0:00:10.564,0:00:14.208
We have a global health challenge[br]in our hands today,

0:00:14.208,0:00:18.782
and that is that the way[br]we currently discover and develop

0:00:18.782,0:00:21.496
new drugs is too costly,

0:00:21.496,0:00:23.993
takes far too long,

0:00:23.993,0:00:27.620
and it fails more often than it suceeds.

0:00:28.070,0:00:30.137
It really just isn't working,

0:00:30.137,0:00:34.574
and that means that patients[br]that badly need new therapies

0:00:34.574,0:00:39.291
are not getting them[br]and diseases are going untreated.

0:00:39.721,0:00:42.589
We seem to be spending[br]more and more money,

0:00:42.589,0:00:46.751
so for every billion dollars[br]we spend in R&D,

0:00:46.751,0:00:50.569
we're getting less drugs[br]approved into the market.

0:00:50.569,0:00:55.650
More money, less drugs.[br]So what's going on here?

0:00:55.650,0:00:58.429
Well, there's a multitude[br]of factors at play,

0:00:58.429,0:01:00.450
but I think one of the key factors

0:01:00.450,0:01:03.991
is that the tools that[br]we currently have available

0:01:03.991,0:01:06.772
to test whether a drug is going to work,

0:01:06.772,0:01:10.107
whether it has efficacy[br]or whether is going to be safe

0:01:10.107,0:01:14.845
before we get it into human[br]clinical trials, are failing us.

0:01:14.845,0:01:18.617
They're not predicting what[br]is going to happen in humans

0:01:18.617,0:01:23.195
and we two main tools[br]available at our disposal:

0:01:23.655,0:01:27.648
there are cells in dishes[br]and animal testing.

0:01:28.118,0:01:31.286
Now, let's talk about[br]the first one: cells in dishes.

0:01:31.286,0:01:33.999
So, cells are happily[br]functioning in our bodies,

0:01:33.999,0:01:37.601
we take them and rip them out[br]of their native environment,

0:01:37.601,0:01:40.746
throw them out in one of these dishes[br]and expect them to work.

0:01:40.746,0:01:42.742
Guess what? They don't.

0:01:42.742,0:01:44.619
They don't like that environment,

0:01:44.619,0:01:47.845
because it's nothing like[br]what they have in the body.

0:01:48.825,0:01:50.815
What about animal testing?

0:01:50.815,0:01:55.821
Well, animals do and can provide[br]extremely useful information.

0:01:55.821,0:01:59.703
They teach us about what happens[br]in the complex organism,

0:01:59.703,0:02:03.228
we learn more about the biology itself.

0:02:03.228,0:02:06.281
However, more often than not,

0:02:06.281,0:02:09.943
animal models fail to predict[br]what will happen in humans,

0:02:09.943,0:02:12.549
when they're treated[br]with a particular drug,

0:02:13.768,0:02:15.508
So we need better tools.

0:02:15.846,0:02:18.977
We need human cells[br]but we need to find a way

0:02:18.977,0:02:21.812
to keep them happy outside the body.

0:02:22.288,0:02:25.249
Now, before I tell how we do that,

0:02:25.249,0:02:27.818
let's do a little exercise together.

0:02:27.818,0:02:29.598
Alright. Everybody close your eyes,

0:02:29.598,0:02:32.868
come on, those of you in the back[br]that I can't see, close your eyes,

0:02:32.868,0:02:34.860
come on, I'm going to do this with you.

0:02:34.860,0:02:39.835
Now, take a deep breath in[br]and breath out,

0:02:39.835,0:02:43.568
and again, breath in, and breath out.

0:02:43.568,0:02:46.120
Now feel the beat of your heart,

0:02:46.120,0:02:49.573
feel it pumping that blood[br]throughout your body.

0:02:49.573,0:02:52.812
And now, ok, now wiggle around[br]a little in your seats

0:02:52.812,0:02:55.544
come on, move, come on,[br]you've been sitting for a while.

0:02:55.544,0:02:57.082
Alright, open your eyes.

0:02:57.082,0:03:00.870
Besides that being a fun exercise[br]that is good for relaxation,

0:03:00.870,0:03:05.589
it helps to illustrate that all bodies[br]are dynamic environments.

0:03:05.589,0:03:09.727
We are in constant motion.[br]Our cells experience that.

0:03:09.727,0:03:12.664
They're in dynamic[br]environments in our body.

0:03:12.664,0:03:15.120
They're under constant mechanical forces.

0:03:15.120,0:03:19.570
So, if we want to make cells[br]happy outside our bodies,

0:03:19.570,0:03:22.370
we need to become cell architects.

0:03:22.370,0:03:26.477
We need to design, build and engineer

0:03:26.477,0:03:29.703
a home away from home for the cells.

0:03:29.703,0:03:33.203
And at the Wyss Institute,[br]we've done just that.

0:03:33.203,0:03:38.538
We call it an "organ on a chip",[br]and I have one right here.

0:03:38.538,0:03:40.425
It's beautiful, isn't it?

0:03:40.425,0:03:42.704
But it's pretty incredible,[br]right here in my hand

0:03:42.704,0:03:47.954
is a breathing, living,[br]human lung-on-a-chip.

0:03:47.954,0:03:50.704
And it's not just beautiful :

0:03:50.704,0:03:53.454
it can do tremendous amounts of things.

0:03:53.454,0:03:56.204
We have living cells in that little chip,

0:03:56.204,0:03:59.508
cells that are dynamic environments,

0:03:59.508,0:04:02.722
interacting with different cell types.

0:04:04.762,0:04:09.316
And, there's been many people[br]trying to grow cells in the lab,

0:04:09.326,0:04:12.090
they've tried many different approaches.

0:04:12.090,0:04:15.341
They've even try to grow[br]little mini organs in the lab.

0:04:15.341,0:04:17.010
We're not trying to do that here,

0:04:17.010,0:04:19.942
we're simply trying[br]to recreate, in this tiny chip,

0:04:19.942,0:04:25.506
the smallest, functional unit[br]that represents the biochemistry,

0:04:25.506,0:04:28.986
the function and the mechanical strain

0:04:28.986,0:04:32.289
that the cells experience in our bodies.

0:04:32.289,0:04:33.840
So, how does it work?

0:04:33.840,0:04:35.628
Let me show you.

0:04:35.628,0:04:39.340
We use techniques from[br]the computer chip manufacturing industry

0:04:39.340,0:04:41.901
to make these structures at a scale

0:04:41.901,0:04:44.704
relevant to both the cells[br]and their environment.

0:04:44.704,0:04:46.592
We have three fluidic channels.

0:04:46.592,0:04:50.257
In the center, we have[br]a porous flexible membrane,

0:04:50.257,0:04:53.746
on which we can add humans cells[br]from, say, our lungs,

0:04:53.746,0:04:56.717
and then underneath,[br]they have capillary cells -

0:04:56.717,0:04:58.510
the cells in our blood vessels.

0:04:58.510,0:05:02.340
And we can then apply[br]mechanical forces to the chip

0:05:02.340,0:05:05.059
that stretch and contract the membrane,

0:05:05.059,0:05:08.840
so the cells experience[br]the same mechanical forces

0:05:08.840,0:05:11.301
that they did when we breathed,

0:05:11.301,0:05:14.423
and how they experienced them[br]like they did in the body.

0:05:14.423,0:05:17.036
There's air flowing through[br]the top channel,

0:05:17.036,0:05:20.424
and then we throw a liquid[br]that contains nutrients,

0:05:20.424,0:05:22.709
through the blood channel.

0:05:23.970,0:05:26.404
Now, the chip is really beautiful.

0:05:26.404,0:05:28.239
But, what can we do with it?

0:05:28.239,0:05:31.654
So when I ask this question,[br]that often sparks a lot of ideas.

0:05:31.654,0:05:34.320
Some of my fellow TEDx presenters[br]have suggested

0:05:34.320,0:05:36.388
we can make jewelry out of them.

0:05:36.388,0:05:37.326
(Laughter)

0:05:37.346,0:05:40.354
Now, I think a "lung-on-a-chip" necklace[br]would look quite nice.

0:05:40.354,0:05:42.823
However, it does much more than this.

0:05:42.823,0:05:46.904
We can get incredible functionality[br]inside these little chips.

0:05:46.904,0:05:49.789
Let me show you:[br]we could, for example,

0:05:49.789,0:05:54.218
make an infection, where we add[br]bacterial cells into the lung,

0:05:54.218,0:05:57.988
then we can add human white bloods cells.

0:05:57.988,0:06:01.927
White blood cells are our bodies' defense[br]against bacterial invaders,

0:06:01.927,0:06:04.794
and when they sense[br]this inflammation due to infection,

0:06:04.794,0:06:07.364
they will enter from[br]the blood into the lung

0:06:07.364,0:06:09.570
and engulf the bacteria.

0:06:09.570,0:06:12.369
Well, now, you're going[br]to see this happening live

0:06:12.369,0:06:15.206
in an actual human lung-on-a-chip.

0:06:15.206,0:06:18.570
We labeled the white bloods cells[br]so you can see them flowing through,

0:06:18.570,0:06:21.946
and when they detect that infection,[br]they begin to stick.

0:06:21.946,0:06:25.200
They stick and then they try to go

0:06:25.200,0:06:28.174
into the lung side[br]from the blood channel.

0:06:28.174,0:06:31.289
And you can see here,[br]we can actually visualize

0:06:31.289,0:06:35.154
a single white blood cell.

0:06:35.154,0:06:39.097
It sticks, it wiggles its way through[br]between the cell layers,

0:06:39.097,0:06:42.566
through the pore, comes out[br]on the other side of the membrane,

0:06:42.566,0:06:47.321
and right there is going to engulf[br]the bacteria labeled in green.

0:06:47.321,0:06:50.238
In that tiny chip, you just witnessed

0:06:50.238,0:06:56.320
one of the most fundamental responses[br]our body has to an infection.

0:06:56.320,0:06:59.849
it's the way we respond,[br]an immune response.

0:06:59.849,0:07:02.070
it's pretty exciting.

0:07:02.070,0:07:04.289
Now, I want to share[br]this picture with you.

0:07:04.289,0:07:08.071
I want to share this with you[br]because it's a beautiful photograph.

0:07:08.763,0:07:10.821
It's almost like art.

0:07:10.821,0:07:14.320
As a cell biologist, I could look[br]at pictures like these all day long.

0:07:14.320,0:07:16.100
But I wanted to share it with you,

0:07:16.100,0:07:18.069
not just because it's so beautiful,

0:07:18.069,0:07:21.739
but because it tells us[br]an enormous amount of information

0:07:21.739,0:07:24.608
about what the cells[br]are doing within the chips.

0:07:24.608,0:07:28.946
It tells us that these cells[br]from the small airways in our lungs

0:07:28.946,0:07:31.489
actually have these hair-like structures

0:07:31.489,0:07:33.571
that you would expect to see in a lung.

0:07:33.571,0:07:36.854
These structures are called cilia[br]and they actually move

0:07:36.854,0:07:40.153
the mucus out of the lung.[br]Yeah, mucus, yuck!

0:07:40.153,0:07:42.527
But mucus is actually very important.

0:07:42.527,0:07:46.196
Mucus traps particulates,[br]viruses, potential allergens

0:07:46.196,0:07:49.432
and these little cilia move[br]and clear the mucus out.

0:07:49.432,0:07:54.304
When they get damaged,[br]say by cigarette smoke, for example,

0:07:54.304,0:07:57.155
they don't work properly[br]and they can't clear that mucus out,

0:07:57.155,0:08:00.877
and that can lead to diseases[br]such as bronchitis.

0:08:01.276,0:08:06.238
Cillia and the clearance of mucus[br]are also involved in awful diseases,

0:08:06.238,0:08:08.321
like cystic fibrosis.

0:08:08.705,0:08:11.903
But now, with the functionality[br]that we get in these chips,

0:08:11.903,0:08:15.738
we can begin to look[br]for potential new treatments.

0:08:15.738,0:08:18.330
We didn't stop with a lung-on-a-chip,

0:08:18.330,0:08:20.153
we have a gut-on-a-chip,

0:08:20.153,0:08:21.864
you can see one right here.

0:08:21.864,0:08:29.071
And we've put intestinal human cells[br]in our gut-on-a-chip,

0:08:29.071,0:08:31.488
and they're under[br]constant peristaltic motion,

0:08:31.488,0:08:34.513
this trickling flow through the cells,

0:08:34.513,0:08:37.381
and we can mimic many of the functions

0:08:37.381,0:08:41.738
that you actually would expect[br]to see in the human intestine.

0:08:41.738,0:08:46.356
Now we can begin[br]to create models of diseases

0:08:46.356,0:08:48.571
such as irritable bowel syndrome.

0:08:48.571,0:08:52.228
This is a disease that affects[br]a large number of individuals,

0:08:52.228,0:08:54.154
it's really debilitating,

0:08:54.154,0:08:57.904
and they aren't really many[br]good treatments for it.

0:08:58.595,0:09:03.140
Now, we have a whole pipeline[br]of different organ chips

0:09:03.140,0:09:06.401
that we are currently[br]working on in our labs.

0:09:06.985,0:09:10.460
Now, the true power[br]of this technology, however,

0:09:10.460,0:09:15.682
really comes from the fact[br]that we can fluidly link them.

0:09:15.682,0:09:17.649
There's fluid flowing across these cells,

0:09:17.649,0:09:21.653
so we can begin to interconnect[br]multiple different chips together

0:09:21.653,0:09:26.543
to form what we call[br]a virtual human-on-a-chip.

0:09:26.543,0:09:28.760
Now, we're really getting excited.

0:09:29.483,0:09:33.625
So, we're not going to ever recreate[br]a whole human in these chips

0:09:33.625,0:09:39.365
but what our goal is, is to be able[br]to recreate sufficient functionality

0:09:39.365,0:09:42.056
so that we can make better predictions

0:09:42.056,0:09:44.747
of what's going to happen in humans

0:09:44.747,0:09:47.898
For example, now we can begin[br]to explore what happens

0:09:47.898,0:09:50.609
when we put a drug like an aerosol drug.

0:09:50.609,0:09:53.661
Those of you like me who have asthma,[br]when you take you inhaler,

0:09:53.661,0:09:56.615
we can explore how that drug[br]comes into your lungs,

0:09:56.615,0:10:00.519
how it enters the body,[br]how it might affect your heart,

0:10:00.519,0:10:02.474
does it change the beating of your heart?

0:10:02.474,0:10:04.169
Does it have a toxicity?

0:10:04.169,0:10:06.715
Does it get cleared by the liver?

0:10:06.715,0:10:09.155
Is it metabolizes in the liver?

0:10:09.155,0:10:11.205
Is it excreted in your kidneys?

0:10:11.205,0:10:13.782
We can begin to study[br]the dynamic response

0:10:13.782,0:10:15.719
of the body to a drug.

0:10:15.719,0:10:18.937
This could really revolutionize[br]and be a game changer,

0:10:18.937,0:10:21.815
for not only[br]the pharmaceutical industry,

0:10:21.815,0:10:24.415
but a whole host[br]of different industries,

0:10:24.415,0:10:26.655
including the cosmetics industry.

0:10:26.655,0:10:29.077
So, how many of you are wearing lipstick?

0:10:29.077,0:10:32.996
Or used soap in the shower this morning?

0:10:32.996,0:10:36.935
We can potentially use the skin-on-a-chip

0:10:36.935,0:10:38.994
that we're currently developing on the lab

0:10:38.994,0:10:42.185
to test whether the ingredients[br]in these products that you're using

0:10:42.185,0:10:44.496
are actually safe to put on your skin,

0:10:44.496,0:10:47.304
without the need for animal testing.

0:10:47.304,0:10:51.605
We could test the safety[br]of chemicals that we're exposed to

0:10:51.605,0:10:53.866
on a daily basis in our environment,

0:10:53.866,0:10:57.148
such as chemicals[br]in regular household cleaners.

0:10:57.148,0:11:00.192
We could also use the organs-on-chips

0:11:00.192,0:11:05.523
for applications in bioterrorism,[br]or radiation exposure.

0:11:05.523,0:11:10.412
We could use them to learn[br]more about these diseases

0:11:10.412,0:11:16.035
such as Ebola or other deadly diseases,[br]such as SARS.

0:11:16.035,0:11:17.449
And why are this useful?

0:11:17.449,0:11:21.083
Because you can't really[br]ask a volunteer in a clinical trial,

0:11:21.083,0:11:24.137
"Let me treat you[br]with a whole bunch of radiation,

0:11:24.137,0:11:27.578
and then i'll see if my new drug[br]can actually repair the damage."

0:11:27.578,0:11:29.480
That's just not going to happen.

0:11:29.480,0:11:32.829
But our organs-on-chips offer[br]a whole new possibility.

0:11:34.781,0:11:36.614
What about clinical trials?

0:11:36.660,0:11:38.925
Organs in chips could[br]also change with the way

0:11:38.925,0:11:40.974
we do clinical trials in the future.

0:11:41.112,0:11:45.932
Right now, the average participant[br]in a clinical trial is that:

0:11:45.932,0:11:50.651
average, tends to be middle age,[br]tends to be female.

0:11:50.651,0:11:55.067
You won't find many clinical trials[br]in which children are involved.

0:11:55.067,0:11:57.978
Yet, everyday we give children medications

0:11:57.978,0:12:01.858
and the only safety data[br]we have on that drug

0:12:01.858,0:12:05.738
is one that we obtained from adults.

0:12:05.738,0:12:07.235
Children are not adults,

0:12:07.235,0:12:10.352
they may not respond[br]in the same way adults do.

0:12:10.352,0:12:13.699
There are other things, like[br]genetic differences in populations

0:12:13.699,0:12:16.933
that may lead to risk populations

0:12:16.933,0:12:20.477
that are at risk of having[br]an adverse drug reaction.

0:12:20.477,0:12:23.871
Now imagine if we could take cells[br]from all those different populations,

0:12:23.871,0:12:27.492
put them on chips[br]and create populations-on-a-chip.

0:12:27.492,0:12:31.442
This could really change[br]the way we do clinical trials.

0:12:31.965,0:12:34.309
Now, I've told you about

0:12:34.309,0:12:36.453
some amazing work[br]and amazing technology.

0:12:36.453,0:12:39.927
And this is the team, the people[br]and the team that are doing this.

0:12:39.927,0:12:44.464
We have engineers, we have[br]cell biologists, we have clinicians,

0:12:44.464,0:12:46.388
all working together.

0:12:46.388,0:12:49.741
We're really seeing something[br]quite incredible at the Weyss Institute,

0:12:49.741,0:12:52.356
it's really a convergence of disciplines,

0:12:52.356,0:12:56.121
where biology and engineering[br]are actually coming together.

0:12:56.121,0:12:59.856
Where biology is influencing[br]the way we design,

0:12:59.856,0:13:02.511
the way we engineer, the way we build.

0:13:02.511,0:13:05.707
It's pretty exciting, and it's happening[br]right here in Boston.

0:13:05.707,0:13:09.713
And that's pretty cool because in Boston[br]we're able to easily collaborate

0:13:09.713,0:13:15.106
with so many academic institutions,[br]hospitals and industry.

0:13:15.106,0:13:16.672
And we're doing just that.

0:13:16.672,0:13:19.868
We're establishing important[br]industry collaborations,

0:13:19.868,0:13:24.251
such as the one we have[br]with a company

0:13:24.251,0:13:28.634
that has expertise in[br]large-scale digital manufacturing.

0:13:28.634,0:13:31.618
They're going to help us make,[br]instead of one of these,

0:13:31.618,0:13:33.782
millions of these chips,

0:13:33.782,0:13:37.587
so that we can get them into the hands[br]of as many researchers as possible.

0:13:37.587,0:13:41.877
And this is key to the potential[br]of that technology.

0:13:42.200,0:13:44.529
Now, let me show you our instrument.

0:13:44.529,0:13:46.475
This is an instrument that our engineers

0:13:46.475,0:13:49.441
are actually prototyping[br]right now, in the lab,

0:13:49.441,0:13:52.708
and this instrument is going to give us[br]the engineering controls

0:13:52.708,0:13:55.598
that we're going to require[br]in order to link

0:13:55.608,0:13:57.998
ten or more organ chips together.

0:13:57.998,0:14:00.568
But it does something else[br]that is very important:

0:14:00.568,0:14:05.329
it creates an easy user interface,[br]so a cell biologist like me can come in,

0:14:05.942,0:14:09.579
take a chip, put it in a cartridge[br]like the prototype you see there,

0:14:09.579,0:14:14.650
put the cartridge into the machine[br]just like you would a CD, and away you go.

0:14:14.650,0:14:16.585
Plug and play. Easy.

0:14:17.538,0:14:21.284
Now, let's imagine a little bit[br]what the future might look like

0:14:21.284,0:14:25.368
if I could take your stem cells[br]and put them on a chip,

0:14:25.368,0:14:28.449
or your stem cells[br]and put them on a chip.

0:14:28.449,0:14:31.989
It would be a personalized chip[br]just for you.

0:14:31.989,0:14:35.330
Now, all of us in here are individuals.

0:14:35.330,0:14:37.759
And those individual differences

0:14:37.759,0:14:40.828
mean that we could react very differently,

0:14:40.828,0:14:43.578
and sometimes in unpredictable ways,[br]to drugs.

0:14:44.761,0:14:49.134
I, myself, a couple of years back,[br]had a really bad headache.

0:14:49.134,0:14:50.597
I just couldn't shake it,

0:14:50.597,0:14:53.290
thought "I'll try something different".[br]I took some Advil.

0:14:53.290,0:14:55.937
15 minutes later, I was on my way[br]to the emergency room

0:14:55.937,0:14:57.594
with a full-blown asthma attack.

0:14:57.594,0:15:01.033
Now, obviously, it wasn't fatal,[br]but unfortunately,

0:15:01.033,0:15:06.002
some of these adverse drug reactions[br]can be fatal.

0:15:06.002,0:15:08.284
So how do we prevent them?

0:15:08.284,0:15:13.316
Well, we could imagine one day[br]having Geraldine-on-a-chip,

0:15:13.316,0:15:16.451
having Danielle-on-a-chip,[br]having you-on-a chip.

0:15:16.451,0:15:18.146
Personalized medicine.

0:15:18.146,0:15:19.071
Thank you.

0:15:19.071,0:15:23.071
(Applause)