0:00:00.692,0:00:02.644
We have a global health challenge

0:00:02.644,0:00:04.413
in our hands today,

0:00:04.413,0:00:06.997
and that is that the way we currently

0:00:06.997,0:00:10.290
discover and develop new drugs

0:00:10.290,0:00:14.269
is too costly, takes far too long,

0:00:14.269,0:00:18.049
and it fails more often than it succeeds.

0:00:18.049,0:00:21.636
It really just isn't working, and that means

0:00:21.636,0:00:24.669
that patients that badly need new therapies

0:00:24.669,0:00:26.518
are not getting them,

0:00:26.518,0:00:29.861
and diseases are going untreated.

0:00:29.861,0:00:32.852
We seem to be spending more and more money.

0:00:32.852,0:00:37.148
So for every billion dollars we spend in R&D,

0:00:37.148,0:00:40.808
we're getting less drugs approved into the market.

0:00:40.808,0:00:44.210
More money, less drugs. Hmm.

0:00:44.210,0:00:46.087
So what's going on here?

0:00:46.087,0:00:48.540
Well, there's a multitude of factors at play,

0:00:48.540,0:00:50.607
but I think one of the key factors

0:00:50.607,0:00:52.942
is that the tools that we currently have

0:00:52.942,0:00:57.021
available to test whether a drug is going to work,

0:00:57.021,0:00:58.861
whether it has efficacy,

0:00:58.861,0:01:00.690
or whether it's going to be safe

0:01:00.690,0:01:03.581
before we get it into human clinical trials,

0:01:03.581,0:01:06.147
are failing us. They're not predicting

0:01:06.147,0:01:09.045
what's going to happen in humans.

0:01:09.045,0:01:11.757
And we have two main tools available

0:01:11.757,0:01:13.925
at our disposal.

0:01:13.925,0:01:18.244
They are cells in dishes and animal testing.

0:01:18.244,0:01:21.286
Now let's talk about the first one, cells in dishes.

0:01:21.286,0:01:24.285
So, cells are happily functioning in our bodies.

0:01:24.285,0:01:26.525
We take them and rip them out

0:01:26.525,0:01:28.213
of their native environment,

0:01:28.213,0:01:29.826
throw them in one of these dishes,

0:01:29.826,0:01:31.353
and expect them to work.

0:01:31.353,0:01:33.237
Guess what. They don't.

0:01:33.237,0:01:35.003
They don't like that environment

0:01:35.003,0:01:36.669
because it's nothing like

0:01:36.669,0:01:39.053
what they have in the body.

0:01:39.053,0:01:41.109
What about animal testing?

0:01:41.109,0:01:44.193
Well, animals do and can provide

0:01:44.193,0:01:46.317
extremely useful information.

0:01:46.317,0:01:48.149
They teach us about what happens

0:01:48.149,0:01:50.463
in the complex organism.

0:01:50.463,0:01:53.455
We learn more about the biology itself.

0:01:53.455,0:01:56.369
However, more often than not,

0:01:56.369,0:02:00.415
animal models fail to predict[br]what will happen in humans

0:02:00.415,0:02:03.219
when they're treated with a particular drug.

0:02:03.219,0:02:05.843
So we need better tools.

0:02:05.843,0:02:07.795
We need human cells,

0:02:07.795,0:02:10.483
but we need to find a way to keep them happy

0:02:10.483,0:02:12.259
outside the body.

0:02:12.259,0:02:15.089
Our body are dynamic environments.

0:02:15.089,0:02:17.019
We're in constant motion.

0:02:17.019,0:02:19.150
Our cells experience that.

0:02:19.150,0:02:22.019
They're in dynamic environments in our body.

0:02:22.019,0:02:24.822
They're under constant mechanical forces.

0:02:24.822,0:02:27.247
So if we want to make cells happy

0:02:27.247,0:02:28.784
outside our bodies,

0:02:28.784,0:02:31.011
we need to become cell architects.

0:02:31.011,0:02:35.515
We need to design, build, and engineer

0:02:35.515,0:02:39.003
a home away from home for the cells.

0:02:39.003,0:02:40.822
And at the ViS Institute,

0:02:40.822,0:02:42.497
we've done just that.

0:02:42.497,0:02:44.783
We call it an Organ-on-a-Chip.

0:02:44.783,0:02:47.219
And I have one right here.

0:02:47.219,0:02:48.835
It's beautiful, isn't it.

0:02:48.835,0:02:50.244
But it's pretty incredible.

0:02:50.244,0:02:54.396
Right here in my hand is a breathing, living

0:02:54.396,0:02:56.795
human lung on a chip.

0:02:56.795,0:02:59.243
And it's not just beautiful.

0:02:59.243,0:03:01.653
It can do a tremendous amount of things.

0:03:01.653,0:03:05.057
We have living cells in that little chip,

0:03:05.057,0:03:07.875
cells that are in a dynamic environment

0:03:07.875,0:03:11.155
interacting with different cell types.

0:03:11.155,0:03:12.763
There's been many people

0:03:12.763,0:03:14.593
trying to grow cells in the lab.

0:03:14.593,0:03:17.242
They've tried many different approaches.

0:03:17.242,0:03:20.469
They've even tried to grow[br]little mini-organs in the lab.

0:03:20.469,0:03:22.219
We're not trying to do that here.

0:03:22.219,0:03:24.019
We're simply trying to recreate

0:03:24.019,0:03:25.874
in this tiny chip

0:03:25.874,0:03:28.723
the smallest functional unit

0:03:28.723,0:03:31.107
that represents the biochemistry,

0:03:31.107,0:03:34.277
the function, and the mechanical strain

0:03:34.277,0:03:38.058
that the cells experience in our bodies.

0:03:38.058,0:03:41.075
So how does it work? Let me show you.

0:03:41.075,0:03:43.459
We use techniques from the computer chip

0:03:43.459,0:03:45.308
manufacturing industry

0:03:45.308,0:03:47.382
to make these structures at a scale

0:03:47.382,0:03:50.308
relevant to both the cells and their environment.

0:03:50.308,0:03:52.219
We have three fluidic channels.

0:03:52.219,0:03:55.915
In the center, we have a porous, flexible membrane

0:03:55.915,0:03:57.916
on which we can add human cells

0:03:57.916,0:03:59.660
from, say, our lungs,

0:03:59.660,0:04:01.964
and then underneath, they had capillary cells,

0:04:01.964,0:04:03.828
the cells in our blood vessels.

0:04:03.828,0:04:07.932
And we can then apply mechanical forces to the chip

0:04:07.932,0:04:10.670
that stretch and contract the membrane,

0:04:10.670,0:04:13.874
so the cells experience the same mechanical forces

0:04:13.874,0:04:16.853
that they did when we breathe.

0:04:16.853,0:04:19.860
And they experience them how they did in the body.

0:04:19.860,0:04:22.428
There's air flowing through the top channel,

0:04:22.428,0:04:25.517
and then we flow a liquid that contains nutrients

0:04:25.517,0:04:28.771
through the blood channel.

0:04:28.771,0:04:31.042
Now the chip is really beautiful,

0:04:31.042,0:04:33.732
but what can we do with it?

0:04:33.732,0:04:35.548
We can get incredible functionality

0:04:35.548,0:04:37.455
inside these little chips.

0:04:37.455,0:04:39.236
Let me show you.

0:04:39.236,0:04:41.220
we could, for example, mimic infection,

0:04:41.220,0:04:44.436
where we add bacterial cells into the lung.

0:04:44.436,0:04:47.828
then we can add human white blood cells.

0:04:47.828,0:04:50.404
White blood cells are our body's defense

0:04:50.404,0:04:51.988
against bacterial invaders,

0:04:51.988,0:04:54.802
and when they sense this[br]inflammation due to infection,

0:04:54.802,0:04:57.828
they will enter from the blood into the lung

0:04:57.828,0:04:59.773
and engulf the bacteria.

0:04:59.773,0:05:01.836
Well now you're going to see this happening

0:05:01.836,0:05:05.177
live in an actual human lung on a chip.

0:05:05.177,0:05:08.844
We've labeled the white blood cells[br]so you can see them flowing through,

0:05:08.844,0:05:11.112
and when they detect that infection,

0:05:11.112,0:05:12.756
they begin to stick.

0:05:12.756,0:05:16.242
They stick, and then they try to go into the lung

0:05:16.242,0:05:18.116
side from blood channel.

0:05:18.116,0:05:21.405
And you can see here, we can actually visualize

0:05:21.405,0:05:25.548
a single white blood cell.

0:05:25.548,0:05:27.820
It sticks, it wiggles its way through

0:05:27.820,0:05:29.628
between the cell layers,

0:05:29.628,0:05:31.404
through the pore,

0:05:31.404,0:05:33.156
comes out on the other side of the membrane,

0:05:33.156,0:05:36.073
and right there, it's going to engulf the bacteria

0:05:36.073,0:05:38.132
labeled in green.

0:05:38.132,0:05:40.444
In that tiny chip, you just witnessed

0:05:40.444,0:05:43.044
one of the most fundamental responses

0:05:43.044,0:05:45.812
our body has to an infection.

0:05:45.812,0:05:49.244
It's the way we respond to an immune response.

0:05:49.244,0:05:51.614
It's pretty exciting.

0:05:51.614,0:05:54.188
Now I want to share this picture with you,

0:05:54.188,0:05:56.795
not just because it's so beautiful,

0:05:56.795,0:05:59.623
but because it tells us an enormous[br]amount of information

0:05:59.623,0:06:02.743
about what the cells are doing within the chips.

0:06:02.743,0:06:04.895
It tells us that these cells

0:06:04.895,0:06:07.159
from the small airways in our lungs,

0:06:07.159,0:06:09.028
actually have these hairlike structures

0:06:09.028,0:06:11.095
that you would expect to see in the lung.

0:06:11.095,0:06:12.799
These structures are called cilia,

0:06:12.799,0:06:15.570
and they actually move the mucus out of the lung.

0:06:15.570,0:06:16.925
Yeah. Mucus. Yuck.

0:06:16.925,0:06:19.626
But mucus is actually very important.

0:06:19.626,0:06:22.047
Mucus traps particulates, viruses,

0:06:22.047,0:06:23.930
potential allergens,

0:06:23.930,0:06:25.498
and these little cilia move

0:06:25.498,0:06:27.410
and clear the mucus out.

0:06:27.410,0:06:29.246
When they get damaged, say,

0:06:29.246,0:06:31.694
by cigarette smoke for example,

0:06:31.694,0:06:34.518
they don't work properly,[br]and they can't clear that mucus out.

0:06:34.518,0:06:38.304
And that can lead to disease such as bronchitis.

0:06:38.304,0:06:40.582
Cilia and the clearance of mucus

0:06:40.582,0:06:45.581
are also involved in all diseases like cystic fibrosis.

0:06:45.581,0:06:48.763
But now, with the functionality[br]that we get in these chips,

0:06:48.763,0:06:50.571
and we can begin to look

0:06:50.571,0:06:53.299
for potential new treatments.

0:06:53.299,0:06:55.099
We didn't stop with the lung on a chip.

0:06:55.099,0:06:57.120
We have a gut on a chip.

0:06:57.120,0:06:59.211
You can see one right here.

0:06:59.211,0:07:02.483
And we've put intestinal human cells

0:07:02.483,0:07:04.235
in a gut on a chip,

0:07:04.235,0:07:06.995
and they're under constant peristaltic motion,

0:07:06.995,0:07:09.955
this trickling flow through the cells,

0:07:09.955,0:07:12.836
and we can mimic many of the functions

0:07:12.836,0:07:15.176
that you actually would expect to see

0:07:15.176,0:07:17.003
in the human intestine.

0:07:17.003,0:07:20.368
Now we can begin to create models of diseases

0:07:20.368,0:07:22.856
such as irritable bowel syndrome.

0:07:22.856,0:07:25.491
This is a disease that affects

0:07:25.491,0:07:27.279
a large number of individuals.

0:07:27.279,0:07:29.003
It's really debilitating,

0:07:29.003,0:07:33.211
and there aren't really many good treatments for it.

0:07:33.211,0:07:35.173
Now we have a whole pipeline

0:07:35.173,0:07:37.115
of different organ chips

0:07:37.115,0:07:41.138
that we are currently working on in our labs.

0:07:41.138,0:07:44.312
Now, the true power of this technology, however,

0:07:44.312,0:07:46.697
really comes from the fact

0:07:46.697,0:07:49.243
that we can fluidically link them.

0:07:49.243,0:07:51.251
There's fluid flowing across these cells,

0:07:51.251,0:07:53.331
so we can begin to interconnect

0:07:53.331,0:07:55.747
multiple different chips together

0:07:55.747,0:08:00.297
to form what we call a virtual human on a chip.

0:08:00.297,0:08:03.192
Now we're really getting excited.

0:08:03.192,0:08:05.525
So, now, we're not going to ever

0:08:05.525,0:08:07.417
recreate a whole human in these chips,

0:08:07.417,0:08:11.478
but what our goal is is to be able to recreate

0:08:11.478,0:08:13.552
sufficient functionality

0:08:13.552,0:08:15.621
so that we can make better predictions

0:08:15.621,0:08:18.203
of what's going to happen in humans.

0:08:18.203,0:08:20.989
For example, now we can begin to explore

0:08:20.989,0:08:24.469
what happens when we put[br]a drug like an aerosol drug.

0:08:24.469,0:08:26.195
Those of you like me who have asthma,

0:08:26.195,0:08:27.702
when you take your inhaler,

0:08:27.702,0:08:30.227
we can explore how that drug comes into your lungs,

0:08:30.227,0:08:32.003
how it enters the body,

0:08:32.003,0:08:33.853
how it might affect, say, your heart.

0:08:33.853,0:08:35.686
Does it change the beating of your heart?

0:08:35.686,0:08:37.496
Does it have a toxicity?

0:08:37.496,0:08:39.349
Does it get cleared by the liver?

0:08:39.349,0:08:41.485
Is it metabolized by the liver?

0:08:41.485,0:08:43.469
Is it excreted in your kidneys?

0:08:43.469,0:08:45.619
We can begin to study the dynamic

0:08:45.619,0:08:47.952
response of the body to a drug.

0:08:47.952,0:08:50.287
This could really revolutionize

0:08:50.287,0:08:51.981
and be a game-changer

0:08:51.981,0:08:54.381
for not only the pharmaceutical industry,

0:08:54.381,0:08:57.154
but a whole host of different industries,

0:08:57.154,0:08:59.477
including the cosmetics industry.

0:08:59.477,0:09:02.390
We can potentially use the skin on a chip

0:09:02.390,0:09:04.427
that we're currently developing in the lab

0:09:04.427,0:09:06.659
to test whether the ingredients in those products

0:09:06.659,0:09:08.820
that you're using are actually safe

0:09:08.820,0:09:10.479
to put on your skin

0:09:10.479,0:09:12.984
without the need for animal testing.

0:09:12.984,0:09:14.851
We could test the safety

0:09:14.851,0:09:16.859
of chemicals that we are exposed to

0:09:16.859,0:09:18.987
on a daily basis in our environment,

0:09:18.987,0:09:22.596
such as chemicals in regular household cleaners.

0:09:22.596,0:09:25.428
We could also use the organs on chips

0:09:25.428,0:09:28.669
for applications in bioterrorism

0:09:28.669,0:09:31.044
or radiation exposure.

0:09:31.044,0:09:34.236
We could use them to learn more about

0:09:34.236,0:09:37.604
diseases such as ebola

0:09:37.604,0:09:41.203
or other deadly diseases such as SARS.

0:09:41.203,0:09:43.098
Organs-on-Chips could also change

0:09:43.098,0:09:46.523
with the way we do clinical trials in the future.

0:09:46.523,0:09:49.155
Right now, the average participant

0:09:49.155,0:09:52.525
in a clinical trial is that: average.

0:09:52.525,0:09:55.928
Tends to be middle aged, tends to be female.

0:09:55.928,0:09:58.523
You won't find many clinical trials

0:09:58.523,0:10:00.331
in which children are involved,

0:10:00.331,0:10:03.278
yet every day, we give children medications,

0:10:03.278,0:10:07.131
and the only safety data we have on that drug

0:10:07.131,0:10:10.636
is one that we obtained from adults.

0:10:10.636,0:10:12.371
Children are not adults.

0:10:12.371,0:10:15.179
They may not respond in the same way adults do.

0:10:15.179,0:10:17.699
There are other things like genetic differences

0:10:17.699,0:10:19.347
in populations

0:10:19.347,0:10:22.192
that may lead to at risk populations

0:10:22.192,0:10:25.720
that are at risk of having an adverse drug reaction.

0:10:25.720,0:10:27.728
Now imagine if we could take cells

0:10:27.728,0:10:29.506
from all those different populations,

0:10:29.506,0:10:31.152
put them on chips,

0:10:31.152,0:10:32.976
and create populations on a chip.

0:10:32.976,0:10:34.800
This could really change the way

0:10:34.800,0:10:36.960
we do clinical trials.

0:10:36.960,0:10:39.700
And this is the team and the people[br]that are doing this.

0:10:39.700,0:10:42.604
We have engineers, we have cell biologists,

0:10:42.604,0:10:46.455
we have clinicians, all working together.

0:10:46.455,0:10:48.488
We're really seeing something quite incredible

0:10:48.488,0:10:50.169
at the ViS Institute.

0:10:50.169,0:10:52.188
It's really a convergence of disciplines,

0:10:52.188,0:10:55.769
where biology is influencing the way we design,

0:10:55.769,0:10:58.815
the way we engineer, the way we build.

0:10:58.815,0:11:00.479
It's pretty exciting.

0:11:00.479,0:11:03.583
We're establishing important industry collaborations

0:11:03.583,0:11:06.955
such as the one we have with a company

0:11:06.955,0:11:10.769
that has expertise in large-scale[br]digital manufacturing.

0:11:10.769,0:11:12.711
They're going to help us make,

0:11:12.711,0:11:14.407
instead of one of these,

0:11:14.407,0:11:16.030
millions of these chips,

0:11:16.030,0:11:17.644
so that we can get them into the hands

0:11:17.644,0:11:20.440
of as many researchers as possible.

0:11:20.440,0:11:24.687
And this is key to the potential of that technology.

0:11:24.687,0:11:27.064
Now let me show you our instrument.

0:11:27.064,0:11:29.536
This is an instrument that our engineers

0:11:29.536,0:11:31.815
are actually prototyping right now in the lab,

0:11:31.815,0:11:33.863
and this instrument is going to give us

0:11:33.863,0:11:36.398
the engineering controls that we're going to require

0:11:36.398,0:11:40.984
in order to link 10 or more organ chips together.

0:11:40.984,0:11:42.965
It does something else that's very important.

0:11:42.965,0:11:45.639
It creates an easy user interface.

0:11:45.639,0:11:49.014
So a cell biologist like me can come in,

0:11:49.014,0:11:50.837
take a chip, put it in a cartridge

0:11:50.837,0:11:52.677
like the prototype you see there,

0:11:52.677,0:11:54.933
put the cartridge into the machine

0:11:54.933,0:11:56.606
just like you would a CD,

0:11:56.606,0:11:58.293
and away you go.

0:11:58.293,0:12:00.061
Plug and play. Easy.

0:12:00.061,0:12:02.477
Now, let's imagine a little bit

0:12:02.477,0:12:04.303
what the future might look like

0:12:04.303,0:12:06.469
if I could take your stem cells

0:12:06.469,0:12:08.085
and put them on a chip,

0:12:08.085,0:12:10.606
or your stem cells and put them on a chip.

0:12:10.606,0:12:14.629
It would be a personalized chip just for you.

0:12:14.629,0:12:17.883
Now all of us in here are individuals,

0:12:17.883,0:12:20.645
and those individual differences mean

0:12:20.645,0:12:23.117
that we could react very differently

0:12:23.117,0:12:27.150
and sometimes in unpredictable ways to drugs.

0:12:27.150,0:12:29.581
I myself, a couple of years back,

0:12:29.581,0:12:32.907
had a really bad headache, just couldn't shake it,

0:12:32.907,0:12:34.562
thought, "Well, I'll try something different."

0:12:34.562,0:12:36.419
I took some Advil. Fifteen minutes later,

0:12:36.419,0:12:38.345
I was on my way to the emergency room

0:12:38.345,0:12:40.269
with a full-blown asthma attack.

0:12:40.269,0:12:42.176
Now, obviously it wasn't fatal,

0:12:42.176,0:12:44.658
but unfortunately, some of these

0:12:44.658,0:12:48.805
adverse drug reactions can be fatal.

0:12:48.805,0:12:50.731
So how do we prevent them?

0:12:50.731,0:12:52.803
Well, we could imagine one day

0:12:52.803,0:12:55.899
having Geraldine on a chip,

0:12:55.899,0:12:57.587
having Danielle on a chip,

0:12:57.587,0:12:59.245
having you on a chip.

0:12:59.245,0:13:01.339
Personalized medicine. Thank you.

0:13:01.339,0:13:05.339
(Applause)