0:00:00.368,0:00:02.505
We have a global health challenge

0:00:02.505,0:00:04.197
in our hands today,

0:00:04.197,0:00:07.257
and that is that the way we currently

0:00:07.257,0:00:10.182
discover and develop new drugs

0:00:10.182,0:00:14.360
is too costly, takes far too long,

0:00:14.360,0:00:18.074
and it fails more often than it succeeds.

0:00:18.074,0:00:21.451
It really just isn't working, and that means

0:00:21.451,0:00:24.498
that patients that badly need new therapies

0:00:24.498,0:00:26.209
are not getting them,

0:00:26.209,0:00:29.707
and diseases are going untreated.

0:00:29.707,0:00:32.790
We seem to be spending more and more money.

0:00:32.790,0:00:36.886
So for every billion dollars we spend in R&D,

0:00:36.886,0:00:40.715
we're getting less drugs approved into the market.

0:00:40.715,0:00:43.932
More money, less drugs. Hmm.

0:00:43.932,0:00:45.852
So what's going on here?

0:00:45.852,0:00:48.447
Well, there's a multitude of factors at play,

0:00:48.447,0:00:50.468
but I think one of the key factors

0:00:50.468,0:00:52.865
is that the tools that we currently have

0:00:52.865,0:00:56.948
available to test whether a drug is going to work,

0:00:56.948,0:00:58.337
whether it has efficacy,

0:00:58.337,0:01:00.103
or whether it's going to be safe

0:01:00.103,0:01:03.655
before we get it into human clinical trials,

0:01:03.655,0:01:05.806
are failing us. They're not predicting

0:01:05.806,0:01:09.034
what's going to happen in humans.

0:01:09.034,0:01:11.757
And we have two main tools available

0:01:11.757,0:01:13.771
at our disposal.

0:01:13.771,0:01:17.812
They are cells in dishes and animal testing.

0:01:17.812,0:01:21.132
Now let's talk about the first one, cells in dishes.

0:01:21.132,0:01:24.285
So, cells are happily functioning in our bodies.

0:01:24.285,0:01:26.340
We take them and rip them out

0:01:26.340,0:01:29.289
of their native environment,[br]throw them in one of these dishes,

0:01:29.289,0:01:30.874
and expect them to work.

0:01:30.874,0:01:33.067
Guess what. They don't.

0:01:33.067,0:01:34.729
They don't like that environment

0:01:34.729,0:01:36.361
because it's nothing like

0:01:36.361,0:01:39.037
what they have in the body.

0:01:39.037,0:01:41.108
What about animal testing?

0:01:41.108,0:01:43.993
Well, animals do and can provide

0:01:43.993,0:01:46.255
extremely useful information.

0:01:46.255,0:01:47.964
They teach us about what happens

0:01:47.964,0:01:50.293
in the complex organism.

0:01:50.293,0:01:53.301
We learn more about the biology itself.

0:01:53.301,0:01:56.199
However, more often than not,

0:01:56.199,0:02:00.415
animal models fail to predict[br]what will happen in humans

0:02:00.415,0:02:03.601
when they're treated with a particular drug.

0:02:03.601,0:02:05.980
So we need better tools.

0:02:05.980,0:02:07.733
We need human cells,

0:02:07.733,0:02:10.483
but we need to find a way to keep them happy

0:02:10.483,0:02:12.074
outside the body.

0:02:12.074,0:02:14.980
Our bodies are dynamic environments.

0:02:14.980,0:02:16.820
We're in constant motion.

0:02:16.820,0:02:19.011
Our cells experience that.

0:02:19.011,0:02:21.820
They're in dynamic environments in our body.

0:02:21.820,0:02:24.575
They're under constant mechanical forces.

0:02:24.575,0:02:27.031
So if we want to make cells happy

0:02:27.031,0:02:28.460
outside our bodies,

0:02:28.460,0:02:30.986
we need to become cell architects.

0:02:30.986,0:02:35.330
We need to design, build and engineer

0:02:35.330,0:02:38.561
a home away from home for the cells.

0:02:38.561,0:02:40.235
And at the Wyss Institute,

0:02:40.235,0:02:42.173
we've done just that.

0:02:42.173,0:02:45.197
We call it an organ-on-a-chip.

0:02:45.197,0:02:46.988
And I have one right here.

0:02:46.988,0:02:49.803
It's beautiful, isn't it?[br]But it's pretty incredible.

0:02:49.803,0:02:54.303
Right here in my hand is a breathing, living

0:02:54.303,0:02:56.961
human lung on a chip.

0:02:56.961,0:02:59.089
And it's not just beautiful.

0:02:59.089,0:03:01.529
It can do a tremendous amount of things.

0:03:01.529,0:03:05.308
We have living cells in that little chip,

0:03:05.308,0:03:07.858
cells that are in a dynamic environment

0:03:07.858,0:03:10.939
interacting with different cell types.

0:03:10.939,0:03:12.578
There's been many people

0:03:12.578,0:03:14.439
trying to grow cells in the lab.

0:03:14.439,0:03:17.595
They've tried many different approaches.

0:03:17.595,0:03:20.222
They've even tried to grow[br]little mini-organs in the lab.

0:03:20.222,0:03:21.771
We're not trying to do that here.

0:03:21.771,0:03:23.897
We're simply trying to recreate

0:03:23.897,0:03:25.474
in this tiny chip

0:03:25.474,0:03:28.491
the smallest functional unit

0:03:28.491,0:03:31.045
that represents the biochemistry,

0:03:31.045,0:03:34.169
the function and the mechanical strain

0:03:34.169,0:03:37.685
that the cells experience in our bodies.

0:03:37.685,0:03:40.717
So how does it work? Let me show you.

0:03:40.717,0:03:43.351
We use techniques from the computer chip

0:03:43.351,0:03:44.984
manufacturing industry

0:03:44.984,0:03:47.181
to make these structures at a scale

0:03:47.181,0:03:50.077
relevant to both the cells and their environment.

0:03:50.077,0:03:52.141
We have three fluidic channels.

0:03:52.141,0:03:55.853
In the center, we have a porous, flexible membrane

0:03:55.853,0:03:57.916
on which we can add human cells

0:03:57.916,0:03:59.260
from, say, our lungs,

0:03:59.260,0:04:01.747
and then underneath, they had capillary cells,

0:04:01.747,0:04:03.535
the cells in our blood vessels.

0:04:03.535,0:04:07.855
And we can then apply mechanical forces to the chip

0:04:07.855,0:04:10.684
that stretch and contract the membrane,

0:04:10.684,0:04:13.781
so the cells experience the same mechanical forces

0:04:13.781,0:04:16.714
that they did when we breathe.

0:04:16.714,0:04:19.874
And they experience them how they did in the body.

0:04:19.874,0:04:22.274
There's air flowing through the top channel,

0:04:22.274,0:04:25.623
and then we flow a liquid that contains nutrients

0:04:25.623,0:04:28.462
through the blood channel.

0:04:28.462,0:04:30.834
Now the chip is really beautiful,

0:04:30.834,0:04:32.931
but what can we do with it?

0:04:32.931,0:04:35.255
We can get incredible functionality

0:04:35.255,0:04:37.006
inside these little chips.

0:04:37.006,0:04:38.512
Let me show you.

0:04:38.512,0:04:41.143
We could, for example, mimic infection,

0:04:41.143,0:04:44.679
where we add bacterial cells into the lung.

0:04:44.679,0:04:47.611
then we can add human white blood cells.

0:04:47.611,0:04:50.202
White blood cells are our body's defense

0:04:50.202,0:04:51.570
against bacterial invaders,

0:04:51.570,0:04:54.739
and when they sense this[br]inflammation due to infection,

0:04:54.739,0:04:57.596
they will enter from the blood into the lung

0:04:57.596,0:04:59.511
and engulf the bacteria.

0:04:59.511,0:05:01.759
Well now you're going to see this happening

0:05:01.759,0:05:05.069
live in an actual human lung on a chip.

0:05:05.069,0:05:08.612
We've labeled the white blood cells[br]so you can see them flowing through,

0:05:08.612,0:05:10.773
and when they detect that infection,

0:05:10.773,0:05:12.170
they begin to stick.

0:05:12.170,0:05:16.057
They stick, and then they try to go into the lung

0:05:16.057,0:05:17.838
side from blood channel.

0:05:17.838,0:05:21.527
And you can see here, we can actually visualize

0:05:21.527,0:05:25.286
a single white blood cell.

0:05:25.286,0:05:27.542
It sticks, it wiggles its way through

0:05:27.542,0:05:29.857
between the cell layers, through the pore,

0:05:29.857,0:05:32.278
comes out on the other side of the membrane,

0:05:32.278,0:05:35.713
and right there, it's going to engulf the bacteria

0:05:35.713,0:05:37.362
labeled in green.

0:05:37.362,0:05:40.366
In that tiny chip, you just witnessed

0:05:40.366,0:05:43.547
one of the most fundamental responses

0:05:43.547,0:05:45.504
our body has to an infection.

0:05:45.504,0:05:49.274
It's the way we respond to -- an immune response.

0:05:49.274,0:05:51.675
It's pretty exciting.

0:05:51.675,0:05:54.018
Now I want to share this picture with you,

0:05:54.018,0:05:56.656
not just because it's so beautiful,

0:05:56.656,0:05:59.992
but because it tells us an enormous[br]amount of information

0:05:59.992,0:06:02.589
about what the cells are doing within the chips.

0:06:02.589,0:06:04.848
It tells us that these cells

0:06:04.848,0:06:07.159
from the small airways in our lungs,

0:06:07.159,0:06:08.910
actually have these hairlike structures

0:06:08.910,0:06:10.918
that you would expect to see in the lung.

0:06:10.918,0:06:12.383
These structures are called cilia,

0:06:12.383,0:06:15.293
and they actually move the mucus out of the lung.

0:06:15.293,0:06:16.832
Yeah. Mucus. Yuck.

0:06:16.832,0:06:19.272
But mucus is actually very important.

0:06:19.272,0:06:21.853
Mucus traps particulates, viruses,

0:06:21.853,0:06:23.312
potential allergens,

0:06:23.312,0:06:24.913
and these little cilia move

0:06:24.913,0:06:27.163
and clear the mucus out.

0:06:27.163,0:06:29.075
When they get damaged, say,

0:06:29.075,0:06:31.494
by cigarette smoke for example,

0:06:31.494,0:06:34.302
they don't work properly,[br]and they can't clear that mucus out.

0:06:34.302,0:06:38.119
And that can lead to diseases such as bronchitis.

0:06:38.119,0:06:40.766
Cilia and the clearance of mucus

0:06:40.766,0:06:45.227
are also involved in awful diseases like cystic fibrosis.

0:06:45.227,0:06:48.777
But now, with the functionality[br]that we get in these chips,

0:06:48.777,0:06:50.601
we can begin to look

0:06:50.601,0:06:53.114
for potential new treatments.

0:06:53.114,0:06:55.066
We didn't stop with the lung on a chip.

0:06:55.066,0:06:56.950
We have a gut on a chip.

0:06:56.950,0:06:58.980
You can see one right here.

0:06:58.980,0:07:02.206
And we've put intestinal human cells

0:07:02.206,0:07:04.111
in a gut on a chip,

0:07:04.111,0:07:06.948
and they're under constant peristaltic motion,

0:07:06.948,0:07:10.139
this trickling flow through the cells,

0:07:10.139,0:07:12.697
and we can mimic many of the functions

0:07:12.697,0:07:14.960
that you actually would expect to see

0:07:14.960,0:07:16.653
in the human intestine.

0:07:16.653,0:07:20.444
Now we can begin to create models of diseases

0:07:20.444,0:07:22.854
such as irritable bowel syndrome.

0:07:22.854,0:07:24.936
This is a disease that affects

0:07:24.936,0:07:26.847
a large number of individuals.

0:07:26.847,0:07:28.621
It's really debilitating,

0:07:28.621,0:07:32.563
and there aren't really many good treatments for it.

0:07:32.563,0:07:34.865
Now we have a whole pipeline

0:07:34.865,0:07:37.144
of different organ chips

0:07:37.144,0:07:40.876
that we are currently working on in our labs.

0:07:40.876,0:07:44.295
Now, the true power of this technology, however,

0:07:44.295,0:07:46.420
really comes from the fact

0:07:46.420,0:07:48.965
that we can fluidically link them.

0:07:48.965,0:07:50.912
There's fluid flowing across these cells,

0:07:50.912,0:07:52.991
so we can begin to interconnect

0:07:52.991,0:07:55.853
multiple different chips together

0:07:55.853,0:08:00.066
to form what we call a virtual human on a chip.

0:08:00.066,0:08:03.075
Now we're really getting excited.

0:08:03.075,0:08:07.170
We're not going to ever recreate [br]a whole human in these chips,

0:08:07.170,0:08:11.339
but what our goal is is to be able to recreate

0:08:11.339,0:08:13.352
sufficient functionality

0:08:13.352,0:08:15.712
so that we can make better predictions

0:08:15.712,0:08:17.926
of what's going to happen in humans.

0:08:17.926,0:08:20.850
For example, now we can begin to explore

0:08:20.850,0:08:24.284
what happens when we put[br]a drug like an aerosol drug.

0:08:24.284,0:08:27.270
Those of you like me who have asthma,[br]when you take your inhaler,

0:08:27.270,0:08:30.196
we can explore how that drug comes into your lungs,

0:08:30.196,0:08:31.822
how it enters the body,

0:08:31.822,0:08:33.576
how it might affect, say, your heart.

0:08:33.576,0:08:35.484
Does it change the beating of your heart?

0:08:35.484,0:08:37.125
Does it have a toxicity?

0:08:37.125,0:08:39.133
Does it get cleared by the liver?

0:08:39.133,0:08:41.285
Is it metabolized in the liver?

0:08:41.285,0:08:43.176
Is it excreted in your kidneys?

0:08:43.176,0:08:45.388
We can begin to study the dynamic

0:08:45.388,0:08:48.013
response of the body to a drug.

0:08:48.028,0:08:49.947
This could really revolutionize

0:08:49.947,0:08:51.596
and be a game changer

0:08:51.596,0:08:54.534
for not only the pharmaceutical industry,

0:08:54.534,0:08:56.907
but a whole host of different industries,

0:08:56.907,0:08:59.307
including the cosmetics industry.

0:08:59.307,0:09:02.189
We can potentially use the skin on a chip

0:09:02.189,0:09:04.150
that we're currently developing in the lab

0:09:04.150,0:09:06.704
to test whether the ingredients in those products

0:09:06.704,0:09:09.987
that you're using are actually [br]safe to put on your skin

0:09:09.987,0:09:12.676
without the need for animal testing.

0:09:12.676,0:09:14.620
We could test the safety

0:09:14.620,0:09:16.873
of chemicals that we are exposed to

0:09:16.873,0:09:18.787
on a daily basis in our environment,

0:09:18.787,0:09:22.518
such as chemicals in regular household cleaners.

0:09:22.518,0:09:25.720
We could also use the organs on chips

0:09:25.720,0:09:28.499
for applications in bioterrorism

0:09:28.499,0:09:31.070
or radiation exposure.

0:09:31.070,0:09:34.420
We could use them to learn more about

0:09:34.420,0:09:37.464
diseases such as ebola

0:09:37.464,0:09:41.356
or other deadly diseases such as SARS.

0:09:41.356,0:09:43.194
Organs on chips could also change

0:09:43.194,0:09:46.568
the way we do clinical trials in the future.

0:09:46.568,0:09:49.155
Right now, the average participant

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

0:09:52.525,0:09:55.851
Tends to be middle aged, tends to be female.

0:09:55.851,0:09:58.323
You won't find many clinical trials

0:09:58.323,0:09:59.838
in which children are involved,

0:09:59.838,0:10:03.385
yet every day, we give children medications,

0:10:03.385,0:10:07.131
and the only safety data we have on that drug

0:10:07.131,0:10:10.205
is one that we obtained from adults.

0:10:10.205,0:10:11.999
Children are not adults.

0:10:11.999,0:10:15.132
They may not respond in the same way adults do.

0:10:15.132,0:10:17.544
There are other things like genetic differences

0:10:17.544,0:10:18.977
in populations

0:10:18.977,0:10:22.083
that may lead to at-risk populations

0:10:22.083,0:10:25.520
that are at risk of having an adverse drug reaction.

0:10:25.520,0:10:28.909
Now imagine if we could take cells[br]from all those different populations,

0:10:28.919,0:10:30.827
put them on chips,

0:10:30.827,0:10:32.791
and create populations on a chip.

0:10:32.791,0:10:34.629
This could really change the way

0:10:34.629,0:10:36.698
we do clinical trials.

0:10:36.698,0:10:39.530
And this is the team and the people[br]that are doing this.

0:10:39.530,0:10:42.787
We have engineers, we have cell biologists,

0:10:42.787,0:10:46.561
we have clinicians, all working together.

0:10:46.561,0:10:48.487
We're really seeing something quite incredible

0:10:48.487,0:10:50.092
at the Wyss Institute.

0:10:50.092,0:10:52.263
It's really a convergence of disciplines,

0:10:52.263,0:10:55.983
where biology is influencing the way we design,

0:10:55.983,0:10:58.645
the way we engineer, the way we build.

0:10:58.645,0:11:00.048
It's pretty exciting.

0:11:00.048,0:11:03.612
We're establishing important industry collaborations

0:11:03.612,0:11:06.985
such as the one we have with a company

0:11:06.985,0:11:10.584
that has expertise in large-scale[br]digital manufacturing.

0:11:10.584,0:11:12.603
They're going to help us make,

0:11:12.603,0:11:14.129
instead of one of these,

0:11:14.129,0:11:15.712
millions of these chips,

0:11:15.712,0:11:17.381
so that we can get them into the hands

0:11:17.381,0:11:20.270
of as many researchers as possible.

0:11:20.270,0:11:24.486
And this is key to the potential of that technology.

0:11:24.486,0:11:27.023
Now let me show you our instrument.

0:11:27.023,0:11:29.012
This is an instrument that our engineers

0:11:29.012,0:11:31.630
are actually prototyping right now in the lab,

0:11:31.630,0:11:33.939
and this instrument is going to give us

0:11:33.939,0:11:36.398
the engineering controls that we're going to require

0:11:36.398,0:11:40.566
in order to link 10 or more organ chips together.

0:11:40.566,0:11:42.795
It does something else that's very important.

0:11:42.795,0:11:45.639
It creates an easy user interface.

0:11:45.639,0:11:48.629
So a cell biologist like me can come in,

0:11:48.629,0:11:50.637
take a chip, put it in a cartridge

0:11:50.637,0:11:52.569
like the prototype you see there,

0:11:52.569,0:11:54.640
put the cartridge into the machine

0:11:54.640,0:11:56.128
just like you would a C.D.,

0:11:56.128,0:11:57.260
and away you go.

0:11:57.260,0:12:00.009
Plug and play. Easy.

0:12:00.009,0:12:02.523
Now, let's imagine a little bit

0:12:02.523,0:12:03.902
what the future might look like

0:12:03.902,0:12:06.315
if I could take your stem cells

0:12:06.315,0:12:07.755
and put them on a chip,

0:12:07.755,0:12:10.974
or your stem cells and put them on a chip.

0:12:10.974,0:12:14.475
It would be a personalized chip just for you.

0:12:14.475,0:12:17.683
Now all of us in here are individuals,

0:12:17.683,0:12:20.521
and those individual differences mean

0:12:20.521,0:12:22.963
that we could react very differently

0:12:22.963,0:12:27.210
and sometimes in unpredictable ways to drugs.

0:12:27.210,0:12:31.778
I myself, a couple of years back,[br]had a really bad headache,

0:12:31.778,0:12:34.191
just couldn't shake it, thought, [br]"Well, I'll try something different."

0:12:34.191,0:12:36.326
I took some Advil. Fifteen minutes later,

0:12:36.326,0:12:38.206
I was on my way to the emergency room

0:12:38.206,0:12:40.099
with a full-blown asthma attack.

0:12:40.099,0:12:41.929
Now, obviously it wasn't fatal,

0:12:41.929,0:12:45.102
but unfortunately, some of these

0:12:45.102,0:12:48.711
adverse drug reactions can be fatal.

0:12:48.711,0:12:50.652
So how do we prevent them?

0:12:50.652,0:12:53.232
Well, we could imagine one day

0:12:53.232,0:12:55.575
having Geraldine on a chip,

0:12:55.575,0:12:57.324
having Danielle on a chip,

0:12:57.324,0:12:58.797
having you on a chip.

0:12:58.797,0:13:01.185
Personalized medicine. Thank you.

0:13:01.185,0:13:05.339
(Applause)