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We find a way. This.

1:03

Is the Science Podcast for April.

1:05

Twenty Six Twenty Twenty Four I'm

1:07

Sarah across the first on the

1:09

show, Assaf Eller Kelly serving explores

1:11

the science of loneliness. Is loneliness

1:14

on the rise or but Mr

1:16

awareness of it? How do we

1:18

deal with the stigma of being

1:20

lonely? How do we treat it

1:22

Next Producer or at a Remo

1:25

talks researcher Tim Shelter about making

1:27

one of organic chemistry his oldest

1:29

reaction, the Sand my reaction safer

1:31

and more versatile. Finally, We kick

1:33

off our Twenty Twenty Four book series

1:35

with Books editor Valerie Thompson and books

1:38

host Angeles Amy. They discuss this year's

1:40

theme, a future to look for, to

1:42

and discuss some of the books. That

1:44

will be reading. I.

1:50

Am unhappy doing so many things alone.

1:53

I. Have nobody to talk to. I.

1:55

Feel as if nobody really understands me.

1:58

these are items on a quest that

2:01

researchers use to formally measure loneliness.

2:05

It's a complicated experience and it can be

2:07

hard to study, but it's

2:09

increasingly being recognized as a public health

2:11

issue. Loneliness and social isolation have been

2:13

linked to all kinds of health problems.

2:17

And recently the World Health Organization even launched a

2:19

commission that will look at

2:21

the evidence on how to build social connection.

2:25

Governments around the world are paying a lot

2:27

of attention to loneliness. I'm Kelly

2:31

Cervic. I'm a writer and editor at Science

2:33

Magazine. And I wrote an

2:35

article in this week's issue about researchers trying to

2:37

understand and alleviate loneliness

2:40

and isolation. It

2:45

might be in the spotlight now, but the study of

2:47

loneliness is not new. So I

2:49

asked some of the experts that I spoke to for this story

2:52

about the moment that we're in. As

2:55

the public starts paying more attention, are there

2:57

misconceptions that need clearing up? And

3:00

what they told me was, yes, there are.

3:02

And those start with basic definitions. Like,

3:05

what exactly does the word loneliness

3:07

mean? The conversations I

3:09

have, people are using the term

3:11

loneliness as this catch-all

3:13

term for all forms of lacking

3:16

social connection. But

3:18

from a scientific standpoint,

3:21

it means something a bit more narrow.

3:24

My name is Julianne Holt-Lunstad, and

3:26

I'm a professor of psychology and

3:28

neuroscience at Brigham Young

3:30

University. Julianne has been studying the

3:33

role of social connection in health for more

3:35

than two decades. Loneliness is one

3:37

piece of that. I

3:39

find it often easiest

3:41

to define by distinguishing

3:43

it from social isolation.

3:46

Social isolation is more

3:48

objectively being alone, having

3:51

few relationships or infrequent

3:53

social contact, whereas

3:56

loneliness is more subjectively

3:58

feeling alone. And it's a

4:01

distressing feeling. So while,

4:03

of course, being objectively alone can

4:05

increase our risk for feeling alone,

4:08

they don't always go together. But

4:12

loneliness seems to be the word that

4:14

politicians and journalists often choose

4:16

as a shortcut for various issues around

4:19

our social lives. And

4:21

that makes sense because loneliness is something

4:23

that we can acutely feel. And

4:25

in fact, there's a good reason we feel it. As

4:28

other researchers pointed out to me, loneliness

4:30

has a purpose. It

4:32

has been defined as a social pain that helps

4:35

us to react. So if I need more

4:37

connection, then I look for more connection. So

4:40

it belongs to this reaction that

4:42

we need to be more adapted. Laura

4:45

Koeplanas is a medical doctor and

4:47

public health researcher at the University

4:49

of Vic, Central University of Catalonia.

4:52

She describes loneliness as a useful

4:55

signal. If we feel tired,

4:57

we rest. If we feel physical

4:59

pain, we might seek medical help. And

5:01

if we feel lonely, we might seek out

5:03

other people for support. It's

5:05

a natural and avoidable aspect

5:08

of all our lives. That's how I

5:10

see it. The tricky thing

5:12

is when to understand that loneliness

5:14

has to be alleviated. Because

5:17

there is some point where loneliness is

5:19

not helping anymore, where it

5:21

becomes chronic and harmful. Julianne

5:23

Holt-Lunstad has studied this hunt, including

5:26

in a meta-analysis of mortality data from

5:28

more than 3.4 million people. Her

5:32

group found that loneliness was linked with a 26% increased

5:35

risk of earlier death, and

5:37

social isolation with a 29% increased risk. Data

5:41

on mortality is consistent with a large

5:44

and growing body of evidence on chronic

5:47

health conditions including increased

5:49

risk for cardiovascular disease,

5:51

stroke, type 2 diabetes,

5:54

depression, anxiety, addiction,

5:56

suicidality, cognitive

5:59

decline, and dementia. All

6:01

these risks are definitely alarming, but

6:03

are they new? Are we getting

6:05

more isolated? Are we getting more

6:07

lonely? This is another place where the

6:10

evidence is more complicated than some of

6:12

the headlines. In the

6:14

US, long-running surveys do show some

6:16

clear trends. Americans over

6:19

the past two decades are

6:21

spending significantly more time alone,

6:24

significantly less time with

6:27

family, both household and

6:29

non-household family. We see

6:31

declines in time spent with friends

6:35

and time spent in companionship.

6:38

This has been a pattern,

6:40

right? First off, while of

6:42

course it was exacerbated by

6:44

the pandemic, but because these

6:46

data started in 2003,

6:49

we can see it did not begin

6:51

there. And certainly that, you know, getting

6:53

back to normal, the normal wasn't necessarily

6:55

good to begin with. Those

6:57

data tell us isolation has increased.

7:00

When it comes to the subjective feeling

7:02

of loneliness, though, it's not so clear.

7:05

Some experts told me the evidence for

7:07

a new epidemic of loneliness is just

7:09

not there. Headlines such

7:11

as, We are Lonelier Than Ever, do

7:13

not really represent findings from longitudinal cohort

7:15

studies that we see where

7:17

loneliness actually doesn't increase over time. Hi,

7:20

I'm Samia Ekdekan. I work at King's College

7:22

London as a PhD candidate. It's

7:25

probably been like five or six years that I've been

7:27

working on the topic of loneliness. Samia

7:29

has been studying loneliness outside of the

7:31

wealthy Western countries where a lot of

7:34

the research data have been collected. She

7:37

moved to Myanmar during her master's degree

7:39

to study loneliness in older adults there.

7:41

I think I was a bit naive

7:43

in the sense that I expected a

7:45

very socially embedded and close-knit society where

7:48

people didn't feel lonely because they didn't live

7:50

alone or were socially isolated. But

7:52

then when I started doing research on this, we

7:55

actually found with the Myanmar Aiding Survey that had

7:57

over 4,000 respondents from all over the country. 42%

8:00

of all the adults felt lonely in the past month.

8:03

That's roughly on par with the rates found in

8:05

some surveys of older adults in the US, for

8:07

example. So it's quite surprising, but

8:09

now I'm a wiser

8:11

person now after doing this research. Interviews

8:15

in Myanmar helped Samia and her colleagues

8:17

develop a theory about the underlying causes

8:19

of loneliness, a list of

8:21

expectations that if they're not met

8:23

can lead to loneliness. One

8:26

of those expectations she calls generativity,

8:28

so contributing meaningfully to society

8:30

or leaving a legacy. Another

8:33

is respect, so feeling valued

8:35

and appreciated maybe also for

8:38

the care you provide. Those

8:40

ideas informed a loneliness intervention that

8:42

Samia and her colleagues tested in

8:44

a small feasibility study. It

8:47

included nine older adults from Myanmar

8:49

who had migrated to Northern Thailand.

8:52

The team used a research method called

8:54

PhotoVoice, where participants learned photography

8:56

to capture their everyday experiences

8:59

and highlight problems their communities

9:01

face. So I remember

9:03

one photo of a

9:05

woman. It was

9:07

a self-portrait, actually. She asked

9:10

her grandchild to take a photo of herself cooking.

9:12

So she's sitting on the floor squatting and

9:14

yeah, she's an older woman, so it's obviously

9:17

not as comfortable for her anymore

9:19

to squat on the floor and cook for her. Grandchildren,

9:22

but she just says how she

9:24

provides this kind of care every day

9:26

in this really hard work, but she

9:28

doesn't feel appreciated and people don't really

9:30

see how she's contributing. Participants

9:34

in that small study did report reduced

9:36

feelings of loneliness and they

9:38

decided to have an exhibition with their photos and

9:40

messages. And the grandchildren,

9:42

for example, saw this photo. Addressing

9:45

them, they were pretty surprised,

9:47

but also in all of

9:50

older people, and I interviewed them as well, so

9:52

people who came to the exhibition, and

9:55

they just said they completely changed how

9:57

the way they saw older people in

9:59

their community. as really meaningful

10:01

contributors to their lives and what

10:03

kind of value they provide. Another

10:08

thing that has emerged from Samia's work with

10:10

older adults in Southeast Asia is a

10:13

sense of how big structural factors

10:15

can drive loneliness. Other

10:17

people list reasons for feeling lonely that were

10:19

related to their financial situation such

10:21

as food insecurity, not being able to buy

10:24

medicine or not being able to

10:26

contribute to community activities as a result of

10:28

poverty. These factors such as

10:30

poverty, stigma, financial distress are definitely risk

10:32

factors for loneliness anywhere. It's just that

10:35

maybe that the focus is not so

10:37

much on these social determinants in research

10:39

in higher income countries because poverty

10:41

is just so much more prevalent in lower

10:44

middle income countries by definition. This

10:46

is another place where the public

10:48

conversation about loneliness might be

10:50

missing something. Some government

10:52

initiatives sometimes position loneliness as the failure

10:54

of an individual or community without

10:57

considering the wider context of factors. I

11:00

heard that from multiple researchers I talked to.

11:03

Loneliness is being treated like a personal problem

11:06

which contributes to stigma as

11:08

in if you're lonely this is a defect with

11:10

you. You need to get out

11:12

more. You need to socialize better. Julianne

11:15

Holt-Lunstad told me we lack evidence

11:17

on how policies might address loneliness

11:19

at the level of communities or

11:21

societies. She recently helped develop

11:23

a map of the evidence we have so far

11:26

for different interventions. The

11:28

majority of these interventions are

11:30

individually based. They are targeted

11:32

to affect change at

11:35

the individual level. That

11:37

might mean organized social activities that a

11:39

person can opt into or a program

11:41

where a volunteer provides companionship to

11:44

someone who's isolated or

11:46

cognitive behavioral therapy to help someone

11:48

who's lonely change their outlook. According

11:51

to reviews of the evidence, Julianne says

11:53

one approach doesn't seem to be way

11:55

better than another. One doesn't rise

11:57

to the surface as like this is the go.

12:00

gold standard in what we should be doing.

12:03

Rather we see success across

12:05

many different types but I

12:07

will caveat that with the

12:09

evidence also shows that the success

12:12

is somewhat limited. These effect sizes

12:14

are small to moderate and

12:16

these reviews and meta-analyses have

12:18

shown that in many cases

12:20

the quality of the evidence

12:22

is quite low. Laura Koyplanas

12:24

and her colleagues are trying to

12:26

build strong evidence for one loneliness

12:29

intervention. It involves weekly

12:31

group activities in urban green spaces

12:34

to support people who may have been cut

12:36

off from social connection for various reasons like

12:39

unemployment, disability, chronic

12:41

illness, discrimination. For

12:44

some people can be unfair to be

12:46

lonely they can have more access

12:48

to social support and social connection

12:50

than they have. We

12:52

can build social opportunities for people

12:55

that can help people to feel better so

12:57

we should do that. In the

12:59

study which is taking place in six different

13:01

countries groups of participants

13:03

do outdoor activities accompanied by

13:06

trained facilitators. We build a

13:08

group, we build a sense of belonging to

13:10

the group, the commitment to the group

13:13

and the group choose which activities they would

13:15

like to discover through a map

13:17

that has been co-created where all

13:19

these natural resources are identified

13:22

and they know what's around me.

13:25

Laura acted as one of the facilitators

13:27

in Barcelona and one group meeting

13:29

stands out in her mind. That

13:31

day we were going for a walk in

13:33

one of the parks nearby

13:36

and it was a very sunny day

13:38

and we thought about sitting in

13:41

a cafe all together and

13:43

we start talking there about

13:46

the very deep things about house

13:48

life and which is the

13:51

meaning of life and that day

13:53

instead of two hours we were like three

13:55

hours together because it

13:57

was such a deep conversation that we

14:00

and really stand up and say, I

14:02

have to go back to my work.

14:04

These are conversations that are sometimes

14:06

very hard to have or impossible

14:08

to have with your best friends,

14:10

sometimes so deep. Laura

14:16

has been thinking about the consequences

14:18

of all these public health campaigns

14:21

against loneliness. It was

14:23

a very interesting moment globally, with

14:26

WHO creating this commission

14:28

on social connection to the

14:30

loneliness. It's good there is

14:33

this awareness on loneliness,

14:35

the social awareness, political awareness. There's

14:38

more money now to research on

14:40

loneliness, but loneliness is not

14:43

an epidemic. Loneliness is not an

14:45

illness. I think the majority of

14:47

the society is

14:49

understanding this message of loneliness kills, so

14:51

we have to end loneliness. So

14:54

we have to make sure how

14:56

this interesting moment doesn't go

14:59

against us and simplifies too

15:01

much and medicalize too much. That

15:08

was Laura Koyplanas, also

15:10

in this story where Julianne Holt-Lunstad

15:12

and Samia Akter Khan. I'm

15:15

Kelly Cervik, and you can read the full

15:17

article at science.org. Stay

15:24

tuned for a chat with producer Ariana Rummel

15:27

and researcher Tim Schulte about

15:29

making the Sandmeier reaction safer.

15:40

When it comes to making complex carbon-based

15:42

compounds from simple building blocks, chemists

15:45

have an extensive toolkit of trusted

15:47

reactions at their disposal. In

15:49

fact, some of the most widely

15:52

used reactions for synthesizing sophisticated molecules

15:54

like pharmaceuticals and fluorescent probes trace

15:56

their origins back to the 19th

15:59

century. These methods have proved

16:01

tried and true for more than a hundred

16:03

years, but some

16:05

still come with the risk of

16:07

explosive consequences. This week

16:09

in Science, Tim Scholte and colleagues

16:11

wrote about a new way to

16:13

make one of organic chemistry's oldest

16:16

reactions both safer and more

16:18

versatile. Welcome to the Science Podcast, Tim.

16:20

Hey, thank you very much. We are so excited

16:23

to have you here talking with our

16:25

listeners about this new chemistry that your

16:27

team has developed. So your research focused

16:29

on a chemical reaction that's commonly called

16:31

the Sandmeyer reaction. What does this reaction

16:34

do and how is it used today?

16:37

The Sandmeyer reaction is a very useful reaction

16:39

in organic chemistry. It's based on diazonium

16:41

salts. It is a very specific group

16:43

of molecules that have dinitrogen as a

16:45

leaving group attached to the molecule, which

16:48

makes these molecules useful because you can

16:50

just substitute that dinitrogen with a different

16:52

functioning group, which means you can

16:54

make a lot of different other molecules. And

16:56

to understand that a bit better, I think

16:59

it's nice to think about organic molecules in

17:01

general as something that we want to assemble.

17:03

Now, when you want to assemble a very

17:05

specific molecule, a lot of these building blocks

17:07

fit together super perfectly. So we have to

17:09

try to find new ways to take the

17:11

building block and basically change it or manipulate

17:13

it into something that we can use in

17:15

a more efficient way. And

17:17

the Sandmeyer reaction basically takes one building

17:20

block, that's an aniline, and transforms it

17:22

into a building block, which is actually

17:24

much more useful called a diazonium salt.

17:27

And it takes these diazonium salts and converts

17:29

them into our halides. So

17:31

just to be clear, an aniline is

17:33

a kind of carbon ring that has

17:36

a nitrogen substituent and amine associated

17:38

with it, right? Yeah, exactly. So

17:40

you basically have a derivative of

17:42

benzene, which is the six-member carbon

17:44

ring, which is aromatic. That is usually the

17:47

flagship structure of organic chemistry. So when you

17:49

Google organic chemistry, the picture that comes up

17:51

probably is a picture of benzene, of an

17:54

arene. And it's basically just an arene connected

17:56

to a nitrogen containing functional group. Okay,

17:58

so the Sandmeyer reaction is using

18:00

these diazonium salts as kind of an

18:02

intermediate to make the original building block

18:05

a little bit easier to stick on

18:07

to the molecules that you're interested in

18:09

building. Diazonium salts are highly

18:11

reactive which I guess makes sense

18:13

for why they're making these initial

18:15

compounds easier to work with in

18:17

terms of forming chemical

18:19

bonds. Diazonium salts are

18:21

also notoriously dangerous to work with. Can

18:23

you tell me a little bit more

18:26

about the safety concerns that chemists face

18:28

when they're performing a sand myer reaction

18:30

or something else that's using diazonium compounds? So

18:32

diazonium salts are actually compounds that are

18:34

prepared quite routinely in labs and every

18:36

chemist in their career probably makes them

18:38

a couple of times but it's definitely

18:40

not a reaction that you just do

18:43

on the side while thinking about something

18:45

else and this sun myer reaction

18:47

the conversion of these anilines to the aryhalides

18:49

which we do in this paper

18:51

is actually only one kind

18:53

of reaction of what you can do with diazonium

18:56

salts. The diazonium compounds as you already said are

18:58

super useful because they have a

19:01

part in their molecule that can leave the

19:03

molecule very easily and in the case of

19:05

diazonium salts this is actually dinitrogen so

19:08

dinitrogen as probably most of the people know

19:10

makes up 80% of the air that

19:12

we breathe and since this dinitrogen

19:14

leaving group is so prone to leave

19:16

the molecule it's very easy to substitute

19:18

it with something else which makes these

19:20

compounds useful but as you can imagine

19:22

if there is dinitrogen in the molecule and just wants

19:24

to go out of the molecule sometimes

19:27

this nitrogen release happens very very fast

19:29

and sometimes it happens so fast that

19:31

this happens in an explosive fashion. So

19:33

you can say that these diazonium salts get

19:36

their properties from dinitrogen leaving the molecule but

19:38

this also makes them very explosive very dangerous.

19:41

So usually you take a lot of

19:43

precautions before you set up these reactions

19:45

so you'll you were your personal protective

19:47

equipment you probably also set up

19:50

a blast shield you always keep your few

19:52

modes sashed down so it's just not something

19:54

that you do while you're not concentrated and

19:56

actually there are some reports about people actually

19:58

dying because of explosions. that happen during

20:01

the synthesis of diazonium salts. And

20:03

when I started working on the project,

20:05

I was actually quite surprised on how

20:07

many publications there are out there that

20:09

report explosions of diazonium salts. And then

20:11

you are even more surprised that people

20:14

actually keep preparing them. Then this

20:16

gets to your new work here.

20:18

You describe a new way of

20:20

doing this kind of Sandmeyer type

20:22

chemistry. What makes your

20:24

protocol different? So what you

20:26

usually do with diazonium chemistry is you

20:28

make a two-step reaction. So you

20:31

always have the first preparation step of the

20:33

diazonium salt. So you start from an aniline,

20:35

you have to put in reagents, and then

20:37

you isolate or at least you accumulate. So

20:39

you prepare a large quantity and solution of

20:42

a diazonium salt. And then

20:44

in the second step, you put your second

20:46

part of reagents that then form your valuable

20:48

product. And you always have to do

20:50

that in two steps because usually the reagents that you

20:52

use for the second step are not compatible with the

20:54

reagents that you use in the first step. So

20:57

for the synthesis of diazonium salts, are

20:59

usually quite harsh reagents. So this always

21:01

forces you to make quite of a large

21:03

quantity of diazonium salt, if you want to

21:06

make a valuable product out of it. And

21:08

what we are doing conceptually different is we

21:10

can do everything in one step. So

21:12

we start from the aniline, which is

21:14

the precursor for the diazonium salt. And

21:16

we go in one step directly to

21:18

the valuable product without making large quantities

21:21

of the diazonium salt in the middle.

21:24

And that means now at no point, you

21:26

have a large quantity of the diazonium salt

21:28

in your flask or in your reaction mixture.

21:30

So therefore your reaction is much safer. So

21:33

in the previous traditional way of doing

21:35

this reaction that probably chemists who have

21:37

done this are more familiar with, you've

21:39

got two steps. The first step is

21:41

to basically make a large enough quantity

21:43

of the diazonium salt, and then react

21:46

that with the second thing that you're

21:48

trying to bond together. But this version,

21:50

you're still making the diazonium salt in

21:52

the process, but it's a fleeting intermediate

21:54

that's getting used up really quickly. Is that right? Yeah,

21:56

that's exactly correct. We never actually observe

21:59

a large quantity. of the diazonium

22:01

salt. So the quantity of diazonium salt

22:03

that's formed at a time is lower

22:05

than our detection limit, which basically means

22:07

it's very, very low. So

22:09

this was also part of the analysis of

22:12

our work is to actually understand if we

22:14

even go through this diazonium salt, because if

22:16

you cannot observe it, then the question is,

22:18

do you even form it? We have some

22:20

really cool experiments in the work that prove

22:22

that the diazonium salt is formed, but as

22:24

it gets converted so fast to the valuable

22:26

product, you never actually see it. So why

22:28

does this reaction work? This is

22:30

a process that's called nitrate reduction that

22:33

changes the oxidation state of our reagent.

22:35

And the reagent that we are using

22:37

is called nitrate. That's a very common

22:39

reagent that's also used in the fertilizer

22:42

industry. And the process we

22:44

are doing is therefore called nitrate reduction. Nitrate

22:46

reduction is a process that's very common in

22:48

nature. So plants use

22:51

nitrate reduction in their metabolism. So we take

22:53

our stuff material, we do the reaction that

22:55

we know from nature. Now our starting materials

22:57

and reagent fit together so we can form

23:00

the diazonium salt and then directly convert them

23:02

into the valuable product that we want to

23:04

have. So we are coupling nitrate reduction to

23:07

the diazonium chemistry. So we talked about

23:09

before with risks of exploding reactions

23:11

in the traditional method. You're using

23:14

blast shields, space guards. What does

23:16

it look like to do this

23:18

reaction that y'all have developed now?

23:21

So the setup is actually quite easy. The

23:23

reagents you can all wait under normal atmosphere.

23:25

You don't have to take any precautions of

23:28

getting a protective atmosphere over your reaction or

23:30

in the reaction flask. That means

23:32

you can just sit on the balance, you wait in

23:34

all the reactions because by themselves they are not dangerous

23:36

at all. Then you can just take

23:38

them to your fume. So we still take

23:40

a lot of precautions and we still put the blast

23:43

shield there. But it doesn't mean that you

23:45

would actually need to be required to do that. It's

23:47

just something that chemists are prone to do because you

23:49

want to take every safety precaution you can, not

23:52

the ones that you must. Yes,

23:54

again, a solid message to our

23:56

listeners. Please always wear your personal protective

23:58

equipment in the lab. Yeah, it doesn't

24:00

really import. So there's clearly

24:03

some safety benefits that have come

24:05

from this new protocol, but how

24:07

does its performance actually compare to

24:10

the original Sandmeier reaction protocols?

24:13

So for a couple of molecules, then actually our

24:15

reaction at least performs the same, but then in

24:17

some cases actually also performs better. So

24:19

it seems like that this reaction is

24:21

not only safer, but sometimes even more

24:23

efficient. There might be some substrates out there

24:25

where the convention is that some of our reactions still

24:27

works much better than ours, which was not the case

24:30

for the ones that we've tried, but you

24:32

never know. You had also mentioned

24:34

before that because the initial reaction conditions are

24:36

not so harsh that you can also use

24:38

different starting materials to begin with. So does

24:41

that mean that this reaction is also allowing

24:43

you to work with a broader set of

24:45

materials than you could before? Yeah,

24:47

exactly. We can now use drug molecules,

24:50

which you can usually not easily functionalize

24:52

with the diazoniums. For example, if it's

24:54

a drug, a pharmaceutical molecule, it usually

24:57

contains many different functional groups. And

24:59

if you have that, then each of these

25:01

groups of molecules usually is sensitive to something

25:03

else. And as I said, for

25:05

the diazonium reaction, you use harsh conditions. So

25:07

if you take these complex molecules with a

25:09

lot of sensitive functional groups, it's very easy

25:11

that you decompose that molecule, which means you

25:13

break it. And we've shown now that you

25:15

can actually use a few, actually

25:17

quite a few of these pharmaceutical molecules

25:19

and do that chemistry with them without

25:21

seeing decomposition. So we get a high

25:23

yield, a high efficiency of converting them

25:26

into even more valuable products. So

25:28

yeah, this is something that you cannot do with conventional

25:30

diazonium chemistry. The Sanmai reaction is like

25:32

140 years old. Why

25:35

did it take so long to come

25:37

up with this new and improved protocol

25:39

to do this kind of chemistry? Yeah,

25:42

that's actually a great question. And that's also a question

25:44

that we ask ourselves why we worked on this. So

25:47

the reagents and the complete conditions that we

25:49

use to do this reaction, that's not something

25:51

that you would usually come up with when

25:53

you just think about how you would design

25:55

this reaction. Some of the

25:57

reagents are actually completely orthogonal.

26:00

to each other. So you would actually think

26:02

when you put these three agents together in

26:04

one pot, they would directly react to each

26:06

other so that you don't have a productive

26:08

diazonium formation. So we didn't actually design this

26:10

reaction. I was working on a completely different

26:12

topic during my PhD. So I actually managed

26:15

to develop a new kind of catalyst that

26:17

were able to functionalize arenes. And then I

26:19

was lucky enough that a postdoc from our

26:21

group who's called Xavier is also a good

26:23

friend. And he's the other equal contributing first

26:25

author on that paper. He has very cool

26:27

ideas. And one idea was to use these

26:30

catalysts that usually functionalize arenes

26:32

to functionalize aniline. So

26:34

together, we came up with some experiments, but none

26:36

of the ideas actually worked. So

26:39

all of the ideas that we had were

26:41

completely useless. The catalyst was not doing anything.

26:43

But we found that something is happening to

26:45

the aniline, which was completely unexpected. And then

26:48

we thought a bit about and luckily we

26:50

asked the questions at that time, what happens

26:52

to the aniline. We did a

26:54

control experiment without the catalyst and the reaction

26:56

was still working, which means it had nothing

26:58

to do with the catalytic reactions that we

27:00

originally had in mind. But still, we found

27:02

that it goes through the isonium salt. And

27:04

then we actually found that you can also do the

27:06

sunmaya reaction with this protocol. Yeah, so

27:09

it was an accidental discovery while working

27:11

on a different project. And

27:13

I think this is why probably no one has

27:15

discovered that before. Yeah, because the reagents that you're

27:17

mixing are not reagents that I would have

27:19

designed on the whiteboard if I wanted to make

27:21

this reaction work. You just have to find this

27:23

kind of reaction. That is

27:25

so interesting. And another great example

27:28

of serendipitous discoveries as you're investigating

27:30

these mechanisms, we love to see

27:32

it. Diasonium salts, of course,

27:34

they show up in reactions far

27:37

beyond just the sandmaya reaction. I'm

27:39

wondering if you can say anything

27:41

about potential broader applications of this

27:43

method that you've developed and the

27:46

mechanisms that you were able to

27:48

uncover and how they might be

27:50

applied to other kinds of diazonium

27:52

chemistry. Yeah, so diazonium chemistry

27:55

in general is incredibly useful. These diazonium

27:57

salts are intermediates that you can have.

28:00

actually used for a lot of different reactions

28:02

and this saguerre reaction, the conversion of these

28:04

anilines to the aryhalides, which we do in

28:06

this paper, it's actually only one kind of

28:09

reaction of what you can do with diazonium

28:11

salts. So what we also hope is that

28:13

other people take our papers and inspiration to

28:15

develop other chemistry that you can do in

28:17

one step from anilines that would usually rely

28:20

on diazonium salts. And maybe there's

28:22

a lot more stuff that you can now do

28:24

in this one step protocol, if you apply this

28:26

strategy that we describe in our paper. This

28:29

is such a fascinating story. Thank you so

28:31

much for joining me on the podcast today,

28:33

Tim. No worries. Yeah, it was a good

28:35

talking to you. And thank you very much for inviting me

28:37

and having me here. Tim Schulte

28:39

is a graduate student at the

28:42

Max Planck Institute for Coal Research

28:44

and RWTH Aachen University. Be

28:46

sure to read the paper from Schulte

28:48

and his colleagues in science this week.

28:50

It's titled nitrate reduction enables safer aryl

28:53

diazonium chemistry. You can find

28:55

a link at science.org/podcast.

28:58

Don't touch that dial. Up next, we hear

29:00

about books that look to the future and

29:03

don't see doom and gloom. And

29:05

this year we have all of our books already

29:07

confirmed you can go to the episode page and

29:09

read along with us month to month. We're

29:18

about to kick off the 2024 book series for the year.

29:20

The theme

29:22

can be summarized a number of different ways

29:24

of future to look forward to the optimist

29:28

toolkit, how to have

29:30

the best apocalypse for you. We

29:33

have our books host Angela Saini and our books

29:35

editor Valerie Thompson, they're going to talk about the

29:37

theme. Let's go with a future to look

29:39

forward to and some of the books we're going

29:41

to hear about for the rest of the year.

29:43

Here's Angela and Valerie. This

29:45

was a tricky year. So

29:49

the theme for everyone was kind of looking

29:51

forward to the future or future to look

29:53

forward to utopian writing, which

29:55

was far trickier than you would

29:57

think. Yeah, yeah, I mean, You

30:00

know, we've done some heavy topics in

30:02

the past. We wanted to

30:04

present some perspectives that are

30:07

counter to the increasingly

30:09

dystopian views of the future that

30:12

are out there, not to say that

30:14

the concerns that people are raising about

30:16

various subjects are not true concerns or

30:18

that we shouldn't be worried about them,

30:20

but just that there are some

30:22

reasons for cautious optimism. Yeah.

30:25

And it is very difficult. I

30:27

think particularly this year with so

30:29

many elections happening, the rise of authoritarianism,

30:31

these threats to democracy, the climate change

30:33

threat just feels to be bearing down

30:36

on us in ways that it

30:38

didn't feel quite as, I mean,

30:41

it always felt urgent. It almost

30:43

feels that we're at kind of

30:46

doomsday now in so many different

30:48

areas, AI, everything, and it

30:50

is quite difficult. I think with the

30:52

literature, when you survey

30:55

it to find hopeful looks forward

30:57

or hopeful scientific ideas that could

30:59

get us out of this. And

31:02

sometimes it feels almost too

31:04

optimistic, you know, that these

31:06

are unrealistic almost. Yeah. I know exactly

31:08

what you mean. Like there's that type

31:10

of science writing that I think of

31:12

more as like science cheerleading, that was

31:14

a trend in, in writing for

31:17

a while, but I feel like there's this new

31:19

trend in media right now that I'm noticing with

31:21

a lot of books and films that are trying

31:23

to emphasize that in all

31:25

these situations that are very

31:27

difficult, you know, dealing with

31:29

climate change, ensuring that artificial

31:31

intelligence is deployed properly, all

31:34

these arenas where we feel

31:36

out of control or we feel like

31:38

it's happening without our agency, that we

31:40

actually do have agency and that

31:42

there are reasons to be cautiously

31:44

optimistic about the future. And so

31:46

that was something that we really

31:48

wanted to make sure came through. Yeah.

31:51

And one of my favorite books, and

31:53

I think it's from the 1960s by Alvin

31:55

Weinberg looks at the technological fix.

31:58

So, you know, that was an age. in

32:00

which everybody thought that technology could

32:02

solve all our social problems. But

32:04

if we just threw enough money

32:06

at research and development that somehow

32:09

we could science our way towards a better

32:11

world, this is the age of the Jetsons

32:13

and these very optimistic ideas about the future.

32:15

And I think we've evolved out of that.

32:18

I don't think we take that approach anymore.

32:20

But I have to say with the list

32:22

that we have, I do

32:24

feel that there is a recognition that

32:26

in certain disciplines, there are little tweaks

32:28

and things that we can do to

32:31

realign the way that societies work in

32:33

such a way as to drive us

32:36

through into a more

32:38

optimistic future. So one of the books, for example,

32:40

that we have on our list is Tokens by

32:42

Rachel O'Dwyer, which looks at the future of money.

32:45

And this may feel like a red flag to many

32:47

people because you think of Bitcoin and crypto and you

32:49

think that that can't be good. But

32:51

you know, our relationship with money is quite

32:54

strained in capitalist democracies, we

32:56

are struggling. So maybe

32:58

there are more radical ways

33:00

of thinking about how we organize

33:02

financial systems and money that can at least

33:05

start to push us out of that. Yeah,

33:07

I really like this one too, because

33:09

she's looking at this idea of how

33:12

these new forms of currency are changing

33:14

the balance of power between digital platforms

33:16

in the state. And in some cases,

33:19

that's really good. And in

33:21

some ways, it's concerning. And so balancing

33:23

those two ideas and thinking about what

33:26

this means moving forward is going to

33:28

be something really interesting. And I'm really

33:30

looking forward to that discussion. And I

33:32

think Climate Capitalism by Akshat Rashi, which

33:34

is one of our books, which is

33:36

going to be appearing in the summer,

33:39

fits into that same vein, which is

33:41

how do we get capitalism to work

33:43

for us? How can we use

33:46

it to our advantage rather than

33:48

exacerbating inequality and environmental degradation? So

33:51

he looks at all these

33:53

different mechanisms and

33:55

schemes out there that can

33:57

harness the capitalist power. power

34:00

that we have in order to improve

34:03

the environment rather than destroy it. Another

34:05

area that we're interested in and that we're planning

34:07

to look at is how these things

34:10

are going to intersect with medicine. And in

34:12

particular, one of the

34:14

books we're going to look at is looking

34:16

at the future of reproductive technology. So Eve,

34:19

The Disobedient Future of Earth, is

34:21

the name of the book. And this is written by a legal

34:23

scholar, Claire Horn. It's

34:25

kind of predicting this future where

34:27

artificial wounds are going to

34:30

be a viable alternative to

34:32

maternal gestation. She's not wrong to

34:34

extrapolate this. Like this is something that

34:36

is the work is progressing in animals. It's

34:39

important to have these conversations now before

34:41

the technology is a reality. But I'm

34:44

really looking forward to her perspective on this

34:46

as a legal scholar, because she's not really

34:48

talking about how is this technology

34:50

going to work. It's more about

34:53

how it's going to be deployed. There's the

34:55

potential for this to be a real game

34:57

changer in terms of reducing gender inequality. But

34:59

then there's also these questions of access and

35:01

how it's going to affect things like

35:04

reproductive rights that we also have to think

35:06

about. And it's long been

35:08

this feminist dream. I think Andrea Dworkin wrote

35:10

about this many years ago, this idea that

35:12

we can, as a species,

35:14

get to a point where the

35:16

burden of reproduction doesn't fall on

35:19

women anymore, that it is evenly

35:21

distributed in some way, and that

35:23

possibly technology could provide an avenue

35:25

towards that. We're very far

35:27

away from it, but Eve does explore that

35:29

possibility that we could one day

35:31

have a world

35:33

in which it's not women's

35:35

job to think about reproduction and birth

35:37

and childcare anymore. I do think we're

35:40

getting there slowly. I mean, there's another

35:42

book coming out this year. It's not

35:44

part of our lineup, but Fatherhood by

35:46

Sarah Bluffer-Herdy, which looks at

35:48

how much

35:50

fatherhood has been underplayed as

35:52

a really important evolutionary mechanism.

35:55

Fathers are actually hugely

35:57

important, but socially we have moved towards

35:59

that moment. much more. And I do feel

36:01

that so many things are happening at once. So

36:03

not just reproductive technology, but also social change

36:06

in the way that we parent that could

36:08

create this revolution that feminists for a long

36:10

time have dreamed of. Right. That book isn't

36:12

appearing in this series, but we do. We

36:14

will have a review of that in the

36:16

magazine. Right. That's good to hear. Yeah,

36:19

we have a great lineup. I'm so excited

36:21

about it. And it is very diverse. You

36:23

know, there is there is medical stuff in

36:25

here. There is technology. There's, like I said,

36:27

stuff about capitalism. And then at the very

36:29

end of the series, we have this wonderful

36:32

interview with Ruha Benjamin, who's a

36:34

scholar who is very kind of

36:37

visionary in the way that she

36:39

imagines what the world

36:41

could be like. And her latest book,

36:43

Imagination, takes that a step further by

36:45

asking how much different could

36:47

life be if it wasn't just rich

36:50

tech billionaires imagining these

36:52

huge, big radical futures

36:55

and everybody got to do it. You know,

36:57

if it wasn't just Peter

36:59

Thiel and Elon Musk dreaming

37:01

that we might settle on the moon or

37:03

on Mars or live forever, but that all

37:05

of us got to have these

37:08

radical visions about the kind of future we

37:10

might want. I feel like what she does really

37:12

well is to ask whose vision of the future

37:14

are we currently living in? Whose

37:17

imagination should inform our next steps?

37:19

Yeah, it is a really exciting

37:22

book. I did actually reach

37:24

out to a few friends of mine who either

37:27

are scholars in this area or write

37:29

sci-fi, and they all struggled with finding

37:31

a science fiction book that was genuinely

37:33

utopian. So there's quite a few books

37:36

that start off utopian and then disintegrate

37:39

into dystopias or, you

37:41

know, dystopias in which there are a

37:43

few utopian believers who

37:45

then disappear or something terrible happens

37:47

to them. But there just genuinely isn't

37:49

that much real utopian

37:52

science fiction out there right now. And maybe that's

37:54

a reflection of the time that we're in. It's

37:56

very hard to be hopeful in

37:59

an era. in which things

38:01

are as bleak as they are. In fact,

38:03

this year I was asked to write a

38:05

piece of speculative non-fictions. So it's kind of

38:08

imagining that you're a few decades in the

38:10

future. And I couldn't come up

38:12

with anything utopian. The thing that I wrote

38:14

was actually quite depressing by the end. It

38:16

was just worse than what we have now.

38:18

Oh, dear. It's just

38:20

not out there, but I can understand why

38:22

fully. I mean, I think like some ways too,

38:24

it's just like, unfortunately, like a

38:27

dystopian story is just often just

38:29

a better story. The utopian narrative

38:32

is like wonderful. And like, I wish that we could all live

38:34

that. But maybe like we like

38:36

to read about people that

38:38

are undergoing struggles. Like we undergo

38:40

struggles. You know, we don't want to

38:43

read about someone who just feels like a

38:45

perfect life. You know, that's very interesting. No,

38:47

I know. Yeah, you're absolutely right. We want

38:49

to see our experience reflected

38:52

back at us. And things are hard. I

38:54

mean, frankly, they are hard for still for

38:56

so many billions of people around the world.

38:59

Right. And that's the way life

39:01

is. But I do hope with the books that we

39:03

have that we can at least

39:05

see the possibility of people being able to dream

39:07

of something better. Yes. And I think

39:09

a nice thing too is that all of

39:12

these authors are very cognizant of the

39:14

perils of these technologies that they're talking about,

39:17

thinking about how this is going to

39:19

affect other social systems. Yeah, you're right.

39:21

I mean, none of this is blind

39:23

optimism. It's definitely tempered with reality. And

39:25

they're very much rooted in the real

39:28

world. Each of these authors. Okay.

39:30

Well, we've talked about most of the books here,

39:32

but there are a few more that we haven't

39:34

been able to talk about. So you're going

39:37

to hear about them in the upcoming

39:39

series. And there will be a blog

39:41

post that is accompanying this intro as

39:43

well that will go into more detail.

39:46

So we look forward to bringing you these stories.

39:49

That was editor Valerie Thompson and host

39:51

Angela Saini taking us through some

39:53

of the 2024 books. We're

39:56

going to see six over the course of the year. The

39:58

come out the last. episode of

40:00

each month starting with the kickoff in April. The

40:02

first book will be May. You

40:05

can check them out on the site, science.org/podcast

40:07

and actually see the full list and

40:09

read along this year. We have every book

40:12

confirmed and the dates are set. So yeah,

40:14

go to science.org/podcast and look at this episode

40:16

page and you will see a full list

40:18

of what we're reading for the year. And

40:23

that concludes this edition of the science

40:25

podcast. If you have any comments or

40:28

suggestions, write to us. That's

40:30

sciencepodcast at aaas.org.

40:33

To find us on podcasting apps,

40:35

search for science magazine or you

40:37

can listen on our website, science.org

40:39

slash podcast. This show was

40:42

edited by me, Sarah Krusty and Kevin McLean.

40:44

Special thanks to Kelly Cervick and Ariana

40:46

Remel for all their work on some

40:49

fantastic stories and a big welcome back

40:51

to Angela Caney as we kick off

40:53

the 2024 book series. We

40:56

also had production help from Megan Tuck at

40:58

Podigy, Jeffrey Cook composed the

41:00

music on behalf of science and

41:02

its publisher, AAAS. Thanks

41:04

for joining us.