演讲MP3+双语文稿:人类正在创造全新的蛋白质，应对 5 大健康挑战

听力课堂TED音频栏目主要包括TED演讲的音频MP3及中英双语文稿，供各位英语爱好者学习使用。本文主要内容为演讲MP3+双语文稿:人类正在创造全新的蛋白质，应对 5 大健康挑战，希望你会喜欢！

【演讲者及介绍】David Baker

大卫·贝克——计算生物学家David Baker从基本原理出发设计了新的生物分子(蛋白质)，以应对21世纪健康和技术方面的挑战。

【演讲主题】我们可以通过设计新的蛋白质来解决5个挑战

【中英文字幕】

翻译者Yanyan Hong 校对者 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.

我想要向你们分享的是 世界上最惊奇的机理，以及我们现在能用它们做些什么。蛋白质， 基本上负责运行我们 身体中所有重要的功能。蛋白质能帮助你消化食物，收缩你的肌肉，激发你的神经元，以及为你的免疫系统提供能量。在生物学上，发生的一切—— 几乎一切—— 归功于蛋白质。

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.

蛋白质是线性链，其组件就是氨基酸。大自然使用了 20 个 氨基酸组成的字母表，其中的一些名称你或许听说过。 氨基酸之间的化学作用力 会导致这些长而细的分子 折叠成独一无二的三维结构。折叠变化的过程，虽然看似随机，但实际上非常精确。每个蛋白质每次都会 折叠成它的特有形状，以及整个折叠的过程仅一秒都不到。而蛋白质的形状 使它们能够产生非凡的生物功能。例如，血红蛋白在肺部的形状非常适合 用于结合氧分子。当血红蛋白进入你的肌肉时，形状会略有改变，氧气随之释放。

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.

蛋白质的形状，以及由此产生的非凡功能，完全由蛋白质链中的氨基酸序列决定。 你基因组中的基因决定了 你的蛋白质分子的氨基酸序列。每个基因编码形成 一个蛋白质的氨基酸序列。这些氨基酸序列 和结构之间的转换 以及蛋白质的功能 被称为蛋白质分子折叠问题。这是一个非常复杂的问题，因为一个蛋白质分子有太多 不同的形状可以采用。因为其复杂性，人类只能通过对我们在自然界中发现的 蛋白质的氨基酸序列 进行微小调整来利用蛋白质的力量。

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.

这类似于我们石器时代的祖先 用我们在周围世界发现的 木棍和石头制造工具 和其他器械的过程。但人类从未通过改造鸟类 来学习飞行。

02:51

(Laughter)

（笑声）

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，科学家们受鸟类启发 揭示了空气动力学的原理。然后，工程师们利用这些原理 来设计定制的飞行器。以同样的方式，通过多年的研究，我们已经揭示蛋白质折叠的基本原理，把这些原理编码在一个叫 Rosetta 的计算机程序中。近年来，我们取得了突破，我们现在可以在电脑上，从头开始设计全新的蛋白质。一旦我们设计出新型的蛋白质，我们把它的氨基酸序列 编码在一个合成基因中。我们必须合成基因，因为蛋白质是全新的，地球上任何现存的生物中 都不存在能够编码它的基因。

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.

蛋白质折叠的研究进展 以及如何设计新型蛋白质，再加上基因合成成本的降低，和摩尔定律提高了的计算机能力，这些都让我们现在能够 设计数万种新型蛋白质，它们有着新的形状，以及新的功能，在电脑上，并编码合成基因中的每一个分子。一旦我们有了这些合成基因，我们把它们放进细菌中，让它们制造出全新的蛋白质。然后我们提取这些蛋白质，并确定它们是否就像 我们设想的那样起作用，以及它们是否安全。

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.

能制造出新型蛋白质 真的很令人激动，因为尽管大自然极具多样性，自然界的进化过程只产生了可能 生成蛋白质总量的一小部分。之前提到，大自然使用 20 个 氨基酸组成的字母表，一个标准的蛋白质是 由 100 个氨基酸组成的链，所以总的可能性是 20 x 20 x 20，这样重复一百次，这是一个 10 的 130 次方的数字，这远远超过了地球生命伊始时 存在的蛋白质的总数。而且它是一个难以想象的大空间，我们现在可以通过计算机 蛋白质设计进行探索。

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.

现在地球上存在的蛋白质 自行进化来面对 大自然进化所产生的问题。例如，再生基因组。但现今我们面临着各种新的挑战。人类的寿命正在延长，所以应对新的疾病很重要。我们的地球正面对着污染 和全球变暖，因此，我们面临着一系列的生态挑战。如果我们还有一百万年可以等待，那么新的蛋白质或许 会为我们解决这些挑战。但是我们并没有一百万年可以等待，相反，通过计算机蛋白质设计，我们现在可以设计新型蛋白质 来应对这些挑战。

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.

我们的大胆想法是 把生物学带出石器时代 通过技术革命来设计新型蛋白质。我们已经证明我们 可以设计出新的蛋白质，有着新的形状及功能。例如，疫苗通过刺激你的 免疫系统来发挥作用，让其做出强烈的反应对抗病原体。为了制造更好的疫苗，我们设计了蛋白质颗粒，我们可以从病原体中融合蛋白质， 为了制造真正充满 病毒蛋白的候选疫苗，我们发现这样的候选疫苗 对病毒产生了比以往测试过的 任何疫苗更强大的免疫反应。 我们还设计出了新型蛋白质 来分解你胃里的麸质，用以治疗乳糜泻，以及其他刺激免疫系统 用以对抗癌症的蛋白质。这些进展成效标志着 蛋白质设计革命的开始。

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.

我们受到了先前技术革命的启发： 数字革命，在很大程度上是 受一个地方的推动，那就是贝尔实验室。贝尔实验室是一个开放、协作的环境，能够吸引到世界各地的顶尖人才。它领导了一系列非凡的创新—— 晶体管、激光器、卫星通信，以及互联网的基础。我们的目标是建立能有助于 蛋白质设计的贝尔实验室。我们正致力于吸引 来自世界各地的天才科学家 来加速蛋白质设计革命，我们将专注于应对 5 大挑战。

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，从世界各地的 流感菌株中提取蛋白质，把它们放置于设计好的蛋白质颗粒上， 我们的目标是制造 一种通用的流感疫苗，一次注射就可以起到 终生预防流感的作用。设计的能力——

08:07

(Applause)

（掌声）

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.

在计算机上设计新疫苗的能力 对预防自然性流感的流行，以及人为的生物恐怖主义都很重要 。

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，我们要超越大自然 有限的字母表，其中只有 20 种氨基酸，转为使用由数千种 氨基酸组成的字母表 来为慢性疼痛等疾病 设计新的治疗方案。

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，我们正在制造 先进的药物输送载体 ，以使现有的药物 能够精确定位体内的目标。例如，对肿瘤的化疗，或者对需要进行基因修复的 组织进行基因治疗。

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，我们正在设计 能在体内进行计算的智能疗法。远远超越当前医疗水平，现在我们使用的 还是较为迟缓的仪器。例如，仅针对一小部分免疫细胞，这些免疫细胞是造成 自身免疫紊乱的原因，从而将其与大多数健康 免疫细胞区分开来。

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，受非凡生物材料的启发，如，丝绸、鲍鱼壳、牙齿等，我们正在设计新型蛋白质材料，用以解决能源和生态问题方面的挑战。

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.

为了实现这一切，我们正在发展我们的研究所。我们致力于吸引来自世界各地，处于任何职业生涯阶段的 富有活力、才华横溢、 多样性的科学人才们 加入我们。您也可以加入蛋白质设计革命，通过我们的在线折叠和设计游戏，“Foldit”。和我们的分布式网络计算项目 rosetta@home，您可以通过笔记本电脑 或安卓智能手机获取。

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.

通过蛋白质设计 使世界变得更好是我一生的工作。我很激动我们能够一同携手。我期待各位的加入，谢谢大家。

10:15

(Applause and cheers)

（掌声和欢呼）