My guest today is Dr. Yusieke Ben Ari.
In 1971, Dr. Ben Ari received a Ph.D. with a focus on neuroplasticity and followed with
postdocs at prestigious universities, including University of Cambridge, University of Oslo,
and McGill University.
In 1986, Ben Ari was appointed head of NSERM in France, focusing on neurobiology and pathophysiology
of development.
In 1999, he founded and led NMED, Neurobiology Institute of the Mediterranean.
In 2008, Ben Ari turned to startups to better understand and study brain disorders.
He's the founder and CEO of Neurochlorie, where they trial humanitine and research the
molecular mechanisms of autism.
In BNA Therapeutics, where they study treatment options for Parkinson's and the regulation
of intracellular chloride effects of GABA signals.
In BNA OncoMedical, where they are dedicated to treat brain tumors.
Dr. Ben Ari is among the top five most quoted French neuroscientists and has over 520 publications
and is a recipient of many awards, including NSERM Grand Prix.
Grand Prix European Society of Epilepsy.
Grand Prix Kanye Van Heck Belgium National Scientific Research, to name a few.
Dr. Ben Ari has over 5 decades of academic and private research with major discoveries
on electrical signals of brain development and pathology.
Being a favorite of mine, GABA is excitatory during the developing immature brain.
Recently, Ben Ari is part of a team using machine learning to identify autism in the
embryo and a priest symptomatic signature called neuroarchaeology that predicts brain
disorders in utero.
In the developing brain, such as during cellular migration.
Remember covering different epochs in the autism and embryo episode and how cells migrate
to common cells to carry out common functions.
Here we will explore more on this critical time.
And now my conversation with Dr. Ben Ari.
The issues I'm going to discuss pertains to the way one can identify early autism.
How can one treat it?
And why is it that studying brain development is crucial to understand and treat autism?
Because the first thing you must remember is that autism is born in the womb and this
is what I'm going to show you in a minute.
And as it's born in the womb, it modifies developmental sequences which are crucial
for brain construction.
This implies that we're not going to cure autism in the sense I have had it, I take
an aspirin, I have no more had it.
Because there are some small malformations in brain construction which are already present
in utero.
Meaning that we, at best, and this is not bad at all, we can attenuate strongly the
disorder we have arrived at through the drugs I'm going to talk about.
Particularly if they're started to be used very early in life.
For a very simple reason is that the first years of post-lateral life once you are born
are crucial for many, many fundamental issues, social interactions.
I mean, if your mother is crying and you laugh because you're looking at her shoes, it's
not like a family, it's an incapacity to look at the eyes.
So there are also very simple reasons why autism is what it is.
And the first two years are absolutely crucial in addition to the maternity period.
So first let's go to the prediction of autism.
Okay, this I remind you a couple of fundamental issues.
The incidence of autism is going up, nobody knows why.
I think it's because of the maternity problem, but this is my point of view.
Is born in the womb?
It can be due to genetic mutations, pesticide, pollution.
No, no.
Now go back to the previous slide.
Yeah, it's generated in the womb by pesticide, pollution, and variety of factors.
Now the question is, if it's generated in the womb, can we identify the baby at birth
with going to be autistic and identify autistic years later?
And that says yes.
Next slide.
What we did is the following.
Well, this we can come back to this later.
I go to the next slide.
It's not the issue now.
Okay, what we did is the following.
We went to a maternity hospital in the south of France and the pedocyclery is identified
as a child with autism.
He was treating.
He went back to the obstetrician, Dr. Kali, which is here below.
And this guy extracted the maternity files of those kids.
In other words, you have a kid who is autistic.
I'm going to extract all the maternity files corresponding to that guy from three to 15
or 18.
In France, maternity files are very rich, between 120 to 150 different parameters, including
at least three ecographies, three brain scans during maternity, paid by the state.
So I mean, we have the collections.
Taking all these parameters, I then recruited two big data analysts shown here, Ahmed and
Marie-Dine.
They are experts of big data analysis.
Because you understand, if you want to analyze 120 parameters in thousands of children and
different conditions, you need big data analysis.
So what they did, now, in addition, we took three times more kids born in the same maternity
in the same conditions, but not autistic as a control.
So you have autistic kids, non-autistic kids born in the same maternity, the mother having
the same age and same conditions.
And then their task of these guys was to see if we can identify the babies without any
upriory, the day of birth, not before.
We need all the parameters going from conception to two days after birth.
Otherwise, my trick doesn't work.
I'm stressing this because I've been accused of being for eugenism, which is, of course,
I'm not.
And killing a baby at two days old, it's not eugenism.
So I'm not in favor of it.
So it's really after birth.
The whole thing requires, it's very important because parturition and birth are crucial
events in this scenery.
So I need parturition and birth.
Then they analyze all this.
Next, click on the same slide.
And what we discovered was we can identify almost 100% of the babies two days after birth
because we're not going to be autistic, they are not going to be.
And almost half those will be autistic years later.
Okay?
Now, this is one trial.
We hope to do more trials.
They are more than 41%.
We anticipate to be able to reach perhaps 60 or 70%, which, by the way, is higher than
any identification of what is growing on genetics.
Much higher.
Yeah, yeah.
We're doing at least as good as genetics.
In fact, much better.
I'll come back to it later, it's my favorite topic and you'll understand why.
Okay, next.
So then the question was, what are the parameters that brought the computer to the side this
baby is going to be autistic?
I mean, why has this decided this, the computer?
It turned out that some of the parameters were expected.
If the mother had to be all these, try to make a levires, viral infection, et cetera,
somewhere completely unexpected.
But this I anticipated because I'm not trying to understand what happens.
I'm simply trying to diagnose.
Okay?
One parameter interesting was, you see here in the middle, the position head down towards
the vagina to get out for birth comes earlier in future autistic babies than in others.
They are prepared to get out earlier.
Now a second important parameter, there are many other funny parameters.
One of them is the size of the femur, second trimester.
I have no idea why the femur should be bigger in fetuses of future autistic.
I have simply no idea.
But I don't care.
I'm not asking that question.
Yeah, we do ambitious to explain that.
Next slide.
But then it becomes even more interesting because we discovered that when you look at the brain
size in utero, second and third trimester, the brain size of future, we're talking here
about fetuses or embryos, the brain size of these fetuses or embryos is bigger in 40%
of the future autistic children already second trimester.
Why is that important?
Because a variety of American groups have shown that babies and infants have a bigger
brain if they're autistic than non-autistic until adolescence.
What I'm saying here is that this is not in utero in fact.
Brain construction is deviated by whatever insult led to autism.
What's more, what's also more interesting is that if you look at the other side of the
curve here, you can see that before delivery, the last image we did a couple of weeks before
delivery, the brain of autistic children is significantly bigger than non-autistic children,
all of them.
As if in preparation to birth, the brain continues to grow because just before birth, it doesn't
make any sense why they should grow more than neurotypic ones.
But of course, and here I come to the issue of parturization.
Parturization is crucial because it's by far the most complicated biological mechanism
in mammals, by far the most complicated.
There is no more complicated issue than parturization in birth.
Among the fundamental issues in parturization is that the brain must be protected from the
condition of delivery, which are tough.
To give you one example, the revision has shown that a baby born by vaginal delivery has a
much bigger, as a different sensitivity to pain than if he is born from C-sections.
They took a drop of blood and they measure along in Christ, basically.
The idea is that oxytocin, and we show this in mice, during delivery plays an important
role as a neuroprotective agent and a neuro-analgesic agent because of its pain, of course, when
he gets out.
And what they did in the revision was to measure the amount of stress molecules in just born
babies.
They show that the number of stress molecules of a baby born by vaginal delivery is huge,
much bigger than the mother who is suffering, much bigger than you and I if we do five marathons
or five hours of sound or God does what.
Now this high concentration of stress molecules is crucial for the lungs because the lungs
to evacuate water read that.
But the brain doesn't like that.
The brain, if your brain or mine were subject to this concentration of stress molecule,
we'd be epileptic.
So we need something to protect the brain from this while keeping this for the lungs.
My suggestion is that oxytocin does a job because we show that oxytocin in mice, shorted
during delivery, reduces a lot intercellar concentration of chloride, reducing thereby
ongoing activity.
And of course, if brain activity is low during delivery, it will be less susceptible to an
oxykin cell because there is a direct link.
If you are hyperactive and you have an oxykin cell, your neurons are going to suffer much
more.
So oxytocin plays sort of a role in addition to triggering delivery by provoking the contraction
of the uterus.
In addition to this, I've suggested, but of course, it's not proven in humans.
It's only proven in mice.
I cannot prove in humans.
I cannot measure before and during contraction and whatever.
It's very difficult to prove in the mice.
But in mice, it is proven.
So what we showed in mice, which is quite amazing, next slide I think, if you click
again, this is the same one.
So future infants, no, let's go back.
Go back one more.
Yeah, here, stop here.
Future infants with ASD have a bigger brain than neurotypic shortly before birth.
Now what we showed in mice, not in humans, is that we measure the size of neurons in
the cortex.
One hour before delivery and one hour after, but taking different mice, sacrificing them
and recording neurons.
The neurons continue to grow in notice and not in controls.
It's as if in aive animals, the brain stops growing, which makes sense.
Not in autistic future mice.
It goes on growing during this very tough period called partiality and birth.
This we cannot prove in humans for obvious reasons, but we are proving this in mice.
Whether it's true in humans is open to debate, but it's not unlikely that this would be
the case.
So brain growth is impacted in whatever mechanism it is building to it in utero, leading to bigger
brains of fetus and embryos, and leading to something which is reminiscent of a different
preparation to delivery and birth.
Okay, next.
This is the conclusion of that part.
Now the advantage of making such an early, by the way, the paper we published with the
first worldwide demonstration that you can identify babies at birth would be autistic.
And there is no genetic cure.
There is not a single genetic parameter.
Forget about genetics.
It's just a waste of time.
It seems like it's a waste of time.
It's a data.
It's a waste of time and money.
Unfortunately, it dominates.
Yes.
For reasons which are very mysterious.
Yes.
I mean, I had discussion with Simon's Foundation on this.
I failed to convince him how genetic is a complete waste of time and money.
But this is a...
I'm glad you put that out.
Because the fact has stopped.
It's four decades promising the boom and nothing happened.
There is not a single treatment based on genetic information.
Yeah, yeah, yeah.
Come on.
Okay.
And I'm providing an explanation here about that is the case.
Okay, next one.
Now we got three quotas.
Next one.
Now this slide summarized what are, of course, the norocology concept.
The idea is the following.
Usually people interested in genetic and all these models of proteomics, genomic, methyl,
bolamic, and Godot's one, they want to treat the inaugurating insult.
So you have an insult associated to his deficit A. I'm going to compensate the deficit A to
block the inaugurating insult.
Now when the inaugurating insult takes place in the womb, there's no way you can do that
by definition.
Why?
Because autism is a clinical diagnostic disorder.
It's not a biological define.
I mean, a child is considered autistic when the pedo-psychiatry says he's autistic.
It's no biological signature straightforward.
Now if the insult comes in neutral, forget about gene therapy or treating their inaugurating
insult.
Why?
Because what I'm going to show now is that the insult modifies brain construction.
And the disorder when you diagnose it is due to the modification, not to the initial insult.
The initial insult is, forget it.
A, you cannot correct it.
It's too late.
For instance, if the inaugurating insult has led to a bigger brain or to misplaced neuron
because they haven't migrated, there's no way you can correct this by genes or anything
else.
Why?
Because there is no more migration.
The space is taken.
I mean, there is no mechanism allowing migration to take place.
So the neuron which is misplaced will remain misplaced.
Yeah, it's final result.
It's final result.
So you cannot.
So what you must do is not treat the initial insult, but the consequences of initial insult.
If you click again, this arrow is going to move to the right.
You want to treat the target, not the initial.
It's completely used.
This is one of the things why genetic stuff is boring and doesn't mean efficient.
Next one.
Now this is an important slide because it summarized something which is simple and complicated.
The idea is basic idea is what?
The basic idea is that I discovered 40 years ago that neurons in the mouse brain have high
concentration of chloride when they are immature and low when they are adult.
Now they have high concentration of chloride initially in development.
This has been confirmed in every animal species until humans, unless all the way to humans,
from fish to birds to whatever.
It has been preserved throughout evolution.
In all animal species, chloride is high initially and low subsequently.
Now this is important why?
Because the principle inhibitor transmits regava, which provides brain inhibition in
adult, in young neurons excites.
It doesn't inhibit why?
Because its actions are dependent on the level of chloride inside.
If you have low level of chloride, it inhibits.
If you have high level of chloride, chloride is going to exit the cell inside of entering,
so the polarity is reversed.
This means for instance that the pregnant woman taking volume, which acts on gava, she
might have different effect on her brain that of the fetus.
Because the system is opposite.
To get a long story short, the developing brain is not a small adult brain.
It has its own rules, its own mechanism, its own function that are not present subsequently.
You must look at it as a special beast, so to speak, not common with what happens later.
It is quite important because A, it means that drugs, for instance, all sorts of common
drugs, proscik and gondos, should not be taken by the pregnant woman because what they do
on the mother is not necessarily what they are going to do on the little one.
Yeah and that's becoming more and more understood and accepted.
Yeah, but I mean, basically the idea is that during pregnancy women must abstain from almost
everything, unfortunately this weight goes, pollution, etc.
For everything there is evidence, everything, pollution, stress, molecules, whatever.
Now I discovered this then, I discovered that in autism there is a reverse situation.
In cortical neurons of mice with autism, gava again excites because chloride again accumulates.
Now the interesting thing is that in most cases it's a reverse image because in the
developing case chloride is high because there is a code transporter called NKCC1, sodium
potassium chloride chloride NKCC1, which is crucial, it's present in all cells and it
controls ion distribution.
As you know, neurons are like a battery.
All the energy is spent to preserve ion distribution.
Low chloride inside, high sodium, high potassium inside, low sodium outside, etc.
If this is deviated, you are epileptic and you have all sorts of disorders.
Now in pathological conditions, again NKCC1 is overactive, as if the neurons are again
immature.
This is an over-simplification by the sadio.
This will be reported in autism, in epilepsies, then it will discover in all the disorders
I'm listing here.
It's an incredible list of disorders in which some neurons are again immature, basically.
Now this means that drugs blocking NKCC1 or activating, you see the chloride concentration
is controlled by an importer and an exporter.
The importer is NKCC1, the exporter is KCC2.
In pathological conditions, the exporter doesn't work well and the importer works a lot, so
chloride accumulates and gava excites.
Now in those all those conditions it works, meaning that the drug blocking NKCC1 is going
to be very useful in a lot of disorders.
So we investigated two pathological conditions.
One I'm not going to talk about, I'm working a lot on this, and this is brain tumors, but
I will talk about the subject of your...
I'm going to talk only about autism next slide.
So what we did, basically this situation.
We have low chloride normally, high chloride in pathology, and if you block NKCC1, this
is a drug called bebetanide, the metanide that's shown here.
This is a generic drug fabricated 50 years ago by a Swiss company to treat hypertension
and brain edema.
Basically you go to the loo, pee pee, you remove water and your tension is reduced, etc.
Now in theory bebetanide should be able to block all of these.
Now this is not only a theory, because this has been shown to be the case experimentally
in all these disorders, animal models.
Next one.
Now the NKCC1 that you can see here is crucially in a lot of systems.
It consumes a lot of energy via sodium potassium ATP as an ATP.
Its structure has been crystallized more or less, you can see to the right, and bebetanide
we know more or less at which site it penetrates to do what it does, and bebetanide is the
best and most specific antagonist of NKCC1.
In fact NKCC1 was partly clothed because of bebetanide.
Thanks to bebetanide.
We did two phase two double blind randomized studies in France.
84 children and I think 67 children.
In both cases it was bebetanide placebo, children 2 to 18 or 3 to 11, treated for three months
with half, one or two milligram bebetanide.
I can show you films in several cases the effect of spectacular.
Now if you see this here, why do you see this?
What you see at your right, every blue column here is one kid in this trial.
The measure is called CAVS, children's autistic scale.
This is done by the pedocyciatrist.
The bigger the column, the better the effect.
If you have 8 to 10 point amelioration and you go from 46 to 36, you're not cured but
you are very strongly less autistic.
And you can see that all the blue columns are treated with only one exception orange
here which is placebo.
So there are exceptions of course, but according to this, the treatment is quite efficient.
Then we did it with the at the right, the table that you have is social responsive scale.
This is another scale made by the parents this time.
Here we gave 0.5, 1 or 2 milligrams to the kids.
According to the FDA, if you have more than 10 point ameliorations, it's extremely good.
You can see here below the last line that we had between 10 and 20 point amelioration
and only 1.5 point amelioration is placebo.
So the difference is quite spectacular.
Of course, we abolished 2 milligrams because the erratic effect are too strong in a young
child.
So we decided to take only 0.5 or 1 milligram twice daily, morning and afternoon.
And this is now used all over the world.
I mean, next line.
More eye contact even.
A meta analysis in fact revealed that 1,050 children have been treated successfully in
nine trials, our two trials and seven others made in China, England, Holland, Egypt, Tunisia,
Iran and Africa to each other country.
All of them doing exactly what we did, open 5 milligram twice daily or 1 milligram twice
daily, three hours.
All of them showed a very significant amelioration.
The Egyptian stuff is quite interesting because they isolated the parameters which seem to
be particularly improved.
And this is agitation and social recognition and a frighten of develop of novelty, facing
novelty problems.
So we fabricated a liquid formulation of the metanide because the pills are very non-tasty
and big.
Next slide.
These are the trials made in different countries confirming what I just told you.
Next one.
Then we did visual interactions and brain imaging on 15 adolescent resultants before
after treatment.
What we found is after treatment the kids recognized better the emotive figures that
you see here, which are different on the neutral ones shown at the right.
So we asked them to recognize the woman if she's crying or laughing, whatever, and the
guitar or the rabbit or whatever.
And there was a significant improvement.
Next slide.
Then we did brain imaging.
One more.
And we found that regions, if you ask the child or the adolescent, these were the adolescents,
to look at the eyes by putting a cross on the nose and asking the kid to look at the
eyes, usually they're frightened.
The activation by the image of the eyes of the amygdala, which is a fear region, is reduced
by the metanide.
They are less frightened.
And we have a direct proof of this that they look more in the eyes after treatment.
Next slide.
Can I ask a question?
Is this interacting at all with oxytocin or vasopressin?
Now the problem with oxytocin, vasopressin to the best of my knowledge was not a significant
demonstration that it's efficient in humans' in clinical trials, to the best of my knowledge
there isn't.
Oxytocin, there have been many, many trials in Europe, in the US, in Japan.
Unfortunately, they are very, very contradictory.
Now, remember, oxytocin does exactly what the metanide does.
Reduce chloride and inhibition.
I agree with that.
The problem is the lifespan of the drug, how fast it's created and so forth.
In addition, and this I'm going to show in a minute, you're going to understand why oxytocin
results have failed.
Just keep the question for one more minute.
Next slide.
Now, unfortunately, in spite of all these results, we need to phase three, finally three,
and four hundred and twenty children in two groups, two, six, seven, eighteen years old,
in Europe, Brazil, Australia, forty centers, a very large study.
It failed.
There was no difference between treatment and placebo.
Now phase three, the problem is you have only one parameter that must differ in placebo
treatment.
And this parameter, for instance, CARS, is a mean of fifteen different items.
SRS is a mean of sixty-five different items, meaning that if the mean is not different,
it does not imply that sub-items, coding for agitation, visual connections, you know,
seizures, whatever, would not be significant.
You see the point?
Centering everything on a mean of something so heterogeneous is something that's meaningless.
This is why they explain why all phase three trials done on fragile eggs, autism, I failed,
even though phase two were successful.
Phase three failed always.
It's originating and lack of taking into account the multiplicity of items that can't be modified
separately.
If I have a drug that treats agitation in kids of autism, it's not bad.
Even if it doesn't treat something else.
You see what I mean?
So what we did again, we did the same thing.
And this was also influenced by a study made by a Dutch group showing that you can identify
by EEG the kids who are going to respond to the metanide.
The Chinese show the same by measuring immunological sample, amount of stress molecules.
The more you have stress molecules, the more you are going to respond to the metanide.
I took a very different approach next slide.
Again going back to machine learning, we decided that all these data we have, we have huge amount
of data on phase three, hundreds or thousands of parameters.
What about using machine learning to identify subpopulations?
So what the computer does, it take all the kids with all the parameters, not only cars,
but all the 15 parameters, sub-items of cars, 65 sub-items of SRS, etc.
And it identifies subpopulations.
The question was, can I identify subpopulation of kids responding to the metanide within
the phase three?
And can I identify them in order to be able to subsequent phase three, in which inclusion
criteria would be the ones I have defined?
So I would not include all children with autism, and I could not include having those features.
And we succeeded.
We have identified 25 to 40% of children responding to the metanide, relying on clinical sub-items,
a mixture of several sub-items.
This is important.
Now this is now being, I hope, patent protected, because this is a private company, I don't
have huge amount of money, I didn't have money to go on, I don't have any financial support
for the moment, and I'm trying to convince a pharma or investor to help me making a phase
three with these criteria.
This will succeed.
Everybody's money is going to genetics though, as we discussed.
No, yeah, but I mean, you see, they have a sense of humor.
There are experts in genetics who have published every month a paper in Nature on the new
mutation, blah, blah, blah, blah.
They have never done it, you know what they're doing now?
They want to use lithium to treat the tissue.
Give me a break.
And I would say more anti-psychotic treatment too.
And I'm...
We don't need to make thousands of studies on specific mutations then to use lithium,
give me a break.
Yeah, it's not...
Yeah, it won't break, by the way, it won't break, we know.
It's so...
No, but they are desperate to propose a treatment, desperate, because I, using stupid old-fashioned
drugs, reach phase three.
What do they have to say in front of this topic?
It's just an anti-diuretic, correct?
It is a diuretic.
A diuretic, yeah.
And the only side effect, in fact, indeed, are diuresis and dehydration.
But this has been given to millions of patients during the last 20 or 40 years.
There is not a single death, we never found anything really serious, nothing.
Yeah, I agree.
You must control potassium down there in the blood, and that's it.
And drink water and go to the loo.
It's alright.
I mean, the side effect of some of the drugs used for epinepsis, or for otitis, by the
way, like the two favorite ones, people get fat, forget about this.
No, no, there is no comparison with other drugs.
So, but the message here is, not only is not genetics, it's really maternity.
And it's really maternity with, by the way, the Americans in San Francisco have proven
that the woman pregnant second trimester close to it, feeling which have pesticide, the
answer to what it goes out.
It's proven it's not stupid ideas of genetic guides.
It's the same thing with pollution, the same thing with stress, the same diabetes, printer
and delivery, C-section in certain cases, etc., etc.
All of these relate to the womb, maternity and delivery, meaning that you really must
protect pregnant women.
This is the most important message of this.
And you know, if there are diabetes, they are poor and they eat fat and etc., etc.,
you know, the consequences are well known.
The problem with genetic, it has to be deterministic, very stupidly, because life is not deterministic.
I mean, you know, you and I have the same genes.
If you go to eat every day to McDonald's, I don't really diabetes, I won't.
It's a simple thing.
And plus, like chimps, we're pretty much identical genetics with chimps and we're
nothing like chimps.
No, no, okay.
By the way, they rely a lot on twin studies to decide the genetics.
I'm just writing a paper, I hope to publish it soon, in which I'm demolishing point by
point everything about genetics.
I'm explaining that twin studies are wrong.
I'm explaining that what they love most is called GWAS, I don't know if you know what
GWAS is.
Yeah.
Polygenic, whatever, blah, blah, blah.
I mean, the basic conditions to use GWAS are never met, never.
This whole blah, blah, blah.
And I'm writing a very detailed paper.
Now, of course, I said it to genetic journals, they rejected it.
But now I said to medical genetic journal, perhaps you'll be published.
It's very, and I'm writing a book in English with a colleague of mine, we're expert evolution.
The title is something like autism is a neutral inflammatory disorder.
Forget about genetics.
Yeah, good, good.
Let's go back to our topics next one.
Okay.
So this is summarized what I told you.
Okay.
So we're aiming to find money to use a phase two, three unidentified responders, which
will work bringing the first drug within two or three years to the market to treat autism.
Next one.
How many additional additives something else?
I decided, you know, farmers don't like to generate drugs because you can buy it in the
farm, it's cheap and they're not going to make money.
Best to cut the long story short.
So I decided to fabricate molecules which belong to me, novel molecules, which block
MQC one, belong to me and are as efficient as we can tonight and perhaps even better.
Next slide.
So working with chemists for years, three years now, we are looking at this.
Well, forget about the oblastomates.
I was saying to do it here, but anyhow, we want to drugs which work as well as the methanol
and our aims are to find money to go to pre-IND studies to phase one.
Basically, if you have a new molecule in vitro, it does what you want to be sure that it does
exactly what methanol does or see shows an activity on gamma, et cetera.
Well now we need to take the best one to pre-IND phase one.
And this costs a lot of money because it's toxicology, it's not toxicity, et cetera.
But next slide.
We have now 120 different molecules.
They all act only in QCC one.
Some of them are better in libido than bimetonite, which is, I don't think anybody has discovered
the molecule, better than bimetonite.
I've tested them in cancer.
Sorry, this area is a mixture with cancer.
But forget about cancer.
The idea is perfectly the same for autism.
Now the idea is that if I have a molecule reaching phase one, not toxic, it's going to
be efficient in so many different molecules that it's going to be extremely valuable,
I mean, I guess even millions, because it could work for us.
By the way, there is a beautiful paper on Alzheimer's disease, which I liked a lot.
Two years ago by an American group, the first auto-established, TAUBES, natural aging.
What they showed was they tested 1,000 molecules, which are widely used, a volume from a barbital,
prozac, whatever.
Which of them is the best on an apoe-dependent Alzheimer's disease?
The answer is bimetonite, out of 1,000.
Then there is something which is even more impressive, epithemological study on 6,065
years old Americans, comparing those who took or not bimetonite for any reason.
Those who took bimetonite have reduced 30 to 70% incidence of Alzheimer's disease.
I think it's very, very striking.
So this drug is not dead.
What I'm trying to say, the phase three died, not the drug.
This one, I think it's the last one.
No, this is simply physiognomy to show it does exactly what you would expect, blocking
seizures and reducing gabae, increasing gabae inhibition.
I think that's it.
Have I summarized everything or are there other questions?
So I would like your idea of the neuroarchaeology and identifying within the womb.
And you comfortably saying, I think pretty confidently, I should say that autism is definitely
in the womb.
What do you think is the biggest barrier for getting that out as being accepted both by
other scientists and how to allow the lay public, just normal common people to understand
this and understand the risk of the environment for the pregnant mother?
This is a very fundamental question.
The answer is complicated, A, because it's also to some extent political.
In countries like France, pregnant women are protected.
They have 12 weeks vacation, all paid by the employers.
To take only one example, in the US, in the case.
So there are ethical aspects I will leave aside.
But the fundamental issue is very simple.
The data we published, and many others, by the way, following our results and others,
are compelling.
I mean, the only issue with the public, which one should be very careful about, is the problem
of A, it's the mother problem.
She's responsible, which has been here decades.
It's very easy to be argument, which makes no sense at all.
It's not the mother responsible.
If the mother lived in a field in which she has pesticide, okay, the pesticides are going
to do what they do.
If her husband is an alcoholic and beats her, and she has nothing to eat or go to, is she
responsible?
I mean, the responsibility of the mother is something disgusting, to be honest.
It makes us...
Right.
I hear that during maternity, this is born for reasons that are so multiple that...
But you know, we're beginning to win.
Women pregnant now smoke less than in the past.
They take less alcohol than in the past.
So we're improving, but it's very slow.
And it's very slow because here I'm not talking about alcohol and smoking.
I'm talking about life conditions.
Yeah, yeah.
You should try not to be obese or diabetic when you're pregnant.
There are hundreds of problems.
Anti-apileptic is a problem.
The woman is epileptic.
The reason anti-apileptic is very well-received.
She becomes pregnant.
Stopping the treatment is problematic because she could lose a child, the baby.
Bringing it up continues is also problematic because it could be malformed.
And there are trials in France against sanofi because a very classical anti-apileptic called
depakine has been shown 30 years ago to increase brain abnormalities and others abnormalities.
But the decision is not simple.
If I am the neurologist, I have a woman, a epileptic, what do I do?
It's not simple questions.
You don't want to stop it and you don't want to go in either.
So the message is any politics should do all its best to protect women during pregnancy.
Yeah.
And this is a...
It's not a priority today.
No.
And as you mentioned, it's much different in the U.S.
The environment of the pregnant mother is typically not great.
And it might sound sexist or something like that, but they're forced to or they choose
to work up into almost the time of labor.
And I've just...
It's just very concerning to me.
Well, you know, in France, you have 12, now 14 months even.
You have protection for a long time and the husband can take part of it to help whatever.
By the way, I wanted to do this study I showed here in neutral measures to detect.
I want to do this, yes.
I spoke to some of my colleagues at the big hospitals in the U.S.
It's impossible because the calligraphy, whatever, are paid by the patients.
So you have very little information.
Yeah.
There is no real collection of maternity data.
So I can't do it in the U.S.
So this stuff would be in France, not in the U.S.
By the way, I cannot apply it as if immediately to England because in England you have only
two calligraphies, not four, not three like in France.
And they have less collection of...
It depends on the countries.
It could work in Norwegian countries, Norway, Sweden, Holland as usual.
These are the best in terms of care of women, et cetera.
Perhaps Switzerland.
Yes, Switzerland probably.
But that's it.
Even in Europe it will not work in Bulgaria or Romania or perhaps even Germany.
So it's an endless problem.
It's a very complicated one, yet a crucial one.
Yeah.
There's a lot of humans that don't understand the problem involved in the decision-making.
Do you know the differences between the rates of autism in the U.S. and let's say France?
I think they're quite similar.
But the answers are not straightforward because in your country you have better epidemiologists
doing this than in New York, France.
I don't think we have as detailed epidemiology.
There's a lot of variables with that question.
Yeah.
We don't have the same amount of studies on epidemiology for autism in France.
Yeah.
But I guess the numbers will not differ tremendously.
And even across U.S. there are areas that have extreme rates.
Like around San Francisco, they have almost like one in 20 children.
Yeah.
So...
No, no, it's frightening.
But it's not only autism.
It's a fact that if you make a very simple financial calculation, which your government
and mine like a lot, it costs much more to treat them afterwards than to do what they
can do on pregnancy.
There is no comparison.
Yes.
I haven't ever seen saying that.
I'm glad you confirmed that.
Oh, the cost.
I mean, people have calculated, I can find the papers, how much a child autistic cost
to the society and parents.
If you calculate everything, the woman not working and blah, blah, everything.
And you include all these.
The sums are huge.
Billions.
Every episode of autism.
You know, in medicine, what's important is prevention, not treatment.
Always.
And U.S., I can't speak of other countries, but the U.S. is awful.
There probably be the worst at this.
They are among the worst.
Yeah.
The life expectancy of Americans is below that of Cubans.
Yeah.
And it's very stagnant and flattened towards the bottom.
Yet our health budget is almost two times the second.
You pay more than us and you have less life expectancy for a very simple reason.
The reason is that socializing health is cheaper than non-socializing it.
In our country, we have one social security.
I paid my part directly from my salary.
They take a percent of my salary to put in social security.
Then I don't have to pay medical, treatments, surgery, whatever.
And it's cheaper.
No, no, it's, again, it's a political problem.
And you know, we're not going to go to politics, but this is really a political problem.
And you're facing an election which, I won't say anything, but you can't be even worse.
The four of the top five revenue industry types are around healthcare, hospitals, big
pharma, health insurance.
But I didn't bring you on to talk about that, but it is an important topic.
I agree, but this is beyond our competence.
You agree with that?
So whenever I first heard GABA was excitatory through that immature, developing brain,
I was blown away.
Because one of the first things I learned about autism was this excitation inhibition
imbalance.
So and I assumed that GABA was excitatory up and through this probably critical period.
Is it because it helps accelerate learning and development?
No, GABA is excitatory only in uterine humans, not afterwards.
But it's excitatory in utero because we and many others have shown that GABA exerts trophic
actions.
GABA controls neural growth, synapse formation, lateral formation.
If you brought GABA, neurons do not establish as many synapses and do not grow as much.
And migration is deficient.
So GABA excites immature neurons for these reasons.
But the result of excitation by glutamate becomes a D3.
Nutri is much cleverer than we are.
Much clever.
Wow.
Okay.
Yeah, I'm looking forward to your future research and especially some of those things
that you're working on.
As you get more results, maybe you can come back on and discuss those with me.
I'm going to be looking out for some of those items that you mentioned today.
I'm very excited.
Yeah, I was thinking, if the English paper would get out, the book will take some time.
Yeah.
I have two books you can advertise in English.
One of them is the first 1000 days, which is published in English now.
It's great.
I really want to read about that.
And the second one is the better life to treat autism.
The two books are now in English and they are accessible via the usual sources.
And the first one I explained why better I treat autism as efficient.
And the second one I explained why the 1000 days going from conception to second years
of life are crucial.
Yeah.
I don't know what everything I told you here.
Now, in general, whole pollution, et cetera, et cetera.
So the two books are related to what we discussed here.
Yeah.
I get frustrated with autism research a lot.
But you're one that I have trust in.
You expand the edges of science instead of just being stuck.
You know, I have always said to my students, if you want to make great discoveries, they're
always inside with never in highways.
If everybody tells this, you will miss.
Yes.
Follow the modes and fashion.
This is why I don't like genetics because it's a modern fashion.
It's going to die one day or another when they discover that.
And the same thing applies to all these big stuff, proteomics, metabolomics, genomics.
We're going to count every protein you have in your body, regardless of the state, why
you or somebody else is autistic.
Give me a break.
You know, if you take a transistor from a television, it doesn't work.
It's a transistor which in fact doesn't tell you anything about what else happened.
Come on.
I would like to give a special thank you to our guest today.
Dr. Ben Ari.
It's not difficult to see Dr. Ben Ari's passion towards autism.
Discovering when, the precise where and when autism is developing.
His research is expanding the edges of the autism community.
It's unfortunate that there are other factors involved with autism research, but we very
much appreciate his voice for the autistic community, autistic research and what is wrong.
Now we went into genetics and it's not uncommon that the podcast speaks about the genetic
factors and how there's not an answer here.
Even her, Dr. Catherine Lord mentioned that she doesn't think there's an answer here.
Yet so many people are invested and they want an outcome here.
They keep searching, but it's incorrect.
I very much appreciate Dr. Ben Ari's five decades of research and knowledge and information
that he has contributed to both the scientific community at large and the autistic community.
He has a lot of good projects going and moving forward.
So this is giving us a lot of hope and something to look forward to as he is publishing and
finding other answers and other alternatives.
I very much appreciate him speaking out on the psychopharmacology that's being used for
autism.
This is very concerning.
If you're listening to the podcast or listening to the episode, please feel free to leave
a review or rating.
In podcasting, reviews, ratings and downloads are huge and I very much appreciate your feedback.
You can contact me on X at RPS 47586 or you can check out the Hop link where you can
find all links to the podcast forms and my contact information and social media.
Thank you for listening too.
From the Spectrum Podcast.