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Cancer affects all of us --

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especially the ones that come[br]back over and over again,

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the highly invasive[br]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[br]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[br]how to address relatively well

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with known and established[br]drugs and surgery.

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But there are some forms of cancer

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that don't respond 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[br]very aggressive forms of cancer

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as kind of supervillains 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 supervillains these days,

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their superpowers come[br]from a genetic mutation.

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The genes that are modified[br]inside these tumor cells

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can enable and encode for new[br]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[br]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,

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before the drug can have any effect.

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Imagine -- the cell effectively[br]spits out the drug.

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This is just one example[br]of the many genetic tricks

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in the bag of our supervillain, cancer.

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All due to mutant genes.

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So, we have a supervillain[br]with incredible superpowers.

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And we need a new and powerful[br]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[br]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[br]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[br]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

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that reside in our bloodstream[br]or our tissues,

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it degrades within seconds.

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It has to be packaged, protected[br]through its journey through the body

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on its way to the final target[br]inside the cancer cell.

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So, here's our strategy.

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First, we'll dose the cancer cell[br]with siRNA, the gene blocker,

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and silence those survival genes,

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and then we'll whop 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 superweapon

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that can travel through the bloodstream.

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It has to be tiny enough[br]to get through the bloodstream,

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

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and it's got to be tiny enough[br]to be taken up inside the cancer cell.

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To do this job well,

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it has to be about one one-hundredth[br]the size of a human hair.

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Let's take a closer look[br]at how we can build this nanoparticle.

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First, let's start[br]with the nanoparticle core.

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It's a tiny capsule that contains[br]the chemotherapy drug.

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This is the poison that will[br]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[br]negatively charged,

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we can protect it

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with a nice, protective layer[br]of positively charged polymer.

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The two oppositely charged[br]molecules stick together

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through charge attraction,

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and that provides us[br]with a protective layer

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that prevents the siRNA[br]from degrading in the bloodstream.

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We're almost done.

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(Laughter)

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But there is one more big obstacle[br]we have to think about.

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In fact, it may be the biggest[br]obstacle of all.

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How do we deploy this superweapon?

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I mean, every good weapon[br]needs to be targeted,

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we have to target this superweapon[br]to the supervillain cells

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that reside in the tumor.

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But our bodies have a natural[br]immune-defense system:

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cells that reside in the bloodstream

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and pick out things that don't belong,

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so that it can destroy or eliminate them.

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And guess what? Our nanoparticle[br]is considered a foreign object.

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We have to sneak our nanoparticle[br]past the tumor defense system.

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We have to get it past this mechanism[br]of getting rid of the foreign object

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by disguising it.

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So we add one more[br]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[br]of the naturally charged,

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highly hydrated polysaccharides[br]that resides in our body.

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It creates a cloud of water molecules[br]around the nanoparticle

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that gives us an invisibility[br]cloaking effect.

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This invisibility cloak allows[br]the nanoparticle

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to travel through the bloodstream

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long and far enough to reach the tumor,

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without getting eliminated by the body.

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Second, this layer contains molecules

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which bind specifically to our tumor cell.

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Once bound, the cancer cell[br]takes up the nanoparticle,

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and now we have our nanoparticle[br]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[br]and block those survival genes.

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We have now disabled[br]those genetic superpowers.

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What remains is a cancer cell[br]with no special defenses.

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Then, the chemotherapy drug[br]comes out of the core

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and destroys the tumor cell[br]cleanly and efficiently.

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With sufficient gene blockers,

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we can address many[br]different kinds of mutations,

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allowing the chance to sweep out tumors,

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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[br]particles in animals

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using a highly aggressive form[br]of triple-negative breast cancer.

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This triple-negative breast cancer[br]exhibits the gene

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that spits out cancer drug[br]as soon as it is delivered.

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Usually, doxorubicin -- let's call[br]it "dox" -- is the cancer drug

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that is the first line of treatment[br]for breast cancer.

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So, we first treated our animals[br]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[br]over a period of two weeks.

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Then, we tried[br]our combination superweapon.

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A nanolayer particle with siRNA[br]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[br]did the tumors stop growing,

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they actually decreased in size

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and were eliminated 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[br]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[br]and tumor defense mechanisms.

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And we can put different drugs[br]into the nanoparticle core.

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As doctors learn how to test patients

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and understand certain[br]tumor genetic types,

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they can help us determine which patients[br]can benefit from this strategy

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and which gene blockers we can use.

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Ovarian cancer strikes[br]a special chord with me.

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It is a very aggressive cancer,

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in part because it's discovered[br]at very late stages,

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when it's highly advanced

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and there are a number[br]of genetic mutations.

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After the first round of chemotherapy,

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this cancer comes back[br]for 75 percent of patients.

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And it usually comes back[br]in a drug-resistant form.

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High-grade ovarian cancer

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is one of the biggest[br]supervillains out there.

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And we're now directing our superweapon

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toward 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,[br]Mimi, and her daughter, Paige.

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I was deeply inspired[br]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[br]about the different technologies

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directed at cancer.

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And Mimi was in tears

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as she explained how learning[br]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[br]really elegant science.

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It's about changing people's lives.

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It's about understanding[br]the power of engineering

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on the scale of molecules.

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I know that as students like Paige[br]move forward in their careers,

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they'll open new possibilities

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in addressing some of the big[br]health problems in the world --

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including ovarian cancer, neurological[br]disorders, infectious disease --

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just as chemical engineering has[br]found a way to open doors for me,

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and has provided a way of engineering

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on the tiniest scale,[br]that of molecules,

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to heal on the human scale.

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Thank you.

0:10:20.979,0:10:29.539
(Applause)