字幕列表 影片播放 列印英文字幕 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.