they have to prepare it. they have to think about it in advance. so if they were in a quick fire conversation, this would all probably go to pieces and be very difficult for them. they would have to revert into previously learned patterns in this case. so i think a lot can be achieved with compensatory learning, that is why i think in fact it is very important to have a cognitive, psychological explanation of what is going on what it means to be autistic, not just a genetic one. not just, you know,-- you need both, a good buy logical, a good psychological theory. because then you can, for example, think about possible ways of making this compensatory learning work

better, being o more efficient. and it also tells you something else. it does, it's terribly important to be aware of the stress and anxiety that autistic people actually suffer on there, when they are trying to do their best. they're trying to fit into the neurotypical world they have learned a lot about mentallizing. and we need to still adapt. we need to-- we need to make a lot of allowances and that is one of the things i think that a psychological explanations throw some light on. so if another person can't take your perspective, not at least unless they have a lot of time to think about it, then it is even more important for you to take that perspective. >> i think points o out this feature of brain plasticity and that compensations are a way of helping people deal with problems that the primary pathways are not providing for them. and we saw this, for example

w chuck close when we had him on the program. here is a person whose face blind and is a portrait painter. and he handles it by compensating. he can handle flat surfaces so he takes a photograph of you, puts it down, then puts a grid over it and puts that on canvas. so he's developed a way of compensating tore that that allows him to present faces o even though it has enormous difficulty with the three dimensionality of it. >> this notion of resilience is, i think, tremendously interesting. so now that we've gotten more of a picture of how the genetics of autism, the landscape and architecture, we found that in fact there are hundreds of spots in the genome, hundreds of regons that can confer risk. and