Katie Wright on the Lack of Precision in Dr. Shafali Jeste's "On the Road to Precision Health: Brain Based Biomarkers.”
By Katie Wright
I recently watched Dr. Shafali Jeste’s* (see bio at end of this post) of the UCLA Jeste Lab for Autism Research and Treatment SFARI presentation “On the Road to Precision Health: Brain Based Biomarkers.”
Dr. Jeste and partner Dr. Dan Geschwind believe they will be able to phenotype and treat ASD people via EEG. Everything about that is crazy. Listen, these are brilliant scientists who sincerely want to help the ASD community, however, they are doing everything wrong. This is what happens when researchers are insulated from the wider community.
It can be very difficult and painful to admit you have been wrong. Believe me, I know something about this. When Christian was an infant, I laughed at a friend of mine who advised me to to give Christian one vaccine at a time over a spread out schedule. Guess whose child had severe adverse vaccine reactions- not hers. The neurologists and geneticists have everything at stake in the “autism is a heritable brain based genetic disorder,” paradigm. Not too long ago researchers including Jeste argued that we would eventually be able to phenotype everyone with autism via genetics. 20 years and almost a billion dollars later, no success. Not only no success phenotyping via genetics no success creating treatment via genetic models. It has been a disaster.
For at least 15 years geneticists have been promising “precision therapy” and “targeted treatment.” These ubiquitous buzzwords are no bereft of meaning. In 2007 I was directed to take Christian to genetics specialist for “targeted treatment.” Sounds good, right? The problem is there is nothing wrong or unusual with his genes, nor the genes of 90% of people with DSMdx autism. A parent may be told that their child this unusual gene or that deletion, yet plenty of non ASD people have those genes. Genetics tests often show vulnerability but almost never causation.
This is because there are no “autism genes.”
There are genetic susceptibilities sure, but autism is not like Downs syndrome. Autism susceptibility genes are like alcoholism or obesity genes. One can be born with a vulnerability to a disorder or disease but it does not manifest itself without an environmental trigger. No one goes to bed 150lb and wakes up 250 lbs- surprise you are obese! A person who never drinks alcohol can never be an alcoholic. It takes a genetic predisposition, a family history and exposure to the environmental trigger for obesity, alcoholism and autism to develop. In the case of autism, there may be no family history of autism but a genetic vulnerability to autoimmune diseases. Parkinson's, Grave’s disease and diabetes, for example, feature prominently in the family history of ASD people.
In most, but not all, cases of moderate to severe ASD, autism is a multifactorial, environmental triggered, immune mediated disease. To be clear I am speaking only about moderate to severe autism. HF ASD, what used to be called Aspergers, seems to be something else entirely.
OK, back to Dr. Jeste. To her credit she catalogued all the failed genetically driven clinical intervention trials. Suffice it to say it is a LONG list. Donepezil, Mavolgurant, Abacoflen....Let’s take a closer look at one of the biggest failures- Seaside Therapeutics.
Former AS Science Director, Dr. Rob Ring, was a diehard believer in the idea that we would soon be able to diagnosis and treat autism solely via genetic profiles. Ring eagerly invested over $2million of AS money (so easy to spend $ you did not earn!) into Seaside Therapeutics’ study on Fragile X/ ASD children. His predecessor, Dr. Geri Dawson was also an enthusiastic proponent of this venture. Neither Dawson nor Ring would listen to any fact based concerns, primarily that Fragile X was a poor autism research model. Ring was especially vehement that the study would succeed. A number of ASD parents tried to make Ring understand how different FX was to non syndromic (the other 90%) autism. Ring, having no experience teaching, treating or even interacting with autistic people, insisted that he knew better and that any FXS treatment would easily translate to to non genetic ASD.
Naturally, Ring and Dawson were completely wrong. The Seaside FXS project was a hugely expensive failure. Interestingly, the FX kids, did indeed, experience behavioral improvements. That makes sense because they were the treatment model! But Bac had no impact on non FX ASD.
Dr. Jeste spoke her clinical intervention failures using 22Q kids as ASD treatment models. Jeste seemed to believe that a bigger sample size would have yielded benefits. No! The idea of more of our tax $ going into this black hole is preposterous. Jeste did briefly mention that the fact that her studies enroll higher functioning, healthy, albeit with genetic disorders kids, may be part of the problem but she clearly believed the real stumbling block was the sample size.
I have been reading through a number of recently published papers on the failure of FXS research. Dr. Tim Chiang found that FXS kids have “very different speech, motor and development issues” than non FX ASD children.” L. Abbeduto’s research concluded that “the onset, symptomology, developmental trajectory between FXS and ASD differs in important ways.” Even more significantly, J. Roberts’ work concluded that “FXS has a unique neuro-endocrine profile,” so different from that of non FX and ASD children. Another important difference is the fact ASD people have high cortisol levels (the struggle with fight or flight), FXS children do not. Finally, if Jeste and others were to argue that these are fringe opinions, Dr. Thurman of the NIH has published numerous studies elucidating the problematic and significant differences between FXS and ASD.
NIH’s Dr. A. Thurman states: “ It has been assumed that ASD symptoms reflect the same underlying psychological and neurobiological impairments in FXS and ASD which has lead to the claim that targeted pharma treatments that are efficacious for the core symptoms of FXS will be beneficial to non FX ASD as well. Yet, neurobiological substrates of behavioral impairments represent important clinical differences...a more symptoms based, less syndromic (genetic) based approach is needed.”
Layman’s terms - FXS, 22Q, Tuberous Sclerosis etc...research will not help the other 9o% of people with ASD.
In the same vein as FX, it’s often cited that 50% of children with Tuberous Sclerosis have autism. TS is a very serious disease involving reoccurring brain tumors. Not surprisingly, TS children frequently suffer from epilepsy and have developmental delays. Rob Ring was insistent, as he was with FX, that a massive investment into TS “autism” would yield real “targeted treatments” for non TS ASD children. Well a decade and many millions of dollars later - nothing, nada, rien...Absolutely no success at all. While there are behavioral and biological overlaps, very, very few TS children meet the official criteria for autism.
Jeste spoke at length about doing EEG work on “ASD” 22q11 children. It has been commonly assumed that 50% of 22Q kids also have ASD. That never made sense to me. The 22Q kids I have meet seem positively happy! They do have significant development delays but always seemed social and have more in common with Downs syndrome kids than ASD children. In 2013 MIND researchers who used the 22Q “autistic” kids as ASD research samples started to ask questions. Dr. Tony Simon noticed that these “autistic” children “have a very high level of social motivation. They (22Q) get a lot of pleasure from social interaction and are socially skilled.” Tony administered the DSM ASD criteria test to each one of his 29 22Q “autistic” subjects and found NONE of them actually had autism. In another 22Q “autism” study researcher K. Angkustsiri re tested her 22Q subjects and found that none of those children meet official ASD criteria either. Indeed, it is obvious that 22Q is a very different disorder altogether, involving heart problems and serious malformations in the head.
Ok, so I think we know that problem with Dr. Jeste’s research is not that she needed a larger sample size of FXS or 22Q “autistic” subjects.
The second critical problem with Jeste’s research is her insistence that we will be able to phenotype ASD kids via EEG! I know, insane, right? If there are ASD Moms and Dads reading this they know what I mean. Despite incredibly kind and patient technicians, it was a torturous process getting my son’s EEG done. Autistic kids, by nature, do not enjoy being touched by strangers or held captive, prone on a table while electrodes are glued to their heads. My son, Christian, absolutely hated the feeling of the nodules on his head. The removal process was just as traumatic. Christian actually has epilepsy and still his 72 hr EEG was minimally remarkable. It is a crude tool unless you are administering a relatively complex test at the time of the EEG. Only HF ASD people would willingly be fitted with an EEG. And only HF ASD people could engage in a conversation while hooked up to an EEG. I think kids like mine would rather hug strangers on the street.
In order to demonstrate that the EEG was a easy tool to use on autistic subjects, De. Jeste shared a video of an autistic girl with an EEG cap on. The girl was smiling and looked so happy, skipping around with the equipment on her head. Indeed, Dr. Jeste said that this girl loved the process and loved the EEG equipment so much she kept it. Guess what? That “autistic” subject had 22Q! NO one with real moderate to severe ASD wants an EEG done, nevermind enjoy the process. How could the investigators make such obvious errors? Are they so wedded to belief that autism is primarily genetic that they refuse to see the obvious signs that most of “syndromic autism,” is not autism at all?
There was much discussion about how EEGs will leverage information about genetic etiologies - sure, but for kids who don’t have autism! So much is wrong with this stubbornly naive assumption. 1) FXS and 22Q “autism” research has been a tremendous failure for a reason- these children don’t have autism and 2) one cannot phenotype autism via genetic etiologies- that has been tried and tried for 20 years and failed. 3) autism is more than a neck up disorder! 4) It is 2018 we know in singleton autism (the most common kind) is 60% environmental in cause and 5) Two factors that are as important, if not more important than genetics (and 100% more actionable), in the phenotyping of autism are and autistic person’s micro biome and the immune system.
I am sure there are many children with genetic disorders who do indeed have DSM dx autism, just far fewer than we have been lead to believe. If I were a parent of a FX child who had some ASD features I would want the ASD dx to get more services for my child. I am all for ANY label that helps children get services. The only thing that needs to change is that researchers must stop using FX, 22Q, Tuberous Sclerosis kids as research templates for autism.
NIH’s Dr. Audrey Thurman is right. We are getting nowhere via the “syndromic autism” studies, symptoms orientated research is the way forward. We can’t waste more time. Most of our children are really struggling and often living with pain and/or life threatening conditions like intractable epilepsy. Research GI issues, GI treatment, the miracle seizure stopper Charlotte’s Web for epilepsy (vs. endless research into epilepsy genes), study the biology of regression (not just the behavioral aspects), study medical marijuana for severe self injurious behavior, study autoimmune interventions for regression and PANDAS, etc...In short help autistic people.
* Dr. Jeste is a behavioral child neurologist specializing in autism and related neurodevelopmental disorders. She is an Associate Professor in Psychiatry and Neurology in the UCLA David Geffen School of Medicine, and a lead investigator within UCLA Center for Autism Research and Treatment (CART).
Dr. Jeste’s research is focused on the use of novel electrophysiological biomarkers to better define early predictors of autism spectrum disorder (ASD) and to define more homogeneous, brain-based subgroups within the autism spectrum in order to inform treatment targets. She has designed innovative studies in early predictors of ASD to focus on the integration of biomarkers with behavior to define atypical development prior to the onset of clinical symptoms. Within this framework, she has been investigating and treating infants and children with neurogenetic syndromes associated with ASD. She is the principal investigator of several studies, including early development and intervention for infants with tuberous sclerosis complex and the UCLA Autism Center of Excellence study of high-risk infant siblings. Dr. Jeste serves as the UCLA site director for a multisite National Institutes of Health Autism Biomarkers Consortium for Clinical Trials research study. Clinically, she evaluates and treats patients with ASD and neurological comorbidities, and directs the UCLA Developmental Neurogenetics Clinic. Dr. Jeste has published more than 50 peer-reviewed articles and has been the recipient of the Child Neurology Foundation’s Researcher-in-Training Award and the American Academy of Neurology’s Clinical Researcher-in- Training Award. She serves on the board of directors for the Child Neurology Foundation and was elected to serve on the board of directors for the International Society for Autism Research
Katie Wright is Contributing Editor to Age of Autism.
Apropos of genetics: corrected misreporting of NASA’s twin research.
“After a stream of erroneous media coverage about how spaceflight affects astronauts' genes, NASA issued an updated statement… Scott's DNA did not fundamentally change. What researchers did observe are changes in gene expression, which is how your body reacts to your environment.”
Posted by: nhokkanen | March 17, 2018 at 11:55 AM
Yes, absolutely yes to all of this. When my son was very young I willingly participated in this research- one of the studies I participated in was word-retrieval in parents of children with autism. That was the first time I thought WTH is going on here?! These PhDs get in their little niche and they can't even see the absolute devastation. Our kids' generation is on fire and they will spend millions doing MRIs of infant siblings for over a decade and come up with absolutely nothing (Joe Piven of UNC- I'm looking at your useless life's work) of any value to eliminate this mass scale suffering of our children. How do they sleep at night? How do they get up in the morning and look at themselves in the mirror and be okay with accepting these millions and hire assistants and set up a lab and not produce ANYTHING? What new treatments are there? How can we PREVENT autism? Joe Piven spoke to an autism group- a large assembly of parents and one parent asked him about the connection between gastrointestinal disease and ASD (the AAP statement had just come out confirming GI disorders were highly prevalent in ASD) and he flat out denied there was any link. Just straight up denied the existence. Can these people be any more irrelevant?
Posted by: Kristine | March 16, 2018 at 02:20 PM
Anna, I was also curious about that comment. I don't think high functioning autism is different. I think it is just a less severe reaction to the environmental trigger and/or the amount of the trigger. Just as people react differently to a drug or drug dose so did ASD infants react to their trigger(s). For many infants that trigger was their vaccines.
Posted by: Greta | March 16, 2018 at 02:16 PM
My post didn't go through yesterday. I want to know how High Functioning Autism is "something else entirely." My son has high functioning autism and this is the first time I've encountered this idea.
Posted by: Anna Quandt | March 16, 2018 at 11:37 AM
In other words we could congratulate this scientist on helping almost no one. Like a weatherman, who gets paid no matter how wrong his is, but does it every day with a smile and an open invitation to come back for more.
Katie, you refer to several other known genetic medical conditions, for instance down's syndrome. At this point, knowing what I know about autism, I can't help but contemplate down's and maybe others are simply a different case of poisoning, maybe vaccine-based poisoning, especially taking into account what is known about auto immune medical patterns in the parent's of patients with autism. In other words, what if those with regressive autism are actually not the most susceptible to vaccine damage, what if they are actually the patients with moderate susceptibility, and those born with down's or non-regressive autism, etc, were actually the most susceptible, provoking the idea that because they are "born with it" that it must be genetic, thereby deeply ingraining the genetic research direction of those medical conditions, surpassing even the efforts to corral regressive autism into a genetic definition. What percentage of down's syndrome is seen in the parental vaccinated population vs the parental non-vaccinated population?
Given the overlap in down's and autism diagnosis and the fact that down's syndrome is often diagnosed inutero, undoubtedly leading to a higher level of terminated pregnancy in that sub-population, I have to assume that today's autism rates, apocalyptic as they are, would be even higher if not for what has happened in the down's world.
Posted by: Jenny | March 16, 2018 at 09:30 AM
Please forgive my typos,............ I am up very early and care for a disabled and incompetent adult son. In this group I likely need not apologize. Autism affects a village.
Posted by: Mark Wax | March 16, 2018 at 07:41 AM
Thank u all for reading and sharing your insight and humor!
Posted by: Katie Wright | March 15, 2018 at 11:36 PM
Thanks for all you do Katie.
Has anyone been over to Autism Speaks to see the present efforts with the search for the “Autism gene?” ... I would suppose those excited scientists could talk for hours about the money rolling in and their "rock star science" efforts.
If the CDC put out a few million dollars for someone to locate the “Thalidomide gene” so they could start using that fine product safely on pregnant mothers to “create wealth” in America... there would be dozens ready to take the money & start searching.
Posted by: go Trump | March 15, 2018 at 08:38 PM
Aimee & Dawn- totally right - why did the NIH not even read the Gov Accountability Report scolding them for redundant work?
Max- agree re COI
Jill & Cia - I hear u- same w/ my son
Brett- I want to be there if they ever find the stupid gene
Nancy- NIH have "Do nothing but look busy!" down to a science
Posted by: Katie Wright | March 15, 2018 at 07:06 PM
I tried to do it right, too, and took my baby for separate appointments to space out the vaccines I permitted her to get: separate appointments for Hib doses 1, 2, 3, DTaP doses 1, 2, 3, and then 4 at 18 months, polio doses 1, 2, and 3 at 12 months. A T booster at nearly 5 years old, by itself. She reacted to the DTaP booster all by itself with losing her only words and being diagnosed with autism two months later. The hep-b at birth, given without permission, was disastrous: giving any vaccine at birth is a calamity for many, many newborns.
I don't think Alzheimer's is completely different. I reacted with screaming syndrome to the first DPT at three months old, and grew up with what I much later (when my daughter was four and I started to read about autism) realized was Asperger's. My brother, who beat his head on the bars of his crib for months after his first DPT, also reacted with Asperger's. His oldest son much later reacted with Asperger's. Mine reacted with screaming syndrome (vaccine encephalitis) and autism. But it's on the same continuum. Those who react to a vaccine, but not extremely severely, may wind up with Asperger's. The more severely you react, the worse the autism. The younger the infant, the more likely the reaction will be severe, but it can be very severe, even fatal, at any age.
Absolutely! Autism depends on an environmental trigger being pulled, nearly always vaccines. Moskowitz discusses this in his brilliant book Vaccination, with regard to many other serious conditions being triggered, not only autism. The " scientists" are going about this all wrong, but I really can't believe that they mean well, all of this is so obvious with minimal research. Like with the language therapy, it's obvious that they need to repair the neural circuits in the brain damaged by the vaccine encephalitis with extensive modeling and practice of each discrete grammatical structure and vocabulary/cultural item over and over, with increasing independence and contextual inventiveness. Why is this not standard therapy for the autistic? It is so obvious.
Posted by: cia parker | March 15, 2018 at 03:46 PM
@Jill - I agree with you - I have almost completely lost my respect for doctors. How can they not care about an epidemic that gets worse every year? How can they not care about the majority of individuals on the ASD spectrum - who have medical and psychological needs that go untreated (except for toxic psychiatric medication). And I really don't get it, for those who are working in the autism research field, how they can feel they are actually accomplishing anything. And wouldn't years of failure be a wakeup call? I guess not.
I agree that Pharma is the enemy and doctors are the supply chain. But I think the neurodiverse movement shares some blame- for portraying autism as a gift, not a disability, but a difference - which of course, makes the epidemic look less serious.
Posted by: Aimee Doyle | March 15, 2018 at 03:25 PM
Whenever I read about these money-wasting genes-only research failures, an old bumper sticker springs to mind: “Jesus Is Coming - Everyone Look Busy.”
In 2002 and beyond, parents filled autism listservs with written reports showing causal patterns amongst their children’s physical symptoms — and their own. It was common knowledge way back then that disproportionately high numbers of autism parents either suffered some form of autoimmune disorder, or it ran through their family history.
Tragically these predispositions to triggered immune dysfunction have largely been ignored by the medical research community. Parental health aberrations would be a critically useful place to start in identifying susceptibility to vaccine injury — but instead, CDC and AAP continue with their irresponsible one-size-fits-all vaccination policy. This refusal to tailor medical treatments toward individual physical tolerance amounts to malpractice.
Posted by: nhokkanen | March 15, 2018 at 12:56 PM
Maybe one day parents of autistic kids will discover a gene in scientists that prevents them from recognizing that the autism epidemic is caused primarily by an epidemic of environmental toxins found primarily in vaccines.
Posted by: Brett Wilcox | March 15, 2018 at 11:05 AM
Great points, Katie! Parents should be directing and approving the research. Until then the government is wasting too much money. Our children are regressing into autism diagnoses, not born with it. It’s not genetic and the overemphasis of genetic research feels deliberately misguided and takes away from truly researching the causes. Genetic research zeal is taking away from our finding out why our children regressed into autism and now have lives with severe multi symptomatic underlying medical conditions which present with autism behaviors.
Posted by: Dawn L | March 15, 2018 at 09:50 AM
Reminder (because we must never let them forget :
JULIE GERBERDING, DR., CDC DIRECTOR: “Well, you know, I don’t have all the facts because I still haven’t been able to review the case files myself. But my understanding is that the child has a — what we think is a rare mitochondrial disorder. And children that have this disease, anything that stresses them creates a situation where their cells just can’t make enough energy to keep their brains functioning normally. Now, we all know that vaccines can occasionally cause fevers in kids. So if a child was immunized, got a fever, had other complications from the vaccines. And if you’re predisposed with the mitochondrial disorder, it can certainly set off some damage. Some of the symptoms can be symptoms that have characteristics of autism.”
The projection for autism is set to be 1 in 2 by 2030 , and 80% of all boys. Seneff
This is a holocaust, deliberate in nature, the bilderbergs \ freemasons are behind it.
Here is the scoundrel Offit admitting vaccines cause autism, and further admitting they plan to deny it forever. Embarrassing film footage for him.
Posted by: Hans Litten | March 15, 2018 at 09:42 AM
Another clever fox in charge of the false autism gene hen house...she missed a bit she never said ,what we do know its nothing whatsoever to do with vaccines.
Pharma For Prison
Posted by: Angus Files | March 15, 2018 at 09:35 AM
Excellent post. However, please don't throw a bone to the neurodiverse crowd by stating "In most, but not all, cases of moderate to severe ASD, autism is a multifactorial, environmental triggered, immune mediated disease. To be clear I am speaking only about moderate to severe autism. HF ASD, what used to be called Aspergers, seems to be something else entirely."
Autism is a spectrum, and there is no evidence that HF ASD is "something else entirely," other than the the fact that it is a milder form. Many infants and children have regressed after environmental assault such as vaccination to HF autism, or have regressed to moderate or severe autism, and then recovered to the point of having HF autism. It's not "something else entirely."
Posted by: Facts R Facts | March 15, 2018 at 09:29 AM
Thank you Katie. You hit the nail on the head. The "research" doctors are completely insulated from the real world of autism, yet they hold themselves as the experts. Any typical (the 90%) parent of a son/daughter with autism will tell you that science needs to concentrate on gut and immune issues (as the gut is the cornerstone of our immune system!) Gee, I'm not even a rocket scientist!. Our community has been saying this for over 20 years. My daughter is 25 this summer. She has come so far. From the get go in 1996 when she was 2 1/2, I knew that the doctors would never help us. They patted me on the shoulder and told me that it was genetic, it was always gong to happen and just to take her home and love her. She lived completely in her own box. No language, no eye contact, constant screaming, major repetitive behavior, black circles under her eyes, etc. Yeah, just take her home and love her. Here is your label, pay at the front desk and don't let the door hit you on the way out. No attempt at all to engage with her, no plan of action. I was in the same boat with many other parents and their children. Just take your kid out of here, buckle her in her car seat (while screaming bloody murder) and go away. After all these years, they are still separate from our reality. I have so little respect for most doctors today. Pharma is the real enemy, but the doctors are the supply chain. The 2016 numbers for autism are staggering. One in 36. If they had One in 36 kids with the measles, it would be front page news, the lead story on the 24 hours news feed. We don't hear about the the numbers for autism because they don't want to have a conversation. They just want to shut us up.
Posted by: Jill | March 15, 2018 at 09:04 AM
Katie and I do not even no one another. No conspiracy possible. The best idea we share is that the most obvious reasoning is usually the best judgement. My son was poisoned. His response to a round of vaccines is no coincidence. That is because there are no coincidences in the universe. Everything is causal. Take a good look around. The masters of the universe are just better equipped at convincing people the relative degree of the causes. Or, the seemingly infinite myriad of possibilities surrounding any event. Their point of view is inextricably tied to their financial interests. They are definitely "predisposed" to that one. There is not one single argument that makes science beholden to the "greater good." In fact, there is no such thing as "settled science." Of this I am certain: You can't find something that you are not looking for. As Katie points out. Most of these folks are not trying to help those suffering from autism. They may call themselves scientists, but I think that is merely the correlation of a few symbols after their name and a society where money rules us all.
Posted by: Mark Wax | March 15, 2018 at 07:52 AM
Katie - I always love your articles. Thank you for another interesting post.
I am so fed up with autism research - and autism researchers. My son is 28 years old. We have tried literally everything to help him - medical (conventional to alternative to downright fringe), educational, therapeutic. He has made progress, but I don't see a cure in his future. Like 2/3 of the ASD spectrum, he will need lifelong care and support.
I don't understand why Congress never listened to the GAO report from a few years back - that panned the IACC. I don't understand why they keeping funding crap genetic studies or eye-gaze studies or (fill in your preferred useless area of research).
Posted by: Aimee Doyle | March 15, 2018 at 07:38 AM
Fascinating, Katie. Thank you.
Posted by: susan welch | March 15, 2018 at 07:03 AM