WEBVTT

00:00:06.221 --> 00:00:07.217
Good evening.

00:00:07.217 --> 00:00:08.218
(Applause)

00:00:08.218 --> 00:00:11.443
Tonight I want to talk to you
about a new area of nanotechnology;

00:00:11.443 --> 00:00:13.755
that is nanomedicines.

00:00:13.755 --> 00:00:14.736
And this is an area

00:00:14.736 --> 00:00:19.306
where nanotechnology is enabling
new and exciting biotechnology.

00:00:19.721 --> 00:00:21.740
Now, over the past few decades,

00:00:21.740 --> 00:00:23.745
deaths due to heart disease
have plummeted,

00:00:23.745 --> 00:00:25.744
as you can see
from the data on this slide,

00:00:25.744 --> 00:00:27.833
and that's a really good story.

00:00:27.833 --> 00:00:30.875
But unfortunately with cancer, 
we can't say the same.

00:00:30.875 --> 00:00:32.432
And so today,

00:00:32.432 --> 00:00:37.622
cancer is now the number one disease
that kills Americans under the age of 85.

00:00:38.076 --> 00:00:41.278
And as you might expect,
this is not just a US problem;

00:00:41.278 --> 00:00:42.522
it's a worldwide problem.

00:00:42.522 --> 00:00:45.672
And from these data, you can see 
that the death rate due to cancer

00:00:45.672 --> 00:00:50.922
exceeds that from tuberculosis, 
malaria, and HIV all combined.

00:00:50.922 --> 00:00:54.550
And unfortunately, it's predicted
to continue to increase in the future.

00:00:55.302 --> 00:00:59.541
So if you look, cancer has
a massive cost to society right now

00:00:59.541 --> 00:01:04.311
in the loss of productivity that we have
from people expiring at an early age,

00:01:04.311 --> 00:01:06.286
but also in the cost of the therapies,

00:01:06.286 --> 00:01:10.489
as these therapies are increasing in price
at rates that are just not sustainable

00:01:10.489 --> 00:01:13.219
when we have to treat
so many people worldwide.

00:01:13.774 --> 00:01:16.259
And, of course, 
you've probably all witnessed

00:01:16.259 --> 00:01:18.760
that many patients
that are on current therapies

00:01:18.760 --> 00:01:22.317
really suffer through poor quality of life
while they're on treatment

00:01:22.317 --> 00:01:24.754
and even after the treatment's over.

00:01:24.754 --> 00:01:29.744
So there's a real strong reason
to try to develop new cancer therapeutics

00:01:29.744 --> 00:01:33.009
that are efficacious,
that have reasonable costs,

00:01:33.009 --> 00:01:36.326
and, of course, can give patients
high quality of life.

00:01:36.326 --> 00:01:39.312
And these issues motivate us
every day of our life.

00:01:39.312 --> 00:01:41.713
We get up, go to the lab,
go to the hospital

00:01:41.713 --> 00:01:45.613
to try to see if we can make
an impact on these issues.

00:01:45.613 --> 00:01:48.595
Now, if we really want to have
an impact on the death rate,

00:01:48.595 --> 00:01:51.502
we're going to have to treat
what's called metastatic disease.

00:01:51.502 --> 00:01:55.797
That's where you have multiple tumors
throughout the body at the same time,

00:01:55.797 --> 00:01:59.518
and this implies that your therapy has
to treat the whole body at the same time

00:01:59.518 --> 00:02:01.978
or it's called systemic treatments.

00:02:02.750 --> 00:02:04.307
Now, what are nanomedicines?

00:02:04.307 --> 00:02:07.708
Well, these are small particles
that are therapeutics,

00:02:07.708 --> 00:02:09.267
and they have the potential

00:02:09.267 --> 00:02:12.604
to try to change the way
that we treat cancer patients.

00:02:12.604 --> 00:02:15.945
Now, the National Cancer Institute
defines these particles

00:02:15.945 --> 00:02:18.979
as particles between
one and 100 nanometers,

00:02:18.979 --> 00:02:22.011
and they're composites
between therapeutic agents

00:02:22.011 --> 00:02:24.571
and other carrier molecules,
like polymers.

00:02:25.320 --> 00:02:27.558
Now, why is the size important?

00:02:27.558 --> 00:02:29.810
This is real nanotechnology.

00:02:29.810 --> 00:02:31.800
These particles are small.

00:02:31.800 --> 00:02:35.290
So if you take 100-nanometer particle 
and increase it to a soccer ball,

00:02:35.290 --> 00:02:39.281
that's the same increase in size 
from the soccer ball to the planet Earth.

00:02:39.281 --> 00:02:43.004
So these very, very small particles,
we can put into the blood of a patient,

00:02:43.004 --> 00:02:45.224
and they will circulate
throughout your body.

00:02:45.789 --> 00:02:48.762
Now, it's interesting
that it's nanotechnology,

00:02:48.762 --> 00:02:52.982
but it's actually large relative
to these chemotherapeutic drugs

00:02:52.982 --> 00:02:55.492
that are less than a nanometer in size.

00:02:55.492 --> 00:02:58.355
And so the analogy
is that the drug is the soccer ball;

00:02:58.355 --> 00:03:01.094
the nanoparticle is actually
the Goodyear blimp.

00:03:01.094 --> 00:03:03.144
So it's a very large entity,

00:03:03.144 --> 00:03:07.224
and because of that, it's restricted
from certain areas in your body.

00:03:07.656 --> 00:03:10.364
It also can carry a large payload of drug.

00:03:10.364 --> 00:03:14.135
Think about how many soccer balls you
might be able to put in the Goodyear blimp

00:03:14.135 --> 00:03:18.395
and how other multiple functions
can be put onto these larger entities.

00:03:19.030 --> 00:03:21.270
Now, my group and others
throughout the world

00:03:21.270 --> 00:03:22.798
have spent the last decade or so

00:03:22.798 --> 00:03:27.368
trying to figure out how to design
and engineer these multifunctional systems

00:03:27.368 --> 00:03:29.840
to treat patients with solid tumors.

00:03:29.840 --> 00:03:33.903
And the field as a whole is converging
to this area of about 50 nanometers,

00:03:33.903 --> 00:03:35.623
plus or minus 20.

00:03:35.623 --> 00:03:38.820
And think of 50 nanometers
as, like, half the Goodyear blimp,

00:03:38.820 --> 00:03:40.540
rather than the full Goodyear blimp.

00:03:40.540 --> 00:03:45.600
And I've given you two illustrations
on this slide of those types of particles.

00:03:45.600 --> 00:03:49.619
And so we're trying to design the size
and what's on the surface

00:03:49.619 --> 00:03:52.939
and what kind of functions
that we can place into these particles.

00:03:53.371 --> 00:03:55.311
And the reason is as follows -

00:03:55.311 --> 00:03:57.589
now, the one panel's not showing up -

00:03:57.589 --> 00:04:01.185
is that when you
infuse these into a patient

00:04:01.185 --> 00:04:03.095
they can circulate in the blood system,

00:04:03.095 --> 00:04:08.058
but they can't access certain areas
that chemotherapeutic drugs access,

00:04:08.058 --> 00:04:09.798
like healthy tissues.

00:04:09.798 --> 00:04:12.700
For example, those drugs
can go into your bone marrow,

00:04:12.700 --> 00:04:15.810
that makes all of your cells
for your immune system, and kill them

00:04:15.810 --> 00:04:18.808
and the molecules of your hair
that make your hair fall out.

00:04:18.808 --> 00:04:21.057
With a nanoparticle, they can't go there,

00:04:21.057 --> 00:04:25.537
and so they're much safer therapies
than the chemotherapeutic drugs.

00:04:25.537 --> 00:04:29.178
But tumors grow new vessels, and so
those vessels are not completed yet,

00:04:29.178 --> 00:04:33.688
and they'll allow these nanoparticles
to actually access that region.

00:04:33.688 --> 00:04:36.786
And so we decorate
the surface of these particles

00:04:36.786 --> 00:04:40.083
with molecules that allow them
to preferentially act

00:04:40.083 --> 00:04:43.741
and interact with surface molecules
on the cancer cells

00:04:43.741 --> 00:04:47.062
that then take these particles 
inside the cell.

00:04:47.062 --> 00:04:50.185
The ones we make at Caltech,
we try to make somewhat intelligent;

00:04:50.185 --> 00:04:52.152
we put chemical sensors on them that say,

00:04:52.152 --> 00:04:54.320
"Okay. I'm inside the cell now.

00:04:54.320 --> 00:04:56.873
Give off my therapeutic payload."

00:04:56.873 --> 00:05:00.598
And we make, by design, 
the remnants of this particle small enough

00:05:00.598 --> 00:05:03.719
that when it disassembles,
those remnants go out into your urine,

00:05:03.719 --> 00:05:07.289
so there's no trace of it left
after the administration.

00:05:08.128 --> 00:05:13.596
So normal cells grow, they divide,
and they die in an orderly fashion.

00:05:13.596 --> 00:05:16.565
And there are many
regulatory systems that are used

00:05:16.565 --> 00:05:19.286
that are turned on
and turned off to control this.

00:05:19.286 --> 00:05:21.504
In cancer, some of these are altered,

00:05:21.504 --> 00:05:23.236
and so what can happen, for example,

00:05:23.236 --> 00:05:26.026
is the pathways that allow
these cells to grow and divide

00:05:26.026 --> 00:05:27.867
get turned on permanently.

00:05:27.867 --> 00:05:32.057
So if you really want to make an effective
therapy that has minimal side effects,

00:05:32.057 --> 00:05:36.090
you'd like to attack 
just at those altered positions.

00:05:36.090 --> 00:05:40.142
And there's some new biotechnology
that may help us do this job,

00:05:40.142 --> 00:05:44.326
and this is called RNA interference,
and it's a method to silence genes,

00:05:44.326 --> 00:05:49.696
where the drug, now, is a small piece
of what's called a duplex of RNA -

00:05:49.696 --> 00:05:52.229
two strands of RNA together.

00:05:52.229 --> 00:05:54.175
And Craig Mello and Andy Fire

00:05:54.175 --> 00:05:57.929
got the Nobel Prize in Physiology
or Medicine in 2006

00:05:57.929 --> 00:06:00.559
for figuring out how this works in worms.

00:06:01.461 --> 00:06:04.144
But when Andy gave his Nobel address,

00:06:04.144 --> 00:06:07.671
he said, "Well, what could happen
if we have a patient that has a tumor

00:06:07.671 --> 00:06:10.628
and there's a gene 
that's causing that tumor to grow?

00:06:10.628 --> 00:06:13.718
Could we, in fact, 
make one of these small RNAs

00:06:13.718 --> 00:06:17.008
and, in fact, give it to the patient
and stop the growth of the tumor?

00:06:17.671 --> 00:06:19.674
If you could get that RNA to the target,

00:06:19.674 --> 00:06:21.856
you could have some
really cool therapeutics."

00:06:21.856 --> 00:06:24.162
I like that term, "cool therapeutics."

00:06:24.162 --> 00:06:25.691
And delivery is the major issue:

00:06:25.691 --> 00:06:28.961
How do you get these to the right place
and to do the right job?

00:06:29.483 --> 00:06:32.022
So, about a year or so ago,

00:06:32.022 --> 00:06:34.032
my colleagues and I were the first to show

00:06:34.032 --> 00:06:36.937
that you could translate this
from a worm to a human,

00:06:36.937 --> 00:06:40.330
and as you might expect,
that's a big translation.

00:06:40.330 --> 00:06:41.334
But just last year,

00:06:41.334 --> 00:06:44.384
we were able to show that you can, 
in fact, do this in patients,

00:06:44.384 --> 00:06:47.298
and so I'll try to illustrate
a few points for you now.

00:06:47.298 --> 00:06:50.361
So what is so interesting
about this technology

00:06:50.361 --> 00:06:54.345
is, unlike most drugs
that attack at the protein level -

00:06:54.345 --> 00:06:56.309
and proteins do many different functions,

00:06:56.309 --> 00:06:58.928
so you have to have drugs
that do many different things,

00:06:58.928 --> 00:07:02.073
and there are lots of protein functions
that you just can't attack,

00:07:02.073 --> 00:07:04.183
and those are called undruggable targets.

00:07:04.731 --> 00:07:08.754
But RNA interference attacks
at what's called the messenger RNA,

00:07:08.754 --> 00:07:12.422
and all we have to do there
is just change the sequence of the letters

00:07:12.422 --> 00:07:15.672
that we can attack and eliminate
any of those messenger RNAs,

00:07:15.672 --> 00:07:18.859
and so any gene, now, 
is druggable by this technology,

00:07:18.859 --> 00:07:21.839
just by changing
the letters on our duplex RNA.

00:07:22.682 --> 00:07:24.211
So what my colleagues and I did

00:07:24.211 --> 00:07:27.895
is we developed a nanoparticle
that carried these small RNAs,

00:07:27.895 --> 00:07:31.086
and we infused these into cancer patients.

00:07:31.086 --> 00:07:34.653
And these particles would circulate
through the body of the cancer patients.

00:07:34.653 --> 00:07:36.062
And we were able to show

00:07:36.062 --> 00:07:40.682
that they would, in fact, go to tumors 
in metastatic melanoma patients,

00:07:40.946 --> 00:07:44.247
and, in fact, they would do it
in a dose-dependent fashion,

00:07:44.247 --> 00:07:45.246
and what that means

00:07:45.246 --> 00:07:48.198
is the more nanoparticles
that we actually put into the body,

00:07:48.198 --> 00:07:51.205
the more we saw ending up in the tumors.

00:07:51.205 --> 00:07:54.885
And we could do this where patients
would have very high quality of life.

00:07:55.405 --> 00:07:58.692
In the few patients
that we were able to get biopsies,

00:07:58.692 --> 00:08:00.519
we were able to look more closely,

00:08:00.519 --> 00:08:02.728
and I've shown two pictures
here on this slide:

00:08:02.728 --> 00:08:05.751
the first is, the light areas 
that are in the tumor area,

00:08:05.751 --> 00:08:07.956
those are actually the nanoparticles.

00:08:07.956 --> 00:08:11.676
And so we were actually able to show
that these nanoparticles go into the tumor

00:08:11.676 --> 00:08:13.464
and into the tumor cells,

00:08:13.464 --> 00:08:16.417
but they didn't localize at all
into the healthy tissue

00:08:16.417 --> 00:08:19.548
that was around the tumor,
as we're trying to do.

00:08:19.548 --> 00:08:23.808
Now, we were able to eliminate
this individual messenger RNA.

00:08:23.808 --> 00:08:27.343
We were able to show that it was
by this RNA interference mechanism.

00:08:27.343 --> 00:08:30.338
And so, it would stop
the production of a protein,

00:08:30.338 --> 00:08:32.440
which I'm showing on this slide as well -

00:08:32.440 --> 00:08:34.459
that we eliminated this protein,

00:08:34.459 --> 00:08:37.759
and this caused the tumors
not to grow in these patients.

00:08:39.144 --> 00:08:42.570
So, what I've shown you
is at least one example

00:08:42.570 --> 00:08:46.468
where, in fact, the nanoparticle
can enable this new biotechnology

00:08:46.468 --> 00:08:50.528
to try to create new cancer therapeutics
with the right type of properties.

00:08:50.908 --> 00:08:54.694
And so we hope that
the potential for these is high

00:08:54.694 --> 00:08:57.056
and mainly to be able
to give cancer patients

00:08:57.056 --> 00:09:00.206
treatment options
with high quality of life.

00:09:00.206 --> 00:09:02.969
Now, what about the future?

00:09:02.969 --> 00:09:04.689
So what we've been able to do so far

00:09:04.689 --> 00:09:08.391
is to take these nanoparticles,
infuse them in the patient,

00:09:08.391 --> 00:09:13.411
and actually inhibit an individual gene
in the tumor of these patients

00:09:13.411 --> 00:09:15.619
while they're having high quality of life.

00:09:15.619 --> 00:09:16.701
Now, there's no reason

00:09:16.701 --> 00:09:19.862
that we couldn't put multiple types 
of RNAs into these particles

00:09:19.862 --> 00:09:22.872
so we could attack
multiple genes simultaneously.

00:09:23.383 --> 00:09:27.132
So, our vision is that
we start to treat patients

00:09:27.132 --> 00:09:30.597
and that we use, then, 
a fingerprick of blood

00:09:30.597 --> 00:09:34.294
and analyze a variety
of biomolecules in blood

00:09:34.294 --> 00:09:37.569
through a variety of other techniques
that people have talked about -

00:09:37.569 --> 00:09:39.486
various arrays and so forth.

00:09:39.486 --> 00:09:40.736
We take that information -

00:09:40.736 --> 00:09:43.833
probably what will happen in the future
is you'll do this at home;

00:09:43.833 --> 00:09:45.358
you'll plug it into your iPhone,

00:09:45.358 --> 00:09:47.354
and your iPhone
will call up your physician

00:09:47.354 --> 00:09:48.957
and say, "Here are the results"

00:09:48.957 --> 00:09:51.447
so that the next time 
you go to the doctor's office,

00:09:51.447 --> 00:09:52.716
they're going to say,

00:09:52.716 --> 00:09:55.380
"Here's the new therapy
that we're going to give to you."

00:09:55.380 --> 00:10:00.290
So not only in a personalized sense 
can you change for these therapies,

00:10:00.290 --> 00:10:04.664
but we're hoping that you can
actually change in a dynamic sense

00:10:04.664 --> 00:10:08.647
for an individual person to actually
follow the course of the disease

00:10:08.647 --> 00:10:12.009
and eradicate it
in the best manner you can.

00:10:12.009 --> 00:10:15.936
So that's the vision for cancer,
and it probably would happen that way -

00:10:15.936 --> 00:10:18.464
and then hopefully
with other diseases as well.

00:10:18.464 --> 00:10:19.460
Thank you.

00:10:19.460 --> 00:10:21.360
(Applause)