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Geraldine Hamilton: Body parts on a chip

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It's relatively easy to imagine a new medicine -- the hard part is testing it, and that can delay promising new cures for years. In this well-explained talk, Geraldine Hamilton shows how her lab creates organs and body parts on a chip, simple structures with all the pieces essential to testing new medications -- perhaps even custom cures made for one specific person.

- Bio researcher
Geraldine Hamilton builds organs and body parts on a chip -- to test new, custom cures. Full bio

We have a global health challenge
00:12
in our hands today,
00:14
and that is that the way we currently
00:16
discover and develop new drugs
00:19
is too costly, takes far too long,
00:22
and it fails more often than it succeeds.
00:26
It really just isn't working, and that means
00:30
that patients that badly need new therapies
00:33
are not getting them,
00:36
and diseases are going untreated.
00:38
We seem to be spending more and more money.
00:41
So for every billion dollars we spend in R&D,
00:44
we're getting less drugs approved into the market.
00:48
More money, less drugs. Hmm.
00:52
So what's going on here?
00:55
Well, there's a multitude of factors at play,
00:57
but I think one of the key factors
01:00
is that the tools that we currently have
01:02
available to test whether a drug is going to work,
01:04
whether it has efficacy,
01:08
or whether it's going to be safe
01:10
before we get it into human clinical trials,
01:12
are failing us. They're not predicting
01:15
what's going to happen in humans.
01:17
And we have two main tools available
01:21
at our disposal.
01:23
They are cells in dishes and animal testing.
01:25
Now let's talk about the first one, cells in dishes.
01:29
So, cells are happily functioning in our bodies.
01:33
We take them and rip them out
01:36
of their native environment,
throw them in one of these dishes,
01:38
and expect them to work.
01:41
Guess what. They don't.
01:42
They don't like that environment
01:45
because it's nothing like
01:46
what they have in the body.
01:48
What about animal testing?
01:51
Well, animals do and can provide
01:53
extremely useful information.
01:55
They teach us about what happens
01:58
in the complex organism.
01:59
We learn more about the biology itself.
02:02
However, more often than not,
02:05
animal models fail to predict
what will happen in humans
02:08
when they're treated with a particular drug.
02:12
So we need better tools.
02:15
We need human cells,
02:17
but we need to find a way to keep them happy
02:19
outside the body.
02:22
Our bodies are dynamic environments.
02:24
We're in constant motion.
02:26
Our cells experience that.
02:28
They're in dynamic environments in our body.
02:31
They're under constant mechanical forces.
02:33
So if we want to make cells happy
02:36
outside our bodies,
02:39
we need to become cell architects.
02:40
We need to design, build and engineer
02:42
a home away from home for the cells.
02:47
And at the Wyss Institute,
02:50
we've done just that.
02:52
We call it an organ-on-a-chip.
02:54
And I have one right here.
02:57
It's beautiful, isn't it?
But it's pretty incredible.
02:58
Right here in my hand is a breathing, living
03:01
human lung on a chip.
03:06
And it's not just beautiful.
03:08
It can do a tremendous amount of things.
03:11
We have living cells in that little chip,
03:13
cells that are in a dynamic environment
03:17
interacting with different cell types.
03:19
There's been many people
03:22
trying to grow cells in the lab.
03:24
They've tried many different approaches.
03:26
They've even tried to grow
little mini-organs in the lab.
03:29
We're not trying to do that here.
03:32
We're simply trying to recreate
03:33
in this tiny chip
03:35
the smallest functional unit
03:37
that represents the biochemistry,
03:40
the function and the mechanical strain
03:43
that the cells experience in our bodies.
03:46
So how does it work? Let me show you.
03:49
We use techniques from the computer chip
03:52
manufacturing industry
03:55
to make these structures at a scale
03:56
relevant to both the cells and their environment.
03:59
We have three fluidic channels.
04:02
In the center, we have a porous, flexible membrane
04:04
on which we can add human cells
04:07
from, say, our lungs,
04:09
and then underneath, they had capillary cells,
04:11
the cells in our blood vessels.
04:13
And we can then apply mechanical forces to the chip
04:15
that stretch and contract the membrane,
04:19
so the cells experience the same mechanical forces
04:22
that they did when we breathe.
04:25
And they experience them how they did in the body.
04:28
There's air flowing through the top channel,
04:31
and then we flow a liquid that contains nutrients
04:34
through the blood channel.
04:37
Now the chip is really beautiful,
04:40
but what can we do with it?
04:42
We can get incredible functionality
04:44
inside these little chips.
04:47
Let me show you.
04:49
We could, for example, mimic infection,
04:50
where we add bacterial cells into the lung.
04:53
then we can add human white blood cells.
04:56
White blood cells are our body's defense
04:59
against bacterial invaders,
05:02
and when they sense this
inflammation due to infection,
05:03
they will enter from the blood into the lung
05:06
and engulf the bacteria.
05:09
Well now you're going to see this happening
05:11
live in an actual human lung on a chip.
05:13
We've labeled the white blood cells
so you can see them flowing through,
05:17
and when they detect that infection,
05:20
they begin to stick.
05:22
They stick, and then they try to go into the lung
05:24
side from blood channel.
05:28
And you can see here, we can actually visualize
05:29
a single white blood cell.
05:33
It sticks, it wiggles its way through
05:37
between the cell layers, through the pore,
05:39
comes out on the other side of the membrane,
05:41
and right there, it's going to engulf the bacteria
05:44
labeled in green.
05:47
In that tiny chip, you just witnessed
05:49
one of the most fundamental responses
05:52
our body has to an infection.
05:55
It's the way we respond to -- an immune response.
05:57
It's pretty exciting.
06:01
Now I want to share this picture with you,
06:03
not just because it's so beautiful,
06:06
but because it tells us an enormous
amount of information
06:08
about what the cells are doing within the chips.
06:11
It tells us that these cells
06:14
from the small airways in our lungs,
06:16
actually have these hairlike structures
06:19
that you would expect to see in the lung.
06:20
These structures are called cilia,
06:22
and they actually move the mucus out of the lung.
06:24
Yeah. Mucus. Yuck.
06:27
But mucus is actually very important.
06:28
Mucus traps particulates, viruses,
06:31
potential allergens,
06:33
and these little cilia move
06:35
and clear the mucus out.
06:36
When they get damaged, say,
06:39
by cigarette smoke for example,
06:41
they don't work properly,
and they can't clear that mucus out.
06:43
And that can lead to diseases such as bronchitis.
06:46
Cilia and the clearance of mucus
06:50
are also involved in awful diseases like cystic fibrosis.
06:52
But now, with the functionality
that we get in these chips,
06:57
we can begin to look
07:00
for potential new treatments.
07:02
We didn't stop with the lung on a chip.
07:05
We have a gut on a chip.
07:07
You can see one right here.
07:08
And we've put intestinal human cells
07:10
in a gut on a chip,
07:14
and they're under constant peristaltic motion,
07:16
this trickling flow through the cells,
07:18
and we can mimic many of the functions
07:22
that you actually would expect to see
07:24
in the human intestine.
07:26
Now we can begin to create models of diseases
07:28
such as irritable bowel syndrome.
07:32
This is a disease that affects
07:34
a large number of individuals.
07:36
It's really debilitating,
07:38
and there aren't really many good treatments for it.
07:40
Now we have a whole pipeline
07:44
of different organ chips
07:46
that we are currently working on in our labs.
07:49
Now, the true power of this technology, however,
07:52
really comes from the fact
07:56
that we can fluidically link them.
07:58
There's fluid flowing across these cells,
08:00
so we can begin to interconnect
08:02
multiple different chips together
08:04
to form what we call a virtual human on a chip.
08:07
Now we're really getting excited.
08:12
We're not going to ever recreate
a whole human in these chips,
08:15
but what our goal is is to be able to recreate
08:19
sufficient functionality
08:23
so that we can make better predictions
08:25
of what's going to happen in humans.
08:27
For example, now we can begin to explore
08:29
what happens when we put
a drug like an aerosol drug.
08:32
Those of you like me who have asthma,
when you take your inhaler,
08:36
we can explore how that drug comes into your lungs,
08:39
how it enters the body,
08:42
how it might affect, say, your heart.
08:43
Does it change the beating of your heart?
08:45
Does it have a toxicity?
08:47
Does it get cleared by the liver?
08:49
Is it metabolized in the liver?
08:51
Is it excreted in your kidneys?
08:53
We can begin to study the dynamic
08:55
response of the body to a drug.
08:57
This could really revolutionize
09:00
and be a game changer
09:01
for not only the pharmaceutical industry,
09:03
but a whole host of different industries,
09:06
including the cosmetics industry.
09:08
We can potentially use the skin on a chip
09:11
that we're currently developing in the lab
09:14
to test whether the ingredients in those products
09:16
that you're using are actually
safe to put on your skin
09:18
without the need for animal testing.
09:21
We could test the safety
09:24
of chemicals that we are exposed to
09:26
on a daily basis in our environment,
09:28
such as chemicals in regular household cleaners.
09:30
We could also use the organs on chips
09:34
for applications in bioterrorism
09:37
or radiation exposure.
09:40
We could use them to learn more about
09:43
diseases such as ebola
09:46
or other deadly diseases such as SARS.
09:49
Organs on chips could also change
09:53
the way we do clinical trials in the future.
09:55
Right now, the average participant
09:58
in a clinical trial is that: average.
10:01
Tends to be middle aged, tends to be female.
10:04
You won't find many clinical trials
10:07
in which children are involved,
10:10
yet every day, we give children medications,
10:11
and the only safety data we have on that drug
10:15
is one that we obtained from adults.
10:19
Children are not adults.
10:22
They may not respond in the same way adults do.
10:23
There are other things like genetic differences
10:27
in populations
10:29
that may lead to at-risk populations
10:30
that are at risk of having an adverse drug reaction.
10:34
Now imagine if we could take cells
from all those different populations,
10:37
put them on chips,
10:40
and create populations on a chip.
10:42
This could really change the way
10:44
we do clinical trials.
10:46
And this is the team and the people
that are doing this.
10:48
We have engineers, we have cell biologists,
10:51
we have clinicians, all working together.
10:54
We're really seeing something quite incredible
10:58
at the Wyss Institute.
11:00
It's really a convergence of disciplines,
11:02
where biology is influencing the way we design,
11:04
the way we engineer, the way we build.
11:07
It's pretty exciting.
11:10
We're establishing important industry collaborations
11:12
such as the one we have with a company
11:15
that has expertise in large-scale
digital manufacturing.
11:18
They're going to help us make,
11:22
instead of one of these,
11:24
millions of these chips,
11:26
so that we can get them into the hands
11:27
of as many researchers as possible.
11:29
And this is key to the potential of that technology.
11:32
Now let me show you our instrument.
11:36
This is an instrument that our engineers
11:39
are actually prototyping right now in the lab,
11:41
and this instrument is going to give us
11:43
the engineering controls that we're going to require
11:45
in order to link 10 or more organ chips together.
11:48
It does something else that's very important.
11:52
It creates an easy user interface.
11:54
So a cell biologist like me can come in,
11:57
take a chip, put it in a cartridge
12:00
like the prototype you see there,
12:02
put the cartridge into the machine
12:04
just like you would a C.D.,
12:06
and away you go.
12:08
Plug and play. Easy.
12:09
Now, let's imagine a little bit
12:12
what the future might look like
12:14
if I could take your stem cells
12:15
and put them on a chip,
12:18
or your stem cells and put them on a chip.
12:19
It would be a personalized chip just for you.
12:22
Now all of us in here are individuals,
12:26
and those individual differences mean
12:29
that we could react very differently
12:32
and sometimes in unpredictable ways to drugs.
12:34
I myself, a couple of years back,
had a really bad headache,
12:39
just couldn't shake it, thought,
"Well, I'll try something different."
12:43
I took some Advil. Fifteen minutes later,
12:46
I was on my way to the emergency room
12:48
with a full-blown asthma attack.
12:50
Now, obviously it wasn't fatal,
12:52
but unfortunately, some of these
12:53
adverse drug reactions can be fatal.
12:57
So how do we prevent them?
13:00
Well, we could imagine one day
13:02
having Geraldine on a chip,
13:05
having Danielle on a chip,
13:07
having you on a chip.
13:09
Personalized medicine. Thank you.
13:10
(Applause)
13:13

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About the speaker:

Geraldine Hamilton - Bio researcher
Geraldine Hamilton builds organs and body parts on a chip -- to test new, custom cures.

Why you should listen

Geraldine Hamilton’s career spans from academic research to biotech start-ups to pharma. Her research focus has been on the development and application of human-relevant in-vitro models for drug discovery. She was one of the founding scientists, VP of Scientific Operations and Director of Cell Products, in a start-up biotech company (CellzDirect), that successfully translated and commercialized technology from academic research to supply the pharmaceutical industry with hepatic cell products and services for safety assessment and drug-metabolism studies.

Hamilton received her Ph.D. in cell biology/toxicology from the University of Hertfordshire (England) in conjunction with GlaxoSmithkline, followed by a post-doctoral research fellowship at the University of North Carolina. Her current research interests and prior experience include: organs on-a-chip, toxicology and drug metabolism, liver cell biology, mechanisms regulating gene expression and differentiation, regulation of nuclear receptors and transcriptional activation in hepatocytes by xenobiotics, human cell isolation and cryopreservation techniques.

More profile about the speaker
Geraldine Hamilton | Speaker | TED.com