A theory of brain development to help treat autism | Yehezkel Ben Ari | TEDxCanebière

In a talk sure to bring hope to many, Yehezkel Ben Ari shows us how his approach to brain development has lead to a new treatment for behavioral disorders in autistic people. More than a merely scientific outlook is expressed as he imparts his own approach to research: never stick to the beaten path, never shy away from unfamiliar routes for they might just get you to where you want to go.

Physiologist and biophysician, Yehezkel Ben-Ari has made major discoveries regarding the stages of development of the brain and various disorders. He has, along with colleagues at the INMED, uncovered the maturation sequences of neurons and neural networks including one which has since become a major area of study: the maturation of inhibitory currents that were first excitatory. His team has also uncovered the changes that occur during birth and their role in the emergence of autism and other cerebral pathologies. Having lead a unit at the INSERM (French National Institute of Health and Medical Research) for more than 20 years, he created the INMED (Mediterranean Institute of Neurobiology) which he managed from its creation until 2009. His discoveries have lead him to create two innovative start-ups: Neurochlore and B&A Therapeutics. His current work focuses on clinical trials and research projects aiming to determine whether or not neurological and psychiatric pathologies can emerge during birth.
Yehezkel Ben-Ari is the author of more than 500 scientific publications. He has received numerous awards including, in 2009, the Biomedical Prize of the INSERM, the FNRS's Prize in Belgium, and the Grand Prize of American and European Foundations for Autism. For more information please consult Yehezkel Ben Ari's blog at http://leblogdebenari.com/ or the Neurochlore website at http://www.neurochlore.fr/

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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.

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!

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)