WEBVTT

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

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

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In the summer, I loved
the electric glow of fireflies

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as they would zip around on muggy nights.

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

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Even winter had its charms,

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with the Christmassy bouquet
emanating from pine trees.

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

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

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

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All the things that I just mentioned,

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from the scents of lilacs and pines

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

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have at least one thing in common:

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they're manufactured by enzymes.

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

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and the Green Bay Packers.

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But let's talk about cheese for a minute.

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For at least the last 7,000 years,

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humans have extracted a mixture of enzymes

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from the stomachs of cows
and sheep and goats

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and added it to milk.

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

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The key enzyme in this mixture
is called chymosin.

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I want to show you how that works.

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Right here, I've got two tubes,

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

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Just a second here.

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Now my son Anthony,
who is eight years old,

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

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

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extracting enzymes from red potatoes

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and doing all kinds of demos
in the kitchen.

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And in the end, though,

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we thought the chymosin demo
was pretty cool.

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And so what's happening here

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is the chymosin
is swimming around in the milk,

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

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What it does then
is it clips the casein --

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it's like a molecular scissors.

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

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

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OK.

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So let me give this a quick zip.

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

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OK.

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If DNA is the blueprint of life,

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enzymes are the laborers
that carry out its instructions.

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An enzyme is a protein that's a catalyst,

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it speeds up or accelerates
a chemical reaction,

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

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But it's not just about cheese.

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

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

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to attacking the biggest
environmental challenges

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we have today.

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The basic building blocks of enzymes
are called amino acids.

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There are 20 common amino acids,

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and we typically designate them
with single-letter abbreviations,

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so it's really an alphabet of amino acids.

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In an enzyme, these amino acids
are strung together,

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like pearls on a necklace.

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

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which letters are in that necklace,

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

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

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Now, this string of amino acids,

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this necklace,

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folds up into a higher-order structure.

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And if you were to zoom in
at the molecular level

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

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you would see it looks like this.

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

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

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Nowadays, we can make enzymes in microbes,

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

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

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

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we insert that into the microbe,

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

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to produce that enzyme for us.

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

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you could get this from a microbe.

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And what's even cooler, I think,

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is we can now dial in
completely custom DNA sequences

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to make whatever enzymes we want,

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stuff that's not out there in nature.

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

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is trying to design an enzyme
for a new application,

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arranging the atoms just so.

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

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tinkering with those letters,

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putting some letters in,
taking some letters out,

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maybe rearranging them a little bit,

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is a little bit like finding a book

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and editing a few chapters
or changing the ending.

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In 2018, the Nobel prize in chemistry

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was given for the development
of this approach,

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which is known as directed evolution.

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Nowadays, we can harness
the powers of directed evolution

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to design enzymes for custom purposes,

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

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like laundry.

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So just as enzymes in your body

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

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enzymes in your laundry detergent

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

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It turns out that about
90 percent of the energy

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that goes into doing the wash

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is from water heating.

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And that's for good reason --

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the warmer water
helps to get your clothes clean.

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

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You certainly would save some money,

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and in addition to that,

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according to some calculations
done by Procter and Gamble,

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

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

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That's a lot,

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that's about the equivalent

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of the carbon dioxide
emitted by 6.3 million cars.

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So, how would we go
about designing an enzyme

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to realize these changes?

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Enzymes didn't evolve
to clean dirty laundry,

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much less in cold water.

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

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We can find an enzyme
that has some starting activity,

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some clay that we can work with.

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

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

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putting some letters in,
taking some letters out,

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rearranging those.

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

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And we can take those enzymes,

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and we can test them
in little plates like this.

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So this plate that I'm holding in my hands

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contains 96 wells,

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

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And we can measure
how well each of these enzymes

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

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

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And we can do this using robotics,

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

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OK, so we do this, and it turns out

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that some of the enzymes
are sort of in the ballpark

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of the starting enzyme.

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That's nothing to write home about.

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Some are worse, so we get rid of those.

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And then some are better.

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Those improved ones
become our version 1.0s.

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Those are the enzymes
that we want to carry forward,

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and we can repeat this cycle
again and again.

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

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something that can do what we want.

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And after several cycles of this,

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we did come up with something new.

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

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

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

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So I've got two more tubes here,

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and these are both milk again.

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And let me show you,

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

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

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And that's the control,

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so nothing should happen in that tube.

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

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But the reason that I'm doing this

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is because milk
is just loaded with proteins,

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

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because it's a master protein chopper,

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that's its job.

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So let me get this in here.

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

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

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to what it would be doing in your laundry.

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

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OK, so those both went in.

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

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

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

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

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Certainly, it will get it faster --

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there are now approaches
for evolving enzymes

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that allow researchers to go
through far more samples

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than I just showed you.

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And in addition to tinkering
with natural enzymes,

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like we've been talking about,

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some scientists are now trying to design
enzymes from scratch,

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using machine learning,
an approach from artificial intelligence,

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to inform their enzyme designs.

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Still others are adding
unnatural amino acids to the mix.

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We talked about
the 20 natural amino acids,

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the common amino acids, before --

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they're adding unnatural amino acids

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

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That's a pretty neat area.

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How will designed enzymes affect you
in years to come?

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Well, I want to focus on two areas:

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human health and the environment.

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Some pharmaceutical companies

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now have teams that are dedicated
to designing enzymes

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to make drugs more efficiently
and with fewer toxic catalysts.

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For example, Januvia,

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which is a medication to treat
type 2 diabetes,

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is made partially with enzymes.

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

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In another area,

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there are certain disorders

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

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An example of this
is called phenylketonuria,

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or PKU for short.

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

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

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The consequence of ingesting phenylalanine
for people with PKU

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is that they are subject
to permanent intellectual disabilities,

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so it's a scary thing to have.

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Now, those of you with kids --

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

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A lot of you.

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So may be familiar with PKUs,

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

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

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

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

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

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but PKU's on another level of toughness.

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However, new enzymes
may soon enable PKU patients

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to eat whatever they want.

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

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This is big news for patients,

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and it's actually very big news

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for the field of enzyme-replacement
therapy more generally,

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

NOTE Paragraph

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So that was a little bit about health.

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Now I'm going to move to the environment.

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When I read about
the Great Pacific Garbage Patch --

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

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somewhere between California and Hawaii --

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and about microplastics
pretty much everywhere,

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it's upsetting.

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Plastics aren't going away anytime soon.

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But enzymes may help us
in this area as well.

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Recently, bacteria producing
plastic-degrading enzymes were discovered.

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Efforts are already underway
to design improved versions

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of these enzymes.

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

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and that are being optimized

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to make non-petroleum-derived
biodegradable plastics.

NOTE Paragraph

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Enzymes may also offer some help
in capturing greenhouse gases,

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such as carbon dioxide, methane
and nitrous oxide.

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

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and none of them are easy.

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

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

NOTE Paragraph

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

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this is the fun part.

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So we'll start with the chymosin samples.

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So let me get these over here.

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And you can see here,

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this is the one that got the water,

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so nothing should happen to this milk.

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This is the one that got the chymosin.

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So you can see that it totally
clarified up here.

00:11:31.665 --> 00:11:33.840
There's all this curdled stuff,
that's cheese,

00:11:33.864 --> 00:11:36.147
we just made cheese
in the last few minutes.

00:11:36.171 --> 00:11:37.324
So this is that reaction

00:11:37.348 --> 00:11:40.664
that people have been doing
for thousands and thousands of years.

00:11:40.688 --> 00:11:43.851
I'm thinking about doing this one
at our next Kids to Work Day demo

00:11:43.875 --> 00:11:45.943
but they can be
a tough crowd, so we'll see.

NOTE Paragraph

00:11:45.967 --> 00:11:47.006
(Laughter)

NOTE Paragraph

00:11:47.030 --> 00:11:50.339
And then the other one
I want to look at is this one.

00:11:50.363 --> 00:11:54.323
So this is the enzyme
for doing your laundry.

00:11:54.347 --> 00:11:57.855
And you can see that it's different
than the one that has the water added.

00:11:57.879 --> 00:11:59.095
It's kind of clarifying,

00:11:59.119 --> 00:12:01.934
and that's just what you want
for an enzyme in your laundry,

00:12:01.958 --> 00:12:04.141
because you want to be able
to have an enzyme

00:12:04.165 --> 00:12:07.117
that can be a protein chowhound,
just chew them up,

00:12:07.141 --> 00:12:10.397
because you're going to get
different protein stains on your clothes,

00:12:10.421 --> 00:12:12.734
like chocolate milk
or grass stains, for example,

00:12:12.758 --> 00:12:15.552
and something like this
is going to help you get them off.

00:12:15.576 --> 00:12:18.165
And this is also going to be
the thing that allows you

00:12:18.189 --> 00:12:20.961
to do the wash in cold water,
reduce your carbon footprint

00:12:20.985 --> 00:12:22.244
and save you some money.

NOTE Paragraph

00:12:24.713 --> 00:12:26.308
Well, we've come a long way,

00:12:26.332 --> 00:12:31.078
considering this 7,000-year journey
from enzymes in cheese making

00:12:31.102 --> 00:12:33.355
to the present day and enzyme design.

00:12:33.689 --> 00:12:35.570
We're really at a creative crossroads,

00:12:35.594 --> 00:12:39.856
and with enzymes,
can edit what nature wrote

00:12:39.880 --> 00:12:42.413
or write our own stories with amino acids.

NOTE Paragraph

00:12:42.880 --> 00:12:46.041
So next time you're outdoors
on a muggy night

00:12:46.065 --> 00:12:47.478
and you see a firefly,

00:12:47.502 --> 00:12:49.136
I hope you think of enzymes.

00:12:49.160 --> 00:12:51.533
They're doing amazing things for us today.

00:12:51.557 --> 00:12:53.160
And by design,

00:12:53.184 --> 00:12:55.714
they could be doing
even more amazing things tomorrow.

NOTE Paragraph

00:12:55.738 --> 00:12:56.889
Thank you.

NOTE Paragraph

00:12:56.913 --> 00:12:58.944
(Applause)