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)