How designing brand-new enzymes could change the world | Adam Garske

Translator: Ivana Korom Reviewer: Krystian Aparta

翻译人员: Archi Xiao 校对人员: psjmz mz

Growing up in central Wisconsin, I spent a lot of time outside.

我在威斯康星州中部长大， 曾在户外度过很多时光。

In the spring, I'd smell the heady fragrance of lilacs.

春天，四周满溢着 令人心动的丁香的香气。

In the summer, I loved the electric glow of fireflies

夏天，萤火虫的点点亮光

as they would zip around on muggy nights.

在闷热潮湿的夜里摇曳。

In the fall, the bogs were brimming with the bright red of cranberries.

秋天，泥塘里满是 鲜红的蔓越莓。

Even winter had its charms,

哪怕冬天都有自己别致的魅力，

with the Christmassy bouquet emanating from pine trees.

松树上装点着圣诞花束。

For me, nature has always been a source of wonder and inspiration.

对于我来说，自然一直是 神奇与灵感的源泉。

As I went on to graduate school in chemistry, and in later years,

当我开始攻读化学研究生， 以及在后来的岁月里，

I came to better understand the natural world in molecular detail.

我从分子层面 对自然有了更深入的了解。

All the things that I just mentioned,

我刚刚所提到的一切，

from the scents of lilacs and pines

从丁香和松树的香气

to the bright red of cranberries and the glow of fireflies,

到蔓越莓的鲜红和 萤火虫的亮光，

have at least one thing in common:

它们都至少有一个共同之处：

they're manufactured by enzymes.

是酶创造了它们。

As I said, I grew up in Wisconsin, so of course, I like cheese

刚提到我在威斯康星州长大， 我喜欢芝士再自然不过了，

and the Green Bay Packers.

当然还有绿湾包装工 橄榄球队。

But let's talk about cheese for a minute.

但让我们先谈谈芝士。

For at least the last 7,000 years,

在过去至少 7000 年里，

humans have extracted a mixture of enzymes

人们从牛、绵羊和山羊的胃里

from the stomachs of cows and sheep and goats

提取出了多种酶的混合物，

and added it to milk.

并把它们添加到牛奶里，

This causes the milk to curdle -- it's part of the cheese-making process.

让牛奶凝固—— 这是制作芝士的环节之一。

The key enzyme in this mixture is called chymosin.

在这个混合物中起关键作用 的酶叫凝乳酶。

I want to show you how that works.

我想给大家展示一下 它的作用原理。

Right here, I've got two tubes,

在这里我有两支试管，

and I'm going to add chymosin to one of these.

我要往其中一支加入凝乳酶，

Just a second here.

稍等一会儿。

Now my son Anthony, who is eight years old,

我儿子安托尼今年 8 岁，

was very interested in helping me figure out a demo for the TED Talk,

他很热心帮我为这场演讲 准备实验展示环节。

and so we were in the kitchen, we were slicing up pineapples,

我们在厨房里切菠萝，

extracting enzymes from red potatoes

从红皮马铃薯提取酶，

and doing all kinds of demos in the kitchen.

在厨房里做了各种实验。

And in the end, though,

最终，

we thought the chymosin demo was pretty cool.

我们觉得凝乳酶的实验 非常厉害。

在这支试管中，

And so what's happening here

is the chymosin is swimming around in the milk,

凝乳酶正在牛奶里畅游，

and it's binding to a protein there called casein.

它在和里面的酪蛋白结合。

What it does then is it clips the casein --

然后它把酪蛋白剪开——

it's like a molecular scissors.

就像是一把分子剪刀。

It's that clipping action that causes the milk to curdle.

正是这个剪开的动作 促使牛奶凝固。

So here we are in the kitchen, working on this.

我们就像这样在厨房里实验。

OK.

好了。

So let me give this a quick zip.

让我快速地摇晃一下。

And then we'll set these to the side and let these simmer for a minute.

然后把它们放到一边， 反应一会儿。

OK.

好了。

If DNA is the blueprint of life,

如果说 DNA 是生命的蓝图，

enzymes are the laborers that carry out its instructions.

那么酶就是执行 DNA 指令的劳动者。

An enzyme is a protein that's a catalyst,

酶是一种蛋白， 也是一种催化剂，

it speeds up or accelerates a chemical reaction,

它能加快化学反应速率，

just as the chymosin over here is accelerating the curdling of the milk.

就像这里的凝乳酶 能让牛奶加速凝固。

But it's not just about cheese.

可这并不仅仅可以 用于芝士的制作。

While enzymes do play an important role in the foods that we eat,

酶在我们的食品中 也起着关键的作用，

they also are involved in everything from the health of an infant

而且在其他情况下， 从婴儿的健康

to attacking the biggest environmental challenges

到克服目前最大的环境挑战，

we have today.

它同样功不可没。

The basic building blocks of enzymes are called amino acids.

酶的基本构成单位叫氨基酸。

There are 20 common amino acids,

一共有 20 种常见的氨基酸，

and we typically designate them with single-letter abbreviations,

我们通常用单个字母的缩写 来给他们命名，

so it's really an alphabet of amino acids.

就像是氨基酸的字母表。

In an enzyme, these amino acids are strung together,

在某种酶中，这些氨基酸 如同项链上的珍珠那样，

like pearls on a necklace.

被串联在一起。

And it's really the identity of the amino acids,

氨基酸的种类，

which letters are in that necklace,

也就是项链上的字母，

and in what order they are, what they spell out,

及其排列、拼写的顺序，

that gives an enzyme its unique properties and differentiates it from other enzymes.

赋予了某种酶独特的属性， 将其与其他酶区分开来。

Now, this string of amino acids,

接着，这些氨基酸，

这个氨基酸项链，

this necklace,

folds up into a higher-order structure.

折叠起来形成了更高级别的结构。

如果你放大到分子大小，

And if you were to zoom in at the molecular level

and take a look at chymosin, which is the enzyme working over here,

看看处于活跃状态的凝乳酶，

你会看见它的样子是这样的。

you would see it looks like this.

线状，环形，螺旋，扭曲，旋转，

It's all these strands and loops and helices and twists and turns,

and it has to be in just this conformation to work properly.

酶必须在这样的形态下才能起作用。

Nowadays, we can make enzymes in microbes,

现在我们可以利用微生物制造酶，

and that can be like a bacteria or a yeast, for example.

可以是细菌，或酵母菌。

And the way we do this is we get a piece of DNA

我们通过截取一小段 DNA，

that codes for an enzyme that we're interested in,

也就是我们感兴趣的酶的代码，

we insert that into the microbe,

再把它放进微生物中，

and we let the microbe use its own machinery, its own wherewithal,

让微生物用其自身的功能， 自身的原料，

to produce that enzyme for us.

来为我们制作出酶。

So if you wanted chymosin, you wouldn't need a calf, nowadays --

所以现在如果你需要凝乳酶， 再也不需要一头小牛犊了——

you could get this from a microbe.

大可从微生物中得到。

我认为更棒的是，

And what's even cooler, I think,

is we can now dial in completely custom DNA sequences

我们可以插入完全定制的 DNA 序列

来制作出我们想要的，

to make whatever enzymes we want,

stuff that's not out there in nature.

非天然存在的任意的酶。

And, to me, what's really the fun part

对于我来说通过排列原子

is trying to design an enzyme for a new application,

来设计一种酶，带来新的应用，

arranging the atoms just so.

才是真正有趣的地方。

The act of taking an enzyme from nature and playing with those amino acids,

从自然界中提取一种酶， 然后尝试这些氨基酸的各种组合，

tinkering with those letters,

对那些字母进行修修补补，

插入一些，抽走一些，

putting some letters in, taking some letters out,

maybe rearranging them a little bit,

或许再调整一下序列，

有点像是拿来一本书，

is a little bit like finding a book

and editing a few chapters or changing the ending.

编辑几个章节或者改写它的结局。

In 2018, the Nobel prize in chemistry

在 2018 年，诺贝尔化学奖

was given for the development of this approach,

就被颁发给了 针对这种方法的开发工作，

which is known as directed evolution.

叫做“定向进化”。

Nowadays, we can harness the powers of directed evolution

现在我们可以利用定向进化的力量

to design enzymes for custom purposes,

任意地设计酶，

and one of these is designing enzymes for doing applications in new areas,

其中一个方面 就是把酶的设计应用到新的领域，

like laundry.

比如说洗衣服。

So just as enzymes in your body

就如大家体内的酶

can help you to break down the food that you eat,

可以帮助你分解吃过的食物，

enzymes in your laundry detergent

在你的洗衣液中的酶

can help you to break down the stains on your clothes.

有助于分解衣物上的污渍。

It turns out that about 90 percent of the energy

有调查表明，用于洗衣的

that goes into doing the wash

90% 的能量

is from water heating.

花在了水的加热上。

And that's for good reason --

这是有原因的——

the warmer water helps to get your clothes clean.

水温更高有助于清洁衣物。

But what if you were able to do the wash in cold water instead?

但是如果你可以用冷水 达到同样的效果呢？

那肯定能省下不少钱，

You certainly would save some money,

除此之外，

and in addition to that,

according to some calculations done by Procter and Gamble,

根据宝洁公司的一些研究，

如果美国的所有家庭 都用冷水进行洗涤，

if all households in the US were to do the laundry in cold water,

we would save the emissions of 32 metric tons of CO2 each year.

我们每年能减少 32 公吨的二氧化碳排放。

That's a lot,

这可不是一个小数目啊，

that's about the equivalent

相当于

of the carbon dioxide emitted by 6.3 million cars.

630 万量汽车的碳排放量。

So, how would we go about designing an enzyme

那么我们怎样设计酶

to realize these changes?

来实现这一转变呢？

Enzymes didn't evolve to clean dirty laundry,

酶不会自己进化到 拥有清洁脏衣物的能力，

much less in cold water.

更不要说在冷水中。

But we can go to nature, and we can find a starting point.

但是我们可以求助于自然， 找到着手点。

We can find an enzyme that has some starting activity,

我们可以找到一种 带有起始活动的酶，

就像可以被加工的一些黏土，

some clay that we can work with.

So this is an example of such an enzyme, right here on the screen.

屏幕上显示的正是这样的一种酶。

And we can start playing with those amino acids, as I said,

就如我刚提到的， 我们可以从这些氨基酸入手，

putting some letters in, taking some letters out,

插入一些，抽走一些，

rearranging those.

重新安排序列。

And in doing so, we can generate thousands of enzymes.

通过这些操作， 我们可以制造成千上万种酶。

And we can take those enzymes,

我们可以拿出这些酶，

and we can test them in little plates like this.

在这样的小碟子上进行测试。

So this plate that I'm holding in my hands

我手上拿着的这只盒子

contains 96 wells,

上面有 96 个槽，

and in each well is a piece of fabric with a stain on it.

每个槽里面有一块 沾有污渍的布料。

And we can measure how well each of these enzymes

我们可以测量每一种酶

are able to remove the stains from the pieces of fabric,

对于去除布料上污渍的效果，

and in that way see how well it's working.

那样就可以知道它们是否有效。

And we can do this using robotics,

我们可以借助机器人 来实现这一操作，

like you'll see in just a second on the screen.

待会儿大家可以在屏幕上看到。

OK, so we do this, and it turns out

那么，我们做了这个实验，

that some of the enzymes are sort of in the ballpark

结果一些酶落在

of the starting enzyme.

起始酶的候选范围中。

That's nothing to write home about.

这并没什么值得大书特书的。

Some are worse, so we get rid of those.

一些表现很差， 于是被我们淘汰了。

And then some are better.

一些表现得还不错。

Those improved ones become our version 1.0s.

那些经改良的酶 成为了我们的 1.0 版本。

Those are the enzymes that we want to carry forward,

它们是我们想要继续研究的酶，

and we can repeat this cycle again and again.

我们可以一遍又一遍地 重复这个过程。

And it's the repetition of this cycle that lets us come up with a new enzyme,

这些循环让我们 制造出了一种新的酶，

something that can do what we want.

可以帮助我们实现目标的酶。

And after several cycles of this,

在多次循环之后，

we did come up with something new.

我们制造出了一种新的东西。

现在你可以到超市里 买到这种洗衣液，

So you can go to the supermarket today, and you can buy a laundry detergent

that lets you do the wash in cold water because of enzymes like this here.

里面就有这样的酶， 能在冷水中清洁衣物。

And I want to show you how this one works too.

接着我想给大家展示其中的原理。

So I've got two more tubes here,

我有两支试管，

and these are both milk again.

里面还是牛奶。

And let me show you,

看好了，

I've got one that I'm going to add this enzyme to

我要往其中一支加入这种酶，

and one that I'm going to add some water to.

往另外一支加一些水。

And that's the control,

作为控制组，

so nothing should happen in that tube.

应该不会有任何的变化。

You might find it curious that I'm doing this with milk.

你也许会好奇为什么 我用牛奶来做实验。

But the reason that I'm doing this

我这么做的原因

is because milk is just loaded with proteins,

是因为牛奶里有大量的蛋白质，

and it's very easy to see this enzyme working in a protein solution,

在蛋白质溶液里 更容易观察到酶的作用，

because it's a master protein chopper,

因为它是一种厉害的蛋白质剪刀手，

that's its job.

天职所在。

So let me get this in here.

我现在放它进去了。

And you know, as I said, it's a master protein chopper

就如我刚说的， 这是一把厉害的蛋白质剪刀手，

and what you can do is you can extrapolate what it's doing in this milk

现在你可以推想一下 它跟牛奶会发生什么反应，

to what it would be doing in your laundry.

它跟你的脏衣服 就有可能产生什么反应。

我们在将这个过程可视化。

So this is kind of a way to visualize what would be happening.

OK, so those both went in.

好了，现在两个试管准备好了。

And I'm going to give this a quick zip as well.

我再来快速摇晃一下。

OK, so we'll let these sit over here with the chymosin sample,

现在把这两个试管跟凝乳酶 样本放到一边。

so I'm going to come back to those toward the end.

临近尾声的时候我再谈谈它们。

Well, what's on the horizon for enzyme design?

那么酶设计的前景如何呢？

可以肯定的是， 它的发展会越来越快——

Certainly, it will get it faster --

there are now approaches for evolving enzymes

现在有各种促使酶进化的手段，

that allow researchers to go through far more samples

能让研究员研究更多的样本

比我刚展示的多得多。

than I just showed you.

And in addition to tinkering with natural enzymes,

除了我们刚刚谈到的，

like we've been talking about,

对自然界的酶进行修修补补之外，

some scientists are now trying to design enzymes from scratch,

一些科学家正着手利用机器学习——

using machine learning, an approach from artificial intelligence,

一种人工智能的方法—— 从零开始设计酶，

to inform their enzyme designs.

并了解酶设计的进展。

Still others are adding unnatural amino acids to the mix.

其他人则是添加 一些非天然的氨基酸。

We talked about the 20 natural amino acids,

我们刚谈到 20 种天然的氨基酸，

the common amino acids, before --

常见的氨基酸——

they're adding unnatural amino acids

有些科学家通过添加 非天然的氨基酸

to make enzymes with properties unlike those that could be found in nature.

来制造出拥有跟自然界被发现的酶 不一样属性的酶。

That's a pretty neat area.

那是个相当高明的领域。

How will designed enzymes affect you in years to come?

那么人工设计的酶 在未来对你有什么影响呢？

Well, I want to focus on two areas:

我想重点谈谈两个方面：

human health and the environment.

人类健康以及环境。

Some pharmaceutical companies

一些医药公司

now have teams that are dedicated to designing enzymes

已经有专门设计酶的团队，

to make drugs more efficiently and with fewer toxic catalysts.

用更少的有毒催化剂 来更高效地生产药物。

For example, Januvia,

举个例子，西他列汀

which is a medication to treat type 2 diabetes,

是一种用来治疗 二型糖尿病的药物，

is made partially with enzymes.

它的一部分成分是酶。

The number of drugs made with enzymes is sure to grow in the future.

含有酶的药物数量 在未来肯定会有所增长。

In another area,

另一方面，

there are certain disorders

对于某些失调性的疾病，

单一酶在病人体内不能正常工作。

in which a single enzyme in a person's body doesn't work properly.

其中一个例子是苯丙酮尿症，

An example of this is called phenylketonuria,

or PKU for short.

或者简称 PKU。

People with PKU are unable to properly metabolize or digest phenylalanine,

苯丙酮尿症病人不能正常地 代谢或消化苯丙氨酸，

which is one of the 20 common amino acids that we've been talking about.

那是我们刚刚提到的 20 种常见氨基酸的一种。

The consequence of ingesting phenylalanine for people with PKU

苯丙酮尿症病人 无法消化苯丙氨酸的后果是，

is that they are subject to permanent intellectual disabilities,

他们会患有永久的智力残疾，

so it's a scary thing to have.

那是非常可怕的疾病。

Now, those of you with kids --

在座为人父母的观众——

do you guys have kids, here, which ones have kids?

在座的有孩子吗？

A lot of you.

有很多啊。

So may be familiar with PKUs,

你们也许对 PKU 挺熟悉的，

because all infants in the US are required to be tested for PKU.

因为在美国，所有婴儿 都被要求进行 PKU 检测。

I remember when Anthony, my son, had his heel pricked to test for it.

我记得我儿子安托尼接受检测的时候， 脚后跟被扎了一下。

The big challenge with this is: What do you eat?

这后面最大的挑战是： 你能吃什么？

Phenylalanine is in so many foods, it's incredibly hard to avoid.

很多食物都含有苯丙氨酸， 几乎避无可避。

Now, Anthony has a nut allergy, and I thought that was tough,

安托尼对坚果过敏， 我已经觉得够受的了，

but PKU's on another level of toughness.

但是 PKU 的严重度 可是另一个级别的。

However, new enzymes may soon enable PKU patients

然而新的酶可能很快 能让苯丙酮尿症病人

to eat whatever they want.

敞开怀抱去吃东西。

Recently, the FDA approved an enzyme designed to treat PKU.

最近，美国药物总局刚批准了 被设计用来治疗 PKU 的酶。

This is big news for patients,

对病人来说是特大喜讯，

and it's actually very big news

对酶替代疗法的领域

for the field of enzyme-replacement therapy more generally,

同样是特大喜讯，

因为对于其他目标病症来说， 这也可能是个好的方法。

because there are other targets out there where this would be a good approach.

So that was a little bit about health.

有关健康的话题就到这里。

Now I'm going to move to the environment.

接下来我想谈谈环境。

When I read about the Great Pacific Garbage Patch --

当我了解到大太平洋垃圾带的时候——

by the way, that's, like, this huge island of plastic,

顺便解释一下， 那就像是一个塑料巨岛，

somewhere between California and Hawaii --

就在加州和夏威夷之间某个地方——

and about microplastics pretty much everywhere,

微塑料几乎无处不在，

it's upsetting.

实在令人不安。

Plastics aren't going away anytime soon.

塑料可不会很快就消失掉。

But enzymes may help us in this area as well.

但是酶可能在这个领域帮到我们。

Recently, bacteria producing plastic-degrading enzymes were discovered.

最近，人们发现了 由细菌产生的塑料降解酶，

Efforts are already underway to design improved versions

并已经在努力设计

和改良这些酶。

of these enzymes.

At the same time, there are enzymes that have been discovered

与此同时，人们还发现

and that are being optimized

并优化了

to make non-petroleum-derived biodegradable plastics.

不以石油为原料的可生物降解塑料。

Enzymes may also offer some help in capturing greenhouse gases,

酶也可能有助于吸收温室气体，

such as carbon dioxide, methane and nitrous oxide.

比如说二氧化碳、 甲烷和一氧化二氮。

Now, there is no doubt, these are major challenges,

毫无疑问，这些是我们 面临的主要挑战，

and none of them are easy.

且都很困难。

But our ability to harness enzymes may help us to tackle these in the future,

但是我们运用酶的能力 可能有助于在未来克服这些挑战，

我认为这是值得期待 的另一个领域。

so I think that's another area to be looking forward.

So now I'm going to get back to the demo --

现在我要回到演示部分——

this is the fun part.

见证奇迹的时刻到了。

So we'll start with the chymosin samples.

我们先从凝乳酶样本开始吧。

So let me get these over here.

让我把它们拿过来。

And you can see here,

你可以看到，

this is the one that got the water,

这是加了水的，

so nothing should happen to this milk.

牛奶不应该有任何变化。

This is the one that got the chymosin.

这是加了凝乳酶的。

So you can see that it totally clarified up here.

你可以看到上面的部分变清了。

There's all this curdled stuff, that's cheese,

下面凝固的部分，就是芝士。

we just made cheese in the last few minutes.

我们刚在短短几分钟内制作出了芝士。

So this is that reaction

这就是

that people have been doing for thousands and thousands of years.

我们做了几千年的事情。

I'm thinking about doing this one at our next Kids to Work Day demo

我打算在我们下一个 《带孩子上班日》中做这个实验，

but they can be a tough crowd, so we'll see.

但那可能会是一批挑剔 的观众，走着瞧吧。

(Laughter)

（笑声）

And then the other one I want to look at is this one.

另外一组结果在这里。

So this is the enzyme for doing your laundry.

这是帮你清洁衣物的酶。

And you can see that it's different than the one that has the water added.

你可以看到跟加了水的那个不一样。

It's kind of clarifying,

它变得有点清了，

and that's just what you want for an enzyme in your laundry,

这就是你洗衣服的时候想要的效果，

because you want to be able to have an enzyme

因为你需要一种酶，

能够像一头蛋白质猎犬那样 把蛋白质咬碎，

that can be a protein chowhound, just chew them up,

because you're going to get different protein stains on your clothes,

因为衣服上有不同的蛋白质污渍，

比如说巧克力牛奶或草污渍，

like chocolate milk or grass stains, for example,

and something like this is going to help you get them off.

这种酶能帮你干掉这些污渍。

And this is also going to be the thing that allows you

它也能让你

在冷水中洗净衣物，减少碳足迹，

to do the wash in cold water, reduce your carbon footprint

and save you some money.

还能帮你省钱。

Well, we've come a long way,

这一切来之不易，

considering this 7,000-year journey from enzymes in cheese making

想想从 7000 年 传统的芝士制作到

to the present day and enzyme design.

今天的酶设计。

We're really at a creative crossroads,

我们此刻正站在创造的十字路口，

and with enzymes, can edit what nature wrote

有了酶，我们可以编辑 自然已经写下的篇章，

or write our own stories with amino acids.

或者用氨基酸 来谱写我们自己的故事。

So next time you're outdoors on a muggy night

那么下次你在闷热潮湿的夜里 外出的时候，

and you see a firefly,

当你看到一只萤火虫，

I hope you think of enzymes.

我希望你能想起酶。

They're doing amazing things for us today.

它们在今天为我们做出了 很多突出的贡献。

And by design,

通过设计，

they could be doing even more amazing things tomorrow.

在未来它们会变得威力无穷。

Thank you.

谢谢大家。

(Applause)

（掌声）