演講MP3+雙語文稿:人類正在創(chuàng)造全新的蛋白質(zhì)，應(yīng)對 5 大健康挑戰(zhàn)

聽力課堂TED音頻欄目主要包括TED演講的音頻MP3及中英雙語文稿，供各位英語愛好者學(xué)習(xí)使用。本文主要內(nèi)容為演講MP3+雙語文稿:人類正在創(chuàng)造全新的蛋白質(zhì)，應(yīng)對 5 大健康挑戰(zhàn)，希望你會喜歡！

【演講者及介紹】David Baker

大衛(wèi)·貝克——計算生物學(xué)家David Baker從基本原理出發(fā)設(shè)計了新的生物分子(蛋白質(zhì))，以應(yīng)對21世紀(jì)健康和技術(shù)方面的挑戰(zhàn)。

【演講主題】我們可以通過設(shè)計新的蛋白質(zhì)來解決5個挑戰(zhàn)

【中英文字幕】

翻譯者Yanyan Hong 校對者 Cissy Yun

00:13

I'm going to tell you about the most amazing machines in the world and what we can now do with them. Proteins, 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.

我想要向你們分享的是 世界上最驚奇的機(jī)理，以及我們現(xiàn)在能用它們做些什么。蛋白質(zhì)， 基本上負(fù)責(zé)運行我們 身體中所有重要的功能。蛋白質(zhì)能幫助你消化食物，收縮你的肌肉，激發(fā)你的神經(jīng)元，以及為你的免疫系統(tǒng)提供能量。在生物學(xué)上，發(fā)生的一切—— 幾乎一切—— 歸功于蛋白質(zhì)。

00:40

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. 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(zhì)是線性鏈，其組件就是氨基酸。大自然使用了 20 個 氨基酸組成的字母表，其中的一些名稱你或許聽說過。 氨基酸之間的化學(xué)作用力 會導(dǎo)致這些長而細(xì)的分子 折疊成獨一無二的三維結(jié)構(gòu)。折疊變化的過程，雖然看似隨機(jī)，但實際上非常精確。每個蛋白質(zhì)每次都會 折疊成它的特有形狀，以及整個折疊的過程僅一秒都不到。而蛋白質(zhì)的形狀 使它們能夠產(chǎn)生非凡的生物功能。例如，血紅蛋白在肺部的形狀非常適合 用于結(jié)合氧分子。當(dāng)血紅蛋白進(jìn)入你的肌肉時，形狀會略有改變，氧氣隨之釋放。

01:40

The shapes of proteins, and hence their remarkable functions, are completely specified by the sequence of amino acids in the protein chain. 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(zhì)的形狀，以及由此產(chǎn)生的非凡功能，完全由蛋白質(zhì)鏈中的氨基酸序列決定。 你基因組中的基因決定了 你的蛋白質(zhì)分子的氨基酸序列。每個基因編碼形成 一個蛋白質(zhì)的氨基酸序列。這些氨基酸序列 和結(jié)構(gòu)之間的轉(zhuǎn)換 以及蛋白質(zhì)的功能 被稱為蛋白質(zhì)分子折疊問題。這是一個非常復(fù)雜的問題，因為一個蛋白質(zhì)分子有太多 不同的形狀可以采用。因為其復(fù)雜性，人類只能通過對我們在自然界中發(fā)現(xiàn)的 蛋白質(zhì)的氨基酸序列 進(jìn)行微小調(diào)整來利用蛋白質(zhì)的力量。

02:35

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.

這類似于我們石器時代的祖先 用我們在周圍世界發(fā)現(xiàn)的 木棍和石頭制造工具 和其他器械的過程。但人類從未通過改造鳥類 來學(xué)習(xí)飛行。

02:51

(Laughter)

（笑聲）

02:53

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，科學(xué)家們受鳥類啟發(fā) 揭示了空氣動力學(xué)的原理。然后，工程師們利用這些原理 來設(shè)計定制的飛行器。以同樣的方式，通過多年的研究，我們已經(jīng)揭示蛋白質(zhì)折疊的基本原理，把這些原理編碼在一個叫 Rosetta 的計算機(jī)程序中。近年來，我們?nèi)〉昧送黄?，我們現(xiàn)在可以在電腦上，從頭開始設(shè)計全新的蛋白質(zhì)。一旦我們設(shè)計出新型的蛋白質(zhì)，我們把它的氨基酸序列 編碼在一個合成基因中。我們必須合成基因，因為蛋白質(zhì)是全新的，地球上任何現(xiàn)存的生物中 都不存在能夠編碼它的基因。

03:42

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.

蛋白質(zhì)折疊的研究進(jìn)展 以及如何設(shè)計新型蛋白質(zhì)，再加上基因合成成本的降低，和摩爾定律提高了的計算機(jī)能力，這些都讓我們現(xiàn)在能夠 設(shè)計數(shù)萬種新型蛋白質(zhì)，它們有著新的形狀，以及新的功能，在電腦上，并編碼合成基因中的每一個分子。一旦我們有了這些合成基因，我們把它們放進(jìn)細(xì)菌中，讓它們制造出全新的蛋白質(zhì)。然后我們提取這些蛋白質(zhì)，并確定它們是否就像 我們設(shè)想的那樣起作用，以及它們是否安全。

04:24

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.

能制造出新型蛋白質(zhì) 真的很令人激動，因為盡管大自然極具多樣性，自然界的進(jìn)化過程只產(chǎn)生了可能 生成蛋白質(zhì)總量的一小部分。之前提到，大自然使用 20 個 氨基酸組成的字母表，一個標(biāo)準(zhǔn)的蛋白質(zhì)是 由 100 個氨基酸組成的鏈，所以總的可能性是 20 x 20 x 20，這樣重復(fù)一百次，這是一個 10 的 130 次方的數(shù)字，這遠(yuǎn)遠(yuǎn)超過了地球生命伊始時 存在的蛋白質(zhì)的總數(shù)。而且它是一個難以想象的大空間，我們現(xiàn)在可以通過計算機(jī) 蛋白質(zhì)設(shè)計進(jìn)行探索。

05:08

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(xiàn)在地球上存在的蛋白質(zhì) 自行進(jìn)化來面對 大自然進(jìn)化所產(chǎn)生的問題。例如，再生基因組。但現(xiàn)今我們面臨著各種新的挑戰(zhàn)。人類的壽命正在延長，所以應(yīng)對新的疾病很重要。我們的地球正面對著污染 和全球變暖，因此，我們面臨著一系列的生態(tài)挑戰(zhàn)。如果我們還有一百萬年可以等待，那么新的蛋白質(zhì)或許 會為我們解決這些挑戰(zhàn)。但是我們并沒有一百萬年可以等待，相反，通過計算機(jī)蛋白質(zhì)設(shè)計，我們現(xiàn)在可以設(shè)計新型蛋白質(zhì) 來應(yīng)對這些挑戰(zhàn)。

05:48

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,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. 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 把生物學(xué)帶出石器時代 通過技術(shù)革命來設(shè)計新型蛋白質(zhì)。我們已經(jīng)證明我們 可以設(shè)計出新的蛋白質(zhì)，有著新的形狀及功能。例如，疫苗通過刺激你的 免疫系統(tǒng)來發(fā)揮作用，讓其做出強烈的反應(yīng)對抗病原體。為了制造更好的疫苗，我們設(shè)計了蛋白質(zhì)顆粒，我們可以從病原體中融合蛋白質(zhì)， 為了制造真正充滿 病毒蛋白的候選疫苗，我們發(fā)現(xiàn)這樣的候選疫苗 對病毒產(chǎn)生了比以往測試過的 任何疫苗更強大的免疫反應(yīng)。 我們還設(shè)計出了新型蛋白質(zhì) 來分解你胃里的麩質(zhì)，用以治療乳糜瀉，以及其他刺激免疫系統(tǒng) 用以對抗癌癥的蛋白質(zhì)。這些進(jìn)展成效標(biāo)志著 蛋白質(zhì)設(shè)計革命的開始。

07:01

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.

我們受到了先前技術(shù)革命的啟發(fā)： 數(shù)字革命，在很大程度上是 受一個地方的推動，那就是貝爾實驗室。貝爾實驗室是一個開放、協(xié)作的環(huán)境，能夠吸引到世界各地的頂尖人才。它領(lǐng)導(dǎo)了一系列非凡的創(chuàng)新—— 晶體管、激光器、衛(wèi)星通信，以及互聯(lián)網(wǎng)的基礎(chǔ)。我們的目標(biāo)是建立能有助于 蛋白質(zhì)設(shè)計的貝爾實驗室。我們正致力于吸引 來自世界各地的天才科學(xué)家 來加速蛋白質(zhì)設(shè)計革命，我們將專注于應(yīng)對 5 大挑戰(zhàn)。

07:46

First, by taking proteins from flu strains from around the world and putting them on top of the designed protein particles , 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，從世界各地的 流感菌株中提取蛋白質(zhì)，把它們放置于設(shè)計好的蛋白質(zhì)顆粒上， 我們的目標(biāo)是制造 一種通用的流感疫苗，一次注射就可以起到 終生預(yù)防流感的作用。設(shè)計的能力——

08:07

(Applause)

（掌聲）

08:12

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.

在計算機(jī)上設(shè)計新疫苗的能力 對預(yù)防自然性流感的流行，以及人為的生物恐怖主義都很重要 。

08:26

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.

第二，我們要超越大自然 有限的字母表，其中只有 20 種氨基酸，轉(zhuǎn)為使用由數(shù)千種 氨基酸組成的字母表 來為慢性疼痛等疾病 設(shè)計新的治療方案。

08:39

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，我們正在制造 先進(jìn)的藥物輸送載體 ，以使現(xiàn)有的藥物 能夠精確定位體內(nèi)的目標(biāo)。例如，對腫瘤的化療，或者對需要進(jìn)行基因修復(fù)的 組織進(jìn)行基因治療。

08:55

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(shè)計 能在體內(nèi)進(jìn)行計算的智能療法。遠(yuǎn)遠(yuǎn)超越當(dāng)前醫(yī)療水平，現(xiàn)在我們使用的 還是較為遲緩的儀器。例如，僅針對一小部分免疫細(xì)胞，這些免疫細(xì)胞是造成 自身免疫紊亂的原因，從而將其與大多數(shù)健康 免疫細(xì)胞區(qū)分開來。

09:17

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.

最后，受非凡生物材料的啟發(fā)，如，絲綢、鮑魚殼、牙齒等，我們正在設(shè)計新型蛋白質(zhì)材料，用以解決能源和生態(tài)問題方面的挑戰(zhàn)。

09:34

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.

為了實現(xiàn)這一切，我們正在發(fā)展我們的研究所。我們致力于吸引來自世界各地，處于任何職業(yè)生涯階段的 富有活力、才華橫溢、 多樣性的科學(xué)人才們 加入我們。您也可以加入蛋白質(zhì)設(shè)計革命，通過我們的在線折疊和設(shè)計游戲，“Foldit”。和我們的分布式網(wǎng)絡(luò)計算項目 rosetta@home，您可以通過筆記本電腦 或安卓智能手機(jī)獲取。

10:05

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.

通過蛋白質(zhì)設(shè)計 使世界變得更好是我一生的工作。我很激動我們能夠一同攜手。我期待各位的加入，謝謝大家。

10:15

(Applause and cheers)

（掌聲和歡呼）