Thank you for joining us for the meaning of life and death with Andrew Steele and Carl Zimmer moderated by Halli Benasutti.

Before we begin, thank you to our founding sponsor, the Kerry and Linda Killinger Foundation Hello, and welcome to the Crosscut Festival.

My name is Halli Benasutti I am currently a doctoral candidate for philosophy at the University of Washington and I'm getting my degree in biochemistry My thesis project is focused on the development of a gene therapy to treat a specific type of muscular dystrophy And as a researcher, I work with indisputable living organisms from a small as a single bacterial cell to a mammalian cell or even up to larger organisms.

such as mice.

I also work with modified viruses , which, as we will likely touch upon today, may or may not be alive We have a lighthearted, fun discussion planned for you today, revolving around death.

Death is the inevitable price we pay for being alive, but we can't.

Conceptual eyes or define death if we don't first discuss what it means to be alive.

One doesn't exist without the other, and as medicines and tech advance, they are changing our understanding of what life means.

My guests today are two authors, one focused on the scientific work to work to define life in another who explores our efforts to extend our lives.

Joining me today is Andrew Steele, a scientist, writer and author of the book Ageless: The New Science of Getting Older Without Getting Old After getting his Ph.D. in physics from the University of Oxford, he decided that aging was the single most important scientific challenge of our time, and he switched fields to computational biology.

We also have with us Carl Zimmer.

He writes.

Matter , a column for the New York Times and is the author of 14 books, including Life's Edge The Search for What it Means to Be Alive.

They have both done a lot of thinking and research on the human experience and the science of life and death.

Harold and Andrew welcome Hello.

Thank you.

All right.

So as we were discussing life and death today, I think it would be good for us to all get on the same page as we go into this conversation.

So I'll get the ball rolling with an easy question.

This one's for Carl.

How should we define life You know, there's no good answer to that, I'm afraid.

People want to have we answer particularly in this political climate.

But there isn't one.

The scientists literally have hundreds of definitions, and they seem to be coming up with new ones every year.

There are variety of them, but each time that people come up with a new definition , others can poke holes in it.

And that really tells us that fundamentally, we really don't understand what life is Sorry.

No, I think that's that's what we're looking for here, right?

That's what we're here to discuss today.

So , yeah, in your research for your book , did you find that there was a definition of life that you sort of settled upon for yourself?

Well, one of the problems with definitions of life is that we tend to we kind of know what life is.

We know Darren Bones.

We know that we're alive.

And so then we try to say like, OK, what What definition can I put together that will satisfy me about life?

And you know, the fact is that like different people, including different scientists, have different things that are important to them.

Is it for example, homeostasis?

That's this amazing ability of keeping like a stable environment inside of yourself.

While the environment around you is changing all the time?

So some people will define life around homeostasis Other people say, Well, no, it's reproduction.

I mean, that's it.

That's what really matters.

OK, fine.

But like you know, if you if I take, you know, one rabbit that one rabbit is not going to reproduce.

So is it alive, you know?

And and others will use evolution and then sometimes people will just try to package it all together.

So Niassa , for example, came up with that definition.

Some nascent scientists working with Niassa came up with definition of basically considering life as a a chemically self-sustaining system capable of Darwinian evolution, trying to pack it all in there.

And they use that as a way, as a guide for looking for life on other planets.

And that's that's fine.

But it's there's no like theory behind it.

It's just sort of a it was it kind of emerged out of an all day bull session, basically.

Yeah, for sure.

That was actually I was just about to ask that how do we feel like we?

What's the thought process for defining life that we might encounter in worlds that aren't our own?

Just because it seems like our definition of life is so limited to what we perceive as life Yeah, yeah.

I mean, you know, you notice how in Star Trek, for example, all the aliens look suspiciously like Hollywood extras.

So does that mean that all aliens on other worlds, if there are will, will look like humans or , you know, will they even be multicellular?

You know, if they are, if they let's say, let's say that there's life microbial life out there.

That's kind of, you know, that that's a possibility Will will they use DNA?

Because like all life that we know of on Earth uses DNA?

So does that mean it has to be DNA?

There's really no strong proof that that's the case, you know, we could do.

It's just that, you know, it's it's conceivable that there were different ways that life got started on Earth.

And you know, the DNA based life won out.

Some people think that actually life started as ANI.

You can almost like if you if you think of the little bubbles of RNA that people get in their Pfizer or Moderna shot, think of that as being the start of life.

RNA based life , little protocells and then DNA based cells kind of evolved out of that.

And then they basically like ate all the RNAi based life, and it's gone.

So you know what?

if there's something even better than DNA out there?

Yep.

Oh, definitely Yeah, that's what we know, because it's what's around us, right?

So Yeah.

My next question is for Andrew.

Welcome back.

Andrew.

How can we age without getting older and maybe even avoid dying?

This is something that you focus a lot of your research on and then that your book also.

Yeah, it's a great question.

I think actually, you might think that aging is one of these things that defines life.

But what's really fascinating is if you look around the animal kingdom , although we age, you know, all our friends, our families, our relatives, everybody we know, humans, all age, a lot of the animals in our lives, age as well.

So if you look at your pets, your cats, your dogs, you know, your mice, they all age in actually remarkably similar ways to human beings.

They all get frail, they all suffer from very similar spectrum of age related diseases.

We've all seen, you know, a dog with cataracts that can't quite see properly and arthritis in its joints.

It really looks as though aging is this universal process.

If we cast an eye bit wider and a really good example of this is a tortoise, which is the reason there's a tortoise on the cover of my book is because Tortoise is despite a property called Negligible Senescence And this is to say basically negligible means.

Not very much, obviously.

And senescence is just the scientific term for aging and the way that we can define this most easily is to look at the risk of death and how that changes with time.

So a human has something called a mortality rate, doubling time.

That's about eight years and that means that, well, let's sort of break that down to an example.

I'm 36 and what that means is this year I've got a risk of death of about one and a thousand.

And actually , I quite like those odds because what that means is I've got less than one a thousand chance of not making my next birthday.

But unfortunately, if you double every eight years time, it's going to be one of the five hundred and eight years time again is going to be one of the 250.

These aren't too bad until you get to older and older ages, and eventually if you keep doubling something, it can start getting very big, very quickly.

And so someone who's in their 90s has roughly a one in six chance of death every year.

That's sort of life and death roll of the dice.

And as a scientist, you look at that and think, Wow, what is this?

You know, seemingly universal process that drags humans into a much increased risk of disease If we look from those negligibly senescent organisms, things like the tortoises , things like fish, even little things called Hydra.

There are a variety of different creatures out there that have this property.

They have a risk of death that doesn't change with time , and that means that they effectively don't age.

And actually, of course, you know what?

We care about isn't really so much the dying itself.

It's the suffering, it's the diseases, it's the frailty It's all those things that come along with it.

And although death is a nice, easy thing to measure and nice , easy thing to get a statistical handle on, actually, we see that these creatures don't experience these things increasing with time either.

So it really does seem that there are lots of examples out there of animals, of plants, of all kinds of different things that get older without getting old.

Yeah.

So it sounds like aging I mean, the way in which you're sort of talking about it, we're talking about aging is being this one general process, but is isn't aging composed of many different things going on within the body?

It is, yeah.

And I think that was one of the things that's actually been a barrier to studying for a very long time because obviously there are, you know, thousands and thousands of processes going on inside an individual cell, let alone inside the sort of complex interplay of our entire bodies.

All these different cells working together in a variety of complicated ways.

And I think scientists, for literally decades from the development of the theory of evolution, people thought that aging was just this impossibly complicated process that was this, you know, if you imagine you know, back in the eighteen hundreds, we had a really good theories of physics, thermodynamics, basically saying that everything falls apart with time.

I one of the conclusions and the second or thermodynamics this law of the universe.

So why should animals be any different from steam engines being any different from rocks and other things that make up the world around us?

Well, actually, of course, now we understand that animals have these self-repair mechanisms, and that's one of the ways that you can stave off the aging process.

But we've also come to understand that aging isn't one monolithic thing.

It's exactly, you know, it's almost as complicated as they would have predicted.

But thankfully, we can break it down into a collection of processes that are sometimes known as the hallmarks of aging.

And these 10 things and then different cellular molecular biochemical signatures of growing older and that things like damage to our DNA at the most fundamental tiny levels inside our bodies.

Then you can get this function of whole cells and get senescent cells.

Science wife, old again.

And then as these sort of things scale up, you can get to a point where a whole systems in the body really exemplifies the immune system.

We've been reminded by coronavirus because it affects older people so much more than younger people.

One of the reasons for that is that the whole immune system, our body's toolkit for fighting off external threats also deteriorates with age.

So luckily, we have mice to break it down into these distinct categories and come up with ideas for treating all of them.

And that's really sort of the dream of the scientists.

It's fascinating to catalog all the different changes that happen as a part of aging.

It really is, you know, fundamental.

It covers every aspect of our biology.

But actually, what's really fascinating to me is the ability to intervene and do something about it.

Yeah.

So then my follow up question, which this is sort of the opposite of what I ask Carl at the beginning.

And Carl, this is a question for you as well.

And I know that this is also a tough question to answer, as we cannot We don't really have a great definition for life right now.

Do we have a great definition for death?

Do you wanna go first?

Carl Or should Charlie Right.

So, so, so just as we think that life is totally obvious and there must be a simple definition for it, we think, well, death, that's got to be obvious, too.

And I mean, clearly , death is a thing.

But when you try to draw that line to separate death from life, that's where things get potentially very tricky.

And you know, scientists have been struggling to define death as well as life for centuries in the early 1800s, there was a French physician they'd be shot who was trying to figure this out, and his one of his favorite things to do was to go and to watch executions.

Or he will get guillotine and then study their heads very carefully to try to figure out, Well, are they dead yet in there?

You know, because the head has been separated from the body and he came up with a definition, which is that that , well, he defined life through death , which is interesting, is that life is the sum of functions by which death is resisted.

So once so death becomes, is this this thing that will just take over one's life?

whatever that is, gives way.

The problem is that I mean, just for humans , leaving aside the animal world, for humans, it's really hard to to determine that because we keep getting better at preserving life.

It used to be thought they'd be shot for example, would believe that that the heart and the brain and the lungs were sort of, you know, inextricably linked together so that any one of them failed and the whole thing failed in your debt , which was OK until people invented the iron lung and ventilators And then it was possible to keep the lungs and heart functioning, even if the brain could no longer have conduct that job.

And that forced doctors eventually to say, You know, this is not this is not really life.

This is this is this is this kind of a death.

And so that led in the 1960s to the definition of brain death.

You know, in other words, we'd have we legally defined death as a death of the brain because for a human being, it's that life in the brain, which which matters , you know, we're not bacteria.

You know, our body, you know, there's still homeostasis going on, metabolism going on in the body of someone who's on a ventilator.

But if there's no hope of that brain recovering any function, then we can say that's what we consider.

That death, although that itself is, can be controversial And people do contests that still , yeah, I think I quite like that definition that it's some sort of some of the forces that resist death is what life is all about.

I think actually, that really does apply to the aging process because there are just so many of these things that I actually think it's quite remarkable that within a thousand figure that I quoted for my risk of death this year is really incredible.

that our bodies do maintain this homeostasis to such a sort of elegant , beautiful, precise degree.

To our chance of sort of falling off to one side or the other is remark below.

And you know, if you look at the safest humans of our current age, in fact, the safest humans in the history of humanity are current 10 year olds.

So if you're a 10 year old in the risk rich world, you have a less than one in 10000 chance and not making your 11th birthday.

Because of that, some of processes that are trying to resist that.

And I think I think cause right, one of the things that really I found remarkable reading about the history of medicine for my book was just how recently a lot of these things have happened.

So, for example, it was thought that after your heart had stopped, you were dead for a very long period of time.

But then, as recently as the 1960s, CPR was developed and rolled out, and he sort of imagined , You know what happens if somebody's heart stops?

It's the most obvious thing in the world to try and give it a pump and start to again, isn't it?

And it's sort of a staple of TV drama and films.

You see this thing happen every night on our TV screens.

And yet this really you know, remarkably obvious.

In hindsight, process wasn't even conceived up until the 1960s and start to be rolled out.

And as a result, you know, people are just living longer and longer and longer because we've completely changed our understanding of how it is that we can preserve life in older ages.

And I think what's really exciting about the idea of researching aging , it's just that we can intervene so long before these death crises happen.

I was thinking about this for this panel earlier.

You know, what is it that causes us to actually be dead?

Well, let's let's say it's brain dead now is in a way a little bit controversial, because it might be that your memories, your personality, all of those things that make you you are still in there in the structure of your brain for example.

That could be that once we get a more fundamental understanding, we account with rather than iron lung and iron brain stem that could maintain that activity.

Maybe we could keep people alive even longer than putting that question to one side and the fact we have been pushing that back further and further What we'd like to do is getting that, you know, we don't want to be giving people CPR because CPR.

In spite of what you might see in films, the huge majority of patients who are at that stage, you know, end up dying.

Unfortunately, what we want to do is you want to prevent the processes that cause these hearts to prevent the processes that cause brain is dying of themselves, things like dementia.

I think that's what really excites me is we do have to understand these processes that are multiple steps removed from the actual process of death.

But understanding the actual process of that and so peeling back the layers.

One of the things I think is most important is understanding why we die ending autopsies, particularly on older people who are often, you know, if a 90 something guys in hospital, it's just considered so unremarkable.

But actually, as you begin to understand this, you realized our our understanding of the causes of death, particularly in the oldest old, are really in their infancy.

And if we want to, you know, do the best medical work we can to try and preserve a healthy life.

And we've really got to understand what that is and what causes it.

Well, this actually leads into sort of my next question is if we need to understand life , then we need to understand death and do we need to understand the beginning of all of that as well for whoever wants to answer?

I think yeah.

And actually, I think this is this is one of the most fascinating things is that we think of the aging process as this inevitable thing.

And yet all of us have experienced in our day to day lives the process by which the human body knows exactly and there are tools in the human body to reverse aging.

And the reason we know that is that you can get an old father.

Yes, men can conceive even in their 60s Women can conceive, perhaps in their 40s, even in their 50s, and they sort of record breaking cases.

And yet, the baby that those two people have will be born young.

And that's a really obvious thing to say.

Almost sounds stupid.

And yet it's clearly the case that whatever damage accumulates to the DNA of the XL, whatever changes happen inside that cell, the body is capable of reversing into a very, very large extent.

It's not the case that the parents are that the children of older parents tend to die before tend to get age related diseases sooner.

They tend to live, you know, pretty much normal lifespan.

They're almost indistinguishable from, you know, people who gave birth at the age of 16.

So what is it that's going on inside our biology?

I think that's really, really fundamental.

And actually, this is this sort of realization has led to some fascinating and exciting movement in the biology of aging in the field.

of actually treating it in the last few years.

Because one of the big news stories in aging at the end of last year was that Jeff Bezos, amongst others, some, you know, a variety of billionaires of whom he was the most famous name have invested $3 billion in a startup called Altos Labs and the science that also slobs are getting behind is this idea of something called epigenetic reprogramming.

And this is the idea that it's actually it was actually originally developed to study this process that happens at the start of life.

There was a scientist called Yamanaka, a Japanese chap who got the Nobel Prize.

A few years later for this discovery.

He was trying to work out what it is that allows the clock to be turned back in those cells, and we can now use these things called the Yamanaka factors These are four genes that are named after the guy who discovered them, and we could take a skin cell out of my arm if your arm.

We could even get out of a super centenarians, and we was 115 years old.

We could take a skins out of their arm.

We can apply these four genes and we can reprogram those cells back to a point where they're what's called pluripotent , who are able to become any cell in the body exactly as a cell that's just been fertilized now in a sperm meets the egg, for example.

You know, just at the very, very beginning of life, And what we found is that we can turn back the clock that whole way, but we probably wouldn't want that as an anti-aging treatment because I don't want to turn into a massive glob of sort of primordial stem cells.

I want my liver cells to stay liver cells doing all the exciting things that liver cells, my brain cells, cystitis, brain cells and so on.

What we've discovered is that by applying these factors rather than applying them to the extent where we turn the clock all the way back, we can actually apply them transiently We can do it briefly and why.

The experiments in mice looked at doing this two days and every seven, rather than doing it for that sort of full duration of the week.

So you can imagine turning on these Yamanaka factors at weekends as it were, and what they found was that was enough to reverse the age of these mice somewhat.

And it seemed to make them live a little bit longer and healthier, but without causing this widespread change to pluripotency inside their bodies.

And so I think I understand the beginning of life has actually given us this incredible technology, potentially to make some changes to what happens to all of us at the end of it.

Yeah.

I mean, what's what What's fascinating is that, you know, even in the 1960s, as some of the early insights into the process that Andrew was talking about, we're really emerging Scientists were recognizing that certainly in the United States, their work was going to be smacking right into some serious political conflicts in life, said you're right about a scientist named Joshua Letter Berg, who had won the Nobel Prize for his work on bacteria And he had a warning for Americans in general that they could not look to science for some simple answer about when life begins.

He actually said in fact, what he wrote was life.

In fact, never begins.

And what he meant by that was that , you know, if you are tracing any person as history, you know, in terms of their cells , you can go back and back and back if you reverse time, you know, you're looking at a person when there are fetus, when they're an embryo, when they're just a little clump of cells, when they're one cell, and before that, there are two cells.

In other words, there are two So there's a an unbroken continuity, a biochemical continuity from that egg in that sperm, in the parents bodies.

You can trace all the components inside of it, all the proteins and the genes , all those elements that are there combined.

And then continue to interact.

And so , you know, for scientists, you know, when they when they're thinking about life, they don't think about it with some sort of legal definition of quote unquote, when life begins And, you know, the Supreme Court, when it made its decision about Roe v. Wade, literally just they said, we don't have to get into when life begins.

But you know, we are looking very much at that now politically because , you know, there is going to be an argument about, well, when does life begin?

You know, there are these personhood movements.

And so on that are claiming that life begins at conception.

And in life surge, I talk about all the problems that science poses to that kind of know very simple view of what we mean by life and beginning Yeah, definitely.

Definitely very relevant topics to be considering right now, for sure.

Another relevant topic that I'm really excited to talk with you all about because I work with modified viruses and us being two years into this pandemic.

What are your thoughts on viruses being alive?

This is something that I know in my field is like every single scientist has a different opinion But do you all have any thoughts that you would like to share You know, I I have the strange experience of getting emails from virologists telling me what to think about viruses and little on one day and literally the same day in the morning, I got an email from one virologist who said, I just read what you were writing about whether viruses are alive or not.

I mean, of course, they're not alive and any virologist will tell you.

And then that afternoon, another virologist emailed me to say, Of course, viruses are alive I mean, you can't understand them if you don't think about them as being alive, it's meaningless.

And any expert will tell you.

So I think that just gives you a sense that like I as a journalist, I'm not going to be stepping in where these virologists will not agree But that's what's so cool in a sinister way about viruses , which is that they they are , you know, you can think of them as half alive.

I mean, in the sense that I mentioned earlier, the NASA definition of life, you know, as a chemically self-sustaining system that is capable of Darwinian evolution So viruses are not self-sustaining in that sense of having like metabolism and homeostasis like they don't have it, they are.

It's a package of genes But evolution?

You bet.

I mean, these variants that we're dealing with now that are just continuing to dry out this pandemic, that's an evolution in action.

And so So here you have something that definitely is not alive in some respects.

and definitely is alive in other respects.

And so , you know, it makes them incredibly interesting You know, partly because maybe that gives us a clue about you know, maybe how life began that made that there might be these sort of intermediate idiot forms that that sort of provide a sort of a jumping off point for for life.

But, you know, viruses don't grow and, you know, and viruses don't grow old.

They they just they just are.

And either they infect a new cell or they don't.

Yeah, I think it's a fascinating question.

I think that the thing that I think that I would say is , Oh, we lost Andrew again when I was Ragnar's.

The area was going to say , I know me too.

Well, yeah, sorry, he's having this camera trouble But anyway, yeah, definitely an interesting thing to think about in terms of when we think about it moving through a population like we do or like in my research, using a modified virus that does not replicate once it enters a cell.

So it's basically kind kind of like a useless virus.

We actually use it for the delivery of therapeutics.

But in that sense, too, it's like, well, if it's not replicating and you know, again, it's yeah, it's definitely a very complicated topic that we're on today.

I'm one of the most what I find one of the one of most thought-provoking ways of thinking about whether viruses are alive or not.

Is this to say sometimes they are, and sometimes they aren't?

And this is this is actually a theory or a model that's been put forward by some scientists It's one in particular in France, He's named Patrick Fortier.

And so so for terror, you know, says, well, you know, when a virus is just out there floating outside of a cell, what sometimes is called a very on , it's not alive.

He'll say , when when it infects a cell, though, that's cell becomes something new.

So he argues that, you know, and we have so sometimes we just think of a cell as just with a virus in it as just sort of like , you know, kind of a beleaguered cell, a cell with a, you know, feeling a little under the weather, you know, just.

But the fact is that that, you know, in so many different ways , a cell that's got a virus inside of it is no longer its former self.

It is it.

It is now a virus factory.

And so far, terror calls it a virus cell Because like when you get SaaS, if you get SaaS, I hope you don't get SaaS.

But you know, when a person gets SaaS , then the virus goes into a cell.

It does this one of the many amazing things that it does.

Is it?

It goes to these factories where our cells make our own proteins from our own genes and plugs them up?

It just it locks the door so that we can't get the rRNA into those factories to make new proteins for ourselves.

Yeah, yep, exactly.

But I'm going to.

Oh, sorry, Hello back.

I was just going to jump in where I left off a please finish your thought.

Oh yeah, I was just going to say that the amazing thing with viruses when they infect cells is that they can so they they they lock the door to those factories, but they have the key.

So in other words, the cell is only making viral proteins, which then assemble into new viruses.

And it so it's this this astonishing, sophisticated switch over to what what some scientists argue is a is a new and distinct form of life that's not like the cell before it.

For viruses go back and forth between being alive and not alive.

Definitely.

And it's hard to think that something that hijacks a cell that way would not be alive to I think that's really not the way of thinking about it.

And what I was going to say is that I think a lot of this debate without coming down hard on one side or the other.

For all the reasons Carl's already outlined , I think that we imagine viruses, you know, they're parasites.

They can't exist without being inside a cell, essentially, or at least occasionally being inside US site in order to replicate themselves.

But actually, if you think about it, basically that's true of all of life, you might say, Am I alive?

Are you alive?

Well, I do depend on quite a lot of things.

I need to eat food, which is essentially, you know, plants.

These animals are the life I need to breathe, the oxygen that's produced by the plants on planet Earth.

So we're all part of this much larger symbiotic system.

And actually one thing that you some sort of a bit of a problem back back when the human genome was first sequenced.

You know, this is back in the early 2000s, we just suddenly had this access to this three billion letter long genetic code that's inside every one of ourselves.

I think some people in computational biology were quite overawed by this incredible use of data.

This power that we had to look inside the human body and decode it on a level that we hadn't previously achieved.

But actually, this led to a sort of reductionism looking at DNA as being this fundamental part of life, when actually you can sort of think of DNA as being like a floppy disk in the sense that if you don't put the floppy disk or let's try this analogy like interest e-card, try and bring that tell you the one in the audience has actually no idea until he a floppy disk.

You can't read an SD card without having the SD card reader on your computer, without having, you know, the software on your computer to decode the data on my SD card.

And it's exactly the same with DNA.

If I got some of the DNA out of one of my cells and just thought on the side will be no more alive than a virus, I'll be no more like than anything else that DNA needs the machinery of the cell to be able to read that information, reproduce it, which sounds, you know, remarkably like a virus, actually when you put it like that.

So I think that I mean this and this is a problem we keep running into, whether it's death, whether it's life, The reason these things are very hard to define is actually where all of this, you know, without getting too happy in a massive symbiotic , you know, you know, where are the boundaries of this organism?

Can we call the whole Earth an organism, you know, in the same way as an anthill might be a more sensible organism in the individual ants themselves?

Drawing these lines is just absolutely nightmarish.

And so I think I'm working towards viruses being alive, but I won't come down on either side again.

Those chats with the virologists might change your mind one way or the other in the middle All right, I actually we have a lot of audience questions and I think that it would be kind of fun to get into some right now.

So the first question I have from Richard Sanford, if we prolong life span, what are some of the ethical issues such as older workers not retiring to get access to life prolonging supplements and interventions, et cetera?

And Andrew, I know that you are well versed in this because I understand that you get this question a lot.

I do.

Yeah, I think actually, it's remarkable.

At the end of a talk of far more often get these kinds of ethical questions.

And, you know, even before how do I extend my own life?

How do I live as long and healthy as possible?

The number one question I get actually is interesting to have them older workers being thought about the question I get most often is what we're going to tell the people about the population of the planet.

If we if we start flowing lifespans and I'm not going to have time.

Unfortunately, to cover every single ethical quandary in the next two or two minutes.

Well, I would say if anyone's interested, there's a free chapter in my book.

You can go and read about this ageless, startling slash ethics, which goes into a far, far more detail I'm have 20 here to specifically address the older workers thing.

I actually think this is a problem that we already have because, you know, if you look back at, well, what's happened to lifespan over the last 200 years, we've been increasing in the best performing country in the world.

The life expectancy by an average of three months per year every single year And the straightness of this line is almost suspicious.

As a statistician looking at this, you think, you know, how is it that this tangle of sociological of medical practices has conspired in some way to have this sort of tick tock three months every single year increase in life expectancy?

And what that means is that kids born in the rich world today are lucky enough to have a life expectancy we think is probably going to be up to around 100, and that means they're going to be living, you know, 20 years longer than their parents, perhaps off.

Just wait and see exactly how that pans out.

But careers are already, you know, substantially longer than they were You know, even a few decades ago, the retirement age of 65, which is, you know, really commonly cited, is where people become old in a quote unquote, if we can again defining old is just as hard as defining life and death is, but that retirement age is first defined in the U.K. in the 1920s, and that was a time when only a handful of people made it to age 65.

And if you did, you're probably very frail and very sick.

And so we introduced the old age pension basically, you know, as a sort of apology to them to allow them to be out of the workforce and live out.

The last few years, the money and peace.

And yet that pension age wasn't changed until 2019. and life expectancy had increased by 23 years over that period, So it's just it's actually incredible blindness by policymakers.

This is a problem that we're going to have to deal with anyway.

And while the sort of common questions you get about aging workers is to look at the field of science, there's this famous quote by Max Planck the science advances funeral by funeral.

And isn't it the case?

You know, if we're going to enable professors to honestly, you know, often stay state, you know, keep working to look at some of these emeritus professors They incredible stamina.

Aren't we slowing down scientific progress by doing this?

You know, you could make a very similar argument and political arguments.

No other kinds of workplaces.

Some clever studies that have been done in find the effect is quite ambiguous.

But if the effect is present, it's actually detectable current scientific.

And so people have looked at premature deaths of sort of superstar scientists with loads and loads of publications, you know, dying a car crash or something And what you find is that that has a hugely detrimental effect on obviously that particular scientist is dead so they can't publish anymore and that direct collaborators who are working on that particular theory.

But it actually encourages growth in other parts of the field.

And so if that is indeed a problem in science and obviously, you know, whether or not continued research on one particular line or broader investigation encouraged by the drop out of that superstar is the preferable model is going to vary from field to field But since that is observable within current careers, maybe current scientific career is already too long and we need to enforce term limits for professorships just like we do for presidencies.

And I think that's the sort of thinking we need to apply to all kinds of different careers because, you know, if people are able to work and work and work and accrue more and more wealth and so on and so on, these are problems I think we need to solve from a political from a societal point of view, because the most common answer I give to all of these questions, whatever they are, is to reverse the question and imagine we lived in a society where there was no aging, where people just left an incredibly long time, you know, in health and vitality with much , much lower levels of disease than currently.

Would we invent aging to solve the problem of intergenerational inequality?

I really don't think we would actually barbaric, you know, this huge, huge cause of human suffering.

We can't with some political right to solve that problem.

And I really think that that's the approach we should be taking now rather than saying, you know, should we are about whether to deploy life saving medicine in order to try and solve that problem for us, Thank you, Carl.

Do you have any thoughts to contribute Oh, it's it's so fascinating.

to think about, partly just because, as Andrew's book demonstrates, that this is not science total science fiction that there's there's there's more and more real biology to look at and to understand and to base our ideas on.

I mean, one question that I have in the back of my mind is actually about minds in the sense that like there could be, you know, in terms of aging You know, there could be some, you know, treatment to to slow down aging that that, you know, work throughout the body.

And, you know, in the sense of, you know, resetting some of the the molecules in our cells that Andrew touched on and talks about more in his book.

But , you know, through time, our brains change and not just in the sense of, you know, that biochemical level, but their network changes.

So the way that the brain functions is different.

At 20 30 , 40, 50, 60 and so on and so, you know, if people are living to be, you know, 150 or 200 years old, how are those brains working?

Are those the brains that are functioning as you know, that young, vibrant scientist full of new ideas Or, you know, maybe somebody who just is , you know, kind of that it sort of has that certain grandparents type wisdom, stubbornness or something else.

What what is that mind of that extremely old person going to be like?

Especially a great question.

They're aging.

Yeah.

I'm actually quite optimistic about this.

And the reason is that if you look at a lot of the studies that have been done where we have demonstrated that my oldest of leading work and this is being done in mice at the moment, you find that not only do you rejuvenate their sort of bodily health side of things, they get low risk of cancer, lower risk of heart disease and that kind of stuff.

They actually seem to have lower cognitive age as well.

And I think the most obvious, it's quite hard.

You know, you can't give a mouse a mouse test or something.

So I tend to do is do things like put them in a maze on a young mouse or have a huge amount of curiosity about this new environment and to look around and see if there's any food.

Older mice tend to be more anxious.

Maybe they just a bit more lazy psychologically.

And so they are much less exploratory, but by a variety of different anti-aging treatments.

We seem to be able to reverse that aging in the brain as well.

And obviously, we can't really do a proper like I sort of alluded to cognitive experiment on mice in terms of how they think or something like that.

But my hope is that we'll have the wisdom that we've accumulated throughout these extended lifespans with the youthful mental agility.

And you know, I guess we'll just have to wait and see Yeah, definitely.

I'm going to move on to another audience question from Melissa Westbrook For people in countries with lower life expectancies, does that mean they will perceive big life differently?

That's a really good question.

I think that actually one of the things that's quite remarkable about this, this is actually when I do an in-person event, I normally do this as an audience quiz.

So I'm going to try and get everyone to imagine this at home.

What do you think is the average life expectancy around the world right now?

So this is not just in the rich countries, but in all, you know, all of all of the countries in sub-Saharan Africa and Asia and that sort of stuff, if you were to average every country in the world, what do you think that number is?

So just give everyone a second to think about that The answer in 2019, which is the most recent data, we have a bunch of strange stuff has happened in the last couple of years for obvious reasons, but it was seventy two point six years as the average life expectancy around the world.

And so that means with that continuously increasing, it's actually increasing faster in the poorer countries that most people in most countries are living.

These fantastically long lives by historical standards.

You know, you look back at most of human history.

Life expectancy was maybe 30 or 40 years old.

We've almost doubled that for every country in the world now, which is just a fantastic achievement.

So I think that there definitely will be some difference in perception But I think what's really remarkable, I think it's a problem that we've got with our perception in the rich countries is that we look around the world and we imagine there's this enormous poor developing world where people are much, much lower life expectancies.

But mercifully, particularly over the last 50 years, that is in large part ceased to exist.

I think about 10 percent of people live in countries now, with life expectancy below 65 , and we've obviously got a huge moral responsibility to do something about that.

But that means that 90 percent of people in, you know, basically most countries in the world are living such long lives that actually that question is less relevant than it might seem.

First, awesome.

Such a cool response.

It's definitely really interesting to think about So, Karl, this one's for you from Sue What do you think about artificial intelligence is about life Yeah, I I actually in life's edge.

I made a very conscious decision not to write about artificial intelligence and not to write about artificial quote-unquote life , just partly because, you know, obviously the subject of life is huge, and I wanted to write a book that would not also substitute also serve as a doorstop And I felt like I had an excuse because I was talking one day with a biologist named Kate Ademola , and Kate is actually trying to create life from scratch She is working with our name on molecules and basically wants to make kind of a protocell that can grow and divide and evolve and do all the kind of things we think of that life can do.

She hasn't gotten there yet, but she's done all sorts of cool research.

And so, you know, here's this scientist on this remarkable quest who thinks a lot about life because she's trying to make it.

And I said , So what do you think?

I'm wondering whether I should write about artificial life , and she's like, No, it's not life.

And I was like, What Not?

And she said, No, no, it's not as like, why not?

And I was like, Well, she said she was so memorable.

She said, Well, I have something I call the goo rule.

So that's g o o r u l. I was like, What is the guru?

And she said if it doesn't have Gou in it , it's not life.

In other words, it's not interesting to her to think about a computer program that kind of behaves in some ways that seem lifelike.

The really hard problem in science is figuring out how is it that real molecules come together and produce something that we call life, even though we're not quite sure what life is like?

That's the problem.

That's the hard problem.

that that does not have an answer yet.

And that people like Kate Adamlar are trying to answer that, that that big question.

And so lets me off the hook.

Although I'm not, I know that I've talked then I've talked to computer scientists are like, what way?

What you can't?

No , no, you have to.

And they get very angry and I sympathize and I think, you know, they feel like, well, you know, whatever it is that we're building, you know, they like to call them digital organisms.

They do something that's really interesting and it's interesting in the same way that conventional life is interesting.

So you can there are these amazing pieces of software that where basically they're these little batches of code that copy themselves and mutate and evolve and develop a acquire amazing new capabilities.

You can actually get them to evolve the ability to do certain kind of logical operations kind of like, you know, the fundamental laws of math and you look at the program, you're like, How are they doing that?

I , you know, I don't know what they're doing, but they're doing it And you can have sexual digital organisms and asexual ones and it's a great fun.

But you know, the question there was about artificial intelligence, which is interesting , are these bits of code I don't think anybody say like, Oh, that's really intelligent.

What?

We are captivated by are these programs that are being put out by places like Google that can play chess and do all sorts of things that we do with our highly evolved, you know, front of the brain Because for us, the life that matters , like I was saying before, is that life of the brain.

And so we kind of want to make artificial intelligence stand in for life.

And it's it's not Artificial intelligence is it?

It's this in some ways, it's a it's mimicry of certain kinds of architectures in our brain, and that's it.

Now could some form of artificial intelligence develop consciousness I don't know.

I'm I'm I'm skeptical But then again, we don't have a good definition of consciousness.

And so , you know, certainly like the fact that the all of us are conscious to us.

That's like the most obvious sign that we're alive, like, well, I'm I'm here , it's me, you know?

And so if a computer becomes conscious and we've decided that that's the hallmark for ourselves, then we would have to say that that thing is alive.

But but that's just all based on what are the assumptions we're going into it.

And, you know, I think they're kind of questionable.

You , Andrew, do you have anything to contribute?

I think it's fascinating I think that we can.

Perhaps if Carl, there's a second edition of life, said five or 10 years, he might revisit this because we're really at this fascinating time in artificial intelligence where I think so said sort of take the side that these things aren't alive and they certainly aren't alive at the moment in any meaningful sense because we have, I think, the world's largest computer.

I'm right in saying the world's largest and this is a supercomputer and this is reams and reams and reams full of computing hardware has about the same processing power as the human brain.

That isn't to say it can do the things the brain can do at all, but it can crunch numbers.

You know, it can do.

Operations is what computer scientists call this at about the same speed as the brain.

So I finally at this hardware point where we can think about doing interesting, you know, brain like things, perhaps the real the challenges , the software and its trying to work out.

You know how it is that life, you know, takes that amount of processing power, but turns it to so much more diverse range of applications , which, you know, we might be able to crunch numbers as fast as the computer.

We can just do so many different tasks.

And so, you know, that's that that's the real fascinating question.

And I think that, you know, looking at the progress that we've had even in the last 12 months is there have been these fascinating, massive called language models, which are artificially intelligent and they basically ingest the entire text of the internet and every book that was ever written.

And you can ask them surprisingly complicated questions and they give you such coherent answers you'd never realize they weren't written by humans.

You can get them to explain jokes even, and that explains of the mechanics of why is this particular statement is funny?

And it's getting really quite eerie now.

And so I'm wondering, you know, there's a there's a theory that we can basically just throw computing power at these things.

And if we give them enough computing power, if we make these models large enough, they'll start to accumulate some of the properties that we would describe as intelligence and consciousness.

Again, Every word we've used in this whole hour has been something that we find impossible to define, but they're really starting to accumulate some of the characteristics of what it might mean to be alive.

And so I think that, you know, potentially within the next five or 10 years, we're gonna have to think about that.

And certainly in the next 50 years, goodness answer is going to happen.

I mean, it's interesting, Andrew, that a lot of the times when people are advocating for all of the kind of, you know, life extension , some of the things that you touch on in your book, it's it's so that we can live long enough that that computers and artificial intelligence will be such that we can find a kind of immortality by being uploaded into a machine And so, you know, and again, like because somehow our consciousness is being transferred into a machine, then that makes us continue to be alive and and to be alive.

As long as you know somebody is keeps that computer plugged in.

Yeah.

And I feel like it's I feel it's very strange that sometimes these things are sort of discussed in the same breath.

I can imagine people today through anti-aging therapy , being able to live a little bit longer and a little bit longer still might give scientists longest about the next anti-aging therapy and so on.

But the challenge of this idea of mind uploading, it's so the biology of it's just incredible.

You realize that it's going to require petabytes of storage.

And, you know, that's like a couple of orders of magnitude several thousand thousand times bigger than current computer hard drives.

And it's going to require so, so much processing power.

I just think and you know, a lot of aging biologists actually hate the word immortality.

I'm among the ranks.

I think we're going to achieve something that looks like biological immortality so long before we're going to start uploading brains.

But I do think artificial intelligence is going to have a huge role to play in terms of helping us build models of the human body that will allow us to really, you know, fundamentally understand not just the aging process, but whole different swathes of disease and count with , you know, really exciting, innovative treatments that are just beyond this time, let alone premature and right in our heads.

Thank you so much I hate to break this conversation because it has been so fun chatting with