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These are the user uploaded subtitles that are being translated: 01:40 good morning everyone it's a pleasure to 01:42 see you all here today my name is Paul 01:44 nurse I'm president of this university 01:47 Rockefeller University and I want to 01:50 warmly welcome you to our full parents 01:53 and science breakfast forum this is the 01:56 first of three lectures that we've 01:59 specially designed the parents this year 02:02 now this parents and science lecture 02:05 series is a resource for new city new 02:07 york city parents who are interested in 02:10 gaining new insight into child and 02:13 adolescent development what we're hoping 02:15 to do is to offer a forum where you can 02:18 learn about great science participate in 02:21 a dialogue and share your perspectives 02:24 all about raising children I 02:27 particularly want to thank the trustees 02:29 of the lubin Family Foundation some of 02:32 whom are here this morning and for 02:34 generously underwriting this second year 02:37 of this initiative it's really greatly 02:39 appreciated I also want to extend a 02:42 special welcome for those of you who are 02:45 visiting the University for the first 02:47 time and I hope that today's program 02:50 will acquaint you with this rather 02:52 extraordinary institution founded in 02:55 1901 as the first biomedical research 02:58 institute in the United States now since 03:02 then Rockefeller has made remarkable 03:04 contributions to biomedicine recognized 03:07 the world over Pratt's on your way into 03:11 the auditorium you noticed our new Nobel 03:14 Prize and Lasker Award wall it was on 03:18 your right as you came in it'll be on 03:20 your left as you go out now there's 23 03:24 scientists associated with Rockefeller 03:27 and were only a small institution who 03:29 have received the Nobel Prize this is 03:32 quite an extraordinary track record of 03:34 success I want to put that number in 03:36 perspective for you if Rockefeller 03:38 University were a country it will be 03:41 ranked in fourth in Nobel prizes in 03:45 medicine in chemistry in the world 03:47 behind the United States Britain and 03:49 Germany and actually ahead of France 03:52 which will be fifth 03:57 so also remarkably for of Rockefellers 04:01 23 noble or its received their prizes in 04:04 the past nine years so it's very current 04:06 but there are other metrics of 04:09 excellence I'll just mention a couple 04:11 over 20 Rockefeller scientists have 04:14 received the albert lasker award this is 04:16 the american nobel often known as that 04:19 for medicine it's frequently a predictor 04:23 of a future Nobel Prize and well over 04:25 half of our tenured faculty are members 04:28 of the National Academy of Sciences do 04:31 refer to your program books if you wish 04:33 to know more about this quite remarkable 04:35 University now today's program we have 04:39 with us several leaders in the effort to 04:42 advanced scientific knowledge about 04:44 autism spectrum disorders and also 04:47 several supporters and thunders of this 04:50 crucial work I want to particularly 04:52 recognize the Simons Foundation for its 04:55 commitment to autism research it 04:58 supports research here at Rockefeller 04:59 and many other institutions and Marilyn 05:02 Simon's is with us today great pleasure 05:05 to have her here and thank her for her 05:07 support in today's program which is the 05:12 autism enigma we're really very pleased 05:15 that dr. Catherine Lord is with us as 05:17 our guest speaker after her presentation 05:21 will hear a brief overview of basic 05:24 autism research from neuroscientist 05:25 Jerry fischbach who is a visiting 05:28 professor here at Rockefeller were very 05:30 pleased to have him here on our faculty 05:32 he also serves as a scientific director 05:34 of the Simon's foundations autism 05:38 research initiative following Jerry 05:41 Fishbach he his remarks heat Jerry will 05:45 moderate a panel discussion with dr. 05:48 Lord and with Rockefeller scientist nap 05:50 Hines are James and Marilyn Simon's 05:53 professor and 2,000 Nobel laureate Paul 05:56 greenguard our vincent astor professor 05:59 dr. heints and greengard worked together 06:02 on an autism research project here at 06:05 the University funded by the sign 06:07 foundation and after the panel 06:08 discussion I will then moderate 06:10 questions and answers from the audience 06:13 so it's a busy program I hope you're 06:16 hanging on to your seats it's my 06:20 pleasure to start it by introducing dr. 06:22 Catherine Lord who directs the 06:24 University of Michigan's autism and 06:26 communication disorders center we're 06:29 really honored to have her here today 06:31 please join me in welcoming dr. Lourdes 06:33 to the podium thank you thank you very 06:44 much for inviting me here and my goals 06:47 today are threefold one is to provide a 06:50 very general introduction to autism 06:52 spectrum disorders or asds some of you I 06:55 know more far more than I will ever know 06:58 about asds but some of you don't so I'm 07:00 going to start very simply second of all 07:03 is to introduce to you the science of 07:06 how we try to understand the behaviors 07:09 that characterize asds and then my 07:12 particular interest which is 07:13 trajectories and development that is how 07:15 children and adults change over time and 07:19 last I'm going to briefly touch upon 07:21 empirical findings about educational and 07:24 behavioral interventions with the idea 07:26 of leading us into the questions of what 07:29 is a SD and how does it respond to 07:32 different behavioral treatments and how 07:34 then my neurobiology help us figure out 07:37 what causes this and what we can do to 07:40 change it so as most of you know it 07:44 autism spectrum disorders are defined at 07:47 this point purely by behavior there's no 07:49 biological marker that will lets us do a 07:52 blood test or measure something and say 07:55 that a child or an adult has autism to 07:58 make things even more complicated asds 08:01 are defined by difficulties in three 08:03 areas social reciprocity communication 08:07 delay or deviants and restricted and 08:09 repetitive behaviors and what we've been 08:12 trying to do in the last few years is 08:14 figure out what are these areas what 08:16 makes them 08:17 obvious in some ways and yet so subtle 08:21 and others now asd at least some aspects 08:25 of asd really fall on a continuum so in 08:28 order to study asd we have to force 08:31 these continuum into categories but 08:36 really we know that the behavioral is 08:38 very the behavior is very and this is 08:41 just from a standardized diagnostic 08:43 instrument where these are scores so 08:46 from low to high high meaning more 08:47 abnormal and this is the cumulative 08:50 proportion of subjects these are all 08:52 children who are very young nonverbal 08:55 and equivalent in nonverbal skills and 08:59 these are typical children it just shows 09:00 you the range this is a hundred percent 09:02 so up to from twenty percent to a 09:04 hundred percent of kids with typical 09:06 kids have scores the very highest scores 09:09 were up to four whereas if we look at 09:11 kids with diagnosis of pdd-nos or mild 09:13 or autism we have much more variability 09:16 overlapping a little bit with the 09:18 typical kids and then we have kids with 09:20 autism without intellectual disabilities 09:23 and kids with autism with intellectual 09:25 disabilities what I want you to see here 09:28 is we can easily separate this group 09:30 from these groups but there is overlap 09:32 and if we need categories we have to 09:35 some degree force the categories and say 09:37 okay if you fall in here you have ASD if 09:41 you fall over here you don't have a SD 09:43 and then here are these kids that fall 09:45 in the middle now I'm going to try to 09:47 make this a little bit more real with 09:49 video tapes in a minute but we can make 09:52 reliable diagnosis of ASD down to age 09:56 two and maybe even younger and all the 09:59 way up through adulthood and we can 10:01 quantify the severity of ASD that is we 10:05 can measure how severe or how impacted 10:08 is a child's life by the behaviors 10:12 associated with ASD the trouble is that 10:15 really a prototype model which is sort 10:17 of like if you think about prototypes of 10:20 birds as sparrows and Robin's it 10:23 probably fits autism more than a linear 10:26 model that is we know a lot about kids 10:28 in here who have the 10:30 most clearly defined behaviors and we 10:33 can measure how different they are from 10:35 kids out here who have less clearly 10:37 defined behaviors and I can teach you to 10:40 draw this line right here if I want to 10:43 but this line isn't a real line between 10:45 autism and PDD I've just kind of made it 10:48 up because we have to figure out how to 10:51 quantify it so we can decide who has the 10:53 spectrum and we can decide how severe it 10:56 is but actually determining what are the 11:00 lines that are associated with biology 11:02 are not well decided in addition to make 11:07 this harder yes these are developmental 11:10 disorders that is they change with 11:12 development a child at two who has 11:14 autism does not look the same as that 11:17 same child will look when they're 10 or 11:19 20 or 30 years old a child who is for 11:23 with autism who is functioning at a 11:25 two-year-old level looks different than 11:28 a child who is for with autism who is 11:30 not intellectually disabled who's 11:32 functioning at his age level so we 11:34 always have to take development into 11:36 account in addition autism affects 11:39 development and I'll show you a little 11:42 bit in a minute how that might be but 11:45 for a child with autism who doesn't for 11:47 example ever have a friend they don't 11:49 get the feedback that friends give you 11:52 so the autism not only affects where you 11:55 start but it affects where you go now I 11:58 think this area is one of the greatest 12:01 areas of hope for treatment because if 12:04 we can change the experiences of 12:05 children with autism and not let them be 12:09 limited by their own disorder we may be 12:11 able to really change the trajectory now 12:15 in addition to that autism is defined 12:18 both by positive or abnormal behaviors 12:21 the things that you see immediately like 12:24 a child who is looking at their fingers 12:26 or smelling things or lining things up 12:28 or talking furiously about buffalo's but 12:33 it's also probably more importantly 12:35 defined by the absence or do munition of 12:39 normal social behaviors but that makes 12:42 the die 12:43 gnosis much more complicated because we 12:45 then have to know what is a normal 12:47 behavior in that context and many of us 12:50 have preconceptions about what normal 12:53 behaviors are that really aren't true at 12:55 all so in coming up with a diagnosis we 12:58 have to try to identify situations where 13:02 typical children do a very restricted 13:05 number of things so that we can see when 13:07 a child isn't doing typical things and I 13:10 put this slide up just because this is 13:12 from a summer camp with kids with autism 13:14 whom you who are not that different than 13:17 the kids i'm going to show you in a 13:18 minute or very little but if you look at 13:21 the very little ones you'd think i would 13:22 never imagine them eating pizza in the 13:24 rain in a summer camp what I'm going to 13:28 do now is show you just a few video 13:31 clips from a standardized observation 13:34 where we're trying to figure out how to 13:35 diagnose autism in two in toddlers and 13:38 what I'm going to show you first it's 13:41 just a short interaction between an 13:43 examiner and a child who's under 2 and 13:46 the first child in each set is a child 13:48 that we think or actually we know 13:50 because we've now followed them has 13:52 autism the second clip is a child who 13:54 does not have autism but has a language 13:57 delay and what I hope you will see is 14:01 that actually the differences are quite 14:03 subtle and are much more obvious when 14:05 you see the second clip that is see the 14:08 child that doesn't have autism when you 14:10 just see the child that does let's hope 14:13 this works so here the examiner is 14:15 teasing you and just seeing what happens 14:18 to this boy if you offer she offers on 14:20 the ball gun 14:22 oh and think about what isn't he doing 14:25 compared to this little boy who does not 14:27 have autism so in fact I know the 14:35 differences are not big but hopefully 14:38 there will be a theme here okay this 14:42 here she's blowing up a balloon letting 14:45 the balloon fly all over the room and 14:47 then she's going to pretend that 14:48 suddenly she can't get that balloon to 14:50 blow up so she's interested in what does 14:53 the child do to get her to blow the 14:55 balloon up or cheer her on as she 14:57 struggles with the balloon this is a 15:01 little boy that has autism and think 15:12 about what is he doing but what is he 15:14 not doing that you would expect a child 15:17 to those contexts and this is a little 15:21 ball with the language 15:26 Oh chadron one more time ya know what I 15:33 wanted you this is both little boys were 15:35 near her both little boys were moving 15:38 their bodies but there are differences 15:40 in how the first little boy and the 15:43 second little boy move their bodies and 15:45 the fact that the first the second 15:47 little boy looks right at her and 15:50 vocalizes even though he can't really 15:52 talk and gestures to her where does the 15:55 second little boy is actually trying to 15:57 use her to inflate that balloon so he 16:00 knows where that balloon goes so it's 16:02 not that he doesn't know what's going on 16:04 okay and then the last one I'm going to 16:07 talk over this because this is a little 16:08 bit long the examiner is and the mother 16:12 who's sitting over in the corner are 16:14 just going to ignore this little boy 16:16 he's been in the room with them for 16:17 about an hour is quite settled and 16:19 they're just going to ignore him this is 16:22 a little boy who has autism and i want 16:24 you to see what he does and again the 16:28 point is this is this is pretty subtle 16:30 we're looking more for the absence of 16:32 behaviors than the presence of abnormal 16:35 behaviors now in this setting the 16:44 average length of time when we ignore a 16:46 child for them to try to get our 16:48 attention is 15 seconds and we will go 16:56 for a minute which seems like a year but 16:59 my point is think about in this child's 17:02 life if for every minute or every five 17:05 minutes when someone isn't engaging him 17:08 if he doesn't engage them what does that 17:10 teach him about social development and 17:14 how does that affect his ability to get 17:16 information and listen this is a little 17:19 brown who is intellectually disabled 17:21 scooch amount maybe like the middle 17:23 between us let's see what his reaction 17:25 is to being ignored against and then you 17:27 can respond it so not autistic 17:52 that was busier with so my point is that 17:58 sorry this again is that that may seem 18:03 to you like we are like the fellow with 18:06 a microscope where we're obsessing over 18:08 tiny things but my point is these are 18:11 important things if a child is getting 18:14 radically different amounts of feedback 18:18 about from people and learning less from 18:22 people starting at 15 months or 18 18:26 months what does that do about brain 18:28 function and also what how can this 18:31 perhaps help us figure out what's going 18:33 awry now genetic studies of ASD began 18:38 with twin studies and what's interesting 18:40 about them are a number of things first 18:43 identical twins if you have a child with 18:46 autism who is an identical twin the 18:48 chances of the other child having a 18:50 autism are about sixty percent so much 18:54 higher than fraternal twins which is 18:56 problem is under ten percent and perhaps 18:59 under five percent so suggest there is a 19:02 genetic component to autism if you 19:05 include the broader phenotype that is 19:08 you include language delays high social 19:12 anxiety social aloofness than the 19:15 concordance or agreement in identical 19:18 twins for ASD like symptoms is ninety 19:20 percent so very high and this was the 19:23 start of autism genetics it was then 19:27 followed up by family studies that 19:29 suggested that if you have a child with 19:31 autism your chances go way up from say 19:35 one in a hundred and fifty to maybe one 19:37 in 20 or even higher of having another 19:41 child with ASD and your chances of 19:44 having a child with some kind of related 19:47 problem and that may be a language delay 19:49 that actually resolves itself are also 19:51 significantly higher now we'll hear more 19:54 from dr. fish back and I'm sure in our 19:56 conversations about them 19:58 ocular genetics that's followed up on 20:00 this but I think one of the important 20:03 behavioral things is that when people 20:05 took all of the twins of the twins study 20:08 so there were about 80 twins and they 20:11 randomly sorted them so instead of 20:12 matching them with their own twin they 20:14 match them with the twin that they 20:16 weren't related to it all and then they 20:18 looked at the pattern of differences in 20:20 verbal IQ between these randomly 20:23 generated to in pairs um this is the 20:26 range of a standard deviation and this 20:28 is this these outside lines are for the 20:32 twins that weren't related to each other 20:33 at all then you look at what is the 20:37 relationship in IQ between the kids the 20:39 twins that are their own identical twin 20:42 and it actually fits right in here with 20:45 the random distribution so what does 20:48 that mean it means that the genetics of 20:51 ASD are affecting autism spectrum but 20:55 there's still huge variation even with 20:58 identical twins in other factors like 21:01 verbal IQ so that you can see look at 21:04 this fifty percent of the population of 21:06 twins have a difference in verbal IQ 21:09 that's huge I mean it's over 60 points 21:13 so whatever is being transmitted is not 21:16 going quite along with verbal IQ now we 21:19 also know that within a population of 21:22 ASD we have incredible heterogeneity or 21:26 variability in language and this is just 21:28 a study we've done where we followed 21:30 about 200 kids from age 22 age 9 and 21:34 each one of these lines is a different 21:36 child learning language and you can see 21:39 this is normal this would be what normal 21:41 is there's everything from kids who are 21:43 doing extraordinarily well to kids who 21:46 are coming along much more slowly so we 21:50 have the case where we may have a number 21:53 of different ideologies we've got to 21:56 find these brain mechanisms that can 21:59 identity for all this all these 22:01 heterogeneity these differences in here 22:03 and I think what the twins remind us is 22:06 that even when we presumably 22:08 have the same ideology we can still have 22:11 heterogeneity we can still have a twin 22:14 who is highly verbal and can talk your 22:17 ear off and another twin who also has a 22:20 SD who is nonverbal now what does this 22:23 mean about treatment the most 22:27 well-established finding and behavioral 22:30 treatment of autism is that intensive 22:32 ABA results in improvements and this is 22:36 the most well-established lending form 22:38 analysed control trials these 22:39 improvements generally have been 22:41 measured in IQ and language scores and 22:44 results in improvements of about 10 or 22:46 20 points so that's great if you are say 22:50 have a verbal IQ I'm not trying to say 22:53 verbal IQ is the end of all of anything 22:55 but just because its measured of 70 22:58 going from 70 90 is incredibly important 23:01 if you have a verbal IQ of 30 going from 23:04 30 to 40 may make a big difference in 23:06 your life but it does not pull you into 23:09 normality on the other hand these are 23:12 very significant changes recently just 23:16 in the last five years there have been a 23:17 lot of very brief primarily parent 23:20 directed interventions around joint 23:23 attention those have shown smaller 23:25 changes they often involve just an hour 23:27 a week of working with parents but they 23:30 have shown consistent changes in 23:32 language attention and IQ in randomized 23:37 control trials there is also a huge 23:39 literature looking at very specific 23:41 kinds of behavioral plans and behavior 23:45 programs to reduce aggression to 23:47 increase communication that involve 23:51 doing very specific things and those 23:53 things are shown improvement so it's not 23:55 that we don't know anything but I think 23:58 we also realize that there are very 24:00 likely interactions between what the 24:02 child can do and can't do and 24:04 differences between children and also 24:07 differences in parents I mean somebody 24:09 just did a study showing that if you're 24:11 teaching a child by responding to their 24:14 initiations and you have a parent who's 24:17 very responsive your change you don't 24:19 change anything very 24:21 much if you have a parent who is not 24:22 very responsive you do so we need to 24:25 take into account the rest of the 24:27 environment now one thing I think we 24:30 have to remember though is autism is 24:32 very responsive to placebo effects now 24:36 the good thing is it means that hope and 24:38 whatever it is that gets to us when 24:40 we're doing interventions can really 24:43 make a difference on the other hand we 24:45 have to be very careful and this is data 24:47 from mystic RCT a randomized control 24:50 trial secretin and you can see these are 24:52 the kids who got the secretin these are 24:54 the placebo and actually this is scores 24:56 and irritability everybody went down and 24:59 in fact this was found in numerous sites 25:03 and I was part of it and actually was 25:05 sure something was actually happening it 25:07 was so exciting except that it was 25:10 happening for our control group just as 25:12 much as for the treatment group so what 25:16 I think I want to propose to you and to 25:19 get the neuroscientist to think about 25:21 today is that we need to understand what 25:24 goes awry and also what goes well and I 25:27 haven't talked about that very much nasd 25:30 as we plan interventions and as we try 25:33 to figure it out and we want to be very 25:34 careful that we're not trying to explain 25:38 a myth of what people thought autism was 25:41 50 years ago that is not really true in 25:45 addition it seems to me that we one way 25:48 to think about ASD is that it really 25:50 should be considered just along the 25:52 lines of like we would check for hearing 25:54 impairments or visual impairments it 25:57 should be a standard we should screen 25:59 for it but we also know that there are 26:01 kids who have multiple or all of us many 26:04 of us have multiple visual impairments 26:06 it's not just one thing it's multiple 26:08 things and all of those things need to 26:10 be addressed and treated and there is no 26:13 reason also that that should be 26:15 stigmatized I want to end just with a 26:18 note and again an example for you to see 26:21 just the variability in autism that I 26:24 think things are changing tremendously 26:27 in terms of changing the trajectories of 26:29 kids with ASD by starting early 26:33 changing social experience we can give 26:36 kids a whole different lease on life and 26:39 this is from our social group in 26:41 Michigan so this is produced directed 26:43 and written by them and I think what you 26:46 can think about here is sometimes I 26:48 would substitute the word ASD for Waldo 26:52 so hopefully this will play Oh welcome 26:59 to the where's father channel usually 27:03 usually mean nobody knows about all 27:07 those pastimes but we decided he's 27:10 always secretive but we decided to find 27:14 him and get an intimate look at his 27:17 personal life so here to enter me for 27:20 this interview is baldo himself where is 27:25 he first we'll know where you go all 27:29 right again so what I wanted you to see 27:33 is just that it is not that people with 27:35 autism have no sense of humor or no 27:38 creativity or no ability to work 27:40 together because this was film directed 27:42 and planned by them and I think the 27:45 point is we need to come up with models 27:47 that encompass everything from the 27:49 little boy that you saw flapping trying 27:52 to put the balloon in the researchers 27:54 now to this young man who's in regular 27:58 school and who sees himself as the next 28:01 marc forster or film director anyway on 28:04 that note let me thank you very much 28:11 hi I'm Jerry push back and I'm going to 28:15 moderate the panel but I'm also going to 28:19 give about 10 minutes of overview of the 28:22 biological and biochemical approaches 28:26 that are currently underway in studying 28:28 autism and the scientific director of 28:31 the Simons Foundation autism research 28:34 initiative and have been very interested 28:38 over the past two years and how to 28:39 approach this complex phenomenon through 28:45 laboratory science and I must tell you 28:47 right off the bat I'm become incredibly 28:50 optimistic this is a tough tough problem 28:53 the complexities we just saw a 28:55 clinically are multiplied when one tries 28:59 to approach this in the laboratory but 29:01 it is an exciting time in both 29:04 neuroscience and in genetics and I 29:07 believe that there is as much hope for 29:10 true insights about autism now than ever 29:13 in my scientific career of 45 years in 29:17 the laboratory so this is a valuable and 29:21 critical effort so Kathy went through 29:26 the definition of autism as changes in 29:29 social cognition changes in verbal 29:33 communication and changes in repetitive 29:35 and restrictive interests and I quite 29:38 agree that one must approach these as in 29:41 the full complexity and not trying to 29:44 explain all things by certain cellular 29:47 mechanisms but it is clear that the 29:52 autism is manifest through its action in 29:56 the nervous system and the brain the 29:59 human brain is I believe one of the most 30:01 complex objects in the known universe 30:03 it's about two and a half pounds but it 30:06 does have 100 to 200 billion cells and 30:10 the real complexity lies in the 30:13 connections between those cells in what 30:17 are called synapses because each cell 30:20 each of the 100 bill 30:22 in cells may make hundreds if not 30:24 thousands of connections with other 30:26 cells and that's not even where the 30:29 complexity lies the complexity lies in 30:32 the ability of those connections to 30:34 change with experience with 30:36 environmental input and with genetic 30:40 factors it's the plasticity of the brain 30:42 that offers its complexity but also 30:46 offers great hope for change and 30:49 recovery and education and therapeutics 30:52 this is a nerve cell it's like any other 30:56 cell in its outlines there's a nucleus 30:59 surrounded by a cytoplasm and a cell 31:03 membrane that keeps the cell intact the 31:06 genetic material is located in the 31:09 nucleus of that cell the DNA is packed 31:13 within the nucleus and instructions in 31:16 the DNA enable the manufacture of 31:19 proteins outside of the nucleus which 31:23 are distributed to all aspects of the 31:25 cell and it's these proteins that are 31:27 the building blocks of the cell that 31:30 ensure cell health and when there is 31:32 damage to a protein they lead to 31:35 disordered function the nerve cell has a 31:39 particular unusual shape it's polarized 31:44 that has a receiving service and a 31:47 communicating surface these genes in the 31:51 nucleus are what has been offered a 31:54 great deal of interest and increasing 31:58 research in recent years the human 32:01 genome and must of this is in recent 32:03 days the human genome the first draft of 32:06 the sequence was published in 2001 and 32:09 it's very clear the differences in our 32:12 genes are what this thing was you from 32:14 your neighbor and lead to diversity in 32:19 physical appearance and mental life 32:24 there are a number of ways people have 32:26 approached the genetics of autism as 32:29 kathy has said there's no question that 32:31 this is a genetic disorder and we must 32:34 undo 32:35 Stan the genetics that put people at 32:38 risk for autism I believe it's the best 32:41 way to understand environmental 32:43 influences is to understand the genes 32:46 that predispose to autism they may not 32:50 cause autism but they enhance the risk 32:53 for all sorts of environmental 32:56 influences and you've heard about many 32:58 of them in the lay press and in the 33:01 literature I think the best way to 33:04 understand truly what the environmental 33:06 risks are is to understand the genetic 33:08 risk factors now many people think of 33:11 genetics as having either an gene that's 33:15 functioning or one that is missing 33:18 perhaps because the the alphabet that 33:22 goes to make up the gene is wrong and 33:24 the genes code is misspelled and it no 33:28 longer makes a protein but it's now 33:31 become clear we really within the last 33:33 three or four years that it's not just a 33:37 yes or no issue one can have more or 33:42 less of the expression of a gene the 33:46 gene may be present but it may not be 33:49 speaking correctly to make proteins it 33:53 may be speaking too much so quantity is 33:56 important and gene expression is 33:59 critical and one approach is to look for 34:02 structural variations in the genome and 34:05 it turns out that ordinarily you inherit 34:08 one gene from your mother and one from 34:10 your father but since 2004 it's become 34:16 clear that some people have only one 34:19 copy of a certain gene some may have 34:21 three instead of the normal to some may 34:24 have four or five so quantity is 34:28 incredibly important and I show you this 34:31 slide simply to show you that the 34:33 technology is such that it is possible 34:36 to look through the whole genome in a 34:39 matter of a few minutes by cutting up 34:43 pieces of DNA 34:44 placing them as little spots microscopic 34:48 size spots on plates that are called 34:51 arrays and comparing one genome a 34:55 reference DNA with DNA from a test 34:59 subject let's say this is from a 35:02 participant in this study who has autism 35:04 and as you read along these gene are the 35:08 genome you can see just following the 35:10 blue line that in some cases the test 35:14 genome has a deletion or it may even 35:18 have a duplication and what has become 35:21 evident since 2007 I mentioning these 35:25 dates to tell you how recent these 35:28 advances have been that children with 35:31 autism have close to ten times as many 35:36 structural variations in their genome as 35:39 do control participants and the search 35:44 is on for what is in these segments of 35:47 deletions and duplications and how do 35:50 they affect the function of cells and 35:54 ultimately how do they affect the 35:56 behavior of children with autism let me 36:00 come back to our nerve cell one thing 36:02 that's very different about nerve cells 36:04 is that they form synapses they 36:09 communicate with other cells and impulse 36:12 once this cell adds up all of its inputs 36:16 from sensory information from activity 36:19 in the brain it send decides to send a 36:22 signal in the form of an electric 36:24 impulse out the the acts on the part of 36:29 the cell that communicates with other 36:31 cells now it's almost a truism but it's 36:35 a very it's an instructive way to think 36:37 of autism as a change in the timing of 36:41 these impulses there's something that's 36:44 not quite right and how these impulses 36:46 are orchestrated how they communicate 36:50 with the next cell in line and one real 36:52 possibility is that the defect may very 36:56 well be at these points of 36:58 or synapses that form between cells this 37:02 is a blown-up view of one of the 37:05 synapses when the impulse arrives right 37:09 at the end the nerve terminal is 37:14 signaled to release a chemical on to the 37:17 next cell in line it's called a 37:19 neurotransmitter and this transmitter 37:23 either excites the cell or it inhibits 37:25 it and it is critical to have the right 37:28 balance of excitation or inhibition to 37:33 in order to perform complex motor acts 37:35 sensory percepts and thoughts and 37:39 behaviors there is a gap between the 37:43 presynaptic the incoming cell and the 37:46 receiving cell and I want to talk about 37:48 that I'm going to give you a little bit 37:50 of detail to show you how rapidly the 37:54 genetics has advanced if I blow up this 37:57 segment the gap between the incoming 38:00 cell and the receiving cell it may look 38:03 like this the input releasing 38:06 transmitter and the postsynaptic 38:08 membrane receiving that transmitter and 38:13 I want to tell you a story at about a 38:15 black widow spider and the reason I've 38:18 included this is that it's my firm 38:20 belief but advances in autism will 38:23 really depend on advances in science in 38:27 many different areas so when we think of 38:30 supporting autism you must always think 38:34 of supporting research which is not 38:36 obviously related to autism it's the 38:39 whole enterprise which is critical this 38:42 story began with an interest in how of 38:45 venom from the black widow spider can 38:49 affect the communication between the 38:52 nerve terminal membrane and the membrane 38:55 on the receiving cell and indeed the 38:59 spider has a toxin that can be very 39:01 devastating to the synapse and within a 39:05 few years scientists in Texas and 39:08 England 39:08 and in other countries isolated this 39:12 venom and found out what molecules it 39:15 was affecting at the synapse this is a 39:19 drawing of the three dimensional 39:22 structure of these molecules this took 39:26 about a year after the discovery of the 39:28 molecules and they encode a family of 39:32 proteins called neuro directions in the 39:36 nerve terminal membrane and neuro 39:38 ligands in the postsynaptic cell 39:42 membrane these molecules are partners 39:44 they bind to each other and not only do 39:48 they cause these synapses to it here but 39:51 they seem to instruct the cell whether 39:54 to make an excitatory or an inhibitory 39:57 synapse now the interest from our view 40:03 this morning is that this is an insight 40:06 into how a synapse communicates and if 40:09 one believes as I do that autism is a 40:13 disorder in communication between cells 40:16 explaining the behaviors Kathy 40:18 Illustrated then we really have to learn 40:22 the whole cast of characters in the 40:25 incoming cell and the postsynaptic cell 40:28 none of these were now when I began in 40:32 science and when I studied synapses 40:34 throughout most of my career most of 40:37 these molecules shown here in this 40:39 cartoon have been discovered within the 40:42 last five to six years five to ten years 40:45 I would say but the striking thing is 40:48 the careful studies of families of those 40:52 copy number variants have pointed to 40:55 several molecules in the postsynaptic 40:58 and the presynaptic membrane that are 41:01 altered in children with autism so one 41:05 has the hope that we are on the right 41:08 track that if we understand more of 41:10 these alterations genetically we will 41:14 have a better handle on how they affect 41:17 synapses and community 41:19 pation and each one of these discoveries 41:22 offers the possibility of a new 41:25 therapeutic target to complement the 41:28 behavioral therapies that Kathy just 41:31 described now we won't be done there i 41:33 will i will tell you there's also hope 41:35 in the genetics maybe i'll end with us 41:39 to say once a gene is identified it can 41:42 be manipulated this is work of jay guy 41:47 and adrian bird in england where they 41:51 have identified a gene that leads to a 41:54 disorder that's similar to autism not 41:57 the same as autism and here they have 42:00 inserted the gene they have excuse me 42:06 they've removed the gene and without 42:08 going into detail it's possible to stop 42:11 the function of a gene by simply 42:14 inserting a stop signal in the genome 42:16 and when they did that the mouse they 42:19 they studied was obese and lethargic 42:29 this is a live movie in the mouse is 42:32 just not moving the striking thing is 42:38 this stop signal illustrating the power 42:42 of modern molecular genetics this stop 42:45 signal can be cut out and removed by 42:48 putting a chemical in the drinking water 42:50 so a jeans action can be stopped in this 42:54 case the stop signal and when they 42:57 looked at the mouse this is the same 42:58 mouse over here as we filmed as was 43:01 filmed here and when that mouse is 43:03 observed oops there it's thin it's 43:11 mobile and it's extremely promising to 43:15 me and hopeful that if a gene is 43:18 discovered hopeful for two counts is a 43:21 way to attack that gene and manipulate 43:24 it but also it says even here 43:28 a mouse that changes in the nervous 43:32 system are not permanent there is hope 43:34 in this type of experiment whether it's 43:36 in flies or worms or mice it suggests 43:41 that the plasticity of the brain is real 43:43 and that individuals can recover from 43:46 genetic and environmental factors now I 43:49 think because of the time I won't 43:51 continue but the next steps once we 43:54 discover genes is to find out where are 43:57 they working in the brain which circuits 44:01 in the brain are particularly vulnerable 44:02 and there's been great progress on that 44:05 front as well and but it perhaps in the 44:09 question-and-answer session we can 44:10 discuss that and then how those circuits 44:13 Walter behavior so we come to the table 44:17 with pull and matt and cathy i'm going 44:25 to start by asking questions and then i 44:27 think paul will come and leave a general 44:29 question and answer session Natalie I've 44:35 used a prototypic nerve cell but we know 44:38 that there are many many many different 44:41 kinds of nerve cells in the brain I know 44:44 that both you and pull are interested in 44:47 how you can study particular nerve cells 44:50 that might be involved in autism yeah I 44:53 would say the key question that we need 44:56 to address in animal models is which 44:58 circuits and cell types are affected in 45:00 these disorders and the way that you do 45:03 that is take genes that have been 45:06 implicated in humans make mouse models 45:09 like the one Jerry showed up there and 45:11 then ask in great detail out of the many 45:15 thousands of cell types that are present 45:17 in the brains in the brains of these 45:19 mice which ones are seriously impacted 45:21 by these genetic perturbations and Paul 45:24 and I over the last five years in our 45:26 laboratories and colleagues develop 45:29 novel methodology so that we can go 45:31 inside each one of those cells and tell 45:34 you exactly which proteins that comprise 45:38 the cell and which ones are altered in 45:41 any condition so this is a tremendous 45:44 advance because it not only gives us the 45:47 fundamental properties of the cell but 45:50 also tells us how those cells change in 45:53 let's say a mouse model of autism this 45:57 is the one way this is one way in which 45:59 you can ask ok and exactly what part of 46:02 the brain and exactly what cell and in 46:04 exactly what circuit are these have 46:07 animals abnormal and because we know 46:10 every protein made in that cell you can 46:14 also ask if these cells are abnormal 46:17 which proteins might we manipulate to 46:19 make them more normal so what we're 46:22 doing now is trying to use this 46:24 methodology to characterize the various 46:26 mouse models of autism and understand 46:29 the circuitry and the molecular 46:31 pathology in each of the cell types that 46:33 are relevant to the disease please 46:38 remember all this so you can ask 46:40 questions because it does bear 46:44 discussion and the only way to really 46:47 push these things as to ask is to ask 46:51 the questions no matter how focused you 46:55 think they are it's just tremendously 46:56 helpful to hearing your thoughts well 46:58 you've been interested in therapeutics 47:00 your whole career how would you approach 47:03 there are no good I think really 47:06 specific medicines independent of 47:09 behavioral therapy for autism but I know 47:11 you've been thinking about this and you 47:13 know how would you approach this the way 47:17 that men are approaching this on our 47:21 labs and by the way one of the most 47:24 important people in this is a young lady 47:26 in the third row Miriam Haman who I 47:28 would ask to stand up but she's very shy 47:30 and she'll be angry with me if I forced 47:33 her to do that I know there's she over 47:35 five years develop this extraordinarily 47:37 powerful technique so that is now as 47:41 matt said possible to look at all of the 47:44 proteins in any given individual nerve 47:46 cell type and try to understand in mouse 47:48 models of autism and the same concepts 47:52 can be applied to other 47:54 neurological and psychiatric disorders 47:56 to understand which cell types are 47:58 involved and which proteins in those 48:00 cells are involved the limitations right 48:03 now are the fact that whether to fold 48:07 let me tell you what the concept with 48:09 our concept was we would take these 48:12 mouse models of autism and then find out 48:16 what's wrong in those models and that's 48:19 what we're trying to do the one 48:22 difficulty there is that it's very hard 48:24 to get mouse mice to do the very 48:26 complicated behavioral things you saw 48:28 Cathy Lord show you it's impossible 48:32 basically so we have to hope that these 48:35 genetic changes that go on in the human 48:37 are in the initial steps very similar 48:40 ones that go on in the mouse and it is 48:42 faith in that possibility that arises 48:45 program another tool that we have 48:47 available is these the various 48:51 medications that have partial ability to 48:55 treat autism perhaps Kathy would like to 48:58 talk more about that but some of them 49:01 are effective with certain aspects of of 49:04 autism and others are not but we're 49:07 hoping using those same drugs that had 49:10 some i'll be at limited clinical 49:12 efficacy to study what happens in the 49:15 behave in the biochemistry of the mouse 49:17 models I'll throw something out there 49:24 and then if it just duds you can move on 49:26 but what like watching your little obese 49:29 Mouse who wasn't moving my first 49:31 reaction is if that was a child we would 49:34 be trying to figure out like why isn't 49:37 it and and what could we do to get it to 49:41 move and why is it obese and I mean and 49:43 in what are the factor how did it get 49:46 there so that's one question and then 49:49 how do we change that behavior partly 49:52 because kids with autism are here and we 49:55 can't just wait you know we can't wait 49:58 for the neuroscience while they're here 50:01 to figure out what to do but it but it 50:03 also struck me even as you are saying 50:05 you can't we can't do a baby a das with 50:07 a mouse and it wouldn't mean anything 50:09 but there's still a question isn't is 50:12 the mouse development so fast that you 50:16 can't look at how you get to a point 50:18 where you have something that you're 50:22 trying to account for does that mean yes 50:24 it does I mean Lee and many people will 50:28 question the use of my sand flies and 50:33 worms with with good reason but in some 50:35 cases but this is a case where a mouse 50:39 is not a human and you have to accept 50:40 what the mouse exhibits so while this is 50:43 not exhibiting social withdrawal or lack 50:48 of social communication we know this 50:52 gene is involved in a human disorder so 50:55 the animal was obese and a mobile that 50:58 points to a certain region of the brain 51:00 called the hypothalamus which is known 51:05 to regulate feeding behavior and weight 51:07 control and so but the hypothalamus has 51:12 many other functions including social 51:15 interaction functions and emotional tone 51:18 so it points to the hypothalamus and I 51:21 think this very important study has 51:24 attracted the interest of scientists to 51:26 go back to the hypothalamus perhaps 51:29 using and I think one of the 51:30 investigators that who does aadmi is 51:33 using your ribosome capture technology 51:38 to study genes in the hypothalamus 51:40 hoping to go from human to mouse and 51:43 then back to human so I think the 51:45 behavior is relevant I think this 51:48 reversibility of the phenotype of the 51:51 mouse that Jerry showed you is very 51:52 important because that's an instance 51:55 where you've provided the normal 51:58 function of the protein back in an adult 52:00 and in reverse the developmental 52:02 phenotypes so that's a stunning example 52:05 that if you can somehow intervene it's 52:09 not a permanent disorder the second 52:11 concept that everybody should take away 52:13 from this is that if we are able to 52:15 identify 52:16 the circuits that are involved in autism 52:19 spectrum disorders and I think we will 52:22 be through all of this intensive 52:24 research there are ways to treat search 52:26 circuits and improve their function that 52:29 don't necessarily require that we 52:31 reverse the initial pathologic event so 52:35 we can treat a piece of a circuit to 52:37 increase its activity or decrease its 52:39 activity to compensate for the 52:41 abnormality that's present this concept 52:45 is very important because in order to do 52:47 that we need to know what targets what 52:49 sells in once circuits we're going to 52:51 treat whole do you want to take some 52:58 question 53:00 I think we're close to time to opening 53:03 it up for questions from the audience I 53:05 think we're hearing that this disorder 53:08 is really an area that will profit from 53:13 study in a very wide range of 53:16 disciplines and models from observation 53:20 of children right down to molecular 53:23 genetics in mice and they all have their 53:25 contribution to make well I want to open 53:28 it up this discussion to questions from 53:30 the audience would you repeat the 53:32 question a question was could we comment 53:35 about vaccines and white noise as they 53:38 pertain to autism I know more about 53:41 vaccines than white noise but I think 53:44 that that there is no evidence that 53:47 vaccines cause autism at we can never 53:53 say and that for an individual child 53:56 that vaccines didn't contribute to 53:59 autism and we need to be careful because 54:00 they're there certainly could be a case 54:03 or cases where this figured in autism 54:07 but the two main reasons why people have 54:11 become concerned about the contribution 54:12 of vaccines to autism has been the 54:15 growing prevalence of autism thinking 54:19 that you know autism is increasing at 54:21 the time that we are having different 54:23 vaccines and babies are getting more 54:25 vaccines but i think it's become clear 54:30 that even when we take the components of 54:32 vaccines out which people had proposed 54:35 were contributing to autism and when the 54:37 particular vaccines I mean it's shifted 54:39 the argument of which vaccines and when 54:41 has changed numerous times in the last 54:44 20 years when those things change that 54:47 the prevalence of autism is continuing 54:50 to it grow certainly to some degree 54:53 because of changes in definition and 54:56 increasing awareness and then we don't 54:58 know but whatever it is it does not 55:00 follow the pattern of vaccines the 55:02 second source of concern about vaccines 55:06 came from work by Andrew Wakefield that 55:09 looked at an association between the MMR 55:12 vaccine and gastrointestinal 55:14 an autism that work has now been 55:16 repudiated on numerous levels numerous 55:20 times and so it's clear that that that 55:23 link is not there so I think where we 55:26 are left is it's very hard to prove the 55:28 null hypothesis to prove that vaccines 55:30 never caused autism and I think but I 55:34 think what we can say is that vaccines 55:37 prevent disease that can have very 55:41 serious effects and that is known and 55:44 there is no known link between vaccines 55:47 and autism now i know many parents 55:50 remain concern because there is a 55:53 phenomenon in autism which involves 55:55 losing skills or regression that does 55:57 occur at about the same time that 55:59 vaccines are given and this the 56:02 phenomenon of regression is very we 56:04 don't know what it means and it's very 56:06 hard to understand and it and it is very 56:09 heartbreaking for anybody who's ever 56:12 seen it and I think that link between 56:14 time and and vaccinations has has meant 56:18 that it's almost impossible to take away 56:21 the fear that families have but there 56:23 there is no controversy really that 56:26 vaccines are do not account for the 56:30 majority of cases of autism or even a 56:33 substantial minority white noise I've 56:36 just probably read you know things in 56:38 the media so so basically i don't i 56:42 don't know i should probably just stay 56:44 out of that one anybody else want to 56:45 comment on white noise i bet there any 56:49 comments from the rest of the panel 56:50 where any more comments from the rest of 56:54 the panel wonder where they kathy my 56:56 expected and why despite many studies 56:59 that have failed to provide evidence in 57:01 support of the vaccines hypothesis or 57:03 what isn't why this keeps on and on and 57:05 on it we took people won't let it die 57:08 it's a very it's a very powerful image 57:12 you know if a child at a certain age 57:15 receives many vaccines in a very short 57:18 period of time 57:19 and then apparently and I think this is 57:21 quite controversial apparently regreses 57:24 although on close observation many of 57:27 these children are exhibiting some signs 57:30 of the subtle ones Kathy pointed out 57:33 even before the vaccines but you know 57:36 the public does is not easily convinced 57:40 by probabilities then it's very hard 57:43 it's an issue i think in how we 57:45 communicate about science and a public 57:49 understanding of science I think the I 57:54 think the argument will keep coming back 57:56 and the concern coming back until we 57:58 understand more about molecular 58:00 mechanisms and the genetics of autism 58:03 there are people interested in immune 58:08 responses and immunology and once we 58:10 understand that I think then we'll have 58:13 a more direct test of the vaccine 58:15 hypothesis but I quite agree with Kathy 58:18 the overwhelming epidemiologic evidence 58:21 is negative there's no correlation with 58:26 vaccines and autism good so we I hope 58:29 the microphones now working who has it 58:30 yes thank you um I'm curious about the 58:34 treatment the potential treatment using 58:36 your obese Mouse study it's a two-part 58:40 question is the chemical stop that you 58:44 would use to reverse the phenotype is 58:47 that irreversible and or how long does 58:51 it last for just briefly i'll be glad to 58:53 talk to you about it later the 58:56 experiment i showed was was artificial 58:59 in the sense that a critical gene had 59:03 been identified and the investigator in 59:05 that study used a molecular trick to 59:09 turn off the gene as the animal 59:11 developed that's not that's not a 59:14 therapeutic it's it's an experimental 59:16 manipulation to turn off the gene and 59:19 then so there was something artificial 59:21 placed in the chromosome and then he was 59:24 able to remove that break on the gene 59:27 action so he demonstrated that when he 59:30 removed the 59:31 the gene could function again and the 59:34 animal recover but that's not a direct 59:36 route to a medicine but it points to the 59:40 possibility of a medicine I think that's 59:42 I think it's important to underline the 59:46 fact that that kind of experiment which 59:49 gave us a fundamental insight into 59:51 reversing the phenotype of these mice 59:53 can't be done in any species of mammal 59:56 except for mice so the genetic tools 60:00 that we have available to investigate 60:02 these diseases in this small animal are 60:05 actually critical for us to get game 60:07 fundamental insights into the disease we 60:10 couldn't do that experiment in a higher 60:13 mammal and the gene actually also wasn't 60:16 a gene for autism the gene was a gene 60:18 for rett syndrome so it's I think the 60:22 jury's point was this is a model for 60:24 what we hope to get to in terms of 60:29 eventual treatment the idea that this 60:31 may be able to work but it's not that 60:34 there's an autism gene that you can turn 60:35 off that makes mice that have autism 60:38 stop being autistic yeah so now I think 60:42 a question just here in the middle I'll 60:44 come to the front in a moment dr. fish 60:47 back you've mentioned environmental 60:49 factors as well but didn't go any 60:52 further so if you have a gene that's not 60:54 functioning that's impaired or the cells 60:57 aren't functioning properly and then 60:58 environmental factors such as toxins are 61:01 you know ingested and two small children 61:04 does this have an effect on their their 61:09 development and could this autism 61:11 spectrum develop at this time I've ever 61:14 read so many articles on children that 61:16 have a reduction of toxins and all of a 61:19 sudden they're seen to have a huge 61:21 improvement you just didn't really go 61:24 any further with the environmental 61:25 factors it's a complex phenomenon I 61:31 think there are many things that can 61:34 modify the action of genes and that's 61:37 what I think offers so much hope that 61:40 there are genes that increase the risk 61:42 and there are modifier genes that might 61:45 actually decrease the risk so it's not 61:48 going to be I think what kathy was 61:50 getting at one gene one disorder I think 61:54 there's we're going to have to deal with 61:56 a mathematical approach to understanding 61:59 how these genes interact and what the 62:02 final cellular result is what the final 62:06 circuit result is and then hopefully 62:08 what the final behavioral result is as 62:11 we move up the ladder so I'm I don't 62:14 know of any modifiers yet but I think we 62:18 can't rule those out right could we in 62:22 the front the gentleman in the front 62:24 could you wait for the microphone is 62:26 just coming so one comment was one of 62:30 the debates is whether this is a 62:31 systemic disease or is really limited to 62:33 the neurologic system the CNB difference 62:36 between autism children and not is that 62:41 limited to a subset of genes or family 62:43 of jeans or is a genome-wide the second 62:46 question which is for or comment for dr. 62:48 Heinz's there are some clinical clues as 62:51 to therapies that at least when you look 62:53 at large registries of data or more 62:55 helpful than others and those might as 62:57 you start identify proteins and families 62:59 of proteins involved give you some some 63:01 greater in size to therapeutic 63:03 approaches so I'll be brief on the first 63:06 one remember the study I cider was 2007 63:10 many people are asking are these copy 63:14 number variants recurrent how common are 63:17 they do they are we seeing them over the 63:20 same ones over and over again the answer 63:23 is there may be fifty to a hundred of 63:25 them 63:26 and they may occur in one to two percent 63:28 of the population at risk but we're just 63:32 now and the Simons Foundation is 63:35 involved in a very large study to see 63:37 are there hot spots in the genome where 63:41 there are certain variants which are 63:43 really much more likely to recur we 63:46 don't know that yet good what was the 63:52 second any more comment not do you want 63:54 to comment further the second part of 63:56 the question was about therapies and I 63:58 think Paul outline this but because we 64:02 can look at the molecular events that 64:04 occur in any cell type in response to 64:06 let's say a genetic perturbation we can 64:09 look also at these events in response to 64:12 any therapy so any therapy that is 64:14 either that is relevant and important 64:17 for our treating autism that's developed 64:20 we can assess in mice and try to figure 64:22 out what circuits it's actually 64:25 impacting this is critical if we're 64:27 going to develop new therapies I think 64:31 there was a question in the front yes 64:33 what is the relationship between a what 64:38 is the relationship between the gastro 64:41 internal problems in autistic children 64:43 as well as behavioral problems and 64:45 autistic children and the toxicity of 64:46 what they eat like unprocessed foods 64:49 processed food excuse me 64:53 we don't know I mean I mean there's 64:58 there's there's certainly reason to 65:01 believe that if you have 65:02 gastrointestinal problems that is going 65:04 to affect your behavior so I think I 65:06 think we need to remember that anybody 65:08 who is uncomfortable or in pain is going 65:11 to act differently and I don't think we 65:13 should negate that I mean I'll say 65:15 quickly of I have there's a 20 year old 65:18 young man that I've known forever who is 65:20 here in New York who I just saw and his 65:23 father told me last weekend he said to 65:25 the boy or young man said to his dad dad 65:29 my heart's on flame and he pulled his 65:32 shirt up and said can you blow on my 65:35 heart and make the flame go down and 65:37 then he said that's you know his name or 65:40 say johnny johnny has sad heart johnny 65:44 wants a happy heart and i think i think 65:47 he probably had heartburn is i mean i 65:50 don't i don't know and i don't think 65:52 anyone knows but i think he was trying 65:54 to say that he had some kind of 65:57 indigestion but out but you know he 66:00 can't talk about that and so I think 66:02 that does contribute to this is a boy 66:05 who can be very aggressive when he's 66:07 unhappy and and we've been trying to 66:10 figure out why has he been so aggressive 66:12 recently so I think that link just you 66:15 know just the same length that it would 66:17 have for anybody is something we can't 66:19 discount in addition you know I think 66:21 that there have been hypotheses about 66:23 more complex links between GI function 66:27 and brain function which so far have not 66:29 stood up on any end as far as like I can 66:33 tell those are not over did you know I 66:35 want to be emphasize a point that the 66:38 the brain is not sitting up here in 66:41 isolation from the rest of the body 66:43 indeed we have nerves throughout every 66:47 organ in the body especially the bowel 66:49 and weary and the brain receives inputs 66:52 and a very real sense our sense of self 66:56 is is is in large part determined by 67:00 impulses that arrived from different 67:03 organs in the body 67:04 do you are you feeling pain are you as 67:08 your stomach upset all these things 67:11 offer a certain continuity to the self 67:13 so I am I especially am interested in 67:16 what are called these autonomic uh most 67:19 unconscious inputs from the body to the 67:23 brain and there's a great deal of 67:24 interest now in neuroscience to 67:27 understand how these inputs eventually 67:30 influence behavior and conscious 67:33 behavior where the union is between 67:35 these unconscious inter effective some 67:39 people call them inputs and conscious 67:42 behavior and I think it's a very 67:44 understudied phenomenon there certainly 67:46 are genes in common between the bowel 67:49 and the brain and many children come to 67:54 the doctors the food this was always my 67:57 night miracle that I would be cool while 68:03 I was saying something brilliant they're 68:08 endangered happen between the brain in 68:11 the bell and and um so we have to be 68:15 aware of all the time but i agree with 68:17 kathy that there's no obvious clinical 68:20 connection yet and how it gets back to 68:22 unprocessed food we don't know but i 68:24 think we probably all wonder pole one 68:29 important aspect of what is it an 68:31 autistic a research that we've not 68:34 really emphasized today and we should 68:35 have has to do with the heterogeneity of 68:38 the disease it was implied in the slides 68:40 and kathy showed on autism spectrum 68:43 disorder but it's actually a whole bunch 68:46 of different diseases and this is 68:48 somewhat slow down progress in fact this 68:51 program that Jerry talked about that the 68:54 Simons Foundation is carrying out 68:57 involves looking at these different 68:59 subclasses of autism and trying to get 69:01 the genetic basis for each of these as 69:03 separate disease entities and once that 69:05 information is generated and from what 69:08 he told me yesterday this will be in the 69:10 next year or two we'll have a pretty 69:12 complete story of the genetic basis for 69:14 each of these subclasses of autism 69:17 we then a lot more rapid progress being 69:19 made in the laboratory and trying to 69:21 understand the molecular consequences of 69:24 these genetic mutations in the 69:26 individual types of participant an 69:28 article appeared just one edition in the 69:31 New England Journal of Medicine last 69:33 year saying the children with autism 69:36 seem to improve when they have a fever 69:40 and this is another example and Marilyn 69:44 and Jim have told me repeatedly from 69:45 from personal experience that this seems 69:49 to be the case and again it's an example 69:51 of these unconscious functions of the 69:54 hypothalamus and fever and we must learn 69:57 what those connections are in the middle 70:01 yeah hi um I think the reason why the 70:07 vaccine issue will keep coming up and 70:10 many of the questions you're receiving 70:13 will keep hounding the scientific 70:15 community is because all parents of 70:17 children anywhere on this spectrum want 70:21 to be partners in resolving this issue 70:23 while we wait for science to catch up to 70:26 the need and so my question is for dr. 70:29 Lord as a parent walks in with a very 70:32 young child and his first thrown into 70:35 this world of a child they can't relate 70:38 to or control or soothe what do you what 70:42 how do you impart if any wisdom to the 70:45 parent to comfort them so that they can 70:47 be a partner at home is there a general 70:52 dietary suggestion to vary the diet to 70:57 limit certain foods or two soothing 71:00 music are there any general therapeutic 71:04 recommendations that you make to a very 71:06 lost parent I think that our focus is 71:13 very much on behavior I mean trying to 71:15 see what it is that the child can do 71:17 because kids can you know all kids can 71:20 do some things I'm trying to see what 71:23 our kids interested in and then trying 71:26 to see what is holding them back and 71:28 then trying to piece together 71:30 they're those aspects of behavior so 71:33 that the world makes more sense to the 71:35 child so that the child can communicate 71:37 the things that they're thinking but 71:39 then also to pull that child into our 71:42 world as much as we can in a pleasant 71:46 way I think we also want parents to be 71:49 parents and I think what's what's hard 71:52 is that I think parents of children with 71:55 autism are immediately tossed into a 71:57 world where they have to be protectors 72:00 advocates business managers you know 72:05 scientific you know wardens in some ways 72:10 and and I think trying to be able to say 72:13 all right what does this what can we do 72:15 with your child now and where is this 72:17 going not in 20 years but for tomorrow 72:20 what do we want your child to be able to 72:23 learn and then let's look at the good 72:25 things or child can do and take those 72:27 strengths and try to use those to build 72:32 up the things that are hard also not 72:34 forget the strengths because in the end 72:35 those strings are going to make it as 72:37 much of a difference as the hard thing 72:39 so I think we don't put people on diets 72:42 I mean many families that we see do have 72:45 kick it said kids on diets and I think 72:47 certainly being sensible about what your 72:49 child eats is true for any parent but I 72:54 think that we don't think there's a 72:55 single key there's just you know taking 72:59 it one step at a time that's hard though 73:02 because it's a pretty overwhelming 73:04 experience and many of you can testify 73:06 about that far far more than I can but I 73:09 think also remembering their kids you 73:12 know and their kid you know there are 73:14 all kinds of things about being kids 73:15 things you like things you don't like 73:17 things you can't do things you won't do 73:19 and how do we work around that and not 73:22 forget ultimately this is a person you 73:25 know they're here and and in a family 73:28 and not let that get you know tossed by 73:31 the wayside I think we still have a 73:35 couple more questions over here at the 73:37 very well there's two there so one there 73:39 and then one at the back 73:41 a question why do we see this more often 73:47 in boys than girls if we could answer 73:51 that question you want to answer the key 73:54 question and you know the what many 73:56 people would say right away is that it 73:59 has something to do with the X 74:00 chromosome but the best data to date are 74:03 that that's not true so again it's these 74:06 modifying factors there's something 74:09 about the women and the dimorphism and 74:13 women are not identical with men 74:17 something about the dimorphism in the 74:19 body and the brain that might be 74:21 protective is one hypothesis hi thank 74:27 you as the mother of an 11 year old 74:29 Asperger's son I'm curious dr. Lord you 74:33 were talking you had a young man at the 74:35 on your video and you you had a social 74:39 group or something I found in my 74:42 experience that I have tried every 74:45 traditional psychotherapy cbt sort of to 74:50 enhance his social ability and it I was 74:55 struck by my suspicion is that your 74:59 group was for observation purposes or 75:01 have you or have you found benefit 75:03 through a social skills group and things 75:07 like that we have found some benefit 75:09 with medication we run groups that mean 75:17 we call social groups there I think that 75:20 partly we feel they work but partly our 75:23 expectations are quite different than a 75:25 social skills group I mean these groups 75:27 run forever I mean the kids now I mean 75:30 they're now a hierarchy so we have eight 75:32 of them in Michigan and like the teens 75:34 all want to move into the older teens 75:36 group and the older teens into the 75:37 adults people do move out of them I mean 75:40 if they get a social life that is that 75:42 you know they have something better to 75:43 do but I think what we our first line of 75:47 our first goal is shared enjoyment we 75:50 want it to be positive we want the kids 75:52 to interact 75:52 each other we also include typical peers 75:55 and then the idea is not to teach us 75:58 skill but for each participant in the 76:01 group these are these are clinical 76:03 groups we have goals for that child so 76:06 that's this the boy that you saw but is 76:08 very interested in interacting he has 76:11 all kinds of approaches the problem is 76:13 not that he doesn't want to be around 76:14 people it said he doesn't know quite 76:16 what to do and he's the kind of kid 76:18 who'd go right up to the nose of the 76:19 person that he likes and talk in their 76:22 face and so a goal is let's back off I 76:25 mean for him and another child the goal 76:29 may be getting them into the group so we 76:31 have very pragmatic goals we just 76:33 readjust those goals about every three 76:35 months with the parents and other 76:37 teachers and then in the groups which 76:39 meet for about an hour and a half once a 76:41 week we try to create positive 76:44 activities that really pull the kids 76:47 into social interaction I think our 76:49 hypothesis is that many almost all kids 76:53 with autism and adults don't have enough 76:56 opportunities to interact with other 76:58 people because other people don't stay 76:59 with them long enough but if you do stay 77:02 with them people like them and they like 77:04 other people so we're trying to create 77:07 that and you know my fantasy is that 77:10 this you know this will move on I mean 77:13 we did have for example a group three 77:15 men in the adult group just rented an 77:18 apartment next door to our clinic much 77:20 to our surprise but they did it I know 77:23 on their own so that's where we're 77:25 trying to go and we have some data where 77:28 we follow this where what we show is 77:31 changes not so much in high level skills 77:34 immediately but long-term changes in the 77:37 positive attitude toward people 77:39 assumption that someone will like you if 77:42 you tolerate them decreases in 77:44 inappropriate behavior and then just 77:47 changes for example in proximity when 77:49 you walk into a room in the group how 77:51 long does it take you to get me 77:53 interacting with someone else that kind 77:55 of thing so we're not claiming we're 77:58 curing anything but it does feel like 78:00 relationships are really developing 78:03 and that's what we want to do we feel 78:05 like if we can set the stage for that to 78:07 happen and then provide guidance sort of 78:11 in the background then then good things 78:13 will happen that again are just one drop 78:16 in the bucket so there are many other 78:18 approaches that need to go on at the 78:20 same time I'm afraid I'm going to have 78:22 to stop the questions there because 78:25 we're over running thank you very much 78:28 to our speakers thank you for our 78:29 panelists thank you 78:41 you73726