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