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To learn more about Morgan

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and their ascension to

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R1, visit morgan.edu/research. This

1:25

is a science podcast for February 16, 2024. I'm

1:29

Sarah Crespi. First up

1:31

this week, former myth buster Adam

1:33

Savage chats with science's editor-in-chief Holden

1:35

Thorpe about how to combat misinformation,

1:37

plus a few myths Savage still

1:39

wants to tackle. Next

1:42

on the show, making blueberries without blue

1:44

pigments. Researcher Rox Middleton

1:46

joins me to talk about how specialized wax

1:48

on the surface of blueberries actually give the

1:51

berries their blue hue. In

1:53

this sponsored segment from our custom publishing

1:55

office, director of custom publishing, Erica

1:58

Berg, talks with professor Jim Wells.

2:00

about the latest advancements in

2:02

organoid therapies for metabolic and

2:04

digestive diseases. It

2:10

may be surprising to you that for many

2:12

working scientists today, MythBusters was

2:15

a foundational introduction to the

2:17

scientific method. Or for

2:19

others, an introduction into the joy of

2:21

designing experiments to figure out how the

2:23

world works. This week,

2:26

MythBuster Adam Savage spoke with

2:28

science's editor-in-chief Holden Thorpe about

2:30

engaging the public in the

2:32

scientific process and importantly, how

2:34

to convey its self-correcting nature.

2:37

They start out talking about

2:39

MythBusters ability to inspire scientific

2:41

careers. My

2:44

son is about to defend

2:46

his PhD thesis in neuroscience

2:48

at Columbia and I think if I

2:50

asked him, you know, are you a

2:52

scientist more because of me or more because of

2:55

the MythBusters, he probably wouldn't want to answer my

2:57

question. Well,

3:01

let him know that one day I'll

3:03

call upon my army, okay? Okay,

3:05

there you go. It has been

3:08

a remarkable progression over the last 20-plus

3:10

years of people saying, hey, you got

3:12

me through high school chemistry to now

3:14

saying, I've sold three startups and MythBusters

3:16

got me interested in science at the

3:18

very beginning. So for

3:20

your fans, tell us what you've been

3:22

up to since the show went off the air.

3:25

We wrapped the show back in 2015. 2016

3:29

officially was the last airing of this

3:31

last season. And since then,

3:34

I've made a couple of television

3:36

shows, MythBusters Jr. with eight amazing

3:38

young colleagues and Savage builds. We

3:41

made 10 episodes of all

3:43

the things I've ever wanted to build

3:45

up till that point, including putting laser

3:47

tag on some Peter Jackson's World War

3:50

I airplanes and enjoying real dog fights

3:52

over New Zealand. And

3:54

then when COVID hit, my

3:56

YouTube channel had always been a kind of

3:58

like the thing on the side while

4:01

I was working on television. And when

4:03

COVID hit that relationship

4:05

reversed and YouTube became

4:08

the main thing that I was

4:10

working on. And frankly, I'm happier

4:13

now professionally, creatively

4:16

than I have ever been in my

4:18

life. And I am in this cave

4:20

here in San Francisco building almost every

4:22

single day. And it is totally dreamy.

4:25

Yeah, that sounds awesome. All

4:27

right, let me ask you some more

4:29

provocative things about what's going on and

4:31

how we can learn from you. So

4:33

you're probably following that research integrity and

4:35

errors in science have kind of taken

4:37

over the zeitgeist. They

4:40

were always there for us. We were

4:42

always processing, you know, mistakes

4:44

that were made in papers and figuring out

4:47

how to correct the record. But now it's

4:49

all over the news. The president

4:51

of Stanford had to resign because he

4:53

published some images that were wrong, a

4:56

huge thing on superconductivity at

4:59

the University of Rochester, a

5:01

whole bunch of stuff about

5:03

behavioral economics. Then we had

5:05

a plagiarism with the Harvard president. Now there's

5:08

a huge thing in Dana-Farber. It's like, we're

5:10

just living through this thing. And

5:13

not everybody agreed with everything,

5:16

all the myths that you either confirmed or

5:18

busted over the years. So

5:20

when people disagreed with your conclusions,

5:22

what did you do? If you

5:24

thought they were credible? We

5:27

took them seriously. I mean, one of my favorite

5:29

things that we did on the show, I think

5:31

before the end of the first season, we were

5:33

getting word that we had gotten some experimental methodology

5:35

wrong and we

5:37

revisited the myth. There

5:39

were several stories like chicken

5:41

gun and rocket car that

5:44

we tackled multiple times based on

5:46

new data, new information, new ways

5:48

of executing it. Discovery

5:50

was never on board. They always had

5:52

to be dragged to do the revisits.

5:56

And to me, it was the most scientific thing

5:58

we did. We're experimenting. mentalist.

6:01

And so the result we have

6:03

isn't a fact, it's the best

6:05

story we currently have. And

6:07

if a new, better story comes up, I'll

6:10

tell you, and I haven't been paying

6:12

attention to the crisis in reproducibility that's

6:14

been happening. And I'm a big proponent

6:16

of open source publishing. I

6:19

personally feel like I can lay a lot

6:21

of the blame for the current crisis in

6:23

science with late stage capitalism and

6:26

the bizarre incentive models that

6:28

lead people, the publish

6:30

or perish pipeline, the

6:33

strained resources we've had for like the

6:35

last 40 years in academia. Absolutely, it's

6:37

unassailable that anything that's government funded should

6:39

be open source immediately. I can't believe

6:41

that's still a debate, but I

6:44

really feel like that holds a lot of the

6:46

blame for the crisis. Yeah, there

6:48

are lots of us working on different solutions

6:50

to that problem. Ours is, we

6:53

allow everybody who publishes with

6:55

us, even if it's

6:57

in a journal that has a paywall, to

7:00

send the accepted version

7:02

of the manuscript to any depository

7:04

they want to. Now, it's

7:06

taken decades to get to that point.

7:09

We've only gotten there recently, and

7:11

we definitely see good things come of

7:13

that. But you said something profound that

7:16

is very, very similar

7:19

to what we see in science, that

7:21

discovery didn't want to do the

7:24

retest. We see the

7:26

same thing with, if somebody

7:28

complains about a paper, a lot

7:31

of times the author will

7:33

fight us on trying to

7:35

work out if there's something wrong. But

7:37

we get by far the worst behavior

7:40

from the institutions who are sending

7:42

us statements that say Stanford

7:45

is very committed to research integrity

7:47

and telling us it's going to

7:49

take forever to do the investigation

7:51

and burying us in paperwork. All

7:54

we want to do is put a correction or retraction on

7:56

the paper. We don't care about all that other

7:58

stuff. We just want people to find the right answer.

8:01

So elaborate on that Hey

8:05

look, we screwed this up. What was the

8:07

reaction? We didn't say we screwed it up.

8:09

We said, hey, there's an opportunity to tell

8:11

a whole new narrative and we've got footage

8:13

we can use from the old narrative and

8:15

get people involved. They want one result. We're

8:17

giving them another. We're giving them another chance

8:19

to yell at us at the television. And

8:21

those ratings for our revisit episodes did great.

8:24

So while I say Discovery was a

8:26

reluctant partner in doing the revisits, it

8:28

wasn't like they fought us tooth and nail. Whenever

8:31

we planted a flag and put our foot

8:33

down and said this is something we want

8:35

to do, they were in general

8:37

from almost the whole run really great

8:39

partners. The third time we wanted

8:42

to do Rocketcar, we were like, hey we want to do

8:44

Rocketcar at third time and this time we need another 50

8:46

or 60 thousand dollars. And they

8:48

were like, absolutely that's great. So did

8:51

you ever have to change whether

8:53

a myth was confirmed or busted

8:56

as a part of one of these redos? Absolutely.

8:59

We came to different results lots of

9:01

times. I think running in the rain

9:03

is one we did three times and

9:05

came up with three different results. And

9:08

what is the final result on running in the rain?

9:10

The final result is that running and

9:13

walking will yield a difference in the amount

9:15

of rain you receive and it depends on

9:17

wind direction and the speed in which you're

9:19

running and the amount of time you are

9:21

spending out in the rain because of course

9:23

over a certain period of time everyone gets

9:25

the same amount of wet. But the

9:27

fundamental difference is on the order

9:30

of grams of water. Walking

9:32

is better than running but literally

9:34

only by about a tablespoon of water. I

9:37

think about it every time I go out

9:39

in the rain I think about your shop.

9:41

To me the lesson is it's not worth

9:43

the extra effort to run. No, it's totally

9:46

not. One of the things that I

9:48

found really interesting was that when we

9:50

would go back we never cared what the result

9:52

was going to be. People are like, did you

9:54

ever want to bust something or want to

9:56

prove something and you didn't? And actually that never

9:58

came about too well. us. We were very,

10:01

I think, pure in a

10:03

lack of bias over a certain result.

10:05

Yeah, that's awesome. All right,

10:07

let me switch to science communication.

10:10

You know, we're living through another crisis which

10:12

has always been there but it's taken

10:14

off in the last five years or

10:17

so with people

10:19

doubting scientific evidence

10:21

and ignoring it. COVID

10:24

accelerated it a lot, political events

10:26

happened at the same time that

10:29

accelerated it in a world

10:31

of whataboutism. You can't advocate for science without

10:33

people saying, you know, you're just saying that

10:35

because you're politics. So it's tough. Right.

10:38

You know, I write a lot about how to

10:40

get more people on board

10:42

with trusting science and it seems to

10:44

me you guys did

10:46

a really good job with this.

10:49

So I guess the first question

10:52

I would have is, was there

10:54

ever anybody who was

10:56

an adult? I mean, I think with kids, it's easier

10:59

but was there anybody who's ever an adult who

11:01

had made their mind up about a myth that

11:05

you either busted or confirmed in a

11:07

different direction from what they believed whose

11:10

mind you were able to change? Oh,

11:13

whose mind we're able to change. Yeah,

11:15

I want to know if there's a climate denier who

11:18

if they watched a Mythbusters about climate

11:20

change would go, okay, I

11:22

get it now. Yeah. First

11:24

of all, that's a question I haven't had, which

11:27

is in and of itself after 20 years of

11:29

talking about this show, totally amazing. Second

11:32

of all, I have so many examples

11:34

of the former. I will open

11:36

by giving you one of those. So one

11:38

of the most vitriolic arguments we settled

11:40

early on in the show was a

11:42

myth called airplane on a conveyor belt.

11:45

And as stated, the myth is if an

11:47

airplane is attempting to take off on a

11:49

runway and the runway is

11:52

in fact a conveyor belt running in

11:54

the opposite direction to the plane matching

11:56

its speed, can the airplane take off?

11:58

And the answer is always. always

12:00

and forever the airplane can take off

12:02

because the question has a bit of

12:05

fakery involved in its phrasing.

12:08

When the question says that the runway is a

12:10

conveyor belt running in the reverse direction of

12:13

the airplane, most people's minds immediately think that

12:15

that plane isn't moving forward as it's trying

12:17

to take off because the runway is matching

12:19

its speed. But

12:21

the airplane's medium is not the ground,

12:24

it's the air. And

12:26

the only reason it has wheels is to keep the propeller

12:28

from hitting the ground. So while a

12:30

car would remain stationary, a plane will always

12:32

move forward no matter how fast that runway

12:34

is operating in reverse. And we took a

12:36

half mile of tarp on an actual runway,

12:39

got an ultra light plane, put it on

12:41

the tarp, ran a pickup truck in

12:43

the opposite direction, and the pilot of

12:45

that plane did not think

12:47

his own plane was going to take off.

12:50

And he was as surprised as anybody when

12:52

it did. We knew it would. And

12:55

when that episode aired, we went and

12:57

looked at the forums and the general

12:59

response was still disagree. We didn't agree

13:01

before with the results and we don't agree

13:03

now even though they've proved it. Like they

13:05

must have gotten something wrong. Literally just like

13:07

that. So people's recalcitrance from

13:11

veering off of their own stance

13:13

on something is incredibly

13:15

rigid. Frankly, I think that one

13:18

of the, I laid some

13:20

of the blame in late-stage capitalism earlier in this

13:22

interview and I lay more of it here because

13:25

as soon as you can question someone's

13:27

integrity, as soon as

13:29

you're wondering what the financial incentives are

13:31

for the results they've been giving, if

13:34

there are financial incentives, that's problematic

13:36

and that needs to be addressed.

13:39

And so to me, full transparency

13:42

is the most important aspect of

13:44

science. We only stand on

13:46

the shoulders of giants because they tell us

13:48

what they did. And when we put stuff

13:50

behind paywalls or we have crazy

13:52

financial incentives for being the first or

13:55

being the newest or coming up with

13:57

something different, we end up with every

13:59

result can be changed. challenged for some reason or

14:01

another. You know, the thing

14:03

that I think we have a hard time

14:05

getting across is that science is set up

14:08

to be self-corrected, right? So the easiest way

14:10

to get a paper in science is

14:12

not by saying, oh, here's this theory that everybody believes

14:15

and I tested it again and it turns out it's

14:17

right. That's usually not going to be a science

14:19

paper. What's a science paper is here's

14:21

something everybody believed and guess what? We have to

14:23

change that now. You know, that'll get

14:25

you on the cover usually. Yeah. That's

14:28

kind of the thing that corrects for

14:30

this, but we have a very

14:32

hard time getting that across to people. They

14:34

don't trust that that's the case. No matter

14:36

how many times I tell them, look,

14:39

whatever contentious issue it is, if

14:41

scientists all believe something and someone disproves it and

14:43

sends me a paper, I'll publish it almost whatever

14:46

it is if it's credible. The

14:48

most beautiful epiphany I had about science

14:50

was looking at this beautiful 3D rendering

14:52

of our current universe model and realizing

14:54

it's not a model of the universe.

14:57

It is simply an amalgam

14:59

of all the current data we have

15:01

to tell ourselves a story. There

15:04

could be these completely fundamental ways

15:06

in which it is wrong and

15:09

we can still go and discover those things.

15:11

But yeah, this is the biggest difficulty is

15:14

when you come to a different result, it often

15:16

means people think like, well, science got it wrong.

15:19

It's like science is always

15:21

getting it certain degrees of wrong. It's not

15:23

like we get things right and then sometimes

15:25

it's wrong. It's like we're getting just less

15:27

and less wrong as we go. And

15:30

do you have any advice on how

15:32

we can get that across to people

15:34

better? For me, the secret sauce is

15:36

always to make it personal, is always

15:38

to find that intersection with my emotionality

15:41

about the things that I'm talking about

15:43

that makes them interesting to tell stories about.

15:46

I find the structure of

15:48

science surpassingly

15:50

beautiful. I find

15:52

the structure of figuring out how wrong

15:54

we are to be a

15:57

great frame to approach the world. That

16:00

frame can easily be weaponized

16:03

for nefarious purposes. My

16:06

favorite science communicators in the

16:08

world are Carl Sagan and

16:10

Richard Feynman, both of whom

16:12

radically personalized their science communication.

16:15

They really made it emotional.

16:17

That spoke to me as

16:19

a young reader. You

16:21

listen to Sagan read the pale

16:24

blue dot and I don't

16:27

think anyone listens to that and

16:29

comes back questioning Sagan's integrity

16:32

for finding the right answer.

16:34

I think that emotionality is one of

16:37

the ways he earns our respect and

16:39

our trust. Of course,

16:41

there's a temptation to go on TV and say,

16:43

I've got the answer. But

16:45

of course, we never have the answer. All we have is

16:47

the answer that we have right now. And

16:50

it's very hard for people to go

16:52

on TV and say, here's what we know

16:54

right now, but I might have to change it. And

16:57

the journalists don't like that because they want things

16:59

that are crisp. So how do we get

17:01

through that? Man, I remember

17:03

reading this thing about Oppenheimer, that when

17:05

he was running the Manhattan Project, he

17:08

was so cognizant of his

17:11

power in his position that if he

17:13

expressed an opinion, it would be assumed

17:15

to be correct that he

17:18

said very little because he

17:20

understood how damaging he

17:22

could be if he was wrong, because

17:24

people would just take it as a fact. Sorry,

17:27

what was your original question? Well,

17:30

I write a lot about how we've

17:33

somehow got to get this across to

17:36

people because we'll never get all

17:38

4 million or whatever it is

17:41

scientists to be communicators

17:43

like Dick Feynman or Carl Sagan

17:45

or Adam Savage. And

17:47

so the only solution

17:49

is to do a better job of

17:52

telling people how science actually works. I

17:55

am always suspicious of statements like, this is the

17:57

best career. This is the most pure art form.

18:00

None of that is true. There is no best career,

18:02

there's no best job. Everyone finds their

18:05

own way. But as I have traveled around

18:07

the world in the last 20 years, meeting

18:09

and talking to scientists, talking to them about

18:11

their work, getting to experience

18:13

them on a level that I never

18:15

imagined, what I've come to

18:17

see is that I don't think I

18:19

have met a working scientist that didn't

18:21

love their job, that didn't

18:24

love the process of their

18:26

job, and was deeply connected

18:28

to both the granular work of their

18:30

day-to-day and how it fit into the

18:32

big picture. And when you spend

18:34

a lot of time around people whose joy

18:37

comes from gathering that

18:39

data and interpreting it and processing it and

18:41

working with others, it's very

18:43

infectious. I feel like

18:45

there is still a story to

18:48

be told that covers that joy.

18:50

That's a story that I think is

18:53

continually worth telling. You

18:55

know, you're right, replicating other

18:57

people's results isn't sexy, but

19:00

it is deeply beautiful and joyful. And

19:03

I find that those are the stories that

19:05

I want to continue telling. So

19:07

those are the stories that I

19:10

seek out, that joy at discovery

19:12

that exists in every working scientist. This

19:14

has been awesome. So one last fun

19:17

question. If there's one myth

19:19

you could have tested that you didn't do, what would it

19:22

be? Oh, I've got it. It's actually one

19:24

I had to give up in the last season. I

19:26

had this beautiful little 15-minute story, and

19:29

we had a tanker car

19:31

implosion went so cattywampus that

19:33

we ended up with like 20 minutes of

19:36

extra material. And as a producer, I had

19:38

to give up one of my stories. And

19:40

this story was a Native American hunting myth.

19:42

And this myth is that if you wanted

19:44

to hunt ducks, Native Americans had a technique

19:46

where they would go to a pond where

19:49

ducks congregated and float pumpkins on the pond

19:51

for a few weeks. And the

19:53

ducks would get familiar with pumpkins floating

19:55

around. And then the hunter, when he

19:57

wanted to eat duck, would put a pumpkin on his head

19:59

and cut two eye holes out of it and

20:01

swim out to the ducks. And they would ignore

20:04

him because he was a pumpkin. I

20:06

talked to a friend of mine who was a hunter who

20:09

said, Oh, it totally works. He said, he's done it with

20:11

grass. And like, he said, you can go up to a

20:13

duck and pull it underwater. And the one next to it

20:15

won't even notice. Now we weren't going to do that on

20:17

the show, but I did go far

20:19

enough to actually build a pumpkin hammer

20:21

platform that I could steer through the

20:23

water so that we could film this

20:25

and we had a duck pond to

20:27

shoot on and everything. It's one I've

20:29

always wanted to test. But sadly,

20:31

when our episode for tanker implosion went too long, I

20:34

had to give it up. So if we were going

20:36

to do another episode, that would be the first one

20:38

I would do. Then I have

20:40

this whole other one in my head actually about

20:42

stirring, because when I go to a coffee shop

20:44

and they give me a cup of coffee and

20:47

I put sugar in it and they give me

20:49

one of those tiny little straws, that's like a

20:52

millimeter in diameter. I

20:54

think this isn't stirring. This

20:56

is barely more than brownie in motion. And so

20:59

then I grabbed like five of those sticks and

21:01

I have this question in my head. What

21:04

do we consider the threshold of stirring? And

21:06

you take wooden sticks, you take spoons, stick

21:08

a bunch of different objects, and you actually

21:10

work with sugar in liquids to come up

21:12

with what you consider the threshold for stirring.

21:14

Cause I don't think that tiny stick is

21:16

actually stirring. Oh, and then there's

21:19

this other one last thing that I

21:21

was interested in about stirring sugar into

21:23

my coffee is I notice every morning

21:25

as I stir sugar into my coffee,

21:27

that the sugar of course thickens the

21:29

water as it dissolves into it. And

21:31

I can hear the tone of my

21:33

spoon hitting the cup getting lower as

21:35

the resonant frequency of the

21:37

water changes. And I've been always

21:39

fascinated by that relationship as well.

21:42

Yeah, I think those are cool experiments

21:44

and worth doing in a gen chem

21:46

class also. So if you ever do those, let me

21:48

know. Well, Adam,

21:50

thank you for everything you've done for

21:53

so many people. And I guess,

21:55

especially giving me a son who's a scientist,

21:57

just like his old man. So I really

21:59

appreciate it. appreciate that. Oh, thank you

22:01

so much. Yeah, it was so much fun. That

22:03

was Miss Busters, Adam

22:05

Savage, and Editor-in-Chief Holden Thorpe

22:07

talking about science communication. You

22:10

can find a link to the

22:12

editorial that Holden wrote based on

22:14

this conversation at science.org/podcast. Stay

22:17

tuned for a chat with researcher

22:19

Rox Middleton about how waxy surfaces

22:21

make blueberries blue. Researchers

22:30

at Queens University Belfast translate research

22:33

into action and make sense of

22:35

a rapidly changing world. They

22:37

keep up with technological, societal,

22:40

and economic advances and

22:42

drive change through collaboration and

22:44

real-world partnerships. Their research

22:47

leads to critical breakthroughs in areas

22:49

such as green technology, food

22:51

and agricultural sustainability, peace building,

22:54

and healthcare. Queens

22:56

University Belfast network of international

22:58

researchers has a reputation for

23:01

global excellence. Over 99%

23:03

of their research was assessed as

23:05

world-leading or internationally excellent in REF

23:07

2021. The impact of this research

23:11

is felt around the world. Visit

23:13

qub.ac.uk to find out

23:16

how Queens University Belfast

23:18

is bringing research to

23:20

reality. Here's

23:29

a puzzle. Blueberries are blue but

23:31

when you squeeze them, the liquid

23:33

that comes out is a pinky

23:35

red color. You're not getting blue

23:38

dye, blue juice, blue pigment out

23:40

of a blueberry. In fact, blue

23:43

pigments are incredibly rare in nature.

23:45

And recently, in

23:47

science advances, Rox Middleton and colleagues

23:49

solved this blueberry puzzle, the

23:52

puzzle of the missing blue in blueberries,

23:54

by looking to the waxy coating on

23:57

the surface of the fruit and finding

23:59

some unexpected properties. Hi, Rox. Welcome

24:01

to the Science Podcast. Hi. Thanks

24:03

for having me. Oh, sure. One

24:05

of our longstanding contributing correspondents, Kai

24:07

Kooperschmidt, he wrote a whole book

24:09

on the color blue and why

24:11

it's so hard to come by

24:13

in nature and why chemists struggle

24:16

so much to make it in the lab. But

24:18

I actually never made this connection after so many

24:20

conversations with him. From blueberries

24:22

being blue to actually, they don't have a blue pigment

24:24

in there. They're not a good source for

24:26

blue. So, why were you

24:28

looking at blueberries and their blueness? What

24:31

were you looking for in particular

24:33

when you started this work? Yeah,

24:35

it was really a kind of similar realization

24:37

for me. I spent my whole PhD looking

24:39

at different blue fruits because I'd been interested

24:42

already in the fruits which

24:44

looked blue, but then they don't have any blue pigment

24:46

in them. And yeah, also a big

24:48

fan of Kai's work and the stuff he's put together.

24:50

But, you know, every time I would talk about blue

24:52

fruits to people, they'd be like, Oh yeah, blue fruits,

24:54

like blueberries. And I'd have to be like, no, no,

24:57

no, it's not. But

24:59

then I just suddenly, it just suddenly affects me like,

25:01

wait, how are blueberries

25:03

blue? Because, yeah, like he's saying, a

25:05

blueberry smoothie, not blue. It's

25:07

so funny. So, there's no blue in the berry

25:10

or a lot of other blue appearing fruits. But

25:13

as I mentioned up top, there's a wax on

25:15

the surface that appears to be doing some of

25:17

this work to make the berry blue. So, what

25:19

happens when you take off the wax? What

25:21

does a blueberry look like when it doesn't have its waxing

25:24

coating? Yes, it just looks sort

25:26

of dark underneath like blackish. And

25:29

I think it is funny when you see them in

25:31

shops and they all look kind of battered. And some

25:34

people think that blooms not good for it. I've

25:36

had people say, that's a fungus, isn't it? No,

25:39

that's definitely a good thing. In fact, like the

25:41

more wax you have on a blueberry, the

25:43

less it's been messed with, right? The less it's been touched. And

25:46

because it just comes off every time it gets touched. And

25:49

actually, if you look at sort of blueberry harvesting

25:51

machines, they have an adaptation from raspberry machines to

25:54

reduce touching to sort of stop the bloom

25:56

coming off. That's so interesting. So,

25:58

what is the wax doing? doing on the

26:00

blueberry? What is it doing to make it

26:03

seem more blue than if you

26:05

take it all off and the fruit kind of

26:07

looks like really, really dark, almost

26:09

black? So the wax itself is also

26:11

not pigmented and you can dissolve it

26:13

and it's not blue. It's transparent right

26:16

up until BPUB. But it

26:19

has tiny nanostructures inside

26:21

the wax and it's

26:23

the interaction of light with those structures which

26:26

are sort of sub-wavelength, which means

26:28

that it scatters light and it scatters more blue

26:30

light than it does colored light and more UV

26:32

light than it does blue light. And

26:34

that's what makes it seem blue or

26:36

UV blue to birds. So we

26:38

should probably talk about this thing called structural color

26:40

that you're describing here and how it's different than

26:43

pigments. So can you talk a little bit about what a

26:45

pigment does with light and what a structural color does

26:47

with light? Sure. Pigments have

26:49

molecules in them which literally absorb

26:52

light and then re-emit it. So

26:55

they have a transition that can happen

26:57

which means that a specific wavelength will

26:59

excite the transition and then it will

27:01

de-excite and that will be the color

27:03

that gets sculpted from the pigment. Whereas

27:05

with structural color, it tends to happen

27:07

in either sort of transparent materials or

27:09

materials which don't have a specific wavelength

27:12

that they do that. So

27:14

structural color doesn't absorb light, certain

27:16

wavelengths and reflect certain wavelengths. It

27:19

actually shapes the light so that

27:21

only certain colors come to you. Exactly. It

27:23

doesn't do any absorbing. The light just passes

27:25

through but because light is a wave, it

27:27

interacts with the differences that you get in

27:30

the structure. So it might be the front

27:32

and the back of a very thin film

27:34

or it could be a periodic structure which

27:36

is often where we see structural color. And

27:38

in this case, it's a really, really random,

27:41

very, very small structure. You

27:43

looked at more than blueberries. You looked at a

27:45

bunch of different blue fruits. They

27:47

all have the same nano structures in

27:49

their waxy coatings that were guiding light

27:51

to make it appear blue. They all

27:53

have structures but that was what surprised

27:55

me because I was really unfamiliar with

27:57

waxy surfaces and so I kind of

28:00

And they would be kind of similar. And

28:02

in fact, there's loads of different shades they

28:04

have. So some are rods and some are

28:06

rings, like, flakes. And they

28:08

have common features. So they are media on the

28:11

same length scale. And actually,

28:13

the spectra, the color that they reflect

28:15

are really similar. And

28:17

that's really important if you're interested in attracting,

28:20

I guess, birds or other animals that

28:22

are going to disperse the

28:24

seeds for you. So what do

28:26

they look like to not

28:29

human eyes? Can we say that this is

28:31

blue for a bird? Yeah, I think we

28:34

can. Although we would say it's UV blue

28:36

for those birds which see in UV. So

28:38

there's a whole bunch of birds which see

28:40

in UV. And I

28:43

think it's important, but it's not just

28:45

UV. It's UV blue because the immature

28:47

fruits, the beginning, they're UV green, when

28:50

they're immature and the underlying pigments haven't

28:52

changed. So this kind of goes

28:54

to another conundrum, I guess, the idea

28:56

that all these fruit-loving birds like

28:58

blue things, but there's just not a lot

29:01

of blue out there in nature. But maybe

29:03

they're seeing the UV blue or

29:05

there's all these other ways that fruits

29:07

are communicating blueness to them besides

29:10

pigments. Exactly. I was just suddenly

29:12

like, oh my goodness, there are so

29:14

many blue fruits. And we just sort of

29:16

ignore it and maybe think, oh, that's just

29:18

a side effect. Like, the plum is fundamentally

29:20

like a dark color. It just happens to look

29:22

blue. No, they're really

29:25

blue. Is

29:27

it important that the fruit is

29:29

very dark colored underneath the wax

29:31

in order to get this blue

29:33

appearance? Yeah, that's really

29:35

important because the cool thing about

29:37

this way of coloring things is

29:39

that it's non-absorptive, which means that

29:42

it is semi-transparent. And so whatever you have underneath,

29:44

you see that fruit. So if you have a

29:46

really bright pigment, then you see that pigment plus

29:49

the color that's reflected from the surface. But

29:52

if it's bright green, then it will look bright green.

29:54

So the way it works is there's

29:56

a super dark pigment underneath, and that allows you

29:58

to see just how blue that's. structure is

30:00

on top. When I think of structural

30:02

color, often I think of, I

30:04

guess, more like the proteins and butterfly

30:06

scales or bird feathers that are interacting

30:09

with light. Is it a lot different

30:11

that a wax is doing this? The

30:13

mechanism is different because it doesn't have this

30:16

periodicity. So it doesn't have, like in a

30:18

butterfly, you get those amazing lattice works. And

30:21

here, there's a lot of randomness. Equally

30:24

what's really nice about the wax is it

30:26

is actually crystallized into these tiny shapes. And

30:29

so the shape that you get are really,

30:31

really stereotyped. The shapes aren't

30:33

random. It's just how they're arranged that's random.

30:36

Oh, interesting. So when you reconstitute

30:38

the wax in the lab, as you said, you

30:41

take it off, you put it in solution, doesn't

30:43

look like a blue solution. It doesn't look

30:45

just clear. But then when you let it

30:47

crystallize in the lab, does it look blue

30:49

then? Yeah, I got all of it

30:51

in solution, sort of dipping a little bit of the fruits

30:53

to get the wax off and then it was clear. And

30:55

then once we'd evaporated all of

30:58

that chloroform, which is how we got

31:00

it, it went white. So there was a

31:02

white powder. And that was

31:04

when I thought, OK, like if we're going

31:06

to recrystallize this, it's got to

31:08

be a bit more controlled. And then as

31:10

we did this controlled recrystallization, the surface went

31:13

blue. Hmm. So cool.

31:15

That was a great day. So

31:19

if you can do this in the lab, then you

31:21

can make things blue with

31:24

wax. Like this is an application

31:26

for the waxy surface. I

31:28

don't know. Could you use it for

31:30

artificial coloration? Yeah, I mean, I

31:32

hope so. It kind of seems that way. It seems pretty

31:35

straightforward to make it. And then it's a

31:37

nice blue. Obviously, we already have blue colorants, but

31:39

most of them depend on a pigment.

31:42

So they stain and it

31:45

means getting hold of that molecule, whatever it is. So

31:47

I kind of like this as an alternative. Yeah. We

31:50

should talk about the lotus leaf, too. I think that

31:52

was a really interesting parallel. Can you talk about that?

31:55

Yeah. So people know loads about

31:57

wax coating. I didn't before I

31:59

started. looking at this stuff, but it

32:01

was very exciting to come across the fact that

32:03

people already knew they were thought, well, these different

32:05

structures and like waxy coatings

32:07

are extremely multifunctional and they hoped

32:10

all of the surfaces of all

32:12

of the land plants that are above ground.

32:15

Not quite, but more or less. And one

32:18

of the things that people were really interested in before

32:20

is the fact that they are super

32:22

hydrophobic. These structures like the legacy,

32:24

that's what that's kind of famous for is that

32:26

you put a drop of water on it and

32:28

it just rolls off. And that means if that

32:30

surface gets nasty and spraying water on

32:32

it, the dust just comes off with

32:34

the water too. So they're self-cleaning. And

32:37

that's because of nanostructures on the surface of

32:39

the land? Yeah, exactly. And

32:41

it's these exact same structures actually. That's

32:44

where you kind of think, okay, so

32:46

this could be just a side effect of being

32:48

super hydrophobic, right? It's

32:50

kind of nice seeing this in such an

32:53

important signaling organ of a

32:55

plant, which is the fruit, but it

32:57

definitely has a visual role to here.

33:00

Do you think that this kind of

33:02

structural color using a wax nanostructure, do you

33:04

think it's going to be able to produce

33:07

other kinds of colors or is blue going

33:09

to be its deal? Do you know what

33:11

I mean? Like, is it going to be

33:13

able to structure light in other

33:15

parts of the spectrum? In this

33:18

particular way, like with this exact mechanism, it's blue

33:20

and it's UV. It could be different shades of

33:22

blue. It could be different shades of UV, but

33:24

fundamentally that. Yeah. So it won't be doing other

33:26

colors. All right. What do

33:28

you want to do next? Are you

33:30

going to look more into structural color in

33:33

fruit? Are you going to look more

33:35

into the color blue? What's next on the

33:37

agenda for you? I'm still

33:40

really interested in all blue things. I

33:42

think there's still some kind of cool

33:44

things to be found there, but I'm

33:46

really excited about the different ways that

33:48

light interacts with different wax structures and

33:51

also excited about wax as an engineering

33:53

material, because it has so much potential,

33:55

like it makes all of these different

33:58

shapes. really

34:00

seems to be sort of underused.

34:03

Mm-hmm. Very cool. Can we

34:05

have a blue candle? Yeah,

34:08

exactly. I suppose there's also like you'll see

34:10

all of the applications for this blue color

34:12

and how we might be able to sort of

34:15

make it in a better way so that it can

34:17

be put on things. Yeah, definitely. Thank

34:19

you so much for coming on the show, Rox. Thanks

34:22

so much for having me. Rox Middleton

34:24

is a postdoctoral fellow at Dresden University

34:26

of Technology and an honorary research associate

34:28

at University of Bristol. You can find

34:30

a link to the Science Advances paper

34:32

we discuss at

34:34

science.org/podcast. Up

34:37

next we have a custom segment sponsored

34:39

by Cincinnati Children's. Custom Publishing

34:41

Director Erica Berg chats with

34:43

researcher Jim Wells about organoid

34:45

therapies for digestive diseases. The

34:48

views of the custom segments are those of the

34:50

guests and do not reflect policies of science or

34:52

AAAS. Hello

35:03

to our listeners and welcome to this

35:05

sponsored interview from the Science

35:07

AAAS Custom Publishing Office and

35:09

brought to you by Cincinnati

35:11

Children's. I'm Erica Berg,

35:13

director and senior editor for Custom

35:16

Publishing at Science. Today I am

35:19

delighted to welcome Dr. Jim

35:21

Wells, chief scientific officer

35:23

of the Center for Stem Cell

35:25

and Organoid Medicine at Cincinnati

35:28

Children's. We'll be

35:30

having a conversation about how

35:32

metabolic and gastrointestinal organs develop

35:35

and what this might mean

35:37

for the treatment of diabetes

35:39

and digestive diseases. Thank

35:41

you so much for joining Jim. You're welcome.

35:43

It's my pleasure. First off,

35:46

I wanted to start with a

35:48

question about the Center for Stem

35:50

Cell and Organoid Medicine, shortened as

35:52

custom. It's one of

35:55

the first centers in the

35:57

world focusing on using human

35:59

organoids in biomedical research. How

36:02

did this happen in Cincinnati? So

36:04

a few decades ago, we actually started to

36:06

build the technology here to use

36:09

human stem cells and to coax

36:11

them to become organoids in

36:13

a wide variety of different organ systems. So

36:16

it was really an organic growth from

36:18

the investment in basic science that Cincinnati

36:20

Children's has made in these

36:22

sort of foundational discoveries on how organs

36:24

form. And

36:26

how did you first get

36:29

interested in your field, which

36:31

is the study of gastrointestinal

36:33

and endocrine organs, which include

36:35

the intestines, the pancreas, probably

36:37

lots of other organs? So

36:40

I trained as a postdoc in a

36:42

lab that was studying pancreas development. And

36:45

I trained with lots of great people. And there's

36:47

a wide variety of

36:49

scientists who study that

36:51

particular organ because of

36:53

its importance with regards to diabetes. But

36:56

I noticed that we've been very little

36:58

about the adjacent organs and

37:01

how they form. So the gastrointestinal

37:03

tract, after having arrived

37:05

at Cincinnati, no, realized that

37:07

there were many diseases impacting these other organs

37:09

that really don't get as much attention

37:12

as the pancreas. So I made a pivot

37:15

to study the gastrointestinal tract

37:17

and diseases affecting those patients,

37:20

again, because they're really wasn't as much

37:23

foundational information on how those organs

37:25

form, how they don't

37:27

form normally sometimes and the diseases

37:30

that impact them. So I

37:32

was hoping to make a bigger impact in

37:34

a field that was underpopulated. So

37:36

what have you learned about how

37:38

these organs develop? Well, over the

37:40

years, my lab and many labs

37:42

around the world have used model

37:46

organisms to study how these organs

37:48

develop. So the organs of the

37:50

GI tract, the esophagus,

37:52

stomach, pancreas, liver, etc.

37:55

And through these studies and model

37:58

organisms, they've identified fundamental

38:00

processes by which first the

38:03

embryo decides which organs

38:05

will form where, how

38:07

to assemble those organs, and then lastly

38:09

how to make them functional. And

38:11

this is all over time during

38:14

the assembly information of these developing

38:16

organs. And decades

38:18

of research really have

38:21

gone into understanding these fundamental

38:23

processes of what we call

38:25

organogenesis. Now

38:27

we're in a position and we

38:29

are actively translating that information that

38:32

we gleaned from studies and model

38:34

organisms to the application of directing

38:37

the differentiation of pluripotent stem cells

38:40

into organoids that

38:42

are facsimiles, if you

38:44

will, of these embryonic organs. Who

38:47

had a study published recently

38:50

where you gave organoids an

38:52

immune system? Can you

38:54

share why an organoid would need

38:56

an immune system and what you

38:58

learned from this research? Sure. So

39:01

you might imagine there's not a disease

39:03

that impacts any person on

39:05

earth. It probably doesn't involve the

39:07

immune system. And all of our

39:09

organs have immune cells and they're involved

39:11

in normal health of the organ, but

39:13

also they get co-opted in the

39:16

context of disease. So if you have

39:18

an organoid and you want to study

39:20

a disease process, it makes

39:22

good sense to incorporate immune cells into

39:24

that organoid so you can better replicate

39:27

both the normal and the disease process.

39:29

So take, for example, inflammatory bowel

39:32

disease. You can't model inflammatory bowel

39:34

disease without inflammatory cells, the immune

39:36

cells. So that's why we thought

39:38

that that was an important component

39:40

to incorporate or engineer into our

39:42

organoid systems. Thank you.

39:45

So switching gears a little bit to

39:47

start talking more about the treatment

39:50

aspect, I know that Cincinnati Children's

39:52

a very collaborative place. Could you

39:54

discuss the role of your collaborations

39:56

with surgeons, gastroenterologists, and any

39:58

other medical experts? endocrinologists

40:01

and how they're impacting your

40:03

research into treatment? If

40:06

you have an hour and a half,

40:08

I can tell you all the great

40:10

interactions we have because it really is

40:12

rich and deep and really rewarding the

40:14

interactions with the clinicians and the scientists.

40:17

So in one example, we

40:20

were interacting with both gastroenterologists

40:22

and endocrinologists working on a

40:24

patient who came into our

40:26

clinic with a

40:28

congenital malformation affecting a number

40:31

of organ systems. And

40:33

what we did actually was we decided

40:36

to model the disease,

40:38

the congenital malformations affecting that

40:40

patient to study them using

40:42

organoids in the lab. So

40:45

we actually studied a wide variety

40:47

of different organoids that

40:49

were all derived from that patient, so

40:52

pancreas and stomach and intestine. And

40:54

we found new pathologies

40:57

in our organoids that were not

40:59

diagnosed yet in the patient.

41:02

So we went back to the gastro

41:04

and endocrinologists and said, we think

41:06

there are other problems that

41:08

maybe your patient's suffering from. You might go

41:10

back and look. And they

41:13

did. They got biopsies from the

41:15

patient and in fact confirmed what our

41:17

organoid diagnostics first discovered, that there were

41:19

certain things that were

41:21

complications that they didn't appreciate. And

41:24

this allowed them to change the patient care

41:26

plan based on what we're

41:28

now calling organoid diagnostics. That

41:31

is bananas and incredible.

41:35

Wow. So how do

41:37

you envision the impact of your research

41:40

on pediatric health care,

41:42

particularly in the treatment

41:44

of diseases related to the

41:46

gastrointestinal and metabolic organs you

41:49

study? So I think

41:51

the best example of that is one of

41:53

our homegrown organoid technologies, as we already mentioned,

41:55

is the growing intestinal organoids.

41:58

And I was fortunate.

42:00

enough to have a collaboration

42:02

with a pediatric surgeon, Mike Helmrath, who's one

42:04

of the co-directors of Custom. And

42:06

his goal, his primary goal is for

42:09

us as a team to

42:11

shift this research organoid

42:14

platform into something that could

42:16

be therapeutically transplantable. And

42:19

the team has come together and gotten

42:21

support from children's and philanthropy to try

42:23

to transition our intestinal organoids from the

42:25

lab into the patient. And

42:28

we now have established an entirely

42:30

new infrastructure here at Cincinnati Children's

42:33

called the Custom Accelerator Program, which

42:35

is a separate lab space that

42:37

is designed to transition basic research

42:39

discoveries to the clinic. So

42:42

in this case, the goal is to start

42:44

learning how to make intestinal organoids that are

42:46

therapeutic quality, to scale

42:49

them up, and eventually to transplant them

42:51

into patients that have really

42:54

profoundly impactful forms of either IBD

42:57

or other intestinal injury that we

42:59

think we might be able to

43:01

repair using intestinal organoids. And

43:04

my town rat, the pediatric surgeon has

43:06

tested some of these early

43:08

preclinical therapeutic organoids in animal models,

43:11

and they really do seem to

43:14

restore integrity to the intestine

43:16

following an injury. Wow.

43:19

And for some

43:21

reason, I can imagine what a

43:23

liver organoid might look like, or

43:25

a pancreas organoid just sort of

43:27

a bundle of cells, but a

43:29

intestinal organoid does it look

43:31

like an intestine? Is it a

43:34

tube? So we haven't made a

43:36

tube, well, we are working towards

43:38

making a tube shaped organoid. We

43:40

are making some good progress on that.

43:42

But I think therapeutically rather than replacing

43:44

an entire organ, the

43:47

stem cell derivatives that that our lab

43:49

and labs around the world are using

43:51

are using more tissue therapeutics on the

43:53

smaller scale. So for example, envision,

43:57

you know, the end of summer, you look out in your

43:59

front lawn. is got all these holes in it.

44:02

Inflammatory bowel disease is a lot like

44:05

that. There are holes basically that have

44:07

worn away in the lining of the

44:10

intestine. The intestine otherwise is structurally intact

44:12

but there are all these damaging

44:15

holes that have been worn away due

44:17

to this disease that we're now

44:19

hoping we can more or less reseed the lawn,

44:22

if you will by analogy, to fill

44:25

up the holes, restore the

44:27

integrity of the organ. Because as you might

44:29

imagine, keep being the bacteria inside

44:31

and not in your, you

44:33

know, leaking out into your body is a pretty important

44:35

job. Once you lose integrity of

44:37

your intestine, you start to get inflammation

44:40

and infections and whatnot. So just

44:42

restoring normal intestinal

44:44

integrity by reseeding the lawn

44:46

with organoids we think might

44:48

be a first therapeutic avenue.

44:51

In the future, yeah, we'd love to be able to

44:53

grow a whole intestine and we

44:55

are working on it. That's definitely further down the

44:57

roads. Jim, thank you so much

44:59

for having this chat with me today.

45:01

It was enlightening. I'm really

45:04

incredibly excited about what's down the

45:06

line with these organoid therapies. Thank

45:08

you. It's been a real pleasure

45:11

and a great opportunity to talk

45:13

about the research and the implications and where I

45:15

hope it's going to go in the future. You

45:19

can learn more about Jim's

45:21

work at Cincinnati Children's dot

45:23

org. Our thanks to Cincinnati

45:25

Children's for making this conversation possible

45:28

and a big thanks to you for

45:30

listening. And

45:35

that concludes this edition of the Science Podcast.

45:37

If you have any questions or comments, read

45:39

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listen on our website, science.org/practice.

45:51

This show was edited by me, Sarah

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Krusty and Kevin McLean with production help

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from Megan Tufts at Prodigy. Jeffrey

45:58

Tufts, Composer Music. The

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