TEDxBoston 2013

Geraldine Hamilton: Body parts on a chip

Filmed:

It's relatively easy to imagine a new medicine, a better cure for some disease. The hard part, though, 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 -- even custom cures for one specific person. (Filmed at TEDxBoston)

- 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
00:29
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,
01:11
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
01:20
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.
01:32
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
01:44
because it's nothing like
01:46
what they have in the body.
01:48
What about animal testing?
01:50
Well, animals do and can provide
01:52
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.
02:23
We're in constant motion.
02:26
Our cells experience that.
02:28
They're in dynamic environments in our body.
02:30
They're under constant mechanical forces.
02:33
So if we want to make cells happy
02:36
outside our bodies,
02:38
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.
02:53
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.
03:10
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
03:42
that the cells experience in our bodies.
03:45
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.
04:01
In the center, we have a porous, flexible membrane
04:03
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.
04:48
We could, for example, mimic infection,
04:50
where we add bacterial cells into the lung.
04:52
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,
05:16
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
05:23
side from blood channel.
05:27
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,
06:05
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
06:18
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,
06:38
by cigarette smoke for example,
06:40
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
06:49
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.
07:04
We have a gut on a chip.
07:06
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,
07:15
this trickling flow through the cells,
07:18
and we can mimic many of the functions
07:21
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.
07:48
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.
08:11
We're not going to ever recreate
a whole human in these chips,
08:14
but what our goal is is to be able to recreate
08:18
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?
08:48
Is it metabolized in the liver?
08:50
Is it excreted in your kidneys?
08:53
We can begin to study the dynamic
08:54
response of the body to a drug.
08:57
This could really revolutionize
08:59
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
09:15
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
09:42
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.
10:00
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.
10:18
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
10:26
in populations
10:29
that may lead to at-risk populations
10:30
that are at risk of having an adverse drug reaction.
10:33
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,
11:01
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
11:11
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,
11:25
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
11:38
are actually prototyping right now in the lab,
11:40
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.
12:07
Plug and play. Easy.
12:09
Now, let's imagine a little bit
12:11
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,
12:51
but unfortunately, some of these
12:53
adverse drug reactions can be fatal.
12:56
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.