0:00:03.215,0:00:06.418
I think we can all pretty much agree

0:00:06.418,0:00:09.934
that germs are really annoying.

0:00:11.063,0:00:14.434
You can take my word for this[br]because I'm kind of an expert.

0:00:14.434,0:00:16.788
Not only because I work[br]with viruses for a living,

0:00:16.788,0:00:18.197
which I do,

0:00:18.197,0:00:21.628
but mainly because I have[br]two young sons at home.

0:00:21.628,0:00:22.878
They're four and two,

0:00:22.878,0:00:25.786
and I swear they are germ factories.

0:00:25.786,0:00:28.985
It seems like every single week[br]they are sick with something.

0:00:28.985,0:00:31.137
They have some upper respiratory,

0:00:31.137,0:00:33.240
lower respiratory, diarrhea, vomiting,

0:00:33.240,0:00:35.939
you name it, they've been infected.

0:00:35.939,0:00:39.790
What that means is I am constantly sick.

0:00:41.073,0:00:43.948
So, yes, germs are a real big pain.

0:00:43.948,0:00:46.196
But luckily if it's a bacterial infection

0:00:46.196,0:00:49.183
you can treat it with antibiotics,

0:00:49.183,0:00:50.662
but if it's a viral infection

0:00:50.662,0:00:52.563
you just kind of wait it out, right?

0:00:52.563,0:00:55.675
But luckily most of the infections[br]are not that bad

0:00:55.675,0:00:59.118
and my kids will cure them[br]in a couple of weeks.

0:00:59.118,0:01:01.694
But we also know[br]that there are a lot of other viruses

0:01:01.694,0:01:03.693
that lead to more significant problems.

0:01:03.693,0:01:07.456
It can range from maybe[br]having life-long cold sores

0:01:07.456,0:01:12.331
to something more serious[br]like debilitation or even death.

0:01:12.331,0:01:15.169
So in general viruses are something

0:01:15.169,0:01:17.264
I want to stay away from.

0:01:17.264,0:01:19.713
They're nasty.

0:01:20.016,0:01:22.338
But now let me introduce you to my mom.

0:01:22.338,0:01:25.315
This picture was taken in December 2008.

0:01:25.315,0:01:26.811
We were visiting my brother,

0:01:26.811,0:01:28.557
who lived in Hawaii at that time.

0:01:28.557,0:01:32.558
My mom loves golf,[br]her family and warm weather.

0:01:33.198,0:01:34.931
Probably in that order.

0:01:34.931,0:01:38.262
So Hawaii is really her paradise.

0:01:38.442,0:01:41.702
We had a really great time,[br]it was really fun.

0:01:42.215,0:01:45.195
Unfortunately, when I took this picture,

0:01:45.486,0:01:48.263
I didn't realize that my mom's body

0:01:48.263,0:01:51.159
was in the process of betraying her.

0:01:51.159,0:01:55.972
Because just six months later[br]she was diagnosed with breast cancer.

0:01:56.289,0:01:58.002
When she was diagnosed,

0:01:58.002,0:01:59.887
I was pregnant with my first son.

0:01:59.887,0:02:04.212
So it became this big[br]emotionally confusing time for me.

0:02:04.212,0:02:06.557
Because there I was,

0:02:06.557,0:02:08.961
growing life in my body,

0:02:08.961,0:02:10.783
and there she was,

0:02:10.783,0:02:12.796
growing what could potentially

0:02:12.796,0:02:14.822
be her death.

0:02:15.434,0:02:17.873
And in addition, since I was pregnant,

0:02:17.873,0:02:20.153
I was starting to appreciate

0:02:20.153,0:02:21.980
the female breasts as something

0:02:21.980,0:02:23.915
that provides sustenance, right?

0:02:23.915,0:02:26.422
They're supposed to support life.

0:02:26.422,0:02:31.535
But hers may ultimately[br]be the source of her demise.

0:02:32.266,0:02:35.227
So it was a very difficult time.

0:02:35.227,0:02:37.805
In a couple months after her diagnosis,

0:02:37.805,0:02:39.989
she started her cancer treatment.

0:02:39.989,0:02:43.303
Chemo, surgery, radiation.

0:02:43.974,0:02:46.366
It was a very difficult time.

0:02:46.366,0:02:48.379
And all the things that you hear

0:02:48.379,0:02:52.403
about cancer treatment,[br]especially chemo being horrible,

0:02:52.403,0:02:55.208
it's true, it is really horrible.

0:02:55.208,0:02:57.697
And this is something[br]that you will not appreciate

0:02:57.697,0:03:01.606
unless you or someone you love[br]goes through it.

0:03:01.814,0:03:03.174
But we've made it.

0:03:03.174,0:03:05.333
We made it through that long, intense year

0:03:05.333,0:03:06.907
and at her cancer hospital

0:03:06.907,0:03:09.229
there's this bell[br]that they hung on the wall

0:03:09.229,0:03:12.387
and at the end of the year[br]you can go and ring that bell,

0:03:12.387,0:03:15.500
telling everyone [br]you're done with treatment,

0:03:15.500,0:03:17.295
you're done with cancer.

0:03:17.295,0:03:19.496
So we were very happy that day,

0:03:19.496,0:03:21.403
but that happiness and that relief

0:03:21.403,0:03:24.812
was extremely short-lived.

0:03:25.567,0:03:27.823
And the worry starts to creep in.

0:03:27.823,0:03:29.848
The source of that worry

0:03:29.848,0:03:31.954
is because of this one word.

0:03:31.954,0:03:33.868
This one word has so much power.

0:03:33.868,0:03:35.874
Metastasis.

0:03:35.874,0:03:37.661
Metastasis is where the cancer

0:03:37.661,0:03:40.231
that originated in one part of the body

0:03:40.231,0:03:43.118
spreads and moves[br]to different parts of your body,

0:03:43.118,0:03:46.417
to set up tumors elsewhere.

0:03:46.837,0:03:49.921
According to the American Cancer Society,

0:03:49.921,0:03:53.227
if the cancer cells[br]are found just in your breasts,

0:03:53.227,0:03:56.542
your 5-year relative survival rate[br]is 99 percent.

0:03:56.542,0:03:57.972
Which is great.

0:03:59.507,0:04:01.554
But you can see that if cancer cells

0:04:01.554,0:04:04.428
are found at distant metastatic sites,

0:04:04.428,0:04:08.695
your survival rate drops to 24 percent.

0:04:09.906,0:04:11.772
That is scary.

0:04:12.949,0:04:15.903
Hence, we have one[br]of the greatest challenges

0:04:15.903,0:04:18.233
to modern medicine.

0:04:18.857,0:04:21.812
Which is, how do we deliver[br]these toxic drugs,

0:04:21.813,0:04:24.019
these messages of death, if you will,

0:04:24.019,0:04:26.450
just to those metastatic cancer cells?

0:04:26.450,0:04:28.417
When we're talking about delivery,

0:04:28.417,0:04:31.437
there are really two factors[br]that you must consider.

0:04:31.437,0:04:33.663
One is efficiency.

0:04:33.663,0:04:36.582
How well can you get these drugs,[br]these messages of death,

0:04:36.582,0:04:38.242
just to the cancer cells, right?

0:04:38.242,0:04:40.011
And the second is specificity.

0:04:40.011,0:04:41.724
That's where you want those drugs

0:04:41.724,0:04:43.878
delivered just to the cancer cells,

0:04:43.878,0:04:45.510
those metastatic cancer cells,

0:04:45.510,0:04:48.918
but leave all the other[br]healthy tissues alone.

0:04:48.918,0:04:52.521
And that will decrease[br]those horrible side effects.

0:04:52.800,0:04:55.251
The question is, how?

0:04:56.406,0:05:00.235
In my work,[br]the answer lies with the virus.

0:05:01.223,0:05:05.337
Viruses are nature's nano-cell machines

0:05:05.337,0:05:08.007
that have evolved to deliver genes,

0:05:08.007,0:05:09.680
or deliver messages

0:05:09.680,0:05:11.999
into those cells.

0:05:11.999,0:05:14.709
They are incredibly good at their job.

0:05:14.709,0:05:16.330
So what we're trying to do

0:05:16.330,0:05:19.523
is engineer viruses to treat cancer.

0:05:21.962,0:05:23.231
Let me introduce you now

0:05:23.231,0:05:24.714
to the virus that we work on.

0:05:24.714,0:05:27.400
It's called the adeno-associated virus,

0:05:27.400,0:05:28.900
it's a very benign virus,

0:05:28.900,0:05:31.368
it is not linked to any disease.

0:05:31.368,0:05:33.967
Actually most of us,[br]80 to 90 percent of us

0:05:33.967,0:05:35.084
sitting here today,

0:05:35.084,0:05:37.728
we've already been infected by this virus.

0:05:38.541,0:05:42.928
So I'm showing you here[br]the outside shell of this virus.

0:05:42.928,0:05:44.726
It is empty on the inside,

0:05:44.726,0:05:47.658
so that it could carry[br]a very small piece of DNA

0:05:47.658,0:05:49.851
that encodes for that message

0:05:49.851,0:05:53.634
that you would want to deliver[br]to the cancer cells.

0:05:54.147,0:05:58.322
And so when I look[br]at images like this, of the virus,

0:05:58.924,0:06:02.532
I am convinced[br]that Mother Nature is an artist.

0:06:03.329,0:06:07.148
Not only that,[br]she is a proficient designer.

0:06:08.055,0:06:11.519
The tight interlock[br]between form and function

0:06:12.303,0:06:15.013
is fundamental for design.

0:06:15.362,0:06:18.578
This virus is only[br]25 nanometers in diameter,

0:06:19.417,0:06:23.857
which is 4,000 times smaller[br]than the width of your hair.

0:06:24.202,0:06:26.742
So, in this tiny little package,

0:06:27.301,0:06:30.017
Nature doesn't really[br]have a lot of wiggle room

0:06:30.017,0:06:32.003
to include things that are not important

0:06:32.003,0:06:34.054
for the ultimate function of the virus.

0:06:34.054,0:06:36.572
Which is to infect cells.

0:06:37.446,0:06:39.698
The other thing I want to point out

0:06:39.698,0:06:42.794
is that viruses are old technology.

0:06:44.298,0:06:47.641
I mean, it's really,[br]really old technology.

0:06:48.140,0:06:49.910
Billions of years.

0:06:49.910,0:06:51.738
What we're trying to do

0:06:51.738,0:06:53.585
is to simply piggy-back

0:06:53.585,0:06:56.497
on Mother Nature's work.

0:06:56.761,0:06:59.878
To program these viruses to kill cancer.

0:07:03.108,0:07:05.682
Our over-arching strategy, in our lab,

0:07:05.682,0:07:08.050
is to program synthetic algorithms

0:07:08.050,0:07:09.827
into the virus structure,

0:07:09.827,0:07:11.546
in order to train it to pick out

0:07:11.546,0:07:14.669
those cancer cells and to destroy them.

0:07:15.830,0:07:18.281
Now, it turns out, that you can already

0:07:18.281,0:07:22.016
think of viruses[br]as nanoscopic computers.

0:07:22.888,0:07:25.321
They have evolved to detect

0:07:25.321,0:07:26.919
biomolecular signals

0:07:26.919,0:07:28.324
in their environment,

0:07:28.324,0:07:29.931
which could include

0:07:29.931,0:07:32.041
biomolecular cues in our bodies,

0:07:32.041,0:07:34.985
in order to have productive infections

0:07:34.985,0:07:38.561
that lead to self-replication ultimately.

0:07:40.088,0:07:43.468
In every step[br]of the virus infectious process

0:07:43.468,0:07:46.512
the virus detects biomolecular signals

0:07:46.512,0:07:48.723
that allow the virus to do the next step

0:07:48.723,0:07:50.959
of that infection,

0:07:50.959,0:07:52.649
and t's actually very fascinating,

0:07:52.649,0:07:54.595
because it turns out that every

0:07:54.595,0:07:58.109
biomolecular signal acts upon the capsid,

0:07:58.109,0:08:01.529
changing it, sometimes just a little bit,

0:08:01.529,0:08:04.281
and sometimes quite dramatically.

0:08:05.314,0:08:06.901
So you can think of viruses

0:08:06.901,0:08:10.192
as some of the most primitive[br]shape-shifters.

0:08:12.419,0:08:15.109
In our work, we're basically taking

0:08:15.109,0:08:18.234
these intrinsic properties of viruses

0:08:18.234,0:08:21.493
as inspiration and we want to re-write

0:08:21.493,0:08:25.042
or re-program what the virus

0:08:25.042,0:08:28.898
detects and computes[br]as biomolecular input.

0:08:31.239,0:08:32.680
Here are some of the viruses

0:08:32.680,0:08:35.568
that we have re-programmed[br]in the laboratory.

0:08:35.568,0:08:36.879
Just by looking at them,

0:08:36.879,0:08:39.334
you actually won't be able[br]to tell the difference

0:08:39.334,0:08:40.762
between our engineered viruses

0:08:40.762,0:08:43.574
and the ones that exist in Nature.

0:08:43.574,0:08:45.347
But these are different.

0:08:45.347,0:08:47.554
These have algorithms

0:08:47.554,0:08:50.283
programmed into their structure

0:08:50.283,0:08:53.546
that turns them into[br]cancer-seeking assassins.

0:08:53.546,0:08:55.737
Let me explain.

0:08:56.475,0:08:57.573
The basic idea

0:08:57.573,0:09:00.047
is that we want to create viruses[br]that will be able

0:09:00.047,0:09:01.610
to travel throughout the body

0:09:01.610,0:09:03.702
in an inert fashion,

0:09:03.702,0:09:06.645
or in a locked configuration, if you will.

0:09:06.645,0:09:08.293
In this locked configuration

0:09:08.293,0:09:10.530
the virus cannot deliver the message

0:09:10.530,0:09:12.530
that it's carrying

0:09:12.530,0:09:16.255
until it comes across[br]some biomolecular cue,

0:09:16.255,0:09:19.940
signal, represented by the key here,

0:09:19.940,0:09:22.079
and that key will open up the capsid

0:09:22.079,0:09:25.109
and now, in this open configuration,

0:09:25.109,0:09:27.550
the virus can deliver that message

0:09:27.550,0:09:30.114
to the cancer cells.

0:09:30.301,0:09:32.382
The other way that I like to conceptualize

0:09:32.382,0:09:34.266
our design strategy is thinking of it

0:09:34.266,0:09:36.645
as if we were programming encryption

0:09:36.645,0:09:38.715
into these viruses.

0:09:39.015,0:09:41.441
So, the message cannot be read

0:09:41.441,0:09:45.445
unless it is deciphered[br]by the appropriate key.

0:09:47.594,0:09:51.284
The next natural question is, what key?

0:09:52.300,0:09:55.043
Luckily, advances in biomedical research

0:09:55.043,0:09:58.007
has been answering that question for us.

0:09:58.007,0:10:00.171
It turns out that if you look[br]at tumor cells,

0:10:00.171,0:10:02.601
tumor masses, there are a lot

0:10:02.601,0:10:05.655
of biochemical signals, these cues,

0:10:05.655,0:10:07.987
that are present at higher concentrations

0:10:07.987,0:10:12.438
in the tumor,[br]either outside of the cancer cells

0:10:12.438,0:10:15.247
or within the cancer cells themselves.

0:10:15.247,0:10:17.854
You can imagine all of these cues

0:10:17.854,0:10:19.699
can act as the key

0:10:19.699,0:10:22.450
that will open up our virus.

0:10:23.540,0:10:25.590
This is a demonstration of how

0:10:25.590,0:10:27.416
one of our devices work.

0:10:27.416,0:10:29.496
In this black part, you don't see anything

0:10:29.496,0:10:32.713
but there's an entire lawn of cells

0:10:33.159,0:10:35.487
and onto this lawn we've added[br]these viruses

0:10:35.487,0:10:37.485
that we have in here, and in this case

0:10:37.485,0:10:40.750
the virus is still in its locked state,

0:10:40.750,0:10:42.854
its encrypted state,

0:10:42.854,0:10:46.219
and as a demonstration[br]this virus is delivering a message

0:10:46.219,0:10:49.074
that, if read properly by that cell,

0:10:49.074,0:10:50.925
would turn that cell green.

0:10:50.925,0:10:53.534
It's a green message.

0:10:53.534,0:10:56.280
You can see there's really not many cells

0:10:56.280,0:10:59.039
that are able to read that green message.

0:10:59.039,0:11:02.595
That's mainly because[br]the virus is encrypted.

0:11:04.039,0:11:07.078
Conversely, when the virus sees

0:11:07.788,0:11:10.657
these biomolecular keys,

0:11:11.265,0:11:13.303
the viruses open,

0:11:13.303,0:11:14.938
that message is decyphered

0:11:14.938,0:11:17.214
and these cells can now read

0:11:17.214,0:11:20.147
these green messages.

0:11:21.769,0:11:24.522
Let's go back to the schematic here.

0:11:24.522,0:11:27.691
I told you that there's a lot of keys

0:11:28.059,0:11:30.269
within the tumor mass,

0:11:30.269,0:11:32.444
greater concentration in the tumor,

0:11:32.444,0:11:35.485
but you may have noticed[br]that there are also keys,

0:11:35.490,0:11:38.226
present at lower concentrations,

0:11:38.226,0:11:40.277
elsewhere in the body.

0:11:40.277,0:11:42.514
And that represents some problem.

0:11:42.514,0:11:46.529
That could lead to these[br]non-targeted side effects,

0:11:46.529,0:11:49.023
that you want to run away from.

0:11:49.023,0:11:51.219
Our answer to this is trying

0:11:51.219,0:11:54.971
to make these viruses open

0:11:54.971,0:11:57.899
only when it detects two,

0:11:57.899,0:12:00.506
both the red and the green.

0:12:00.506,0:12:02.244
As shown here.

0:12:02.244,0:12:04.162
And we have successfully generated

0:12:04.162,0:12:07.045
one of these devices recently.

0:12:07.045,0:12:09.109
Another way to think about this

0:12:09.109,0:12:12.958
is to program an "AND" logic operator

0:12:12.958,0:12:15.236
into this virus structure.

0:12:15.236,0:12:18.991
I believe that the virus[br]biotechnology community

0:12:18.991,0:12:20.790
we are dreaming the same dream,

0:12:20.790,0:12:22.970
we have the same vision.

0:12:22.970,0:12:24.275
In the very near future,

0:12:24.275,0:12:26.900
we want to be able to program viruses,

0:12:26.900,0:12:30.169
real viruses, as we would[br]computer programs.

0:12:30.169,0:12:32.028
And we want this design process

0:12:32.028,0:12:35.335
to be standardized, modular

0:12:35.335,0:12:38.493
and lead to a predictable outcome.

0:12:40.761,0:12:43.629
I leave you with a cliff-hanger.

0:12:44.030,0:12:45.727
The big looming question is,

0:12:45.727,0:12:49.102
how will these devices work[br]in the human body?

0:12:50.511,0:12:54.017
Will they actually do[br]what we are proposing?

0:12:54.690,0:12:57.880
We don't know the answers[br]to these questions yet.

0:13:01.268,0:13:04.103
But I work with a really great team,

0:13:04.687,0:13:07.651
of very hard-working[br]and passionate students

0:13:07.651,0:13:09.613
on this research.

0:13:09.613,0:13:11.664
So follow us and see our progress

0:13:11.664,0:13:14.005
over the next several years.

0:13:14.005,0:13:17.142
I invite you. Go viral with us.

0:13:17.848,0:13:19.132
Thank you.

0:13:19.132,0:13:21.379
(Applause)