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← A new superweapon in the fight against cancer

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Showing Revision 3 created 04/03/2016 by Cynthia Betubiza.

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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 find 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
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    a cell, 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 bad 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
    called 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 and 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 its 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 viral 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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    nanometer-think 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
    stick together throough charge attracttion,
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    and that provides us with a protective
    layer
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    that prevents the sIRNA from
    degrading 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, i tmay 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 need to target this super weapon
    to the super villain cells
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    that we find in the tumor.
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    But, our bodies have a natural
    immune defense system.
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    Cells that reside in teh 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 dfense system,
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    we have to get it past this mechanism
    of getting rid of the foreign object
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    bu 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 nano-strucutre 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, ?, let's call it ?
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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 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 doxs 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
    regressin.
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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)