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I'm a protein designer. And I'd like to discuss a new type of medicine.
我是一名蛋白质设计师。我想跟大家谈谈一种新型药物。
It's made from a molecule called a constrained peptide.
它是由一种名为限制性肽的分子构成的。
There are only a few constrained peptide drugs available today,
现在市面上只有少量限制性肽药物，
but there are a lot that will hit the market in the coming decade.
但是在接下来的十年里将会有更多这样的药物面世。
Let's explore what these new medicines are made of,
我们来看看这些新药是由什么构成的，
how they're different and what's causing this incoming tidal wave of new and exciting medicines.
有什么不同，以及是什么正掀起一场崭新又振奋人心的药物浪潮。
Constrained peptides are very small proteins.
限制性肽是非常小的蛋白质分子。
They've got extra chemical bonds that constrain the shape of the molecule,
它们拥有额外的化学键来约束分子结构，
and this makes them incredibly stable as well as highly potent.
因此它们异常稳定，效力强大。
They're naturally occurring, our bodies actually produce a few of these
它们是天然生成的分子，人体自身就会产生一些限制肽
that help us to combat bacterial, fungal and viral infections.
来帮助我们对抗细菌、真菌和病毒感染。
And animals like snakes and scorpions use constrained peptides in their venom.
像蛇和蝎子一类的动物，它们的毒液里也含有限制性肽。
Drugs that are made of protein are called biologic drugs.
由蛋白质制成的药物被称为生物药品。
So this includes constrained peptides, as well as medicines like insulin or antibody drugs like Humira or Enbrel.
其中包括限制性肽，还有胰岛素，或者抗体药物，如修美乐或恩博。
And in general, biologics are great, because they avoid several ways that drugs can cause side effects.
一般来说，生物药品很好，因为它们能避免若干药物引发的副作用。
First, protein. It's a totally natural, nontoxic material in our bodies.
首先，我们来说说蛋白质。它是我们体内纯天然、无毒性的物质。
Our cells produce tens of thousands of different proteins, and basically, all of our food has protein in it.
我们的细胞能合成成千上万种不同的蛋白质，我们的食物基本都含有蛋白质。
And second, sometimes drugs interact with molecules in your body that you don't want them to.
第二，有时候药物会跟你体内的分子反应，这是你不希望发生的。
Compared to small molecule drugs, and by this I mean regular drugs, like aspirin, biologics are quite large.
相比起小分子药物，这里我指的是阿司匹林之类的常规药物，生物药品分子挺大的。
Molecules interact when they adopt shapes that fit together perfectly. Much like a lock and key.
当分子的形状能天衣无缝地契合，它们便会相互作用。就像是锁配钥匙一样。
Well, a larger key has more grooves, so it's more likely to fit into a single lock.
一把较大的钥匙有更多的沟槽，因此很可能只匹配单个锁。
But most biologics also have a flaw. They're fragile.
但是多数生物药品都有一个缺陷。它们往往比较脆弱。
So they're usually administered by injection,
因此通常是注射给药，
because our stomach acid would destroy the medicine if we tried to swallow it.
因为当我们试图口服的时候，胃酸可能会让药物失效。
Constrained peptides are the opposite. They're really durable, like regular drugs.
限制性肽刚好相反。它们跟常规药一样很耐久。
So it's possible to administer them using pills, inhalers, ointments.
因此给药方式可以是药丸、气雾剂、药膏。
This is what makes constrained peptides so desirable for drug development.
这正是限制性肽在药物开发中备受青睐的原因。
They combine some of the best features of small-molecule and biologic drugs into one.
它们把小分子药和生物药品最好的一些特征合为一体。
But unfortunately, it's incredibly difficult to reengineer the constrained peptides that we find in nature to become new drugs.
但不幸的是，要想重组自然界中的限制性肽，将其制成新药，是异常困难的。
So this is where I come in. Creating a new drug is a lot like crafting a key to fit a particular lock.
这就是我的领域了。创造一种新型药物就好像是为某把特定的锁打造匹配的钥匙。
We need to get the shape just right.
我们需要把形状设置的刚刚好。
But if we change the shape of a constrained peptide by too much,
但是如果我们过度改变限制性肽的形状，
those extra chemical bonds are unable to form and the whole molecule falls apart.
那些额外的化学键便无法形成，整个分子结构也会随之瓦解。
So we needed to figure out how to gain control over their shape.
因此我们得解决如何控制好它们的形状的问题。
I was part of a collaborative scientific effort that spanned a dozen institutions across three continents
我当时是来自三大洲的十几个机构组成的一个科研合作小组中的一员，
that came together and solved this problem.
我们聚在一起，来解决这个问题。
We took a radically different approach from previous efforts.
我们采取了与之前的尝试截然不同的方法。
Instead of making changes to the constrained peptides that we find in nature,
我们并没有选择改变天然的限制性肽，
we figured out how to build new ones totally from scratch.
而是发现了如何从零开始制造全新的限制性肽。
To help us do this, we developed freely available open-source peptide-design software that anyone can use to do this, too.
为了达到目标，我们开发了免费开源的限制性肽设计软件，任何人都可以使用。
To test our method out, we generated a series of constrained peptides that have a wide variety of different shapes.
为了测试我们的方法，我们生成了一系列限制性肽，形状不一、种类繁多。
Many of these had never been seen in nature before.
其中很多是自然界前所未有的。
Then we went into the laboratory and produced these peptides.
接着我们到实验室制造这些限制性肽。
Next, we determined their molecular structures, using experiments.
接下来，我们用实验确定了它们的分子结构。
When we compared our designed models with the real molecular structures,
当我们将自己所设计的模型跟真实的分子结构作对比的时候，
we found that our software can position individual atoms with an accuracy that's at the limit of what's possible to measure.
我们发现该软件能以可测量的最大精度来设计单个原子的位置。
Three years ago, this couldn't be done.
这在三年前是不可能办到的。
But today, we have the ability to create designer peptides with shapes that are custom-tailored for drug development.
但是今天，我们拥有制造设计肽的能力，能为药物开发定制（限制肽的）形状。
So where is this technology taking us?
那么这项技术将引导我们前往何方？
Well, recently, my colleagues and I designed constrained peptides that neutralize influenza virus,
最近，我和同事们设计出了能消除流感病毒、
protect against botulism poisoning and block cancer cells from growing.
能防止肉毒杆菌中毒、能抑制癌细胞增长的限制性肽。
Some of these new drugs have been tested in preclinical trials with laboratory animals.
其中一些新型药物已经在实验室里用动物进行了临床前试验。
And so far, they're all safe and highly effective.
目前来看，它们都很安全，且非常高效。
Constrained peptide design is a cutting-edge technology, and the drug development pipeline is slow and cautious.
限制性肽设计是一项前沿技术，同时药物开发的进程漫长而谨慎。
So we're still three to five years out from human trials.
因此我们还需三到五年才能开始人体试验。
But during that time, more constrained peptide drugs are going to be entering the drug development pipeline.
但与此同时，有更多的限制性肽药物将进入药物开发进程中。
And ultimately, I believe that designed peptide drugs
最终，我相信限制性肽药物
are going to enable us all to break free from the constraints of our diseases. Thank you.
将让我们从疾病的枷锁中得到彻底的解放。谢谢大家。
