Transcriber: Claire Ghyselen Reviewer: Kim Key
This is Emile.
Emile is my grandfather.
He died 40 years ago.
And he died at the age of 78.
He died peacefully.
He was perfectly conscious,
with bright memory
until the very last day of his life.
A pleasure to live with him.
This, on the other hand, is my father, my father Roland.
My father lived 10 more years.
He lived up to the age of 88.
During the last 10 years of his life,
my father developed brain degenerescence,
what most people would call Alzheimer.
The last 10 years of his life were difficult.
He couldn't remember the name
of his grandsons.
He couldn't remember
my own name at the end of his life.
So it was really challenging
to see someone who was bright,
a bright intellectual, soft mannered,
decline to a stage where it was difficult for him
to communicate with others.
So, the topic I am talking about today
is the topic of degenerative diseases.
And this is an epidemic,
because we are ageing,
society is ageing,
we're changing our food habits
pollution is there.
Degenerative diseases are becoming
more and more frequent.
It is a real issue.
By the way, my father died 15 years ago.
Do you think if he would have lived today,
he would have had a different fate,
than 15 years ago, for Alzheimer?
Mildly but probably not very much.
But do you think 10 years from now,
or 15 years from now,
this situation could change?
The topic of my talk is just that:
Can we actually do something different
for those people?
I'm focusing myself, my studies on cardiology
I'm focusing on heart failure,
and I'm going to take that as an example of degenerative diseases.
Why? Because heart failure is also an epidemic.
Among this audience,
how many of you are more than 40 years old?
Please raise your hand.
OK, quite a few. Keep your hands up!
The bad news is that 1 out of 5 of you,
and it includes me by the way,
1 out of 5 of you will develop
heart failure in the remainder of your life.
Do you want something worse?
Out of the ones who developed heart failure
1 out of 3 will die within a year of diagnosis.
Scary!
First, why does heart failure exist?
Think about a heart, your heart,
your own heart that pumps
100 ml out, at each beat,
every second, for your life time.
It pumps out against a pressure
that is about the same pressure
as you have in the tyre of your car.
So think about putting 100 ml of air
in the tyre of your car, every second
for the remainder of your life.
That happens from the time you're born,
until the time you're dead.
There is only one machine in the world
that can do that: that's the heart.
Nothing else can do it.
So you can imagine, as we get older
that machine starts getting tired.
About 50% of the heart failures are due
to heart attacks,
what we call myocardial infraction.
Myocardial infraction occurs
when the blood vessel that feeds the heart,
called the coronary artery, gets blocked.
It gets blocked by a thrombosis,
or by anything that stops it.
What happens: the blood stops flowing to the ventricle
and that portion of the heart dies.
It becomes a scar.
When I was practicing 20 years ago,
out of 5 patients who were coming
into intensive care for heart attack,
one would die within 30 days.
1 out of 5: 20%!
Today, 1 out of 30 dies.
It's great, we saved a lot of people.
But, all the people that died,
but do not die anymore,
have a very big scar.
And they suffer from heart failure
because of that very big scar.
So this is the first cause of heart failure.
The other causes are hypertension,
valvular diseases etc.
there are a number of different other causes.
Now, the problem if you have a big scar,
is that the rest of your heart has to pump
and compensate for the part that does not beat.
How do we solve this?
Imagine if we could...
This is the heart that beats,
This is the portion that does not beat.
Imagine we could replace that portion,
with a portion that beats again.
Imagine we could re-construct that scar,
and have a heart that beats again.
We would have erased heart failure.
And why is it important?
Cardiovascular diseases
are the first cause of death in the world today.
People think of cancer,
they think about infectious diseases.
No! Cardiovascular is the first cause of death,
twice the second cause, which is cancer.
And twice the third cause, which is,
infectious diseases.
So is it worth trying to do something about it?
Probably.
How can we replace that scar?
How can we actually get that tissue that is not beating,
to repair itself?
Look back into the time.
Look at some species that we currently know.
In science, there is a specific animal
that is called the zebra fish
that can heal itself very easily.
But in your everyday life,
you see, lizards, salamanders.
If you chop the limb of a lizard,
or of a salamander,
it's going to grow again. Right?
We've all seen that in our science course.
What grows?
The bones grow.
The muscles grow. The tissues grow.
The vessels grow. Everything.
You have a new perfectly functional limb,
a few days after the accident happened.
We, humans, have lost that capacity.
Have we completely lost it?
Not really.
Some organs have kept that capacity.
Why have the bones, for example,
kept that capacity?
Why has the skin kept that capacity?
Well it's simple. This is about evolution.
10,000 years ago,
our ancestors lived until 15, 20,
sometimes 25,
sometimes 30 for the very old ones.
But they were dying after that.
And the "noble organs",
like the heart, the kidney, the spleen,
all those organs did not have the time
to age, get sick and fail.
However, those early humans
were still hurting themselves,
were still getting wounded,
were still breaking their bones.
So Nature, in its intelligence,
has kept the capacity to repair
those particular organs,
and has lost it for the others.
Why? Because it's an equilibrium.
If you have the capacity to repair yourself,
you have more propensity to make cancers.
So, Nature, basically the evolution,
managed to keep that capacity
for the organs that were at high risk,
and loose that capacity -
remember, we talk about people
who were living up to the age of 30 -
and lost that capacity for the other organs,
Can we teach the heart to regain that capacity?
There is an organ that we can look at,
that does this very well: the bone.
When you look at the bone,
there are little cells in that bone,
little factories, [whose] task is to repair the bone.
They are called "osteoblasts".
That's their only job to do that.
The heart and the other organs that are non-reparative,
do not have those cells.
So what scientists did in the early 2000 was:
Let's try to take cells that are close to that,
and try to inject them into the heart.
So, what we did was to take cells from the hip,
from the bone marrow.
People call them stem cells.
They are not really stem cells, but people call them so.
We injected them into the heart of patients,
and, it did some repair.
But it did it in about 20% of the patients.
20% of the patients had the repair capacity
using those cells.
80% of the patients, did not.
Now, we needed to understand
why some patients were repairing themselves
and some patients did not.
So, actually you need to think about it
as clues, cause, how to resolve this issue.
Here we see that the patients
who did not repair themselves,
the cells are very different
from those of the patients who repaired themselves.
You see on the bottom part of the slide,
the cells are of a different color
than those in the upper part of the chart.
So the question is:
Can we transform the cells that are non reparative
into cells that are reparative?
It seems easy.
It's a little bit more complex than that.
So, what we did for that
is go back into the embryology.
Try to understand,
when the cells are still in kindergarden,
they can still do about anything.
They can become heart,
they can become liver, or bone.
The same thing as kids.
They can become doctors, engineers,
they can become artists.
So we need to teach that cell
to become something
that it was not programmed to do.
And how do we do this?
To give you an order of magnitude,
the way a cell transforms itself
is through receptors
that are on the surface of the cells.
Consider them as locks. Those are locks.
Then you have keys that go into those locks.
Those are the signals,
the proteins that activate that lock.
Picture a safe, a big safe,
in which there are many many doors,
and you have a hundred locks
that open one specific door.
And that door is the door of cardiac reprogramming.
First, you need to find which are the locks.
Among those thousands of locks,
which are the right hundred locks
that are responsible for that.
Second, I'm going to give you a bag
full of one hundred thousand keys.
100,000 keys.
Those are the the proteins that exist in the body
that activate all the locks.
Now that you have found the lock,
I want you to find the key
that is going to open each one of those locks.
Each one in the right sequence.
To spare you the calculation,
the odds of finding this by accident,
is less than winning the lotto
one thousand time in a row.
But we had again a code.
Why?
Because in the early 2000, what we did was
we found a protein.
And when we were putting those cells in culture,
and putting the protein with it,
instead of having 1 or 2% of the cells
becoming heart cells,
we had 50% of cells becoming heart cells.
So, now we started having some signals,
what is happening
and we figured out what this protein is doing.
And the protein is doing this.
I'm going to quizz you on this at the end of the show.
(Laughter)
So, the protein activates all those signals.
That is the code that makes the cell,
from a non cardiac cell,
to become a cardiac cell.
This is the secret, the code.
Next thing, now that we know how to do the cells,
we go back to our original concept:
Do those cells actually work better
than non-modified cells?
So we did this:
we injected those cells into animals, into mice.
And this is the result we got:
On the left, you have a mouse
that was treated with cells that were not modified.
You see within the doted line,
the scar, the white part, is still there.
You do a section through this,
you see the scar, at about 12 o'clock,
or 1 o'clock, you see the scar on the top.
On the right side,
this animal was treated with cells
from the same patient, that were modified
and the scar is not there anymore.
It's interesting, we seem to see,
for the first time in the world,
someone was able to reconstruct a heart
an adult heart, using cells from patient.
The next step was:
Does it actually work in patients?
And we did a study of 45 patients,
we've published that data recently,
and we have been able to see the patients
were actually walking better, living better.
Some patients could go, and do their grocery
while they were not able
to go from their bed to their chair.
We had some very positive signals.
But I want to be careful,
because it's not the first time,
when we do a small study of 45 patients,
then, when we do a big study,
we cannot replicate what we've found in the small study.
I hope we are on the way of resolving something.
But I'm not sure that we have yet done it.
We are in the process of doing this now.
Imagine just for a second,
that we could do this with the brain.
Imagine we could do this with the pancreas
to cure diabetes.
Imagine we could do this for Parkinson's disease.
This is the field of regenerative medicine.
This is the dream that we are trying to achieve.
Don't misunderstand the challenges of this.
From using powders to treat symptoms,
and drugs and injectibles,
we need to produce living things: cells.
We need to ship those cells.
We need to inject those cells.
We need to preserve those cells.
We need the social security system
to be able to support these type of treatments.
So, it's not an insignificant challenge
that is still ahead of us.
There are still many other challenges that we need to solve.
But think of a world, for a second,
where we will still die,
but die healthy!
Thank you.
(Applause)