Transcriber: H Maria Castro Reviewer: Shlomo Adam
I think we can all pretty much agree
that germs are really annoying.
You can take my word for this because I'm kind of an expert.
Not only because I work with viruses for a living,
which I do,
but mainly because I have two young sons at home.
They're four and two,
and I swear they are germ factories.
It seems like every single week they are sick with something.
They have some upper respiratory,
lower respiratory, diarrhea, vomiting,
you name it, they've been infected.
What that means is I am constantly sick.
So, yes, germs are a real big pain.
But luckily if it's a bacterial infection
you can treat it with antibiotics,
but if it's a viral infection
you just kind of wait it out, right?
But luckily most of the infections are not that bad
and my kids will cure them in a couple of weeks.
But we also know that there are a lot of other viruses
that lead to more significant problems.
It can range from maybe having life-long cold sores
to something more serious like debilitation or even death.
So in general viruses are something
I want to stay away from.
They're nasty.
But now let me introduce you to my mom.
This picture was taken in December 2008.
We were visiting my brother,
who lived in Hawaii at that time.
My mom loves golf, her family and warm weather.
Probably in that order.
So Hawaii is really her paradise.
We had a really great time, it was really fun.
Unfortunately, when I took this picture,
I didn't realize that my mom's body
was in the process of betraying her.
Because just six months later she was diagnosed with breast cancer.
When she was diagnosed,
I was pregnant with my first son.
So it became this big emotionally confusing time for me.
Because there I was,
growing life in my body,
and there she was,
growing what could potentially
be her death.
And in addition, since I was pregnant,
I was starting to appreciate
the female breasts as something
that provides sustenance, right?
They're supposed to support life.
But hers may ultimately be the source of her demise.
So it was a very difficult time.
In a couple months after her diagnosis,
she started her cancer treatment.
Chemo, surgery, radiation.
It was a very difficult time.
And all the things that you hear
about cancer treatment, especially chemo being horrible,
it's true, it is really horrible.
And this is something that you will not appreciate
unless you or someone you love goes through it.
But we've made it.
We made it through that long, intense year
and at her cancer hospital
there's this bell that they hung on the wall
and at the end of the year you can go and ring that bell,
telling everyone you're done with treatment,
you're done with cancer.
So we were very happy that day,
but that happiness and that relief
was extremely short-lived.
And the worry starts to creep in.
The source of that worry
is because of this one word.
This one word has so much power.
Metastasis.
Metastasis is where the cancer
that originated in one part of the body
spreads and moves to different parts of your body,
to set up tumors elsewhere.
According to the American Cancer Society,
if the cancer cells are found just in your breasts,
your 5-year relative survival rate is 99 percent.
Which is great.
But you can see that if cancer cells
are found at distant metastatic sites,
your survival rate drops to 24 percent.
That is scary.
Hence, we have one of the greatest challenges
to modern medicine.
Which is, how do we deliver these toxic drugs,
these messages of death, if you will,
just to those metastatic cancer cells?
When we're talking about delivery,
there are really two factors that you must consider.
One is efficiency.
How well can you get these drugs, these messages of death,
just to the cancer cells, right?
And the second is specificity.
That's where you want those drugs
delivered just to the cancer cells,
those metastatic cancer cells,
but leave all the other healthy tissues alone.
And that will decrease those horrible side effects.
The question is, how?
In my work, the answer lies with the virus.
Viruses are nature's nano-cell machines
that have evolved to deliver genes,
or deliver messages
into those cells.
They are incredibly good at their job.
So what we're trying to do
is engineer viruses to treat cancer.
Let me introduce you now
to the virus that we work on.
It's called the adeno-associated virus,
it's a very benign virus,
it is not linked to any disease.
Actually most of us, 80 to 90 percent of us
sitting here today,
we've already been infected by this virus.
So I'm showing you here the outside shell of this virus.
It is empty on the inside,
so that it could carry a very small piece of DNA
that encodes for that message
that you would want to deliver to the cancer cells.
And so when I look at images like this, of the virus,
I am convinced that Mother Nature is an artist.
Not only that, she is a proficient designer.
The tight interlock between form and function
is fundamental for design.
This virus is only 25 nanometers in diameter,
which is 4,000 times smaller than the width of your hair.
So, in this tiny little package,
Nature doesn't really have a lot of wiggle room
to include things that are not important
for the ultimate function of the virus.
Which is to infect cells.
The other thing I want to point out
is that viruses are old technology.
I mean, it's really, really old technology.
Billions of years.
What we're trying to do
is to simply piggy-back
on Mother Nature's work.
To program these viruses to kill cancer.
Our over-arching strategy, in our lab,
is to program synthetic algorithms
into the virus structure,
in order to train it to pick out
those cancer cells and to destroy them.
Now, it turns out, that you can already
think of viruses as nanoscopic computers.
They have evolved to detect
biomolecular signals
in their environment,
which could include
biomolecular cues in our bodies,
in order to have productive infections
that lead to self-replication ultimately.
In every step of the virus infectious process
the virus detects biomolecular signals
that allow the virus to do the next step
of that infection,
and t's actually very fascinating,
because it turns out that every
biomolecular signal acts upon the capsid,
changing it, sometimes just a little bit,
and sometimes quite dramatically.
So you can think of viruses
as some of the most primitive shape-shifters.
In our work, we're basically taking
these intrinsic properties of viruses
as inspiration and we want to re-write
or re-program what the virus
detects and computes as biomolecular input.
Here are some of the viruses
that we have re-programmed in the laboratory.
Just by looking at them,
you actually won't be able to tell the difference
between our engineered viruses
and the ones that exist in Nature.
But these are different.
These have algorithms
programmed into their structure
that turns them into cancer-seeking assassins.
Let me explain.
The basic idea
is that we want to create viruses that will be able
to travel throughout the body
in an inert fashion,
or in a locked configuration, if you will.
In this locked configuration
the virus cannot deliver the message
that it's carrying
until it comes across some biomolecular cue,
signal, represented by the key here,
and that key will open up the capsid
and now, in this open configuration,
the virus can deliver that message
to the cancer cells.
The other way that I like to conceptualize
our design strategy is thinking of it
as if we were programming encryption
into these viruses.
So, the message cannot be read
unless it is deciphered by the appropriate key.
The next natural question is, what key?
Luckily, advances in biomedical research
has been answering that question for us.
It turns out that if you look at tumor cells,
tumor masses, there are a lot
of biochemical signals, these cues,
that are present at higher concentrations
in the tumor, either outside of the cancer cells
or within the cancer cells themselves.
You can imagine all of these cues
can act as the key
that will open up our virus.
This is a demonstration of how
one of our devices work.
In this black part, you don't see anything
but there's an entire lawn of cells
and onto this lawn we've added these viruses
that we have in here, and in this case
the virus is still in its locked state,
its encrypted state,
and as a demonstration this virus is delivering a message
that, if read properly by that cell,
would turn that cell green.
It's a green message.
You can see there's really not many cells
that are able to read that green message.
That's mainly because the virus is encrypted.
Conversely, when the virus sees
these biomolecular keys,
the viruses open,
that message is decyphered
and these cells can now read
these green messages.
Let's go back to the schematic here.
I told you that there's a lot of keys
within the tumor mass,
greater concentration in the tumor,
but you may have noticed that there are also keys,
present at lower concentrations,
elsewhere in the body.
And that represents some problem.
That could lead to these non-targeted side effects,
that you want to run away from.
Our answer to this is trying
to make these viruses open
only when it detects two,
both the red and the green.
As shown here.
And we have successfully generated
one of these devices recently.
Another way to think about this
is to program an "AND" logic operator
into this virus structure.
I believe that the virus biotechnology community
we are dreaming the same dream,
we have the same vision.
In the very near future,
we want to be able to program viruses,
real viruses, as we would computer programs.
And we want this design process
to be standardized, modular
and lead to a predictable outcome.
I leave you with a cliff-hanger.
The big looming question is,
how will these devices work in the human body?
Will they actually do what we are proposing?
We don't know the answers to these questions yet.
But I work with a really great team,
of very hard-working and passionate students
on this research.
So follow us and see our progress
over the next several years.
I invite you. Go viral with us.
Thank you.
(Applause)