I'm going to tell you about the most amazing machines in the world and what we can now do with them. Proteins, some of which you see inside a cell here, carry out essentially all the important functions in our bodies. Proteins digest your food, contract your muscles, fire your neurons and power your immune system. Everything that happens in biology -- almost -- happens because of proteins.
我將講述世界上最神奇的機器 以及我們現在能用它來做什麼。 你在細胞中看到的一些蛋白質, 基本上在我們體內 執行所有重要的功能。 蛋白質可消化食物、 收縮肌肉、 激發神經元, 為免疫系統提供動力。 生物學中發生的一切, 幾乎全都因蛋白質而發生。
Proteins are linear chains of building blocks called amino acids. Nature uses an alphabet of 20 amino acids, some of which have names you may have heard of. In this picture, for scale, each bump is an atom. Chemical forces between the amino acids cause these long stringy molecules to fold up into unique, three-dimensional structures. The folding process, while it looks random, is in fact very precise. Each protein folds to its characteristic shape each time, and the folding process takes just a fraction of a second. And it's the shapes of proteins which enable them to carry out their remarkable biological functions. For example, hemoglobin has a shape in the lungs perfectly suited for binding a molecule of oxygen. When hemoglobin moves to your muscle, the shape changes slightly and the oxygen comes out.
蛋白質是由稱為「氨基酸」的 積木構成的線性鏈。 大自然用了 20 種氨基酸字母, 你們可能聽過其中若干名稱。 這圖中比例相對的 每個凹凸都是個原子。 氨基酸間的化學力 使這些長而細的分子 折疊成獨特的立體結構。 雖然折疊的過程看似隨機, 實際上非常的精確。 蛋白質總是折疊成其特徵的形狀, 而折疊的過程只需幾分之一秒。 蛋白質的形狀 使其能夠發揮卓越的生物功能。 例如, 肺裡的血紅蛋白 具有完全適合結合氧分子的形狀。 當血紅蛋白移到肌肉時, 形狀會稍微改變, 釋出氧氣。
The shapes of proteins, and hence their remarkable functions, are completely specified by the sequence of amino acids in the protein chain. In this picture, each letter on top is an amino acid. Where do these sequences come from? The genes in your genome specify the amino acid sequences of your proteins. Each gene encodes the amino acid sequence of a single protein. The translation between these amino acid sequences and the structures and functions of proteins is known as the protein folding problem. It's a very hard problem because there's so many different shapes a protein can adopt. Because of this complexity, humans have only been able to harness the power of proteins by making very small changes to the amino acid sequences of the proteins we've found in nature.
蛋白質的形狀及其奇妙的功能 完全由蛋白質鏈的氨基酸序列所定。 這張圖片頂部的每個字母都是氨基酸。 這些序列來自哪裡? 基因組中的基因 訂定蛋白質的氨基酸序列。 每個基因 為單個蛋白質的氨基酸序列編碼。 這些氨基酸序列 與蛋白質的結構和功能之間的翻譯 被稱為蛋白質的折疊問題。 這是個非常困難的問題, 因為蛋白質能有許多不同的形狀。 由於它這麼複雜, 人類只能透由稍微更動 自然界蛋白質的氨基酸序列 來利用蛋白質的能量。
This is similar to the process that our Stone Age ancestors used to make tools and other implements from the sticks and stones that we found in the world around us. But humans did not learn to fly by modifying birds.
這相當於石器時代祖先用來製作 我們在周遭世界發現的 木棒、石製工具和其他工具的過程。 但是人類並非透由 修改鳥類來學習飛行。
(Laughter)
(笑聲)
Instead, scientists, inspired by birds, uncovered the principles of aerodynamics. Engineers then used those principles to design custom flying machines. In a similar way, we've been working for a number of years to uncover the fundamental principles of protein folding and encoding those principles in the computer program called Rosetta. We made a breakthrough in recent years. We can now design completely new proteins from scratch on the computer. Once we've designed the new protein, we encode its amino acid sequence in a synthetic gene. We have to make a synthetic gene because since the protein is completely new, there's no gene in any organism on earth which currently exists that encodes it.
相反地,受鳥類啟發的科學家 發現氣體動力學的原理, 接著工程師用這些原理 來設計和製作飛行機器。 多年來,我們已經用類似的方式 揭示蛋白質折疊的基本原理, 並用名為 Rosetta 的 電腦軟體將這些原理編碼。 我們近年來有了突破, 能夠在電腦上從頭開始 設計全新的蛋白質。 一旦設計出新的蛋白質, 我們就會在合成基因中 將其氨基酸序列編碼。 我們必須合成基因 是因為蛋白質是全新的, 目前地球上沒有任何生物體 有它的基因編碼。
Our advances in understanding protein folding and how to design proteins, coupled with the decreasing cost of gene synthesis and the Moore's law increase in computing power, now enable us to design tens of thousands of new proteins, with new shapes and new functions, on the computer, and encode each one of those in a synthetic gene. Once we have those synthetic genes, we put them into bacteria to program them to make these brand-new proteins. We then extract the proteins and determine whether they function as we designed them to and whether they're safe.
我們在理解蛋白質的折疊 和如何設計蛋白質方面取得的進展, 加上基因合成費用的降低, 以及符合摩爾定律提高的運算能力, 使我們現在能夠設計出成千上萬種 具有新形狀和新功能的新蛋白質, 在電腦上設計, 並編碼合成每個基因。 一旦擁有這些合成的基因, 我們將其置入細菌, 讓它們製造這些全新的蛋白質。 然後我們提取蛋白質, 看它們的功能是否符合我們的設計, 以及它們是否安全。
It's exciting to be able to make new proteins, because despite the diversity in nature, evolution has only sampled a tiny fraction of the total number of proteins possible. I told you that nature uses an alphabet of 20 amino acids, and a typical protein is a chain of about 100 amino acids, so the total number of possibilities is 20 times 20 times 20, 100 times, which is a number on the order of 10 to the 130th power, which is enormously more than the total number of proteins which have existed since life on earth began. And it's this unimaginably large space we can now explore using computational protein design.
能製造新的蛋白質令人振奮, 因為儘管自然界多姿多樣, 卻只演化出 所有可能的蛋白質 總數中的一小部分。 我說過大自然用了 20 個氨基酸字母, 典型的蛋白質是 大約 100 個氨基酸的長鏈, 所以可能性的總數 是 20 乘以 20 乘以 20, 乘 100 次, 是 10 的 130 次方, 遠遠超過自地球出現生命以來 曾經存在過的蛋白質總數。 而這正是我們現在能用運算能力 來設計和探索蛋白質的 難以想像的廣大空間。
Now the proteins that exist on earth evolved to solve the problems faced by natural evolution. For example, replicating the genome. But we face new challenges today. We live longer, so new diseases are important. We're heating up and polluting the planet, so we face a whole host of ecological challenges. If we had a million years to wait, new proteins might evolve to solve those challenges. But we don't have millions of years to wait. Instead, with computational protein design, we can design new proteins to address these challenges today.
現存地球的蛋白質以進化 來解決自然演化所面臨的問題。 例如,複製基因組。 但我們今天面臨新的挑戰。 我們活得更長, 因此新疾病極其重要。 我們正污染地球和令其升溫, 因此面臨著一系列的生態挑戰。 如果我們能等百萬年, 新的蛋白質演化 或許能解決這些挑戰。 但我們無法等上百萬年。 取而代之,透由運算來設計蛋白質, 我們能設計新的蛋白質 來對付當前的挑戰。
Our audacious idea is to bring biology out of the Stone Age through technological revolution in protein design. We've already shown that we can design new proteins with new shapes and functions. For example, vaccines work by stimulating your immune system to make a strong response against a pathogen. To make better vaccines, we've designed protein particles to which we can fuse proteins from pathogens, like this blue protein here, from the respiratory virus RSV. To make vaccine candidates that are literally bristling with the viral protein, we find that such vaccine candidates produce a much stronger immune response to the virus than any previous vaccines that have been tested. This is important because RSV is currently one of the leading causes of infant mortality worldwide. We've also designed new proteins to break down gluten in your stomach for celiac disease and other proteins to stimulate your immune system to fight cancer. These advances are the beginning of the protein design revolution.
我們的大膽想法 是透由蛋白質設計的技術革命 帶生物學跳脫石器時代。 我們已經證明能夠設計出 具有新形狀、新功能的新蛋白質。 例如,疫苗透由刺激免疫系統 對病原體產生強烈的反應作用。 為了製造更好的疫苗, 我們設計蛋白質顆粒 來融合病原體中的蛋白質—— 就像此處藍色的蛋白質, 取自呼吸道融合病毒 RSV。 (Respiratory Syncytial Virus) 為確認候選的疫苗 真的含有病毒蛋白, 我們發現這候選疫苗 對病毒的免疫反應 勝過先前已經測試過的任何疫苗。 這很重要,因為 呼吸道融合病毒 RSV 目前是全球嬰兒夭折的主要原因之一。 我們還設計新的蛋白質 來分解胃中的麩質, 對付腹腔疾病; 也設計其他的蛋白質 來刺激免疫系統對抗癌症。 這些進步是蛋白質設計革命的開始。
We've been inspired by a previous technological revolution: the digital revolution, which took place in large part due to advances in one place, Bell Laboratories. Bell Labs was a place with an open, collaborative environment, and was able to attract top talent from around the world. And this led to a remarkable string of innovations -- the transistor, the laser, satellite communication and the foundations of the internet. Our goal is to build the Bell Laboratories of protein design. We are seeking to attract talented scientists from around the world to accelerate the protein design revolution, and we'll be focusing on five grand challenges.
我們受先前技術革命的啟發。 數位革命大大歸功於 貝爾實驗室所取得的進步。 貝爾實驗室是個開放、協作的環境, 吸引世界各地的頂尖人才。 這引領一系列的創新: 電晶體、雷射、衛星通信 和網際網路的基礎。 我們的目標是建立 蛋白質設計的貝爾實驗室。 我們正尋求吸引 世界各地的優秀科學家 來一起加速蛋白質設計的革命, 我們將專注於五大挑戰。
First, by taking proteins from flu strains from around the world and putting them on top of the designed protein particles I showed you earlier, we aim to make a universal flu vaccine, one shot of which gives a lifetime of protection against the flu. The ability to design --
首先經由從世界各地的流感病毒株中 提取蛋白質, 並將它們放在我之前展示的 蛋白質設計顆粒的頂部, 我們著眼於製造 一種通用的流感疫苗, 打一針就能保護終生免於流感。 設計能力——
(Applause)
(掌聲)
The ability to design new vaccines on the computer is important both to protect against natural flu epidemics and, in addition, intentional acts of bioterrorism.
在電腦上設計新疫苗的能力 對於防止自然的流感疫情 和防範刻意的生物恐攻都很重要。
Second, we're going far beyond nature's limited alphabet of just 20 amino acids to design new therapeutic candidates for conditions such as chronic pain, using an alphabet of thousands of amino acids.
其次,我們用遠遠超出大自然 有限的 20 個氨基酸字母 來設計新的治療候選藥物, 來對付像是慢性疼痛, 用的是數千種氨基酸字母。
Third, we're building advanced delivery vehicles to target existing medications exactly where they need to go in the body. For example, chemotherapy to a tumor or gene therapies to the tissue where gene repair needs to take place.
第三,我們正在建立先進的載運工具, 以便將現有的藥物準確定位在 它們應該進入的體內位置。 例如,腫瘤的化療, 或修復組織的基因治療。
Fourth, we're designing smart therapeutics that can do calculations within the body and go far beyond current medicines, which are really blunt instruments. For example, to target a small subset of immune cells responsible for an autoimmune disorder, and distinguish them from the vast majority of healthy immune cells.
第四,我們正在設計 能在體內運算的智慧療法, 遠遠超出目前的藥物, 那些是非常遲鈍的藥物。 例如,目標對準 造成自身免疫疾病的 一小部分免疫細胞, 將其與絕大多數 健康的免疫細胞區隔開來。
Finally, inspired by remarkable biological materials such as silk, abalone shell, tooth and others, we're designing new protein-based materials to address challenges in energy and ecological issues.
最後,靈感來自 絲綢、鮑魚殼、牙齒等 非凡的生物材料, 以及其他材料, 我們正在設計新的蛋白質基底材料, 以對付能源和生態問題的挑戰。
To do all this, we're growing our institute. We seek to attract energetic, talented and diverse scientists from around the world, at all career stages, to join us. You can also participate in the protein design revolution through our online folding and design game, "Foldit." And through our distributed computing project, Rosetta@home, which you can join from your laptop or your Android smartphone.
為要做到這一切, 我們正在擴展我們機構。 我們尋求吸引世界各地 精力充沛、才華橫溢、 多元的科學家—— 涵蓋所有的職涯階段—— 來加入我們。 你還可以透由我們線上的 折疊和設計遊戲「Foldit」 參與蛋白質設計革命。 透由我們的分散式運算專案 Rosetta@home, 可以在筆記型電腦 或安卓智慧手機上操作。
Making the world a better place through protein design is my life's work. I'm so excited about what we can do together. I hope you'll join us, and thank you.
透由設計蛋白質使世界變得更好 是我的終生職志。 我們能一起做點什麼的想法 深深鼓舞著我。 希望你能加入我們。 謝謝。
(Applause and cheers)
(掌聲)