9:59:59.000,9:59:59.000
Cancer affects all of us,

9:59:59.000,9:59:59.000
especially the ones that come back[br]over and over again.

9:59:59.000,9:59:59.000
The highly invasive [br]and drug-resistant ones,

9:59:59.000,9:59:59.000
the ones that defy medical treatment,

9:59:59.000,9:59:59.000
even when we throw our best drugs at them.

9:59:59.000,9:59:59.000
Engineering at the molecular level,

9:59:59.000,9:59:59.000
working at the smallest of scales,

9:59:59.000,9:59:59.000
can provide exciting new ways

9:59:59.000,9:59:59.000
to find the most aggressive[br]forms of cancer.

9:59:59.000,9:59:59.000
Cancer is a very clever disease.

9:59:59.000,9:59:59.000
There are some forms of cancer,

9:59:59.000,9:59:59.000
which, fortunately, we've learned[br]how to address relatively well

9:59:59.000,9:59:59.000
with known and established drugs[br]and surgery.

9:59:59.000,9:59:59.000
But, there's some forms of cancer[br]that don't respond

9:59:59.000,9:59:59.000
to these approaches

9:59:59.000,9:59:59.000
and the tumor survives[br]or comes back,

9:59:59.000,9:59:59.000
even after an onslaught of drugs.

9:59:59.000,9:59:59.000
We can think of these[br]very aggresive forms of cancer

9:59:59.000,9:59:59.000
as kind of super villains in a comic book.

9:59:59.000,9:59:59.000
They're clever, they're adaptable,

9:59:59.000,9:59:59.000
and they're very good at staying alive.

9:59:59.000,9:59:59.000
And, like most super villains[br]these days,

9:59:59.000,9:59:59.000
their super powers come from[br]a genetic mutation.

9:59:59.000,9:59:59.000
The genes that are modified[br]inside these tumor cells

9:59:59.000,9:59:59.000
can enable and encode for new[br]and unimagined modes of survival,

9:59:59.000,9:59:59.000
allowing the cancer cell[br]to live through

9:59:59.000,9:59:59.000
even our best chemotherapy treatments.

9:59:59.000,9:59:59.000
One example is a trick [br]in which a gene allows

9:59:59.000,9:59:59.000
a cell, even as the drug[br]approaches the cell,

9:59:59.000,9:59:59.000
to push the drug out before the drug[br]can have any effect.

9:59:59.000,9:59:59.000
Imagine the cell effectively[br]spits out the drug.

9:59:59.000,9:59:59.000
This is just one example[br]of the many genetic tricks

9:59:59.000,9:59:59.000
in the bad of our super villain, cancer.

9:59:59.000,9:59:59.000
All due to mutant genes.

9:59:59.000,9:59:59.000
So, we have a super villain[br]with incredible super powers

9:59:59.000,9:59:59.000
and we need a new and [br]powerful mode of attack.

9:59:59.000,9:59:59.000
Actually, we can turn off a gene,

9:59:59.000,9:59:59.000
the key is a set of molecules[br]called siRNA.

9:59:59.000,9:59:59.000
siRNA are short sequences[br]of genetic code

9:59:59.000,9:59:59.000
that guide a cell to block[br]a certain gene.

9:59:59.000,9:59:59.000
Each siRNA molecule[br]can turn off a specific gene

9:59:59.000,9:59:59.000
inside the cell.

9:59:59.000,9:59:59.000
For many years since its discovery,

9:59:59.000,9:59:59.000
scientists have been very excited

9:59:59.000,9:59:59.000
about how we can apply[br]these gene blockers in medicine.

9:59:59.000,9:59:59.000
But, there is a problem.

9:59:59.000,9:59:59.000
siRNA works well inside the cell.

9:59:59.000,9:59:59.000
But if it gets exposed to the enzymes[br]that reside

9:59:59.000,9:59:59.000
in our bloodstream and our tissues,

9:59:59.000,9:59:59.000
it degrades within seconds.

9:59:59.000,9:59:59.000
It has to be packaged, protected[br]through its journey through the body

9:59:59.000,9:59:59.000
on its way to its final target[br]inside the cancer cell.

9:59:59.000,9:59:59.000
So, here's our strategy:

9:59:59.000,9:59:59.000
first, we'll dose the cancer cell[br]with siRNA, the gene blocker,

9:59:59.000,9:59:59.000
and silence those viral genes,

9:59:59.000,9:59:59.000
and they'll we'll whap (?) it[br]with a chemo drug.

9:59:59.000,9:59:59.000
But how do we carry that out?

9:59:59.000,9:59:59.000
Using molecular engineering,

9:59:59.000,9:59:59.000
we can actually design [br]a super weapon

9:59:59.000,9:59:59.000
that can travel through the blood stream.

9:59:59.000,9:59:59.000
It has to be tiny enough[br]that it can get through the blood stream,

9:59:59.000,9:59:59.000
it's got to be small enough[br]to penetrate the tumor tissue,

9:59:59.000,9:59:59.000
and it's got to be tiny enough[br]to be taken up

9:59:59.000,9:59:59.000
inside the cancer cell.

9:59:59.000,9:59:59.000
To do this job well, it has to be[br]about one 100th the size

9:59:59.000,9:59:59.000
of a human hair.

9:59:59.000,9:59:59.000
Let's take a closer look[br]at how we can build this nanoparticle.

9:59:59.000,9:59:59.000
First, let's start with [br]the nanoparticle core.

9:59:59.000,9:59:59.000
It's a tiny capsule that contains[br]the chemotherapy drug.

9:59:59.000,9:59:59.000
This is the poison that will[br]actually end the tumor cell's life.

9:59:59.000,9:59:59.000
Around this core, we'll wrap[br]a very thin,

9:59:59.000,9:59:59.000
nanometer-think blanket[br]of siRNA.

9:59:59.000,9:59:59.000
This is our gene blocker.

9:59:59.000,9:59:59.000
Because siRNA is strongly negatively charged,

9:59:59.000,9:59:59.000
we can protect it with a nice[br]protect layer

9:59:59.000,9:59:59.000
of postively charged polymer.

9:59:59.000,9:59:59.000
The two oppositely charged molecules[br]stick together throough charge attracttion,

9:59:59.000,9:59:59.000
and that provides us with a protective[br]layer

9:59:59.000,9:59:59.000
that prevents the sIRNA from[br]degrading the blood stream.

9:59:59.000,9:59:59.000
We're almost done.

9:59:59.000,9:59:59.000
(Laughter)

9:59:59.000,9:59:59.000
But there is one more big obstacle[br]we have to think about.

9:59:59.000,9:59:59.000
In fact, i tmay be the biggest[br]obstacle of all.

9:59:59.000,9:59:59.000
How do we deploy this super weapon?

9:59:59.000,9:59:59.000
I mean, every good weapon[br]needs to be targeted,

9:59:59.000,9:59:59.000
we need to target this super weapon[br]to the super villain cells

9:59:59.000,9:59:59.000
that we find in the tumor.

9:59:59.000,9:59:59.000
But, our bodies have a natural[br]immune defense system.

9:59:59.000,9:59:59.000
Cells that reside in teh blood stream

9:59:59.000,9:59:59.000
and pick out things that don't belong

9:59:59.000,9:59:59.000
so that it can destroy or elinate them.

9:59:59.000,9:59:59.000
And guess that, our nanoparticle[br]is considered a foreign object.

9:59:59.000,9:59:59.000
We have to sneak our nanoparticle

9:59:59.000,9:59:59.000
past the tumor dfense system,

9:59:59.000,9:59:59.000
we have to get it past this mechanism[br]of getting rid of the foreign object

9:59:59.000,9:59:59.000
bu disguising it.

9:59:59.000,9:59:59.000
So we add one more negatively charged layer

9:59:59.000,9:59:59.000
around this nanoparticle,

9:59:59.000,9:59:59.000
which serves two purposes.

9:59:59.000,9:59:59.000
First, this outer layer is one of[br]the naturally charged,

9:59:59.000,9:59:59.000
highly hydrated polysaccarides[br]that resides in our bodies.

9:59:59.000,9:59:59.000
It creates a cloud of water molecules[br]around the nanoparticle

9:59:59.000,9:59:59.000
that gives us an invisibility cloaking affect.

9:59:59.000,9:59:59.000
This invisibility cloak allows[br]the nanoparticle

9:59:59.000,9:59:59.000
to travel through the bloodstream[br]long and far enough

9:59:59.000,9:59:59.000
to reach the tumor without getting[br]eliminated by the body.

9:59:59.000,9:59:59.000
Second, this layer contains molecules[br]which bind specifically

9:59:59.000,9:59:59.000
to our tumor's cell.

9:59:59.000,9:59:59.000
Once bound, the cancer cell takes up[br]the nanoparticle

9:59:59.000,9:59:59.000
and now we have our nanoparticle[br]inside the cancer cell

9:59:59.000,9:59:59.000
and ready to deploy.

9:59:59.000,9:59:59.000
Alright, I feel the same way,[br]let's go.

9:59:59.000,9:59:59.000
(Applause)

9:59:59.000,9:59:59.000
The siRNA IS DEPLOYED FIRST.

9:59:59.000,9:59:59.000
It acts for hours,

9:59:59.000,9:59:59.000
giving enough time to silence[br]and block those survival genes.

9:59:59.000,9:59:59.000
We have now disabled those[br]genetic superpowers.

9:59:59.000,9:59:59.000
What remains is a cancer cell[br]with no special defenses.

9:59:59.000,9:59:59.000
Then, the chemotherapy drug[br]comes out of the core

9:59:59.000,9:59:59.000
and destroys the tumor cell[br]cleanly and efficiently.

9:59:59.000,9:59:59.000
With sufficient gene blockers,

9:59:59.000,9:59:59.000
we can address many different kinds [br]of mutations.

9:59:59.000,9:59:59.000
Allowing the chance to sweep out tumors,[br]without leaving behind any bad guys.

9:59:59.000,9:59:59.000
So, how does our strategy work?

9:59:59.000,9:59:59.000
We've tested these nano-strucutre particles[br]in animals

9:59:59.000,9:59:59.000
using a highly aggresive form[br]of triple negative breast cancer.

9:59:59.000,9:59:59.000
This triple negative breast cancer[br]exhibits the gene

9:59:59.000,9:59:59.000
that spits out cancer drugs[br]as soon as its delivered.

9:59:59.000,9:59:59.000
Usually, ?, let's call it ?

9:59:59.000,9:59:59.000
is the cancer drug that is [br]the first line of treatment

9:59:59.000,9:59:59.000
for breast cancer.

9:59:59.000,9:59:59.000
So, we first treated our animals[br]with dox core, dox only.

9:59:59.000,9:59:59.000
The tumor slowed their rate of growth,

9:59:59.000,9:59:59.000
but they still grew rapidly,

9:59:59.000,9:59:59.000
doubling in size over a period of two weeks.

9:59:59.000,9:59:59.000
Then, we tried our combination super weapon.

9:59:59.000,9:59:59.000
And now layer a particle[br]with siRNA against the chemo pump,

9:59:59.000,9:59:59.000
plus, we have the doxs in the core.

9:59:59.000,9:59:59.000
And look, we found that not only[br]did the tumors stop growing,

9:59:59.000,9:59:59.000
they actually decerased in size

9:59:59.000,9:59:59.000
and were elimintaed [br]in some cases.

9:59:59.000,9:59:59.000
The tumors were actually[br]regressin.

9:59:59.000,9:59:59.000
(Applause)

9:59:59.000,9:59:59.000
What's great about this approach[br]is that it can be personalized,

9:59:59.000,9:59:59.000
we can add many different layers[br]of siRNA

9:59:59.000,9:59:59.000
to address different mutations[br]and tumor defense mechanisms

9:59:59.000,9:59:59.000
and we can put different drugs[br]into the nanoparticle core.

9:59:59.000,9:59:59.000
As doctors learn how to test patients[br]and understand

9:59:59.000,9:59:59.000
certain tumor genetic types,

9:59:59.000,9:59:59.000
they can help us determine[br]which patients

9:59:59.000,9:59:59.000
can benefit from this strategy

9:59:59.000,9:59:59.000
and which gene blockers we can use.

9:59:59.000,9:59:59.000
Ovarian cancer strikes [br]a special chord with me.

9:59:59.000,9:59:59.000
It is a very aggresive cancer,

9:59:59.000,9:59:59.000
in part because it's discovred[br]at very late stages

9:59:59.000,9:59:59.000
when its highly advanced

9:59:59.000,9:59:59.000
and there are a number [br]of genetic mutations.

9:59:59.000,9:59:59.000
After the first round of chemotherapy,

9:59:59.000,9:59:59.000
this cancer comes back[br]for 75 percent of patients.

9:59:59.000,9:59:59.000
And it usually comes back[br]in a drug resistant form.

9:59:59.000,9:59:59.000
High-grade ovarian cancer[br]is one of

9:59:59.000,9:59:59.000
the biggest super villains out there.

9:59:59.000,9:59:59.000
And we're now directlng[br]this super weapon[br]

9:59:59.000,9:59:59.000
towards its defeat.

9:59:59.000,9:59:59.000
As a researcher,

9:59:59.000,9:59:59.000
I usually don't get to work with patients,

9:59:59.000,9:59:59.000
but I recently met a mother

9:59:59.000,9:59:59.000
who is an ovarian cancer survivor,[br]Mimi and her daughter pAIGE.

9:59:59.000,9:59:59.000
I was deeply inspired

9:59:59.000,9:59:59.000
by the optimism and strength

9:59:59.000,9:59:59.000
that both mother and daughter displayed.

9:59:59.000,9:59:59.000
And by their story of courage and support.

9:59:59.000,9:59:59.000
At this event, we spoke about[br]the different technologies

9:59:59.000,9:59:59.000
directed at cancer.

9:59:59.000,9:59:59.000
And Mimi was in tears[br]as she explained how

9:59:59.000,9:59:59.000
learning about these efforts

9:59:59.000,9:59:59.000
gives her hope for future generations,

9:59:59.000,9:59:59.000
including her own daughter.

9:59:59.000,9:59:59.000
This really touched me.

9:59:59.000,9:59:59.000
It's not just about building[br]really elegant science,

9:59:59.000,9:59:59.000
it's about changing people's lives.

9:59:59.000,9:59:59.000
It's about understanding the power[br]of engineering

9:59:59.000,9:59:59.000
on the scale of molecules.

9:59:59.000,9:59:59.000
I know that as students like Paige

9:59:59.000,9:59:59.000
move forward in their careers,

9:59:59.000,9:59:59.000
they'll open new possibilites

9:59:59.000,9:59:59.000
in addressing some of the big [br]health problems in the world.

9:59:59.000,9:59:59.000
Including, ovarian cancer,[br]neurological disorders,

9:59:59.000,9:59:59.000
and infectious disease.

9:59:59.000,9:59:59.000
Just as chemical engineering[br]has found a way

9:59:59.000,9:59:59.000
to open doors for me.

9:59:59.000,9:59:59.000
Has provided a way of engineering[br]on the tiniest scale

9:59:59.000,9:59:59.000
that of molecules

9:59:59.000,9:59:59.000
to heal on the human scale.

9:59:59.000,9:59:59.000
Thank you

9:59:59.000,9:59:59.000
(Applause)