WEBVTT

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I think we can all pretty much agree

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that germs are really annoying.

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You can take my word for this
because I'm kind of an expert.

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Not only because I work
with viruses for a living,

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which I do,

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but mainly because I have
two young sons at home.

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They're four and two,

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and I swear they are germ factories.

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It seems like every single week
they are sick with something.

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They have some upper respiratory,

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lower respiratory, diarrhea, vomiting,

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you name it, they've been infected.

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What that means is I am constantly sick.

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So, yes, germs are a real big pain.

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But luckily if it's a bacterial infection

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you can treat it with antibiotics,

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but if it's a viral infection

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you just kind of wait it out, right?

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But luckily most of the infections
are not that bad

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and my kids will cure them
in a couple of weeks.

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But we also know
that there are a lot of other viruses

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that lead to more significant problems.

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It can range from maybe
having life-long cold sores

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to something more serious
like debilitation or even death.

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So in general viruses are something

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I want to stay away from.

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They're nasty.

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But now let me introduce you to my mom.

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This picture was taken in December 2008.

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We were visiting my brother,

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who lived in Hawaii at that time.

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My mom loves golf,
her family and warm weather.

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Probably in that order.

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So Hawaii is really her paradise.

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We had a really great time,
it was really fun.

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Unfortunately, when I took this picture,

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I didn't realize that my mom's body

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was in the process of betraying her.

NOTE Paragraph

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Because just six months later
she was diagnosed with breast cancer.

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When she was diagnosed,

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I was pregnant with my first son.

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So it became this big
emotionally confusing time for me.

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Because there I was,

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growing life in my body,

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and there she was,

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growing what could potentially

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be her death.

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And in addition, since I was pregnant,

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I was starting to appreciate

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the female breasts as something

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that provides sustenance, right?

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They're supposed to support life.

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But hers may ultimately
be the source of her demise.

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So it was a very difficult time.

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In a couple months after her diagnosis,

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she started her cancer treatment.

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Chemo, surgery, radiation.

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It was a very difficult time.

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And all the things that you hear

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about cancer treatment,
especially chemo being horrible,

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it's true, it is really horrible.

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And this is something
that you will not appreciate

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unless you or someone you love
goes through it.

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But we've made it.

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We made it through that long, intense year

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and at her cancer hospital

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there's this bell
that they hung on the wall

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and at the end of the year
you can go and ring that bell,

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telling everyone 
you're done with treatment,

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you're done with cancer.

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So we were very happy that day,

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but that happiness and that relief

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was extremely short-lived.

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And the worry starts to creep in.

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The source of that worry

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is because of this one word.

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This one word has so much power.

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Metastasis.

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Metastasis is where the cancer

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that originated in one part of the body

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spreads and moves
to different parts of your body,

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to set up tumors elsewhere.

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According to the American Cancer Society,

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if the cancer cells
are found just in your breasts,

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your 5-year relative survival rate
is 99 percent.

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Which is great.

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But you can see that if cancer cells

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are found at distant metastatic sites,

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your survival rate drops to 24 percent.

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That is scary.

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Hence, we have one
of the greatest challenges

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to modern medicine.

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Which is, how do we deliver
these toxic drugs,

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these messages of death, if you will,

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just to those metastatic cancer cells?

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When we're talking about delivery,

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there are really two factors
that you must consider.

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One is efficiency.

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How well can you get these drugs,
these messages of death,

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just to the cancer cells, right?

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And the second is specificity.

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That's where you want those drugs

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delivered just to the cancer cells,

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those metastatic cancer cells,

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but leave all the other
healthy tissues alone.

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And that will decrease
those horrible side effects.

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The question is, how?

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In my work,
the answer lies with the virus.

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Viruses are nature's nano-cell machines

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that have evolved to deliver genes,

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or deliver messages

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into those cells.

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They are incredibly good at their job.

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So what we're trying to do

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is engineer viruses to treat cancer.

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Let me introduce you now

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to the virus that we work on.

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It's called the adeno-associated virus,

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it's a very benign virus,

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it is not linked to any disease.

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Actually most of us,
80 to 90 percent of us

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sitting here today,

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we've already been infected by this virus.

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So I'm showing you here
the outside shell of this virus.

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It is empty on the inside,

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so that it could carry
a very small piece of DNA

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that encodes for that message

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that you would want to deliver
to the cancer cells.

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And so when I look
at images like this, of the virus,

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I am convinced
that Mother Nature is an artist.

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Not only that,
she is a proficient designer.

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The tight interlock
between form and function

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is fundamental for design.

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This virus is only
25 nanometers in diameter,

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which is 4,000 times smaller
than the width of your hair.

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So, in this tiny little package,

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Nature doesn't really
have a lot of wiggle room

NOTE Paragraph

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to include things that are not important

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for the ultimate function of the virus.

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Which is to infect cells.

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The other thing I want to point out

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is that viruses are old technology.

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I mean, it's really,
really old technology.

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Billions of years.

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What we're trying to do

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is to simply piggy-back

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on Mother Nature's work.

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To program these viruses to kill cancer.

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Our over-arching strategy, in our lab,

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is to program synthetic algorithms

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into the virus structure,

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in order to train it to pick out

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those cancer cells and to destroy them.

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Now, it turns out, that you can already

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think of viruses
as nanoscopic computers.

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They have evolved to detect

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biomolecular signals

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in their environment,

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which could include

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biomolecular cues in our bodies,

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in order to have productive infections

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that lead to self-replication ultimately.

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In every step
of the virus infectious process

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the virus detects biomolecular signals

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that allow the virus to do the next step

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of that infection,

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and t's actually very fascinating,

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because it turns out that every

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biomolecular signal acts upon the capsid,

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changing it, sometimes just a little bit,

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and sometimes quite dramatically.

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So you can think of viruses

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as some of the most primitive
shape-shifters.

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In our work, we're basically taking

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these intrinsic properties of viruses

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as inspiration and we want to re-write

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or re-program what the virus

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detects and computes
as biomolecular input.

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Here are some of the viruses

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that we have re-programmed
in the laboratory.

NOTE Paragraph

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Just by looking at them,

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you actually won't be able
to tell the difference

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between our engineered viruses

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and the ones that exist in Nature.

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But these are different.

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These have algorithms

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programmed into their structure

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that turns them into
cancer-seeking assassins.

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Let me explain.

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The basic idea

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is that we want to create viruses
that will be able

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to travel throughout the body

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in an inert fashion,

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or in a locked configuration, if you will.

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In this locked configuration

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the virus cannot deliver the message

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that it's carrying

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until it comes across
some biomolecular cue,

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signal, represented by the key here,

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and that key will open up the capsid

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and now, in this open configuration,

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the virus can deliver that message

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to the cancer cells.

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The other way that I like to conceptualize

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our design strategy is thinking of it

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as if we were programming encryption

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into these viruses.

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So, the message cannot be read

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unless it is deciphered
by the appropriate key.

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The next natural question is, what key?

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Luckily, advances in biomedical research

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has been answering that question for us.

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It turns out that if you look
at tumor cells,

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tumor masses, there are a lot

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of biochemical signals, these cues,

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that are present at higher concentrations

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in the tumor,
either outside of the cancer cells

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or within the cancer cells themselves.

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You can imagine all of these cues

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can act as the key

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that will open up our virus.

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This is a demonstration of how

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one of our devices work.

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In this black part, you don't see anything

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but there's an entire lawn of cells

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and onto this lawn we've added
these viruses

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that we have in here, and in this case

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the virus is still in its locked state,

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its encrypted state,

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and as a demonstration
this virus is delivering a message

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that, if read properly by that cell,

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would turn that cell green.

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It's a green message.

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You can see there's really not many cells

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that are able to read that green message.

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That's mainly because
the virus is encrypted.

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Conversely, when the virus sees

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these biomolecular keys,

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the viruses open,

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that message is decyphered

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and these cells can now read

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these green messages.

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Let's go back to the schematic here.

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I told you that there's a lot of keys

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within the tumor mass,

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greater concentration in the tumor,

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but you may have noticed
that there are also keys,

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present at lower concentrations,

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elsewhere in the body.

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And that represents some problem.

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That could lead to these
non-targeted side effects,

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that you want to run away from.

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Our answer to this is trying

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to make these viruses open

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only when it detects two,

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both the red and the green.

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As shown here.

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And we have successfully generated

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one of these devices recently.

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Another way to think about this

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is to program an "AND" logic operator

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into this virus structure.

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I believe that the virus
biotechnology community

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we are dreaming the same dream,

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we have the same vision.

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In the very near future,

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we want to be able to program viruses,

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real viruses, as we would
computer programs.

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And we want this design process

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to be standardized, modular

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and lead to a predictable outcome.

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I leave you with a cliff-hanger.

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The big looming question is,

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how will these devices work
in the human body?

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Will they actually do
what we are proposing?

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We don't know the answers
to these questions yet.

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But I work with a really great team,

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of very hard-working
and passionate students

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on this research.

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So follow us and see our progress

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over the next several years.

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I invite you. Go viral with us.

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Thank you.

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(Applause)