0:00

Oh, watch your step. Wow, your attic

0:03

is so dark. Dark? I

0:05

know, right? It's the perfect place

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to stream horror movies. Flee me.

0:10

What movie is that? I haven't pressed

0:12

play yet. Ahh!

0:15

AT&T Fiber with All-Fi covers your whole house.

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Even your really, really creepy attic turned home

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theater. Jimmy, what have I told you

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about scaring our guests? Get AT&T

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Fiber with All-Fi and live like a

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gillionaire. Limited availability covers may require

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extenders at additional charge. This

0:31

program is sponsored by the

0:33

Kavli Prize, which honors scientists

0:35

for breakthroughs in astrophysics, nanoscience,

0:37

and neuroscience. The

0:39

Kavli Prize is a partnership among

0:42

the Norwegian Academy of Science and

0:44

Letters, the Norwegian Ministry of Education

0:46

and Research, and the

0:48

U.S.-based Kavli Foundation in Los

0:50

Angeles, California. I'm

0:57

Alan Alder, and this is Clear

0:59

and Vivid, conversations about

1:01

connecting and communicating. In

1:07

this, the last of our four special

1:10

episodes celebrating the Kavli Prize, I'll

1:12

be talking with two of the winners of

1:14

this year's Kavli Prize for nanotechnology. Chad

1:18

Merkin developed microscopic carriers able to

1:20

deliver new types of medicines. Robert

1:23

Langer also made breakthroughs in drug delivery

1:26

by devising ways for drugs to be released

1:28

in the body slowly over time. Both

1:32

Merkin and Langer have played major

1:34

roles in developing the biotechnology industry.

1:37

Between them, they've filed thousands of patents

1:39

and they've helped found multiple companies. First,

1:42

my conversation with Chad Merkin. You

1:47

know, I've been excited about nanotechnology since

1:49

I first heard about it. You've

1:51

been doing incredible work in this field. You're

1:54

the person to ask this question that all

1:56

of us can understand a little better. How

1:58

would you describe nanotechnology? It's

2:00

a study of the small. It's an interesting field

2:02

in the sense that everything

2:05

when miniaturized is different.

2:08

If you take anything and shrink it down to the

2:10

nanometer length scale it has different properties. The

2:13

thing that's hard for most of us to get

2:15

I think is how small small

2:17

is. You say nanometer or nanometer? Tomato

2:19

or tomato. You can go either way.

2:23

So a nanometer, it's a

2:25

billionth of a meter? Well the way I like

2:27

to think about it is a human red blood

2:29

cell is about 80 microns in

2:32

diameter. So 80,000 nanometers.

2:35

So it's huge compared to

2:37

a nanoparticle, a 10 nanometer

2:39

nanoparticle. This is a really, really

2:42

tiny length scale. It's not the tiniest of length

2:44

scales because atoms are even smaller.

2:47

But it's a length scale that actually

2:49

is in between what I call

2:51

the chemistry length scale and the biological length scale. That's one

2:53

of the reasons it's so interesting especially

2:56

when you talk about advances in

2:58

biology and medicine. I

3:00

think it was around 1959 when Richard

3:02

Feynman gave that talk called Plenty of

3:05

Room at the Bottom, meaning there's a

3:07

lot to be learned about the smallest

3:09

particles, nanoparticles. He was predicting a lot

3:11

of new research. But

3:14

it was quite a bit later before you got into

3:16

it. What got you into it? Was there still plenty

3:18

of room at the bottom or was it a thriving

3:20

field by then? All the room

3:22

was still at the bottom. So

3:25

I always say I hit my

3:27

career with perfect timing. Timing

3:29

is everything in many careers, especially the case

3:32

in science. So I'd come from a lab

3:34

where people were beginning to

3:36

understand that really interesting things happen when

3:38

you miniaturize them. And we were miniaturizing

3:40

them to the micro scale. And

3:43

then right when I moved to Northwestern, these

3:45

really powerful tools called scanning tunneling microscopes and

3:47

atomic force microscopes that allow you to manipulate

3:50

atoms one at a time were

3:52

coming online and in fact becoming commercially available.

3:55

And I began to get interested in

3:57

them and began to develop a real

3:59

path. for really looking at

4:02

the chemical consequences of miniaturization and

4:04

ultimately began to build a very

4:07

large effort in my own research operation and

4:09

now we've built the largest Institute of Northwestern

4:11

for nanotechnology. It's called the International Institute

4:14

for Nanotechnology. So spherical

4:16

nucleic acid which is what you

4:18

won the Cauley Prize for, right?

4:21

Correct. You start off with a

4:23

particle that's spherical and

4:25

you somehow can attach little bits

4:27

of DNA to it and yeah

4:30

let me let me take you back a little

4:33

bit so so so it's been known for a

4:35

long time that you can make materials called colloids

4:37

these are dispersions of particles nanoparticles. Gold

4:40

is a great example of this importance of

4:42

miniaturization. If I take and shrink gold down

4:44

to the nanometer length scale it's no longer

4:46

golden color. The tiny little particles

4:48

are actually red in color. Oh I read

4:50

they use that ability for it to turn

4:52

color to make stained glass in the Middle

4:55

Ages. That's exactly right so so so in

4:57

the middle age and even to this day

4:59

a lot of the colors in

5:01

stained glass windows come from these particles. We

5:04

then take those same particles we've learned how to

5:06

make them and make them in large quantities and

5:09

we can also synthesize DNA short

5:12

little strands of DNA that have n groups that

5:14

can chemically react with the particles and

5:16

arrange themselves in the surface of the particle and

5:19

at high density you get kind of

5:21

a kushball like structure a globular

5:23

form of DNA that has

5:26

no natural equivalent it's only made through

5:28

chemistry and nanotechnology concepts but

5:30

it has properties that allow

5:33

it to interact with living and biological systems

5:35

in ways that we've never seen before. Now

5:37

whose DNA is it? Is it the DNA of

5:40

a person or the DNA of an invading

5:42

microorganism or what? It's

5:45

a great question it's actually any sort

5:47

of DNA we'd like we

5:49

can make whatever code we'd like in the course of

5:51

an afternoon using something called

5:53

a gene machine. This is what makes

5:55

it so powerful with respect to your

5:58

question everything living has a in

6:00

each genetic code. You do, I

6:02

do, any organism does, any

6:05

infectious disease organism, viruses, bacteria. If

6:07

I know those codes, I now

6:10

can create tiny particles that are

6:12

complementary to those codes and

6:14

they can latch onto them. So one of the

6:16

first things that we invented and

6:18

developed based upon spherical nucleic acids, really

6:21

sensitive and selective point

6:23

of care medical diagnostic tools that allowed

6:25

you to detect in

6:28

a sample different disease

6:30

elements. And you could do

6:32

it very rapidly and you could look for many different signatures

6:35

of disease in parallel with

6:37

one another. That must make a tremendous difference

6:39

to be able to diagnose a

6:41

disease in the hospital or perhaps even

6:44

in a doctor's office. That's

6:46

exactly right. So we wanna go ultimately to the doctor's

6:48

office, but it would turn out at the time, so

6:50

this goes back to the early 2000s, we

6:52

invented one of the first point of care

6:54

medical diagnostic tools of the nano age based

6:57

upon spherical nucleic acids.

7:00

And the idea was to try to

7:02

move these testing capabilities from remote labs

7:05

at the very least to the hospital. Apparently

7:07

you can use this not only to diagnose

7:09

a disease, but to treat a disease as

7:11

well, is that right? Well,

7:13

it's interesting. Yeah, the same constructs are

7:15

used also for the development of therapeutics.

7:18

The world has opened up to

7:20

the idea of genetic medicines through

7:22

the COVID era, right? That's a

7:24

fantastic class of genetic medicines. And

7:27

that's the reason why we're talking about the

7:29

mRNA vaccines. Well, it turns out

7:31

that DNA and RNA delivered in

7:34

different forms can be used for anything ranging

7:36

from creating medicines that downregulate the

7:39

production of certain proteins that cause disease. So if you

7:42

have a certain disease that causes you to produce too

7:44

much of a given protein, you

7:46

can use these types of drugs

7:48

to downregulate that. You can

7:50

cause cancer cells to selectively die, and

7:53

you can use these types of

7:55

therapies for not just infectious disease, but

7:58

for many forms of cancer that basically Now

12:00

the vast majority of nanoparticles are

12:03

spherical. So that was the obvious

12:05

one to start with. Hence when

12:07

we made the first DNA modified particle,

12:09

it was a spherical nucleic acid as

12:11

opposed to a cubic nucleic acid or

12:13

whatever else you'd like to work with

12:15

respect to shape. ["The

12:24

I'm interested in the fact that

12:26

your companies, and you've created a

12:28

number of companies, some of them

12:30

seem to go much broader than

12:32

the field of medication. For instance,

12:34

you have one that helps create

12:36

the smallest 2D printer. What

12:38

do you need a small 2D printer for?" Ah,

12:41

that's interesting. Okay, so yeah, we invented what's

12:44

often referred to as the

12:46

world's smallest pen, the world's smallest printer. We

12:48

took one of these tools that

12:51

we talked about at the start of this podcast that

12:54

was used to manipulate atoms, something called

12:56

an atomic force microscope. And

12:58

it was invented to actually get a

13:00

topological map of a surface, to

13:02

look at the contour of a surface on the

13:05

nanometer length scale. Basically it's a

13:07

feeler. And we

13:09

converted it from a reader to a writer

13:12

by putting chemicals on the tip that could chemically

13:14

react then with the surface that you were moving

13:16

it over. So would you

13:18

use the world's smallest pen to write an

13:20

apology letter? Well, what do

13:22

you need it for? We, one

13:24

stunt we did was we used the world's smallest pen

13:26

to write Feynman's speech, plenty of room at the bottom

13:29

to prove a point. And I'll

13:31

send you a copy of that. That's actually quite interesting.

13:33

Great. What use does that have?

13:36

Or are you waiting to find the use? It

13:38

has a lot of uses. So the first thing

13:40

you can do is you can begin to make

13:42

miniaturized electronics. This allowed us to

13:44

make devices out of molecules, asking instead of

13:46

using silicon, can we make molecules that behave,

13:48

for example, as transistors and can we place

13:51

them between the components of devices so that

13:53

we can make measurements on them. On

13:55

the biological side of things, we

13:58

can now begin to pattern proteins on.

14:00

surfaces and different types of chemical structures

14:02

that could control what cells do. So

14:04

we could pattern underneath a single cell

14:07

thousands of different types of chemical components

14:10

that could regulate how that cell moves on a

14:12

surface, how it grows, if it's a stem cell,

14:14

how it differentiates, how it becomes a bone cell,

14:16

how it becomes a nerve cell, how it becomes

14:18

a fat cell. All sorts

14:20

of things become possible when you can

14:23

fabricate on this tiniest of length scales.

14:25

This is really mind-boggling. And

14:28

it sounds incredibly promising to me

14:30

to learn that you're dealing with

14:32

nanomaterials that can accelerate

14:34

the energy transition, I understand. How does that

14:36

work? Well, this is very... So take that

14:39

same tools. We came up with a way,

14:41

instead of using one tiny tip, we

14:43

now have commercial tools that use

14:46

up to 11 million tips. And

14:49

each of those tips you

14:51

can kind of think of as individual people that

14:54

are all chemically synthesizing something different

14:56

in different locations on the chip. So

14:59

now imagine having a two by two centimeter chip

15:02

where we can make millions to billions

15:04

of new materials, all positionally

15:06

encoded on the chip. This

15:09

allows you to begin to look at

15:11

different combinations of elements to find the

15:14

next materials that matter. And so

15:16

we have a company called Matik,

15:18

MatIQ, that is trying

15:20

to basically use this to find the

15:23

materials that will allow you to convert

15:25

CO2 into high value

15:27

products, ethylene, propylene, methane,

15:31

acetic acid, that will

15:33

allow you to capture solar energy efficiently,

15:35

that will allow you to create very

15:37

efficient solar displays, that will allow you

15:40

to electrify almost anything and convert it

15:42

into... Take a low

15:44

value feedstock and turn it into a

15:46

high value product. But

15:49

the advantage is we've

15:51

gone from this tool that was designed for

15:53

fabrication to the world's most

15:55

parallel synthesis tool. So that's the

15:57

equivalent of having 11 million people coming

15:59

to your... lab and all making

16:02

things simultaneously. We've dramatically accelerated how

16:04

fast the world finds materials that

16:06

ultimately matter. And to me, that's

16:08

a game changer because if you

16:11

think of history, right? We've

16:13

had the Stone Age, the Bronze

16:15

Age, the Iron Age, we're living

16:18

through the Silicon Age. New materials

16:20

drive new capabilities. They change civilization

16:22

in a significant way. And

16:24

so if you can make things faster than anybody else

16:27

can, good things are going to happen. This

16:33

sounds like an impossible question to answer given

16:35

what you just said. But

16:37

do you have a vision of what could be the

16:39

next thing in nano beyond where you can go now?

16:42

That's, I think,

16:45

so dependent upon the person that you talk

16:47

to. In my two areas, I want

16:49

to do two things. One, on the medical side, I

16:52

want to completely change the way vaccines are produced.

16:54

And I don't mean by mRNA. I

16:56

mean completely change the way we develop vaccines

16:58

using the vaccine. We call it vaccines using

17:00

nanotechnology to put together the components in

17:03

a vaccine that matter, the adjuvant that's

17:05

the stimulator of the immune system and the antigen,

17:07

which is a trainer of the immune system, some

17:09

sort of peptide that tells your immune system to

17:12

only kill certain cancer cells, but not touch the

17:14

healthy cells. Putting those together in

17:16

the form of a

17:18

nanostructure where you find the

17:20

structural arrangement that maximizes vaccine

17:23

performance. We call that rational vaccinology.

17:25

That is vaccines 3.0. That's coming down the pike.

17:27

We're going to see that over the next 10

17:29

years. I think you're going to see tremendous

17:31

advances in that area. The

17:34

second area is a little

17:36

bit builds off what I just said with respect

17:38

to the world's most parallel synthesis tools. So

17:42

when I make a chip that has billions

17:44

of new materials and I screen it to

17:46

find the materials that allow me to convert,

17:48

for example, CO2 into ethanol.

17:50

That's fantastic. But

17:52

those chips also represent

17:56

the largest amount of high

17:58

quality data in the immune system. materials

18:00

discovery space. So we're

18:02

naturally creating an incredible database

18:05

that can be used to train artificial

18:08

intelligence algorithms so that

18:10

machines can now begin to tell us

18:12

what types of materials to go after, what types of

18:14

nanostructures to go after that will really

18:17

make a difference depending upon our need. And

18:19

that is the ultimate in terms of using these

18:21

types of tools to get to a game-changing,

18:24

world-changing capability. Well,

18:27

your work is extraordinary, and it's

18:29

been really, really enlightening to talk

18:31

to you. I very

18:33

much appreciate you taking the time because I

18:36

can't imagine anybody busier than you doing

18:38

the things you've just described. And

18:40

thanks for being with us today. It was just great. I

18:43

appreciate it. Thank you very much. When

18:50

we come back from our break, my guest is Robert

18:52

Langer, a chemical engineer

18:54

famed for his prolific inventiveness. Langer's

18:58

Covelry Prize announcement cites his

19:00

role in using nanotechnology to

19:03

help develop techniques to deliver drugs in

19:05

new ways by controlling how

19:07

they're released in the body. Our

19:12

program is sponsored by the

19:15

Covelry Prize, which honors scientists

19:17

for breakthroughs in astrophysics, nanoscience,

19:19

and neuroscience that transform

19:22

our understanding of the very big,

19:24

the very small, and the

19:26

very complex. From

19:28

scientific breakthroughs like the discovery

19:30

of CRISPR-Cas9 and the detection

19:33

of gravitational waves, to

19:35

inventing new fields of research, Covelry

19:37

Prize Laureates push the limits of what

19:40

we know and advance science in ways

19:42

that could not have been imagined. The

19:45

Covelry Prize is a partnership among

19:47

the Norwegian Academy of Science and

19:49

Letters, the Norwegian Ministry of Education

19:51

and Research, and the

19:53

US-based Covelry Foundation in Los

19:56

Angeles, California. The

38:01

music is courtesy of the Stefan Koenig

38:03

Trio. Next

38:12

week we'll be back with a conversation on

38:14

my favorite topic, connecting and

38:17

communicating. And not just

38:19

communicating, but super communicating. That's

38:22

the subject of a new book by journalist

38:24

Charles Duhigg. When they've talked to

38:27

folks who are consistent super communicators, because we're all

38:29

super communicators at one time or another, but

38:31

people who can connect with almost anyone, who are

38:33

really good at this. And they

38:35

ask them, have you always been good at communication?

38:39

Most often they say no. They say

38:41

something like, you know, when I was

38:43

in high school I had trouble making friends, so

38:45

I really had to study how kids talk to each other. Or

38:48

my parents got divorced and I had to be the

38:50

peacemaker between them. Or my dad was

38:52

a salesman and my grandfather was a con man. And

38:55

so I really had to think about, like, study them

38:57

and try and figure out what's going on. And I

39:00

think what's happening there is that oftentimes

39:02

thinking, just a little, like half

39:04

an inch deeper, thinking about communication

39:07

is what makes us better at communication. Charles

39:10

Duhigg and how those he calls super

39:12

communicators unlock the secret language

39:15

of connection. Next

39:17

time on Clear and Vivid. For

39:20

more details about Clear and Vivid and to sign

39:22

up for my newsletter, please

39:24

visit alanalda.com. And

39:27

you can also find us on Facebook and

39:29

Instagram at Clear and Vivid. Thanks

39:32

for listening. Bye-bye. Ben

39:44

hadn't had a decent night's sleep in a

39:47

month. So, during

39:49

one of his restless nights, he booked

39:51

a package triple broth on Expedia. When

39:54

he arrived at his beachside hotel,

39:56

he discovered a miraculous bed slump

39:58

between two trees. and fell into

40:00

the best sleep of his life.

40:04

You were made to be rechargeable.

40:07

We were made to package flights and

40:09

hotels and hammocks for less. Expedia,

40:12

made to travel.