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)
我想讓大家看一段模特兒的影片 他們是我的工作夥伴 他們都有完美的身材,各個穠纖合度 我有說過他們超美的嗎? 還有他們是科學模特兒嗎?(笑聲)
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.
你們可能會猜我是個組織工程學家吧 然後這段影片是在拍攝跳動的心臟 這是我在實驗室設計的 我們希望有一天,這些組織 可以當作某些人體器官的替代品 但是我今天要跟大家說的 是為什麼這些組織能成為頂尖的模特兒(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,讓我們先來看看藥物檢驗的流程 從藥物配方、實驗室測試、動物測試 到臨床測試,也可以稱之為人體實驗 完成這些步驟才會上市 這樣的流程很花錢,很費時 甚至有時候連已經上市的藥物 都會讓人體產生無法預測的反應,造成實質的傷害 而且問題發現得越晚,後果就會越嚴重
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.
我們將之簡化為兩個問題。第一,人類不是老鼠 第二,儘管人和人之間的差異微乎其微 但是我們之間這些微小的差異 卻讓我們代謝藥物的反應和藥效 有天壤之別
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,如果說我們的實驗室使用了更好的模型 而這些模型不單只是比老鼠更接近人類 還可以反映出人體的多元性呢? 我們來看看,組織工程學能做些什麼
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.
其中一項至關重要的關鍵科技 我們稱之為"誘導性多功能幹細胞" 最近由日本發展出來的 好,誘導性多功能幹細胞 和胚胎幹細胞有許多相似之處 只是沒有道德爭議性 我們誘導細胞生長,舉例來說,皮膚細胞 的方式是植入微量的基因,培養它們 接著就可以採收 所以我們可以欺騙這些皮膚細胞 可以說是讓細胞罹患失憶症,讓他們變回胚胎模式 因此沒有道德爭議性,這是第一個好處 第二個好處是,你可以用它培養出任何的組織 大腦、心臟、肝臟,你們都知道的 都是出於自己的細胞 所以我們可以做出你的心臟,你的大腦的模版 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.
培育出密度和行為模式可預測的組織 是第二步驟,這個進展非常重要 使得這些模型能應用於藥物測試 這張圖是我們實驗室正在發展的生物反應器 它能提高組織工程進行時的模式性和控制性 未來,你們想像一下許多台這種儀器並聯在一起的樣子 裡面有數以千計的人類組織 就好像在晶片上面進行臨床試驗
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.
關於誘導性多功能幹細胞,還有另外一件事 那就是如果我們採集了一些皮膚細胞,例如說 從有遺傳性疾病的人身上 然後我們從中培育出一些組織 我們可以實際利用組織工程的技術 在實驗室裡培育這些疾病的模型 這個例子來自Kevin Eggin在哈佛的實驗室 他培養出神經元 從誘導性多功能幹細胞中 樣本來自Lou Gehrig症 (肌肉萎縮性側索硬化症) 的病患 他將它們分化成神經元,不可思議的是 這些神經元也反應出該疾病的症狀 所以有了這些疾病的模型,我們能以前所未有的速度 反擊它們,還能以前所未有的角度 了解它們,甚至能加快藥物研發的腳步 這是另一個例子,這種遺傳性疾病幹細胞 培育自色素性視網膜炎的患者 這種病是視網膜的衰退 這是我們家族成員常罹患的疾病,我們真的很希望 這類的幹細胞可以幫助我們找到解藥
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,有些人認為這些模型看起來完美無缺 但是他們會問: "這些細胞真的跟小白鼠一樣好用嗎?" 畢竟老鼠是完整的生物體 器官之間有完整的互動網路 用於心臟的藥會在肝臟代謝 而且有些藥效副產品可能會儲存在脂肪 這些效果在組織工程的模型上不是都看不出來嗎? 沒錯,這是這領域的另外一個研究趨勢 將組織工程的技術與微流學結合在一起 實際上,這個領域正朝這個方向發展 人體全生態系統的模型 必須包含複合的器官系統才得以測試 為了控制血壓而服用的藥物 可能會影響你的肝臟,服用抗憂鬱劑或許會影響你的心臟 這些系統很難架構,但是我們開始著手進行了 所以,等著看吧
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.
但是這還不是全部,因為一旦藥物獲得許可 組織工程的技術真的能幫助我們 使療程更符合個人需求 未來的某天你可能需要了解這些相關資訊 但是我希望這一天永遠不會來 因為你想像,自己可能接到了一通電話 帶來的是壞消息,你可能罹患癌症了 你難道不想先試用那些治療癌症的藥物 看看那些藥是否真的可以對抗你的癌症嗎? 這是Karen Burg的實驗室的例子,他們那裏 使用噴墨技術來標的乳癌細胞 並研究細胞的發展及療效 我們Tufts有幾個同事正在結合不同模型 例如結合那些組織工程研發的骨頭,觀察癌症如何 從身體這個區域擴散到下一個區域 你可以想像一下,那些包含多種組織的晶片 會在下個世代,成為這類研究的主流
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,回想我們剛剛討論的這些模型 你會發現,未來的組織工程學 有助於藥物檢驗,我們努力過程的每一步 都能使其產生突破性的變革 疾病模型可以製作出更好的藥物配方 多樣而大量的人類組織模型 有助於實驗室測試的變革 減少動物臨床測試及人類臨床測試 使療程個人化,改變我們以往的想法 認為一套療程適用於所有人 而我們實際的數據回饋 也以戲劇化的速度增加 實驗內容是培養單一分子,並研究其 在人體中的反應為何 我們的所作所為,其實就是 將生物科技跟藥理學轉換成資訊科技 幫助我們加快藥物開發與評估的速度 減少成本,提高效率 比起動物試驗,這樣的作法更有意義,不是嗎? 謝謝大家 (鼓掌)