0:00:00.913,0:00:04.016
Growing up in central Wisconsin,[br]I spent a lot of time outside.

0:00:04.040,0:00:07.087
In the spring, I'd smell[br]the heady fragrance of lilacs.

0:00:07.666,0:00:10.331
In the summer, I loved[br]the electric glow of fireflies

0:00:10.355,0:00:12.529
as they would zip around on muggy nights.

0:00:12.553,0:00:16.029
In the fall, the bogs were brimming[br]with the bright red of cranberries.

0:00:16.776,0:00:18.553
Even winter had its charms,

0:00:18.577,0:00:21.149
with the Christmassy bouquet[br]emanating from pine trees.

0:00:21.173,0:00:24.339
For me, nature has always been[br]a source of wonder and inspiration.

0:00:25.292,0:00:28.347
As I went on to graduate school[br]in chemistry, and in later years,

0:00:28.371,0:00:31.497
I came to better understand[br]the natural world in molecular detail.

0:00:31.521,0:00:33.291
All the things that I just mentioned,

0:00:33.315,0:00:35.514
from the scents of lilacs and pines

0:00:35.538,0:00:38.307
to the bright red of cranberries[br]and the glow of fireflies,

0:00:38.331,0:00:40.156
have at least one thing in common:

0:00:40.482,0:00:42.615
they're manufactured by enzymes.

0:00:43.180,0:00:46.330
As I said, I grew up in Wisconsin,[br]so of course, I like cheese

0:00:46.354,0:00:48.069
and the Green Bay Packers.

0:00:48.093,0:00:50.061
But let's talk about cheese for a minute.

0:00:50.085,0:00:51.712
For at least the last 7,000 years,

0:00:51.736,0:00:54.014
humans have extracted a mixture of enzymes

0:00:54.038,0:00:56.760
from the stomachs of cows[br]and sheep and goats

0:00:56.784,0:00:57.998
and added it to milk.

0:00:58.022,0:01:01.451
This causes the milk to curdle --[br]it's part of the cheese-making process.

0:01:01.475,0:01:03.855
The key enzyme in this mixture[br]is called chymosin.

0:01:03.879,0:01:05.704
I want to show you how that works.

0:01:05.728,0:01:07.626
Right here, I've got two tubes,

0:01:07.650,0:01:09.856
and I'm going to add chymosin[br]to one of these.

0:01:09.880,0:01:11.147
Just a second here.

0:01:11.744,0:01:15.206
Now my son Anthony,[br]who is eight years old,

0:01:15.230,0:01:18.508
was very interested in helping me[br]figure out a demo for the TED Talk,

0:01:18.532,0:01:22.652
and so we were in the kitchen,[br]we were slicing up pineapples,

0:01:22.676,0:01:26.610
extracting enzymes from red potatoes

0:01:26.634,0:01:28.713
and doing all kinds of demos[br]in the kitchen.

0:01:28.737,0:01:29.896
And in the end, though,

0:01:29.920,0:01:32.086
we thought the chymosin demo[br]was pretty cool.

0:01:32.110,0:01:33.506
And so what's happening here

0:01:33.530,0:01:37.529
is the chymosin[br]is swimming around in the milk,

0:01:37.553,0:01:40.672
and it's binding to a protein[br]there called casein.

0:01:40.696,0:01:42.974
What it does then[br]is it clips the casein --

0:01:42.998,0:01:44.800
it's like a molecular scissors.

0:01:45.102,0:01:49.141
It's that clipping action[br]that causes the milk to curdle.

0:01:49.165,0:01:51.935
So here we are in the kitchen,[br]working on this.

0:01:52.332,0:01:53.506
OK.

0:01:53.530,0:01:55.664
So let me give this a quick zip.

0:01:56.180,0:01:59.657
And then we'll set these to the side[br]and let these simmer for a minute.

0:01:59.681,0:02:00.831
OK.

0:02:03.506,0:02:05.085
If DNA is the blueprint of life,

0:02:05.109,0:02:07.985
enzymes are the laborers[br]that carry out its instructions.

0:02:08.009,0:02:10.055
An enzyme is a protein that's a catalyst,

0:02:10.079,0:02:12.898
it speeds up or accelerates[br]a chemical reaction,

0:02:12.922,0:02:16.398
just as the chymosin over here[br]is accelerating the curdling of the milk.

0:02:16.914,0:02:18.669
But it's not just about cheese.

0:02:18.693,0:02:22.010
While enzymes do play an important role[br]in the foods that we eat,

0:02:22.034,0:02:25.478
they also are involved in everything[br]from the health of an infant

0:02:25.502,0:02:27.812
to attacking the biggest[br]environmental challenges

0:02:27.836,0:02:28.986
we have today.

0:02:29.720,0:02:33.093
The basic building blocks of enzymes[br]are called amino acids.

0:02:33.482,0:02:35.054
There are 20 common amino acids,

0:02:35.078,0:02:38.435
and we typically designate them[br]with single-letter abbreviations,

0:02:38.459,0:02:40.887
so it's really an alphabet of amino acids.

0:02:41.236,0:02:43.776
In an enzyme, these amino acids[br]are strung together,

0:02:43.800,0:02:45.239
like pearls on a necklace.

0:02:45.263,0:02:47.815
And it's really the identity[br]of the amino acids,

0:02:47.839,0:02:49.525
which letters are in that necklace,

0:02:49.549,0:02:51.819
and in what order they are,[br]what they spell out,

0:02:51.843,0:02:55.926
that gives an enzyme its unique properties[br]and differentiates it from other enzymes.

0:02:55.950,0:02:58.266
Now, this string of amino acids,

0:02:58.290,0:02:59.456
this necklace,

0:02:59.480,0:03:01.356
folds up into a higher-order structure.

0:03:01.380,0:03:03.688
And if you were to zoom in[br]at the molecular level

0:03:03.712,0:03:06.908
and take a look at chymosin,[br]which is the enzyme working over here,

0:03:06.932,0:03:08.545
you would see it looks like this.

0:03:08.569,0:03:11.680
It's all these strands and loops[br]and helices and twists and turns,

0:03:11.704,0:03:14.612
and it has to be in just[br]this conformation to work properly.

0:03:15.038,0:03:17.768
Nowadays, we can make enzymes in microbes,

0:03:17.792,0:03:20.627
and that can be like a bacteria[br]or a yeast, for example.

0:03:20.982,0:03:23.411
And the way we do this[br]is we get a piece of DNA

0:03:23.435,0:03:25.800
that codes for an enzyme[br]that we're interested in,

0:03:25.824,0:03:27.387
we insert that into the microbe,

0:03:27.411,0:03:30.871
and we let the microbe use[br]its own machinery, its own wherewithal,

0:03:30.895,0:03:33.029
to produce that enzyme for us.

0:03:33.053,0:03:36.460
So if you wanted chymosin,[br]you wouldn't need a calf, nowadays --

0:03:36.484,0:03:38.198
you could get this from a microbe.

0:03:38.222,0:03:39.761
And what's even cooler, I think,

0:03:39.785,0:03:42.277
is we can now dial in[br]completely custom DNA sequences

0:03:42.301,0:03:43.888
to make whatever enzymes we want,

0:03:43.912,0:03:45.732
stuff that's not out there in nature.

0:03:45.756,0:03:47.608
And, to me, what's really the fun part

0:03:47.632,0:03:50.283
is trying to design an enzyme[br]for a new application,

0:03:50.307,0:03:52.617
arranging the atoms just so.

0:03:53.450,0:03:57.570
The act of taking an enzyme from nature[br]and playing with those amino acids,

0:03:57.594,0:03:59.006
tinkering with those letters,

0:03:59.030,0:04:01.371
putting some letters in,[br]taking some letters out,

0:04:01.395,0:04:03.140
maybe rearranging them a little bit,

0:04:03.164,0:04:04.855
is a little bit like finding a book

0:04:04.879,0:04:07.997
and editing a few chapters[br]or changing the ending.

0:04:08.720,0:04:10.696
In 2018, the Nobel prize in chemistry

0:04:10.720,0:04:12.911
was given for the development[br]of this approach,

0:04:12.935,0:04:15.030
which is known as directed evolution.

0:04:15.966,0:04:19.799
Nowadays, we can harness[br]the powers of directed evolution

0:04:19.823,0:04:21.910
to design enzymes for custom purposes,

0:04:21.934,0:04:26.887
and one of these is designing enzymes[br]for doing applications in new areas,

0:04:26.911,0:04:28.069
like laundry.

0:04:28.093,0:04:29.592
So just as enzymes in your body

0:04:29.616,0:04:32.236
can help you to break down[br]the food that you eat,

0:04:32.260,0:04:33.856
enzymes in your laundry detergent

0:04:33.880,0:04:37.109
can help you to break down[br]the stains on your clothes.

0:04:37.515,0:04:40.125
It turns out that about[br]90 percent of the energy

0:04:40.149,0:04:41.626
that goes into doing the wash

0:04:41.650,0:04:42.800
is from water heating.

0:04:43.165,0:04:44.591
And that's for good reason --

0:04:44.615,0:04:46.947
the warmer water[br]helps to get your clothes clean.

0:04:46.971,0:04:49.998
But what if you were able[br]to do the wash in cold water instead?

0:04:50.022,0:04:51.768
You certainly would save some money,

0:04:51.792,0:04:52.967
and in addition to that,

0:04:52.991,0:04:55.720
according to some calculations[br]done by Procter and Gamble,

0:04:55.744,0:04:58.831
if all households in the US[br]were to do the laundry in cold water,

0:04:58.855,0:05:03.870
we would save the emissions[br]of 32 metric tons of CO2 each year.

0:05:03.894,0:05:05.077
That's a lot,

0:05:05.101,0:05:06.417
that's about the equivalent

0:05:06.441,0:05:09.616
of the carbon dioxide[br]emitted by 6.3 million cars.

0:05:09.640,0:05:11.996
So, how would we go[br]about designing an enzyme

0:05:12.020,0:05:13.338
to realize these changes?

0:05:13.362,0:05:16.123
Enzymes didn't evolve[br]to clean dirty laundry,

0:05:16.147,0:05:17.747
much less in cold water.

0:05:18.282,0:05:21.347
But we can go to nature,[br]and we can find a starting point.

0:05:21.371,0:05:23.982
We can find an enzyme[br]that has some starting activity,

0:05:24.006,0:05:25.687
some clay that we can work with.

0:05:25.711,0:05:28.807
So this is an example of such an enzyme,[br]right here on the screen.

0:05:28.831,0:05:31.688
And we can start playing[br]with those amino acids, as I said,

0:05:31.712,0:05:34.149
putting some letters in,[br]taking some letters out,

0:05:34.173,0:05:35.340
rearranging those.

0:05:35.364,0:05:38.434
And in doing so, we can generate[br]thousands of enzymes.

0:05:38.458,0:05:40.966
And we can take those enzymes,

0:05:40.990,0:05:43.566
and we can test them[br]in little plates like this.

0:05:44.339,0:05:47.220
So this plate that I'm holding in my hands

0:05:47.244,0:05:48.855
contains 96 wells,

0:05:48.879,0:05:52.966
and in each well is a piece of fabric[br]with a stain on it.

0:05:52.990,0:05:55.331
And we can measure[br]how well each of these enzymes

0:05:55.355,0:05:58.014
are able to remove the stains[br]from the pieces of fabric,

0:05:58.038,0:06:00.060
and in that way see how well it's working.

0:06:00.084,0:06:01.807
And we can do this using robotics,

0:06:01.831,0:06:04.345
like you'll see[br]in just a second on the screen.

0:06:07.427,0:06:09.744
OK, so we do this, and it turns out

0:06:09.768,0:06:12.220
that some of the enzymes[br]are sort of in the ballpark

0:06:12.244,0:06:13.434
of the starting enzyme.

0:06:13.458,0:06:15.149
That's nothing to write home about.

0:06:15.173,0:06:17.561
Some are worse, so we get rid of those.

0:06:17.585,0:06:18.910
And then some are better.

0:06:18.934,0:06:21.569
Those improved ones[br]become our version 1.0s.

0:06:21.593,0:06:24.033
Those are the enzymes[br]that we want to carry forward,

0:06:24.037,0:06:26.133
and we can repeat this cycle[br]again and again.

0:06:26.157,0:06:29.936
And it's the repetition of this cycle[br]that lets us come up with a new enzyme,

0:06:29.960,0:06:31.782
something that can do what we want.

0:06:31.806,0:06:33.394
And after several cycles of this,

0:06:33.418,0:06:35.068
we did come up with something new.

0:06:35.092,0:06:38.632
So you can go to the supermarket today,[br]and you can buy a laundry detergent

0:06:38.656,0:06:42.553
that lets you do the wash in cold water[br]because of enzymes like this here.

0:06:42.577,0:06:45.037
And I want to show you[br]how this one works too.

0:06:45.061,0:06:47.761
So I've got two more tubes here,

0:06:47.785,0:06:50.185
and these are both milk again.

0:06:50.518,0:06:51.669
And let me show you,

0:06:51.693,0:06:54.010
I've got one that I'm going[br]to add this enzyme to

0:06:54.034,0:06:56.343
and one that I'm going[br]to add some water to.

0:06:56.367,0:06:57.519
And that's the control,

0:06:57.543,0:06:59.371
so nothing should happen in that tube.

0:06:59.395,0:07:02.617
You might find it curious[br]that I'm doing this with milk.

0:07:02.641,0:07:04.283
But the reason that I'm doing this

0:07:04.307,0:07:07.196
is because milk[br]is just loaded with proteins,

0:07:07.220,0:07:10.939
and it's very easy to see[br]this enzyme working in a protein solution,

0:07:10.963,0:07:13.601
because it's a master protein chopper,

0:07:13.625,0:07:14.775
that's its job.

0:07:15.133,0:07:16.933
So let me get this in here.

0:07:18.323,0:07:22.307
And you know, as I said,[br]it's a master protein chopper

0:07:22.331,0:07:26.243
and what you can do is you can extrapolate[br]what it's doing in this milk

0:07:26.267,0:07:28.283
to what it would be doing in your laundry.

0:07:28.307,0:07:31.286
So this is kind of a way to visualize[br]what would be happening.

0:07:31.310,0:07:33.044
OK, so those both went in.

0:07:34.081,0:07:38.168
And I'm going to give this[br]a quick zip as well.

0:07:43.017,0:07:46.787
OK, so we'll let these sit over here[br]with the chymosin sample,

0:07:46.811,0:07:49.192
so I'm going to come back[br]to those toward the end.

0:07:51.152,0:07:54.085
Well, what's on the horizon[br]for enzyme design?

0:07:54.109,0:07:55.789
Certainly, it will get it faster --

0:07:55.813,0:07:57.924
there are now approaches[br]for evolving enzymes

0:07:57.948,0:08:00.440
that allow researchers to go[br]through far more samples

0:08:00.464,0:08:02.084
than I just showed you.

0:08:02.108,0:08:04.494
And in addition to tinkering[br]with natural enzymes,

0:08:04.518,0:08:05.950
like we've been talking about,

0:08:05.974,0:08:08.918
some scientists are now trying to design[br]enzymes from scratch,

0:08:08.942,0:08:12.682
using machine learning,[br]an approach from artificial intelligence,

0:08:12.706,0:08:14.664
to inform their enzyme designs.

0:08:14.688,0:08:18.791
Still others are adding[br]unnatural amino acids to the mix.

0:08:18.815,0:08:21.030
We talked about[br]the 20 natural amino acids,

0:08:21.054,0:08:22.637
the common amino acids, before --

0:08:22.661,0:08:24.416
they're adding unnatural amino acids

0:08:24.440,0:08:28.050
to make enzymes with properties unlike[br]those that could be found in nature.

0:08:28.074,0:08:29.728
That's a pretty neat area.

0:08:30.211,0:08:34.848
How will designed enzymes affect you[br]in years to come?

0:08:34.872,0:08:36.872
Well, I want to focus on two areas:

0:08:36.896,0:08:39.096
human health and the environment.

0:08:40.142,0:08:41.563
Some pharmaceutical companies

0:08:41.587,0:08:44.933
now have teams that are dedicated[br]to designing enzymes

0:08:44.957,0:08:48.825
to make drugs more efficiently[br]and with fewer toxic catalysts.

0:08:48.849,0:08:50.445
For example, Januvia,

0:08:50.469,0:08:52.707
which is a medication to treat[br]type 2 diabetes,

0:08:52.731,0:08:54.262
is made partially with enzymes.

0:08:54.286,0:08:57.630
The number of drugs made with enzymes[br]is sure to grow in the future.

0:08:58.536,0:08:59.694
In another area,

0:08:59.718,0:09:01.004
there are certain disorders

0:09:01.028,0:09:04.147
in which a single enzyme[br]in a person's body doesn't work properly.

0:09:04.171,0:09:06.393
An example of this[br]is called phenylketonuria,

0:09:06.417,0:09:07.631
or PKU for short.

0:09:08.180,0:09:12.303
People with PKU are unable to properly[br]metabolize or digest phenylalanine,

0:09:12.327,0:09:15.961
which is one of the 20 common amino acids[br]that we've been talking about.

0:09:15.985,0:09:19.802
The consequence of ingesting phenylalanine[br]for people with PKU

0:09:19.826,0:09:24.357
is that they are subject[br]to permanent intellectual disabilities,

0:09:24.381,0:09:26.228
so it's a scary thing to have.

0:09:26.252,0:09:28.046
Now, those of you with kids --

0:09:28.070,0:09:30.617
do you guys have kids, here,[br]which ones have kids?

0:09:30.641,0:09:31.799
A lot of you.

0:09:31.823,0:09:33.609
So may be familiar with PKUs,

0:09:33.633,0:09:38.553
because all infants in the US[br]are required to be tested for PKU.

0:09:38.577,0:09:41.941
I remember when Anthony, my son,[br]had his heel pricked to test for it.

0:09:42.639,0:09:45.219
The big challenge with this[br]is: What do you eat?

0:09:45.243,0:09:48.743
Phenylalanine is in so many foods,[br]it's incredibly hard to avoid.

0:09:48.767,0:09:51.688
Now, Anthony has a nut allergy,[br]and I thought that was tough,

0:09:51.712,0:09:54.172
but PKU's on another level of toughness.

0:09:54.196,0:09:57.323
However, new enzymes[br]may soon enable PKU patients

0:09:57.347,0:09:59.141
to eat whatever they want.

0:09:59.165,0:10:03.355
Recently, the FDA approved an enzyme[br]designed to treat PKU.

0:10:03.379,0:10:05.006
This is big news for patients,

0:10:05.030,0:10:06.522
and it's actually very big news

0:10:06.546,0:10:09.339
for the field of enzyme-replacement[br]therapy more generally,

0:10:09.363,0:10:13.275
because there are other targets out there[br]where this would be a good approach.

0:10:14.726,0:10:16.544
So that was a little bit about health.

0:10:16.568,0:10:18.726
Now I'm going to move to the environment.

0:10:19.155,0:10:21.845
When I read about[br]the Great Pacific Garbage Patch --

0:10:21.869,0:10:25.117
by the way, that's, like,[br]this huge island of plastic,

0:10:25.141,0:10:27.410
somewhere between California and Hawaii --

0:10:27.434,0:10:30.682
and about microplastics[br]pretty much everywhere,

0:10:30.706,0:10:31.872
it's upsetting.

0:10:31.896,0:10:33.918
Plastics aren't going away anytime soon.

0:10:33.942,0:10:36.474
But enzymes may help us[br]in this area as well.

0:10:36.498,0:10:40.363
Recently, bacteria producing[br]plastic-degrading enzymes were discovered.

0:10:40.387,0:10:43.022
Efforts are already underway[br]to design improved versions

0:10:43.046,0:10:44.196
of these enzymes.

0:10:44.585,0:10:47.450
At the same time, there are enzymes[br]that have been discovered

0:10:47.474,0:10:48.839
and that are being optimized

0:10:48.863,0:10:51.878
to make non-petroleum-derived[br]biodegradable plastics.

0:10:53.171,0:10:56.845
Enzymes may also offer some help[br]in capturing greenhouse gases,

0:10:56.869,0:11:00.512
such as carbon dioxide, methane[br]and nitrous oxide.

0:11:00.536,0:11:02.948
Now, there is no doubt,[br]these are major challenges,

0:11:02.972,0:11:04.815
and none of them are easy.

0:11:04.839,0:11:08.990
But our ability to harness enzymes[br]may help us to tackle these in the future,

0:11:09.014,0:11:11.530
so I think that's another area[br]to be looking forward.

0:11:11.554,0:11:13.561
So now I'm going to get back[br]to the demo --

0:11:13.585,0:11:14.799
this is the fun part.

0:11:14.823,0:11:18.236
So we'll start with the chymosin samples.

0:11:19.863,0:11:21.593
So let me get these over here.

0:11:21.617,0:11:23.022
And you can see here,

0:11:23.046,0:11:24.951
this is the one that got the water,

0:11:24.975,0:11:26.815
so nothing should happen to this milk.

0:11:26.839,0:11:28.990
This is the one that got the chymosin.

0:11:29.014,0:11:31.641
So you can see that it totally[br]clarified up here.

0:11:31.665,0:11:33.840
There's all this curdled stuff,[br]that's cheese,

0:11:33.864,0:11:36.147
we just made cheese[br]in the last few minutes.

0:11:36.171,0:11:37.324
So this is that reaction

0:11:37.348,0:11:40.664
that people have been doing[br]for thousands and thousands of years.

0:11:40.688,0:11:43.851
I'm thinking about doing this one[br]at our next Kids to Work Day demo

0:11:43.875,0:11:45.943
but they can be[br]a tough crowd, so we'll see.

0:11:45.967,0:11:47.006
(Laughter)

0:11:47.030,0:11:50.339
And then the other one[br]I want to look at is this one.

0:11:50.363,0:11:54.323
So this is the enzyme[br]for doing your laundry.

0:11:54.347,0:11:57.855
And you can see that it's different[br]than the one that has the water added.

0:11:57.879,0:11:59.095
It's kind of clarifying,

0:11:59.119,0:12:01.934
and that's just what you want[br]for an enzyme in your laundry,

0:12:01.958,0:12:04.141
because you want to be able[br]to have an enzyme

0:12:04.165,0:12:07.117
that can be a protein chowhound,[br]just chew them up,

0:12:07.141,0:12:10.397
because you're going to get[br]different protein stains on your clothes,

0:12:10.421,0:12:12.734
like chocolate milk[br]or grass stains, for example,

0:12:12.758,0:12:15.552
and something like this[br]is going to help you get them off.

0:12:15.576,0:12:18.165
And this is also going to be[br]the thing that allows you

0:12:18.189,0:12:20.961
to do the wash in cold water,[br]reduce your carbon footprint

0:12:20.985,0:12:22.244
and save you some money.

0:12:24.713,0:12:26.308
Well, we've come a long way,

0:12:26.332,0:12:31.078
considering this 7,000-year journey[br]from enzymes in cheese making

0:12:31.102,0:12:33.355
to the present day and enzyme design.

0:12:33.689,0:12:35.570
We're really at a creative crossroads,

0:12:35.594,0:12:39.856
and with enzymes,[br]can edit what nature wrote

0:12:39.880,0:12:42.413
or write our own stories with amino acids.

0:12:42.880,0:12:46.041
So next time you're outdoors[br]on a muggy night

0:12:46.065,0:12:47.478
and you see a firefly,

0:12:47.502,0:12:49.136
I hope you think of enzymes.

0:12:49.160,0:12:51.533
They're doing amazing things for us today.

0:12:51.557,0:12:53.160
And by design,

0:12:53.184,0:12:55.714
they could be doing[br]even more amazing things tomorrow.

0:12:55.738,0:12:56.889
Thank you.

0:12:56.913,0:12:58.944
(Applause)