152. Hunting for the Origins of Life

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I'm sure you're familiar with Darwin's theory of evolution, which explains how simple life forms evolved over billions of years into complex life forms.

But what evolution doesn't tell us about at all is how those simple life forms came into being in the first place.

How did we go from non-life to life?

And that is the question that keeps today's guest, Jack Szostak, up at night.

Life everywhere is cells, right?

So there had to be a first cell.

That means there had to be some kind of primitive cell membrane that defined the boundaries of the first cells.

Welcome to People I Mostly Admire with Steve Levitt.

Jack Szostak is a University of Chicago chemist who first earned recognition for his work on chromosomes.

In fact, he won a Nobel Prize in 2009 for that work.

Now, a lot of researchers who hit upon a Nobel-worthy idea, they devote their life to that idea.

But not Jack, his interests evolved.

27 years ago, he landed on the question of how life first emerged on Earth, a question that's still captivating him today.

He's co-authored a book on the topic called, Is Earth Exceptional?

The Quest for Cosmic Life.

So what exactly does it mean to study the origin of life in a lab?

That's where we start our conversation today.

I've never been very interested in all these efforts to define life, but what life

does is it evolves.

The way I got interested in the origins of life is because for 10 years we'd been studying the evolution of molecules in the lab with all kinds of fancy instruments and really brilliant students.

And then I started to wonder, like, how in the world could evolution get started all by itself on the early Earth?

You need to understand how to go just from chemical reactions and geological scenarios to some kind of simple system that can start to evolve.

How simple?

Bacteria are really complicated.

They have thousands of moving parts, thousands of enzymes, thousands of metabolic reactions, typically millions of base pairs of DNA to encode all of those functions.

So that's the result of a long process of evolution and adaptation to new environments and competition against other organisms.

So the first cells had to be much, much simpler than that.

Just maybe some small bit of genetic information enclosed in some kind of simple cell membrane.

So finding out how to make those parts and have them come together is basically the core of the issue.

I think of bacteria as incredibly simple.

They don't seem to do much, but you'd say that there are millions of base pairs.

There's all these enzymes.

It seems so simple, but in fact, it is so ridiculously complicated that you can barely believe it could ever come to exist.

And so what you are interested in is trying to figure out how you get to something

orders of magnitude simpler than a bacterium, but that still, in some sense, represents life.

And so to live, you're saying you got to have some kind of a cell wall because you got to be able to contain yourself.

I guess you have to be able to replicate and make new output.

Yeah, you have to be able to grow and divide and have progeny.

So all of that sounds so crazy that it could happen.

And as I read your book, on the origin of life and trying to put together the chemistry of it, what I realized was that I had been walking around with a completely wrong idea in my head for the last 40 years.

And I think a lot of people do this because sometime long ago in school, I got taught about that famous experiment that they did at the University of Chicago.

The Miller Urie.

Yes.

Yeah.

It was in the 1950s.

And the way I remember it is a couple of researchers put some of the compounds into a container that might have been on earth billions of years ago and they zapped it with electricity and I think that was supposed to represent lightning.

And when they opened it up and looked at it, they had made something.

Was it amino acids had been created?

Yeah, a few amino acids.

And the message I took away from that, and I think the message the textbook wanted me to take away from that, was that modern science can explain how life emerged.

But now I realize a couple of strands of amino acids are probably the least of the difficulties in getting from no life to life.

Yeah, exactly.

So at the time, it was an amazing breakthrough that some of the fundamental building blocks of biology turned out to be easy to make, in a sense.

So that led to a lot of optimism that the whole problem would be solved pretty quickly.

But then it turned out, as you said, it's more complicated than that.

So in the Miller-Urey experiment, You don't just get these amino acids.

You get thousands, probably millions of different chemical compounds because you're just blasting everything to atoms and letting them come apart, come back together again in all kinds of different configurations.

Whereas, what you need to get life started is a small number of the right things in a large amount.

And so it took decades to work out how that could happen.

And one of the biggest breakthroughs that happened was that people came to see that RNA was really central.

I think outside of science in everyday speak, RNA doesn't really get much attention compared to DNA.

The recent mRNA vaccines kind of changed that, made mRNA into a household word.

That's true.

But scientists have come to believe that DNA was not even in the picture in these early cells, but RNA was.

Can you explain what's so special about RNA?

Yeah.

So if you look at modern cells, even for example bacteria,

RNA plays a lot of roles.

DNA is the archival storage of information, and it gets transcribed into RNA.

And then the RNA is used to code for the sequences of proteins, which are made on these complicated molecular machines called ribosomes.

But it turns out ribosomes themselves are actually mostly RNA.

They have some little proteins here and there, but the important parts are RNA.

And when you're making proteins, the amino acids that make up the proteins are delivered by yet another set of RNAs called tRNAs.

And then it turns out RNA does a whole bunch of other functions.

it's really playing a lot of roles in cells.

It's really central.

And so if you think back to how the whole thing could have gotten started, it just makes a lot more sense to think of a primordial cell with an RNA genome.

And since RNA today is necessary for making all of our proteins, it seems pretty clear that proteins, at least coded proteins, came later.

And RNA is what you need first.

Something that's really special about RNA is

that it can act as an enzyme.

Do you want to explain that?

Yeah.

So for decades, from the say 50s through the 80s, people were studying enzymes that were protein molecules.

So different enzymes catalyze different chemical reactions in cells.

There are a lot of enzymes that catalyze a lot of different essential reactions.

And except for a very few people, no one ever imagined that RNA could also act as an enzyme.

The fact that making proteins is such a complicated process made it really hard for people to think rationally about the origin of life.

How could you get started if you needed all this complexity?

And then, when Tom Chek and Sid Altman discovered that RNA molecules could act as enzymes, it broke that log jam.

You could imagine a simple cell with an RNA genome that maybe encoded an RNA enzyme or a bunch of RNA enzymes that would do the fundamental jobs of biochemistry.

And then proteins could come along as a later evolutionary invention.

The problem became much simpler because you just have to work out how could the chemistry of the early Earths give rise to the building blocks of RNA?

How could you assemble and replicate RNA?

And that would provide a path.

Where's the current state of knowledge?

Are we almost there?

Have we largely figured out the pathway to these first cells?

Or are we wandering around not so sure?

I'm an optimist.

I think we're almost there.

It's true that I've been saying that for a while.

You were quoted back in 2014 as predicting that we would create life in the lab within three to five years.

Now, that hasn't happened.

What's made it harder than you expected?

There have been a lot of surprising discoveries along the way.

There were problems that we haven't even imagined.

And some of those we've solved.

Some we're still working on.

The process of copying RNA without enzymes turned out to be harder than I thought, but we've made a a huge amount of progress on that.

I still hold with that statement.

We'll get it all figured out, I think, within the next three to five years.

Okay, so that's your current prediction?

Yes.

I can hold you to we will have life in the lab in three to five years.

And what is life in the lab?

What does that mean?

To me, what that means is a simple protocell has a membrane that encloses some RNA molecules.

And we know how to make the membrane part grow and divide.

And I think soon we'll be able to show that we can make the RNA genome part replicate without enzymes.

So the whole system then is like an ultra-simplified version of a modern cell.

It can grow and divide.

It can replicate its genetic information.

And in a system like that, as you go through continued rounds of growth and division, it will start to evolve.

Sequences that do something that make the cell better adapted will come to dominate.

And that's what we want to see.

And when you and others are seeking life in the lab, do you have to play by the rules that existed in the primordial Earth so you can only put the kinds of materials in there that we think would have been there?

Or do you start by just saying, look, if we can get this any way, shape, or form, then we'll go back and figure out how to fit the constraints of what might have been happening on Earth.

That's the way we think about it.

We would like to have a system that is totally plausible as something that could have happened on the early Earth, but there's a lot of puzzles there.

So we'll start with something that's a little bit artificial, and that'll give us ideas.

And then I think we'll gradually work out step by step to get something that's more realistic.

Okay, so just to ground me, let's take something like it's going to be a cell, so it's got some exterior to it that keeps things on the inside.

So if I understand, you start with just a stew of chemicals, and out of that, you want to emerge a cell wall.

Yeah, it turns out that's actually pretty simple.

So modern cells use really complicated molecules to make their cell membranes.

They're phospholipids and things like cholesterol and other even more complicated lipids.

Probably none of those things would have been around on the early Earth.

So you need to think of a simpler kind of system to get started.

And it turns out, probably the simplest thing you could think of to make primitive membranes would be just fatty acids.

Basically, these molecules have two ends.

One likes to be away from water, one likes to be in water.

And they spontaneously assemble into membranes, where the hydrophobic parts, the parts that want to be away from water are in the middle.

The parts that want to be in water are on the outside.

And it's just a spontaneous process.

So if you take a simple fatty acid like oleic acid, which can come from olive oil, for example, you shake it up in water.

If you're not too acidic, not too basic, have a little salt.

It'll spontaneously form membranes, and they'll spontaneously close up into beautiful spherical vesicles that really just visually look like what you'd think a primitive cell would look like.

Okay, so that part's surprisingly easy, maybe.

Yeah, maybe, yeah.

The problem is not assembling these primitive membranes.

The problem is how do you get them to grow and divide without any evolved biological machinery?

It turns out that's also not so hard.

In fact, we now know several different ways of doing it.

And the other problem is: okay, the primitive membrane has to let nutrients that are made in the external environment into the protocell, but not be too permeable because you don't want useful molecules to leak out.

So there's kind of a fine balance there.

And it also has to be stable under relevant environmental conditions.

So those are the kind of harder parts of that problem.

There may be many different ways to solve those.

And so that's a lot of what we're looking at in the lab now on the membrane side of things.

And then somehow you have to have some information, some genetic information that gets passed on from one cell to the next when it replicates.

Yeah, from generation to generation.

And that's where RNA is so critical, right?

Yes, yeah.

So we think that RNA, or something like RNA, maybe not exactly like modern RNA, but something similar, is the best candidate we know of so far for that early genomic material.

And there the problem is how to copy the information, how to replicate it.

In other words, how to copy the copies so that information can be passed on from generation to generation.

How do new functions arise?

And so the idea is if you look through enough sequences, eventually by chance, you'll hit on a sequence that does something useful.

And then the cell that contains that sequence, its descendants will be more fit and will take over the population.

And that is the process of Darwinian evolution in a nutshell.

We'll be right back with more of my conversation with chemist Jack Szostak after this short break.

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Water seems to be really important too, but not for the reason that we think about water being important today.

Obviously, these protocells weren't drinking anything.

Why is water so important?

What can these protocells develop in methane or whatever else was around back in the old days?

Yeah, this comes up a lot.

Maybe the larger picture is, does life have to emerge in water?

Could it emerge in very different environments?

The methane, ethane, lakes of Titan are always cited as a potential alternative environment.

So, water is an amazing solvent, and you can do all of the chemistry that gives rise to the building blocks of life.

That can all be done in water.

We don't have any other examples.

We can't really say that life has to start in water.

But if you start to think about alternatives, none of them actually look very promising.

And

in particular, those lakes on Titan, they're so cold

that complicated molecules that you might need to make primitive cells would not be very soluble.

So

I would not be very optimistic about finding life in those seas.

Now, I think there's something interesting, though, that can be looked at.

Could we, as chemists, make something

that would behave kind of like DNA, could be like a genetic polymer a genetic material, but in a different solvent.

That's a huge challenge.

We played around with that in my lab for a while.

And I think the main thing that we learned was, wow, that's really, really hard.

There are a few labs pursuing this.

It'd be super cool if people could figure out a way to make genetic materials that worked under very different conditions.

So I hope.

people carry on with that type of work.

As I read your book, I had to laugh out loud because you describe in detail the various compounds that are seen to be critical in the path to early life, and water is one of them.

And then after that, it's just a laundry list of the most noxious things imaginable.

What is it?

Ammonia, cyanide, sulfur, formaldehyde.

They sound like a terrible basis for life.

Could you just explain the taste of the chemistry of the kinds of reactions that you think were going on that are the building blocks of life?

It's what you said, it's exactly true.

All of the starting materials for prebiotic chemistry are the most horrible, poisonous, noxious things you can imagine.

And the most ironic of all, I think, is that the best starting material for building more complicated molecules turns out to be cyanide.

You know, it's a beautiful irony there.

But there's a reason for all of this.

Cyanide Cyanide is basically a carbon atom with three bonds to a nitrogen atom.

So it's a kind of high-energy molecule.

It'll spontaneously react in different ways.

So the puzzle has been how to exploit that energy, how to accumulate cyanide, and then how to make use of that as a high-energy starting material that you can channel in really efficient reactions to make the right subset of molecules.

Aaron Ross Powell, so there's something called called LUCA, L-U-C-A, the last universal common ancestor.

I think the idea being that all currently living things shared a single ancestor.

So let me ask you, do you think it's likely that life emerged only once on Earth?

Or do you think that it might have emerged lots of times, but only this one evolutionary line survived to the present?

That's a great question.

So Luca was a very complicated organism, not all that different from a modern bacteria.

It had DNA, had RNA, could make proteins, had lots of enzymes.

We know Luka had these characteristics because every living thing that we see on the planet has remarkably similar inputs, like DNA.

And it's not at all obvious that every single creature we've ever found would be replicating using DNA.

Right.

And making proteins on ribosomes, which look pretty much the the same in all living organisms.

Which is strange, because this is true even of those things they find at the bottom of the ocean in the sea vents, too.

Yeah.

Yeah, everything.

Okay.

Yeah.

So it's common ancestor.

But that common ancestor is a long, long way in terms of evolution from the first cells.

We can't answer that question of whether life arose only once.

If it was an incredibly rare process, it's certainly possible that that life only arose once and then started to spread.

And certainly many of the subsequent lineages would have gone extinct.

And ultimately, the survivors are now what we call Luka.

But it could equally well be that life was popping up all over the planet, but by competition or by environmental accidents, only one line survived.

Or it could even be that life arose independently several times, started to evolve new functions, and that those functions were exchanged between cells.

And the surviving lineage actually took RNA sequences from different starting points.

But all of that history has been erased.

It's interesting to think because when you talk about competition, these protocells weren't very good.

at doing whatever they wanted to do, but they were probably really good to eat.

And in a world in which they were trying to get started, if another set of protocells had a head start, it probably was not a very happy environment for these new ones to try to launch.

Yeah, I think there would have been very intense competition.

These first cells would have been barely hanging on in an environment that's constantly changing.

And it would have taken some evolutionary progress to make cells that were robust enough that they could spread across the planet, dominate life worldwide.

And once they got good enough, I think it would have been very hard for any new origin of life to take hold.

How big a research community is there working on these problems?

How many labs?

How many scientists?

It's a pretty small community, and it's also very broad because there are people working on all different aspects of this problem.

But in terms of the actual prebiotic chemistry, there's only a handful of labs worldwide working on that.

And in terms of taking those molecules molecules and trying to understand how they come together to make primitive cells, it's an even smaller number of labs.

For those two areas combined, we're probably talking only 10 or 15 labs globally.

And there's a lot more people working on other parts of it.

How do planets form?

Could there be life on planets around other stars?

That's also a huge part of it.

We need to understand how planets have assembled and what the environments are like on young planets.

That's like a critical aspect of the whole pathway.

Do you work on this because you think it might have practical implications or you just think it's an amazing question to try to answer?

I just think it's a wonderful question.

I'm not expecting any practical applications to come out of this.

Is it hard because of that to get funding?

Yes, it is hard.

I think research in this area is grossly underfunded.

For about 10 years, the field had pretty good funding from the Simons Foundation.

But that's that's over, so we are all struggling to get funding to continue this research.

And especially to help young people who are excited about this field to enable them to carry on.

I've heard a lot about something called mirror bacteria.

Is this something that any of these labs are working on?

Can you explain what it is and its potential importance?

So the molecules...

that cells are built out of are

almost always what we call chiral, which just means that they're not the same as their mirror image.

Like you're right and left hand.

They're not superimposable.

Amino acids of the same handedness and nucleotides of the same handedness and sugars.

So in Siri, you could make cells or cells could form

where all of the molecules are in the mirror image form to what we see in modern life on our planet today.

We don't think that's because being, say, right-handed for a sugar is good or bad.

It's just chance because evolution only happened once.

That's right.

And not only that, but for example, if you think about RNA or DNA, if you tried to make an RNA molecule where some of the nucleotides were right-handed and some were left-handed, it wouldn't work.

It wouldn't have a regular structure.

It couldn't be copied, couldn't be replicated.

So life had to get started with molecules of one-handedness.

But

which handedness that is, we think is completely arbitrary.

It doesn't matter.

So now, if you think about, okay, what if it was technically possible to build a bacterial cell using molecules all with the opposite handedness to what we find in normal bacteria?

We would expect that kind of mirror bacterium to work just as well as a normal bacterium, as long as it had mirror food.

The complication comes in terms of thinking of how would it interact with our normal life.

And that's where we're really worried, because if you think of

how our immune system protects us from infection with bacteria,

it's because the molecules of our immune system recognize molecules on bacteria in a way that wouldn't work

if the bacteria was a mirror bacteria.

So we think there's a significant likelihood that mirror bacteria would escape immune surveillance and that therefore they could potentially be really, really dangerous pathogens.

And by extension, the same thing would apply to animals and plants that could be unable to fight back against an infection by mirror bacteria.

And it also extends to microbial ecology.

So there are a lot of microbes that live in, say, the soil or the oceans and so on.

And one of the main reasons those bacteria die is through infection with viruses.

And that process would also not happen.

So we think the consequences for infections and ecology would be potentially extremely severe.

One more thing to worry about that we didn't know we had on our plate.

Yeah, we're trying to get people to just universally agree that, okay, let's just not make mirror bacteria in the first place and avoid any of these problems.

This is People I Mostly Admire.

I'm Steve Levitt.

And after this short break, Jack Szostak and I will return to talk about the possibility of extraterrestrial life.

I think none of those steps look super difficult.

So that would be an argument for life potentially being really common and widespread.

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We help you understand what's happening and how it impacts your life.

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Jack Shostak has thought a lot about the origin of life, what it looks like and under what conditions it could form.

So I'm curious what he thinks the chances are that life exists elsewhere in the universe.

I no longer have a strong opinion on that.

So when I give talks on this subject, what I've started to do is ask the audience, how many of you think that life is common in the universe, widespread on planets around other stars?

And usually about half of the people will raise their hands.

And then I ask, well, how many of you think that life is so complicated and so hard to get to?

that it might have only started once.

And in fact, we could be the only place in the universe where there's life.

And then a lot of people raise their hands for that as well.

The title of my book, Is Earth Exceptional, is a question.

And it's a question because we don't know the answer.

And because we don't know the answer, that's why I'm doing the work that I'm doing in my lab, and why other people in the field are doing their experiments, and why astronomers are looking for life out there because we don't know the answer, but we sure would like to.

The one thing I will say is that a lot of the

steps towards getting to life

that we once thought were really hard turned out to be really easy.

On the other hand, what I have come to appreciate is that having multiple steps happen on an environment in the early Earth could have been really, really rare.

And just to give you a sense of why that might be,

the path from cyanide to the building blocks of biology, It's a series of chemical reactions.

And what has to happen is you build up a a reservoir of some intermediate.

It has to survive on the early Earth for a while.

And then conditions have to change so that material can go through one or two or three more chemical reactions until you get to something else that can build up as a reservoir.

And then that also has to survive.

It has to be not washed away and in a flood or obliterated by a meteorite impact.

It has to survive and then get transformed into the next intermediate.

And having a whole series of steps like that, that could be really rare.

If life is rare, that's why I think it's rare.

But of course, we just really don't know.

The earlier it's a big place, lots of environments, lots of time.

Maybe the whole thing turns out to be easy.

Let's say that life turns out to be common in the universe.

How about intelligent life?

It seems like the path from life to intelligent life is a pretty torturous one too.

Exactly, it is.

And in fact, you could break it down at least into two steps.

So we have primitive life, protocells, getting to something like Leuka.

There's a lot of steps, a lot of evolution there.

I don't see fundamental roadblocks there, but we do know from the history of life on our planet.

that things stalled out at that level of complexity for a couple of billion years.

And the reason is from the geochemistry.

To make more complicated cells,

you probably need to have the ability to

generate more energy in an efficient way, which means maybe you need oxygen.

And oxygen didn't start to build up in our atmosphere until roughly two billion years ago.

And it only built because these little board were the cyanobacteria.

Cyanobacteria, right.

We're plugging away for billions of years to fill the air with oxygen.

And then you start to get more complicated organisms.

But again,

life was kind of simple, low-level organisms, for another one and a half billion years.

And then you start to see larger multicellular organisms, animals, eventually plants, fungi.

So

the reasons for these long

periods of stasis are not really clear, right?

There's a lot of debate around those issues.

And then,

okay, going from animals to intelligent animals.

Wow.

It's really hard to even think about.

Super interesting, but hard to think about.

What do you think history will judge as the most important chemistry breakthroughs of your lifetime?

Oh, wow.

Well, given the field that I work in, I think

understanding how we went from

really simple starting materials like cyanide and things like that up to the molecules of life, I think that's a really amazing development in chemistry.

Now, I know Jennifer Doudna did her PhD under you, and she would later go on to win the Nobel Prize for her work on CRISPR.

Do you think CRISPR would be a candidate for one of those chemistry breakthroughs that history will really remember and celebrate?

Well, that's an interesting question.

It's obviously been transformative for our ability to manipulate genomes and as a tool for studying how biology works.

But new tools tools are constantly being developed.

How long will people be using CRISPR?

I don't know.

Before CRISPR, there was RNAi,

which also won a Nobel Prize.

People still use RNAi, but a lot of the applications of RNAi are now taken over by CRISPR.

And

I would guess that a lot of things that people are using CRISPR for will eventually be taken over by other new methods.

So maybe I'm wrong.

I don't know anything about RNA, but what was so striking to me about CRISPR is that it really

put

a godlike capability into human hands, the ability to pick and choose exactly how one would rewrite DNA.

Do you see that philosophical jump as being a big one or not so big?

It's a big jump when you...

get to the point of manipulating human genomes, for sure.

The ability to manipulate simpler genomes, starting with viruses and bacteria, goes back a long way.

That's really been the basis of a lot of biotechnology.

And the ability to manipulate the human genome obviously raises all kinds of new issues, both practical and in terms of the future of our species.

So last question.

You have been working for so long and so hard to try to create life in the lab.

When it happens, are you going to know that you did it?

Is it going to be this aha moment where suddenly you have done it?

Well, I guess we won't really know until we've done it.

Actually, what I expect is that it will happen gradually.

We'll get there step by step.

We'll see low-level forms of evolution, just because some sequences are easier to replicate than others, for example.

I think the real breakthrough is if we see the emergence of a new RNA enzyme.

At that point, yeah, we'll know and that will be very clear.

That would be super exciting.

And do you think if it happens, will it happen in your lab or will it happen somewhere else?

I hope that it happens in my lab in the next few years.

If we don't manage to solve all of the problems in the next few years, it will probably be one of those problems that gets passed on to the next generation.

which would also be great.

Is your retirement decision affected by whether whether or not you've created life?

Are you going to try to stick around as long as you can so you do it?

Or is that not what's driving you?

Well, it is in a way, because when I decided to start working on the origin of life, I was actually

at that time thinking, I would like to find a subject that will keep me engaged.

And I think maybe I chose too well because the subject is so engaging that

I can't let go.

I feel like I have to keep working on this until I drop.

I love talking to academics who are so passionate about their work.

I always wanted to be like that, a professor who derived great joy from going into the office each day, even as I got older.

But myself, I ran out of both enthusiasm and good ideas.

I'm just glad I had the wisdom to retire when I did.

I sure do hope that Jack gets to see life created.

And of course, it would be especially great if his own lab was the one to pull it off.

So now is the point in the show where I welcome my producer, Morganon, to tackle a listener question.

Hi, Steve.

In our last new episode, we interviewed psychologist and neurobiologist Owen Flanagan, who recently wrote a book on addiction.

It's based on research, but also is part memoir because Owen was an addict for 20 years.

So we asked listeners if they had any follow-up questions for Owen.

And a listener named Andrea from Brazil wrote in.

And her question was, I've heard that a lot of addiction is rooted in trauma and that it is very hard to treat addiction without addressing that underlying trauma.

I was just wondering what you think about that and if you have any data on it.

So we sent that question to Owen and you have his response.

So Owen gave a response that actually surprised me.

He said that 50% of addicts statistically suffer from a preexisting psychological condition.

God, among the people I know who have been addicts, it sure felt like it was higher than 50%.

I'm not really answering the question right because I'm supposed to be giving Owen's answer.

But here, let me give my answer too, which is I see a lot of self-medication out there.

And I think Andrew's exactly right.

If you have an underlying problem and you're using drugs to self-medicate, it doesn't really seem very likely that getting rid of of the drugs are going to solve the problem.

But I think it's actually good news for the world if only half of the addicts have preexisting psychological conditions, because I think it's a lot easier in many ways to beat an addiction than it is to beat a long-standing psychological problem with an addiction tacked on top of it.

So at the end of that episode, you had sort of mused about addiction.

And to you, a substance abuse addiction felt like a worse addiction than maybe an iPhone addiction or your golf hobby, which you claim is an addiction.

And we had some listeners respond to that.

So we had someone named Karen say, I think the difference between a healthy addiction and a substance abuse is that the resulted harm is often less directed by the form of addiction.

The compulsive urge to do something, however, is a sign of an unhealthy mental state and is related to other underlying issues like body dysmorphia or some form of OCD.

And that sort of relates to Andrea's question.

And then we also had Liz who wrote that addiction isn't about what you do or how you feel when you do something.

It's about what happens when you can't do something.

So Liz said she struggled with an eating disorder.

And she said when she was most struggling, the food and exercise controlled her like a drug.

She was addicted and obsessed with them.

She also said that she thought an eating disorder was a really hard addiction to kick because you can't go cold turkey.

Obviously, you need to eat.

You have to find the right balance, and that's tough.

Yeah, I think, Liz, again, let me talk from personal experience, which is not embedded at all in data.

But when I watched my daughter Lily go through an eating disorder, I had that exact same feeling that it's really tough to break because eating is so central to life.

And so you can't just walk away from it, like, say, you could alcohol.

We got so many responses from listeners.

And I would say the overwhelming majority of them on things like cell phone addictions were trying

to portray cell phone addictions as being like alcohol or drug addictions.

And I have to say, I'm still unconvinced.

I think lots of behaviors we have have addictive characteristics to them.

And the thing that matters is whether it destroys your life or not.

And messing around on your phone, people complain about it, but they do it because it's fun.

And the consequences are a little bit of wasted time not destroying your body, not overdosing on fentanyl and dying.

It seems like the research is pointing to phone addictions being most destructive for young people who are really impressionable and might get addicted to social media and watching other people do things they might be jealous of or the comparison that happens.

A lot of the research is then pointing to mental health issues.

What do you think about it in that regard?

So look, I'm not saying that I think it's great for kids to be on phones all the time.

But on the other hand, I kind of think growing up has always been hard.

And maybe phones make it harder in some dimensions, easier in others.

I guess what I'm saying is it's not that I think phones are all milk and honey and rosebuds, but compared to really bad things, they just don't get me that worried.

So we had a listener named Kyle, a 26-year-old from Ohio, and he shared that most everyone he knows is in some way actively trying to limit their usage on their phones.

And so he thinks that perhaps this is the start of a trend that we'll see in the future.

I think that might be overly optimistic, but Kyle has a positive outlook on the world.

I mean, phones are fun.

And part of it is that the social media companies have figured out how to make them really, really fun.

In order for us to be worried about phones, you have to think that the short-term enjoyment we're getting out of our phones is somehow in the long term really really punishing us because maybe we're not forming strong relationships or we're forgetting how to work hard or concentrate.

And that might be true.

And there is social learning.

Let's go back to drugs.

Heroin was a terrible wave of drug addiction in the 1960s.

But the next generation looked at the generation before them that got destroyed by heroin in the inner cities and they didn't do heroin.

The same was true of crack.

The crack epidemic went really quickly because the initial set of folks who got addicted to it were such a mess that the young people growing up in those neighborhoods said, I don't want to be like that.

I don't want to be a crack addict.

So it's possible we'll see something like that with phones.

But again, I hold my stance, which is that phones are about 85% positive and 15% negative.

And in life, sometimes you just take.

those kind of trade-offs.

So we'll see.

Maybe in the future, everyone's going to treat their phone like it's toxic waste, but I don't think so.

Steve, what's your favorite thing to do on your phone?

Oh, God, I thought you were going to say, what's my favorite thing?

And I was going to admit that it was my phone.

I love my phone.

I actually am not that interested in social media.

I don't believe that at all.

All you talk about is Instagram and how you love the ads.

I do.

It's not that I like other people.

I do love the ads on Instagram.

I don't really care very much about the other content.

Mostly the only thing I use my phone for is email.

and news and texting.

And it's the way that I practice trivia with flashcards.

Thank you to everyone who wrote in with their thoughts on addiction and with their questions for Owen Flanagan.

If you have a question for Steve Levitt or just thoughts about our show, our email is pima at freakonomics.com.

That's P-I-M-A at freakonomics.com.

We really do read every email that's sent and we look forward to reading yours.

So a listener wrote in.

She was so angry at that last statement you just made because you make the same statement every time.

She said, why does Morgan always say read every email that's sent?

You can only read emails that are received and some emails that are sent might not be received.

Yep.

I've seen her emails.

I liked it.

I thought that was a really good point.

Let me rephrase.

Thank you, Rachel, for your critique.

We read every email that we receive and we look forward to receiving your email in the future.

See, we're a learning organization.

We are evolving.

Next week, we've got an encore presentation of my conversation with Reginald Duane Betts.

He has an absolutely amazing personal story.

And in two weeks, it's a brand new episode with physician Suzanne O'Sullivan.

She's a neurologist who focuses on psychosomatic illness.

As always, thanks for listening, and we'll see you back soon.

People I Mostly Admire is part of the Freakonomics Radio Network, which also includes Freakonomics Radio and the Economics of Everyday Things.

All our shows are produced by Stitcher and Renbud Radio.

This episode was produced by Morgan Levy and mixed by Greg Ripon.

We had research assistance from Daniel Moritz Rabson.

Our theme music was composed by Luis Guerra.

We can be reached at Pima at freakonomics.com.

That's P-I-M-A at freakonomics.com.

Thanks for listening.

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That's fine.

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