Translator: J Lodge Reviewer: Hélène Vernet
Sometimes, I wonder if I’m not a bit masochistic,
because to spend your life trying to understand
how the brain works you kind of have to be so.
That said, I may have mitigating circumstances.
After having been born into a Jewish family in Cairo;
spoken Hebrew at home, then Arab, and French of course;
gone to a Catholic school St Jean-Baptiste de la Salle, to learn catechism;
learned a grasp of the Coran;
then lived in Israel and seen the other side of the fence,
I concluded: one, a secular atheist country is pretty cool,
and two, we can approach any subject no matter how complicated.
Now, life is complicated, for sure.
The brain is very complex.
There are a million billion connections in the human brain,
a million billion connections and each one of them
is far more complicated than a mobile phone,
because it learns and the phone doesn’t.
That would mean that each human being
possesses the equivalent of 200,000 mobile phones.
We can understand why this "telephone exchange" is so complex
and tends to be overloaded.
So, in 1986, I was appointed
unit director at the INSERM, in Paris, at Port Royal,
in a maternity ward that had four floors where there were women giving birth,
planned cesareans, premature births, etc.
I was in charge of the top floor.
I took over the post after a great guy, Alexandre Nikovski,
who was the first to understand that pregnant women need protection
because pregnancy is the period "of living dangerously."
He fought to ensure that during pregnancy, there could be some time off, etc.
He was a really great person.
My wife and I went with him out to lunch after my appointment,
and he said finally, "All is well!
We’re replacing an Azhkenazi Jew with a Sephardic Jew.
Your wife is fairly smart, so necessarily, you must be good!"
So apparently, proficiency was not the main criterion.
So, I began to work on the development of the brain
about which we know very little.
These are unborn childs.
One seems to be working on a math problem,
scratching his head.
This one wants to go out as the food isn’t very good.
And this one can’t decide if he wants to play football with OM or PSG.
Why am I showing you this? What does this mean?
Well, it means there are lots of things happening in the womb.
In a monkey's brain for example,
a cortical neuron has 7,000 connections before birth and 10,000 after birth.
So this is not at all a period of inertia.
The first thing to take from this is that the brain in utero moves a lot,
develops rapidly and is highly active.
Obviously, to make a comparison,
a brain is a lot more complex than a plane, a submarine or a boat.
The major difference is that when we assemble a plane -
I’ve never built a plane but I can imagine -
the engine isn’t running, but in this case, it is.
The engine is running while the brain is being built.
The process is identical: an architect creates a blueprint,
then there are site meetings to ensure all is going well,
otherwise everything would go wrong.
So the first thing to understand is that the brain in utero works a lot.
The second thing to understand is that not only it does all this work,
but the electric currents - brain electric currents are my specialty -
the currents that are generated by these neurons as they’re being formed
are nothing like those of adults.
The immature brain is not a small adult brain.
It has its own language, one that’s totally different from that of the adult.
By the way, this explains
the reason why it took me years to convince the administrators
that we can't give to a baby the drug of an adult and just split the dose.
It makes no sense because the processes are totally different.
We must understand how the brain develops in order to heal it.
Now why this image?
Well, Imagine I’m a conductor - unfortunately, I’m not -
and we're going to play Brahms' Second Symphony with Jascha Heifetz on violon,
then I’m telling you they should be playing Brahms during the rehearsals.
Well, in this case, they didn't. A group is playing rock.
Another is playing Bach, and yet another is playing whatever.
Then, comes showtime, and they all play Brahms.
So it has nothing to do with an adult brain.
The question to ask, obviously, is why is it like that?
Let's take the visual system.
The human retina is formed
almost at the end of the first trimester of pregnancy.
We see nothing, we forget everything.
In all animal species,
the retina generates an activity caled "retinal waves"
which does not enable vision at all,
but which is critical because if we block it,
the visual system develops badly.
So here is this activity that is not related to the senses
but has a major function.
So, with my friend Nick Spitzer,
we came up with what we called: "the checkpoint theory."
The idea is while something is being built,
this building or anything else, we have to check what’s being done.
The construction of the brain isn't like pushing a button,
and then from one cell I get a brain, thanks to genetics. That's ridiculous!
Indeed, there are checks.
So we proposed to call them "checkpoints."
For example, when the Channel tunnel was built,
there were these enormous machines on both sides of the Channel -
they hadn’t left Europe at the time -
that drilled until they came face to face.
Without GPS, they could have gone like this or this,
but not like this.
It takes continuous checking.
What I proposed was that this continuous checking
is this electrical activity present during the brain development.
While the cell is maturing, just like an apple,
it sends electrical signals that indicate its state and its stage of construction.
The aim of this activity in the retina is to tell the visual brain
"I’m here, not there," like basically, a GPS.
All that sounds good but you’ll probably ask,
"That’s interesting but what happens when things goes wrong?"
We see cases of neurological and psychiatric illnesses
and, as you know,
we’ve been trying to treat them for centuries without success
for lots of reasons, in part because they arise very early,
and we don’t know what they do to the brain.
But if we think a little bit, there're two ways to go about it.
The first is like in "The Imaginary Invalid" by Moliere,
when Argan's servant says, "The lungs! The lungs, I say to you."
Well, geneticists say, '"The genes! The genes! it’s all genetic!"
Now, after pondering a little more,
I proposed a concept called "neuro-archeology."
The idea's very simple: if one day this building collapses,
we’ll discover that in one spot, there was a poorly built post
that rose out of one floor that itself collided something else,
and at one point, everything collapsed.
The idea is exactly the same:
during the maturation of the brain,
there are sequences of maturation as I told you before,
in case something happens in the womb such as a gene, a mutation,
pesticides, stress, alcohol,
whatever that can happens in life or in the environment basically.
This is important because, if we come back to genetics for a second,
contrary to what is told,
the vast majority of psychiatric illnesses are not of genetic origin.
They do not involve genetics such as Alzheimer or Parkinson.
They may involve mutations in very few patients.
They are not monogenic, which means that if, for example,
a kid who has a mutation that predisposes him to be diabetic,
goes to McDonald's everyday, he’ll indeed be diabetic.
If he chooses to live on an island and eats fresh fish
and pesticide-free tomatoes, he probably won’t be diabetic.
So it is about susceptibility. what we call "epigenetic."
It means that the environment creates a susceptibility
that will be expressed as an illness in some cases and not in others.
Now, the second way is the following.
It consists in trying to understand how the brain is built,
how the sequence of maturation is deviated,
and from there, start to think.
Imagine the fundamental thesis is confirmed,
I believe it will be a major step forward in the understanding
and the treatment of neurological and psychiatric illnesses.
I’m saying that when there is an "attack" in the womb,
whatever the cause may be, genetic or not,
it modifies the sequence of maturation,
and the neuron that was supposed to mature does not mature,
just like an apple that doesn’t ripen.
It doesn't connect where it should, it doesn't go where it should.
So the thesis is that this misplaced neuron
remains immature in the adult brain.
In this perspective, many neurological or psychiatric ailments
would be due to displaced neurons
that have kept immature electrical characteristics.
Ar first, I explained that the developing brain
has a different function than the adult one.
Those neurons that are here, here or there,
produce activities that interfere with their surroundings.
So, what I propose is a kind of pharmacological intervention
using drugs that only block these immature neurons in an adult brain
since their properties are precisely different, right?
That's the idea and it needed to be proved.
This can’t be demonstrated on humans but on experiments with animals,
be it for Parkinson, Alzheimer or autism.
In fact, we have noticed
that a neuron is an electrical machine.
Ions come in and go out: potassium, sodium, calcium, chlorine, etc.
It produces electricity that codes what we are.
Everything that we integrate is just that.
Among the ions that play an important role,
one is particularly important: chlorine.
We have discovered that in an adult naive neuron,
there's very little chlorine.
In a young naive neuron, there is a lot of chlorine.
It completely changes the neuron' stability.
We also discovered that in animal models of autism,
the situation is somewhat similar to that of an immature brain.
So, it's just like what I said.
A neuron that is young has a lot of chlorine.
it matures, and then has none.
If it matures "in the wrong way," it retains a lot of chlorine.
So, as you see, the consequence is that chlorine comes in here,
but here it goes out, so the electrical response is totally different.
Me and my friend Éric Lemonnier,
one of the best French experts on the treatment of autism,
who has been working with autistic children for ages,
we've thought ... Well, chance has a role.
Five or six years ago, I didn’t know what autism was.
I wasn’t working on it at all.
I was helding a conference for parents of autistic children
and spoke about chlorine and so on,
and Eric said to me, "You know, if there’s a lot of chlorine,
there’s reason to think that these kids are autistic due to clinical reasons,
since when we give them Valium, instead of going to sleep as adults would,
they get extremely agitated, so this probably means
there’s a lot of chlorine inside."
So we made the extremely naive hypothesis that we could reduce the chlorine levels,
by using a diuretic which is a molecule
that, when ingested, makes you need to urinate. Why?
Because the same happens in the kidneys.
The same system that exists in the kidneys, exists in the brain.
There are diuretics on the market that people have used for a long time
to treat hypertension and cerebral edema.
We took five kids in Brest and gave them a diuretic
and it seemed to have a positive effect.
We did a second trial with about 50 children,
a double blind trial and it worked.
I’m going to show you one of those kids.
You’re going to see a child before and after treatment
using diuretics for three months.
(Video) Woman: ... for baby’s birthday.
So for baby's birthday ...
Please come, Allan!
Y.B.A.: Notice that he doesn’t make eye-contact.
(Video) Woman: Come!
(Child' screams)
Y.B.A.: He stimulates himself by playing with the light, you'll see.
(Child' screams)
Child: Mama ...
Y.B.A.: She has a lot more patience than me.
(Video) Woman : And on baby’s birthday cake, I put some candles.
Please come and put the candle on?
Put the candle on.
Y.B.A.: Not once did he look her in the eye.
Here is three months after treatment.
(Video) Woman: For baby's birthday, let's make a cake.
Let's stick the candles on top. Do you want to put one on?
Hop!
Good job!
Let's light the candles. It’s hot!
And let's sing: Happy Birthday to you.
(Singing) Happy Birthday to you.
Y.B.A.: Notice, he’s looking her in the eye.
(Video: Child blows the candles out)
Woman clapping hands: Yay! Good job, Allan!
Let’s take the candles off.
Y.B.A.: You’ve probably guessed I don’t believe in miracles,
and this is no miracle.
This child wasn’t speaking before and he still isn’t, okay?
But parents are all telling us the same thing :
"There are more present. They interact with us more."
That’s important because with autism,
it’s not just the children that suffer but parents as well.
So the fact that they become more sociable is extremely important.
It means they participate more in society.
I don’t think there will be a pill that will cure this illness
such as one can take an aspirin for a headache
because, if you’ve understood what I’ve told you so far,
it's an early occurring condition that modifies parts of the brain,
and this can't be undone with some miracle cure.
However, schooling will cure it.
If we can get these kids into school, it will make them more sociable.
Why am I showing you this image?
The not-so-young among you will know.
It's an extract from "Who’s afraid of Virginia Woolf ?"
with Richard Burton and Elizabeth Taylor.
Indeed, you see what’s going on:
they’re screaming at each other because he made a move on this one, etc.
But if you were looking at the plate here,
as an autistic child would do when avoiding eye-contact,
you wouldn't understand anything.
So, it’s not that they're not empathetic but they don’t look where they should.
If you don’t look at peoples eyes,
you don't know if the other is crying or laughing.
With Nouchine Hadjikhani, we chose some autistic children
and showed them pictures that were sad or joyful,
before and after the treatment, and we noticed
that they watched the eyes more than before as parents have confirmed.
So, it works but it’s not a miracle cure.
It’s a treatment with secondary effects
such as less potassium in the blood which must be kept under control,
but for the moment, no other medication on the market can help those kids.
We've initiated a second phase.
Recently, we were authorized by the European authorities
to do a phase 3.
Now, I’m focusing on the brain during birth about which we know very little.
How does a brain get ready for birth? How complex that is!
What does it do? What happen if things go wrong?
The mother might have hyper tension or diabetes, whatever.
How does that work? What are the consequences?
It’s one of the major public health issues we’re not dealing with
since neither the pharmaceutical industry nor our politicians are interested
because obviously, it’s a complicated issue.
In conclusion, art and science are not the same thing.
But sometimes, they do have similarities.
The process we call "creativity" is precisely as follow:
a process by which we leave the beaten path,
we leave all orthodoxies behind,
and we think about things differently.
The last picture I will show you is this
because I’m a fan of Modigliani.
When he painted that cellist,
one student said to his master at the Grande Chaumière school:
"That arm isn’t right, it’s too long,"
to which the master answered majestically:
"An arm that is so well painted is never too long."
He expressed what creativity expresses,
that is the leaving of the beaten path to really show what a cellist does.
Thank you.
(Applause)