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Thanks, John.
I'm delighted to be here today
to talk about my favorite cell:
the stem cell.
That might be a funny thing to say.
Most people have a favorite animal or a favorite color.
I actually have a favorite cell,
because this cell has two amazing properties:
it can make more of itself,
it can renew indefinitely
and it can also make any of the cells in your body.
As you know, all your tissues and organs
are made up of cells.
And so, here we have a cell
that can make anything in your body.
I'm going to tell you in the next 10 minutes
that this is the beginning of a revolution
in Biomedicine,
not unlike the revolution the transistor caused
in electronics.
Most all of you have a cellphone and use a computer.
Those wouldn't exist if it wasn't for a transistor.
Before transistors, there were vacuum tubes.
This cell, which we now can gain some mastery over,
will change the way you think about making
and maintaining human beings and fighting disease.
Now, I could talk about this in a number of contexts
for lots of diseases,
but I'm going to pick one, today.
I'm going to talk about diabetes.
I'll come back to other diseases
but I want to share with you the idea
that we could create a world
which got rid of diabetes.
There are two kinds of diabetes, known to most people.
The one which you're reading about all the time in the newspaper now
is related to excess food, lack of exercise, obesity.
It's called type 2 diabetes.
And many type 2 diabetics require insulin, but not all.
Some take a pill which makes them
more sensitive to insulin.
The kind of diabetes I want to talk about
is the one that affects children,
called juvenile or type 1 diabetes.
I have pictures here you see, where these children
have to test their blood
to know how much sugar is in it,
3 to 5 times a day,
and then inject themselves with a needle or with an insulin pump,
to provide insulin which is life saving.
Without the insulin, of course,
people wouldn't survive,
and you need the insulin to make use of the food you eat.
We've enjoyed, as John has just reminded us, a nice lunch,
with care of Summer Shack.
Well, as you're sitting here,
and your body is digesting that food and turn it into sugar,
your brain and the rest of your tissues
can't make use of that without this hormone insulin.
So now I'm going to bring you back to sort of high school biology,
for just about 4 or 5 slides in my presentation
and it's going to remind you
about things you have some intuitive knowledge of
and then I'm going to try to connect that with stem cells.
So, you all have inside you,
right sort of in this region of your body
an organ called the pancreas,
which is about the size of a banana.
Think about that like a piece of bread,
like raisin bread, with little raisins peppered in it.
There are 100,000 of these little spheres,
shown here on the top right,
that make hormones,
and the blue cells in those spheres
are making insulin.
In diabetics, those cells are destroyed.
So, as you see on the bottom right, the cells are gone.
There's no beta cells, as they're called.
So, the patient can't make insulin.
Insulin, from the drug industry's perspective,
has largely become not a blockbuster drug.
It's widely beyond that.
It's a commodity.
Nearly 25 billion dollars a year --
that's not million, billion dollars a year --
is bought and sold and injected into people.
So the project I'm going to tell you about
is relatively simple:
instead of injecting yourself with insulin,
why not give your body the cells,
the factories that make insulin
control your blood sugars and get rid of diabetes?
I've already hinted that the way one would think about doing that
is using my favorite cell --
these human stem cells can make any part of the body
and I showed you this chart
because you might have a different favorite part of your body.
So you can look at this and think,
"Well, if you were coming to the lab,
which part would you kind of make?"
I'm interested as you know, as I've said,
in this part of the pancreas
that makes the beta cells, the cells that produce insulin.
So I'm going to show you now
just a couple of slides that, in an unfair way,
summarize about 10 years of work,
trying to do what Marco Tempest called magic,
that is, to take a cell
and to create mastery and dominion over it
and make it become a pancreatic beta cell,
make it do what we want.
I'm going to just tell you how we've done that.
So we begin with this stem cell
sometimes called an embryonic stem cell,
or an induced pluripotent stem cell
and we have to instruct it as to what to do
because, remember, it can do anything.
You can think of it like being in kindergarten
and there's all sorts of options before it.
We have to first tell it to become part of the gut tube.
That's the tube, during development,
that runs from your mouth to your ***
as your lung, your liver, your stomach, your pancreas.
That's its first decision.
its second decision, then, is to become pancreas.
It could be the part of the pancreas that make enzymes
or the part that makes hormones.
Then it has to become hormone producing,
but finally our goal, our target,
is this beta cell, the cell that makes insulin.
Now, cells make decisions about their fate in life,
the same way people do,
by influences of their neighbors,
their friends, their parents, their teachers.
But in the case of cells,
those influences are other cells
sending signals to them.
Those signals can be small molecules,
like drugs showing here, a chemical,
or they can be proteins.
There's a picture of a protein
made by one cell and signaling the other.
These are what we call inducing signals.
Now what I'm going to show you
is that, after about a decade of work,
we have pretty much figured out
the molecular biography of a beta cell.
We know all of the signals that it's received
and how it's responded
and we're now trying to mimic or copy those,
outside of the body,
to make billions of cells.
We do that in a little blender,
kind of like what you might make a milkshake in.
And I'll show you pictures of that here.
If I could have you start this movie...
Here's one of these blenders
inside a sterile hood,
and the three orange caps, two on the right and left,
are used to add and take the chemical signals out.
That was the first day where we just began.
Two hours later, you see they're already dividing.
And they grow like weeds.
They grow into these cells that are big clusters.
And here I wanted to show you this picture,
because you can kind of see how fuzzy it is inside there.
Those are clusters of thousands of cells.
And the point I want to make in this one incubator
is we're making enough cells for 10 people.
So we can now, in a blender the size of something
you'd find in your kitchen,
make billions of cells
that are like beta cells.
So, John told me that you are such a smart audience.
I'm going to show you one science slide.
So, here is the evidence
that we are really close to our end goal.
For those of you that are football fans,
I would say we're in the red zone.
We're almost over the goal line
at making perfect cells.
On the top, you see a graph
and it has insulin on the left
and time across the bottom.
And if you look here, when we challenge
those human cells
isolated from a person who's passed away,
from a cadaver,
you give them low sugar,
you see they squirt out just the right amount of insulin,
right here.
If we give them high amount of sugar,
they now squirt out more insulin.
And if we depolarize the membrane,
they squirt out a lot.
Here are the cells that we are making
from these human embryonic stem cells.
The best way I can describe the magic to you here
is that if when I was an undergraduate
someone had told me that you can take a human cell
and grow it into a dish
and it would behave like a human cell,
I would have fallen out of my chair.
At that time, the only thing you could do
was study these things in rodents and other animals.
So now, for the first time,
we have the possibility
of gaining mastery and dominion
over the cells that make up our bodies.
To conclude, I dream of the time
when diabetic children won't have to test
their blood sugar and take insulin injections,
but instead could make use of the human stem cells
I've described today,
turning those into pancreatic beta cells,
which are then transplanted into their bodies,
giving them normal blood sugars,
freedom from insulin injections
and a normal life like other children.
Thanks for your attention.
(Applause)