How designing brand-new enzymes could change the world
-
0:01 - 0:04Growing up in central Wisconsin,
I spent a lot of time outside. -
0:04 - 0:07In the spring, I'd smell
the heady fragrance of lilacs. -
0:08 - 0:10In the summer, I loved
the electric glow of fireflies -
0:10 - 0:13as they would zip around on muggy nights.
-
0:13 - 0:16In the fall, the bogs were brimming
with the bright red of cranberries. -
0:17 - 0:19Even winter had its charms,
-
0:19 - 0:21with the Christmassy bouquet
emanating from pine trees. -
0:21 - 0:24For me, nature has always been
a source of wonder and inspiration. -
0:25 - 0:28As I went on to graduate school
in chemistry, and in later years, -
0:28 - 0:31I came to better understand
the natural world in molecular detail. -
0:32 - 0:33All the things that I just mentioned,
-
0:33 - 0:36from the scents of lilacs and pines
-
0:36 - 0:38to the bright red of cranberries
and the glow of fireflies, -
0:38 - 0:40have at least one thing in common:
-
0:40 - 0:43they're manufactured by enzymes.
-
0:43 - 0:46As I said, I grew up in Wisconsin,
so of course, I like cheese -
0:46 - 0:48and the Green Bay Packers.
-
0:48 - 0:50But let's talk about cheese for a minute.
-
0:50 - 0:52For at least the last 7,000 years,
-
0:52 - 0:54humans have extracted a mixture of enzymes
-
0:54 - 0:57from the stomachs of cows
and sheep and goats -
0:57 - 0:58and added it to milk.
-
0:58 - 1:01This causes the milk to curdle --
it's part of the cheese-making process. -
1:01 - 1:04The key enzyme in this mixture
is called chymosin. -
1:04 - 1:06I want to show you how that works.
-
1:06 - 1:08Right here, I've got two tubes,
-
1:08 - 1:10and I'm going to add chymosin
to one of these. -
1:10 - 1:11Just a second here.
-
1:12 - 1:15Now my son Anthony,
who is eight years old, -
1:15 - 1:19was very interested in helping me
figure out a demo for the TED Talk, -
1:19 - 1:23and so we were in the kitchen,
we were slicing up pineapples, -
1:23 - 1:27extracting enzymes from red potatoes
-
1:27 - 1:29and doing all kinds of demos
in the kitchen. -
1:29 - 1:30And in the end, though,
-
1:30 - 1:32we thought the chymosin demo
was pretty cool. -
1:32 - 1:34And so what's happening here
-
1:34 - 1:38is the chymosin
is swimming around in the milk, -
1:38 - 1:41and it's binding to a protein
there called casein. -
1:41 - 1:43What it does then
is it clips the casein -- -
1:43 - 1:45it's like a molecular scissors.
-
1:45 - 1:49It's that clipping action
that causes the milk to curdle. -
1:49 - 1:52So here we are in the kitchen,
working on this. -
1:52 - 1:54OK.
-
1:54 - 1:56So let me give this a quick zip.
-
1:56 - 2:00And then we'll set these to the side
and let these simmer for a minute. -
2:00 - 2:01OK.
-
2:04 - 2:05If DNA is the blueprint of life,
-
2:05 - 2:08enzymes are the laborers
that carry out its instructions. -
2:08 - 2:10An enzyme is a protein that's a catalyst,
-
2:10 - 2:13it speeds up or accelerates
a chemical reaction, -
2:13 - 2:16just as the chymosin over here
is accelerating the curdling of the milk. -
2:17 - 2:19But it's not just about cheese.
-
2:19 - 2:22While enzymes do play an important role
in the foods that we eat, -
2:22 - 2:25they also are involved in everything
from the health of an infant -
2:26 - 2:28to attacking the biggest
environmental challenges -
2:28 - 2:29we have today.
-
2:30 - 2:33The basic building blocks of enzymes
are called amino acids. -
2:33 - 2:35There are 20 common amino acids,
-
2:35 - 2:38and we typically designate them
with single-letter abbreviations, -
2:38 - 2:41so it's really an alphabet of amino acids.
-
2:41 - 2:44In an enzyme, these amino acids
are strung together, -
2:44 - 2:45like pearls on a necklace.
-
2:45 - 2:48And it's really the identity
of the amino acids, -
2:48 - 2:50which letters are in that necklace,
-
2:50 - 2:52and in what order they are,
what they spell out, -
2:52 - 2:56that gives an enzyme its unique properties
and differentiates it from other enzymes. -
2:56 - 2:58Now, this string of amino acids,
-
2:58 - 2:59this necklace,
-
2:59 - 3:01folds up into a higher-order structure.
-
3:01 - 3:04And if you were to zoom in
at the molecular level -
3:04 - 3:07and take a look at chymosin,
which is the enzyme working over here, -
3:07 - 3:09you would see it looks like this.
-
3:09 - 3:12It's all these strands and loops
and helices and twists and turns, -
3:12 - 3:15and it has to be in just
this conformation to work properly. -
3:15 - 3:18Nowadays, we can make enzymes in microbes,
-
3:18 - 3:21and that can be like a bacteria
or a yeast, for example. -
3:21 - 3:23And the way we do this
is we get a piece of DNA -
3:23 - 3:26that codes for an enzyme
that we're interested in, -
3:26 - 3:27we insert that into the microbe,
-
3:27 - 3:31and we let the microbe use
its own machinery, its own wherewithal, -
3:31 - 3:33to produce that enzyme for us.
-
3:33 - 3:36So if you wanted chymosin,
you wouldn't need a calf, nowadays -- -
3:36 - 3:38you could get this from a microbe.
-
3:38 - 3:40And what's even cooler, I think,
-
3:40 - 3:42is we can now dial in
completely custom DNA sequences -
3:42 - 3:44to make whatever enzymes we want,
-
3:44 - 3:46stuff that's not out there in nature.
-
3:46 - 3:48And, to me, what's really the fun part
-
3:48 - 3:50is trying to design an enzyme
for a new application, -
3:50 - 3:53arranging the atoms just so.
-
3:53 - 3:58The act of taking an enzyme from nature
and playing with those amino acids, -
3:58 - 3:59tinkering with those letters,
-
3:59 - 4:01putting some letters in,
taking some letters out, -
4:01 - 4:03maybe rearranging them a little bit,
-
4:03 - 4:05is a little bit like finding a book
-
4:05 - 4:08and editing a few chapters
or changing the ending. -
4:09 - 4:11In 2018, the Nobel prize in chemistry
-
4:11 - 4:13was given for the development
of this approach, -
4:13 - 4:15which is known as directed evolution.
-
4:16 - 4:20Nowadays, we can harness
the powers of directed evolution -
4:20 - 4:22to design enzymes for custom purposes,
-
4:22 - 4:27and one of these is designing enzymes
for doing applications in new areas, -
4:27 - 4:28like laundry.
-
4:28 - 4:30So just as enzymes in your body
-
4:30 - 4:32can help you to break down
the food that you eat, -
4:32 - 4:34enzymes in your laundry detergent
-
4:34 - 4:37can help you to break down
the stains on your clothes. -
4:38 - 4:40It turns out that about
90 percent of the energy -
4:40 - 4:42that goes into doing the wash
-
4:42 - 4:43is from water heating.
-
4:43 - 4:45And that's for good reason --
-
4:45 - 4:47the warmer water
helps to get your clothes clean. -
4:47 - 4:50But what if you were able
to do the wash in cold water instead? -
4:50 - 4:52You certainly would save some money,
-
4:52 - 4:53and in addition to that,
-
4:53 - 4:56according to some calculations
done by Procter and Gamble, -
4:56 - 4:59if all households in the US
were to do the laundry in cold water, -
4:59 - 5:04we would save the emissions
of 32 metric tons of CO2 each year. -
5:04 - 5:05That's a lot,
-
5:05 - 5:06that's about the equivalent
-
5:06 - 5:10of the carbon dioxide
emitted by 6.3 million cars. -
5:10 - 5:12So, how would we go
about designing an enzyme -
5:12 - 5:13to realize these changes?
-
5:13 - 5:16Enzymes didn't evolve
to clean dirty laundry, -
5:16 - 5:18much less in cold water.
-
5:18 - 5:21But we can go to nature,
and we can find a starting point. -
5:21 - 5:24We can find an enzyme
that has some starting activity, -
5:24 - 5:26some clay that we can work with.
-
5:26 - 5:29So this is an example of such an enzyme,
right here on the screen. -
5:29 - 5:32And we can start playing
with those amino acids, as I said, -
5:32 - 5:34putting some letters in,
taking some letters out, -
5:34 - 5:35rearranging those.
-
5:35 - 5:38And in doing so, we can generate
thousands of enzymes. -
5:38 - 5:41And we can take those enzymes,
-
5:41 - 5:44and we can test them
in little plates like this. -
5:44 - 5:47So this plate that I'm holding in my hands
-
5:47 - 5:49contains 96 wells,
-
5:49 - 5:53and in each well is a piece of fabric
with a stain on it. -
5:53 - 5:55And we can measure
how well each of these enzymes -
5:55 - 5:58are able to remove the stains
from the pieces of fabric, -
5:58 - 6:00and in that way see how well it's working.
-
6:00 - 6:02And we can do this using robotics,
-
6:02 - 6:04like you'll see
in just a second on the screen. -
6:07 - 6:10OK, so we do this, and it turns out
-
6:10 - 6:12that some of the enzymes
are sort of in the ballpark -
6:12 - 6:13of the starting enzyme.
-
6:13 - 6:15That's nothing to write home about.
-
6:15 - 6:18Some are worse, so we get rid of those.
-
6:18 - 6:19And then some are better.
-
6:19 - 6:22Those improved ones
become our version 1.0s. -
6:22 - 6:24Those are the enzymes
that we want to carry forward, -
6:24 - 6:26and we can repeat this cycle
again and again. -
6:26 - 6:30And it's the repetition of this cycle
that lets us come up with a new enzyme, -
6:30 - 6:32something that can do what we want.
-
6:32 - 6:33And after several cycles of this,
-
6:33 - 6:35we did come up with something new.
-
6:35 - 6:39So you can go to the supermarket today,
and you can buy a laundry detergent -
6:39 - 6:43that lets you do the wash in cold water
because of enzymes like this here. -
6:43 - 6:45And I want to show you
how this one works too. -
6:45 - 6:48So I've got two more tubes here,
-
6:48 - 6:50and these are both milk again.
-
6:51 - 6:52And let me show you,
-
6:52 - 6:54I've got one that I'm going
to add this enzyme to -
6:54 - 6:56and one that I'm going
to add some water to. -
6:56 - 6:58And that's the control,
-
6:58 - 6:59so nothing should happen in that tube.
-
6:59 - 7:03You might find it curious
that I'm doing this with milk. -
7:03 - 7:04But the reason that I'm doing this
-
7:04 - 7:07is because milk
is just loaded with proteins, -
7:07 - 7:11and it's very easy to see
this enzyme working in a protein solution, -
7:11 - 7:14because it's a master protein chopper,
-
7:14 - 7:15that's its job.
-
7:15 - 7:17So let me get this in here.
-
7:18 - 7:22And you know, as I said,
it's a master protein chopper -
7:22 - 7:26and what you can do is you can extrapolate
what it's doing in this milk -
7:26 - 7:28to what it would be doing in your laundry.
-
7:28 - 7:31So this is kind of a way to visualize
what would be happening. -
7:31 - 7:33OK, so those both went in.
-
7:34 - 7:38And I'm going to give this
a quick zip as well. -
7:43 - 7:47OK, so we'll let these sit over here
with the chymosin sample, -
7:47 - 7:49so I'm going to come back
to those toward the end. -
7:51 - 7:54Well, what's on the horizon
for enzyme design? -
7:54 - 7:56Certainly, it will get it faster --
-
7:56 - 7:58there are now approaches
for evolving enzymes -
7:58 - 8:00that allow researchers to go
through far more samples -
8:00 - 8:02than I just showed you.
-
8:02 - 8:04And in addition to tinkering
with natural enzymes, -
8:05 - 8:06like we've been talking about,
-
8:06 - 8:09some scientists are now trying to design
enzymes from scratch, -
8:09 - 8:13using machine learning,
an approach from artificial intelligence, -
8:13 - 8:15to inform their enzyme designs.
-
8:15 - 8:19Still others are adding
unnatural amino acids to the mix. -
8:19 - 8:21We talked about
the 20 natural amino acids, -
8:21 - 8:23the common amino acids, before --
-
8:23 - 8:24they're adding unnatural amino acids
-
8:24 - 8:28to make enzymes with properties unlike
those that could be found in nature. -
8:28 - 8:30That's a pretty neat area.
-
8:30 - 8:35How will designed enzymes affect you
in years to come? -
8:35 - 8:37Well, I want to focus on two areas:
-
8:37 - 8:39human health and the environment.
-
8:40 - 8:42Some pharmaceutical companies
-
8:42 - 8:45now have teams that are dedicated
to designing enzymes -
8:45 - 8:49to make drugs more efficiently
and with fewer toxic catalysts. -
8:49 - 8:50For example, Januvia,
-
8:50 - 8:53which is a medication to treat
type 2 diabetes, -
8:53 - 8:54is made partially with enzymes.
-
8:54 - 8:58The number of drugs made with enzymes
is sure to grow in the future. -
8:59 - 9:00In another area,
-
9:00 - 9:01there are certain disorders
-
9:01 - 9:04in which a single enzyme
in a person's body doesn't work properly. -
9:04 - 9:06An example of this
is called phenylketonuria, -
9:06 - 9:08or PKU for short.
-
9:08 - 9:12People with PKU are unable to properly
metabolize or digest phenylalanine, -
9:12 - 9:16which is one of the 20 common amino acids
that we've been talking about. -
9:16 - 9:20The consequence of ingesting phenylalanine
for people with PKU -
9:20 - 9:24is that they are subject
to permanent intellectual disabilities, -
9:24 - 9:26so it's a scary thing to have.
-
9:26 - 9:28Now, those of you with kids --
-
9:28 - 9:31do you guys have kids, here,
which ones have kids? -
9:31 - 9:32A lot of you.
-
9:32 - 9:34So may be familiar with PKUs,
-
9:34 - 9:39because all infants in the US
are required to be tested for PKU. -
9:39 - 9:42I remember when Anthony, my son,
had his heel pricked to test for it. -
9:43 - 9:45The big challenge with this
is: What do you eat? -
9:45 - 9:49Phenylalanine is in so many foods,
it's incredibly hard to avoid. -
9:49 - 9:52Now, Anthony has a nut allergy,
and I thought that was tough, -
9:52 - 9:54but PKU's on another level of toughness.
-
9:54 - 9:57However, new enzymes
may soon enable PKU patients -
9:57 - 9:59to eat whatever they want.
-
9:59 - 10:03Recently, the FDA approved an enzyme
designed to treat PKU. -
10:03 - 10:05This is big news for patients,
-
10:05 - 10:07and it's actually very big news
-
10:07 - 10:09for the field of enzyme-replacement
therapy more generally, -
10:09 - 10:13because there are other targets out there
where this would be a good approach. -
10:15 - 10:17So that was a little bit about health.
-
10:17 - 10:19Now I'm going to move to the environment.
-
10:19 - 10:22When I read about
the Great Pacific Garbage Patch -- -
10:22 - 10:25by the way, that's, like,
this huge island of plastic, -
10:25 - 10:27somewhere between California and Hawaii --
-
10:27 - 10:31and about microplastics
pretty much everywhere, -
10:31 - 10:32it's upsetting.
-
10:32 - 10:34Plastics aren't going away anytime soon.
-
10:34 - 10:36But enzymes may help us
in this area as well. -
10:36 - 10:40Recently, bacteria producing
plastic-degrading enzymes were discovered. -
10:40 - 10:43Efforts are already underway
to design improved versions -
10:43 - 10:44of these enzymes.
-
10:45 - 10:47At the same time, there are enzymes
that have been discovered -
10:47 - 10:49and that are being optimized
-
10:49 - 10:52to make non-petroleum-derived
biodegradable plastics. -
10:53 - 10:57Enzymes may also offer some help
in capturing greenhouse gases, -
10:57 - 11:01such as carbon dioxide, methane
and nitrous oxide. -
11:01 - 11:03Now, there is no doubt,
these are major challenges, -
11:03 - 11:05and none of them are easy.
-
11:05 - 11:09But our ability to harness enzymes
may help us to tackle these in the future, -
11:09 - 11:12so I think that's another area
to be looking forward. -
11:12 - 11:14So now I'm going to get back
to the demo -- -
11:14 - 11:15this is the fun part.
-
11:15 - 11:18So we'll start with the chymosin samples.
-
11:20 - 11:22So let me get these over here.
-
11:22 - 11:23And you can see here,
-
11:23 - 11:25this is the one that got the water,
-
11:25 - 11:27so nothing should happen to this milk.
-
11:27 - 11:29This is the one that got the chymosin.
-
11:29 - 11:32So you can see that it totally
clarified up here. -
11:32 - 11:34There's all this curdled stuff,
that's cheese, -
11:34 - 11:36we just made cheese
in the last few minutes. -
11:36 - 11:37So this is that reaction
-
11:37 - 11:41that people have been doing
for thousands and thousands of years. -
11:41 - 11:44I'm thinking about doing this one
at our next Kids to Work Day demo -
11:44 - 11:46but they can be
a tough crowd, so we'll see. -
11:46 - 11:47(Laughter)
-
11:47 - 11:50And then the other one
I want to look at is this one. -
11:50 - 11:54So this is the enzyme
for doing your laundry. -
11:54 - 11:58And you can see that it's different
than the one that has the water added. -
11:58 - 11:59It's kind of clarifying,
-
11:59 - 12:02and that's just what you want
for an enzyme in your laundry, -
12:02 - 12:04because you want to be able
to have an enzyme -
12:04 - 12:07that can be a protein chowhound,
just chew them up, -
12:07 - 12:10because you're going to get
different protein stains on your clothes, -
12:10 - 12:13like chocolate milk
or grass stains, for example, -
12:13 - 12:16and something like this
is going to help you get them off. -
12:16 - 12:18And this is also going to be
the thing that allows you -
12:18 - 12:21to do the wash in cold water,
reduce your carbon footprint -
12:21 - 12:22and save you some money.
-
12:25 - 12:26Well, we've come a long way,
-
12:26 - 12:31considering this 7,000-year journey
from enzymes in cheese making -
12:31 - 12:33to the present day and enzyme design.
-
12:34 - 12:36We're really at a creative crossroads,
-
12:36 - 12:40and with enzymes,
can edit what nature wrote -
12:40 - 12:42or write our own stories with amino acids.
-
12:43 - 12:46So next time you're outdoors
on a muggy night -
12:46 - 12:47and you see a firefly,
-
12:48 - 12:49I hope you think of enzymes.
-
12:49 - 12:52They're doing amazing things for us today.
-
12:52 - 12:53And by design,
-
12:53 - 12:56they could be doing
even more amazing things tomorrow. -
12:56 - 12:57Thank you.
-
12:57 - 12:59(Applause)
- Title:
- How designing brand-new enzymes could change the world
- Speaker:
- Adam Garske
- Description:
-
"If DNA is the blueprint of life, enzymes are the laborers that carry out its instructions,' says chemical biologist Adam Garske. In this fun talk and demo, he shows how scientists can now edit and design enzymes for specific functions -- to help treat diseases like diabetes, create energy-efficient laundry detergent and even capture greenhouse gases -- and performs his own enzyme experiment onstage.
- Video Language:
- English
- Team:
- closed TED
- Project:
- TEDTalks
- Duration:
- 13:12
Oliver Friedman edited English subtitles for How designing brand-new enzymes could change the world | ||
Oliver Friedman edited English subtitles for How designing brand-new enzymes could change the world | ||
Oliver Friedman edited English subtitles for How designing brand-new enzymes could change the world | ||
Brian Greene edited English subtitles for How designing brand-new enzymes could change the world | ||
Erin Gregory approved English subtitles for How designing brand-new enzymes could change the world | ||
Erin Gregory edited English subtitles for How designing brand-new enzymes could change the world | ||
Krystian Aparta accepted English subtitles for How designing brand-new enzymes could change the world | ||
Krystian Aparta edited English subtitles for How designing brand-new enzymes could change the world |