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.
我们面临全球性的医疗挑战 今时今日, 我们目前发现并开发 新药物的方式 太昂贵,耗时太长 研究结果失败多而成功少 很多情况下完全无用,这意味着 当病人急切地需要新的疗法时 却无法获得药物, 疾病也无从治疗。 似乎我们花的钱也越来越多。 在研究中我们每花费十亿美元, 而获准在市场上销售的新药却更少了。 花更多的钱,研究出更少的新药。嗯。
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.
那么到底问题在哪? 好,这里有一系列影响因素, 但我认为主因之一是 我们目前的工具, 测试新药是否可用, 是否有疗效, 是否是安全的药品, 在开展人体临床试验之前, 这些工具都无法满足我们的要求。这些工具 不能预测药物将对人体产生何种作用。 我们有两大主要工具 可供使用。 它们是培养皿和动物实验。
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.
首先让我们讨论一下第一种工具,培养皿中的细胞。 一般,细胞在我们体内快乐的工作。 我们取出细胞,将它们从原生环境中 剥离出来,放进一个培养皿中, 并希望它们能照常工作。 猜怎么着。它们不工作了。 它们不喜欢新环境 因为新环境 和它们生长的身体环境大不相同。
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.
至于动物实验呢? 好,动物们确实可以提供 十分有用的信息。 它们使我们明白 在复杂的有机体中药物如何作用。 我们学到更多关于生物学本身的信息。 但是往往, 动物体实验不能预测人类 在使用特定药物时会发生的情况。
So we need better tools. We need human cells, but we need to find a way to keep them happy outside the body.
所以我们需要更好的工具。 我们确实需要人类细胞, 但是我们需要找到一个方式在体外 保持细胞活性。
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.
人类身体有着动态的环境。 我们在不断的运动中。 细胞也是如此。 细胞生活在身体的动态环境中。 细胞经受长期的机械力。 所以如果想让细胞, 在身体外存活, 我们就必须成为细胞建筑师。 我们需要设计、 策划和建造 细胞在身体以外的家。
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.
而在哈佛大学维斯研究所(Wyss Institute), 我们已经这样做了。 我们叫它芯片上的器官。 我这里有一个。 它很美丽,不是吗?但它是相当令人难以置信。 就在我的手中,细胞就在这里呼吸生活, 一个生活在芯片上的人类肺细胞。
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.
它并不只是美丽。 它可以做大量的事情。 我们将活细胞放入那个小小的芯片, 在动态环境之中的细胞 与不同的细胞类型进行交互。 有很多人 尝试在实验室里培养细胞。 他们尝试了许多不同的方法。 甚至试图在实验室里培育小型迷你器官。 但这不是我们想做的。 我们只想在这个小小的芯片里 重新创建 一个最小的功能单位 它能模拟细胞的生物化学环境, 功能和在身体中经历的 机械拉力。 它是如何工作的?让我展示给你看。 我们使用芯片技术 和制造技术 按照细胞及其环境情况 建造具有相应规模的结构。 我们有三个流体通道。 在芯片中心,我们有一个多孔的、 可渗透的膜 在膜上,我们可以添加人体细胞 比如说说,人类的肺细胞, 然后在肺细胞下,加入毛细血管细胞, 一种我们的血管中的细胞。 我们然后可以对芯片施以机械力 来伸展和收缩膜, 所以细胞能受到与我们呼吸时 感受的相同机械力。 细胞经历着与在身体中相同的环境。 顶部通道有空气流过, 然后使含有的营养物质的液体 流过血液通道。 现在,这张芯片是真的很美, 但它能做什么呢? 我们可以使用这些小芯片 获得惊人的功能。 让我来展示下。 比如说,我们可以模仿感染, 将细菌细胞添加到肺细胞上 然后再添加人类白细胞。 白细胞是人类身体的防御者 专门针对细菌入侵者, 当白细胞感觉到这种炎症感染, 它们将从血液进入肺 并吞噬细菌。 现在你能通过芯片上的活生生的人类肺细胞 观测到这种情况的发生。 我们已经标记过这些白细胞,所以你可以看到它们流过, 当白细胞发现感染, 就会粘在细胞壁上。 白细胞聚集在感染处,然后试着从血液通道一侧 进入肺细胞一侧。 你可以看到,我们其实使每个白细胞 可视化了。 这个白细胞粘住后,扭动并通过 细胞层,通过孔洞, 从膜的另一边出来 而在膜的这边,它将会去吞噬 标记为绿色的细菌。 在那小小的芯片里,你刚刚目睹了 当我们的身体受到感染时做出的 一种最基本的反应。 这就是我们身体回应的方式 — — 免疫反应。 这是很令人兴奋的。
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.
现在我想跟你们分享这张照片, 不只是因为它特别美丽, 而是因为它告诉了我们大量的 关于细胞在芯片中活动的信息。 它告诉我们,这些 从我们的肺气道里提取的细胞 其实有一些绒毛般的结构 就像人们常常在肺里看到绒毛一样。 这些结构被称为纤毛, 它们的作用是将肺里的痰清除出来。 是这样的。痰。恶心。 但痰其实是非常重要的。 痰液捕获大气尘、 病毒、 潜在过敏原, 这些小纤毛移动 并将痰液清除。 当纤毛被损坏时,比如说 被香烟烟雾损坏时, 它们就停止正常工作,也不能清除痰液。 就会导致支气管炎等疾病。 纤毛和痰液清除 也会与可怕的疾病有关,比如囊胞性纤维症。 但现在,通过使用这些芯片的功能, 我们可以开始探索 潜在的新疗法。
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.
我们并没有止步于芯片上的肺细胞。 我们有肠细胞芯片。 大家可以看到我这里就有一个。 我们已经把人类肠道中的细胞 放在在芯片上, 它们生活在不断的肠道蠕动下 有条滴流通过肠细胞, 我们可以模仿许多 大家能想到的 在发生在人体肠道内的身体功能。 现在我们可以开始创建疾病的模型 如肠易激综合症。 这是一种疾病, 影响许多病患。 此病会使人衰弱, 确实还没有很多好的治疗方法。
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.
现在,我们研发出了一整套 不同器官的芯片, 用在实验室中对该疾病进行研究。 这项技术的真正力量 是从这一事实衍生而来: 我们可以将细胞通过液体连接起来。 有流体流过这些细胞, 然后我们可以开始互连 多个不同芯片 以形成我们称之为虚拟的芯片人体。 现在我们真的很兴奋。 我们并不会建造一个芯片人体, 我们的目标是要能够重新创建 足够的细胞功能 使我们能够更好的预测 人体反应。 例如,现在我们可以开始探索 当我们使用气雾剂药物时,身体将如何反应。 那些像我一样有哮喘的人,使用吸入器时 我们可以研究药物如何进入肺细胞, 如何进入人体, 如何影响,比如说,心脏。 它会改变心脏的跳动吗? 有没有毒性吗? 会被肝脏清除吗? 它是通过肝脏代谢吗? 它是通过肾脏排泄吗? 我们可以开始研究 药物对身体的动态反应。
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.
这是一项创举, 并将改变游戏规则, 不管是制药业, 还是其他不同的许多行业, 包括化妆品行业。 我们可能会使用皮肤细胞芯片, 我们目前正在实验室中开发, 并测试您使用的化妆品中的成分 是不是对皮肤安全, 而无需动物试验。 我们可以测试我们接触到的 化学品的安全, 比如基于我们的日常生活环境的, 在普通家用清洁剂中使用的化学品。 我们也可将芯片器官 应用在生物反恐中 或测试辐射暴露上。 我们可以用它们来了解更多关于 疾病的特点,比如埃博拉病毒, 或其他致命的疾病,如非典型肺炎(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.
芯片器官也可以改变 我们在未来做临床试验的方式。 现在,一般参与 临床试验的被测者都是平均值。 往往是中年人,往往是女性。 临床试验并不多, 特别是涉及到儿童, 然而日常生活中,我们给孩子用药, 使用药物的安全数据 却是从测试成年人时取得的。 儿童不同于成人。 儿童对药物的反应也可能与成人不同。 还有其他的影响因素,像不同人群间的 遗传差异 可能会导致一部分高危人群, 承受药物不良反应的风险。 现在想象一下, 我们是否可以从不同人群中提取细胞 把它们放上芯片, 并在芯片上创建这些人群。 这真的可以改变 我们做临床试验的方式。 这正是我们团队和成员正在做的事。 我们中有工程师,有细胞生物学家, 有临床医生在一起工作。 在 VIS 研究所我们确实观察到了 一些很不可思议的东西。 这真是一门综合学科, 生物学正在影响我们设计的方式, 策划的方式,和建造的方式。 这很令人兴奋。
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.
我们要建立重要的产业合作 比如我们已与一家熟知 大型数字化制造的公司合作。 他们会帮助我们制造, 不是一枚, 而是数以百万计的芯片, 这样,我们可以让尽可能多的研究人员 使用这些芯片。 这是该技术至关重要的潜能。
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.
现在让我给大家看看我们的仪器。 这是一台我们的工程师 正在实验室中建造的样机, 这台仪器能使我们 工程控制需要实现的功能, 那就是将 10 个或更多器官芯片连接在一起。 这台机器做的事情是非常重要的。 它将创建一个简单的用户界面。 所以像我这样的细胞生物学家可以来 拿起一块芯片,把它放在盒子里 像你看到的原型一样 将盒子放入机器里, 这就像你放 C.D.一样 然后就好了。 即插即用。很容易。
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.
现在,让我们想象一下 未来可能会是什么样子 如果能把你的干细胞 放在芯片上, 或者把你的干细胞,放在一个芯片上。 它将只为你一个人创造一枚个性化的芯片。
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.
今天在座的各位都是单独个体, 而那些个体差异意味着 我们对药物的反应方式有可能非常不同, 有时甚至无法预知身体反应的方式。 就我自己来说,过去有两年,头痛得真的很厉害, 完全不能摆脱它,我当时想,"嗯,我要试点不同的药方", 我吃了几片雅维。十五分钟后, 我就在去急救室的路上了, 哮喘全面发作。 现在,当然没有致命, 但不幸的是,有些 药品的不良反应确是致命的。
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.
所以我们如何防范呢? 嗯,我们可以想象一下有一天 在芯片上,载有杰拉尔丁细胞 在芯片上,载有丹妮细胞 有你的细胞在芯片上。
Personalized medicine. Thank you.
个体化用药。谢谢。
(Applause)
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