如何通过设计全新的酶来改变世界
日期:2020-06-04 14:43

(单词翻译:单击)

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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 as they would zip around on muggy nights.
夏天,萤火虫的点点亮光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, with the Christmassy bouquet emanating from pine trees.
哪怕冬天都有自己别致的魅力,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,
当我开始攻读化学研究生,
and in later years, I came to better understand the natural world in molecular detail.
以及在后来的岁月里,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 to the bright red of cranberries and the glow of fireflies,
从丁香和松树的香气到蔓越莓的鲜红和萤火虫的亮光,
have at least one thing in common: they're manufactured by enzymes.
它们都至少有一个共同之处:是酶创造了它们。
As I said, I grew up in Wisconsin, so of course, I like cheese and the Green Bay Packers.
刚刚提到我在威斯康星州长大,我喜欢芝士再自然不过了,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 from the stomachs of cows and sheep and goats and added it to milk.
人们从牛、绵羊和山羊的胃里提取出了多种酶的混合物,并把它们添加到牛奶里。
This causes the milk to curdle -- it's part of the cheese-making process.
这会让牛奶凝固--这是制作芝士的环节之一。
The key enzyme in this mixture is called chymosin. I want to show you how that works.
在这个混合物中起关键作用的酶叫凝乳酶。我想给大家展示一下它的作用原理。
Right here, I've got two tubes, and I'm going to add chymosin to one of these. Just a second here.
在这里我有两支试管,我要往其中一支加入凝乳酶,稍等一会儿。
Now my son Anthony, who is eight years old, was very interested in helping me figure out a demo for the TED Talk,
我儿子安托尼今年8岁,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 and doing all kinds of demos in the kitchen.
从红皮马铃薯提取酶,在厨房里做了各种实验。
And in the end, though, we thought the chymosin demo was pretty cool.
最终,我们觉得凝乳酶的实验非常厉害。
And so what's happening here is the chymosin is swimming around in the milk,
在这支试管中,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 -- it's like a molecular scissors.
然后它把酪蛋白剪开--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. OK. So let me give this a quick zip.
我们就像这样在厨房里实验。好了。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. OK.
然后把它们放到一边,反应一会儿。好了。
If DNA is the blueprint of life, enzymes are the laborers that carry out its instructions.
如果说DNA是生命的蓝图,那么酶就是执行DNA指令的劳动者。
An enzyme is a protein that's a catalyst, it speeds up or accelerates a chemical reaction,
酶是一种蛋白,也是一种催化剂,它能加快化学反应速率,
just as the chymosin over here is accelerating the curdling of the milk. But it's not just about cheese.
就像这里的凝乳酶能让牛奶加速凝固。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 to attacking the biggest environmental challenges we have today.
而且在其他情况下,从婴儿的健康到克服目前最大的环境挑战,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, and we typically designate them with single-letter abbreviations,
一共有20种常见的氨基酸,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, like pearls on a necklace.
在某种酶中,这些氨基酸如同项链上的珍珠那样,被串联在一起。
And it's really the identity of the amino acids, which letters are in that necklace,
氨基酸的种类,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, this necklace, folds up into a higher-order structure.
接着,这些氨基酸,这个氨基酸项链,折叠起来形成了更高级别的结构。
And if you were to zoom in at the molecular level
如果你放大到分子大小,
and take a look at chymosin, which is the enzyme working over here, you would see it looks like this.
看看处于活跃状态的凝乳酶,你会看见它的样子是这样的。
It's all these strands and loops and helices and twists and turns,
线状,环形,螺旋,扭曲,旋转,
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, and that can be like a bacteria or a yeast, for example.
现在我们可以利用微生物制造酶,可以是细菌,或酵母菌。
And the way we do this is we get a piece of DNA that codes for an enzyme that we're interested in,
我们通过截取一小段DNA,也就是我们感兴趣的酶的代码,
we insert that into the microbe, and we let the microbe use its own machinery, its own wherewithal, to produce that enzyme for us.
再把它放进微生物中,让微生物用其自身的功能,自身的原料,来为我们制作出酶。
So if you wanted chymosin, you wouldn't need a calf, nowadays -- you could get this from a microbe.
所以现在如果你需要凝乳酶,再也不需要一头小牛犊了--大可从微生物中得到。
And what's even cooler, I think, is we can now dial in completely custom DNA sequences
我认为更棒的是,我们可以插入完全定制的DNA序列
to make whatever enzymes we want, stuff that's not out there in nature.
来制作出我们想要的,非天然存在的任意的酶。
And, to me, what's really the fun part is trying to design an enzyme for a new application, arranging the atoms just so.
对于我来说,通过排列原子来设计一种酶,带来新的应用,才是真正有趣的地方。
The act of taking an enzyme from nature and playing with those amino acids, tinkering with those letters,
从自然界中提取一种酶,然后尝试这些氨基酸的各种组合,对那些字母进行修修补补,
putting some letters in, taking some letters out, maybe rearranging them a little bit,
插入一些,抽走一些,或许再调整一下序列,
is a little bit like finding a book and editing a few chapters or changing the ending.
有点像是拿来一本书,编辑几个章节或者改写它的结局。
In 2018, the Nobel prize in chemistry was given for the development of this approach, which is known as directed evolution.
在2018年,诺贝尔化学奖就被颁发给了针对这种方法的开发工作,叫做“定向进化”。
Nowadays, we can harness the powers of directed evolution to design enzymes for custom purposes,
现在我们可以利用定向进化的力量任意地设计酶,
and one of these is designing enzymes for doing applications in new areas, like laundry.
其中一个方面就是把酶的设计应用到新的领域,比如说洗衣服。
So just as enzymes in your body can help you to break down the food that you eat,
就如大家体内的酶可以帮助你分解吃过的食物,
enzymes in your laundry detergent can help you to break down the stains on your clothes.
在你的洗衣液中的酶有助于分解衣物上的污渍。
It turns out that about 90 percent of the energy that goes into doing the wash is from water heating.
有调查表明,用于洗衣的90%的能量花在了水的加热上。
And that's for good reason -- the warmer water helps to get your clothes clean.
这是有原因的--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?
You certainly would save some money, and in addition to that, according to some calculations done by Procter and Gamble,
那肯定能省下不少钱,除此之外,根据宝洁公司的一些研究,
if all households in the US were to do the laundry in cold water,
如果美国的所有家庭都用冷水进行洗涤,
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, that's about the equivalent of the carbon dioxide emitted by 6.3 million cars.
这可不是一个小数目啊,相当于630万量汽车的碳排放量。
So, how would we go about designing an enzyme to realize these changes?
那么我们怎样设计酶来实现这一转变呢?
Enzymes didn't evolve to clean dirty laundry, much less in cold water.
酶不会自己进化到拥有清洁脏衣物的能力,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, some clay that we can work with.
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。
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, putting some letters in, taking some letters out, rearranging those.
就如我刚提到的,我们可以从这些氨基酸入手,插入一些,抽走一些,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, and we can test them in little plates like this.
我们可以拿出这些酶,在这样的小碟子上进行测试。
So this plate that I'm holding in my hands contains 96 wells, and in each well is a piece of fabric with a stain on it.
我手上拿着的这只盒子上面有96个槽,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 are able to remove the stains from the pieces of fabric,
我们可以测量每一种酶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, like you'll see in just a second on the screen.
我们可以借助机器人来实现这一操作,待会儿大家可以在屏幕上看到。
OK, so we do this, and it turns out that some of the enzymes are sort of in the ballpark of the starting enzyme.
那么,我们做了这个实验,结果一些酶落在起始酶的候选范围中。
That's nothing to write home about. Some are worse, so we get rid of those.
这并没什么值得大书特书的。一些表现很差,于是被我们淘汰了。
And then some are better. Those improved ones become our version 1.0s.
一些表现得还不错。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, and we can repeat this cycle again and again.
它们是我们想要继续研究的酶,我们可以一遍又一遍地重复这个过程。

如何通过设计全新的酶来改变世界

And it's the repetition of this cycle that lets us come up with a new enzyme, something that can do what we want.
这些循环让我们制造出了一种新的酶,可以帮助我们实现目标的酶。
And after several cycles of this, we did come up with something new.
在多次循环之后,我们制造出了一种新的东西。
So you can go to the supermarket today, and you can buy a laundry detergent
现在你可以到超市里买到这种洗衣液,
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, and these are both milk again.
我有两支试管,里面还是牛奶。
And let me show you, I've got one that I'm going to add this enzyme to and one that I'm going to add some water to.
看好了,我要往其中一支加入这种酶,往另外一支加一些水。
And that's the control, so nothing should happen in that tube.
作为控制组,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 is because milk is just loaded with proteins,
我这么做的原因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, that's its job.
因为它是一种厉害的蛋白质剪刀手,天职所在。
So let me get this in here. And you know, as I said, it's a master protein chopper
我现在放它进去了。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 to what it would be doing in your laundry.
现在你可以推想一下它跟牛奶会发生什么反应,它跟你的脏衣服就有可能产生什么反应。
So this is kind of a way to visualize what would be happening. OK, so those both went in.
我们在将这个过程可视化。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, so I'm going to come back to those toward the end.
现在把这两个试管跟凝乳酶样本放到一边。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?
Certainly, it will get it faster -- there are now approaches for evolving enzymes
可以肯定的是,它的发展会越来越快--现在有各种促使酶进化的手段,
that allow researchers to go through far more samples than I just showed you.
能让研究员研究更多的样本比我刚展示的多得多。
And in addition to tinkering with natural enzymes, like we've been talking about,
除了我们刚刚谈到的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, to inform their enzyme designs.
一种人工智能的方法,从零开始设计酶,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, the common amino acids, before
我们刚谈到20种天然的氨基酸,常见的氨基酸,
they're adding unnatural amino acids to make enzymes with properties unlike those that could be found in nature.
有些科学家通过添加非天然的氨基酸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: human health and the environment.
我想重点谈谈两个方面:人类健康以及环境。
Some pharmaceutical companies now have teams that are dedicated to designing enzymes
一些医药公司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, which is a medication to treat type 2 diabetes, is made partially with enzymes.
举个例子,西他列汀是一种用来治疗二型糖尿病的药物,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, there are certain disorders in which a single enzyme in a person's body doesn't work properly.
另一方面,对于某些失调性的疾病,单一酶在病人体内不能正常工作。
An example of this is called phenylketonuria, or PKU for short.
其中一个例子是苯丙酮尿症,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, so it's a scary thing to have.
他们会患有永久的智力残疾,那是非常可怕的疾病。
Now, those of you with kids -- do you guys have kids, here, which ones have kids? A lot of you.
在座为人父母的观众,在座的有孩子吗?有很多啊。
So may be familiar with PKUs, because all infants in the US are required to be tested for PKU.
你们也许对PKU挺熟悉的,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, but PKU's on another level of toughness.
安托尼对坚果过敏,我已经觉得够受的了,但是PKU的严重度可是另一个级别的。
However, new enzymes may soon enable PKU patients to eat whatever they want.
然而新的酶可能很快能让苯丙酮尿症病人敞开怀抱去吃东西。
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, and it's actually very big news for the field of enzyme-replacement therapy more generally,
对病人来说是特大喜讯,对酶替代疗法的领域同样是特大喜讯,
because there are other targets out there where this would be a good approach.
因为对于其他目标病症来说,这也可能是个好的方法。
So that was a little bit about health. Now I'm going to move to the environment.
有关健康的话题就到这里。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, somewhere between California and Hawaii
顺便解释一下,那就像是一个塑料巨岛,就在加州和夏威夷之间某个地方,
and about microplastics pretty much everywhere, it's upsetting.
微塑料几乎无处不在,实在令人不安。
Plastics aren't going away anytime soon. But enzymes may help us in this area as well.
塑料可不会很快就消失掉。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 of these enzymes.
并已经在努力设计和改良这些酶。
At the same time, there are enzymes that have been discovered and that are being optimized to make non-petroleum-derived biodegradable plastics.
与此同时,人们还发现并优化了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, such as carbon dioxide, methane and nitrous oxide.
酶也可能有助于吸收温室气体,比如说二氧化碳、甲烷和一氧化二氮。
Now, there is no doubt, these are major challenges, and none of them are easy.
毫无疑问,这些是我们面临的主要挑战,并且都很困难。
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,
so I think that's another area to be looking forward.
我认为这是值得期待的另一个领域。
So now I'm going to get back to the demo -- this is the fun part.
现在我要回到演示部分--见证奇迹的时刻到了。
So we'll start with the chymosin samples. So let me get these over here.
我们先从凝乳酶样本开始吧。让我把它们拿过来。
And you can see here, this is the one that got the water, so nothing should happen to this milk.
你可以看到,这是加了水的,牛奶不应该有任何变化。
This is the one that got the chymosin. So you can see that it totally clarified up here.
这是加了凝乳酶的。你可以看到上面的部分变清了。
There's all this curdled stuff, that's cheese, we just made cheese in the last few minutes.
下面凝固的部分,就是芝士,我们刚在短短几分钟内制作出了芝士。
So this is that reaction that people have been doing for thousands and thousands of years.
这就是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 but they can be a tough crowd, so we'll see.
我打算在我们下一个《带孩子上班日》中做这个实验,但那可能会是一批挑剔的观众,走着瞧吧。
And then the other one I want to look at is this one. So this is the enzyme for doing your laundry.
另外一组结果在这里。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, and that's just what you want for an enzyme in your laundry,
它变得有点清了,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 that can be a protein chowhound, just chew them up,
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,
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,
like chocolate milk or grass stains, for example, and something like this is going to help you get them off.
比如说巧克力牛奶或草污渍,这种酶能帮你干掉这些污渍。
And this is also going to be the thing that allows you to do the wash in cold water,
它也能让你在冷水中洗净衣物,
reduce your carbon footprint and save you some money.
减少碳足迹,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 to the present day and enzyme design.
想想从7000年传统的芝士制作到今天的酶设计。
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 or write our own stories with amino acids.
有了酶,我们可以编辑自然已经写下的篇章,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 and you see a firefly, I hope you think of enzymes.
那么下次你在闷热潮湿的夜里外出的时候,当你看到一只萤火虫,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, they could be doing even more amazing things tomorrow. Thank you.
通过设计,在未来它们会变得威力无穷。谢谢大家。

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