Translator: Thomas Tam Reviewer: Zsófia Herczeg
It was 1990, and I was a seven-year-old pruning tobacco on my family farm.
I was happy because I was in the row next to my grandfather.
He was different than most grandpas, but I didn't care - I loved that man.
He had these old weathered hands with big blue veins,
and when he wasn't paying attention, I'd poke at those things.
(Laugher)
This particular day, we played our usual game.
Who could get to the end of their tobacco row the fastest?
I won.
But when I finished, I looked down on the dirt
to see a Mason jar with clear liquid in it.
I picked it up and asked,
"Grandpa,
I thought you weren't supposed to have any more of these lying around."
(Laugher)
"Son, that's been there a week or more, yeah.
Maybe even five or six days."
A week or more? Five or six days?
As a seven-year-old even I knew how many days are in a week.
(Laughter)
But that wasn't the first time my grandfather was confused.
Ralph Mabe was a moonshine-making,
law-breaking, cool grandpa.
(Laughter)
He would sneak off into the woods where he ran a moonshine still.
Now, this led to grandpa going to "college" a lot.
(Laugher)
That was our family slang for prison.
(Laugher)
I was twelve when we buried him.
That impacted me.
I remember crying in the attic of 317 Summit Street.
That was the first time, I'd dealt with death and with addiction,
but it wasn't my last.
In my early 20s, I moved to Wilmington, North Carolina,
and I fell in love with that city.
There I met a guy named Bridge, who was my best friend,
and he's in the audience today.
He was battling addiction,
and he told me of this implant that he had, which kept him off drugs.
This fascinated me.
This was my spark.
I felt like Sir Isaac Newton when that apple fell and he thought,
"Gravity?"
Being around Bridge, I saw the faces come and go of treatment centers.
Now, these people knew pain.
They would be happy and healthy one day,
relapse,
and become completely consumed by their addiction.
I thought of grandpa.
Treatments for addiction have improved some
since that hot summer day in 1990, but not drastically.
Of the people who seek treatment,
93% fail.
So we're doing a terrible job of treating this disease.
Would Goodyear Tire be in business if 93% of their product failed?
No.
So it's time to think differently about this issue.
Nanoscience may be the solution.
Before we go down the "nano" trail,
let's take a look at the challenges that current medications are up against.
So when you swallow a pill,
what happens to it?
It goes down the esophagus,
and from that point, it has to get past five barriers.
Let's think of this like a video game.
Our character, Peter Pillhead,
has a pill for a head.
So you need to pay attention to three areas for our video game:
his strength indicator - shown by that battery -
each barrier,
and his head.
Ready to play?
(Video game sound effect)
So the first barrier is the stomach.
This acidic environment can degrade our drug.
For Peter, this is an obstacle.
After 37 minutes, Peter enters the intestine.
The intestinal wall - to cross that, we have to be small and chemically fit.
As you may see by his head, Peter loses some of the pill.
(Sound effect)
The liver is the next barrier.
Now, this is the organ
that's responsible for eliminating the harmful effects of medication.
So the enzymes in here degrade Peter as seen by his decaying head.
(Sound effect)
Level four, or barrier four: our proteins and enzymes in the bloodstream.
The proteins can bind to the drug, and the enzymes can put him in a headlock.
So this will take us,
if we get past this - you've seen Peter already lost most of his head -
(Sound effect)
to the final barrier: the blood-brain barrier.
This is a protective barrier
that only allows small, fat-soluble drugs to pass through.
For Peter, this is a total loss,
he loses all of this head and ...
(Sound effect)
the game's over - we lose.
So,
if we even make it to this point, we still have issues.
The graph you've seen is called peak-and-valley delivery.
So the medicine has to be ingested over and over again
to remain effective in the body.
The blue dashed line you're seeing
is the level at which the medicine becomes effective,
and the green is the level
at which the medicine becomes harmful or toxic.
So, the name of the game is to stay in between those two lines.
Think about taking a Tylenol.
If you don't take enough, your headache doesn't go away.
But if you take too much, it could shut down your liver.
So this brings us to the issue of side effects.
Side effects occur when medicines bind somewhere else,
other than their intended target.
Now, as seen in our video game,
some of the medicine was lost along the way.
So,
when you take a pill,
the dose could be 100 times more than what's needed.
Because so much of the medicine is lost along the way,
like we saw at each barrier,
a massive dose is required.
So in some cases, as much as 95% of the medicine is lost along the way.
A guy named David Anderson in his TED Talk had an analogy that I really like.
He said, "Current medication is like getting a can of oil
and pouring it all over your car engine.
Some of that oil will dribble into the right spot,
but the majority of it is wasted, and some even does harm."
So, we need a way to target the medicine
so that it's only released at specific sites.
If we could do this, the dose would decrease,
and as a result, side effects would decrease.
So, we need a way for the medicine to not wonder off
and bind in the other sites in the body.
So there are two ways to solve this.
One, we continue down the same rabbit trail
where big pharma spends over a billion dollars in 15 years
to develop one single drug.
Or two, we could use the drugs that are known to work,
that just have a hard time getting to where they need to go,
so change the way they're delivered.
The latter is how nanoscience emerges as a potential solution.
What is nanoscience?
Nanoscience is the science of the small,
and we're using that to solve big problems.
But how small?
The diameter of a baseball is 7.5 centimeters,
75 billion - billion! - nanometers.
If we went down further in size to like a marble,
a marble is about 1.5 centimeters.
You in the back probably can't even see it,
but a marble is 15 billion nanometers.
If we went down even further to a BB,
and I've glued one onto a piece of cardboard, like from a kid's BB gun.
That's half of a centimeter,
5 billion nanometers across.
So in our lab, we make nanoparticles between 2 and 20 nanometers.
So these things are really, really small.
What's so cool about that?
What's cool is that you can put things inside of them;
even though they are small, a single drug molecule is smaller.
So I've made a model just to show you all.
What I'm holding would be a nanoparticle,
and that blue ball on the inside would be like a drug molecule.
This really isn't an accurate size description.
If you wanted to see something more accurate,
it would be like putting - say this is our nanoparticle,
and these are our drugs.
If this was hollow, we could fit a lot BBs inside there, right!
These things are small, and they can carry a large payload of drugs.
They can go through the body and function like a vehicle, like a truck.
For our case, let's call it as a "nanotruck."
It can travel through the bloodstream, carry drugs in the truck bed.
It has a GPS that we programmed to go wherever we desire.
The scientists call this "targeting."
So that aims to deliver medicine only at specific places -
only at diseased sites.
This is achieved by adding compounds on the outside
that function like "molecular keys."
How do we make these things?
Well, I spent months trying to make a unique nanoparticle,
and no matter what I did, the synthesis was unsuccessful.
My father always says that the struggle is in the details.
He's right.
After months of botched experiments, I finally found out
that the pipette I was using was contaminating my nanoparticles.
Synthesis like this can be very tedious.
So as I was going through all of this trouble,
wouldn't it be great if the nanoparticle could just make itself,
if it could self-assemble?
It kind of can.
Think of oil in water.
What happens when you pour oil into water?
They don't mix.
But if we had a heavy oil that would go to the bottom of the water,
it would self-assemble into these little balls.
So let's see a lab video of just that.
So, those red balls would be the oil-like substance.
So what we could do is we could take that,
mix drugs with it,
drop both of them in water,
and those little balls would form with the drug molecules on the inside.
From that point, we could start reducing the size
and decorating the outside with the homing molecules, the "GPS."
Now, this is a very simplified version
of how the nanoparticle can essentially make itself.
I'm not inventing a new drug here,
all we're doing is making little bitty vehicles
that transport current drugs -
essentially teaching old dogs, well, old drugs, new tricks.
So, the chemistry is still magic to me; it still gets me excited.
I love piddling around in the lab.
The benefits of this research are vast
and could potentially save millions of lives.
And it could also get us past those five barriers.
Do you remember them?
Let's play our game again - I hate losing.
I do not like losing. I'm very competitive.
And I think some of the people in the audience will attest to that.
But let's play our video game again.
This time let me introduce you to our new character:
"Super Nan," or "Super Nano," right?
So now, our medicine is encased in our little nanoparticle
and is protected.
The outside is decorated with fat-like molecules.
So,
(Video game sound effect)
let's play.
(Sound effect)
Level one, or barrier one, is the stomach.
The acid degraded the pill from before.
So this time,
we're protected by Super Nan, and glide right through, fully intact.
(Sound effect)
Level two was the intestinal wall.
Before, Peter couldn't really get through that,
but Super Nan kind of knows the secret handshake -
he's got that oil on the outside -
so he can pass right through to barrier three.
(Sound effect)
Barrier three is the liver;
it has enzymes in it that degraded the pill from before.
Super Nan passes right through this.
(Sound effect)
Level four, proteins and enzymes in the bloodstream.
Remember before they put Peter in a headlock?
The Super Nan passes right through this onto the fifth barrier.
(Sound effect)
That was the blood-brain barrier.
Remember we had to be small and fat-soluble to get through this?
We decorate the outside of Super Nan with those fat-like molecules,
so we can pass right through.
Now, we're inside the brain.
Super Nan now has a mission,
and that's to go around and identify the bad guys, or the bad cells.
He goes, "Good cell, good cell, good cell, good cell - bad cell."
Target acquired.
So then, like a Trojan horse, it moves inside,
opens and releases the drugs.
So let's see a video, or an animation, of just that.
(Sound effect)
So we win.
I told you, I don't like to lose.
(Sound effect ends)
So here's our video.
This is our nanovehicle,
and the blue cells are the healthy ones, and the red is the bad.
We target.
I think it's cute that the little drug molecule say TED on it.
But as you can see by the video, the blue cells were just simply ignored,
and the red ones were targeted,
or the red one was targeted.
So now, let's compare the delivery profile of the nanomedicine
to that of traditional medicine.
So, you remember the peak-and-valley profile?
And the name of the game was to stay in between the effective and toxic level.
It was clearly evident by the graph
that the nanomedicine does this far better.
It would eventually fall,
but we can program that to last days, weeks or months.
For chronic medicine, you would want the medicine inside of a person
for a long period of time.
So to achieve this, you could either make the delivery profile stay for months,
or we could put in an implant like Bridge had
and work on making those last longer.
I think his only worked for about two months,
but we desire them to last much longer.
So a personal goal of mine is to make a drug delivery system
that lasts about 12 months.
So, how is this currently impacting our world?
This technology can be applied to any drug and for any disease.
The drug Doxil is already being applied to cancer,
and that's already seeing the benefits.
Type 2 diabetes has a drug called Bydureon,
which is already showing the benefits of sustained release as well.
My passion to unravel addiction is what drives me.
Seeing so many talented people experience senseless pain was upsetting.
A good friend told me
that addiction is when you can't get enough
of what you do not want.
I love that.
He said, "Addiction is when you can't get enough of what you don't want."
I'm sure Ralph Mabe didn't want that Mason jar hiding in the dirt.
And I'm sure
he didn't want to let his family down over and over again.
And I am sure he didn't want to leave me in the attic of Summit Street, crying.
But nanoscience may be onto a solution,
and there are people like Bridge who are living proof that people change.
Thank you.
(Applause)