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I would like to share with you today

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a very interesting experience
I had in my neurosurgical life.

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I am a neurosurgeon,

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and I have to deal
with human tragedies daily.

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It's a real disaster to see people
after a car accident or after a stroke.

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If you have a big part
of your brain that is destroyed,

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unfortunately, the central nervous system
has very little ability for self-repair.

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One of my neurosurgical dreams was
always to try to give back a function

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to someone who has lost it

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because people remain
severely handicapped,

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and it's revolting to see that every day.

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So that's probably
why I've chosen this specialty

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called functional neurosurgery.

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Functional neurosurgeons try

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to give back functions or to improve them
through surgical strategies

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like deep brain stimulation, for example,
that's the most famous strategy.

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14 years ago, I participated

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in a major discovery that, in my opinion,

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would have an important impact
on the patient's recovery

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after a major insult
to the central nervous system.

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That's the story
I would like to tell you today.

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Before telling you the story,

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I have to introduce you to
two very important and different actors;

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without them it'd never have been
possible to have this story today.

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The first one is not in the room.

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You can understand why.

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It's not exactly this cow,
but she represents her cousin,

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the South American cow.

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Without the serum
of this South American cow,

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we would not have been able
to grow adult brain cells.

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The second actor, he is not in the room,
but he is not eating grass.

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He is my very good friend
and collaborator, Jean-François Brunet,

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who is a biologist and without
whose patience and pugnacity,

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we would never have been able
to grow brain cells.

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So now, let's go back to the story.

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You have to imagine
that about 14 years ago,

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I was a chief resident in neurosurgery,

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and chief residents work a lot,
day and night, doing a lot of emergencies.

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And sometimes, during these emergencies
you have to remove a piece of the brain.

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It's not for fun, it's because
someone had a car accident,

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has a swollen brain,
and you have to do craniectomy,

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otherwise the patient is going to die;

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so, sometimes, you have to
remove a piece of the brain.

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And we thought with Jean-François
who is a biologist in his lab:

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"Why shouldn't we do something

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with these pieces of the brain
that we have to sample so often?"

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Jean-François and his patient said:

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"I'm sure I am going to do
something very interesting with that."

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He tried with different types of serums,

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and he saw, finally,
after many, many attempts,

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that the serums from the cow
I introduced to you previously...

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One day he saw that under his microscope.

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And you have to realize
is that this type of culture

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really looks like a stem cell culture.

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But you also have to know
that at that time, 14 years ago,

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we thought that the only stem cells
we have in the central nervous system

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were really deeply located
in the brain in two very small niches.

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But here, Jean-François with any type
of samples he got from cortex,

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got this type of cells,
which was incredible.

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And what you can see,
on this type of cells,

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the green cells here are astrocytes

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those are the cells that are supporting
the neurons in the normal brain,

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and inside these little round cells are
immature neurons, immature little cells

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that could turn into mature cells.

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So when we showed that
to people at that time, they said:

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"That's not possible to have stem cells
in this type of culture from the cortex,

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you must have taken some stem cells
[from the cortex into the culture]."

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We said, "No," because they
do not behave like stem cells,

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they divide much more slowly,
and they never form tumors,

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and they are really more indolent,

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and after awhile, 10 or 15 weeks
of culture, they also die.

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It's not like something
which is renewing and renewing.

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Finally, we realized
where these cells came from

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- because they were not coming
from stem cells -

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these blue cells you see here.

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All of you have these cells in your brain.

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And that's something
that was discovered quite recently.

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These cells are called
doublecortin positive cells.

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They are very abundant in fetuses

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because they help the formation
of the folding of the cortex.

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Our cortex is like a folded structure,
and these cells help with that.

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But we thought
that they disappear in adults,

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but we discovered more recently
that it was not true.

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4% of the cortical cells are
doublecortin positive cells.

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We don't know what they are for.

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Or what they are.

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Do they help us when we have a lesion
somewhere? We don't exactly know that.

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But what we know is that from these cells

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we got this cell culture
that I showed you.

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So of course, when biologists
work with neurosurgeons,

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neurosurgeons are always very pragmatic:

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"Wow, that's a great source of cells.
We may do something."

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I told you that we are so frustrated

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because the central nervous system
has so little ability for self-repair.

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Maybe we've found
something to help our patients.

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We thought a little bit,
and we came up with one concept.

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Why shouldn't we take
a biopsy of one individual?

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-Because we know how to do it;

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we put these cells in culture
- we know how to do it -

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we labeled the cells,

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and then we re-implant
the cells somewhere else in the brain.

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Great. Let's do it.

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Of course, you can't do it
on a human first,

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everybody knows you have to
do it first in a rodent model.

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But unfortunately, rodents don't have

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these double-quotient
positive cells in their cortex.

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We don't know why,
but a rodent doesn't help us.

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So we had to find
another type of animal to work with.

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Fortunately, we met...

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- I already knew him, he was a good friend
and he believed in our concept -

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Eric Rouiller, Professor of Physiology
in Fribourg, who has

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the biggest monkey facility in Switzerland

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and he helped us.

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He said: "Your concept is great,
I believe in what you are doing.

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Try with these two monkeys."

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We were very excited.

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First we could prove

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that we were able to do exactly
the same culture as that in humans,

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because monkeys have exactly
the same cell composition as us.

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Then, we did the cell culture labeling
and re-implantation.

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The first question we had was:

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how will these cells behave,
if are re-implanted in a normal brain?

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What will they become if are re-implanted
in a lesion or close to a lesion?

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Very interestingly, when they're implanted
close in a normal brain, they disappear.

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It's as if you take a biopsy,
you take the cells out from their home,

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you put them in culture,
re-implant them in the same individuals

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- so you don't have immunoresponse,

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they recognize they're here,
but they see the space is already busy,

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so they say: "I am not necessary
here, so bye-bye, I go."

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But if you implant them close to a lesion,

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they go back home and they say,
"There's an empty space,"

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they start to accommodate,

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and it would take them
a month, a month and half,

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but then they start to grow
and become mature neurons.

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That was exactly what we saw three months
after a re-implantation close to a lesion.

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You see these red cells
which are those we re-implanted,

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and note they are not little round cells
I showed you in the beginning,

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but they are bigger neurons with axons;

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we were under the impression
that they recolonized the area.

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We could also prove very nicely
that these were the same cells

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we had used in our culture.

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Because here you see here that's the dye
we use in our culture, the red dye,

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while the green dye is
the marker for the mature neurons.

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So you see that these two cells
have a double labeling:

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it means there are both green and red;

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it means they are mature neurons
that were previously in the culture,

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as immature neurons,

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and they turned into mature neurons.

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Of course what is the next step?

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Especially for a neurosurgeon, you want
to know what the implications are:

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Is it working? Is it good
to have these cells in?

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So that's what we did.

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What we did was we trained
a few monkeys to do a specific task

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- to take and grab some food pellets
in a drawer on a tray -

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and they were really good at it.

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It took some time to train them well.

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They reached a very good level
of performance.

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When they were stable
at this level of performance,

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we performed a little lesion
in the central motor cortex

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corresponding to the hand motion.

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So of course, immediately
after that, they are plegic,

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they can not move the arm any more;
they are not able to do the task.

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But nature's done quite well.

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We are able of recovery,
spontaneous recovery,

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- probably due to the spasticity -

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and performance becomes better
but only to a certain extent.

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So they are able to so something
but not as well as before.

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At that stage, we took the biopsy,
we did the culture, we re-implanted.

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And what we saw,

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and I think this picture
is better than any graph...

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So you see, on the left

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there is the money at the end
of his best recovery,

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when he has spontaneously recovered.

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On the right, a monkey
two months after re-implantation.

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So all the monkeys we re-implanted

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performed better than those
that haven't been re-implanted.

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Well, I think it's a nice story.

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So now what is the next step?

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Of course, we have a lot of experiments
done, with different models,

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and we have understood
many things since then.

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But still, my aim, and from the beginning
of my talk, is to apply this to humans.

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I must say that enthusiasm
decreases a little bit

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when you realize how difficult it is
to go through all these processes.

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And to obtain the authorization
to go into human trials.

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But, I still hope I'll be able
to do it before I retire.

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Thank you so much for your attention.

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(Applause)