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Cancer affects all of us,
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especially the ones that come back
over and over again.
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The highly invasive
and drug-resistant ones,
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the ones that defy medical treatment,
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even when we throw our best drugs at them.
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Engineering at the molecular level,
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working at the smallest of scales,
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can provide exciting new ways
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to fight the most aggressive
forms of cancer.
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Cancer is a very clever disease.
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There are some forms of cancer,
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which, fortunately, we've learned
how to address relatively well
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with known and established drugs
and surgery.
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But, there's some forms of cancer
that don't respond
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to these approaches
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and the tumor survives
or comes back,
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even after an onslaught of drugs.
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We can think of these
very aggresive forms of cancer
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as kind of super villains in a comic book.
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They're clever, they're adaptable,
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and they're very good at staying alive.
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And, like most super villains
these days,
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their super powers come from
a genetic mutation.
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The genes that are modified
inside these tumor cells
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can enable and encode for new
and unimagined modes of survival,
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allowing the cancer cell
to live through
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even our best chemotherapy treatments.
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One example is a trick
in which a gene allows a cell,
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even as the drug
approaches the cell,
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to push the drug out before the drug
can have any effect.
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Imagine the cell effectively
spits out the drug.
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This is just one example
of the many genetic tricks
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in the bag of our super villain, cancer.
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All due to mutant genes.
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So, we have a super villain
with incredible super powers
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and we need a new and
powerful mode of attack.
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Actually, we can turn off a gene,
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the key is a set of molecules
known as siRNA.
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siRNA are short sequences
of genetic code
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that guide a cell to block
a certain gene.
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Each siRNA molecule
can turn off a specific gene
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inside the cell.
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For many years since its discovery,
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scientists have been very excited
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about how we can apply
these gene blockers in medicine.
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But, there is a problem.
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siRNA works well inside the cell.
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But if it gets exposed to the enzymes
that reside
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in our bloodstream or our tissues,
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it degrades within seconds.
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It has to be packaged, protected
through its journey through the body
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on its way to the final target
inside the cancer cell.
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So, here's our strategy:
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first, we'll dose the cancer cell
with siRNA, the gene blocker,
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and silence those survival genes,
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and they'll we'll whap it
with a chemo drug.
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But how do we carry that out?
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Using molecular engineering,
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we can actually design
a super weapon
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that can travel through the blood stream.
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It has to be tiny enough
that it can get through the blood stream,
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it's got to be small enough
to penetrate the tumor tissue,
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and it's got to be tiny enough
to be taken up
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inside the cancer cell.
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To do this job well, it has to be
about one 100th the size
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of a human hair.
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Let's take a closer look
at how we can build this nanoparticle.
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First, let's start with
the nanoparticle core.
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It's a tiny capsule that contains
the chemotherapy drug.
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This is the poison that will
actually end the tumor cell's life.
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Around this core, we'll wrap
a very thin,
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nanometers-thin blanket
of siRNA.
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This is our gene blocker.
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Because siRNA is strongly
negatively charged,
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we can protect it with a nice
protect layer
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of postively charged polymer.
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The two oppositely charged molecules
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stick together through charge attraction
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and that provides us with
a protective layer
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that prevents the siRNA from
degrading in the blood stream.
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We're almost done.
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(Laughter)
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But there is one more big obstacle
we have to think about.
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In fact, it may be the biggest
obstacle of all.
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How do we deploy this super weapon?
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I mean, every good weapon
needs to be targeted,
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we have to target this super weapon
to the super villain cells
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that reside in the tumor.
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But, our bodies have a natural
immune defense system.
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Cells that reside in the blood stream
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and pick out things that don't belong
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so that it can destroy or elinate them.
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And guess that, our nanoparticle
is considered a foreign object.
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We have to sneak our nanoparticle
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past the tumor defense system,
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we have to get it past this mechanism
of getting rid of the foreign object
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by disguising it.
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So we add one more
negatively charged layer
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around this nanoparticle,
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which serves two purposes.
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First, this outer layer is one of
the naturally charged,
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highly hydrated polysaccarides
that resides in our bodies.
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It creates a cloud of water molecules
around the nanoparticle
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that gives us
an invisibility cloaking affect.
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This invisibility cloak allows
the nanoparticle
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to travel through the bloodstream
long and far enough
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to reach the tumor without getting
eliminated by the body.
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Second, this layer contains molecules
which bind specifically
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to our tumor's cell.
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Once bound, the cancer cell takes up
the nanoparticle
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and now we have our nanoparticle
inside the cancer cell
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and ready to deploy.
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Alright, I feel the same way,
let's go.
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(Applause)
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The siRNA is deployed first.
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It acts for hours,
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giving enough time to silence
and block those survival genes.
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We have now disabled those
genetic superpowers.
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What remains is a cancer cell
with no special defenses.
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Then, the chemotherapy drug
comes out of the core
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and destroys the tumor cell
cleanly and efficiently.
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With sufficient gene blockers,
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we can address many different kinds
of mutations.
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Allowing the chance to sweep out tumors,
without leaving behind any bad guys.
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So, how does our strategy work?
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We've tested these
nanostructure particles in animals
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using a highly aggresive form
of triple negative breast cancer.
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This triple negative breast cancer
exhibits the gene
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that spits out cancer drugs
as soon as its delivered.
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Usually, doxorubicin,
let's call it dox,
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is the cancer drug that is
the first line of treatment
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for breast cancer.
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So, we first treated our animals
with a dox core, dox only.
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The tumor slowed their rate of growth,
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but they still grew rapidly,
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doubling in size
over a period of two weeks.
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Then, we tried our
combination super weapon.
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And now layer a particle
with siRNA against the chemo pump,
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plus, we have the dox in the core.
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And look, we found that not only
did the tumors stop growing,
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they actually decerased in size
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and were elimintaed
in some cases.
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The tumors were actually
regressing.
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(Applause)
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What's great about this approach
is that it can be personalized,
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we can add many different layers
of siRNA
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to address different mutations
and tumor defense mechanisms
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and we can put different drugs
into the nanoparticle core.
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As doctors learn how to test patients
and understand
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certain tumor genetic types,
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they can help us determine
which patients
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can benefit from this strategy
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and which gene blockers we can use.
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Ovarian cancer strikes
a special chord with me.
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It is a very aggresive cancer,
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in part because it's discovred
at very late stages
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when its highly advanced
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and there are a number
of genetic mutations.
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After the first round of chemotherapy,
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this cancer comes back
for 75 percent of patients.
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And it usually comes back
in a drug resistant form.
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High-grade ovarian cancer
is one of
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the biggest super villains out there.
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And we're now directlng
this super weapon
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towards its defeat.
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As a researcher,
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I usually don't get to work with patients,
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but I recently met a mother
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who is an ovarian cancer survivor,
Mimi and her daughter pAIGE.
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I was deeply inspired
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by the optimism and strength
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that both mother and daughter displayed.
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And by their story of courage and support.
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At this event, we spoke about
the different technologies
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directed at cancer.
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And Mimi was in tears
as she explained how
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learning about these efforts
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gives her hope for future generations,
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including her own daughter.
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This really touched me.
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It's not just about building
really elegant science,
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it's about changing people's lives.
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It's about understanding the power
of engineering
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on the scale of molecules.
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I know that as students like Paige
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move forward in their careers,
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they'll open new possibilites
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in addressing some of the big
health problems in the world.
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Including, ovarian cancer,
neurological disorders,
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and infectious disease.
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Just as chemical engineering
has found a way
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to open doors for me.
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Has provided a way of engineering
on the tiniest scale
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that of molecules
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to heal on the human scale.
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Thank you
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(Applause)