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My guest today is Dr. Yusieke Ben Ari.

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In 1971, Dr. Ben Ari received a Ph.D. with a focus on neuroplasticity and followed with

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postdocs at prestigious universities, including University of Cambridge, University of Oslo,

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and McGill University.

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In 1986, Ben Ari was appointed head of NSERM in France, focusing on neurobiology and pathophysiology

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of development.

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In 1999, he founded and led NMED, Neurobiology Institute of the Mediterranean.

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In 2008, Ben Ari turned to startups to better understand and study brain disorders.

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He's the founder and CEO of Neurochlorie, where they trial humanitine and research the

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molecular mechanisms of autism.

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In BNA Therapeutics, where they study treatment options for Parkinson's and the regulation

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of intracellular chloride effects of GABA signals.

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In BNA OncoMedical, where they are dedicated to treat brain tumors.

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Dr. Ben Ari is among the top five most quoted French neuroscientists and has over 520 publications

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and is a recipient of many awards, including NSERM Grand Prix.

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Grand Prix European Society of Epilepsy.

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Grand Prix Kanye Van Heck Belgium National Scientific Research, to name a few.

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Dr. Ben Ari has over 5 decades of academic and private research with major discoveries

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on electrical signals of brain development and pathology.

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Being a favorite of mine, GABA is excitatory during the developing immature brain.

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Recently, Ben Ari is part of a team using machine learning to identify autism in the

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embryo and a priest symptomatic signature called neuroarchaeology that predicts brain

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disorders in utero.

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In the developing brain, such as during cellular migration.

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Remember covering different epochs in the autism and embryo episode and how cells migrate

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to common cells to carry out common functions.

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Here we will explore more on this critical time.

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And now my conversation with Dr. Ben Ari.

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The issues I'm going to discuss pertains to the way one can identify early autism.

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How can one treat it?

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And why is it that studying brain development is crucial to understand and treat autism?

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Because the first thing you must remember is that autism is born in the womb and this

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is what I'm going to show you in a minute.

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And as it's born in the womb, it modifies developmental sequences which are crucial

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for brain construction.

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This implies that we're not going to cure autism in the sense I have had it, I take

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an aspirin, I have no more had it.

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Because there are some small malformations in brain construction which are already present

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in utero.

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Meaning that we, at best, and this is not bad at all, we can attenuate strongly the

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disorder we have arrived at through the drugs I'm going to talk about.

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Particularly if they're started to be used very early in life.

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For a very simple reason is that the first years of post-lateral life once you are born

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are crucial for many, many fundamental issues, social interactions.

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I mean, if your mother is crying and you laugh because you're looking at her shoes, it's

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not like a family, it's an incapacity to look at the eyes.

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So there are also very simple reasons why autism is what it is.

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And the first two years are absolutely crucial in addition to the maternity period.

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So first let's go to the prediction of autism.

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Okay, this I remind you a couple of fundamental issues.

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The incidence of autism is going up, nobody knows why.

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I think it's because of the maternity problem, but this is my point of view.

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Is born in the womb?

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It can be due to genetic mutations, pesticide, pollution.

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No, no.

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Now go back to the previous slide.

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Yeah, it's generated in the womb by pesticide, pollution, and variety of factors.

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Now the question is, if it's generated in the womb, can we identify the baby at birth

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with going to be autistic and identify autistic years later?

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And that says yes.

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Next slide.

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What we did is the following.

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Well, this we can come back to this later.

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I go to the next slide.

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It's not the issue now.

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Okay, what we did is the following.

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We went to a maternity hospital in the south of France and the pedocyclery is identified

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as a child with autism.

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He was treating.

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He went back to the obstetrician, Dr. Kali, which is here below.

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And this guy extracted the maternity files of those kids.

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In other words, you have a kid who is autistic.

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I'm going to extract all the maternity files corresponding to that guy from three to 15

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or 18.

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In France, maternity files are very rich, between 120 to 150 different parameters, including

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at least three ecographies, three brain scans during maternity, paid by the state.

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So I mean, we have the collections.

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Taking all these parameters, I then recruited two big data analysts shown here, Ahmed and

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Marie-Dine.

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They are experts of big data analysis.

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Because you understand, if you want to analyze 120 parameters in thousands of children and

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different conditions, you need big data analysis.

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So what they did, now, in addition, we took three times more kids born in the same maternity

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in the same conditions, but not autistic as a control.

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So you have autistic kids, non-autistic kids born in the same maternity, the mother having

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the same age and same conditions.

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And then their task of these guys was to see if we can identify the babies without any

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upriory, the day of birth, not before.

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We need all the parameters going from conception to two days after birth.

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Otherwise, my trick doesn't work.

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I'm stressing this because I've been accused of being for eugenism, which is, of course,

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I'm not.

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And killing a baby at two days old, it's not eugenism.

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So I'm not in favor of it.

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So it's really after birth.

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The whole thing requires, it's very important because parturition and birth are crucial

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events in this scenery.

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So I need parturition and birth.

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Then they analyze all this.

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Next, click on the same slide.

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And what we discovered was we can identify almost 100% of the babies two days after birth

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because we're not going to be autistic, they are not going to be.

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And almost half those will be autistic years later.

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Okay?

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Now, this is one trial.

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We hope to do more trials.

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They are more than 41%.

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We anticipate to be able to reach perhaps 60 or 70%, which, by the way, is higher than

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any identification of what is growing on genetics.

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Much higher.

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Yeah, yeah.

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We're doing at least as good as genetics.

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In fact, much better.

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I'll come back to it later, it's my favorite topic and you'll understand why.

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Okay, next.

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So then the question was, what are the parameters that brought the computer to the side this

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baby is going to be autistic?

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I mean, why has this decided this, the computer?

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It turned out that some of the parameters were expected.

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If the mother had to be all these, try to make a levires, viral infection, et cetera,

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somewhere completely unexpected.

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But this I anticipated because I'm not trying to understand what happens.

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I'm simply trying to diagnose.

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Okay?

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One parameter interesting was, you see here in the middle, the position head down towards

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the vagina to get out for birth comes earlier in future autistic babies than in others.

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They are prepared to get out earlier.

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Now a second important parameter, there are many other funny parameters.

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One of them is the size of the femur, second trimester.

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I have no idea why the femur should be bigger in fetuses of future autistic.

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I have simply no idea.

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But I don't care.

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I'm not asking that question.

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Yeah, we do ambitious to explain that.

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Next slide.

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But then it becomes even more interesting because we discovered that when you look at the brain

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size in utero, second and third trimester, the brain size of future, we're talking here

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about fetuses or embryos, the brain size of these fetuses or embryos is bigger in 40%

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of the future autistic children already second trimester.

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Why is that important?

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Because a variety of American groups have shown that babies and infants have a bigger

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brain if they're autistic than non-autistic until adolescence.

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What I'm saying here is that this is not in utero in fact.

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Brain construction is deviated by whatever insult led to autism.

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What's more, what's also more interesting is that if you look at the other side of the

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curve here, you can see that before delivery, the last image we did a couple of weeks before

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delivery, the brain of autistic children is significantly bigger than non-autistic children,

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all of them.

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As if in preparation to birth, the brain continues to grow because just before birth, it doesn't

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make any sense why they should grow more than neurotypic ones.

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But of course, and here I come to the issue of parturization.

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Parturization is crucial because it's by far the most complicated biological mechanism

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in mammals, by far the most complicated.

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There is no more complicated issue than parturization in birth.

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Among the fundamental issues in parturization is that the brain must be protected from the

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condition of delivery, which are tough.

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To give you one example, the revision has shown that a baby born by vaginal delivery has a

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much bigger, as a different sensitivity to pain than if he is born from C-sections.

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They took a drop of blood and they measure along in Christ, basically.

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The idea is that oxytocin, and we show this in mice, during delivery plays an important

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role as a neuroprotective agent and a neuro-analgesic agent because of its pain, of course, when

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he gets out.

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And what they did in the revision was to measure the amount of stress molecules in just born

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babies.

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They show that the number of stress molecules of a baby born by vaginal delivery is huge,

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much bigger than the mother who is suffering, much bigger than you and I if we do five marathons

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or five hours of sound or God does what.

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Now this high concentration of stress molecules is crucial for the lungs because the lungs

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to evacuate water read that.

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But the brain doesn't like that.

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The brain, if your brain or mine were subject to this concentration of stress molecule,

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we'd be epileptic.

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So we need something to protect the brain from this while keeping this for the lungs.

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My suggestion is that oxytocin does a job because we show that oxytocin in mice, shorted

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during delivery, reduces a lot intercellar concentration of chloride, reducing thereby

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ongoing activity.

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And of course, if brain activity is low during delivery, it will be less susceptible to an

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oxykin cell because there is a direct link.

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If you are hyperactive and you have an oxykin cell, your neurons are going to suffer much

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more.

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So oxytocin plays sort of a role in addition to triggering delivery by provoking the contraction

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of the uterus.

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In addition to this, I've suggested, but of course, it's not proven in humans.

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It's only proven in mice.

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I cannot prove in humans.

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I cannot measure before and during contraction and whatever.

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It's very difficult to prove in the mice.

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But in mice, it is proven.

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So what we showed in mice, which is quite amazing, next slide I think, if you click

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again, this is the same one.

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So future infants, no, let's go back.

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Go back one more.

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Yeah, here, stop here.

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Future infants with ASD have a bigger brain than neurotypic shortly before birth.

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Now what we showed in mice, not in humans, is that we measure the size of neurons in

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the cortex.

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One hour before delivery and one hour after, but taking different mice, sacrificing them

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and recording neurons.

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The neurons continue to grow in notice and not in controls.

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It's as if in aive animals, the brain stops growing, which makes sense.

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Not in autistic future mice.

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It goes on growing during this very tough period called partiality and birth.

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This we cannot prove in humans for obvious reasons, but we are proving this in mice.

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Whether it's true in humans is open to debate, but it's not unlikely that this would be

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the case.

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So brain growth is impacted in whatever mechanism it is building to it in utero, leading to bigger

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brains of fetus and embryos, and leading to something which is reminiscent of a different

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preparation to delivery and birth.

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Okay, next.

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This is the conclusion of that part.

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Now the advantage of making such an early, by the way, the paper we published with the

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first worldwide demonstration that you can identify babies at birth would be autistic.

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And there is no genetic cure.

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There is not a single genetic parameter.

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Forget about genetics.

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It's just a waste of time.

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It seems like it's a waste of time.

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It's a data.

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It's a waste of time and money.

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Unfortunately, it dominates.

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Yes.

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For reasons which are very mysterious.

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Yes.

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I mean, I had discussion with Simon's Foundation on this.

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I failed to convince him how genetic is a complete waste of time and money.

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But this is a...

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I'm glad you put that out.

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Because the fact has stopped.

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It's four decades promising the boom and nothing happened.

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There is not a single treatment based on genetic information.

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Yeah, yeah, yeah.

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Come on.

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Okay.

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And I'm providing an explanation here about that is the case.

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Okay, next one.

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Now we got three quotas.

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Next one.

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Now this slide summarized what are, of course, the norocology concept.

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The idea is the following.

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Usually people interested in genetic and all these models of proteomics, genomic, methyl,

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bolamic, and Godot's one, they want to treat the inaugurating insult.

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So you have an insult associated to his deficit A. I'm going to compensate the deficit A to

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block the inaugurating insult.

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Now when the inaugurating insult takes place in the womb, there's no way you can do that

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by definition.

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Why?

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Because autism is a clinical diagnostic disorder.

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It's not a biological define.

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I mean, a child is considered autistic when the pedo-psychiatry says he's autistic.

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It's no biological signature straightforward.

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Now if the insult comes in neutral, forget about gene therapy or treating their inaugurating

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insult.

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00:17:43,520 --> 00:17:44,520
Why?

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Because what I'm going to show now is that the insult modifies brain construction.

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And the disorder when you diagnose it is due to the modification, not to the initial insult.

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The initial insult is, forget it.

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A, you cannot correct it.

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It's too late.

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For instance, if the inaugurating insult has led to a bigger brain or to misplaced neuron

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because they haven't migrated, there's no way you can correct this by genes or anything

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else.

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Why?

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Because there is no more migration.

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The space is taken.

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I mean, there is no mechanism allowing migration to take place.

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So the neuron which is misplaced will remain misplaced.

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Yeah, it's final result.

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It's final result.

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So you cannot.

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00:18:27,600 --> 00:18:37,000
So what you must do is not treat the initial insult, but the consequences of initial insult.

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If you click again, this arrow is going to move to the right.

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You want to treat the target, not the initial.

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00:18:45,000 --> 00:18:46,000
It's completely used.

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This is one of the things why genetic stuff is boring and doesn't mean efficient.

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Next one.

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Now this is an important slide because it summarized something which is simple and complicated.

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00:19:04,920 --> 00:19:06,800
The idea is basic idea is what?

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The basic idea is that I discovered 40 years ago that neurons in the mouse brain have high

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concentration of chloride when they are immature and low when they are adult.

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00:19:20,600 --> 00:19:26,720
Now they have high concentration of chloride initially in development.

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This has been confirmed in every animal species until humans, unless all the way to humans,

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from fish to birds to whatever.

283
00:19:34,720 --> 00:19:36,880
It has been preserved throughout evolution.

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In all animal species, chloride is high initially and low subsequently.

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00:19:43,440 --> 00:19:45,080
Now this is important why?

286
00:19:45,080 --> 00:19:50,800
Because the principle inhibitor transmits regava, which provides brain inhibition in

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adult, in young neurons excites.

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00:19:53,320 --> 00:19:55,320
It doesn't inhibit why?

289
00:19:55,320 --> 00:20:00,440
Because its actions are dependent on the level of chloride inside.

290
00:20:00,440 --> 00:20:03,240
If you have low level of chloride, it inhibits.

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00:20:03,240 --> 00:20:08,760
If you have high level of chloride, chloride is going to exit the cell inside of entering,

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so the polarity is reversed.

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00:20:13,200 --> 00:20:17,360
This means for instance that the pregnant woman taking volume, which acts on gava, she

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might have different effect on her brain that of the fetus.

295
00:20:20,800 --> 00:20:21,800
Because the system is opposite.

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To get a long story short, the developing brain is not a small adult brain.

297
00:20:26,840 --> 00:20:33,440
It has its own rules, its own mechanism, its own function that are not present subsequently.

298
00:20:33,440 --> 00:20:40,080
You must look at it as a special beast, so to speak, not common with what happens later.

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00:20:40,080 --> 00:20:49,000
It is quite important because A, it means that drugs, for instance, all sorts of common

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drugs, proscik and gondos, should not be taken by the pregnant woman because what they do

301
00:20:54,440 --> 00:20:57,680
on the mother is not necessarily what they are going to do on the little one.

302
00:20:57,680 --> 00:21:01,600
Yeah and that's becoming more and more understood and accepted.

303
00:21:01,600 --> 00:21:08,680
Yeah, but I mean, basically the idea is that during pregnancy women must abstain from almost

304
00:21:08,680 --> 00:21:12,400
everything, unfortunately this weight goes, pollution, etc.

305
00:21:12,400 --> 00:21:19,920
For everything there is evidence, everything, pollution, stress, molecules, whatever.

306
00:21:19,920 --> 00:21:27,440
Now I discovered this then, I discovered that in autism there is a reverse situation.

307
00:21:27,440 --> 00:21:35,560
In cortical neurons of mice with autism, gava again excites because chloride again accumulates.

308
00:21:35,560 --> 00:21:41,280
Now the interesting thing is that in most cases it's a reverse image because in the

309
00:21:41,280 --> 00:21:48,560
developing case chloride is high because there is a code transporter called NKCC1, sodium

310
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potassium chloride chloride NKCC1, which is crucial, it's present in all cells and it

311
00:21:55,000 --> 00:21:57,360
controls ion distribution.

312
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As you know, neurons are like a battery.

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All the energy is spent to preserve ion distribution.

314
00:22:03,800 --> 00:22:11,120
Low chloride inside, high sodium, high potassium inside, low sodium outside, etc.

315
00:22:11,120 --> 00:22:17,200
If this is deviated, you are epileptic and you have all sorts of disorders.

316
00:22:17,200 --> 00:22:23,080
Now in pathological conditions, again NKCC1 is overactive, as if the neurons are again

317
00:22:23,080 --> 00:22:24,080
immature.

318
00:22:24,080 --> 00:22:27,160
This is an over-simplification by the sadio.

319
00:22:27,160 --> 00:22:32,640
This will be reported in autism, in epilepsies, then it will discover in all the disorders

320
00:22:32,640 --> 00:22:34,000
I'm listing here.

321
00:22:34,000 --> 00:22:41,200
It's an incredible list of disorders in which some neurons are again immature, basically.

322
00:22:41,200 --> 00:22:47,040
Now this means that drugs blocking NKCC1 or activating, you see the chloride concentration

323
00:22:47,040 --> 00:22:49,920
is controlled by an importer and an exporter.

324
00:22:49,920 --> 00:22:54,080
The importer is NKCC1, the exporter is KCC2.

325
00:22:54,080 --> 00:22:57,880
In pathological conditions, the exporter doesn't work well and the importer works a lot, so

326
00:22:57,880 --> 00:23:01,360
chloride accumulates and gava excites.

327
00:23:01,360 --> 00:23:06,920
Now in those all those conditions it works, meaning that the drug blocking NKCC1 is going

328
00:23:06,920 --> 00:23:10,360
to be very useful in a lot of disorders.

329
00:23:10,360 --> 00:23:13,080
So we investigated two pathological conditions.

330
00:23:13,080 --> 00:23:17,400
One I'm not going to talk about, I'm working a lot on this, and this is brain tumors, but

331
00:23:17,400 --> 00:23:20,240
I will talk about the subject of your...

332
00:23:20,240 --> 00:23:25,640
I'm going to talk only about autism next slide.

333
00:23:25,640 --> 00:23:29,280
So what we did, basically this situation.

334
00:23:29,280 --> 00:23:34,880
We have low chloride normally, high chloride in pathology, and if you block NKCC1, this

335
00:23:34,880 --> 00:23:38,560
is a drug called bebetanide, the metanide that's shown here.

336
00:23:38,560 --> 00:23:45,560
This is a generic drug fabricated 50 years ago by a Swiss company to treat hypertension

337
00:23:45,560 --> 00:23:47,640
and brain edema.

338
00:23:47,640 --> 00:23:53,680
Basically you go to the loo, pee pee, you remove water and your tension is reduced, etc.

339
00:23:53,680 --> 00:24:00,520
Now in theory bebetanide should be able to block all of these.

340
00:24:00,520 --> 00:24:04,720
Now this is not only a theory, because this has been shown to be the case experimentally

341
00:24:04,720 --> 00:24:09,440
in all these disorders, animal models.

342
00:24:09,440 --> 00:24:16,720
Next one.

343
00:24:16,720 --> 00:24:21,240
Now the NKCC1 that you can see here is crucially in a lot of systems.

344
00:24:21,240 --> 00:24:26,120
It consumes a lot of energy via sodium potassium ATP as an ATP.

345
00:24:26,120 --> 00:24:31,400
Its structure has been crystallized more or less, you can see to the right, and bebetanide

346
00:24:31,400 --> 00:24:36,680
we know more or less at which site it penetrates to do what it does, and bebetanide is the

347
00:24:36,680 --> 00:24:39,760
best and most specific antagonist of NKCC1.

348
00:24:39,760 --> 00:24:43,720
In fact NKCC1 was partly clothed because of bebetanide.

349
00:24:43,720 --> 00:24:45,360
Thanks to bebetanide.

350
00:24:45,360 --> 00:24:57,120
We did two phase two double blind randomized studies in France.

351
00:24:57,120 --> 00:25:00,920
84 children and I think 67 children.

352
00:25:00,920 --> 00:25:10,800
In both cases it was bebetanide placebo, children 2 to 18 or 3 to 11, treated for three months

353
00:25:10,800 --> 00:25:14,600
with half, one or two milligram bebetanide.

354
00:25:14,600 --> 00:25:20,160
I can show you films in several cases the effect of spectacular.

355
00:25:20,160 --> 00:25:23,680
Now if you see this here, why do you see this?

356
00:25:23,680 --> 00:25:30,120
What you see at your right, every blue column here is one kid in this trial.

357
00:25:30,120 --> 00:25:35,800
The measure is called CAVS, children's autistic scale.

358
00:25:35,800 --> 00:25:38,920
This is done by the pedocyciatrist.

359
00:25:38,920 --> 00:25:42,040
The bigger the column, the better the effect.

360
00:25:42,040 --> 00:25:48,760
If you have 8 to 10 point amelioration and you go from 46 to 36, you're not cured but

361
00:25:48,760 --> 00:25:51,720
you are very strongly less autistic.

362
00:25:51,720 --> 00:25:56,040
And you can see that all the blue columns are treated with only one exception orange

363
00:25:56,040 --> 00:26:00,240
here which is placebo.

364
00:26:00,240 --> 00:26:05,640
So there are exceptions of course, but according to this, the treatment is quite efficient.

365
00:26:05,640 --> 00:26:10,200
Then we did it with the at the right, the table that you have is social responsive scale.

366
00:26:10,200 --> 00:26:15,320
This is another scale made by the parents this time.

367
00:26:15,320 --> 00:26:20,520
Here we gave 0.5, 1 or 2 milligrams to the kids.

368
00:26:20,520 --> 00:26:26,400
According to the FDA, if you have more than 10 point ameliorations, it's extremely good.

369
00:26:26,400 --> 00:26:32,480
You can see here below the last line that we had between 10 and 20 point amelioration

370
00:26:32,480 --> 00:26:36,520
and only 1.5 point amelioration is placebo.

371
00:26:36,520 --> 00:26:39,360
So the difference is quite spectacular.

372
00:26:39,360 --> 00:26:44,440
Of course, we abolished 2 milligrams because the erratic effect are too strong in a young

373
00:26:44,440 --> 00:26:45,440
child.

374
00:26:45,440 --> 00:26:53,080
So we decided to take only 0.5 or 1 milligram twice daily, morning and afternoon.

375
00:26:53,080 --> 00:26:55,520
And this is now used all over the world.

376
00:26:55,520 --> 00:27:04,440
I mean, next line.

377
00:27:04,440 --> 00:27:06,440
More eye contact even.

378
00:27:06,440 --> 00:27:15,080
A meta analysis in fact revealed that 1,050 children have been treated successfully in

379
00:27:15,080 --> 00:27:22,560
nine trials, our two trials and seven others made in China, England, Holland, Egypt, Tunisia,

380
00:27:22,560 --> 00:27:25,720
Iran and Africa to each other country.

381
00:27:25,720 --> 00:27:30,120
All of them doing exactly what we did, open 5 milligram twice daily or 1 milligram twice

382
00:27:30,120 --> 00:27:32,320
daily, three hours.

383
00:27:32,320 --> 00:27:35,280
All of them showed a very significant amelioration.

384
00:27:35,280 --> 00:27:40,720
The Egyptian stuff is quite interesting because they isolated the parameters which seem to

385
00:27:40,720 --> 00:27:42,400
be particularly improved.

386
00:27:42,400 --> 00:27:50,440
And this is agitation and social recognition and a frighten of develop of novelty, facing

387
00:27:50,440 --> 00:27:53,000
novelty problems.

388
00:27:53,000 --> 00:27:59,080
So we fabricated a liquid formulation of the metanide because the pills are very non-tasty

389
00:27:59,080 --> 00:28:00,240
and big.

390
00:28:00,240 --> 00:28:07,120
Next slide.

391
00:28:07,120 --> 00:28:11,720
These are the trials made in different countries confirming what I just told you.

392
00:28:11,720 --> 00:28:17,200
Next one.

393
00:28:17,200 --> 00:28:24,800
Then we did visual interactions and brain imaging on 15 adolescent resultants before

394
00:28:24,800 --> 00:28:26,600
after treatment.

395
00:28:26,600 --> 00:28:30,960
What we found is after treatment the kids recognized better the emotive figures that

396
00:28:30,960 --> 00:28:37,600
you see here, which are different on the neutral ones shown at the right.

397
00:28:37,600 --> 00:28:42,040
So we asked them to recognize the woman if she's crying or laughing, whatever, and the

398
00:28:42,040 --> 00:28:44,680
guitar or the rabbit or whatever.

399
00:28:44,680 --> 00:28:46,840
And there was a significant improvement.

400
00:28:46,840 --> 00:28:47,840
Next slide.

401
00:28:47,840 --> 00:28:51,040
Then we did brain imaging.

402
00:28:51,040 --> 00:28:53,600
One more.

403
00:28:53,600 --> 00:29:02,000
And we found that regions, if you ask the child or the adolescent, these were the adolescents,

404
00:29:02,000 --> 00:29:06,320
to look at the eyes by putting a cross on the nose and asking the kid to look at the

405
00:29:06,320 --> 00:29:09,840
eyes, usually they're frightened.

406
00:29:09,840 --> 00:29:16,440
The activation by the image of the eyes of the amygdala, which is a fear region, is reduced

407
00:29:16,440 --> 00:29:17,440
by the metanide.

408
00:29:17,440 --> 00:29:19,880
They are less frightened.

409
00:29:19,880 --> 00:29:27,120
And we have a direct proof of this that they look more in the eyes after treatment.

410
00:29:27,120 --> 00:29:28,120
Next slide.

411
00:29:28,120 --> 00:29:31,200
Can I ask a question?

412
00:29:31,200 --> 00:29:39,000
Is this interacting at all with oxytocin or vasopressin?

413
00:29:39,000 --> 00:29:45,440
Now the problem with oxytocin, vasopressin to the best of my knowledge was not a significant

414
00:29:45,440 --> 00:29:50,240
demonstration that it's efficient in humans' in clinical trials, to the best of my knowledge

415
00:29:50,240 --> 00:29:51,240
there isn't.

416
00:29:51,240 --> 00:29:55,320
Oxytocin, there have been many, many trials in Europe, in the US, in Japan.

417
00:29:55,320 --> 00:29:58,320
Unfortunately, they are very, very contradictory.

418
00:29:58,320 --> 00:30:04,800
Now, remember, oxytocin does exactly what the metanide does.

419
00:30:04,800 --> 00:30:06,360
Reduce chloride and inhibition.

420
00:30:06,360 --> 00:30:07,360
I agree with that.

421
00:30:07,360 --> 00:30:13,080
The problem is the lifespan of the drug, how fast it's created and so forth.

422
00:30:13,080 --> 00:30:18,400
In addition, and this I'm going to show in a minute, you're going to understand why oxytocin

423
00:30:18,400 --> 00:30:20,080
results have failed.

424
00:30:20,080 --> 00:30:22,480
Just keep the question for one more minute.

425
00:30:22,480 --> 00:30:25,480
Next slide.

426
00:30:25,480 --> 00:30:36,320
Now, unfortunately, in spite of all these results, we need to phase three, finally three,

427
00:30:36,320 --> 00:30:43,320
and four hundred and twenty children in two groups, two, six, seven, eighteen years old,

428
00:30:43,320 --> 00:30:47,320
in Europe, Brazil, Australia, forty centers, a very large study.

429
00:30:47,320 --> 00:30:48,320
It failed.

430
00:30:48,320 --> 00:30:51,280
There was no difference between treatment and placebo.

431
00:30:51,280 --> 00:30:56,440
Now phase three, the problem is you have only one parameter that must differ in placebo

432
00:30:56,440 --> 00:30:57,440
treatment.

433
00:30:57,440 --> 00:31:02,280
And this parameter, for instance, CARS, is a mean of fifteen different items.

434
00:31:02,280 --> 00:31:10,880
SRS is a mean of sixty-five different items, meaning that if the mean is not different,

435
00:31:10,880 --> 00:31:18,560
it does not imply that sub-items, coding for agitation, visual connections, you know,

436
00:31:18,560 --> 00:31:21,560
seizures, whatever, would not be significant.

437
00:31:21,560 --> 00:31:24,600
You see the point?

438
00:31:24,600 --> 00:31:29,320
Centering everything on a mean of something so heterogeneous is something that's meaningless.

439
00:31:29,320 --> 00:31:35,640
This is why they explain why all phase three trials done on fragile eggs, autism, I failed,

440
00:31:35,640 --> 00:31:37,640
even though phase two were successful.

441
00:31:37,640 --> 00:31:39,200
Phase three failed always.

442
00:31:39,200 --> 00:31:46,840
It's originating and lack of taking into account the multiplicity of items that can't be modified

443
00:31:46,840 --> 00:31:47,840
separately.

444
00:31:47,840 --> 00:31:53,400
If I have a drug that treats agitation in kids of autism, it's not bad.

445
00:31:53,400 --> 00:31:55,800
Even if it doesn't treat something else.

446
00:31:55,800 --> 00:31:57,280
You see what I mean?

447
00:31:57,280 --> 00:31:59,360
So what we did again, we did the same thing.

448
00:31:59,360 --> 00:32:06,200
And this was also influenced by a study made by a Dutch group showing that you can identify

449
00:32:06,200 --> 00:32:11,720
by EEG the kids who are going to respond to the metanide.

450
00:32:11,720 --> 00:32:17,200
The Chinese show the same by measuring immunological sample, amount of stress molecules.

451
00:32:17,200 --> 00:32:21,360
The more you have stress molecules, the more you are going to respond to the metanide.

452
00:32:21,360 --> 00:32:28,360
I took a very different approach next slide.

453
00:32:28,360 --> 00:32:34,240
Again going back to machine learning, we decided that all these data we have, we have huge amount

454
00:32:34,240 --> 00:32:38,440
of data on phase three, hundreds or thousands of parameters.

455
00:32:38,440 --> 00:32:45,040
What about using machine learning to identify subpopulations?

456
00:32:45,040 --> 00:32:49,800
So what the computer does, it take all the kids with all the parameters, not only cars,

457
00:32:49,800 --> 00:32:55,760
but all the 15 parameters, sub-items of cars, 65 sub-items of SRS, etc.

458
00:32:55,760 --> 00:33:00,360
And it identifies subpopulations.

459
00:33:00,360 --> 00:33:06,320
The question was, can I identify subpopulation of kids responding to the metanide within

460
00:33:06,320 --> 00:33:08,920
the phase three?

461
00:33:08,920 --> 00:33:14,160
And can I identify them in order to be able to subsequent phase three, in which inclusion

462
00:33:14,160 --> 00:33:18,080
criteria would be the ones I have defined?

463
00:33:18,080 --> 00:33:25,320
So I would not include all children with autism, and I could not include having those features.

464
00:33:25,320 --> 00:33:26,820
And we succeeded.

465
00:33:26,820 --> 00:33:34,440
We have identified 25 to 40% of children responding to the metanide, relying on clinical sub-items,

466
00:33:34,440 --> 00:33:38,640
a mixture of several sub-items.

467
00:33:38,640 --> 00:33:39,640
This is important.

468
00:33:39,640 --> 00:33:44,880
Now this is now being, I hope, patent protected, because this is a private company, I don't

469
00:33:44,880 --> 00:33:49,320
have huge amount of money, I didn't have money to go on, I don't have any financial support

470
00:33:49,320 --> 00:33:54,840
for the moment, and I'm trying to convince a pharma or investor to help me making a phase

471
00:33:54,840 --> 00:33:56,600
three with these criteria.

472
00:33:56,600 --> 00:33:59,280
This will succeed.

473
00:33:59,280 --> 00:34:01,800
Everybody's money is going to genetics though, as we discussed.

474
00:34:01,800 --> 00:34:08,840
No, yeah, but I mean, you see, they have a sense of humor.

475
00:34:08,840 --> 00:34:12,480
There are experts in genetics who have published every month a paper in Nature on the new

476
00:34:12,480 --> 00:34:14,160
mutation, blah, blah, blah, blah.

477
00:34:14,160 --> 00:34:17,600
They have never done it, you know what they're doing now?

478
00:34:17,600 --> 00:34:20,200
They want to use lithium to treat the tissue.

479
00:34:20,200 --> 00:34:21,200
Give me a break.

480
00:34:21,200 --> 00:34:25,000
And I would say more anti-psychotic treatment too.

481
00:34:25,000 --> 00:34:26,000
And I'm...

482
00:34:26,000 --> 00:34:31,760
We don't need to make thousands of studies on specific mutations then to use lithium,

483
00:34:31,760 --> 00:34:32,760
give me a break.

484
00:34:32,760 --> 00:34:33,760
Yeah, it's not...

485
00:34:33,760 --> 00:34:36,200
Yeah, it won't break, by the way, it won't break, we know.

486
00:34:36,200 --> 00:34:37,200
It's so...

487
00:34:37,200 --> 00:34:46,600
No, but they are desperate to propose a treatment, desperate, because I, using stupid old-fashioned

488
00:34:46,600 --> 00:34:48,600
drugs, reach phase three.

489
00:34:48,600 --> 00:34:52,360
What do they have to say in front of this topic?

490
00:34:52,360 --> 00:34:55,640
It's just an anti-diuretic, correct?

491
00:34:55,640 --> 00:34:56,640
It is a diuretic.

492
00:34:56,640 --> 00:34:57,640
A diuretic, yeah.

493
00:34:57,640 --> 00:35:03,680
And the only side effect, in fact, indeed, are diuresis and dehydration.

494
00:35:03,680 --> 00:35:08,680
But this has been given to millions of patients during the last 20 or 40 years.

495
00:35:08,680 --> 00:35:13,680
There is not a single death, we never found anything really serious, nothing.

496
00:35:13,680 --> 00:35:15,520
Yeah, I agree.

497
00:35:15,520 --> 00:35:18,320
You must control potassium down there in the blood, and that's it.

498
00:35:18,320 --> 00:35:20,280
And drink water and go to the loo.

499
00:35:20,280 --> 00:35:21,280
It's alright.

500
00:35:21,280 --> 00:35:25,840
I mean, the side effect of some of the drugs used for epinepsis, or for otitis, by the

501
00:35:25,840 --> 00:35:30,000
way, like the two favorite ones, people get fat, forget about this.

502
00:35:30,000 --> 00:35:33,320
No, no, there is no comparison with other drugs.

503
00:35:33,320 --> 00:35:39,440
So, but the message here is, not only is not genetics, it's really maternity.

504
00:35:39,440 --> 00:35:44,640
And it's really maternity with, by the way, the Americans in San Francisco have proven

505
00:35:44,640 --> 00:35:49,280
that the woman pregnant second trimester close to it, feeling which have pesticide, the

506
00:35:49,280 --> 00:35:51,400
answer to what it goes out.

507
00:35:51,400 --> 00:35:55,120
It's proven it's not stupid ideas of genetic guides.

508
00:35:55,120 --> 00:36:02,160
It's the same thing with pollution, the same thing with stress, the same diabetes, printer

509
00:36:02,160 --> 00:36:06,120
and delivery, C-section in certain cases, etc., etc.

510
00:36:06,120 --> 00:36:13,080
All of these relate to the womb, maternity and delivery, meaning that you really must

511
00:36:13,080 --> 00:36:14,760
protect pregnant women.

512
00:36:14,760 --> 00:36:18,160
This is the most important message of this.

513
00:36:18,160 --> 00:36:22,080
And you know, if there are diabetes, they are poor and they eat fat and etc., etc.,

514
00:36:22,080 --> 00:36:25,480
you know, the consequences are well known.

515
00:36:25,480 --> 00:36:32,600
The problem with genetic, it has to be deterministic, very stupidly, because life is not deterministic.

516
00:36:32,600 --> 00:36:35,760
I mean, you know, you and I have the same genes.

517
00:36:35,760 --> 00:36:39,200
If you go to eat every day to McDonald's, I don't really diabetes, I won't.

518
00:36:39,200 --> 00:36:41,200
It's a simple thing.

519
00:36:41,200 --> 00:36:46,360
And plus, like chimps, we're pretty much identical genetics with chimps and we're

520
00:36:46,360 --> 00:36:47,880
nothing like chimps.

521
00:36:47,880 --> 00:36:49,960
No, no, okay.

522
00:36:49,960 --> 00:36:56,920
By the way, they rely a lot on twin studies to decide the genetics.

523
00:36:56,920 --> 00:37:01,160
I'm just writing a paper, I hope to publish it soon, in which I'm demolishing point by

524
00:37:01,160 --> 00:37:02,880
point everything about genetics.

525
00:37:02,880 --> 00:37:05,400
I'm explaining that twin studies are wrong.

526
00:37:05,400 --> 00:37:08,800
I'm explaining that what they love most is called GWAS, I don't know if you know what

527
00:37:08,800 --> 00:37:09,800
GWAS is.

528
00:37:09,800 --> 00:37:10,800
Yeah.

529
00:37:10,800 --> 00:37:13,360
Polygenic, whatever, blah, blah, blah.

530
00:37:13,360 --> 00:37:18,960
I mean, the basic conditions to use GWAS are never met, never.

531
00:37:18,960 --> 00:37:20,440
This whole blah, blah, blah.

532
00:37:20,440 --> 00:37:22,040
And I'm writing a very detailed paper.

533
00:37:22,040 --> 00:37:26,720
Now, of course, I said it to genetic journals, they rejected it.

534
00:37:26,720 --> 00:37:30,320
But now I said to medical genetic journal, perhaps you'll be published.

535
00:37:30,320 --> 00:37:35,720
It's very, and I'm writing a book in English with a colleague of mine, we're expert evolution.

536
00:37:35,720 --> 00:37:39,480
The title is something like autism is a neutral inflammatory disorder.

537
00:37:39,480 --> 00:37:40,480
Forget about genetics.

538
00:37:40,480 --> 00:37:41,480
Yeah, good, good.

539
00:37:41,480 --> 00:37:45,480
Let's go back to our topics next one.

540
00:37:45,480 --> 00:37:47,480
Okay.

541
00:37:47,480 --> 00:37:53,320
So this is summarized what I told you.

542
00:37:53,320 --> 00:37:54,320
Okay.

543
00:37:54,320 --> 00:37:59,880
So we're aiming to find money to use a phase two, three unidentified responders, which

544
00:37:59,880 --> 00:38:05,960
will work bringing the first drug within two or three years to the market to treat autism.

545
00:38:05,960 --> 00:38:06,960
Next one.

546
00:38:06,960 --> 00:38:12,040
How many additional additives something else?

547
00:38:12,040 --> 00:38:17,680
I decided, you know, farmers don't like to generate drugs because you can buy it in the

548
00:38:17,680 --> 00:38:19,400
farm, it's cheap and they're not going to make money.

549
00:38:19,400 --> 00:38:21,240
Best to cut the long story short.

550
00:38:21,240 --> 00:38:26,360
So I decided to fabricate molecules which belong to me, novel molecules, which block

551
00:38:26,360 --> 00:38:33,360
MQC one, belong to me and are as efficient as we can tonight and perhaps even better.

552
00:38:33,360 --> 00:38:34,880
Next slide.

553
00:38:34,880 --> 00:38:41,720
So working with chemists for years, three years now, we are looking at this.

554
00:38:41,720 --> 00:38:45,000
Well, forget about the oblastomates.

555
00:38:45,000 --> 00:38:52,320
I was saying to do it here, but anyhow, we want to drugs which work as well as the methanol

556
00:38:52,320 --> 00:38:56,000
and our aims are to find money to go to pre-IND studies to phase one.

557
00:38:56,000 --> 00:39:00,200
Basically, if you have a new molecule in vitro, it does what you want to be sure that it does

558
00:39:00,200 --> 00:39:05,560
exactly what methanol does or see shows an activity on gamma, et cetera.

559
00:39:05,560 --> 00:39:09,280
Well now we need to take the best one to pre-IND phase one.

560
00:39:09,280 --> 00:39:14,360
And this costs a lot of money because it's toxicology, it's not toxicity, et cetera.

561
00:39:14,360 --> 00:39:17,240
But next slide.

562
00:39:17,240 --> 00:39:20,720
We have now 120 different molecules.

563
00:39:20,720 --> 00:39:23,320
They all act only in QCC one.

564
00:39:23,320 --> 00:39:29,240
Some of them are better in libido than bimetonite, which is, I don't think anybody has discovered

565
00:39:29,240 --> 00:39:32,640
the molecule, better than bimetonite.

566
00:39:32,640 --> 00:39:34,200
I've tested them in cancer.

567
00:39:34,200 --> 00:39:37,200
Sorry, this area is a mixture with cancer.

568
00:39:37,200 --> 00:39:38,200
But forget about cancer.

569
00:39:38,200 --> 00:39:42,000
The idea is perfectly the same for autism.

570
00:39:42,000 --> 00:39:46,160
Now the idea is that if I have a molecule reaching phase one, not toxic, it's going to

571
00:39:46,160 --> 00:39:51,800
be efficient in so many different molecules that it's going to be extremely valuable,

572
00:39:51,800 --> 00:39:56,640
I mean, I guess even millions, because it could work for us.

573
00:39:56,640 --> 00:40:02,240
By the way, there is a beautiful paper on Alzheimer's disease, which I liked a lot.

574
00:40:02,240 --> 00:40:07,880
Two years ago by an American group, the first auto-established, TAUBES, natural aging.

575
00:40:07,880 --> 00:40:15,960
What they showed was they tested 1,000 molecules, which are widely used, a volume from a barbital,

576
00:40:15,960 --> 00:40:17,720
prozac, whatever.

577
00:40:17,720 --> 00:40:22,920
Which of them is the best on an apoe-dependent Alzheimer's disease?

578
00:40:22,920 --> 00:40:27,200
The answer is bimetonite, out of 1,000.

579
00:40:27,200 --> 00:40:34,080
Then there is something which is even more impressive, epithemological study on 6,065

580
00:40:34,080 --> 00:40:40,720
years old Americans, comparing those who took or not bimetonite for any reason.

581
00:40:40,720 --> 00:40:47,840
Those who took bimetonite have reduced 30 to 70% incidence of Alzheimer's disease.

582
00:40:47,840 --> 00:40:52,680
I think it's very, very striking.

583
00:40:52,680 --> 00:40:54,160
So this drug is not dead.

584
00:40:54,160 --> 00:41:00,960
What I'm trying to say, the phase three died, not the drug.

585
00:41:00,960 --> 00:41:05,080
This one, I think it's the last one.

586
00:41:05,080 --> 00:41:13,520
No, this is simply physiognomy to show it does exactly what you would expect, blocking

587
00:41:13,520 --> 00:41:17,280
seizures and reducing gabae, increasing gabae inhibition.

588
00:41:17,280 --> 00:41:19,280
I think that's it.

589
00:41:19,280 --> 00:41:25,560
Have I summarized everything or are there other questions?

590
00:41:25,560 --> 00:41:42,200
So I would like your idea of the neuroarchaeology and identifying within the womb.

591
00:41:42,200 --> 00:41:48,440
And you comfortably saying, I think pretty confidently, I should say that autism is definitely

592
00:41:48,440 --> 00:41:50,680
in the womb.

593
00:41:50,680 --> 00:41:57,960
What do you think is the biggest barrier for getting that out as being accepted both by

594
00:41:57,960 --> 00:42:07,000
other scientists and how to allow the lay public, just normal common people to understand

595
00:42:07,000 --> 00:42:12,920
this and understand the risk of the environment for the pregnant mother?

596
00:42:12,920 --> 00:42:16,720
This is a very fundamental question.

597
00:42:16,720 --> 00:42:22,120
The answer is complicated, A, because it's also to some extent political.

598
00:42:22,120 --> 00:42:25,400
In countries like France, pregnant women are protected.

599
00:42:25,400 --> 00:42:28,760
They have 12 weeks vacation, all paid by the employers.

600
00:42:28,760 --> 00:42:33,040
To take only one example, in the US, in the case.

601
00:42:33,040 --> 00:42:36,040
So there are ethical aspects I will leave aside.

602
00:42:36,040 --> 00:42:40,720
But the fundamental issue is very simple.

603
00:42:40,720 --> 00:42:47,240
The data we published, and many others, by the way, following our results and others,

604
00:42:47,240 --> 00:42:48,240
are compelling.

605
00:42:48,240 --> 00:42:55,080
I mean, the only issue with the public, which one should be very careful about, is the problem

606
00:42:55,080 --> 00:42:59,800
of A, it's the mother problem.

607
00:42:59,800 --> 00:43:02,080
She's responsible, which has been here decades.

608
00:43:02,080 --> 00:43:06,920
It's very easy to be argument, which makes no sense at all.

609
00:43:06,920 --> 00:43:08,360
It's not the mother responsible.

610
00:43:08,360 --> 00:43:13,320
If the mother lived in a field in which she has pesticide, okay, the pesticides are going

611
00:43:13,320 --> 00:43:14,800
to do what they do.

612
00:43:14,800 --> 00:43:21,640
If her husband is an alcoholic and beats her, and she has nothing to eat or go to, is she

613
00:43:21,640 --> 00:43:22,640
responsible?

614
00:43:22,640 --> 00:43:27,160
I mean, the responsibility of the mother is something disgusting, to be honest.

615
00:43:27,160 --> 00:43:28,160
It makes us...

616
00:43:28,160 --> 00:43:29,160
Right.

617
00:43:29,160 --> 00:43:39,440
I hear that during maternity, this is born for reasons that are so multiple that...

618
00:43:39,440 --> 00:43:41,640
But you know, we're beginning to win.

619
00:43:41,640 --> 00:43:44,640
Women pregnant now smoke less than in the past.

620
00:43:44,640 --> 00:43:46,720
They take less alcohol than in the past.

621
00:43:46,720 --> 00:43:49,800
So we're improving, but it's very slow.

622
00:43:49,800 --> 00:43:54,280
And it's very slow because here I'm not talking about alcohol and smoking.

623
00:43:54,280 --> 00:43:56,480
I'm talking about life conditions.

624
00:43:56,480 --> 00:43:57,480
Yeah, yeah.

625
00:43:57,480 --> 00:44:01,360
You should try not to be obese or diabetic when you're pregnant.

626
00:44:01,360 --> 00:44:04,160
There are hundreds of problems.

627
00:44:04,160 --> 00:44:08,120
Anti-apileptic is a problem.

628
00:44:08,120 --> 00:44:09,120
The woman is epileptic.

629
00:44:09,120 --> 00:44:14,560
The reason anti-apileptic is very well-received.

630
00:44:14,560 --> 00:44:17,000
She becomes pregnant.

631
00:44:17,000 --> 00:44:23,960
Stopping the treatment is problematic because she could lose a child, the baby.

632
00:44:23,960 --> 00:44:29,000
Bringing it up continues is also problematic because it could be malformed.

633
00:44:29,000 --> 00:44:33,880
And there are trials in France against sanofi because a very classical anti-apileptic called

634
00:44:33,880 --> 00:44:42,840
depakine has been shown 30 years ago to increase brain abnormalities and others abnormalities.

635
00:44:42,840 --> 00:44:43,840
But the decision is not simple.

636
00:44:43,840 --> 00:44:47,920
If I am the neurologist, I have a woman, a epileptic, what do I do?

637
00:44:47,920 --> 00:44:49,720
It's not simple questions.

638
00:44:49,720 --> 00:44:53,640
You don't want to stop it and you don't want to go in either.

639
00:44:53,640 --> 00:45:04,640
So the message is any politics should do all its best to protect women during pregnancy.

640
00:45:04,640 --> 00:45:05,640
Yeah.

641
00:45:05,640 --> 00:45:06,640
And this is a...

642
00:45:06,640 --> 00:45:09,640
It's not a priority today.

643
00:45:09,640 --> 00:45:10,640
No.

644
00:45:10,640 --> 00:45:14,480
And as you mentioned, it's much different in the U.S.

645
00:45:14,480 --> 00:45:21,080
The environment of the pregnant mother is typically not great.

646
00:45:21,080 --> 00:45:27,120
And it might sound sexist or something like that, but they're forced to or they choose

647
00:45:27,120 --> 00:45:32,520
to work up into almost the time of labor.

648
00:45:32,520 --> 00:45:34,480
And I've just...

649
00:45:34,480 --> 00:45:36,320
It's just very concerning to me.

650
00:45:36,320 --> 00:45:42,480
Well, you know, in France, you have 12, now 14 months even.

651
00:45:42,480 --> 00:45:50,200
You have protection for a long time and the husband can take part of it to help whatever.

652
00:45:50,200 --> 00:45:56,840
By the way, I wanted to do this study I showed here in neutral measures to detect.

653
00:45:56,840 --> 00:45:58,480
I want to do this, yes.

654
00:45:58,480 --> 00:46:02,840
I spoke to some of my colleagues at the big hospitals in the U.S.

655
00:46:02,840 --> 00:46:08,800
It's impossible because the calligraphy, whatever, are paid by the patients.

656
00:46:08,800 --> 00:46:10,200
So you have very little information.

657
00:46:10,200 --> 00:46:11,200
Yeah.

658
00:46:11,200 --> 00:46:13,880
There is no real collection of maternity data.

659
00:46:13,880 --> 00:46:15,880
So I can't do it in the U.S.

660
00:46:15,880 --> 00:46:18,280
So this stuff would be in France, not in the U.S.

661
00:46:18,280 --> 00:46:24,720
By the way, I cannot apply it as if immediately to England because in England you have only

662
00:46:24,720 --> 00:46:28,240
two calligraphies, not four, not three like in France.

663
00:46:28,240 --> 00:46:29,960
And they have less collection of...

664
00:46:29,960 --> 00:46:31,520
It depends on the countries.

665
00:46:31,520 --> 00:46:36,000
It could work in Norwegian countries, Norway, Sweden, Holland as usual.

666
00:46:36,000 --> 00:46:41,240
These are the best in terms of care of women, et cetera.

667
00:46:41,240 --> 00:46:42,240
Perhaps Switzerland.

668
00:46:42,240 --> 00:46:43,240
Yes, Switzerland probably.

669
00:46:43,240 --> 00:46:44,240
But that's it.

670
00:46:44,240 --> 00:46:51,720
Even in Europe it will not work in Bulgaria or Romania or perhaps even Germany.

671
00:46:51,720 --> 00:46:58,120
So it's an endless problem.

672
00:46:58,120 --> 00:47:01,440
It's a very complicated one, yet a crucial one.

673
00:47:01,440 --> 00:47:02,440
Yeah.

674
00:47:02,440 --> 00:47:08,480
There's a lot of humans that don't understand the problem involved in the decision-making.

675
00:47:08,480 --> 00:47:17,880
Do you know the differences between the rates of autism in the U.S. and let's say France?

676
00:47:17,880 --> 00:47:20,800
I think they're quite similar.

677
00:47:20,800 --> 00:47:25,200
But the answers are not straightforward because in your country you have better epidemiologists

678
00:47:25,200 --> 00:47:27,120
doing this than in New York, France.

679
00:47:27,120 --> 00:47:32,080
I don't think we have as detailed epidemiology.

680
00:47:32,080 --> 00:47:34,080
There's a lot of variables with that question.

681
00:47:34,080 --> 00:47:35,080
Yeah.

682
00:47:35,080 --> 00:47:40,360
We don't have the same amount of studies on epidemiology for autism in France.

683
00:47:40,360 --> 00:47:41,360
Yeah.

684
00:47:41,360 --> 00:47:43,720
But I guess the numbers will not differ tremendously.

685
00:47:43,720 --> 00:47:49,160
And even across U.S. there are areas that have extreme rates.

686
00:47:49,160 --> 00:47:54,800
Like around San Francisco, they have almost like one in 20 children.

687
00:47:54,800 --> 00:47:55,800
Yeah.

688
00:47:55,800 --> 00:47:56,800
So...

689
00:47:56,800 --> 00:47:57,800
No, no, it's frightening.

690
00:47:57,800 --> 00:48:01,240
But it's not only autism.

691
00:48:01,240 --> 00:48:07,360
It's a fact that if you make a very simple financial calculation, which your government

692
00:48:07,360 --> 00:48:14,120
and mine like a lot, it costs much more to treat them afterwards than to do what they

693
00:48:14,120 --> 00:48:15,120
can do on pregnancy.

694
00:48:15,120 --> 00:48:16,120
There is no comparison.

695
00:48:16,120 --> 00:48:17,120
Yes.

696
00:48:17,120 --> 00:48:18,840
I haven't ever seen saying that.

697
00:48:18,840 --> 00:48:21,560
I'm glad you confirmed that.

698
00:48:21,560 --> 00:48:22,560
Oh, the cost.

699
00:48:22,560 --> 00:48:27,720
I mean, people have calculated, I can find the papers, how much a child autistic cost

700
00:48:27,720 --> 00:48:30,720
to the society and parents.

701
00:48:30,720 --> 00:48:34,720
If you calculate everything, the woman not working and blah, blah, everything.

702
00:48:34,720 --> 00:48:35,720
And you include all these.

703
00:48:35,720 --> 00:48:36,720
The sums are huge.

704
00:48:36,720 --> 00:48:37,720
Billions.

705
00:48:37,720 --> 00:48:39,720
Every episode of autism.

706
00:48:39,720 --> 00:48:47,200
You know, in medicine, what's important is prevention, not treatment.

707
00:48:47,200 --> 00:48:48,200
Always.

708
00:48:48,200 --> 00:48:53,760
And U.S., I can't speak of other countries, but the U.S. is awful.

709
00:48:53,760 --> 00:48:56,240
There probably be the worst at this.

710
00:48:56,240 --> 00:48:57,720
They are among the worst.

711
00:48:57,720 --> 00:48:58,720
Yeah.

712
00:48:58,720 --> 00:49:03,720
The life expectancy of Americans is below that of Cubans.

713
00:49:03,720 --> 00:49:04,720
Yeah.

714
00:49:04,720 --> 00:49:07,440
And it's very stagnant and flattened towards the bottom.

715
00:49:07,440 --> 00:49:11,240
Yet our health budget is almost two times the second.

716
00:49:11,240 --> 00:49:16,200
You pay more than us and you have less life expectancy for a very simple reason.

717
00:49:16,200 --> 00:49:23,440
The reason is that socializing health is cheaper than non-socializing it.

718
00:49:23,440 --> 00:49:26,600
In our country, we have one social security.

719
00:49:26,600 --> 00:49:31,120
I paid my part directly from my salary.

720
00:49:31,120 --> 00:49:35,320
They take a percent of my salary to put in social security.

721
00:49:35,320 --> 00:49:39,120
Then I don't have to pay medical, treatments, surgery, whatever.

722
00:49:39,120 --> 00:49:41,120
And it's cheaper.

723
00:49:41,120 --> 00:49:44,120
No, no, it's, again, it's a political problem.

724
00:49:44,120 --> 00:49:47,720
And you know, we're not going to go to politics, but this is really a political problem.

725
00:49:47,720 --> 00:49:54,840
And you're facing an election which, I won't say anything, but you can't be even worse.

726
00:49:54,840 --> 00:50:01,840
The four of the top five revenue industry types are around healthcare, hospitals, big

727
00:50:01,840 --> 00:50:04,120
pharma, health insurance.

728
00:50:04,120 --> 00:50:08,920
But I didn't bring you on to talk about that, but it is an important topic.

729
00:50:08,920 --> 00:50:11,640
I agree, but this is beyond our competence.

730
00:50:11,640 --> 00:50:13,440
You agree with that?

731
00:50:13,440 --> 00:50:19,800
So whenever I first heard GABA was excitatory through that immature, developing brain,

732
00:50:19,800 --> 00:50:21,320
I was blown away.

733
00:50:21,320 --> 00:50:26,240
Because one of the first things I learned about autism was this excitation inhibition

734
00:50:26,240 --> 00:50:28,040
imbalance.

735
00:50:28,040 --> 00:50:37,320
So and I assumed that GABA was excitatory up and through this probably critical period.

736
00:50:37,320 --> 00:50:41,640
Is it because it helps accelerate learning and development?

737
00:50:41,640 --> 00:50:46,880
No, GABA is excitatory only in uterine humans, not afterwards.

738
00:50:46,880 --> 00:50:54,880
But it's excitatory in utero because we and many others have shown that GABA exerts trophic

739
00:50:54,880 --> 00:50:55,880
actions.

740
00:50:55,880 --> 00:51:00,720
GABA controls neural growth, synapse formation, lateral formation.

741
00:51:00,720 --> 00:51:06,920
If you brought GABA, neurons do not establish as many synapses and do not grow as much.

742
00:51:06,920 --> 00:51:08,800
And migration is deficient.

743
00:51:08,800 --> 00:51:13,360
So GABA excites immature neurons for these reasons.

744
00:51:13,360 --> 00:51:18,400
But the result of excitation by glutamate becomes a D3.

745
00:51:18,400 --> 00:51:23,000
Nutri is much cleverer than we are.

746
00:51:23,000 --> 00:51:25,000
Much clever.

747
00:51:25,000 --> 00:51:26,000
Wow.

748
00:51:26,000 --> 00:51:27,000
Okay.

749
00:51:27,000 --> 00:51:33,200
Yeah, I'm looking forward to your future research and especially some of those things

750
00:51:33,200 --> 00:51:36,760
that you're working on.

751
00:51:36,760 --> 00:51:41,000
As you get more results, maybe you can come back on and discuss those with me.

752
00:51:41,000 --> 00:51:46,000
I'm going to be looking out for some of those items that you mentioned today.

753
00:51:46,000 --> 00:51:47,000
I'm very excited.

754
00:51:47,000 --> 00:51:51,000
Yeah, I was thinking, if the English paper would get out, the book will take some time.

755
00:51:51,000 --> 00:51:52,000
Yeah.

756
00:51:52,000 --> 00:51:55,920
I have two books you can advertise in English.

757
00:51:55,920 --> 00:52:00,000
One of them is the first 1000 days, which is published in English now.

758
00:52:00,000 --> 00:52:01,000
It's great.

759
00:52:01,000 --> 00:52:03,000
I really want to read about that.

760
00:52:03,000 --> 00:52:05,920
And the second one is the better life to treat autism.

761
00:52:05,920 --> 00:52:10,000
The two books are now in English and they are accessible via the usual sources.

762
00:52:10,000 --> 00:52:14,920
And the first one I explained why better I treat autism as efficient.

763
00:52:14,920 --> 00:52:20,000
And the second one I explained why the 1000 days going from conception to second years

764
00:52:20,000 --> 00:52:21,000
of life are crucial.

765
00:52:21,000 --> 00:52:22,000
Yeah.

766
00:52:22,000 --> 00:52:24,000
I don't know what everything I told you here.

767
00:52:24,000 --> 00:52:28,400
Now, in general, whole pollution, et cetera, et cetera.

768
00:52:28,400 --> 00:52:32,000
So the two books are related to what we discussed here.

769
00:52:32,000 --> 00:52:33,000
Yeah.

770
00:52:33,000 --> 00:52:36,600
I get frustrated with autism research a lot.

771
00:52:36,600 --> 00:52:41,680
But you're one that I have trust in.

772
00:52:41,680 --> 00:52:46,600
You expand the edges of science instead of just being stuck.

773
00:52:46,600 --> 00:52:53,200
You know, I have always said to my students, if you want to make great discoveries, they're

774
00:52:53,200 --> 00:52:55,600
always inside with never in highways.

775
00:52:55,600 --> 00:52:59,600
If everybody tells this, you will miss.

776
00:52:59,600 --> 00:53:00,600
Yes.

777
00:53:00,600 --> 00:53:01,600
Follow the modes and fashion.

778
00:53:01,600 --> 00:53:05,320
This is why I don't like genetics because it's a modern fashion.

779
00:53:05,320 --> 00:53:09,640
It's going to die one day or another when they discover that.

780
00:53:09,640 --> 00:53:15,320
And the same thing applies to all these big stuff, proteomics, metabolomics, genomics.

781
00:53:15,320 --> 00:53:19,400
We're going to count every protein you have in your body, regardless of the state, why

782
00:53:19,400 --> 00:53:21,200
you or somebody else is autistic.

783
00:53:21,200 --> 00:53:22,200
Give me a break.

784
00:53:22,200 --> 00:53:26,040
You know, if you take a transistor from a television, it doesn't work.

785
00:53:26,040 --> 00:53:30,440
It's a transistor which in fact doesn't tell you anything about what else happened.

786
00:53:30,440 --> 00:53:31,440
Come on.

787
00:53:31,440 --> 00:53:34,560
I would like to give a special thank you to our guest today.

788
00:53:34,560 --> 00:53:36,160
Dr. Ben Ari.

789
00:53:36,160 --> 00:53:42,520
It's not difficult to see Dr. Ben Ari's passion towards autism.

790
00:53:42,520 --> 00:53:50,040
Discovering when, the precise where and when autism is developing.

791
00:53:50,040 --> 00:53:56,320
His research is expanding the edges of the autism community.

792
00:53:56,320 --> 00:54:02,560
It's unfortunate that there are other factors involved with autism research, but we very

793
00:54:02,560 --> 00:54:11,560
much appreciate his voice for the autistic community, autistic research and what is wrong.

794
00:54:11,560 --> 00:54:20,480
Now we went into genetics and it's not uncommon that the podcast speaks about the genetic

795
00:54:20,480 --> 00:54:24,400
factors and how there's not an answer here.

796
00:54:24,400 --> 00:54:29,760
Even her, Dr. Catherine Lord mentioned that she doesn't think there's an answer here.

797
00:54:29,760 --> 00:54:35,800
Yet so many people are invested and they want an outcome here.

798
00:54:35,800 --> 00:54:38,600
They keep searching, but it's incorrect.

799
00:54:38,600 --> 00:54:47,840
I very much appreciate Dr. Ben Ari's five decades of research and knowledge and information

800
00:54:47,840 --> 00:54:57,160
that he has contributed to both the scientific community at large and the autistic community.

801
00:54:57,160 --> 00:55:01,080
He has a lot of good projects going and moving forward.

802
00:55:01,080 --> 00:55:07,840
So this is giving us a lot of hope and something to look forward to as he is publishing and

803
00:55:07,840 --> 00:55:12,000
finding other answers and other alternatives.

804
00:55:12,000 --> 00:55:18,000
I very much appreciate him speaking out on the psychopharmacology that's being used for

805
00:55:18,000 --> 00:55:19,560
autism.

806
00:55:19,560 --> 00:55:25,080
This is very concerning.

807
00:55:25,080 --> 00:55:29,480
If you're listening to the podcast or listening to the episode, please feel free to leave

808
00:55:29,480 --> 00:55:31,840
a review or rating.

809
00:55:31,840 --> 00:55:39,800
In podcasting, reviews, ratings and downloads are huge and I very much appreciate your feedback.

810
00:55:39,800 --> 00:55:52,600
You can contact me on X at RPS 47586 or you can check out the Hop link where you can

811
00:55:52,600 --> 00:56:00,000
find all links to the podcast forms and my contact information and social media.

812
00:56:00,000 --> 00:56:02,240
Thank you for listening too.

813
00:56:02,240 --> 00:56:25,600
From the Spectrum Podcast.