Translator: Reiko Bovee Reviewer: Ellen Maloney
Hi, I really hate being bored.
So, when I was trying to decide what I wanted to do with my life,
I decided that I would be an engineer.
And then I decided I would be a researcher.
And then I chose a problem to work on,
and I wanted the hardest problem I could possibly find.
So I thought cancer, that's a good one;
it's been around thousands of years, still not solved.
So, that could easily provide me a lifetime of work.
At the time that I was starting my career, nanotechnology was just taking off,
so I decided that I'm going to work in the area of nanotechnology
and seeing how we can apply it to cancer.
So, that's what I'm going to talk about today.
Before we start, it's kind of hard for me to see with the lights,
maybe raise the house lights a little.
How many people in the audience have heard of nanotechnology?
Just raise your hand.
Almost everybody, that's good.
How many of you can give an example of nanotechnology
that is used today in medicine,
like, you go to your doctor's office, and they're using it?
Anybody? Nobody in the front.
Here, you go, it's getting a little.
One person in the back and they might just be talking to somebody.
Alright.
(Laughter)
Fine, that's a good observation.
We have not made it all the way to the clinic yet.
It's still kind of its early phases.
Now how many of you can give an example of nanotechnology
that's been written about in books, portrayed in movies,
something from popular culture, nanotechnology?
Anybody? Yeah.
A whole lot more.
I see some "Star Trek" fans out there.
Good job, guys.
(Laughter)
Let's look first at popular culture.
Many of you might be familiar with Michael Crichton's book "Prey,"
which is about these nanobots that are sentients,
and they can reproduce and are chasing us down.
We're not there yet.
I would be so excited if I could build that.
I would have a Noble Prize for sure.
It would be wonderful.
We are absolutely nowhere close to being able to make anything like that.
Next, let's think a little bit about the "Fantastic Voyage."
This is an old movie from the 70s as well as a book,
about these nanoparticles or nano robots
that can travel through your blood vessels,
they're going to repair you from the inside out,
they are going to have cameras, you can see everything.
This is a little more like what I'm trying to work on.
But we are still nowhere close to being able to achieve this either,
although that is more of the goal.
So, in terms of pop culture, science fiction writers and visionaries
have been much more creative in terms of what this might accomplish
than whatever researchers have been able to actually create.
This is the future.
So, first I think we should talk about what's so great about nanotech.
You've probably heard about it,
but maybe it's not clear why it's so exciting.
There's basically two reasons why nanotechnology is exciting.
The first is you get really unique properties at the nanoscale.
And that's because nano materials are inbetween atoms and molecules
and a bulk material like the seat you are sitting on.
So they have properties of both materials.
They can exude properties related to quantum mechanics,
as well as properties that you know everyday
from Newtonian mechanics.
If you look at the picture behind me on the top row
are fluorescent semiconductor "quantum dots,"
and that's actually what most of my research is about.
These are small particles that glow in the dark.
And they are useful because if I can attach them
to a molecule, a cell, or part of your body,
I can see it.
It's like a beacon, it lights up.
"Oh, yeah, the green thing. That's the thing I'm looking for."
That's basically what I'm trying to use these for.
If we look at the particles on the bottom, magnetic iron-oxide...
those are particles that respond to a magnet.
So, what you see are the arrows pointing, those are the particles,
and they can drag the fluid itself with it attracted to a magnet.
Those are great for two reasons.
One is they can be an imagining agent like for magnetic resonance imaging, MRI,
can be a contrast agent.
The second is they respond to a magnet.
So, I can now move things at the nanoscale,
non-invasively, using magnetic fields.
So that's pretty exciting.
Next to that, we see gold nanoparticles.
And if any of you raised your hand on products in medicine
that use nanoparticles today, gold is a great example.
if you've ever, ladies, taken the EPT home pregnancy test
so you can know three days early,
that's test is based on gold nanoparticles.
Gold nanoparticles change color when they aggregate, from red to blue.
Blue line, yeah?
(Laughter)
They can be used as a biosensor.
That's a great example of nanotechnology in commercial medical products.
Alright, so they have these really unique properties.
You'll notice that your seat isn't glowing in the dark,
so these result from the quantum mechanical properties.
But, the second thing that's really great about them is their size.
They are really, really small.
You can fit five million of these inside a cell if you packed it solid.
You can see the nanoparticle there in the middle is about five nanometers,
the ones that I work with.
That is only double the width of the DNA within your cells,
it's about half the size of a biomarker.
Biomarkers are these receptors on cells within your cells.
that we want to try to stain to determine if you have a certain disease.
So, they are going to be like prostate-specific antigen,
or your PSA level.
That's the kind of thing that they're looking for.
So, they are about the same size as biomarkers,
and they are much, much smaller than a virus.
Ebola virus there is probably 1/50 of the size of that.
So, they are very very small.
So, the two reasons we are excited about nanotechnology:
cool properties, small size.
So, the ideal nanoparticle for cancer treatment has been envisioned,
and this particle consists of a few parts.
The first is a targeting agent that's going to bind to that biomarker,
so I'm going to look for the cancer cell, and I'm going to find it, seek it out,
and bind to it, great.
The second part would be an imaging agent.
Maybe a quantum dot, maybe a magnetic particle.
So I can do MRI, but something that would allow me to see the cancer.
And then the third part would be a treatment, a drug that I could release
to treat the cancer.
And this type of particle is called a theranostic
because it provides therapy and diagnostics in the same particle.
This is still pretty early stages.
We haven't been able to achieve all of this
and certainly not in a clinical setting.
Most of my work has been focused on the first part of the diagnostic part.
Do I have cancer?
If I have cancer, how is my cancer responding to treatment?
So we are working on the imaging part.
To do that, we have to work a lot with pathologists.
This is an example of a biopsy specimen for glioma,
which is a type of brain cancer that I do most of my work on.
And if you are looking at the picture and saying,
"I have absolutely no idea what that is,"
neither do I.
You have to be a trained pathologist to be able to interpret these images.
And it can take years of training,
and basically all day long people look at these slides.
The way the slides are made: they take your biopsy samples,
they either freeze it or put it into wax,
and they section it into pieces, put a piece on the slide.
And first they stain it with pink and purple stain that is known as H&E.
And they look at it and magically say that cancer is there.
The next step is to look for those biomarkers
to figure out what type of cancer we are looking at.
So, for that, we go to the next slide,
and the little brown color that is the biomarker
So, this particular case is a slide from a breast cancer patient
and we are looking at HER-2 marker
which, if you have this, indicates
that you would respond to treatment with Herceptin.
This is a little easier to read; however, there is only one biomarker on this slide.
So if I want to look at the three molecular panel,
that is currently the gold standard for breast cancer,
which is progesterone, estrogen, and HER-2.
I have to take three of those, and I can't look at them in combination,
like, "Are they always expressed together in the same cell?"
because I'm only looking at them one at a time,
using this method I can look at one marker.
It's usually always brown, sometimes purple,
and that's all I see.
So the vision that nanotechnology, and particularly quantum dots
are trying to bring to the table
is to look at lots of markers at the same time.
Like this.
If you look in the bottom panel, the original,
that's the image that you see.
These are cells that have been spun on a slide,
and we've seen them for three markers,
two of which are cancer markers, EGFR and EpCAM,
and CD45 which is a normal white blood cell marker.
We can see all three markers in the image.
and we also can deconstruct the image into the individual parts.
For this, you would only need one slide.
So I've cut the number of biopsy tissue that you need in one third,
which is good for you because biopsies can be painful,
I am also able to get more information.
I can look at interactions between the particles,
or between the markers with the particles.
So being a researcher when I start this type of work,
I start with cells in a dish.
And I see the cells, and it works, I'm very excited.
Then I might ask for a slice of animal tissue to stain,
and I look, yes, that works.
Then I might move to a patient sample.
And, so, this was sort of the process.
Again my background is mostly neuro,
so I work a lot with the brain cancer docs.
I've been working on that a little bit,
there was a lot of excitement about my work,
and then I started working a little bit in breast cancer.
And three months after I started working in breast cancer
I found a lump.
I'm going to take a moment, ladies:
those self exams, you should be doing them.
Gentlemen, you have mothers, sisters daughters, wives, girlfriends.
You need to encourage them to do them.
Because I'm under 40, so I don't get mammograms,
and I had to find it myself.
And, unfortunately it was fairly advanced at the time that was caught.
So, I was lucky because I knew all of the cancer docs.
(Laughter)
But I had to have a mastectomy of my right side
with complete reconstruction.
I had chemotherapy, I had radiation.
Overall my treatment took about two years.
And one of the first things I can tell you is knowledge is not always power.
Unlike a typical patient, I was not ignorant.
I knew exactly what was wrong with me.
I knew exactly how bad my cancer was.
And there was no hiding.
And when I got my pathology report which yes, I could read and interpret.
I knew what that meant, and I, frankly, cried for a long time,
because I knew what I was facing was not going to be an easy journey.
After my diagnosis, I went to my research lab
because of course I had to tell them.
And their immediate response was, "What can we do?"
"How can we help you?"
And I thought about it, and I said,
"You know, what would help me most is data."
I really love my job, I love my research, and I just want to keep doing it.
And so, they definitely rose to the challenge.
But another thing that I decided
was I was going to change the way that I do research entirely.
So, when you do basic research, this is the standard paradigm.
I come up with this really awesome idea, it's so fantastic, it's going to be great.
And, then I have to convince someone to fund that.
It could be a private foundation, it could be the federal government,
it could be my university.
But I raise money, and once I've got the money,
we all go into the lab, we do experiments,
and we check to see if our idea works.
And then it works or it doesn't, but hopefully it does,
and then we write up a nice paper that we publish in a journal,
and we all pat ourselves on the back, and we go have a beer.
"That was awesome, guys. Good job, way to go."
The truth is that when we do research in this way,
we're not actually taking it out of the lab.
It stays on the bench top in the laboratory, and you never see it,
no matter how exciting it is.
So, the second thing I told my research group is,
"I want to change the way I do research entirely."
I want to do something called "translational research,"
which is really hard.
Because it adds extra steps into this path.
So the new path starts out the same.
Got my awesome idea, I go raise money for it,
I do my experiments.
But now it's a little different because I want to commercialize this.
I want this to go into the clinic.
So the next step is I file for patent protection
or other intellectual property protection.
Then I published the paper.
I can still pat myself on the back and have a beer,
But it's only half-way through the journey now.
So, the next thing I have to do is raise more money,
because I need to take this idea that worked in my lab, in the mouse,
and I needed to take it to a person.
And I need to do 200 patients, not just one patient.
Which means when I make those nanoparticles,
I can't make a little beaker full, I need a vat of nanoparticles.
So there's an engineering challenge as well,
and learning how to make much, much more of the product.
And for that, I need additional funding.
Only this funding is not so easy to get.
Most of the funding in science is for basic science,
not for translational work,
because the big idea's already been proven.
We just want to fund the big ideas the first time,
but they're conceived, we don't want to fund the follow-on.
So if I'm lucky, I get the funding, and I do the scale-up,
and hopefully my clinical trial goes amazing,
and the FDA is wowed and thrilled with my awesomeness,
and then I can actually translate to the clinic.
So this is now what we're doing with our work.
We've basically changed the way that we do science and research in my lab.
So, looking forward, I can say that they never tell you,
you are completely cancer free.
Everyone in this audience has at least one abnormal cell circulating
in your body right now.
It would technically be called cancer if someone actually saw it.
As far as anyone can tell, I am healthy, and things are going well.
But I can't say "cancer free."
(Applause)
Thank you.
So I'm pleased to still be with you.
And as far as the research is going,
we've done some limited trials, up to five patients,
and things appear to be working.
What you see behind you is a sample from a metastatic breast cancer patient,
and we're staining for that HER-2 receptor,
and you can see some cells are white, and some cells are not so white.
And that's basically what we are trying to see.
So, the physician can look at this and say,
"Well, the patient would respond to this drug,
or would not respond to this drug,"
based on how white the different cells are.
So, we are very excited about our research.
In closing, I'd like to say that life is not fair.
Life throws us a lot of lemons, you've got to make lemonade.
And I encourage everyone to fight, and keep on fighting.
For me this is not just a personal journey.
Obviously I had to fight my personal cancer,
but I've been gifted with the opportunity
to fight cancer in a way that very few people can,
because I can actually create change for everyone, not just myself.
So whatever challenges you are facing,
I encourage you to not only solve your own problems
but solve it for everyone else, and go out there and keep fighting.
Thank you.
(Applause)