How to pronounce "functionality"

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 succeeds.

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. Hmm.

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 it's going to be safe

before we get it into human clinical trials,

are failing us. They're not predicting

what's going to happen in humans.

And we have two main tools available

at our disposal.

They 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 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.

Our bodies are dynamic environments.

We're 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 a tremendous amount of things.

We have living cells in that little chip,

cells that are in a dynamic environment

interacting with different cell types.

There's been many people

trying to grow cells in the lab.

They've tried many different approaches.

They've even tried 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 human cells

from, say, our lungs,

and then underneath, they had 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 breathe.

And they experience them how they did in the body.

There's air flowing through the top channel,

and then we flow a liquid that contains nutrients

through the blood channel.

Now the chip is really beautiful,

but what can we do with it?

We can get incredible functionality

inside these little chips.

Let me show you.

We could, for example, mimic infection,

where we add bacterial cells into the lung.

then we can add human white blood cells.

White blood cells are our body's 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've labeled the white blood 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 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, it's 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 to -- an immune response.

It's pretty exciting.

Now I want to share this picture 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 hairlike structures

that you would expect to see in the 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.

Cilia 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 the 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 a 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 there 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 fluidically 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.

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 your inhaler,

we can explore how that drug comes into your lungs,

how it enters the body,

how it might affect, say, your heart.

Does it change the beating of your heart?

Does it have a toxicity?

Does it get cleared by the liver?

Is it metabolized 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.

We can potentially use the skin on a chip

that we're currently developing in the lab

to test whether the ingredients in those 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 are 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

diseases such as ebola

or other deadly diseases such as SARS.

Organs on chips could also change

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 aged, tends to be female.

You won't find many clinical trials

in which children are involved,

yet every day, 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 at-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.

And this is the team and the people 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 Wyss Institute.

It's really a convergence of disciplines,

where biology is influencing the way we design,

the way we engineer, the way we build.

It's pretty exciting.

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 10 or more organ chips together.

It does something else that's 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 C.D.,

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,

just couldn't shake it, thought, "Well, I'll try something different."

I took some Advil. Fifteen 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)