Nanomedicines: nanobiotech vs cancer | Mark E. Davis | TEDxCaltech

Mark E. Davis is the Warren and Katharine Schlinger Professor of Chemical Engineering at Caltech and a member of the Experimental Therapeutics Program of the Comprehensive Cancer Center at the City of Hope.  He has over 350 scientific publications, two textbooks, and over 50 patents.  He is the recipient of numerous awards and was the first engineer to win the NSF Alan T. Waterman Award. He was elected to the National Academy of Engineering in 1997 and the National Academy of Sciences in 2006. Mark's research efforts involve materials synthesis in two general areas: namely, solids that can be used for molecular recognition and catalysis, and polymers for the delivery of a broad range of therapeutics. He is the founder of two biotech companies. Professor Davis has achieved All-American status for masters track and field in both the 400-meter and 200-meter dashes.

This talk was given at a TEDx event using the TED conference format but independently organized by a local community. Learn more at http://ted.com/tedx

Good evening.

(Applause)

Tonight I want to talk to you
about a new area of nanotechnology;

that is nanomedicines.

And this is an area

where nanotechnology is enabling
new and exciting biotechnology.

Now, over the past few decades,

deaths due to heart disease
have plummeted,

as you can see
from the data on this slide,

and that's a really good story.

But unfortunately with cancer,
we can't say the same.

And so today,

cancer is now the number one disease
that kills Americans under the age of 85.

And as you might expect,
this is not just a US problem;

it's a worldwide problem.

And from these data, you can see
that the death rate due to cancer

exceeds that from tuberculosis,
malaria, and HIV all combined.

And unfortunately, it's predicted
to continue to increase in the future.

So if you look, cancer has
a massive cost to society right now

in the loss of productivity that we have
from people expiring at an early age,

but also in the cost of the therapies,

as these therapies are increasing in price
at rates that are just not sustainable

when we have to treat
so many people worldwide.

And, of course,
you've probably all witnessed

that many patients
that are on current therapies

really suffer through poor quality of life
while they're on treatment

and even after the treatment's over.

So there's a real strong reason
to try to develop new cancer therapeutics

that are efficacious,
that have reasonable costs,

and, of course, can give patients
high quality of life.

And these issues motivate us
every day of our life.

We get up, go to the lab,
go to the hospital

to try to see if we can make
an impact on these issues.

Now, if we really want to have
an impact on the death rate,

we're going to have to treat
what's called metastatic disease.

That's where you have multiple tumors
throughout the body at the same time,

and this implies that your therapy has
to treat the whole body at the same time

or it's called systemic treatments.

Now, what are nanomedicines?

Well, these are small particles
that are therapeutics,

and they have the potential

to try to change the way
that we treat cancer patients.

Now, the National Cancer Institute
defines these particles

as particles between
one and 100 nanometers,

and they're composites
between therapeutic agents

and other carrier molecules,
like polymers.

Now, why is the size important?

This is real nanotechnology.

These particles are small.

So if you take 100-nanometer particle
and increase it to a soccer ball,

that's the same increase in size
from the soccer ball to the planet Earth.

So these very, very small particles,
we can put into the blood of a patient,

and they will circulate
throughout your body.

Now, it's interesting
that it's nanotechnology,

but it's actually large relative
to these chemotherapeutic drugs

that are less than a nanometer in size.

And so the analogy
is that the drug is the soccer ball;

the nanoparticle is actually
the Goodyear blimp.

So it's a very large entity,

and because of that, it's restricted
from certain areas in your body.

It also can carry a large payload of drug.

Think about how many soccer balls you
might be able to put in the Goodyear blimp

and how other multiple functions
can be put onto these larger entities.

Now, my group and others
throughout the world

have spent the last decade or so

trying to figure out how to design
and engineer these multifunctional systems

to treat patients with solid tumors.

And the field as a whole is converging
to this area of about 50 nanometers,

plus or minus 20.

And think of 50 nanometers
as, like, half the Goodyear blimp,

rather than the full Goodyear blimp.

And I've given you two illustrations
on this slide of those types of particles.

And so we're trying to design the size
and what's on the surface

and what kind of functions
that we can place into these particles.

And the reason is as follows -

now, the one panel's not showing up -

is that when you
infuse these into a patient

they can circulate in the blood system,

but they can't access certain areas
that chemotherapeutic drugs access,

like healthy tissues.

For example, those drugs
can go into your bone marrow,

that makes all of your cells
for your immune system, and kill them

and the molecules of your hair
that make your hair fall out.

With a nanoparticle, they can't go there,

and so they're much safer therapies
than the chemotherapeutic drugs.

But tumors grow new vessels, and so
those vessels are not completed yet,

and they'll allow these nanoparticles
to actually access that region.

And so we decorate
the surface of these particles

with molecules that allow them
to preferentially act

and interact with surface molecules
on the cancer cells

that then take these particles
inside the cell.

The ones we make at Caltech,
we try to make somewhat intelligent;

we put chemical sensors on them that say,

"Okay. I'm inside the cell now.

Give off my therapeutic payload."

And we make, by design,
the remnants of this particle small enough

that when it disassembles,
those remnants go out into your urine,

so there's no trace of it left
after the administration.

So normal cells grow, they divide,
and they die in an orderly fashion.

And there are many
regulatory systems that are used

that are turned on
and turned off to control this.

In cancer, some of these are altered,

and so what can happen, for example,

is the pathways that allow
these cells to grow and divide

get turned on permanently.

So if you really want to make an effective
therapy that has minimal side effects,

you'd like to attack
just at those altered positions.

And there's some new biotechnology
that may help us do this job,

and this is called RNA interference,
and it's a method to silence genes,

where the drug, now, is a small piece
of what's called a duplex of RNA -

two strands of RNA together.

And Craig Mello and Andy Fire

got the Nobel Prize in Physiology
or Medicine in 2006

for figuring out how this works in worms.

But when Andy gave his Nobel address,

he said, "Well, what could happen
if we have a patient that has a tumor

and there's a gene
that's causing that tumor to grow?

Could we, in fact,
make one of these small RNAs

and, in fact, give it to the patient
and stop the growth of the tumor?

If you could get that RNA to the target,

you could have some
really cool therapeutics."

I like that term, "cool therapeutics."

And delivery is the major issue:

How do you get these to the right place
and to do the right job?

So, about a year or so ago,

my colleagues and I were the first to show

that you could translate this
from a worm to a human,

and as you might expect,
that's a big translation.

But just last year,

we were able to show that you can,
in fact, do this in patients,

and so I'll try to illustrate
a few points for you now.

So what is so interesting
about this technology

is, unlike most drugs
that attack at the protein level -

and proteins do many different functions,

so you have to have drugs
that do many different things,

and there are lots of protein functions
that you just can't attack,

and those are called undruggable targets.

But RNA interference attacks
at what's called the messenger RNA,

and all we have to do there
is just change the sequence of the letters

that we can attack and eliminate
any of those messenger RNAs,

and so any gene, now,
is druggable by this technology,

just by changing
the letters on our duplex RNA.

So what my colleagues and I did

is we developed a nanoparticle
that carried these small RNAs,

and we infused these into cancer patients.

And these particles would circulate
through the body of the cancer patients.

And we were able to show

that they would, in fact, go to tumors
in metastatic melanoma patients,

and, in fact, they would do it
in a dose-dependent fashion,

and what that means

is the more nanoparticles
that we actually put into the body,

the more we saw ending up in the tumors.

And we could do this where patients
would have very high quality of life.

In the few patients
that we were able to get biopsies,

we were able to look more closely,

and I've shown two pictures
here on this slide:

the first is, the light areas
that are in the tumor area,

those are actually the nanoparticles.

And so we were actually able to show
that these nanoparticles go into the tumor

and into the tumor cells,

but they didn't localize at all
into the healthy tissue

that was around the tumor,
as we're trying to do.

Now, we were able to eliminate
this individual messenger RNA.

We were able to show that it was
by this RNA interference mechanism.

And so, it would stop
the production of a protein,

which I'm showing on this slide as well -

that we eliminated this protein,

and this caused the tumors
not to grow in these patients.

So, what I've shown you
is at least one example

where, in fact, the nanoparticle
can enable this new biotechnology

to try to create new cancer therapeutics
with the right type of properties.

And so we hope that
the potential for these is high

and mainly to be able
to give cancer patients

treatment options
with high quality of life.

Now, what about the future?

So what we've been able to do so far

is to take these nanoparticles,
infuse them in the patient,

and actually inhibit an individual gene
in the tumor of these patients

while they're having high quality of life.

Now, there's no reason

that we couldn't put multiple types
of RNAs into these particles

so we could attack
multiple genes simultaneously.

So, our vision is that
we start to treat patients

and that we use, then,
a fingerprick of blood

and analyze a variety
of biomolecules in blood

through a variety of other techniques
that people have talked about -

various arrays and so forth.

We take that information -

probably what will happen in the future
is you'll do this at home;

you'll plug it into your iPhone,

and your iPhone
will call up your physician

and say, "Here are the results"

so that the next time
you go to the doctor's office,

they're going to say,

"Here's the new therapy
that we're going to give to you."

So not only in a personalized sense
can you change for these therapies,

but we're hoping that you can
actually change in a dynamic sense

for an individual person to actually
follow the course of the disease

and eradicate it
in the best manner you can.

So that's the vision for cancer,
and it probably would happen that way -

and then hopefully
with other diseases as well.

Thank you.

(Applause)