February 3, 2025 • 54 mins
In this episode, we explore the intricate world of autism research with Jill Escher, a dedicated philanthropist, lawyer, and parent to two Autistic young adults. Jill's journey into Autism advocacy was sparked by her children's diagnoses, with no prior family history, leading her to significant roles like president of the National Council on Severe Autism and leadership at the Autism Society in the San Francisco Bay Area. Through the Escher Fund for Autism, she examines the causes beyond genetics, investigating how environmental and biological factors might alter gene expression, contributing to Autism's heritability.
Jill challenges the conventional genetic focus in Autism research, arguing that it fails to explain the increasing prevalence of Autism. She delves into complex topics like epigenetics and transcriptional regulation, proposing these might unlock the heritability puzzle of Autism. Her research includes looking at how factors like general anesthesia can affect future generations. Escher also discusses the hurdles in Autism research, including scientific dogma and the influence of the neurodiversity movement, urging for a more comprehensive approach to address what she sees as a looming national health crisis.
Jill Escher https://www.jillescher.com
Other Resources
Autism and the Womb https://youtu.be/NOVp4mIroug
The Relationship of the Placenta, Womb, and Development https://youtu.be/Mj5h5DOMcRw
0:00 Intro
1:18 Jill's Journey into Autism
4:25 Jill's Family & Autism
7:19 Research & Advocacy in Autism
10:19 Genetic & Heritability Explanation
13:05 Non-Genetic Factors; Epigenetics
21:08 Anesthesia; Germ Cell; Proliferation
26:29 Early Brain Development; Gene Expression; RNA; Molecular level
27:56 Research needs; Genetics & Dead End data; Society & Preparation of Prevalence
33:57 Rates of Autism & Future (& Current) Emergency
38:16 Vaccination
41:25 Migration; Excitation/Inhibition Imbalance; Functional Connectivity
48:02 Barriers in Autism; Jill's Contact Information
53:33 Reviews/Ratings
Hopp: https://www.hopp.bio/fromthespectrum
YT: https://www.youtube.com/channel/UCGxEzLKXkjppo3nqmpXpzuA
email: info.fromthespectrum@gmail.com
Mark as Played
Transcript
Episode Transcript
Available transcripts are automatically generated. Complete accuracy is not guaranteed.
(00:00):
My guest today is Jill Escher.
(00:03):
Jill is a philanthropist focused on autism research,
a lawyer, and a mother of two autistic children.
More accurately, there are now young adults.
Jill is the president of the National Council on Severe Autism,
and a former president and current board member of the Autism Society, San Francisco Bay Area.
(00:26):
Through her work with the Escher Fund for Autism,
Jill leads innovative research investigating the causes of autism.
Her research enhances our understanding and pushes the boundaries of what we know about autism.
One example Jill explains during the episode involves research on germ cells.
(00:49):
The ability to question and expand research allows us to explore new regions of interest
for understanding the causes of the autistic phenotype.
Please see the show notes for links to Jill's work in her research.
In addition, there are resources from previous episodes that support the timelines discussed in today's episode.
(01:14):
And now my conversation with Jill Escher.
Jill, can we start with you kind of telling us your journey into autism?
And I really want to add that I've heard you say recently that, and I'll quote, I wasn't looking for autism.
Autism found me.
(01:36):
Yeah, pretty much, pretty much, I mean, I grew up in the 60s and 70s into the 80s, and I had hardly heard of autism at all.
I had never met anybody with autism.
Even somebody who we might apply the label to today, I really can't think of anybody, you know, with traits, like my kids are similar,
(01:58):
all that ever come across.
Then I had three children, my husband and I have a 27 year old young man, a 25, almost 26 year old young man, and an 18 year old young lady.
And the latter two, the 20, almost 26 year old man and the 18 year old young woman are both profoundly autistic and nonverbal.
(02:24):
So, you know, these were very shocking, both times very shocking diagnoses.
Again, we had nothing like autism in our family histories.
We didn't know people with autism.
It was not something we read about nothing we saw in the news.
It was not on our radar at all.
(02:47):
Like when I was pregnant with my sons, I mean, it just, it just didn't even occur to me that it was something I would even think about.
Like, I thought, you know, you know, you're pregnant, you think about, oh, maybe you're a kid with Down syndrome or maybe a kid would have a birth defect or whatever.
It just didn't even occur to me that, you know, autism would be a possibility.
(03:09):
So when Johnny, who was born in 1999 was diagnosed in 2001, it was like, what are you even talking about?
Like, you know, the neurologist who had assessed him when he was about two and a half, you know, saw very obviously that he had very severe classic autism.
(03:30):
But we're like, where did, where did that come from?
And even I will say, Ryan, to this day, nobody knows where these devastating disorders came from in our son Johnny or our daughter Sophie.
They are idiopathic as are the majority of cases of autism.
(03:51):
There were no risk factors in my pregnancies. Again, nothing up our family trees to suggest that autism could be a risk.
So this remains to me a, a, a, a, a, a, a, abominable mystery as it is in most cases.
So that's how autism came to me.
It was not something I was, I was at all looking for.
I was a lawyer at the time that I had Johnny and I had anticipated a career in land use law.
(04:21):
I had a whole other world going on.
And then this just sort of got dropped like a bomb.
Wow.
How long was it after,
I have a couple of questions about what you just said,
but the first one is,
how long was it after the birth of Johnny,
did you kind of say something,
(04:44):
what is going on here?
And then kind of take that role into now,
what you do now?
Right, well, the birth of Johnny,
again, it was very shocking,
it kind of threw our life course
in a completely different direction.
This happens with, I'd say most autism families, right?
(05:05):
You're going a certain direction,
you have certain understandings about the world,
you have certain expectations about what your children will be,
you have certain expectations about how your family
is gonna operate, and then boom,
you just get flung in a completely different direction.
And at first, I think like most families,
you really wanna figure out what to do to help your child.
(05:26):
That was the first priority out the bat.
You're like, well, there must be something
we can do about it.
So Johnny was really a poster child for autism.
I mean, when he was little,
he was flapping his hands,
he would always look at little things,
little objects, little corners, little intersections,
he went in the pavement,
he would chew things all the time,
he couldn't talk, he didn't respond to his name,
(05:48):
he never pointed, he never shared or showed,
he was very irritable, he had trouble sleeping,
he had very weird food, no predilections,
I mean, there's so many different things
that Johnny had, it's like every check mark,
check, check, check, check, check, he had all of them.
But he was physically quite normal,
(06:09):
except he had an abnormally large head,
which again is seen in the subset of kids with autism,
autism is abnormally large head circumference.
And that persists to this day, actually.
Yeah, again, really unexplained,
because the CT scan that was done at 12 months was abnormal,
(06:31):
was normal, and so of course it remains idiopathic.
But he's a normal guy, healthy guy,
nothing else, nothing you would expect
from a disorder, a mental disorder of this magnitude,
usually when you have an intellectual disability
of this magnitude, it's accompanied
by physical abnormalities, facial dysmorphisms,
(06:53):
things like that, and that was not the case with Johnny.
So anyway, so I got flung in this other direction,
very interested in how to help my kids.
And like most moms, I tried everything,
like I tried the diet, I tried taking him to speech therapy,
I tried taking him to occupational therapy,
(07:13):
I tried sensory therapies,
different kinds of classes, ABA, intervention programs.
I mean, I didn't do like the weirder things,
like hyperbaric oxygen,
or some of the crazier interventions you hear of.
(07:35):
But nothing really seemed to move Johnny
off of his trajectory at all, at all.
So that was pretty fearless.
By the time Sophie was born,
and she was displaying all those check marks of autism,
she had some language, I was like echolalic,
but she didn't have any conversational language.
(07:56):
She wasn't playing with toys, right?
That's really a hallmark when they're not playing with toys
and they're not demonstrating the capacity
for abstract thought.
And when they're not imitating,
and they're not sharing and showing and pointing
and acquiring words, like whenever I'm with
like a typical two-year-old,
I'm always astonished at what sponges they are, right?
(08:16):
They're just taking in everything
and they're learning vocabulary very rapidly.
My kids, none of that.
So by the time Sophie came along,
you know, we knew what was going on.
And she was identified with autism by 18 months.
Such an eye mirror.
Yeah, I mean, this was like two kids with severe,
(08:40):
you know, neurodevelopmental abnormality.
And again, you know, we don't know why.
So, you know, I've really been devoting my life
to pushing for answers.
Yeah.
My understanding is you sorted a couple of,
correct me if I'm wrong, a nonprofit
(09:01):
or this organization or foundation
that can you tell me a little bit about that?
I know there's a couple of them actually, but.
Yeah, so I've been involved with several,
several nonprofits.
So everyone kind of fits a different bucket.
So I'm very interested in research.
So I have a fund, a philanthropic fund,
(09:23):
which we call Escher Fund for Autism.
And all it does is it funds pilot research studies
that look at novel ideas
about what might be causing autism.
We also do quite a bit of advocacy for research,
research advocacy, but I think our primary goal
(09:44):
is to fund pilot studies.
I've also published quite a bit
in the scientific literature in partnership
with other scientists about these questions
that we explore.
And I'm involved in other ways in the autism field,
non-research things.
For example, I'm a co-founder
of the National Council on Severe Autism,
(10:05):
and I'm past president of Autism Society,
San Francisco Bay Area.
Yeah, yeah, it's still on the wall.
Yeah, so I do a lot and other things too,
but those are the main ones.
Okay.
What are some of the highlights
of the pilot study research?
Yeah, so we, yeah, like our focus,
so I'm sure a lot of your listeners are aware
(10:28):
that autism is highly heritable, right?
It's conjectured to be strongly genetic
because it's highly heritable.
So for example, if you have one child with autism,
you have like a 16 to 20% chance
of having a second child with autism.
That's how strongly heritable it is.
Not that autism really runs down ancestries.
(10:49):
We don't see any strong evidence for that at all.
It's not like, great-grandparent, grandparent,
you know, blah, blah, blah, blah.
I mean, that'll happen from time to time,
but that's not a strong driver of autism.
Most of the heritability is seen
because of increased risk among siblings
or even, you know, among half siblings
and to a slightly lesser degree.
(11:12):
So the question is why?
What is causing this herit?
Why does autism, quote unquote, run in families like that?
That is the question that we focus on.
Almost all, I would say 99.9% of the attention
in the funding has gone into genetics.
Thinkin', well, Jill has, you know,
(11:35):
Johnny and Sophie and they both have profound autism.
So therefore Jill and or her husband must be carrying genes
that, you know, raise that risk of autism in their children.
Right, and that's the thinking.
That's been the paradigm that has dominated autism research
for, I don't know, 15 years.
(11:55):
I would say a good 15 years is hunting for the genes
that cause autism.
Now those genes come in two flavors.
The first flavor is what they call a rare variant.
And that's usually something that,
like a mutation of some sort
that causes some fairly severe phenotype.
(12:17):
And we can think of lots and lots of examples of that.
You know, you can look up on the Simon's Foundation gene list,
you know, the 100-ish genes that are associated
with autism in that way.
The other flavor that the genes come in,
(12:39):
it are what they call common variants.
So they're variants that are normally harmless
and they occur in more than 5% of people.
They're normally harmless.
But the idea is, their theory is that
those common variants can, you know,
somehow conflate together to increase the risk
(13:01):
for autism in the child.
Now there is almost no evidence for that.
There's a little bit of evidence, but it's so weak
that it's, you know, it doesn't amount to much.
There's very strong evidence for rare variants
causing autism in rare cases.
(13:21):
And by the way, with those rare variants,
none of them explain more than 1% of the autism.
So they are indeed very rare even in the autism world.
So my kids, you know, have none of that.
And most of the kids with autism
and adults with autism don't have any genetic factors
that are known.
So I look at, well, what else is causing the heritability
(13:44):
if it's not the genes where everyone else is looking, right?
9.9% of the people,
they're looking at genes.
I'm looking at non-genetic factors, if that makes sense.
Yeah.
What are some of the interesting findings you found
with the non-genetic factors?
Yeah, it's a little complex.
And so I do want to kind of say at the outset
(14:05):
that I apologize for anything that's complicated.
I really try not to make things too hard
because people tend to resist complex biology.
It's not because they're stupid,
but because it's not something they're schooled in.
(14:25):
But the stuff I do is I have to say
pretty advanced molecular biology,
but I'll try to do my best to simplify it.
All right, so everyone knows what a gene is, I think.
A gene is a sequence of letters, really.
Sequence of bases in your DNA.
(14:46):
They are transcribed and they are made into a protein,
and that protein does something.
For example, in the brain,
that protein can help create a neuron
or help create something that moves a neuron
from one place to another in development.
So the proteins have multiple functions.
(15:07):
If something goes wrong in the gene,
that means something goes wrong in the protein there,
it means something goes wrong in the tissue,
which means something goes wrong in the organ,
right, and you have some sort of disorder or condition.
All right, that's pretty straightforward.
That's textbook high school biology.
What's not textbook high school biology
is something called epigenetics
(15:28):
or transcriptional regulation.
Okay, so again, people hear these words,
they get a little bit scared, don't run away,
it's not that hard.
So you can have the effect of a mutation
without having a mutation,
i.e. all of those letters, all those base pairs
(15:49):
in the DNA can be perfectly normal.
You will have a perfectly normal scan of your genome
if you're genetically tested.
However, the problem is it's not just
the genetic code that matters.
What also matters is how those genes are expressed.
(16:13):
What happens to them, right, how do they get transcribed?
Are the genes turned off?
Are the genes turned on?
Are the genes turned up?
Are the genes turned down?
There are a whole bunch of regulatory processes
around genes that affect how they are expressed.
(16:37):
That's sometimes called epigenetics.
It's actually a broader world than just epigenetics,
but I'll use the word epigenetics for simplicity now.
So we focus on that.
What can be going wrong with the gene expression
in the child that can give rise
(16:58):
to abnormal neurodevelopment and then abnormal phenotypes
like autism.
And again, this is a little complex.
I'm sorry, I'm really sorry.
There's almost, everyone says,
Jill, Jill, Jill, you need like an elevator pitch.
Like you need an elevator to explain this.
I'm like, there's no elevator pitch.
It's really complex.
But then to go back to the heritability point.
(17:22):
Things are heritable if they come basically
from the sperm or the egg of the parents.
Does that make sense?
So I contribute an egg, my husband contributes a sperm.
Those are the heritable components, right?
(17:42):
That fuse and then create the child, right?
And those heritable components,
those what they call germ cells, contain DNA,
but they contain much, much, much more than DNA.
They contain all these regulatory factors,
epigenetic and other regulatory factors.
(18:03):
So this is to me the ultimate question in autism.
What could be happening in the germ cells
that influence these regulatory factors?
Now, I mean, it seems like a crazy question.
Like, okay, here's my drink.
So if I drink my, whatever this is, my lemonade or whatever,
(18:30):
is that going to affect my germ cells?
Then if we're gonna affect my child?
The answer is like, no.
Most things don't affect your germ cells.
Your germ cells are very well protected from damage.
Almost, there's almost nothing.
You know, the air you breathe isn't gonna matter.
You know, the food you eat for the most part
(18:51):
isn't gonna matter.
You know, the amount of steps you take today
isn't gonna matter.
But some things do matter.
And I work on one, I work on a couple of things,
but for example, here's an example of one thing
that we work on, which is,
(19:13):
when you are put under general anesthesia,
you are anesthetized, right?
You are put into a state of basically,
you're basically an induced coma, essentially.
And you lose all sensory function.
(19:36):
And you're unconscious, it's a state of unconsciousness,
it's induced unconsciousness.
And what we see, for example, in animal studies
is that these general anesthetics
can affect your germ cells too.
So it's not just affecting your body,
it's also affecting your reproductive cells.
(20:01):
And in the animal models, when we anesthetize the rats
or the mice, and then we breed them,
these animals are more likely to have offspring
with neurodevelopmental abnormalities
and behavioral abnormalities.
So again, it's so complex.
(20:24):
I can't even believe I'm even talking to you about this
because I almost exclusively talk to scientific audiences.
I don't really deal with lay audiences,
except here and there.
And that's because it is a very, very complicated thing.
But unlike the vast majority of exposures,
(20:45):
this is an exposure that can damage your reproductive cells,
which is to say, you're sperm and egg in their precursor,
at precursors.
And then the offspring are at enhanced risk
for having autism-like phenotypes.
So we've seen this in a couple of studies.
(21:08):
The question is, are we seeing it in humans?
And the answer is we don't know
because there hasn't been any human studies done.
So what I try to do is convince researchers
who are in this space that these are very important questions,
that we need to look beyond the genetic sequence
(21:32):
to look for the missing heritability of autism.
It's complex.
Really, again, I apologize to everybody.
Two questions to follow up.
So are you thinking that it's within the specific germ cell
or is it once they start proliferation?
Yeah, okay.
Well, this is a really incredibly good question.
(21:54):
So we are born with something called primordial germ cells.
And then again, in when you're in high school biology,
you learn about the process of meiosis, right?
So you start with these primordial germ cells
and then the males and females completely diverge,
completely in terms of what happens
(22:16):
in germ cell development.
What happens in males is a pool of germ cells
called spermatogonial stem cells
kind of are right there in the gonads.
And those spermatogonial stem cells
are constantly churning out, or after puberty,
constantly churning out sperm.
(22:37):
So sperm tids to the mature spermatizoma.
But if the pool of the spermatogonial stem cells
are perturbed in some way, right?
Let's say that you are three years old, right?
And you undergo surgery and for some reason,
(22:59):
and it perturbs your germ cells.
Well, if it's not repaired,
and by the way, we have really robust repair processes
in the gonads, but if it's not repaired, for example,
if you have like surgery after surgery
after surgery after surgery,
then those defects will stay in the spermatogonial stem cells
(23:21):
and therefore translate into at least some
of the mature sperm later on.
So you're right to ask because it's a long process, right?
It's not like it's a one day thing
because you can have a hit when you're two years old
or 12 years old and that might not manifest
until your child is three years old,
(23:41):
which is a crazy thing to think, right?
With females, we're born with all of our eggs.
Like we, I think that's sort of a cliche, right?
Girls are born with all their eggs and they are,
you know, pretty much.
So if there's damage to the eggs that's not repaired,
the pool of OO sites, you know, those could be,
(24:06):
you know, those can carry into the next generation
if it's not repaired.
So yeah, it's different for the males and the females,
but definitely what we've seen in the animal studies
is it doesn't matter where the hit is.
The hit can be when they're in the womb, like a fetus.
The hit can be when they're neonates.
The hit can be when they're young adults.
(24:27):
The hit can be when they're pre-conception, right?
Adults, it doesn't matter that these compounds,
which are highly, highly toxic by the way,
can affect the germ cells.
So that's kind of scary to think that the germ cells
can be affected at any point in the life cycle.
Yeah, but again, this is the only scene in animal models.
(24:49):
Have we done a single human study?
No, we do know from human studies,
however that these compounds can damage germ cells generally.
We just haven't looked at the heritability part.
It's some of these rats and mice.
Do they show like stereotype movements,
like licking and their social withdrawal and so forth?
Yeah, what a good, good, good question.
(25:12):
So I have a couple of videos linked on my website,
at least two on my website.
So for the supergeeks who want to dive in
and see each of the studies summarized,
because they each look at something slightly different.
(25:33):
There are no two studies that are exactly the same.
But go to gelesher.com, ESCHER.com.
I gave one at Harvard this year and UCLA,
or that was 2024, Harvard, UCLA was 2023, I believe.
And those I think have pretty decent amount of detail.
So for the supergeeks, look at those.
(25:55):
But generally, yes, you're right.
They will look at social behaviors.
They will look at anxiety-like behaviors.
They will look at sometimes motor behaviors.
Again, everyone's different.
Communication, vocalization type behaviors.
It depends on what the scientist thinks is salient.
(26:17):
Yeah, we need a lot more of them.
I mean, right now we don't have, I think there've been
a total of 10 studies over time.
It's just not enough, we need a lot more.
So hopefully we'll see a couple more published this year, 2025.
Yeah, I'm very interested with how impactful-
(26:39):
When they look at the brain too,
I should say it's not just behavior.
So depending on the lab and depending on the scientist,
they'll chop up the brain, right?
And they'll see like, oh, has the brain developed abnormally?
Or they'll look for abnormal gene expression.
They'll look for the RNAs, et cetera.
I won't get into too much,
(27:01):
but they can look on a molecular level
and a tissue level as well.
And there's some data that's-
Yeah, and there's data showing that,
oh, there's this, I mean, I don't have my notes in front of me.
Yeah, that's fine.
Yeah, sorry, sorry about that.
But yeah, yeah, most definitely they see some differences
in the brain of the off-screen.
(27:23):
The rodents, the rats and mice are very,
you can turn them autistic quite easily.
I mean, I don't want to say quite easily,
but it is possible.
Yeah, you can induce, quote unquote,
I would get an autism doesn't really exist in rodents.
So these are just signal behaviors.
I wouldn't call them autism at all,
(27:45):
but you can induce an autism-like phenotype
in the rodents using these exposures.
Yeah.
Are your plans moving forward
is to expand on those or replicate them or?
Yeah, we need more animal studies.
(28:05):
And I really am hoping to get
some human studies off the ground this year.
I've already talked to two labs
that are very, very interested
in doing human epidemiological studies.
So let's hope that, you know, that can happen
or at least start this year.
These things take several years to do
(28:27):
these epidemiological studies minimum three years.
Yeah, well, they need a big data set with two generations.
They need really robust data with two,
and that's not easy to do.
It's not easy.
So animals and humans, you know, we need them both.
I've also funded some studies that are more molecular
(28:50):
and in vitro.
So in vitro people, what it means is basically like
doing something in a test tube or in a petri dish
rather than doing something in an animal.
So you can take a cell culture,
do something to the cell culture, you know, an exposure
and then see the consequences of that.
So I funded that too.
It's a very uncharted territory.
(29:11):
It's wide open for all kinds of approaches.
It's just, it's so off the radar of mainstream research
that most researchers just won't even think about going there
because they're only interested in genes.
Yeah, and that's a dead end road.
(29:31):
Well, I think they've already found out 99%
of what they're ever gonna find out in genetics.
You know, there's not much more to be discovered.
They're honestly, even when I talk to the geneticists,
you know, they say that too.
Yeah, but I think we'll keep going.
I think, I don't think the research will stop on it.
Might slow down, but I don't know with the genetics.
(29:55):
Well, there's still so much money going into genetics.
That's who's money.
The Simons Foundation funds almost exclusively genetics.
A lot of the NIH money has gone to genetics.
It's just not, you're right.
It's probably not slowing down,
but I think it's unfortunate
because we're missing the opportunity
to look at other hypotheses because, you know,
(30:17):
genetics cannot possibly explain the incredible explosion
and prevalence that we've seen in autism
over the past 30 years.
I mean, you know, we were talking before
about prevalence data, but you know, it's just,
there's such overwhelming evidence
that we've experienced a stupendous increase
in autism that started with births
(30:39):
in like the late 80s, early 90s.
That was sort of the inflection point.
And then from there, we've seen exponential growth
in autism, even when it's pretty strictly defined,
you know, I'm not talking about like TikTok autism
and you know, quirky autism.
Even when it's clearly and observably a disorder,
(31:03):
we've seen those rates really climb.
And you know, we're not taking it seriously enough.
We're not doing anything to figure out what's causing it.
We're not doing anything to really meaningfully prevent it.
And I think it, honestly, it could have,
it's something that could have insanely dire consequences
for our country, you know, for our families,
(31:24):
in calculably huge costs.
You know, we ran some numbers based primarily
on California data,
because California is such good birthyear data on autism.
And you know, we're gonna see right now,
I can actually have the numbers
because I was just working on a slide.
(31:45):
Let me find it one second
because I want to, I'll be accurate this time.
Here it is.
Okay, so in California, right now,
we have about 8,000 cases of autism
with parents, you know, above approximately age 65.
(32:09):
Right, so these are parents who are getting older,
harder, more difficult to care for their children,
having more health issues, et cetera.
And right now that number is about 8,000.
We can project based on the current California caseload
and the birthyear data
(32:30):
that that number is going to be 160,000 in 30 years.
In case that's a 20-fold, you know, increase.
It's a 20-fold increase.
I mean, I can't begin to tell you what a calamity it is already
(32:51):
with respect to these adult autism cases in California
with older parents or dying parents.
It's already horrible.
And the system is already completely bursting
at the seams, it's completely maxed out, completely.
Like I just talked to a family today,
they can't find a single placement for their adult son
(33:15):
in the entire state of California,
in the entire state of California.
This is not uncommon.
And this is a state that has better services than most.
Yet this situation will be 20-fold worse
in terms of demand in 30 years.
I mean, it's unbelievable to even contemplate.
(33:37):
We have not come close to grappling with the reality
that lies ahead of us.
It's really horrible.
But, you know, we're so caught up in this idea.
We're so caught up in the genetic studies.
We spent so much-
Well, the genetic studies and the idea that,
oh, you know, we're just diagnosing it more.
(34:00):
You know, it's that the increasing rates isn't really real.
It's an artifact of awareness.
It's an artifact of changing conceptions.
It's not a real biological thing,
which is complete nonsense.
It's utter nonsense.
I mean, as I said, the evidence is absolutely overwhelming
for true increase and there is no evidence, none, zero,
(34:20):
zero evidence that can explain this increase
through non-idiological or what do you say, non-biological,
non-sociological effects.
I don't really like when people say
that it's things like we're diagnosing more.
(34:41):
Because even if we normalize that,
it doesn't account for hardly any,
especially on a significant level of the actual increase.
It might account for some, but nothing like-
No, it can't.
It depends on the system.
See, each system is a little bit different, right?
(35:04):
Because you have data, for example,
from developmental services, you have data from the schools,
you have data from epidemiology,
you have data from medical records.
There's all kinds of different data.
And they all use different kind of criteria,
different assessment methods.
So I get it, it's not super-duper clean.
But no matter which segment you look at,
whether it's the school data or hospital records
(35:27):
or whatever, they all show the same thing.
They're all showing the exact same trends
at the exact same time.
It's stupendous and what there is not
is anything in the literature that explains it
through some other mechanisms.
Oh, like for example, here's a popular one.
The popular one is, oh, we are just relabeling
(35:48):
intellectual disability, which used to be called MR, right?
We are just relabeling intellectual disability as autism.
Well, that's a nice idea,
except there's no evidence for it.
There might be a little evidence
over a short period of time here and there
that it can explain like little wobbles.
(36:10):
But nothing that can explain
this overwhelming surge of autism from any other label.
So it's nice that they come up with these ideas,
but it's not enough to just conjecture, show me the data.
I've read it, I've poured through the school data.
I've poured through the developmental systems data.
(36:31):
I've poured through the epidemiological data,
not just in the US, but in 10 countries.
It's not, this is not subtle stuff.
None of this is subtle.
These are overwhelming numbers.
You know, as I say, on California, 1989,
we had about 3,000 cases of autism.
(36:52):
We now have 190,000 cases of autism
in the developmental system.
So I'm not talking about broad spectrum.
I'm talking about just the developmental services definition,
the Medicaid definition.
So same data set.
This is your definition.
Same data point or data set.
Yeah, so same data set, same criteria.
In fact, the criteria became narrower, not broader,
(37:16):
in 2003 in California.
So we're talking about significant functional disability.
You can't qualify to be in this system
with just a label of autism.
You have to have autism plus.
Autism plus significant functional disability
across three major areas of life functioning.
(37:37):
It's serious.
And yeah, the numbers are just enormous.
And it's not like we can go back and find this missing
hoard of adults with autism that weren't found before.
Those have never been found ever, ever.
I mean, it's absurd.
And it's frustrating to have to be at this point
(37:59):
that we're still fighting against the myth of better
diagnosis.
I think we should be well past the point of all
of this past the point of doubt.
There's no doubt.
Yeah.
There's just no doubt.
If you're increasing.
(38:19):
Yeah.
What are your thoughts on the relationship with vaccine?
I don't think there's any evidence at all
to suggest that vaccines are responsible for the increase
in autism.
OK.
And that's on many levels.
First of all, we don't see it in the epidemiology.
So when we've done the big studies looking
(38:42):
at large populations and people with various levels
of vaccine exposure, we are not seeing any relationship
between that vaccine exposure and the development of autism
in children.
We also don't have a molecular rationale for it.
We don't have a mechanistic rationale for it.
(39:04):
Like why would a vaccine cause, given at, let's say,
18 months or whatever, cause abnormal brain development
in utero?
Autism is by and large something that
stems from abnormal brain development
during the fetal period and early life.
(39:28):
And vaccines, there's no mechanistic rationale
connecting a vaccine to that biological phenomenon.
So it can't explain that.
It can't really explain the timing of the increase.
Like people say, oh, you have the Marisol.
There was some mercury in the vaccines.
(39:49):
Well, they took it out.
And autism rates kept going up and up.
There's a slight lag there with the vaccine schedule
and the safety act and then the increase, I think.
There's a little bit of a lag there.
Yeah.
When I've looked at the temporal associations,
they just didn't make sense to me.
(40:09):
It doesn't explain why more males are affected than females.
Yeah.
You know, why would it disrupt, for example,
this is getting into neuroscience,
but the GABA-ergic system, which is something
seen in autism, it doesn't make sense.
(40:31):
The EI imbalance is the data.
Yeah, the EI imbalance is really central to autism,
exactly, exactly bingo.
And that's the motor movements, too.
That explains the motor movements with the indirect pathway
of the basal ganglia.
That's interesting.
And this is going to be a problem,
because autistics, as they get older,
they're going to have a lot of autism in Parkinson's.
(40:54):
And they're going to hit various dementias.
That's going to be a problem.
There was just a study that came out looking at.
Directly.
AJ, you're excellent.
Yeah.
And I only glanced at it.
I haven't read it.
But for example, people with autism
are at higher risk for seizures.
(41:16):
And that's because of the poor connectivity
in parts of the brain.
Autism is mostly this connectivity problem.
And so you have this electrical energy
that can't be dispersed, that isn't going
to where it's supposed to go.
If a buildup of excitatory activity,
and it results in seizures, I mean, that's a really bad,
(41:38):
bad summary of it.
But if you have these widespread microstructural
abnormalities in the brain, it stands
to reason that there could be an increased risk for degeneration
or late in life neurological problems.
I would completely believe that.
(41:59):
Yeah.
Yeah, I was wondering, as you were explaining the rodent studies
and your other information on the molecular stuff,
if you found specific cells underdeveloped or migration
problems in your brain.
Yeah.
Yeah, yeah, yeah.
Very, very good question.
The answer is yes.
(42:20):
So I was talking about, for example,
the example of general anesthesia.
And by the way, general anesthesia isn't the only thing
that I'm concerned about.
It just happens to be a focus right now
because we're seeing so much plausibility via the animal
models.
But for example, those are agents that are well known
(42:40):
to impair neural migration for those who are directly exposed.
So let's say you're a directly exposed neonatal rat
or fetal rat who's exposed to these compounds.
We do know for sure that these can impact neural migration
(43:02):
proper.
And they can cause basically, what are they called?
Oh my gosh.
Oh my god.
Blanking.
It's too late here in California.
Oh my gosh.
But anyway, they can basically raise the risk for seizures
because the neurons end up in the wrong place
(43:22):
and can't discharge properly.
I'm sorry that I can't remember the scientific term.
I'll stop my head.
But whether this is happening in the second generation,
the answer is probably yes because we
have seen these neurological abnormalities in mouse models.
(43:44):
So there's not enough stuff.
We need to do a lot more study to really dig deeper
and see and connect all the dots.
UCLA published a paper this year or last year now, I guess,
2024 on the abnormal connectivity with the salience
network.
On six weeks, so humans.
(44:05):
OK.
Salience network is huge in autism.
Did I see that paper?
Was it an imaging study?
What was it?
I think I don't really recall the methods of some of my head.
But it's a very well studied paper.
Lucinda Oudin, she's a pioneer on this salience network
(44:28):
and the insula.
I want to look that up for sure.
Yeah, and they were six weeks old.
And then they followed them up to confirm the autistic diagnosis
later in life.
Wow.
They were six weeks old.
But how did they do it if it wasn't imaging?
I think it was imaging.
But I can't.
I don't want to say for sure.
(44:49):
OK.
Oh, I'll have to look it up.
I'm clueless.
I could send it to you.
Yeah.
Yeah, I'll look it up.
But one thing that is really seen in quite a number of papers
is this unexplained transcriptional dysregulation
in early brain development.
So they can see that it's happening,
(45:11):
even if it's not caused by a genetic defect.
They can see this, basically, abnormal RNA expression.
And this has been seen in several studies.
And do they know why?
No, they don't know why.
So to me, that's the million dollar question in autism.
Well, what's causing that transcriptional dysregulation
in early brain development?
(45:33):
Are you thinking some sort of environmental signal?
Well, that's what I'm saying.
It's embedded in the programming of the child
via these epigenetic factors.
Now, right, it talks about regulatory factors
in the sperm and egg that can have the effect of a mutation
(45:55):
without being a mutation.
And those things, I mean, you have very techie people.
I mean, we have one paper that's really outstanding.
And basically, it showed abnormal binding
of transcription factors at enhancers
at autism-related genes.
So those transcription factors basically turned off
(46:23):
or on genes in abnormal ways.
And I can't really, it's complex.
They found it at many genes.
And I can't tell you which is which.
But that should be very worrisome, right?
If you have abnormal binding of transcription factors,
you're bound to have abnormal expression of the genes
(46:45):
and then possibly abnormality in brain development.
Yeah, it's just a domino effect.
And those were caused by a general anesthetic exposure.
So yeah, it's complex.
And I didn't know we were going to talk so much science.
But I would have brought it on all my notes
because I always get the genes wrong.
(47:07):
I didn't either.
But I'm glad we did because I prefer that.
There's a lot of.
Watch my Harvard talk because I think that one will get
into enough of the details.
And a lot of them are centered around proteins
that are responsible for excitation, which
(47:28):
would cause the EIM balance even more.
Excitation and then the GABA being low.
And cellular functioning and synaptic functioning too.
The pre and post-synaptic.
There's a lot of stuff there, which all
makes sense downstream for the autistic phenotype.
(47:49):
Yeah.
Yeah, I mean, I think so.
I definitely think so.
These are acting on genes that are associated
with neural development and neural functioning.
Last question, and I'll let you go, I guess.
I bored you to death.
I bored your poor listeners to death.
(48:10):
No.
It kind of fits in line with my episode.
So I don't think it's a word.
What's the biggest barrier for you and your research right now?
Or the biggest barrier plural?
The biggest barrier is dogma.
The biggest barrier is dogma.
And there's two dogma that are really problematic.
(48:31):
The first dogma is the genetics dogma.
They just have to expand the way they
think about heritability.
Full stop.
Full stop.
They have to just be willing to ask new questions.
And so far, that field is not willing to move.
(48:52):
And so that's the first dogma problem.
The second dogma problem comes via the neurodiversity movement
because of their fanaticism.
And I will say fanaticism about the idea
that autism is perfectly natural.
And it's just a normal way of being.
And we're just appreciating it now.
(49:13):
We're just noticing it now.
And it just has to be accepted.
And it shouldn't be treated.
And it's not something we should worry about.
And the problem is with society.
The problem isn't with the brain.
That is just dumb.
It's just stupid.
And while I definitely appreciate efforts
to promote inclusion and support and services,
(49:35):
I'm completely on board 100% with all of that,
we don't have to pretend that autism is just
a variant of normal.
We don't have to normalize autism to get there.
We don't.
So those are the two biggest barriers right now.
And I do think there's a third barrier, which is
(49:58):
we were really burned by the vaccine hypothesis.
And no one wants to make that mistake again.
Nobody wants to start blaming autism on something erroneous.
And I get that.
So I think people are very ultra cautious about introducing
any new ideas.
The problem is we are now seeing more than 3% of US children
(50:22):
having autism.
And it is a huge, massive national emergency,
beyond national emergency.
So I don't care if you're uncomfortable.
I get that the vaccine hypothesis was debacle.
Like, I get it.
I've been fighting that for a long time.
(50:43):
I've been fighting that battle too.
But we have to roll up our sleeves and do the serious work.
Right now, autism is just an unserious area.
It's just unserious.
It's become silly.
And we have to move away from that in a new direction.
So it's hard.
We're in a very hard place now.
(51:06):
And I just do my best to try to convince people
to think out of the box.
Yeah, thank you for that.
And I can't agree more with you.
Hopefully there will be a little bit of changes
on the direction moving forward.
Well, research.
Let's hope.
(51:26):
Maybe someone will hear this podcast and go, you know.
Genetics is a dead end.
But they're going to go.
Let's ask some new questions.
Well, Jill, thank you so much.
And oh, you mentioned it earlier.
But how's how give us a couple of ways
that we can contact or look into your research?
(51:50):
And you mentioned your website.
Yeah, the easiest thing is I have a website where I just,
you know, plop down the links to various things I've written
or spoken at.
But it's Jill Escher.
One more J-I-L-L-E-S-C-H-E-R dot com.
And my contact is there, but it's Jill dot Escher at gmail.com.
(52:13):
So yeah.
I'm grateful for the opportunity.
And I really appreciate the fact that you have so much curiosity
about autism etiology and so willing to ask new questions.
That's exactly what we need.
Yeah, it happens some time along this timeline
(52:36):
of the mother, father placenta womb through pregnancy.
And I'm pretty agreed more.
Yeah, it's a developmental quirk that has an origin, right?
It's not like random.
My argument is we have to look for what's originating,
(52:59):
you know, these perturbations of development.
So hopefully we'll get there.
Hopefully we can have a part two and talk more science.
Yeah, I'll be more prepared next time.
After I haven't read a study for a couple of months,
you know, the details go to mush.
But I will definitely, you know, be prepared with much more
(53:21):
science next time, I promise.
I was pleased that we went there.
OK.
That's great.
All right.
Have a good day.
Thanks, Ryan.
Appreciate it.
If you're listening to the podcast
or listening to the episode, please feel free to leave
a review or ratings.
(53:42):
In podcasting, review and ratings are crucial.
And I very much appreciate your feedback.
You can contact me on X at RPS 47586
or click on the hop link so you can have links to all the show
platforms and contact information.
(54:03):
You can email me info.
FromTheSpectrum at gmail.com.
And thank you for listening to FromTheSpectrum podcast.
My guest today is Jill Escher.
(00:03):
Jill is a philanthropist focused on autism research,
a lawyer, and a mother of two autistic children.
More accurately, there are now young adults.
Jill is the president of the National Council on Severe Autism,
and a former president and current board member of the Autism Society, San Francisco Bay Area.
(00:26):
Through her work with the Escher Fund for Autism,
Jill leads innovative research investigating the causes of autism.
Her research enhances our understanding and pushes the boundaries of what we know about autism.
One example Jill explains during the episode involves research on germ cells.
(00:49):
The ability to question and expand research allows us to explore new regions of interest
for understanding the causes of the autistic phenotype.
Please see the show notes for links to Jill's work in her research.
In addition, there are resources from previous episodes that support the timelines discussed in today's episode.
(01:14):
And now my conversation with Jill Escher.
Jill, can we start with you kind of telling us your journey into autism?
And I really want to add that I've heard you say recently that, and I'll quote, I wasn't looking for autism.
Autism found me.
(01:36):
Yeah, pretty much, pretty much, I mean, I grew up in the 60s and 70s into the 80s, and I had hardly heard of autism at all.
I had never met anybody with autism.
Even somebody who we might apply the label to today, I really can't think of anybody, you know, with traits, like my kids are similar,
(01:58):
all that ever come across.
Then I had three children, my husband and I have a 27 year old young man, a 25, almost 26 year old young man, and an 18 year old young lady.
And the latter two, the 20, almost 26 year old man and the 18 year old young woman are both profoundly autistic and nonverbal.
(02:24):
So, you know, these were very shocking, both times very shocking diagnoses.
Again, we had nothing like autism in our family histories.
We didn't know people with autism.
It was not something we read about nothing we saw in the news.
It was not on our radar at all.
(02:47):
Like when I was pregnant with my sons, I mean, it just, it just didn't even occur to me that it was something I would even think about.
Like, I thought, you know, you know, you're pregnant, you think about, oh, maybe you're a kid with Down syndrome or maybe a kid would have a birth defect or whatever.
It just didn't even occur to me that, you know, autism would be a possibility.
(03:09):
So when Johnny, who was born in 1999 was diagnosed in 2001, it was like, what are you even talking about?
Like, you know, the neurologist who had assessed him when he was about two and a half, you know, saw very obviously that he had very severe classic autism.
(03:30):
But we're like, where did, where did that come from?
And even I will say, Ryan, to this day, nobody knows where these devastating disorders came from in our son Johnny or our daughter Sophie.
They are idiopathic as are the majority of cases of autism.
(03:51):
There were no risk factors in my pregnancies. Again, nothing up our family trees to suggest that autism could be a risk.
So this remains to me a, a, a, a, a, a, a, abominable mystery as it is in most cases.
So that's how autism came to me.
It was not something I was, I was at all looking for.
I was a lawyer at the time that I had Johnny and I had anticipated a career in land use law.
(04:21):
I had a whole other world going on.
And then this just sort of got dropped like a bomb.
Wow.
How long was it after,
I have a couple of questions about what you just said,
but the first one is,
how long was it after the birth of Johnny,
did you kind of say something,
(04:44):
what is going on here?
And then kind of take that role into now,
what you do now?
Right, well, the birth of Johnny,
again, it was very shocking,
it kind of threw our life course
in a completely different direction.
This happens with, I'd say most autism families, right?
(05:05):
You're going a certain direction,
you have certain understandings about the world,
you have certain expectations about what your children will be,
you have certain expectations about how your family
is gonna operate, and then boom,
you just get flung in a completely different direction.
And at first, I think like most families,
you really wanna figure out what to do to help your child.
(05:26):
That was the first priority out the bat.
You're like, well, there must be something
we can do about it.
So Johnny was really a poster child for autism.
I mean, when he was little,
he was flapping his hands,
he would always look at little things,
little objects, little corners, little intersections,
he went in the pavement,
he would chew things all the time,
he couldn't talk, he didn't respond to his name,
(05:48):
he never pointed, he never shared or showed,
he was very irritable, he had trouble sleeping,
he had very weird food, no predilections,
I mean, there's so many different things
that Johnny had, it's like every check mark,
check, check, check, check, check, he had all of them.
But he was physically quite normal,
(06:09):
except he had an abnormally large head,
which again is seen in the subset of kids with autism,
autism is abnormally large head circumference.
And that persists to this day, actually.
Yeah, again, really unexplained,
because the CT scan that was done at 12 months was abnormal,
(06:31):
was normal, and so of course it remains idiopathic.
But he's a normal guy, healthy guy,
nothing else, nothing you would expect
from a disorder, a mental disorder of this magnitude,
usually when you have an intellectual disability
of this magnitude, it's accompanied
by physical abnormalities, facial dysmorphisms,
(06:53):
things like that, and that was not the case with Johnny.
So anyway, so I got flung in this other direction,
very interested in how to help my kids.
And like most moms, I tried everything,
like I tried the diet, I tried taking him to speech therapy,
I tried taking him to occupational therapy,
(07:13):
I tried sensory therapies,
different kinds of classes, ABA, intervention programs.
I mean, I didn't do like the weirder things,
like hyperbaric oxygen,
or some of the crazier interventions you hear of.
(07:35):
But nothing really seemed to move Johnny
off of his trajectory at all, at all.
So that was pretty fearless.
By the time Sophie was born,
and she was displaying all those check marks of autism,
she had some language, I was like echolalic,
but she didn't have any conversational language.
(07:56):
She wasn't playing with toys, right?
That's really a hallmark when they're not playing with toys
and they're not demonstrating the capacity
for abstract thought.
And when they're not imitating,
and they're not sharing and showing and pointing
and acquiring words, like whenever I'm with
like a typical two-year-old,
I'm always astonished at what sponges they are, right?
(08:16):
They're just taking in everything
and they're learning vocabulary very rapidly.
My kids, none of that.
So by the time Sophie came along,
you know, we knew what was going on.
And she was identified with autism by 18 months.
Such an eye mirror.
Yeah, I mean, this was like two kids with severe,
(08:40):
you know, neurodevelopmental abnormality.
And again, you know, we don't know why.
So, you know, I've really been devoting my life
to pushing for answers.
Yeah.
My understanding is you sorted a couple of,
correct me if I'm wrong, a nonprofit
(09:01):
or this organization or foundation
that can you tell me a little bit about that?
I know there's a couple of them actually, but.
Yeah, so I've been involved with several,
several nonprofits.
So everyone kind of fits a different bucket.
So I'm very interested in research.
So I have a fund, a philanthropic fund,
(09:23):
which we call Escher Fund for Autism.
And all it does is it funds pilot research studies
that look at novel ideas
about what might be causing autism.
We also do quite a bit of advocacy for research,
research advocacy, but I think our primary goal
(09:44):
is to fund pilot studies.
I've also published quite a bit
in the scientific literature in partnership
with other scientists about these questions
that we explore.
And I'm involved in other ways in the autism field,
non-research things.
For example, I'm a co-founder
of the National Council on Severe Autism,
(10:05):
and I'm past president of Autism Society,
San Francisco Bay Area.
Yeah, yeah, it's still on the wall.
Yeah, so I do a lot and other things too,
but those are the main ones.
Okay.
What are some of the highlights
of the pilot study research?
Yeah, so we, yeah, like our focus,
so I'm sure a lot of your listeners are aware
(10:28):
that autism is highly heritable, right?
It's conjectured to be strongly genetic
because it's highly heritable.
So for example, if you have one child with autism,
you have like a 16 to 20% chance
of having a second child with autism.
That's how strongly heritable it is.
Not that autism really runs down ancestries.
(10:49):
We don't see any strong evidence for that at all.
It's not like, great-grandparent, grandparent,
you know, blah, blah, blah, blah.
I mean, that'll happen from time to time,
but that's not a strong driver of autism.
Most of the heritability is seen
because of increased risk among siblings
or even, you know, among half siblings
and to a slightly lesser degree.
(11:12):
So the question is why?
What is causing this herit?
Why does autism, quote unquote, run in families like that?
That is the question that we focus on.
Almost all, I would say 99.9% of the attention
in the funding has gone into genetics.
Thinkin', well, Jill has, you know,
(11:35):
Johnny and Sophie and they both have profound autism.
So therefore Jill and or her husband must be carrying genes
that, you know, raise that risk of autism in their children.
Right, and that's the thinking.
That's been the paradigm that has dominated autism research
for, I don't know, 15 years.
(11:55):
I would say a good 15 years is hunting for the genes
that cause autism.
Now those genes come in two flavors.
The first flavor is what they call a rare variant.
And that's usually something that,
like a mutation of some sort
that causes some fairly severe phenotype.
(12:17):
And we can think of lots and lots of examples of that.
You know, you can look up on the Simon's Foundation gene list,
you know, the 100-ish genes that are associated
with autism in that way.
The other flavor that the genes come in,
(12:39):
it are what they call common variants.
So they're variants that are normally harmless
and they occur in more than 5% of people.
They're normally harmless.
But the idea is, their theory is that
those common variants can, you know,
somehow conflate together to increase the risk
(13:01):
for autism in the child.
Now there is almost no evidence for that.
There's a little bit of evidence, but it's so weak
that it's, you know, it doesn't amount to much.
There's very strong evidence for rare variants
causing autism in rare cases.
(13:21):
And by the way, with those rare variants,
none of them explain more than 1% of the autism.
So they are indeed very rare even in the autism world.
So my kids, you know, have none of that.
And most of the kids with autism
and adults with autism don't have any genetic factors
that are known.
So I look at, well, what else is causing the heritability
(13:44):
if it's not the genes where everyone else is looking, right?
9.9% of the people,
they're looking at genes.
I'm looking at non-genetic factors, if that makes sense.
Yeah.
What are some of the interesting findings you found
with the non-genetic factors?
Yeah, it's a little complex.
And so I do want to kind of say at the outset
(14:05):
that I apologize for anything that's complicated.
I really try not to make things too hard
because people tend to resist complex biology.
It's not because they're stupid,
but because it's not something they're schooled in.
(14:25):
But the stuff I do is I have to say
pretty advanced molecular biology,
but I'll try to do my best to simplify it.
All right, so everyone knows what a gene is, I think.
A gene is a sequence of letters, really.
Sequence of bases in your DNA.
(14:46):
They are transcribed and they are made into a protein,
and that protein does something.
For example, in the brain,
that protein can help create a neuron
or help create something that moves a neuron
from one place to another in development.
So the proteins have multiple functions.
(15:07):
If something goes wrong in the gene,
that means something goes wrong in the protein there,
it means something goes wrong in the tissue,
which means something goes wrong in the organ,
right, and you have some sort of disorder or condition.
All right, that's pretty straightforward.
That's textbook high school biology.
What's not textbook high school biology
is something called epigenetics
(15:28):
or transcriptional regulation.
Okay, so again, people hear these words,
they get a little bit scared, don't run away,
it's not that hard.
So you can have the effect of a mutation
without having a mutation,
i.e. all of those letters, all those base pairs
(15:49):
in the DNA can be perfectly normal.
You will have a perfectly normal scan of your genome
if you're genetically tested.
However, the problem is it's not just
the genetic code that matters.
What also matters is how those genes are expressed.
(16:13):
What happens to them, right, how do they get transcribed?
Are the genes turned off?
Are the genes turned on?
Are the genes turned up?
Are the genes turned down?
There are a whole bunch of regulatory processes
around genes that affect how they are expressed.
(16:37):
That's sometimes called epigenetics.
It's actually a broader world than just epigenetics,
but I'll use the word epigenetics for simplicity now.
So we focus on that.
What can be going wrong with the gene expression
in the child that can give rise
(16:58):
to abnormal neurodevelopment and then abnormal phenotypes
like autism.
And again, this is a little complex.
I'm sorry, I'm really sorry.
There's almost, everyone says,
Jill, Jill, Jill, you need like an elevator pitch.
Like you need an elevator to explain this.
I'm like, there's no elevator pitch.
It's really complex.
But then to go back to the heritability point.
(17:22):
Things are heritable if they come basically
from the sperm or the egg of the parents.
Does that make sense?
So I contribute an egg, my husband contributes a sperm.
Those are the heritable components, right?
(17:42):
That fuse and then create the child, right?
And those heritable components,
those what they call germ cells, contain DNA,
but they contain much, much, much more than DNA.
They contain all these regulatory factors,
epigenetic and other regulatory factors.
(18:03):
So this is to me the ultimate question in autism.
What could be happening in the germ cells
that influence these regulatory factors?
Now, I mean, it seems like a crazy question.
Like, okay, here's my drink.
So if I drink my, whatever this is, my lemonade or whatever,
(18:30):
is that going to affect my germ cells?
Then if we're gonna affect my child?
The answer is like, no.
Most things don't affect your germ cells.
Your germ cells are very well protected from damage.
Almost, there's almost nothing.
You know, the air you breathe isn't gonna matter.
You know, the food you eat for the most part
(18:51):
isn't gonna matter.
You know, the amount of steps you take today
isn't gonna matter.
But some things do matter.
And I work on one, I work on a couple of things,
but for example, here's an example of one thing
that we work on, which is,
(19:13):
when you are put under general anesthesia,
you are anesthetized, right?
You are put into a state of basically,
you're basically an induced coma, essentially.
And you lose all sensory function.
(19:36):
And you're unconscious, it's a state of unconsciousness,
it's induced unconsciousness.
And what we see, for example, in animal studies
is that these general anesthetics
can affect your germ cells too.
So it's not just affecting your body,
it's also affecting your reproductive cells.
(20:01):
And in the animal models, when we anesthetize the rats
or the mice, and then we breed them,
these animals are more likely to have offspring
with neurodevelopmental abnormalities
and behavioral abnormalities.
So again, it's so complex.
(20:24):
I can't even believe I'm even talking to you about this
because I almost exclusively talk to scientific audiences.
I don't really deal with lay audiences,
except here and there.
And that's because it is a very, very complicated thing.
But unlike the vast majority of exposures,
(20:45):
this is an exposure that can damage your reproductive cells,
which is to say, you're sperm and egg in their precursor,
at precursors.
And then the offspring are at enhanced risk
for having autism-like phenotypes.
So we've seen this in a couple of studies.
(21:08):
The question is, are we seeing it in humans?
And the answer is we don't know
because there hasn't been any human studies done.
So what I try to do is convince researchers
who are in this space that these are very important questions,
that we need to look beyond the genetic sequence
(21:32):
to look for the missing heritability of autism.
It's complex.
Really, again, I apologize to everybody.
Two questions to follow up.
So are you thinking that it's within the specific germ cell
or is it once they start proliferation?
Yeah, okay.
Well, this is a really incredibly good question.
(21:54):
So we are born with something called primordial germ cells.
And then again, in when you're in high school biology,
you learn about the process of meiosis, right?
So you start with these primordial germ cells
and then the males and females completely diverge,
completely in terms of what happens
(22:16):
in germ cell development.
What happens in males is a pool of germ cells
called spermatogonial stem cells
kind of are right there in the gonads.
And those spermatogonial stem cells
are constantly churning out, or after puberty,
constantly churning out sperm.
(22:37):
So sperm tids to the mature spermatizoma.
But if the pool of the spermatogonial stem cells
are perturbed in some way, right?
Let's say that you are three years old, right?
And you undergo surgery and for some reason,
(22:59):
and it perturbs your germ cells.
Well, if it's not repaired,
and by the way, we have really robust repair processes
in the gonads, but if it's not repaired, for example,
if you have like surgery after surgery
after surgery after surgery,
then those defects will stay in the spermatogonial stem cells
(23:21):
and therefore translate into at least some
of the mature sperm later on.
So you're right to ask because it's a long process, right?
It's not like it's a one day thing
because you can have a hit when you're two years old
or 12 years old and that might not manifest
until your child is three years old,
(23:41):
which is a crazy thing to think, right?
With females, we're born with all of our eggs.
Like we, I think that's sort of a cliche, right?
Girls are born with all their eggs and they are,
you know, pretty much.
So if there's damage to the eggs that's not repaired,
the pool of OO sites, you know, those could be,
(24:06):
you know, those can carry into the next generation
if it's not repaired.
So yeah, it's different for the males and the females,
but definitely what we've seen in the animal studies
is it doesn't matter where the hit is.
The hit can be when they're in the womb, like a fetus.
The hit can be when they're neonates.
The hit can be when they're young adults.
(24:27):
The hit can be when they're pre-conception, right?
Adults, it doesn't matter that these compounds,
which are highly, highly toxic by the way,
can affect the germ cells.
So that's kind of scary to think that the germ cells
can be affected at any point in the life cycle.
Yeah, but again, this is the only scene in animal models.
(24:49):
Have we done a single human study?
No, we do know from human studies,
however that these compounds can damage germ cells generally.
We just haven't looked at the heritability part.
It's some of these rats and mice.
Do they show like stereotype movements,
like licking and their social withdrawal and so forth?
Yeah, what a good, good, good question.
(25:12):
So I have a couple of videos linked on my website,
at least two on my website.
So for the supergeeks who want to dive in
and see each of the studies summarized,
because they each look at something slightly different.
(25:33):
There are no two studies that are exactly the same.
But go to gelesher.com, ESCHER.com.
I gave one at Harvard this year and UCLA,
or that was 2024, Harvard, UCLA was 2023, I believe.
And those I think have pretty decent amount of detail.
So for the supergeeks, look at those.
(25:55):
But generally, yes, you're right.
They will look at social behaviors.
They will look at anxiety-like behaviors.
They will look at sometimes motor behaviors.
Again, everyone's different.
Communication, vocalization type behaviors.
It depends on what the scientist thinks is salient.
(26:17):
Yeah, we need a lot more of them.
I mean, right now we don't have, I think there've been
a total of 10 studies over time.
It's just not enough, we need a lot more.
So hopefully we'll see a couple more published this year, 2025.
Yeah, I'm very interested with how impactful-
(26:39):
When they look at the brain too,
I should say it's not just behavior.
So depending on the lab and depending on the scientist,
they'll chop up the brain, right?
And they'll see like, oh, has the brain developed abnormally?
Or they'll look for abnormal gene expression.
They'll look for the RNAs, et cetera.
I won't get into too much,
(27:01):
but they can look on a molecular level
and a tissue level as well.
And there's some data that's-
Yeah, and there's data showing that,
oh, there's this, I mean, I don't have my notes in front of me.
Yeah, that's fine.
Yeah, sorry, sorry about that.
But yeah, yeah, most definitely they see some differences
in the brain of the off-screen.
(27:23):
The rodents, the rats and mice are very,
you can turn them autistic quite easily.
I mean, I don't want to say quite easily,
but it is possible.
Yeah, you can induce, quote unquote,
I would get an autism doesn't really exist in rodents.
So these are just signal behaviors.
I wouldn't call them autism at all,
(27:45):
but you can induce an autism-like phenotype
in the rodents using these exposures.
Yeah.
Are your plans moving forward
is to expand on those or replicate them or?
Yeah, we need more animal studies.
(28:05):
And I really am hoping to get
some human studies off the ground this year.
I've already talked to two labs
that are very, very interested
in doing human epidemiological studies.
So let's hope that, you know, that can happen
or at least start this year.
These things take several years to do
(28:27):
these epidemiological studies minimum three years.
Yeah, well, they need a big data set with two generations.
They need really robust data with two,
and that's not easy to do.
It's not easy.
So animals and humans, you know, we need them both.
I've also funded some studies that are more molecular
(28:50):
and in vitro.
So in vitro people, what it means is basically like
doing something in a test tube or in a petri dish
rather than doing something in an animal.
So you can take a cell culture,
do something to the cell culture, you know, an exposure
and then see the consequences of that.
So I funded that too.
It's a very uncharted territory.
(29:11):
It's wide open for all kinds of approaches.
It's just, it's so off the radar of mainstream research
that most researchers just won't even think about going there
because they're only interested in genes.
Yeah, and that's a dead end road.
(29:31):
Well, I think they've already found out 99%
of what they're ever gonna find out in genetics.
You know, there's not much more to be discovered.
They're honestly, even when I talk to the geneticists,
you know, they say that too.
Yeah, but I think we'll keep going.
I think, I don't think the research will stop on it.
Might slow down, but I don't know with the genetics.
(29:55):
Well, there's still so much money going into genetics.
That's who's money.
The Simons Foundation funds almost exclusively genetics.
A lot of the NIH money has gone to genetics.
It's just not, you're right.
It's probably not slowing down,
but I think it's unfortunate
because we're missing the opportunity
to look at other hypotheses because, you know,
(30:17):
genetics cannot possibly explain the incredible explosion
and prevalence that we've seen in autism
over the past 30 years.
I mean, you know, we were talking before
about prevalence data, but you know, it's just,
there's such overwhelming evidence
that we've experienced a stupendous increase
in autism that started with births
(30:39):
in like the late 80s, early 90s.
That was sort of the inflection point.
And then from there, we've seen exponential growth
in autism, even when it's pretty strictly defined,
you know, I'm not talking about like TikTok autism
and you know, quirky autism.
Even when it's clearly and observably a disorder,
(31:03):
we've seen those rates really climb.
And you know, we're not taking it seriously enough.
We're not doing anything to figure out what's causing it.
We're not doing anything to really meaningfully prevent it.
And I think it, honestly, it could have,
it's something that could have insanely dire consequences
for our country, you know, for our families,
(31:24):
in calculably huge costs.
You know, we ran some numbers based primarily
on California data,
because California is such good birthyear data on autism.
And you know, we're gonna see right now,
I can actually have the numbers
because I was just working on a slide.
(31:45):
Let me find it one second
because I want to, I'll be accurate this time.
Here it is.
Okay, so in California, right now,
we have about 8,000 cases of autism
with parents, you know, above approximately age 65.
(32:09):
Right, so these are parents who are getting older,
harder, more difficult to care for their children,
having more health issues, et cetera.
And right now that number is about 8,000.
We can project based on the current California caseload
and the birthyear data
(32:30):
that that number is going to be 160,000 in 30 years.
In case that's a 20-fold, you know, increase.
It's a 20-fold increase.
I mean, I can't begin to tell you what a calamity it is already
(32:51):
with respect to these adult autism cases in California
with older parents or dying parents.
It's already horrible.
And the system is already completely bursting
at the seams, it's completely maxed out, completely.
Like I just talked to a family today,
they can't find a single placement for their adult son
(33:15):
in the entire state of California,
in the entire state of California.
This is not uncommon.
And this is a state that has better services than most.
Yet this situation will be 20-fold worse
in terms of demand in 30 years.
I mean, it's unbelievable to even contemplate.
(33:37):
We have not come close to grappling with the reality
that lies ahead of us.
It's really horrible.
But, you know, we're so caught up in this idea.
We're so caught up in the genetic studies.
We spent so much-
Well, the genetic studies and the idea that,
oh, you know, we're just diagnosing it more.
(34:00):
You know, it's that the increasing rates isn't really real.
It's an artifact of awareness.
It's an artifact of changing conceptions.
It's not a real biological thing,
which is complete nonsense.
It's utter nonsense.
I mean, as I said, the evidence is absolutely overwhelming
for true increase and there is no evidence, none, zero,
(34:20):
zero evidence that can explain this increase
through non-idiological or what do you say, non-biological,
non-sociological effects.
I don't really like when people say
that it's things like we're diagnosing more.
(34:41):
Because even if we normalize that,
it doesn't account for hardly any,
especially on a significant level of the actual increase.
It might account for some, but nothing like-
No, it can't.
It depends on the system.
See, each system is a little bit different, right?
(35:04):
Because you have data, for example,
from developmental services, you have data from the schools,
you have data from epidemiology,
you have data from medical records.
There's all kinds of different data.
And they all use different kind of criteria,
different assessment methods.
So I get it, it's not super-duper clean.
But no matter which segment you look at,
whether it's the school data or hospital records
(35:27):
or whatever, they all show the same thing.
They're all showing the exact same trends
at the exact same time.
It's stupendous and what there is not
is anything in the literature that explains it
through some other mechanisms.
Oh, like for example, here's a popular one.
The popular one is, oh, we are just relabeling
(35:48):
intellectual disability, which used to be called MR, right?
We are just relabeling intellectual disability as autism.
Well, that's a nice idea,
except there's no evidence for it.
There might be a little evidence
over a short period of time here and there
that it can explain like little wobbles.
(36:10):
But nothing that can explain
this overwhelming surge of autism from any other label.
So it's nice that they come up with these ideas,
but it's not enough to just conjecture, show me the data.
I've read it, I've poured through the school data.
I've poured through the developmental systems data.
(36:31):
I've poured through the epidemiological data,
not just in the US, but in 10 countries.
It's not, this is not subtle stuff.
None of this is subtle.
These are overwhelming numbers.
You know, as I say, on California, 1989,
we had about 3,000 cases of autism.
(36:52):
We now have 190,000 cases of autism
in the developmental system.
So I'm not talking about broad spectrum.
I'm talking about just the developmental services definition,
the Medicaid definition.
So same data set.
This is your definition.
Same data point or data set.
Yeah, so same data set, same criteria.
In fact, the criteria became narrower, not broader,
(37:16):
in 2003 in California.
So we're talking about significant functional disability.
You can't qualify to be in this system
with just a label of autism.
You have to have autism plus.
Autism plus significant functional disability
across three major areas of life functioning.
(37:37):
It's serious.
And yeah, the numbers are just enormous.
And it's not like we can go back and find this missing
hoard of adults with autism that weren't found before.
Those have never been found ever, ever.
I mean, it's absurd.
And it's frustrating to have to be at this point
(37:59):
that we're still fighting against the myth of better
diagnosis.
I think we should be well past the point of all
of this past the point of doubt.
There's no doubt.
Yeah.
There's just no doubt.
If you're increasing.
(38:19):
Yeah.
What are your thoughts on the relationship with vaccine?
I don't think there's any evidence at all
to suggest that vaccines are responsible for the increase
in autism.
OK.
And that's on many levels.
First of all, we don't see it in the epidemiology.
So when we've done the big studies looking
(38:42):
at large populations and people with various levels
of vaccine exposure, we are not seeing any relationship
between that vaccine exposure and the development of autism
in children.
We also don't have a molecular rationale for it.
We don't have a mechanistic rationale for it.
(39:04):
Like why would a vaccine cause, given at, let's say,
18 months or whatever, cause abnormal brain development
in utero?
Autism is by and large something that
stems from abnormal brain development
during the fetal period and early life.
(39:28):
And vaccines, there's no mechanistic rationale
connecting a vaccine to that biological phenomenon.
So it can't explain that.
It can't really explain the timing of the increase.
Like people say, oh, you have the Marisol.
There was some mercury in the vaccines.
(39:49):
Well, they took it out.
And autism rates kept going up and up.
There's a slight lag there with the vaccine schedule
and the safety act and then the increase, I think.
There's a little bit of a lag there.
Yeah.
When I've looked at the temporal associations,
they just didn't make sense to me.
(40:09):
It doesn't explain why more males are affected than females.
Yeah.
You know, why would it disrupt, for example,
this is getting into neuroscience,
but the GABA-ergic system, which is something
seen in autism, it doesn't make sense.
(40:31):
The EI imbalance is the data.
Yeah, the EI imbalance is really central to autism,
exactly, exactly bingo.
And that's the motor movements, too.
That explains the motor movements with the indirect pathway
of the basal ganglia.
That's interesting.
And this is going to be a problem,
because autistics, as they get older,
they're going to have a lot of autism in Parkinson's.
(40:54):
And they're going to hit various dementias.
That's going to be a problem.
There was just a study that came out looking at.
Directly.
AJ, you're excellent.
Yeah.
And I only glanced at it.
I haven't read it.
But for example, people with autism
are at higher risk for seizures.
(41:16):
And that's because of the poor connectivity
in parts of the brain.
Autism is mostly this connectivity problem.
And so you have this electrical energy
that can't be dispersed, that isn't going
to where it's supposed to go.
If a buildup of excitatory activity,
and it results in seizures, I mean, that's a really bad,
(41:38):
bad summary of it.
But if you have these widespread microstructural
abnormalities in the brain, it stands
to reason that there could be an increased risk for degeneration
or late in life neurological problems.
I would completely believe that.
(41:59):
Yeah.
Yeah, I was wondering, as you were explaining the rodent studies
and your other information on the molecular stuff,
if you found specific cells underdeveloped or migration
problems in your brain.
Yeah.
Yeah, yeah, yeah.
Very, very good question.
The answer is yes.
(42:20):
So I was talking about, for example,
the example of general anesthesia.
And by the way, general anesthesia isn't the only thing
that I'm concerned about.
It just happens to be a focus right now
because we're seeing so much plausibility via the animal
models.
But for example, those are agents that are well known
(42:40):
to impair neural migration for those who are directly exposed.
So let's say you're a directly exposed neonatal rat
or fetal rat who's exposed to these compounds.
We do know for sure that these can impact neural migration
(43:02):
proper.
And they can cause basically, what are they called?
Oh my gosh.
Oh my god.
Blanking.
It's too late here in California.
Oh my gosh.
But anyway, they can basically raise the risk for seizures
because the neurons end up in the wrong place
(43:22):
and can't discharge properly.
I'm sorry that I can't remember the scientific term.
I'll stop my head.
But whether this is happening in the second generation,
the answer is probably yes because we
have seen these neurological abnormalities in mouse models.
(43:44):
So there's not enough stuff.
We need to do a lot more study to really dig deeper
and see and connect all the dots.
UCLA published a paper this year or last year now, I guess,
2024 on the abnormal connectivity with the salience
network.
On six weeks, so humans.
(44:05):
OK.
Salience network is huge in autism.
Did I see that paper?
Was it an imaging study?
What was it?
I think I don't really recall the methods of some of my head.
But it's a very well studied paper.
Lucinda Oudin, she's a pioneer on this salience network
(44:28):
and the insula.
I want to look that up for sure.
Yeah, and they were six weeks old.
And then they followed them up to confirm the autistic diagnosis
later in life.
Wow.
They were six weeks old.
But how did they do it if it wasn't imaging?
I think it was imaging.
But I can't.
I don't want to say for sure.
(44:49):
OK.
Oh, I'll have to look it up.
I'm clueless.
I could send it to you.
Yeah.
Yeah, I'll look it up.
But one thing that is really seen in quite a number of papers
is this unexplained transcriptional dysregulation
in early brain development.
So they can see that it's happening,
(45:11):
even if it's not caused by a genetic defect.
They can see this, basically, abnormal RNA expression.
And this has been seen in several studies.
And do they know why?
No, they don't know why.
So to me, that's the million dollar question in autism.
Well, what's causing that transcriptional dysregulation
in early brain development?
(45:33):
Are you thinking some sort of environmental signal?
Well, that's what I'm saying.
It's embedded in the programming of the child
via these epigenetic factors.
Now, right, it talks about regulatory factors
in the sperm and egg that can have the effect of a mutation
(45:55):
without being a mutation.
And those things, I mean, you have very techie people.
I mean, we have one paper that's really outstanding.
And basically, it showed abnormal binding
of transcription factors at enhancers
at autism-related genes.
So those transcription factors basically turned off
(46:23):
or on genes in abnormal ways.
And I can't really, it's complex.
They found it at many genes.
And I can't tell you which is which.
But that should be very worrisome, right?
If you have abnormal binding of transcription factors,
you're bound to have abnormal expression of the genes
(46:45):
and then possibly abnormality in brain development.
Yeah, it's just a domino effect.
And those were caused by a general anesthetic exposure.
So yeah, it's complex.
And I didn't know we were going to talk so much science.
But I would have brought it on all my notes
because I always get the genes wrong.
(47:07):
I didn't either.
But I'm glad we did because I prefer that.
There's a lot of.
Watch my Harvard talk because I think that one will get
into enough of the details.
And a lot of them are centered around proteins
that are responsible for excitation, which
(47:28):
would cause the EIM balance even more.
Excitation and then the GABA being low.
And cellular functioning and synaptic functioning too.
The pre and post-synaptic.
There's a lot of stuff there, which all
makes sense downstream for the autistic phenotype.
(47:49):
Yeah.
Yeah, I mean, I think so.
I definitely think so.
These are acting on genes that are associated
with neural development and neural functioning.
Last question, and I'll let you go, I guess.
I bored you to death.
I bored your poor listeners to death.
(48:10):
No.
It kind of fits in line with my episode.
So I don't think it's a word.
What's the biggest barrier for you and your research right now?
Or the biggest barrier plural?
The biggest barrier is dogma.
The biggest barrier is dogma.
And there's two dogma that are really problematic.
(48:31):
The first dogma is the genetics dogma.
They just have to expand the way they
think about heritability.
Full stop.
Full stop.
They have to just be willing to ask new questions.
And so far, that field is not willing to move.
(48:52):
And so that's the first dogma problem.
The second dogma problem comes via the neurodiversity movement
because of their fanaticism.
And I will say fanaticism about the idea
that autism is perfectly natural.
And it's just a normal way of being.
And we're just appreciating it now.
(49:13):
We're just noticing it now.
And it just has to be accepted.
And it shouldn't be treated.
And it's not something we should worry about.
And the problem is with society.
The problem isn't with the brain.
That is just dumb.
It's just stupid.
And while I definitely appreciate efforts
to promote inclusion and support and services,
(49:35):
I'm completely on board 100% with all of that,
we don't have to pretend that autism is just
a variant of normal.
We don't have to normalize autism to get there.
We don't.
So those are the two biggest barriers right now.
And I do think there's a third barrier, which is
(49:58):
we were really burned by the vaccine hypothesis.
And no one wants to make that mistake again.
Nobody wants to start blaming autism on something erroneous.
And I get that.
So I think people are very ultra cautious about introducing
any new ideas.
The problem is we are now seeing more than 3% of US children
(50:22):
having autism.
And it is a huge, massive national emergency,
beyond national emergency.
So I don't care if you're uncomfortable.
I get that the vaccine hypothesis was debacle.
Like, I get it.
I've been fighting that for a long time.
(50:43):
I've been fighting that battle too.
But we have to roll up our sleeves and do the serious work.
Right now, autism is just an unserious area.
It's just unserious.
It's become silly.
And we have to move away from that in a new direction.
So it's hard.
We're in a very hard place now.
(51:06):
And I just do my best to try to convince people
to think out of the box.
Yeah, thank you for that.
And I can't agree more with you.
Hopefully there will be a little bit of changes
on the direction moving forward.
Well, research.
Let's hope.
(51:26):
Maybe someone will hear this podcast and go, you know.
Genetics is a dead end.
But they're going to go.
Let's ask some new questions.
Well, Jill, thank you so much.
And oh, you mentioned it earlier.
But how's how give us a couple of ways
that we can contact or look into your research?
(51:50):
And you mentioned your website.
Yeah, the easiest thing is I have a website where I just,
you know, plop down the links to various things I've written
or spoken at.
But it's Jill Escher.
One more J-I-L-L-E-S-C-H-E-R dot com.
And my contact is there, but it's Jill dot Escher at gmail.com.
(52:13):
So yeah.
I'm grateful for the opportunity.
And I really appreciate the fact that you have so much curiosity
about autism etiology and so willing to ask new questions.
That's exactly what we need.
Yeah, it happens some time along this timeline
(52:36):
of the mother, father placenta womb through pregnancy.
And I'm pretty agreed more.
Yeah, it's a developmental quirk that has an origin, right?
It's not like random.
My argument is we have to look for what's originating,
(52:59):
you know, these perturbations of development.
So hopefully we'll get there.
Hopefully we can have a part two and talk more science.
Yeah, I'll be more prepared next time.
After I haven't read a study for a couple of months,
you know, the details go to mush.
But I will definitely, you know, be prepared with much more
(53:21):
science next time, I promise.
I was pleased that we went there.
OK.
That's great.
All right.
Have a good day.
Thanks, Ryan.
Appreciate it.
If you're listening to the podcast
or listening to the episode, please feel free to leave
a review or ratings.
(53:42):
In podcasting, review and ratings are crucial.
And I very much appreciate your feedback.
You can contact me on X at RPS 47586
or click on the hop link so you can have links to all the show
platforms and contact information.
(54:03):
You can email me info.
FromTheSpectrum at gmail.com.
And thank you for listening to FromTheSpectrum podcast.
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