Soon we'll cure diseases with a cell, not a pill

I want to talk to you
about the future of medicine,

but before I do that, I want to talk
a little bit about the past.

Now, throughout much
of the recent history of medicine,

we've thought about illness and treatment

in terms of a profoundly simple model.

In fact, the model is so simple

that you could summarize it in six words:

have disease, take pill, kill something.

Now, the reason for
the dominance of this model

is of course the antibiotic revolution.

Many of you might not know this,
but we happen to be celebrating

the hundredth year of the introduction
of antibiotics into the United States,

but what you do know

is that that introduction
was nothing short of transformative.

Here you had a chemical,
either from the natural world

or artificially synthesized
in the laboratory,

and it would course through your body,

it would find its target,

lock into its target --

a microbe or some part of a microbe --

and then turn off a lock and a key

with exquisite deftness,
exquisite specificity,

and you would end up taking
a previously fatal, lethal disease,

a pneumonia, syphilis, tuberculosis,

and transforming that into a curable,
or treatable illness.

You have a pneumonia,
you take penicillin,

you kill the microbe,

and you cure the disease.

So seductive was this idea,

so potent the metaphor of lock and key

and killing something,

that it really swept through biology.

It was a transformation like no other,

and we've really spent the last 100 years

trying to replicate that model
over and over again

in noninfectious diseases,

in chronic diseases like diabetes
and hypertension and heart disease.

And it's worked,
but it's only worked partly.

Let me show you.

You know, if you take the entire universe

of all chemical reactions
in the human body,

every chemical reaction
that your body gets,

most people think that that number
is on the order of a million.

Let's call it a million.

And now you ask the question,

what number or fraction of reactions

can actually be targeted

by the entire pharmacopia,
all of medicinal chemistry?

That number is 250.

The rest is chemical darkness.

In other words, 0.025 percent
of all chemical reactions in your body

are actually targetable
by this lock and key mechanism.

You know, if you think about
human physiology

as a vast global telephone network

with interacting nodes
and interacting pieces,

then all of our medicinal chemistry

is all operating on one tiny corner

at the edge, the outer edge,
of that network.

It's like all of our
pharmaceutical chemistry

is a pole operator in Wichita, Kansas

who is tinkering with
about 10 or 15 telephone lines.

So what do about this idea?

What if we reorganized this approach?

In fact, it turns out
that the natural world

gives us a sense of how one
might think about illness

in a radically different way,

rather than disease, medicine, target.

In fact, the natural world
is organized hierarchically upwards,

not downwards, but upwards,

and we begin with a self-regulating,
semi-autonomous unit called a cell.

These self-regulating,
semi-autonomous units

give rise to self-regulating,
semi-autonomous units called organs,

and these organs coalesce
to form things called humans,

and these organisms ultimately live
in environments,

which are partly self-regulating
and partly semi-autonomous.

What's nice about this scheme,
this hierarchical scheme

building upwards rather than downwards

is that it allows us to think
about illness as well

in a somewhat different way.

Take a disease like cancer.

Since the 1950s, we've tried
rather desperately to apply

this lock and key model to cancer.

We've tried to kill cells using a variety
of chemotherapies or targeted therapies,

and as most of us know, that's worked.

It's worked for diseases like leukemia.

It's worked for some forms
of breast cancer,

but eventually you run
to the ceiling of that approach,

and it's only in the last 10 years or so

that we've begun to think
about using the immune system,

remembering that in fact the cancer cell
doesn't grow in a vacuum.

It actually grows in a human organism,

and could you use the organismal capacity,

the fact that human beings
have an immune system, to attack cancer?

In fact, it's led to the some of the most
spectacular new medicines in cancer.

And finally, I mean, there's the level
of the environment, isn't there.

You know, we don't think of cancer
as altering the environment.

Let me give you an example
of a profoundly carcinogenic environment.

It's called a prison.

You take loneliness, you take depression,
you take confinement,

and you add to that,

rolled up in a little white
sheet of paper,

one of the most potent neurostimulants
that we know, called nicotine,

and you add to that one of the most potent
addictive substances that you know,

and you have a pro-carcinogenic
environment.

But you can have anti-carcinogenic
environments too.

There are attempts to create milieus,

change the hormonal milieu
for breast cancer, for instance.

We're trying to change the metabolic
milieu for other forms of cancer.

Or take another disease, like depression.

Again, working others,

since the 1960s and 1970s,
we've tried, again, desperately

to turn off molecules that operate
between nerve cells --

serotonin, dopamine --

and tried to cure depression that way,
and that's worked,

but then that leads to the limit.

And we now know that what you
really probably need to do

is to change the physiology
of the organ, the brain,

rewire it, remodel it,

and that of course, we know
study upon study has shown

that talk therapy does exactly that,

and study upon study has shown
that talk therapy combined

with medicines, pills,

really is much more effective
than either one alone.

Can we imagine a more immersive
environment that will change depression?

Can you lock out the signals
that elicit depression?

Again, moving upwards along this
hierarchical chain of organization.

What's really at stake perhaps here

is not the medicine itself but a metaphor.

Rather than killing something,

in the case of the great
chronic degenerative diseases --

kidney failure, diabetes,
hypertension, osteoarthritis --

maybe what we really need to do is change
the metaphor to growing something.

And that's the key, perhaps,

to reframing our thinking about medicine.

Now, this idea of changing,

of creating a perceptual shift,
as it were,

came home to me to roost in a very,
very personal matter about 10 years ago.

About 10 years ago --
I've been a runner most of my life --

I went for a run, a Saturday morning run,

I came back and woke up
and I basically couldn't move.

My right knee was swollen up,

and you could hear that ominous crunch
of bone against bone.

And one of the perks of being a physician
is that you get to order your own MRIs.

And I had an MRI the next week,
and it looked like that.

Essentially, the meniscus of cartilage
that is between bone

had been completely torn
and the bone itself had been shattered.

Now, if you're looking at me
and feeling sorry,

let me tell you a few facts.

If I was to take an MRI
of every person in this audience,

60 percent of you would show signs

of bone degeneration
and cartilage degeneration like this;

85 percent of all women by the age of 70

would show moderate to severe
cartilage degeneration;

50 to 60 percent of the men in
this audience would also have such signs.

So this is a very common disease.

Well, the second perk of being a physician

is that you can get to experiment
on your own ailments.

So about 10 years ago we began,

we brought this process
into the laboratory,

and we began to do simple experiments,

mechanically trying
to fix this degeneration.

We tried to inject chemicals
into the knee spaces of animals

to try to reverse cartilage degeneration,

and to put a short summary
on a very long and painful process,

essentially it came to naught.

Nothing happened.

And then about seven years ago,
we had a research student from Australia.

Now, the nice thing about Australians
is that they're habitually used

to looking at the world upside down,
and so -- (Laughter) --

Dan suggested to me, "You know,
maybe it isn't a mechanical problem.

Maybe it isn't a chemical problem.
Maybe it's a stem cell problem."

In other words, he had two hypotheses.

Number one, there is such a thing
as a skeletal stem cell

that builds up the entire
vertebrate skeleton:

bone, cartilage,
and the fibrous elements of skeleton,

just like there's a stem cell in blood,

just like there's a stem cell
in the nervous system,

and two, that maybe that, the degeneration
or dysfunction of this stem cell

that is causing osteochondral arthritis,
a very common ailment.

So really the question was,
were we looking for a pill

when we should have really
been looking for a cell.

So we switched our models,

and now we began to look
for skeletal stem cells,

and to cut again a long story short,

about five years ago,
we found these cells.

They live inside the skeleton.

Here's a schematic and then
a real photograph of one of them.

The white stuff is bone,

and these red columns that you see
and the yellow cells

are cells that have arisen
from one single skeleton stem cell,

columns of cartilage, columns of bone
coming out a single cell.

These cells are fascinating.
They have four properties.

Number one is that they live
where they're expected to live.

They live just underneath
the surface of the bone,

underneath cartilage.