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

Translator: Ivana Korom Reviewer: Krystian Aparta

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

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

In the summer, I loved the electric glow of fireflies

as they would zip around on muggy nights.

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

Even winter had its charms,

with the Christmassy bouquet emanating from pine trees.

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

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

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

All the things that I just mentioned,

from the scents of lilacs and pines

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

have at least one thing in common:

they're manufactured by enzymes.

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

and the Green Bay Packers.

But let's talk about cheese for a minute.

For at least the last 7,000 years,

humans have extracted a mixture of enzymes

from the stomachs of cows and sheep and goats

and added it to milk.

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

The key enzyme in this mixture is called chymosin.

I want to show you how that works.

Right here, I've got two tubes,

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

Just a second here.

Now my son Anthony, who is eight years old,

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

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

extracting enzymes from red potatoes

and doing all kinds of demos in the kitchen.

And in the end, though,

we thought the chymosin demo was pretty cool.

And so what's happening here

is the chymosin is swimming around in the milk,

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

What it does then is it clips the casein --

it's like a molecular scissors.

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

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

OK.

So let me give this a quick zip.

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

OK.

If DNA is the blueprint of life,

enzymes are the laborers that carry out its instructions.

An enzyme is a protein that's a catalyst,

it speeds up or accelerates a chemical reaction,

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

But it's not just about cheese.

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

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

to attacking the biggest environmental challenges

we have today.

The basic building blocks of enzymes are called amino acids.

There are 20 common amino acids,

and we typically designate them with single-letter abbreviations,

so it's really an alphabet of amino acids.

In an enzyme, these amino acids are strung together,

like pearls on a necklace.

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

which letters are in that necklace,

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

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

Now, this string of amino acids,

this necklace,

folds up into a higher-order structure.

And if you were to zoom in at the molecular level

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

you would see it looks like this.

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.

Nowadays, we can make enzymes in microbes,

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

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

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

we insert that into the microbe,

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

to produce that enzyme for us.

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

you could get this from a microbe.

And what's even cooler, I think,

is we can now dial in completely custom DNA sequences

to make whatever enzymes we want,

stuff that's not out there in nature.

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

is trying to design an enzyme for a new application,

arranging the atoms just so.

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

tinkering with those letters,

putting some letters in, taking some letters out,

maybe rearranging them a little bit,

is a little bit like finding a book

and editing a few chapters or changing the ending.

In 2018, the Nobel prize in chemistry

was given for the development of this approach,

which is known as directed evolution.

Nowadays, we can harness the powers of directed evolution

to design enzymes for custom purposes,

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

like laundry.

So just as enzymes in your body

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

enzymes in your laundry detergent

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

It turns out that about 90 percent of the energy

that goes into doing the wash

is from water heating.

And that's for good reason --

the warmer water helps to get your clothes clean.

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

You certainly would save some money,

and in addition to that,

according to some calculations done by Procter and Gamble,

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.

That's a lot,

that's about the equivalent

of the carbon dioxide emitted by 6.3 million cars.

So, how would we go about designing an enzyme

to realize these changes?

Enzymes didn't evolve to clean dirty laundry,

much less in cold water.

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

We can find an enzyme that has some starting activity,

some clay that we can work with.

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

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

putting some letters in, taking some letters out,

rearranging those.

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

And we can take those enzymes,

and we can test them in little plates like this.

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.

And we can measure how well each of these enzymes

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

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

And we can do this using robotics,

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

OK, so we do this, and it turns out

that some of the enzymes are sort of in the ballpark

of the starting enzyme.

That's nothing to write home about.

Some are worse, so we get rid of those.

And then some are better.

Those improved ones become our version 1.0s.

Those are the enzymes that we want to carry forward,

and we can repeat this cycle again and again.

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

something that can do what we want.

And after several cycles of this,

we did come up with something new.

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.

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

So I've got two more tubes here,

and these are both milk again.

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.

And that's the control,

so nothing should happen in that tube.

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

But the reason that I'm doing this

is because milk is just loaded with proteins,

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

because it's a master protein chopper,

that's its job.

So let me get this in here.

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

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.

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

OK, so those both went in.

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

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.

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

Certainly, it will get it faster --

there are now approaches for evolving enzymes

that allow researchers to go through far more samples

than I just showed you.

And in addition to tinkering with natural enzymes,

like we've been talking about,

some scientists are now trying to design enzymes from scratch,

using machine learning, an approach from artificial intelligence,

to inform their enzyme designs.

Still others are adding unnatural amino acids to the mix.

We talked about the 20 natural amino acids,

the common amino acids, before --

they're adding unnatural amino acids

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

That's a pretty neat area.

How will designed enzymes affect you in years to come?

Well, I want to focus on two areas:

human health and the environment.

Some pharmaceutical companies

now have teams that are dedicated to designing enzymes

to make drugs more efficiently and with fewer toxic catalysts.

For example, Januvia,

which is a medication to treat type 2 diabetes,

is made partially with enzymes.

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

In another area,

there are certain disorders

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

An example of this is called phenylketonuria,

or PKU for short.

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

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

The consequence of ingesting phenylalanine for people with PKU

is that they are subject to permanent intellectual disabilities,

so it's a scary thing to have.

Now, those of you with kids --

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

A lot of you.

So may be familiar with PKUs,

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

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

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

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

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

but PKU's on another level of toughness.

However, new enzymes may soon enable PKU patients

to eat whatever they want.

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

This is big news for patients,

and it's actually very big news

for the field of enzyme-replacement therapy more generally,

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

So that was a little bit about health.

Now I'm going to move to the environment.

When I read about the Great Pacific Garbage Patch --

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

somewhere between California and Hawaii --

and about microplastics pretty much everywhere,

it's upsetting.

Plastics aren't going away anytime soon.

But enzymes may help us in this area as well.

Recently, bacteria producing plastic-degrading enzymes were discovered.

Efforts are already underway to design improved versions

of these enzymes.

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

and that are being optimized

to make non-petroleum-derived biodegradable plastics.

Enzymes may also offer some help in capturing greenhouse gases,

such as carbon dioxide, methane and nitrous oxide.

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

and none of them are easy.

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

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

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

this is the fun part.

So we'll start with the chymosin samples.

So let me get these over here.

And you can see here,

this is the one that got the water,

so nothing should happen to this milk.

This is the one that got the chymosin.

So you can see that it totally clarified up here.

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

we just made cheese in the last few minutes.

So this is that reaction

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

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

(Laughter)

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

So this is the enzyme for doing your laundry.

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

It's kind of clarifying,

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

because you want to be able to have an enzyme

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

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

like chocolate milk or grass stains, for example,

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

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

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

and save you some money.

Well, we've come a long way,

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

to the present day and enzyme design.

We're really at a creative crossroads,

and with enzymes, can edit what nature wrote

or write our own stories with amino acids.

So next time you're outdoors on a muggy night

and you see a firefly,

I hope you think of enzymes.

They're doing amazing things for us today.

And by design,

they could be doing even more amazing things tomorrow.

Thank you.

(Applause)