Your body in a microchip: Geraldine Hamilton at TEDxBoston

The development of new medicine is problematic because laboratories cannot replicate the human body's environment, making it difficult to determine how patients will respond to treatment. At TEDxBoston, Geraldine Hamilton demonstrates how scientists can implant living human cells into microchips that mimic the body's conditions. These "organs-on-a-chip" can be used to study drug toxicity, identify potential new therapies, and could lead to safer clinical trials.

We have a global health challenge
in our hands today,

and that is that the way
we currently discover and develop

new drugs is too costly,

takes far too long,

and it fails more often than it suceeds.

It really just isn't working,

and that means that patients
that badly need new therapies

are not getting them
and diseases are going untreated.

We seem to be spending
more and more money,

so for every billion dollars
we spend in R&D,

we're getting less drugs
approved into the market.

More money, less drugs.
So what's going on here?

Well, there's a multitude
of factors at play,

but I think one of the key factors

is that the tools that
we currently have available

to test whether a drug is going to work,

whether it has efficacy
or whether is going to be safe

before we get it into human
clinical trials, are failing us.

They're not predicting what
is going to happen in humans

and we two main tools
available at our disposal:

there are cells in dishes
and animal testing.

Now, let's talk about
the first one: cells in dishes.

So, cells are happily
functioning in our bodies,

we take them and rip them out
of their native environment,

throw them out in one of these dishes
and expect them to work.

Guess what? They don't.

They don't like that environment,

because it's nothing like
what they have in the body.

What about animal testing?

Well, animals do and can provide
extremely useful information.

They teach us about what happens
in the complex organism,

we learn more about the biology itself.

However, more often than not,

animal models fail to predict
what will happen in humans,

when they're treated
with a particular drug,

So we need better tools.

We need human cells
but we need to find a way

to keep them happy outside the body.

Now, before I tell how we do that,

let's do a little exercise together.

Alright. Everybody close your eyes,

come on, those of you in the back
that I can't see, close your eyes,

come on, I'm going to do this with you.

Now, take a deep breath in
and breath out,

and again, breath in, and breath out.

Now feel the beat of your heart,

feel it pumping that blood
throughout your body.

And now, ok, now wiggle around
a little in your seats

come on, move, come on,
you've been sitting for a while.

Alright, open your eyes.

Besides that being a fun exercise
that is good for relaxation,

it helps to illustrate that all bodies
are dynamic environments.

We are in constant motion.
Our cells experience that.

They're in dynamic
environments in our body.

They're under constant mechanical forces.

So, if we want to make cells
happy outside our bodies,

we need to become cell architects.

We need to design, build and engineer

a home away from home for the cells.

And at the Wyss Institute,
we've done just that.

We call it an "organ on a chip",
and I have one right here.

It's beautiful, isn't it?

But it's pretty incredible,
right here in my hand

is a breathing, living,
human lung-on-a-chip.

And it's not just beautiful :

it can do tremendous amounts of things.

We have living cells in that little chip,

cells that are dynamic environments,

interacting with different cell types.

And, there's been many people
trying to grow cells in the lab,

they've tried many different approaches.

They've even try to grow
little mini organs in the lab.

We're not trying to do that here,

we're simply trying
to recreate, in this tiny chip,

the smallest, functional unit
that represents the biochemistry,

the function and the mechanical strain

that the cells experience in our bodies.

So, how does it work?

Let me show you.

We use techniques from
the computer chip manufacturing industry

to make these structures at a scale

relevant to both the cells
and their environment.

We have three fluidic channels.

In the center, we have
a porous flexible membrane,

on which we can add humans cells
from, say, our lungs,

and then underneath,
they have capillary cells -

the cells in our blood vessels.

And we can then apply
mechanical forces to the chip

that stretch and contract the membrane,

so the cells experience
the same mechanical forces

that they did when we breathed,

and how they experienced them
like they did in the body.

There's air flowing through
the top channel,

and then we throw a liquid
that contains nutrients,

through the blood channel.

Now, the chip is really beautiful.

But, what can we do with it?

So when I ask this question,
that often sparks a lot of ideas.

Some of my fellow TEDx presenters
have suggested

we can make jewelry out of them.

(Laughter)

Now, I think a "lung-on-a-chip" necklace
would look quite nice.

However, it does much more than this.

We can get incredible functionality
inside these little chips.

Let me show you:
we could, for example,

make an infection, where we add
bacterial cells into the lung,

then we can add human white bloods cells.

White blood cells are our bodies' defense
against bacterial invaders,

and when they sense
this inflammation due to infection,

they will enter from
the blood into the lung

and engulf the bacteria.

Well, now, you're going
to see this happening live

in an actual human lung-on-a-chip.

We labeled the white bloods cells
so you can see them flowing through,

and when they detect that infection,
they begin to stick.

They stick and then they try to go

into the lung side
from the blood channel.

And you can see here,
we can actually visualize

a single white blood cell.

It sticks, it wiggles its way through
between the cell layers,

through the pore, comes out
on the other side of the membrane,

and right there is going to engulf
the bacteria labeled in green.

In that tiny chip, you just witnessed

one of the most fundamental responses
our body has to an infection.

it's the way we respond,
an immune response.

it's pretty exciting.

Now, I want to share
this picture with you.

I want to share this with you
because it's a beautiful photograph.

It's almost like art.

As a cell biologist, I could look
at pictures like these all day long.

But I wanted to share it with you,

not just because it's so beautiful,

but because it tells us
an enormous amount of information

about what the cells
are doing within the chips.

It tells us that these cells
from the small airways in our lungs

actually have these hair-like structures

that you would expect to see in a lung.

These structures are called cilia
and they actually move

the mucus out of the lung.
Yeah, mucus, yuck!

But mucus is actually very important.

Mucus traps particulates,
viruses, potential allergens

and these little cilia move
and clear the mucus out.

When they get damaged,
say by cigarette smoke, for example,

they don't work properly
and they can't clear that mucus out,

and that can lead to diseases
such as bronchitis.

Cillia and the clearance of mucus
are also involved in awful diseases,

like cystic fibrosis.

But now, with the functionality
that we get in these chips,

we can begin to look
for potential new treatments.

We didn't stop with a lung-on-a-chip,

we have a gut-on-a-chip,

you can see one right here.

And we've put intestinal human cells
in our gut-on-a-chip,

and they're under
constant peristaltic motion,

this trickling flow through the cells,

and we can mimic many of the functions

that you actually would expect
to see in the human intestine.

Now we can begin
to create models of diseases

such as irritable bowel syndrome.

This is a disease that affects
a large number of individuals,

it's really debilitating,

and they aren't really many
good treatments for it.

Now, we have a whole pipeline
of different organ chips

that we are currently
working on in our labs.

Now, the true power
of this technology, however,

really comes from the fact
that we can fluidly link them.

There's fluid flowing across these cells,

so we can begin to interconnect
multiple different chips together

to form what we call
a virtual human-on-a-chip.

Now, we're really getting excited.

So, we're not going to ever recreate
a whole human in these chips

but what our goal is, is to be able
to recreate sufficient functionality

so that we can make better predictions

of what's going to happen in humans

For example, now we can begin
to explore what happens

when we put a drug like an aerosol drug.

Those of you like me who have asthma,
when you take you inhaler,

we can explore how that drug
comes into your lungs,

how it enters the body,
how it might affect your heart,

does it change the beating of your heart?

Does it have a toxicity?

Does it get cleared by the liver?

Is it metabolizes in the liver?

Is it excreted in your kidneys?

We can begin to study
the dynamic response

of the body to a drug.

This could really revolutionize
and be a game changer,

for not only
the pharmaceutical industry,

but a whole host
of different industries,

including the cosmetics industry.

So, how many of you are wearing lipstick?

Or used soap in the shower this morning?

We can potentially use the skin-on-a-chip

that we're currently developing on the lab

to test whether the ingredients
in these products that you're using

are actually safe to put on your skin,

without the need for animal testing.

We could test the safety
of chemicals that we're exposed to

on a daily basis in our environment,

such as chemicals
in regular household cleaners.

We could also use the organs-on-chips

for applications in bioterrorism,
or radiation exposure.

We could use them to learn
more about these diseases

such as Ebola or other deadly diseases,
such as SARS.

And why are this useful?

Because you can't really
ask a volunteer in a clinical trial,

"Let me treat you
with a whole bunch of radiation,

and then i'll see if my new drug
can actually repair the damage."

That's just not going to happen.

But our organs-on-chips offer
a whole new possibility.

What about clinical trials?

Organs in chips could
also change with the way

we do clinical trials in the future.

Right now, the average participant
in a clinical trial is that:

average, tends to be middle age,
tends to be female.

You won't find many clinical trials
in which children are involved.

Yet, everyday we give children medications

and the only safety data
we have on that drug

is one that we obtained from adults.

Children are not adults,

they may not respond
in the same way adults do.

There are other things, like
genetic differences in populations

that may lead to risk populations

that are at risk of having
an adverse drug reaction.

Now imagine if we could take cells
from all those different populations,

put them on chips
and create populations-on-a-chip.

This could really change
the way we do clinical trials.

Now, I've told you about

some amazing work
and amazing technology.

And this is the team, the people
and the team that are doing this.

We have engineers, we have
cell biologists, we have clinicians,

all working together.

We're really seeing something
quite incredible at the Weyss Institute,

it's really a convergence of disciplines,

where biology and engineering
are actually coming together.

Where biology is influencing
the way we design,

the way we engineer, the way we build.

It's pretty exciting, and it's happening
right here in Boston.

And that's pretty cool because in Boston
we're able to easily collaborate

with so many academic institutions,
hospitals and industry.

And we're doing just that.

We're establishing important
industry collaborations,

such as the one we have
with a company

that has expertise in
large-scale digital manufacturing.

They're going to help us make,
instead of one of these,

millions of these chips,

so that we can get them into the hands
of as many researchers as possible.

And this is key to the potential
of that technology.

Now, let me show you our instrument.

This is an instrument that our engineers

are actually prototyping
right now, in the lab,

and this instrument is going to give us
the engineering controls

that we're going to require
in order to link

ten or more organ chips together.

But it does something else
that is very important:

it creates an easy user interface,
so a cell biologist like me can come in,

take a chip, put it in a cartridge
like the prototype you see there,

put the cartridge into the machine
just like you would a CD, and away you go.

Plug and play. Easy.

Now, let's imagine a little bit
what the future might look like

if I could take your stem cells
and put them on a chip,

or your stem cells
and put them on a chip.

It would be a personalized chip
just for you.

Now, all of us in here are individuals.

And those individual differences

mean that we could react very differently,

and sometimes in unpredictable ways,
to drugs.

I, myself, a couple of years back,
had a really bad headache.

I just couldn't shake it,

thought "I'll try something different".
I took some Advil.

15 minutes later, I was on my way
to the emergency room

with a full-blown asthma attack.

Now, obviously, it wasn't fatal,
but unfortunately,

some of these adverse drug reactions
can be fatal.

So how do we prevent them?

Well, we could imagine one day
having Geraldine-on-a-chip,

having Danielle-on-a-chip,
having you-on-a chip.

Personalized medicine.

Thank you.

(Applause)