>> rose: welcome to our program. to want, a special edition, the charlie rose brain series, year two. in our sixth episode we consider autism. >> we learn enormous amount about the normal human brain from studying disorders of brain function. in the selective defect of consciousness we've learned about normal consciousness. we learned about face regularisim in and in autism we' learning an enormous amount about the social brain, how individuals interact with each other. >> episode six of the charlie rose brain series two underwritten by the simons foundation coming up.

captioning sponsored by rose communications froour 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 perplexing disorders: autism. autism is a developmental 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. donald triplet was the first child ever diagnosed with autism. in 1938 at the age of five he was examined by austrian psychiatrist leo caner who was puzzled by his symptoms. five years later caner sited him as the initial subject in a journal article of a condition unlike anything reported so far, today approximately 1 in 110 children in the united states are diagnosed with some form of autism. no one is sure whether this is due to increase and better awareness or a substantial rise in the disorder autism's rise is not clear. researchers view it as a neurological condition resulting from one or more genetic abnormalities in combination with environmental triggers. the diagnose has a devastating impact on individuals and their families. alison singer know this is

difficulty firsthand. she's the parent of an autistic daughter jodi. she's also co-founder and president of the autism science foundation also joining me, gerald fischbach, a scientific director of the simons foundation, uta frith is at the university of ledge london's ins opportunity. matthew state is the donald j. professor of psychiatry and genetics at the university of medicine and my co-host is dr. eric kandel. he's a nobel laureate, a professor of columbia university and a howard hues medical investigator. >> autism is a developmeal disdisorder tat manifests itself in a disturbance of social interaction. people with autism don't 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 ambitions

and ideas about the world. the underlying cause for this is a file your of optimal development of a biological function called theory of mind. you and i have a theory of mind. when you and i ha a conversation i'veot a good id whe you're going in the conversation and you've got a very good of where i'm going in the conversation so we're in some ways predicting each other's actions. an autistic person, not being able to put themselves in your position, can't predict where you're going to go and your thinking and your desires, everything else. and this as you can see is a very serious handicap. as we've often pointed out and you've emphasized in this series of programs we learn an enormous amoun about the normal human brain from studying disorders of brain function. in the ig nose ya selective

defect ofness we learn a lot about how to recognize faces and so in autism we're learning an enormous amount about the social brain, how individuals interact with each other. now, the mere discovery of this is a fantastic and interesting story. to begin with,t was not recognized until 1940. until then, all of these children were misdiagnosed. they were called intellectually retarded, all kinds of other categories because they didn't understand this was a special syndrome, number one. number two, remarkably, this disorder, which has not been described until the 1940s was simultaneously described in '42 and '43 by two people working in completely different countries hat haablutely no contact with one another

lee yo kann ere are and understand berger. this is answer newtly amazing. but both kanner and abc asperger called it the same name, they call it autism. autism was a term that the guy who founded the term schizophrenia used in order to describe the social isolation that schizophrenic people can feel. kahner wrote a classic paper in 1942 in ich he described what he saw as the three defining features of the syndrome. an unbelievable aloneness, of wanting to be alone and not wanting social interaction, is number one. number two, a stereotypeing... wanting to do the same thing over and over again and getting terribly upset if you make the slightest change at all. and, three, despite the fact that there are areas of suboptimal function, there were

islets of rath satisfacty function so kahner study add group of 11 kids. and asperger made one realize this is a spectrum. that among the four children he studied almost all of them had good language and some were very bright. he called them "my little professors." if you got them going they could talk unendingly about their stamp collection, haydn, mozart, beethoven, vieese mdernist artists. get them going and they 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 disorder, some from being able to use language in a creative

way. for a number of years people thought that asperger's, that eseighly well-functioning iividls rmed very special category called the asperger's syndrome and we'll have more of a discussion about this as we go on but that this is part of a spectrum and you can't subdivide any particular points this all an autism spectrum disorder. jerry fischbach, who's really a profound student of the biology of autism and social implications is going to describe what we understand about the syndrome and also its biological underpinnings. allin singeis 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 knows what it's like to be a caretaker of a person with autism. so we're going to get a double perspective of hers. 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 the defining feature of it. she not only characterized in the psychological terms but she also began to stud stud the biology of it and she'll describe the difference between the social network in normal kids and kids. and the genetics of the disease which matthew state is going to describe is really quite fascinating because several new insights into human genetics emerge as the genetics of autism was being explored and they reinforce each other and we'll learn a lot about the normal human genetics.

>> rose: gerald, tell me more about and define and understand the biology and the incidents of autism. >> charlie i have a 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 boy in a bubble is the way kanner described i and th oth 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 heterogeneity in this syndrome and there are many other aspects of it. some people call them integral parts of autism some say they're co-morbidities. 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. some children are mute. don't speak at all. so there's a wide range of disability in this regard. other co-morbidities are... many children with autism have seizures. many children have intellectual disability ranging from very mild in the asperger case to severe intellectual disabilies bderg on ment retardation the point is that this spectrum blends into the normal population at one end and the severely disabled population at the other. there's always some arbitrary dividing line when you say this is something that needs therapy or not. but the co-morbidities aside you

have to realize also this is an extremely prevalent disorder, largely beuse it blends in normal bavio on e one hand and severe disabilities on the other. it's estimated one in a hundred... the c.d.c. estimates that one in a hundred children are on the autism spectrum that's a big increase the 19 80s. >> rose: do they also show there's 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 parnalnd in some evidence maternal life as well. so someone in their 40s having their first child has a three to four times greater risk of having an autistic child than an individual in their 20s. so that... 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 in prevalence? >> well, i hope we'll talk about that. >> rose: alison understds, givme aense of the ving 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 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 wavedye-e. sh nev shk her head yes or no. she really struggled to make eye contact when i would take her to the playground or play groups. she never showed any interest in the other children. she did have some words, but all

of those words were, as jerry 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 manufacters inteed them to be played with. and she had tantrums that were off the charts. she needed everything to be in exactly the same order everyday or she really couldn't deal with that. as she got older-- now she's 14 and a half-- some symptoms have become more ingrained, more entrenched. she has certain schedules that she needs to follow and if there's any deviation from those schedule she is really melts down and becom 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 everyday for families. it's financially exhausting. it's emotionally exhausting. it's 24/7 taking care of someone with whom i can't really communicate, i have to surmise most of the time what she's trying to say. our families are in crisis and we really need moreresearch to helus uerstand how we can find treatments that will help our family members to improve. >> rose: let me turn to uta and tell me the sense of what we more understand. how are they not only like other children and how are they unlike what don't they have in common? >> i should say that we shouldn't only be talking about children, because they all grow up to be adults. there are many more adults with autism than there are children. and that is one of theeasons why we have such great variety.

we have to take into account the age of the person and we do also take into account the development, usually with some improvement, so we find often much milder symptoms than, for example, in the case of alison just described and i really hope that her daughter will really continue to be... improve and it will be much easier to interact with her because we know they learn. so t big difference and the hing that's really in common across this huge spectrum, all this heterogeneity are these social communication difficulties. and that's not so easy to define because we really need to delve quite deep. we need experimental psychology to tell us what's going on. so let's start with a really common observation and perhaps we can see a picture here that

tells us that people with autism-- a i man alt in this case-- don't look other people in the eyes. >> they have different eye movements. >> these are actual tracings of eye movements. you can measure it precisely. they look at the mouth as you can see. and you look at the contrast. here is a neurotypical person, non-autistic person who really concentrates very much the center of the face to be able to take into account the eyes. and the question is why? w do we normal pay souch atntio to the eyes? and then you have to remember the saying, 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 autistic people-- behave as if they can observe them directly of course th are invisible but this sort of... makes us understand the psychology of people, why they do things. that's how we explain behavior, that's how we predict behavior. and we are born with this ability. let me show you and example 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 clearly communicate with each other. there's 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 collusion with him. we can already predict there's something going on, they will

defraud this very rich young man on the right side because he has a stack of gold coins in front of him. he doesn't know what's going on. so how can we understand the this kind of complex scene that a painter has presented ceturies ago. i think the painter can rely on us t make sense using the cues that he's given, the language of the eyes, the situation that they are sitting with each other we can translate that into everyday life. we do it 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 rely manipulat hi and actually cheat him. so autistic people tend to be very honest and they're

certainly not hypocritical, they're certainly not subject to certain social pressures that we are otherwise subject to. but it's not just sort of talking about words like theory of mind or mentalizing is a new word that we coin 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 aazin capacity which ielieve we are born with. so i'd just like to illustrate it by one of our experiments. just imagine yourself as a participant, as a person lying in the scanner being very relaxed, they're just little triangles, it's a big one, a little one. they seem to be playing, the big one is going outside, coming back and the little one is pulling as if the little one didn't want to go out it's being pushed out. an, indeed,the big triangles

blocking the door. so here they are playing happily outside. >> a lot of social interaction. >> so this is this is something we can do very, very easily. it's using our mentalizing ability even though they are just triangles but it's the movement, the patterns. that triggers us. and it's not all movements and all patterns that trigger it. so we see another little movie. imagine yourself in a scanner, you just watch this one. and just avenue a few seconds y ben to get very bor because there's nothing happening. they're just these triangles floating, just 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 mentalizing 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 lored dots. this shows us where the brain there is extra activity where we show this spontaneous mentalizing, is spontaneous attribution of mental states. you can see that there is a whole system very active and very important. all the components are incredibly well connected with each other. now, you look at the image that has been obtained for an average of an autisticroup-- they are adults,y th way-- and you can see here much reduced activity in this mentalizing system and very 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 something that

points towards the basic mechanism in building connections in the brain. the synapse. >> rose: if you try to understand why they can't engage in the theory of mind or mentalizing it's probably something to do th t synae andhe abnce of a cnnection? >> that is the nature of the theory. >> just a theory or... >> my theory doesn't grow on to the level of the synapse. i'm just making a connection. i'm reaching out a hand. the bridge has to be built very carefully. i'm looking at millions of nerves... >> 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 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. >> rose: matthew, tell us the genetic component. i mean, i think i've... i understand that 99% of our genes are all alike but the 1% is crucial. >> exactly. so we've known for a long time that genes play an important role in autism but it's really ly been in theast several years that wee had the tools and we're able 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 us to look at that 1%, the part of the genome that varies between people in a way we've never been able to before. so in doing that we found there are different types of variation that we either didn't know about or didn't pay attention to that are very important for autism. >> rose: and what are they? >> so we've known for a long time ifyou look at o people nd exmine eir genomthere is wl be cnges or differences in the letter code of d.n.a. one particular position.

we've known that for a long time. what we've now found out through high resolution genomic studys is the fine structure of chromosomes also varies between people. so in everybody cell we have 23 pairs of chromosomes-- one from mom, one from dad. and that carries our genome. and because we have one from mom and one from dad up until recently the thinking wa that tt met had two copies of every section of the genome in every gene. so you'd have one for from mom and one from dad. that was the dogma. again, as we then developed the ability to look very carefully at the d.n.a. what we found is that that was not the case at all. so you can take a look at the very fine structure of a chromosome and when you hone in what you'll find is there's a section of d.n.a. that would typically be present in one copy on a chromosome but sometimes that duplicates. it would have copies on one chromose a anothern

ather chmosome. so many people are walking around with only two copies of that section and other people are walking around with three copies of that section. conversely you can lose sections of d.n.a. this is not just a single nucleotide, a single d.n.a. letter but a rill tivoli large but still submicroscopic section of d.n.a. that may contain many genes. so this idea that the structure of the chromosomes were not inviolable was really a revolutionary change. >> and the implication is so profound. before we were all thinks 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 genetics we have. but it now turns out that you can have significant portions of a chromosome, lots of genes either duplicated or missing. >> yes. >> it's a completely new concept of a major mutation in the genome.

>> and we've only been able to see that over the last few years. now, that's part of the normal spectrum of human genetic vartio we're all sitting at this table... >> we all have this. >> we have these things called copy number variations. it's a completely new insight that emerged within the last five years. >> five or six years, yes. but now what we found, once we were able to see that that was an important source of genetic variation, we found out that there were reasons of the genome that were highly vulnerable so if you have a copy number variation sometimes they are a gain or a loss in a given region that you're at tremendously increased risk for autism and, in fact, for other neuropsychiatric disorders and other developmental disorders so thatas really a fundamental change. we also found out that as we were able to look very carefully at the sequence of the d.n.a. that spontaneous mutations actually play a very important role in autism. so, again, when most people think about genetic disorders they think about genetic factors

being transmitted from one generation to the next. we think about familialty and often use that as a synonym for genetics. >> all of the early schizophrenia studies, all the depression studies were based upon family histories. >> ys. >> and tis h completely given us a new perspective that another mechanism is possible. >> so in this case... so, in fact, genetic 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 than what you'll have is a situation in which the mutation will be carried in the sperm or the egg if it's female and that subsequentedly child in every cell in their body will have that mutation. but when you lo at the pants, t paren 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 with

great resolution and lo and we hold we found out the variation turns out to be tremendously important, particularly in families where there's only a single affected child with autism. >> rose: what is the williams syndrome? >> interesting question. so williams syndrome is a neurodevelopmental disorder and what's so interesting about it is... so work from our laboratory looking at copy number variations found that in one region on chromosome 7 that if you have an extra copy on one chromosome-- so you have a total of three copies-- you're at very very high risk to have autism spectrum disorder. as soon as we found that we recognized that that was exactly the same region of the genome that when lost leads to this other condition called william syndrome. the difference between the two in terms of the social reciprocity, the interest, it's just extraordinarily interesting. remember what we're looking at is one spot, 26 genes out of 21,000 in the genome where if you have too much of them you're

at risk for autism and if you have too little... >> hello, buddy, how are you? >> oh, thank you! thank you! >> what's your favorite t.v. show? >> kids love to ask questions but not as much as these kids. >> my favorite color is blue. i have met barney the dinosaur. >> yeah! >> where do you live? >> i live in n yorcity. >> do you have any sons or daughters? >> i do. i have two daughters and a son. >> and kids love to make friends. but not like these two. >> what nationality are you? >> i'm italian. >> 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 pow 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 tease apart at the cellular level these tremendously complex biological processes. >> and the beauty of the biology that has emerged-- and this has emerged in the last three years, of de novo mutations what is known periocall witut understanding it is that 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 de novo mutation. that 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. that's number one.

number two it is known for elderly fathers, it's probably known for elderly mothers th this more lkelyccurs in elderly sperm and elderly ova. and so one possibility is that as the population ages people have children later. this is one of the contributing factors to the increase incidents of autism. there are probably many, including increased sensitivity to the disorder and better diagnostic procedures. >> i was going to make the same point. i think it's very important to make this 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's the new revelation and insight and the incidents of de novo mutations is high. it may explain up to 20%, 30% of

all cases of idiopathic autism at present. we don't know. maybe even higher than that. we're just now turning up the number of these genetic varian. and it'san eremely exciting time. as eric has emphasized, i think the first really profound paper in this area-- well, there were two-- were in 2007. >> rose: wow. so five years ago. >> for example, there have been historically i guess since the 1940s genetic studies of schizophrenia. all of them familiar. and now we know that there are de novo mutations in schizophrenia as well. so this is revolutionizing psychiatric genetics. >> rose: let me go back and talk about cognitive pshology c platio th might be there and ask the question obviously that, you know, can an autistic child develop increased ability? >> indeed. i've talked about the... the

struggle 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 have good understand aing, to come to grips of different desires from other people. but is this the same as the normal ability to mentalize? that... i doubt that very much. there are various reasons for saying this. first of all, it takes them a very long time to learn it so we get these developmental delays in understanding different mental states, being able to take a different perspecti and so on tak a ve ng time. and once it is achieved it does tend to remain rather fragile.

so in the very fast everyday communication it really doesn't work very well. where it works extremely well is in remote or offline or when you use e-mail or when you write about something. when you use written communication with autistic people have this understanding of mental states you can get an enormous amount of insight from th th they can give you, but they have to prepare it. they have to think about in the 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. and that's why i think, in fact, it is very important to have a cognitive psychological explanation of what's going on, what it means to be autistic,, not just aenetic one.

not jus.. you need both a good biological and a good psychological theory because you can then for for example think about possible ways of making this compensatory learning work better being more efficient and it also tells you something else. it's terribly important to be aware of the stress and anxiety that autistic people actually suffer under when they are trying to do their best. they're trying to fit into the neurotypal world. they have learned a lot about mentalizing. and we need to still adapt. we need to make a lot of allowances and that is one of the thing i think that a psychological explanation sheds 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's even more important for you to

take their perspective. >> i think it points out this feature of brain plasticity and compensations are a y of helping peop deawith problems that the primary pathways are not providing for them. and we saw this for example with chuck close when we had him on the program. here is a person who is 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 it on cam vas. so he's developed a way of compensating this that allows him to paint faces even though he has difficulty with the three dimensionaltof it. >> this notion o resilience is tremendously interesting. so now that we've gotten more of a picture of how the genetics of autism, the landscape, the architecture, we found that, in fact, there are hundreds of spots in the genome, hundreds of regions that can confer risk. and so on the one hand it's

tremendously heterogeneous disorder, as it is both in terms of the clinical presentation as well as the biology. but there's also important observation which is that these variations in the geno don't dtate necearily that somee will have autism. so already we're seeing that once we've identified regions that are clearly related to autism that there may be people who have that risk and do not end up with autism. there may be people who have that risk and, in fact, end up with schizophrenia. >> and also some who may not end up with either because they have genetic protective factors. >> exactly. so one of the beauties, i think, of gene discovery is that in some ways finding the genes is the simplest part of the problem everything sells more complicated in this case than the genome. but it gives you a starting point to begin to ask some of the same kinds of questions that are being asked at the most complex level down at the molecular level. how does a person with this mutation, what's the molecular mechanism of compensation or

resilience. >> as eric is implying, between the psychology and the genetics is the brain. and... (laughter) the hope is that although there may be 300 or 400 genetic risk factors they will mee on common thys. so a these genes are in that little sphere tucked inside the cell body. >> the nucleus. >> the nucleus. and all that genetic information is read and it maintain it is shape of the nerve cell and the function of the nerve cell. and one key function we've all been talking about is the connection that nerve cell makes with the next cell in line, called the synapse which literally means "to clasp." and some synapses are stimulating the next cell in line and some inhibit it. and the general theory-- which i ascribe to-- is that there is an

imbalance between this xi station and inhibition. almost too... the world is too much with us and the autistic child can't process information because of imbalances in those synapses in key areas of the brain. perhaps those areas in the temporal lobe, the superior temporal gyrus that were pointed out in your diagrams. but there are many, many, many proteins that influece notjust the function of the synapse but the stability of the synapse and the ability of that synapse to change with experience. so i think all of our hopes is the genetics will show us the way the key targets in the synapse which may be new therapeutic targets and which we can use as bio markers for whether we're going in the right direction, whether it's behavioral therapy or form a logic intervention. you asked is this a theory.

well, it is. but i think... everything we know about the brain is a sense of theory. this, to me, is one of the more compelling obvious areas ff further investigation and it thereby key for understanding neuropsychiatric disorders. >> i think it's fair to say that our understanding of the psychiatric... of the genetics of any strike disorder is extremely primitive. in the case of autism, it's probably somewhat more sophisticated than it is inthe ther areas. that's number one. number two, it isn't completely a theory. we have the finding that these areas don't communicate as well from uta's work and we have the findings from your work and from other people's work that some of the genes involved are actually involved in synaptic function. so certainly this is one of the contributing factors. >> i also think that the

genetics work is really leading us towards more personalized treatment. >> yes. >> and as we're discovering the different genetic underpinnings or the underlying biology we're better able to target treatment. particularly pharmaceutical treatments so where in the past i would take my daughter to see the psychiatrist he would say "well, you can try a little prozac or a little clonidine." and i would say "explain to me the mechanism of action by which that's going to help her." and there was no explanation. you could try this, maybe it will work; maybe not. but now that we're understanding the genetics and proteins associated with these gene it is treatments we're looking ain animal models are targeted and have a very defined mechanism of action and that's really hopeful for a lot of families. >> i think you make an absolutely beautiful point. this is true in all of medicine. our new insights into breast cancer and colon cancer come from seeing a disease that we used to think was unitary having

many subdivisions based on genetic subdivisions. and the reason we can treat some of these things better is because drugs that were quite effective but we didn't appreciate them were being used against inappropriate targets. once we know this particular gene is involved, this kind of colon cancer, we can direct the drug specifically for that and the outcome in some cases are really quite extraordinary. >> you know, one thing that's been remarkable is the influx of talent into this field. that people are coming to the field of autism both from cognitive science, from genetic ifs, if molecular, cellular biology to shed new light on it. i think it's been remarkable in the last five years the influx of talent. matt is an em. o psychiatrists interested in other disorders. your own work has uncovered key synaptic protein genes and we're finding that more and more and it's going to need a community

of scholars to really take these different hints and get to them >> i think it's completely understandable and you yourself appreciate, you know, the brain is hot. we really want to understand how we work and the brain is a way to get there so there's a tremendous influx into brain science, per se. but the thing tat is unique about he hum ain is socia interaction. this is a disease where the most uniquely human characteristic-- a child interacting with its mother-- what is more fundamental to human existence. so this is obviously an area that draws a lot of interest. >> rose: are you optimistic, alison? >> i'm more optimistic now than i have been over the last ten years. i think the investment we've made at the federal level and from individual advocacy organizations in autism is really starting to show dividends. i thk you heard about some of the research that's come to light in just the last few years

and how critical that's been to changing our view on how we can treat autism and how we can personalize treatment. i also think that there's been a large increase in awareness of autism and that that's led to a more compassionate community, one where our families don't to feel so afraid to take their children or their adults with autism out into the community. it really reduces the soci isolationhat a lotofur families have described for a long time. >> rose: as we learn new things, are we discarding old ideas about autism? >> i think one important idea that's been discarded... >> the mother. >> exactly. that it was the result of bad parenting and that parents of children with autism were too cold to properly bond with their child and that's what caused the child to retreat into their own world. my brother was diagnosed in the 1960s.

my mother was told that she w a refrigerator mother, too cold to bond with my brother and that his autism was her fault and that she should try hard we are the next child. >> the guilt that that spreads. >> oh! >> the suffering on the part of mothers is still evident today. >> we have to continue, actually to tell them. >> to make it clear to this has nothing to do with them. >> yes. >> many people feel guilty for passing on genes. even if it's in the sperm or the eggs, that it's their fault somehow and it's a major societal issue. >> rose: are you as excited about the genetic developments as matthew is? >> i find it very interesting but i would like to have that bridge built, you know, from the gene to the synapse to the whole nervous system to the brain networks and to the behavior. we do need to go from one to the other and there are many, many

steps to build in between. we can't just go along one thing and say we've dealt with the whole question. >> i think the oppornities to that now are just... >> they're just fantastic. >> rose: because we know more about genetics? >> because we have the tools now. >> and because of uta frith's work we know a lot about cognitive psychology. she and her husband have been very interested in and have received major awards for their work on social cognition. i should point out since i really like uta a great deal, she was the one that brought the attention of the scientific community in the united states and england to asperger. he was working in vienna, none was reading the german literature. she comes from germany. she translated his paper. this is written in 1943. 1991 she translated it. it's the first time that the english speaking scientific community became aware of his

work. so she brought this together and made them realize it's a much more heterogeneous disease because she emphasized that it's actually capable kids. >> can i add one other thing which i think really important in this story? it heed us so much more to understand the neurotypical social brain as well. >> yes. >> things that we would never have thought of. >> absolutely. >> who would have thought that there's an innate capacity to attribute mental state? we'd be crazy. but if you can look at the window through the pathology to look at what is actually happening. >> also, some soor m other things came out. the fact that there are some kids with autism who are quite creative. >> the interesting thing that we on't have here is a kind of disabilityble that is general. the interesting thing is that it tells you certain things can be great strengths, great independence of thought.

co-existing together with some real weaknesses in some other kinds of... >> it's so interesting because there's a real discussion-- you may have insights into this-- to what degree is their theory of mind in any other species besides hours? obviously there's capability for social interaction in many gup but whether or not this involves being able to mentalize is not at all clear. >> uta, i think you said something which is very avant-garde and very important. just using the words "the social brain" is a controversial concept. i think we must recognize the cost to society and to families of this predicament and i think the cost of not just the individual but to families and close relatives is enormous and it's unrelating. i know childr may ry well imroveithagebut is is a life long commitment to the child and for each family

member. i think alison... >> autism affects not only the person who's diagnosed but their entire extended family. the fact that my daughter only sleeps three or four hours a night and everyone. in my household is awake certainly affects the way my younger daughter performs in school the next day. one of us always has to be awake with her at night because we worry she'll leave the house, wander away. we know that children with autism sometimes wander and are hiby cars or drown or mee wit a terrible fate. but i think every parent wants to know wants to get inside their child's head even if just for two minutes and say what is the meaning of your behavior? what are you trying to tell me? how can i better help you? what is it that you want me to know? just to have that one minute window of understanding i think is every parent's greatest wish. >> so there's an urgency to-the-this that is... really

ourgt toe de clear. >> my daughter is severely affected. she is not really... she has severe cognitive disabilities. she has very minimal functional language. she's not really aware of the needs of other people. and, frankly, i... sometimes i think of that as a blessing. i think many of the kids who are hire functioning become so aware of the fact that they're different from their peers that that adds another layer of psychological issue to their autism. but my daughter is... the thing that concerns me most is that as e gs older her world is getting smaller and smaller. with most teenagers and adolescents as they get older their world expands. they have new experiences. they have experiences without their parents. that they go and they enter the world. the world for my daughter is getting smaller and smaller. she still watches the same "sesame street" videos as a 14-year-old that she watched

when she was two years old. her interests are not broadening they're narrowing. so we're constantly trying to think of ways to introduce her to new experience but in a wa that is comfortable for her. and that really requires going to a place ten times before she can even feel comfortable in that environment. and this requires patience and vigilance that i think a lot of the families describe. but it's... it's... it's something to aspire to. i think one of the things about families with children with autism is that they never give up hope. they're constantly trying to help their children improve. they're extremely resilient and hopeful and i think will ctinue to rse money and raise awareness and support research until we know what's causing autism and until we have treatments that are effective for all of our children. >> rose: i think we've just heard here what makes this whole understanding, this whole quest to understand the brain so exciting for those of us who put

together this program and also for people with just a general curiosity to understand who we are and why we are the way we are. and how central the brain is to that. so that's part of what makes this series and previous series so exciting f uso do. we've been talking here about the cognitive mind. >> next time we're going to speak about moods. you said, eric, next time we talk about moods. so we're going to talk about depression, when cep lynn began to focus on psychotic disorders he realized there were two major classes: dementia precox, schizophrenia, and disorders of mood. depression and manic-depressive scow sis. we'll consider that next time. depression is the most common psychiatric illness. aut 20million america sufr fr itevery year. and between the ages of about 15 and 40 it's the major cause of disability so not only is it a fascinating problem but it's an

enormous public health issue. >> rose: can't wait, thank you very much. and thank you. this extraordinary journey we take to understand the brain, to understand the diseased brain, to understand the functioning brain, to understand all of this as i said earlier who define who we are and why we are the way we are. see you next time. captioning sponsored by rose communications captioned by media access group at wgbh access.wgbh.org