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  • Transcriber: Angélica Zetina González Reviewer: Elisabeth Buffard

  • 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.