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

Translator: Ivana Korom Reviewer: Krystian Aparta

譯者: Pei-Chen Benson Liu 審譯者: 易帆 余

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

我在威斯康辛州中部長大 很常待在戶外

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

春天時，我會聞聞 紫丁香醉人的花香

In the summer, I loved the electric glow of fireflies

夏天時，螢火蟲 在悶熱的夜晚疾疾飛行

as they would zip around on muggy nights.

發散出閃閃火光，深得我心

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

秋天時，鮮紅色的莓果佈滿了泥塘

Even winter had its charms,

即使是冬天

松樹散發聖誕節氣息也令人陶醉其中

with the Christmassy bouquet emanating from pine trees.

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

大自然總是令我感到驚奇 又處處充滿靈感

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

我一路讀到化學研究所，幾年過後

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

我對於大自然的分子結構 瞭解愈加詳細

All the things that I just mentioned,

我剛提到的事物

from the scents of lilacs and pines

從紫丁香和松果的香氣

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

到莓果的鮮紅色澤、螢火蟲的閃爍光點

have at least one thing in common:

都至少有一個共通點：

they're manufactured by enzymes.

全都是酵素作用後的結果

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

我剛提到，我在威斯康辛州長大

所以當然很愛吃起司 也支持綠灣包裝工

and the Green Bay Packers.

But let's talk about cheese for a minute.

我們接著來聊聊起司

For at least the last 7,000 years,

少說 7,000 年前開始

humans have extracted a mixture of enzymes

人們就從乳牛、綿羊、山羊 這些動物的胃裡

from the stomachs of cows and sheep and goats

萃取出綜合類型的酵素

and added it to milk.

接著加進乳品裡

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

乳品會因此凝結

這便是製作起司的環節之一

The key enzyme in this mixture is called chymosin.

當中的關鍵酵素是凝乳酶

I want to show you how that works.

讓我帶著大家看看如何運作

Right here, I've got two tubes,

這裡有兩根試管

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

接著在其中一根試管中加入凝乳酶

Just a second here.

然後稍待一下

Now my son Anthony, who is eight years old,

我兒子叫安東尼 ，今年八歲

他一直在幫我想辦法

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

如何在這次的 TED Talk 做示範

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

所以我們在廚房花了點時間

切了鳳梨

extracting enzymes from red potatoes

又從紅薯中提煉了酵素

and doing all kinds of demos in the kitchen.

試了好多不同的方法

And in the end, though,

最後我們決定

we thought the chymosin demo was pretty cool.

用凝乳酶來示範再有趣不過了

And so what's happening here

在這根試管裡

is the chymosin is swimming around in the milk,

凝乳酶在牛奶中四處遊走

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

吸附其中一種蛋白質，名為酪蛋白

What it does then is it clips the casein --

凝乳酶就像是一把分子剪刀

it's like a molecular scissors.

會切斷酪蛋白

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

正是這個切斷的動作讓牛奶凝結

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

我們那時在廚房就是在忙這件事

OK.

好的

So let me give this a quick zip.

我先把試管封上

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

接著放在旁邊醞釀一陣子

OK.

好的

If DNA is the blueprint of life,

若說 DNA 是生命的藍圖

enzymes are the laborers that carry out its instructions.

那酵素便是執行指令的勞工

An enzyme is a protein that's a catalyst,

酵素這種蛋白質是催化劑

it speeds up or accelerates a chemical reaction,

能讓化學反應加速

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

像是這邊的凝乳酶 正在讓牛奶更快凝結

But it's not just about cheese.

起司只是其中一個例子

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

酵素不僅對食物來說很重要

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

在其他地方更是隨處可見

像是維持嬰兒健康或 打擊現今最棘手的環境問題

to attacking the biggest environmental challenges

we have today.

The basic building blocks of enzymes are called amino acids.

酵素的基本結構是胺基酸

There are 20 common amino acids,

常見的胺基酸有 20 種

and we typically designate them with single-letter abbreviations,

通常用個別字母縮寫來命名

so it's really an alphabet of amino acids.

所以胺基酸種類 其實就像是英文字母

In an enzyme, these amino acids are strung together,

酵素裡的胺基酸相互串在一塊

like pearls on a necklace.

如珍珠項鍊一般

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

每種酵素的特性和相異之處

which letters are in that necklace,

取決於這條項鍊裡有哪些字母

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

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

還有這些字母的排列順序 和拼出來的樣子

Now, this string of amino acids,

這一串胺基酸

或說這一串項鍊

this necklace,

folds up into a higher-order structure.

會摺疊成更繁複的結構

如果把凝乳酶放大到分子大小

And if you were to zoom in at the molecular level

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

也就是此處的酵素

會是長這個樣子

you would see it looks like this.

滿是纏繞的線段和扭曲的螺旋

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.

並且一定得要是如此結構

酵素才能正常運作

Nowadays, we can make enzymes in microbes,

現代科技能透過細菌或酵母

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

這樣的微生物製造酵素

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

要製作我們有興趣的酵素時

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

需要擷取酵素原出處的 DNA

we insert that into the microbe,

將其植入微生物之中

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

接著微生物會用自身的機制

to produce that enzyme for us.

為我們製造出酵素

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

所以如果今天需要凝乳酶

就再也不需要一整頭牛

you could get this from a microbe.

只需微生物即可

And what's even cooler, I think,

我認為更有趣的是

is we can now dial in completely custom DNA sequences

現在我們可以植入 任何特製的 DNA 序列

我們也能創造出來

to make whatever enzymes we want,

stuff that's not out there in nature.

大自然中沒有的酵素

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

對我來說，真正好玩的地方是

is trying to design an enzyme for a new application,

試著設計出有新用途的酵素

arranging the atoms just so.

排列著微小的物質

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

從大自然取得酵素、 任意移動胺基酸、

tinkering with those letters,

修飾那些英文字母、

putting some letters in, taking some letters out,

把一些字母放進去、又取一些出來

maybe rearranging them a little bit,

或是稍微更動順序

is a little bit like finding a book

這些動作就好像是找一本書來

and editing a few chapters or changing the ending.

接著改編一些章節或修改結局

In 2018, the Nobel prize in chemistry

2018 年，諾貝爾化學獎就是頒發給

was given for the development of this approach,

發展相關技術的科學家

which is known as directed evolution.

這項技術也稱為定向進化

Nowadays, we can harness the powers of directed evolution

現今人們可以操控定向進化

to design enzymes for custom purposes,

為了特定目的設計酵素

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

其中也有些設計能應用在新的領域

like laundry.

像是洗衣服這件事

So just as enzymes in your body

就像是身體裡的酵素

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

幫忙分解吃下去的食物一樣

enzymes in your laundry detergent

洗衣精裡的酵素

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

會幫忙分解衣服上的污漬

It turns out that about 90 percent of the energy

其實洗衣服消耗的能源

that goes into doing the wash

有百分之九十都用在加熱

is from water heating.

And that's for good reason --

這其實不無道理

the warmer water helps to get your clothes clean.

熱一點的水能讓衣服更乾淨

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

但是如果用冷水就能把衣服洗乾淨呢？

那絕對會省下一筆錢

You certainly would save some money,

and in addition to that,

除此之外

according to some calculations done by Procter and Gamble,

根據寳鹼公司的計算結果

如果全美國的家庭都用冷水洗衣服

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.

每年能減少排放 32 公噸的二氧化碳

That's a lot,

這是個龐大的數字

大約相當於六百三十萬輛汽車的排放量

that's about the equivalent

of the carbon dioxide emitted by 6.3 million cars.

So, how would we go about designing an enzyme

那我們該如何設計酵素

to realize these changes?

來讓這些改變實現呢？

Enzymes didn't evolve to clean dirty laundry,

酵素並沒有進化出洗衣服這個功能

much less in cold water.

更別說用冷水洗了

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

但若是在大自然找找 還是能發現出發點

We can find an enzyme that has some starting activity,

我們在黏土中找到一種酵素

some clay that we can work with.

能有初步的反應

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

螢幕上是個例子

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

我剛提到，我們可以操縱這些胺基酸

putting some letters in, taking some letters out,

把一些字母放進去、取一些出來

rearranging those.

或是更動順序

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

如此能製造出數以千計種類的酵素

And we can take those enzymes,

我們可以把這些酵素

and we can test them in little plates like this.

放在細胞培養盤中

So this plate that I'm holding in my hands

我手中的這一個

contains 96 wells,

有 96 個細胞培養孔

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

每個培養裡都放進了一塊布料

上頭沾有污漬

And we can measure how well each of these enzymes

我們便能夠測量，哪幾種酵素

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

比較能夠把污漬從布料除去

藉由這個方法 便能瞭解酵素是否有效

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

And we can do this using robotics,

我們也能應用自動化技術

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

像是螢幕上這樣

OK, so we do this, and it turns out

我們發現有些酵素

that some of the enzymes are sort of in the ballpark

跟一開始相比沒什麼進展

of the starting enzyme.

That's nothing to write home about.

這樣就是無特別之處

Some are worse, so we get rid of those.

有些表現得更糟 所以我們也拿掉了

And then some are better.

有些表現得很好

Those improved ones become our version 1.0s.

這些成效較佳的酵素 便是我們的第一個版本

Those are the enzymes that we want to carry forward,

我們會繼續研究這些酵素

and we can repeat this cycle again and again.

也會持續重複這些步驟

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

這樣的循環讓我們能找出新的酵素

something that can do what we want.

且能達到我們想要的目的

And after several cycles of this,

經過幾番嘗試後

we did come up with something new.

我們真的有所發現

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

而就是因為這些酵素

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

現在超市可以買到冷衣精

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

我想讓各位看看這一組酵素

So I've got two more tubes here,

跟剛剛的牛奶實驗相同

and these are both milk again.

這邊有兩根試管

And let me show you,

這一根試管我加了酵素進去

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

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

這一根裡面只有水

And that's the control,

也就是對照組

so nothing should happen in that tube.

試管裡什麼事都不會發生

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

你也許覺得用牛奶示範很奇怪

But the reason that I'm doing this

原因是牛奶有豐富的蛋白質

is because milk is just loaded with proteins,

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

而因為酵素的主要工作 便是切斷蛋白質

because it's a master protein chopper,

在蛋白質溶液中 要觀察酵素作用容易許多

that's its job.

So let me get this in here.

我把這倒進來

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

我剛說酵素很擅長切斷蛋白質

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

所以能推斷酵素在洗衣服時

to what it would be doing in your laundry.

跟在牛奶裡會有一樣的效果

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

所以這個方法讓大家

能想像洗衣服時會發生什麼事

OK, so those both went in.

倒進去之後

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

把試管封起來

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

跟剛剛的牛奶實驗一樣靜置一會

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

最後再帶大家看結果

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

目前設計酵素的能力到哪了呢？

Certainly, it will get it faster --

進展一定會越來越快

there are now approaches for evolving enzymes

如今要讓酵素進化有很多方法

that allow researchers to go through far more samples

跟今天的實驗相比

研究人員會有遠遠更多樣本做實驗

than I just showed you.

And in addition to tinkering with natural enzymes,

除了我們剛提到

like we've been talking about,

能修補天然的酵素之外

some scientists are now trying to design enzymes from scratch,

科學家目前正嘗試設計全新的酵素

using machine learning, an approach from artificial intelligence,

利用人工智慧的機器學習能力

to inform their enzyme designs.

找到設計方向

Still others are adding unnatural amino acids to the mix.

另外也能加入不那麼尋常的胺基酸

We talked about the 20 natural amino acids,

我們剛有提到 20 種 常見的天然胺基酸

the common amino acids, before --

they're adding unnatural amino acids

那些不尋常的胺基酸並非天然的

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

酵素因此會擁有 自然界物質缺少的特性

That's a pretty neat area.

這個領域很有發展性

How will designed enzymes affect you in years to come?

那這些設計出來的酵素 未來對各位會有什麼影響呢？

Well, I want to focus on two areas:

主要有兩個部分：

human health and the environment.

人體健康和自然環境

Some pharmaceutical companies

有些製藥商佈署了團隊

now have teams that are dedicated to designing enzymes

致力設計酵素

to make drugs more efficiently and with fewer toxic catalysts.

讓藥物更有效 並且減少使用有毒的催化劑

For example, Januvia,

像是 Januvia

which is a medication to treat type 2 diabetes,

這種治療第二型糖尿病的藥物

is made partially with enzymes.

就有些部分是用酵素製造

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

未來想必會有更多藥物使用酵素生產

In another area,

其他領域也是如此

there are certain disorders

有些疾病是源自 病人體內的酵素出了問題

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

An example of this is called phenylketonuria,

苯丙酮尿症就是個例子

or PKU for short.

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

患有此疾病的病患

無法代謝或消化苯丙胺酸

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

但苯丙胺酸又正好 在那 20 種常見的胺基酸之中

The consequence of ingesting phenylalanine for people with PKU

苯丙酮尿症病人若是攝取到苯丙胺酸

is that they are subject to permanent intellectual disabilities,

智力容易會出現缺陷

so it's a scary thing to have.

這種疾病非常可怕

Now, those of you with kids --

所以家長—

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

這邊有多少人有小孩？

A lot of you.

很多人都有

So may be familiar with PKUs,

因為美國規定嬰兒需要 經過苯丙酮尿症檢測

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

所以各位可能對此有所瞭解

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

我還記得我兒子檢測時 腳跟被扎了一針

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

這件事情棘手在於飲食

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

很多食物含有苯丙胺酸，難以避免

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

我兒子對花生過敏 這件事我非常頭痛

but PKU's on another level of toughness.

苯丙酮尿症麻煩更是難以想像

However, new enzymes may soon enable PKU patients

然而，新的酵素

也許很快能讓 苯丙酮尿症病人盡情吃喝

to eat whatever they want.

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

最近美國食品藥品監督管理局（FDA）

核准一款酵素，來治療苯丙酮尿症

This is big news for patients,

這對病人來說是天大的好消息

and it's actually very big news

for the field of enzyme-replacement therapy more generally,

對酵素替代療法領域亦是如此

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

因為許多問題仍亟待 靠著這個方法解決

So that was a little bit about health.

以上是健康方面的例子

Now I'm going to move to the environment.

接著說說環境問題

When I read about the Great Pacific Garbage Patch --

我之前讀到太平洋垃圾帶

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

也可以說是加州和夏威夷之間

somewhere between California and Hawaii --

有一座大型塑膠島

and about microplastics pretty much everywhere,

還有到處都有微塑膠

it's upsetting.

不免感到難過

Plastics aren't going away anytime soon.

塑膠問題短期之內無法解決

But enzymes may help us in this area as well.

但酵素也許可以使上一些力

Recently, bacteria producing plastic-degrading enzymes were discovered.

近期人們發現有一種細菌

能製造酵素、分解塑膠

Efforts are already underway to design improved versions

大家也正盡力設計出 這種酵素更好的版本

of these enzymes.

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

同時，我們不僅發現了一些酵素

and that are being optimized

還做出改良

to make non-petroleum-derived biodegradable plastics.

這些酵素能夠製造出 非石油製、可生物分解的塑膠

Enzymes may also offer some help in capturing greenhouse gases,

酵素也許還能在捕捉溫室氣體時

助我們一臂之力

such as carbon dioxide, methane and nitrous oxide.

像是二氧化碳、甲烷和一氧化二氮

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

解決這幾個問題很明顯是當務之急

and none of them are easy.

也無不棘手

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

不過操縱酵素的能力

未來也許能 讓解決這些問題更容易

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

我認為在這領域，酵素大有前途

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

現在請各位看看剛才的示範

this is the fun part.

這才是有趣的地方

So we'll start with the chymosin samples.

我們先從凝乳酶開始

So let me get these over here.

我拿到這邊來

And you can see here,

各位可以看到 這一根試管裡是水

this is the one that got the water,

so nothing should happen to this milk.

所以牛奶沒有任何變化

This is the one that got the chymosin.

這一管裡面有凝乳酶

So you can see that it totally clarified up here.

各位可以看到裡面變得非常清澈

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

這些凝固的東西就是起司

we just made cheese in the last few minutes.

在短短幾分鐘裡，我們就做出起司了

So this is that reaction

人們幾千年來就是一直 在應用這個化學反應

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

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

我下一次辦公室親子日 也想做這個實驗

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

不過小孩很難取悅，到時候再看看吧

(Laughter)

（笑聲）

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

我們接著看這一根試管

So this is the enzyme for doing your laundry.

這是洗衣服用的酵素

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

各位應該能看到 跟裝水的試管有所不同

It's kind of clarifying,

裡面也變得很清澈

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

各位洗衣服時想必也希望如此

because you want to be able to have an enzyme

我們都希望酵素是大胃王

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

吃掉所有蛋白質

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

因為衣服上的污漬就是各種蛋白質

like chocolate milk or grass stains, for example,

像是巧克力牛奶、青草污漬

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

這種類型的酵素 可以幫忙洗掉那些污漬

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

也能讓你用冷水洗衣服

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

減少碳足跡、又省錢

and save you some money.

Well, we've come a long way,

人類研究酵素有非常久的歷史

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

想想 7000 年前 就開始用酵素做起司

to the present day and enzyme design.

到今天設計酵素的技術

We're really at a creative crossroads,

我們正位於創意的轉捩點

and with enzymes, can edit what nature wrote

我們能以酵素改寫大自然

or write our own stories with amino acids.

甚至利用胺基酸創造出自己的故事

So next time you're outdoors on a muggy night

所以改天某個悶熱的夜晚

各位走出屋外，看到螢火蟲

and you see a firefly,

I hope you think of enzymes.

希望各位會想到酵素

They're doing amazing things for us today.

幫了我們很大的忙

And by design,

透過設計，酵素未來還會有更多成就

they could be doing even more amazing things tomorrow.

Thank you.

謝謝

(Applause)

（掌聲）