I'd like to show you a video of some of the models I work with. They're all the perfect size, and they don't have an ounce of fat. Did I mention they're gorgeous? And they're scientific models? (Laughs)
我想让大家看一段模特儿的影片 他们是我的工作伙伴 他们都有完美的身材,没有一丁点脂肪 我有说过他们超美的吗? 还有他们是科学模特儿吗? (笑声)
As you might have guessed, I'm a tissue engineer, and this is a video of some of the beating heart that I've engineered in the lab. And one day we hope that these tissues can serve as replacement parts for the human body. But what I'm going to tell you about today is how these tissues make awesome models.
你们可能会猜对了,我是个组织工程学家 这段影片是在拍摄跳动的心脏 这是我在实验室设计的 我们希望有一天,这些组织 可以当作某些人体器官的替代品 但是我今天要跟大家说的 是为什么这些组织能成为顶尖的模特儿(模型)
Well, let's think about the drug screening process for a moment. You go from drug formulation, lab testing, animal testing, and then clinical trials, which you might call human testing, before the drugs get to market. It costs a lot of money, a lot of time, and sometimes, even when a drug hits the market, it acts in an unpredictable way and actually hurts people. And the later it fails, the worse the consequences.
好,让我们先来看看药物检验的流程 从药物配方、实验室测试、动物测试 到临床测试,也可以称之为人体实验 完成这些步骤才会上市 这样的流程很花钱,很费时 甚至有时候连已经上市的药物 都会让人体产生无法预测的反应,造成实质的伤害 而且问题发现得越晚,后果就会越严重
It all boils down to two issues. One, humans are not rats, and two, despite our incredible similarities to one another, actually those tiny differences between you and I have huge impacts with how we metabolize drugs and how those drugs affect us.
我们将之简化为两个问题。 第一,人类不是老鼠 第二,尽管人和人之间的差异微乎其微 但是我们之间这些微小的差异 却让我们代谢药物的反应和药效 有天壤之别
So what if we had better models in the lab that could not only mimic us better than rats but also reflect our diversity? Let's see how we can do it with tissue engineering.
所以,如果说我们的实验室使用了更好的模型 而这些模型不单只是比老鼠更接近人类 还可以反映出人体的多元性呢? 我们来看看,组织工程学能做些什么
One of the key technologies that's really important is what's called induced pluripotent stem cells. They were developed in Japan pretty recently. Okay, induced pluripotent stem cells. They're a lot like embryonic stem cells except without the controversy. We induce cells, okay, say, skin cells, by adding a few genes to them, culturing them, and then harvesting them. So they're skin cells that can be tricked, kind of like cellular amnesia, into an embryonic state. So without the controversy, that's cool thing number one. Cool thing number two, you can grow any type of tissue out of them: brain, heart, liver, you get the picture, but out of your cells. So we can make a model of your heart, your brain on a chip.
其中一项至关重要的关键科技 我们称之为"诱导性多功能干细胞" 最近由日本发展出来的 好,诱导性多功能干细胞 和胚胎干细胞有许多相似之处 只是前者没有道德争议性 我们诱导细胞生长,举例来说,皮肤细胞 的方式是植入微量的基因,培养它们 接着就可以采收 所以我们可以欺骗这些皮肤细胞 可以说是让细胞罹患失忆症,让他们变回胚胎模式 因此没有道德争议性,这是第一个好处 第二个好处是,你可以用它培养出任何的组织 大脑、心脏、肝脏,你们都知道的 都是出于自己的细胞 所以我们可以做出你的心脏,你的大脑的模版 在晶片上
Generating tissues of predictable density and behavior is the second piece, and will be really key towards getting these models to be adopted for drug discovery. And this is a schematic of a bioreactor we're developing in our lab to help engineer tissues in a more modular, scalable way. Going forward, imagine a massively parallel version of this with thousands of pieces of human tissue. It would be like having a clinical trial on a chip.
培育出密度和行为模式可预测的组织 是第二步骤,这个进展非常重要 使得这些模型能应用于药物测试 这张图是我们实验室正在发展的生物反应器 它能提高组织工程进行时的模式性和控制性 未来,你们想像一下许多台这种仪器并联在一起的样子 里面有数以千计的人类组织 就好像在晶片上面进行临床试验
But another thing about these induced pluripotent stem cells is that if we take some skin cells, let's say, from people with a genetic disease and we engineer tissues out of them, we can actually use tissue-engineering techniques to generate models of those diseases in the lab. Here's an example from Kevin Eggan's lab at Harvard. He generated neurons from these induced pluripotent stem cells from patients who have Lou Gehrig's Disease, and he differentiated them into neurons, and what's amazing is that these neurons also show symptoms of the disease. So with disease models like these, we can fight back faster than ever before and understand the disease better than ever before, and maybe discover drugs even faster. This is another example of patient-specific stem cells that were engineered from someone with retinitis pigmentosa. This is a degeneration of the retina. It's a disease that runs in my family, and we really hope that cells like these will help us find a cure.
关于诱导性多功能干细胞,还有另外一件事 那就是如果我们采集了一些皮肤细胞,例如说 从有遗传性疾病的人身上 然后我们从中培育出一些组织 我们可以实际利用组织工程的技术 在实验室里培育这些疾病的模型 这个例子来自Kevin Eggin在哈佛的实验室 他培养出神经元 从诱导性多功能干细胞中 样本来自Lou Gehrig症(肌肉萎缩性侧索硬化症) 的病患 他将它们分化成神经元,不可思议的是 这些神经元也反应出该疾病的症状 所以有了这些疾病的模型,我们能以前所未有的速度 反击它们(疾病),还能以前所未有的角度 了解它们,甚至能加快药物研发的脚步 这是另一个例子,这种遗传性疾病干细胞 是从自色素性视网膜炎的患者培育出来的 这种病导致视网膜的衰退 这是我们家族成员常罹患的疾病,我们真的很希望 这类的干细胞可以帮助我们找到解药
So some people think that these models sound well and good, but ask, "Well, are these really as good as the rat?" The rat is an entire organism, after all, with interacting networks of organs. A drug for the heart can get metabolized in the liver, and some of the byproducts may be stored in the fat. Don't you miss all that with these tissue-engineered models? Well, this is another trend in the field. By combining tissue engineering techniques with microfluidics, the field is actually evolving towards just that, a model of the entire ecosystem of the body, complete with multiple organ systems to be able to test how a drug you might take for your blood pressure might affect your liver or an antidepressant might affect your heart. These systems are really hard to build, but we're just starting to be able to get there, and so, watch out.
因此,有些人认为这些模型看起来完美无缺 但是他们会问: "这些细胞真的跟小白鼠一样好用吗?" 毕竟老鼠是完整的生物体 器官之间有完整的互动网路 用于心脏的药会在肝脏代谢 而且有些药效副产品可能会储存在脂肪 这些效果在组织工程的模型上不是都看不出来吗? 没错,这是这领域的另外一个研究趋势 将组织工程的技术与微流学结合在一起 实际上,这个领域正朝这个方向发展 人体全生态系统的模型 必须包含复合的器官系统才得以测试 为了控制血压而服用的药物 可能会影响你的肝脏,服用抗忧郁剂或许会影响你的心脏 这些系统很难架构,但是我们开始着手进行了 所以,等着看吧
But that's not even all of it, because once a drug is approved, tissue engineering techniques can actually help us develop more personalized treatments. This is an example that you might care about someday, and I hope you never do, because imagine if you ever get that call that gives you that bad news that you might have cancer. Wouldn't you rather test to see if those cancer drugs you're going to take are going to work on your cancer? This is an example from Karen Burg's lab, where they're using inkjet technologies to print breast cancer cells and study its progressions and treatments. And some of our colleagues at Tufts are mixing models like these with tissue-engineered bone to see how cancer might spread from one part of the body to the next, and you can imagine those kinds of multi-tissue chips to be the next generation of these kinds of studies.
但是这还不是全部,因为一旦药物获得许可 组织工程的技术真的能帮助我们使疗程更加符合个人需求 未来的某天你可能需要了解这些相关资讯 虽然我希望这一天永远不会来 因为你想像,自己可能接到了一通电话 带来的是坏消息,你可能罹患癌症了 你难道不想先试用那些治疗癌症的药物 看看那些药是否真的可以对抗你的癌症吗? 这是Karen Burg的实验室的例子,他们那里 使用喷墨技术来标的乳癌细胞 并研究细胞的发展及疗效 我们Tufts有几个同事正在结合不同模型 例如结合那些组织工程研发的骨头,观察癌症如何 从身体这个区域扩散到下一个区域 你可以想像一下,那些包含多种组织的晶片 会在下个世代,成为这类研究的主流
And so thinking about the models that we've just discussed, you can see, going forward, that tissue engineering is actually poised to help revolutionize drug screening at every single step of the path: disease models making for better drug formulations, massively parallel human tissue models helping to revolutionize lab testing, reduce animal testing and human testing in clinical trials, and individualized therapies that disrupt what we even consider to be a market at all. Essentially, we're dramatically speeding up that feedback between developing a molecule and learning about how it acts in the human body. Our process for doing this is essentially transforming biotechnology and pharmacology into an information technology, helping us discover and evaluate drugs faster, more cheaply and more effectively. It gives new meaning to models against animal testing, doesn't it? Thank you. (Applause)
所以,回想我们刚刚讨论的这些模型 你会发现,未来的组织工程学 有助于药物检验,我们努力过程的每一步 都能使其产生突破性的变革 疾病模型可以制作出更好的药物配方 多样而大量的人类组织模型有助于实验室测试的变革 减少动物临床测试及人类临床测试 使疗程个人化,改变我们以往的想法 认为一套疗程适用于所有人 而我们实际的数据回馈也以戏剧化的速度增加 实验内容是培养单一分子,并研究其 在人体中的反应为何 我们的所作所为,其实就是 将生物科技跟药理学转换成资讯科技 帮助我们加快药物开发与评估的速度 减少成本,提高效率 比起动物试验,这样的作法更有意义,不是吗? 谢谢大家(鼓掌)