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us keep big biology going strong. Now.

2:00

Onto the him. To

2:09

do so deals with to general problems

2:11

that plague biologists really, biology specific versions

2:13

of problems that plague all of us.

2:15

As we interact and think about the

2:17

world, the first thing is that we

2:19

see what we expect to see and

2:22

not what's actually there. Maybe. To

2:24

see that seen as image of the young

2:26

and old woman both trapped in the optical

2:28

illusion that first appeared on an Eighteen Eighty

2:30

Eight German postcard. Most people see either one

2:32

or the other at first, but if you

2:34

look more intently, what you see flips back

2:36

and forth. The young and the old women

2:39

are both there, but we naturally see one

2:41

of the other more readily, and it takes

2:43

real mental effort to see the other form.

2:46

Why? The some people see the old form

2:48

first and others the young? The some evidence

2:50

that people are more likely to see the

2:52

form that corresponds to their own age and

2:54

the group of people with whom they socialize

2:56

most often. And. It's also possible

2:58

that people just filter information about their

3:01

worlds and different ways. Recall that two

3:03

thousand and fifteen viral sensation. They're basically

3:05

broke the internet. The famous blue and

3:07

black stripe dress? You mean white and

3:10

gold, right? Ah, Ok, was not go

3:12

there. rather. onto the second problem, which

3:14

is related to but distinct from the

3:16

first. It's what we might call a

3:18

naming problem which you may have heard

3:21

of in relation to of all things

3:23

Buddhism. Although. Buddhism doesn't outright

3:25

claim that naming things constraints are

3:27

view of the world. It doesn't

3:29

acknowledge that words and language more

3:31

generally shape our perceptions and can

3:33

lead to attachment, suffering, and misunderstanding.

3:35

For those more scientifically inclined, a

3:38

similar objection could be raised to

3:40

using metaphors and science. Think.

3:42

The tree. Of life, molecular machines,

3:44

scenes as blueprints, information superhighway,

3:46

and others. He's metaphors provide

3:48

a beautiful shorthand for conveying

3:50

concepts and prophecies, but conversely,

3:52

they can become mental handcuffs

3:54

if we take them to

3:56

literally. These problems loom large

3:58

and a conversation today. The science writer

4:01

Fill Ball, film written over twenty

4:03

five books and contributes regularly to

4:05

publications such as The Do Scientists,

4:07

The New York Times, The Guardian,

4:09

and The Financial Times. He was

4:11

also an editor at the journal

4:13

Nature for over twenty years, with

4:15

gave him an unusually broad look

4:17

at breaking discoveries in Chemistry, physics,

4:19

and biology. We focus our conversation

4:21

on fills latest book called how

4:23

Life Works, in which he describes

4:25

recent advances across all levels of

4:28

biological organization. As you might imagine,

4:30

The book covers highly diverse topics that

4:32

there's a subtle kind of met a

4:34

theme that runs through all of the

4:36

chapters. And that is we consistently don't

4:38

really know what we think we do.

4:40

Both. Because we're usually not looking at

4:43

the process or problem for the right

4:45

angle, and even if we do, we

4:47

tend to construct metaphors that harden rapidly

4:50

into dogma. Disheartening can prevent us from

4:52

seeing readily beyond the metaphors walls. That

4:55

was a metaphor for that metaphors. I

4:58

know. But onward take for example, fills

5:00

chapter on how proteins work. We all

5:02

know how they work, right? Well in

5:05

the prevailing metaphors, the day proteins are

5:07

tiny molecular machines. We say that their

5:09

chemistries and shapes or evolved to carry

5:11

out some process, often by a fitting

5:14

together like a lock and key with

5:16

a handful of other molecules. But.

5:18

Still argues that's all wrong. The

5:20

past ten years or so have

5:22

revealed that many proteins do not

5:24

has six well defined structures, But

5:26

the rather expansive, floppy and promiscuous

5:28

and he interacted large and small

5:30

ways with hundreds, even thousands of

5:32

other molecules is fundamentally changes How

5:34

we should think about the functions

5:36

of proteins and also about the

5:38

structures of intercellular networks and the

5:40

standing Verizon available to natural selection.

5:43

For. Sure not what you get out

5:45

of most standard textbook in biology and

5:47

fill is not nearly done with big

5:50

questions including the biggest one that we

5:52

can ask which is what is life

5:54

here. Film talks about where causation comes

5:57

from in living systems most of and

5:59

therefore Scottish. It's a highly reductionist

6:01

or bottom up view of causation

6:03

feel argues. Instead that some causation.

6:05

Comes from higher levels of organization

6:07

with causality flowing downward. The basic.

6:10

Gist is it is living systems get

6:12

more complex. The information inherent. To the

6:14

new structure least the whole system to

6:16

be more than the sum of it's

6:19

parts. In other words, here we get

6:21

into yet another extended but interesting discussion

6:23

about agency, purpose and goals, and biology.

6:26

And. Finally, a significant chunk of our talk. Focuses

6:28

on what our new understanding of biology

6:30

means for medicine, how we could manipulate

6:32

complex systems to keep people healthy, and

6:34

whether they are better ways to treat

6:37

cancer. And as we do been reading

6:39

fills book, you may feel the vertigo

6:41

that comes with your point of view

6:43

suddenly flipping into an expansive new configuration.

6:46

You are such a nerd. sometimes I'm

6:48

not even sure what to say. I'm

6:50

Window Star and I'm a little embarrassed.

6:52

Okay, I'm Art Woods and I Marty

6:55

Martin and you're listening to Big Biology.

7:12

Biology Harden I read your new book How

7:14

Life Works and we both absolutely loved it

7:17

as a shared it with a lot of

7:19

friends including what a biologist who probably be

7:21

surprised as I was about how much we've

7:23

learned about how life works at different levels

7:25

of organization. Things are very different since we

7:28

learn them as students with wanna spend most

7:30

of our time on discoveries in the book

7:32

the we do wanna hear little bit more

7:34

about your method and and maybe a little

7:36

bit about why some people have been upset

7:39

and Juri seen it is controversial in a

7:41

way that Melissa really. Slowly and let's talk

7:43

about that method. Sync your a chemist and a

7:45

physicist right? What was it a made? Was it

7:47

your time at Nature is an editor's in and

7:49

you did that for quite awhile? Was it those

7:52

experiences or what was? It is sort of first

7:54

planet that see the gets you thinking about these

7:56

things. With. Us right on. So my

7:58

first degree was in chemistry and then. Kind

8:00

of switch fields and went into condense

8:02

metaphysics. So a you could say my

8:04

qualifications for writing about biology a close

8:07

to zero. As a chemist, you come

8:09

across some of these ideas you know

8:11

you come across the ideas about for

8:13

example, the way proteins were. You know

8:16

what these molecules looked like, the way

8:18

they interact. but very much for the

8:20

canvas point of view. So yes, it

8:22

was the site that I spent years

8:24

as an editor at Nature. This the

8:27

science journal which exposes in those days

8:29

is is. Back in the late nineteen

8:31

eighties, early nineteen nineties, Nature wasn't this big

8:33

publishing empire that it is now. it was

8:35

just a journal. and it was a journal

8:38

with very small south. So it meant that

8:40

he spoke to everyone handling every subject you

8:42

came across. Everything. That was why it wasn't

8:44

a fantastic. Such an exciting place to be

8:47

on. It meant though there were a lot

8:49

of very steep learning curve said I had

8:51

to go off the in order to get

8:53

some kind of handle on a lot of

8:56

this stuff because as an editor I was

8:58

handling papers in biochemistry. and by. Physics as

9:00

well as in straight physics, material science

9:02

and so on. so I had to

9:04

learn a lot there. But also I

9:07

was good daily hearing about the latest

9:09

things that were happening. A bar with

9:11

it's trying to make some sense of

9:13

them are being able to talk to

9:15

colleagues. Do it, At least get some

9:17

handle on that. That was what really

9:19

not just stay something of an education

9:21

in biology but also made me aware

9:23

of some of the cutting edge issues

9:26

in biology gadgets. A link in the

9:28

bookie write something about the the Went

9:30

Jeans. With those a particular inspiration and

9:32

if the answer is yes but to

9:34

talk about what those scenes and what

9:37

they're involved and they seem to me

9:39

to be a very good example of

9:41

the way of the way that we

9:43

understand. James has changed over the past

9:46

several decades said the wind genes that

9:48

their genes that are involved. Really. I

9:50

think all we can say about them

9:52

is their genes that have roles in

9:55

our development in our development from an

9:57

embryo to are you know to a

9:59

baby. We can be no

10:01

more specific about it than that

10:03

because they crop up in all

10:05

sorts of places and if you

10:07

look into the name it's a

10:09

kind of portmanteau may Bavaria things

10:11

including they began as genes of

10:13

are identified in that prove rise

10:15

in for sophal us were a

10:17

mutation of the wind Jane created

10:19

flies the has no wings so

10:21

the W N as for wingless

10:23

and in a so the idea

10:25

was that the natural assumption at

10:27

that point would have been. Were

10:30

maybe these genes seasons fly genes that

10:32

has something to do with making wings

10:34

and innocence? They do clearly.this absolutely not

10:37

their function because we have dreams like

10:39

this as well and you know love

10:41

be. Hope we don't have wings so

10:43

they do something else as well. In

10:46

fact it turned out our version of

10:48

the genes were discovered in a completely

10:50

different context in some other developmental process

10:52

and they were given another name. And

10:55

then people realized hang on this gene

10:57

seems to actually be the same as

10:59

or and the human equivalent of what's

11:02

in fruit flies. So what's really going

11:04

on here? what do these things really

11:06

doing and then they crop up Indiana

11:08

Lots of other different developmental process is

11:11

because they are example in there are

11:13

other genes like this. Sonic Hedgehog is

11:15

another was my favorite that has absolutely

11:17

I have it in okay with that

11:20

name for and you know there there

11:22

again is another interesting kind of etymology

11:24

of how he got that name. but

11:26

you know their these genes that just

11:29

seem to have many. Different roles

11:31

in development processes and in a

11:33

way that's not the they do

11:35

anything. They're almost like general purpose

11:37

genes that development use as if

11:40

you like that ourselves use in

11:42

order to make different sorts of

11:44

body structures. A So it's a

11:47

reflection of the fact that there

11:49

are lots of things that we

11:51

have that you can't assign specific

11:53

tasks to. You can't draw a

11:56

line granny from the teen in

11:58

our genome to to. Treat

12:00

some developmental seen a to meet you

12:02

know, somebody safe or whatever. The that's

12:05

not the way it works so there

12:07

isn't a sort of planned rarely. That

12:09

does, from the genome to the

12:12

phenotype. Something else is going on and

12:14

these genes the way I talk about it

12:16

in the book is that is better to

12:18

see a lot of them as just resources

12:20

of a very general thoughts that the cells

12:23

can draw upon in order to do the

12:25

things they do to make us. And

12:27

our beautiful i want to echo at

12:30

Marty said about Justice loving a book

12:32

yeah I had a sunny feeling reading

12:34

it as you know in each chapter

12:36

thinking okay I know if chapters about

12:38

and then suddenly feeling like wow the

12:40

something like really new here that I

12:42

didn't expect. like the chapter on protein

12:44

functions are parties come about, unfold and

12:47

and do the jobs they do. And

12:49

I was thinking about this in relation

12:51

also to just the basic teaching a

12:53

biology which I feel unsatisfied about. I've

12:55

been quite unsatisfied with my own teaching.

12:57

A Biology and I think many, many university

12:59

courses restructured in a way where it's just

13:02

kind of a slog through a bunch of

13:04

facts that. That. We know in that

13:06

have been known for a long time and I

13:08

thought reading your book that they would be a

13:10

really inspiring thing for students to have a book

13:13

like that and to have the course follow the

13:15

progression of that book because it's you know it.

13:17

It just pushes you so rapidly out onto the

13:19

edge of where are the interesting questions and what

13:22

are we in a won't let me think about

13:24

next So I guess my question is did you

13:26

have that in mind when you're writing this and

13:28

you envision it being used for teaching and any.

13:32

I. Would be delighted if it was used

13:34

for teaching. And you know one of the

13:36

things that are obviously the I wanted to

13:38

do was to try to bring up to

13:40

date the stories that we tell about the

13:42

different levels of what's going on in biology

13:45

from Dna to our innate broke into someone's

13:47

house Rt and I'm so pleased that you

13:49

say that that was your experience because it

13:51

was very deliberate that for each chapter yet

13:53

it works in a way that could sound

13:56

very dry and tix with a but i

13:58

hope doesn't turn out that way. It

14:00

works through the different levels of biology

14:02

from starting with jeans with Dna, getting

14:04

to iron, A, going to proteins, going

14:06

to in a network, and cells and

14:08

so on. But at what I wanted

14:10

to try to do with this show

14:12

house each of those levels. A.

14:15

Any to those levels, Something significant has

14:17

changed over the past ten twenty years

14:19

or so in the way we think

14:21

about what's getting on. so you know

14:24

the the standards. Think that sunni the

14:26

school kids at automated and agree to

14:28

talk is that it of we have

14:31

these genes. He include proteins, the proteins

14:33

of the enzymes. that kind of some

14:35

have put us together on this is

14:38

how it works and that story isn't

14:40

wrong, but it's far more complex than

14:42

that and it's not so linear as.

14:44

That and also I mean as he

14:47

either you mentioned proteins This was a

14:49

real revelation to me on this was

14:51

something that was brought home during that

14:53

time I spent in twenty nineteen at

14:55

Harvard Medical School that I had as

14:57

a chemist. I had this idea that

14:59

just very neat and intuitive that we

15:02

know these cells are full of molecules

15:04

in other thousands of different proteins in

15:06

every cell. How on earth do they

15:08

ever find the right targets and do

15:10

the right thing without getting distracted by

15:12

all this other stuff? And the idea

15:14

is. That there's this molecular recognition

15:16

whereby eat protein as a particular site.

15:19

That means it sits the target molecule,

15:21

that it's meant to fit and ignores

15:23

all the others because they're the wrong.

15:25

Say yes, that that's the iconic vision

15:28

that we all have, right? Absolutely yeah

15:30

of the of that to in a

15:32

recent wrong there at protein to work

15:34

that way. Lots of enzymes do work

15:37

that way, but lots of them don't

15:39

and all hub in our really had

15:41

no conception of this until a few

15:44

years ago and. It was a

15:46

revelation that sleep there are plenty

15:48

of proteins particularly in ourselves or

15:50

in this House of Lords. Creatures

15:52

like our Sarah many more proteins

15:54

of they sought in law screeches

15:56

than in smaller ones and certainly

15:58

than in bacteria that. Don't

16:02

have a nice fluffy they won't

16:04

the break it is to intrinsically

16:06

disordered owned a country based upon

16:08

this picture because it means because

16:10

her coffee we're currently shutters indiscriminately

16:12

sticking to thing the fair promiscuous

16:14

I've added for so they were

16:16

by and him up for different

16:18

things have happened after hat work

16:20

at your hobbies. Proteins that you

16:22

know that not selective in this

16:24

way. And not only that it's

16:26

not a so this is just

16:28

something that by what he has

16:30

been forced to do because it

16:32

can't make proteins in a specific

16:34

and often structured enough we know

16:36

that he can because twenty all

16:38

I batted. In fact most of

16:40

the proteins he bacteria on like

16:42

that. So during the course of

16:44

evolution as organisms got more complex

16:46

it seems that the proteins many

16:48

of the protein for got less

16:51

structured and more promiscuous. Why is

16:53

that? How does that work when

16:55

they don't dismiss more complex and

16:57

that's one of those send to

16:59

I think one. Of the central

17:01

themes throughout the book because it

17:03

points to a different kind of

17:05

set of operational principles at the

17:08

molecular level that involve this promiscuity

17:10

of molecular interactions and what tends

17:12

to happen is rather than isn't

17:15

a good for logic of this.

17:17

Speaking to that. We have

17:19

groups of things that all kind of

17:21

speak. To each other in some way

17:24

and they get together. And these groups

17:26

in various ways. right? Brain is much

17:28

more smeared out. Logic? Yeah, absolutely. As

17:30

so I talk about it is kind

17:32

of committees of molecules and you know

17:35

they're all sorts of process is crucial.

17:37

Processes in ourselves particularly have genes gets

17:39

switched on and off that rely on

17:41

these committees where the molecules. Are all

17:43

kind of speaking to each other in

17:45

fairly indiscriminate. Ways of more or less

17:48

discriminate and somehow out of that

17:50

process just as out as often

17:52

to the committees that we make.

17:54

A decision arises as a decision

17:56

right. Turn this gene off, Turn

17:58

it on. Do that. Do that,

18:00

but it's not anything that you

18:03

can attribute to a nice clean

18:05

digital. Logic of one molecule speaking

18:07

to another. Yeah. There are

18:09

a monitor sorry to hear about in

18:11

of the title of your blood which

18:14

I met proteins and I could infer

18:16

how that works. but your book is

18:18

beyond what one might initially assumed to

18:20

come from a book called how Life

18:23

Works as you just represented the novel

18:25

ways that with come to understand protein

18:27

function you alluded briefly to the novel

18:29

ways that genes operate relative to the

18:31

classic ways of the ways of this

18:34

may Art teachers them for talks and

18:36

is biology classes. But when you

18:38

when you titled the book How Life Works,

18:40

it's not what you meant something. Broader? maybe?

18:42

Let's start with your definition of life

18:45

because life also has the evolutionary dimensions

18:47

mingle and one other things as distinguishes

18:49

about life evolves. So how do you

18:52

define life? You quoted francoise zip code

18:54

saying that living organisms of the site

18:56

of a triple flow matter, energy and

18:59

information that are abstract things that you

19:01

return to them over and over again.

19:04

When you're with height of the book this how life worth. How

19:06

did it sort of include evolution and had a

19:08

the goal is sort of comes together to tell

19:10

it the way we think about. like generally. Yeah.

19:13

We're sisters. This is the biggest active ago question I

19:15

know that's a big was I'm I'm A, I'm in

19:18

her. First of all I have to say. Giving.

19:20

The book this title with an act

19:22

of incredible hubris and I hope it's

19:24

gonna be say the Friday's hugging see

19:26

because you know what are Vegas to

19:28

pray But you're gonna say in the

19:30

book this is how wife was, sit

19:32

back and alone are. Actually I hope

19:34

it becomes clear that my aim is

19:37

is to say we don't understand how

19:39

life works. You know there's so much

19:41

we don't understand about it but I

19:43

think we can safely say now but

19:45

it doesn't work the way we thought

19:47

it did or least our life because

19:49

a lot of what I'm talking. About

19:51

as I sort of, you know dried

19:53

already a lot of what I'm talking

19:55

about. a price to us as modes,

19:57

complex organisms so you know and one

19:59

of the key Id in the book

20:01

and this again was a revelation to

20:03

me is that the way we work.

20:06

Doesn't. Seem too often

20:08

have the same basic principles as

20:10

the way that here world often

20:12

we study bacteria were understandably because

20:14

and much simpler that single celled

20:17

organisms you know you consider. See

20:19

him to the much more plainly

20:21

said we've study then as a

20:23

first step and they often assumed

20:26

and you ventured Francois Sack of

20:28

you know that Jack of Amano

20:30

were the ones who first talked

20:32

about gene regulation in the Nineteen

20:35

sixties and the assumption. With lung

20:37

made that the way they explained

20:39

it is probably get as the

20:41

similar in humans as it turns

20:43

out that it's not. that I

20:45

see the molecular principles of gene

20:47

regulation are largely different enough so

20:49

that was one of the key

20:51

messages that actually we can't generalize

20:53

often for bacteria to us there

20:55

are some basic things had a

20:57

similar of course we all have

20:59

Dna, we'll have our and I

21:01

will have proteins it as France

21:03

is correct. Central Dogma is kind

21:05

of basically. Still the same all

21:08

along, but the real. Principles.

21:11

By which our cells work on

21:13

the same as those and bacteria

21:15

so that was one of the

21:17

key messages. How life works is

21:20

not a single question and how

21:22

our life works is not the

21:24

same desire bacterial life was inmates

21:26

t respect.e of the question as

21:28

well. What is life Anyway,

21:31

in a what are we talking about

21:33

here? That's actually something that I sidestepped

21:35

in the books. I say I up

21:37

front that people like in a from

21:39

Jbs How Dying To Earn Shrouding Ass

21:42

and as a lovely recent book by

21:44

pool nurse as well it's all a

21:46

Cold War his life and none of

21:48

them on cigarettes A thousand is the

21:50

wisest fake as he begins at the

21:53

very first sentence in that book or

21:55

our essay is I'm not going to

21:57

answer this question and you know that's

21:59

right, Because there is no consensus about

22:01

that, there's a lovely but By tells

22:04

him a good life said was explore

22:06

that question and can't rightly points out

22:08

in a we don't know net net

22:10

there is no agreement. basic rights that

22:12

so the approach zeit of these well

22:14

I don't have to answer that question

22:16

in a sense because I'm talking about

22:19

we know the were alive, we're form

22:21

of lies had a we work is

22:23

rarely what I'm talking about but inevitably

22:25

and trying to answer that question. If.

22:28

I do have to come back to the

22:30

question of what what is it that is

22:32

going on it which he really is about.

22:35

You know, what is it is going on

22:37

in life. So you do have to take

22:39

a step back because all of these complexities

22:41

are set. You know there's some from brakes.

22:44

It's so extraordinary. That you have as

22:46

many different levels from seems to proteins

22:48

to that was the cells to tissues.

22:51

That somehow, even though

22:53

they have different operational

22:55

principles themselves, somehow they're

22:57

all operating together. In.

22:59

Ways that support each other to build

23:02

something. So what's keeping the show on

23:04

the rise? What is it over all

23:06

that life is doing and that led

23:09

to some questions that really go. Yeah,

23:11

we certainly go beyond the molecular specifics

23:13

and you get into questions of what

23:15

is it that life is if you

23:18

like trying to do and we get

23:20

to this question of agency. So I

23:22

have a chapter towards the end of

23:25

the book on agency and really, I

23:27

think the key point I wanted. To

23:29

make there is it's a real question

23:32

is one that biology has.it's one that

23:34

ballsy still seems to be uncomfortable about

23:36

because you have to start talking about

23:38

things like function and even purpose which

23:40

I eat out to do Words I

23:43

have often be takes to village of

23:45

Biology but you really have to think

23:47

about those if we going to grasp

23:49

agency. and I think what Biles he

23:52

needs is a proper theory of agency

23:54

and there's nothing of that sort of

23:56

the my mom. Mass for

23:58

beautiful and me couldn't agree. I

24:01

want to just continue on this feet. So

24:03

you know if we think about agency and

24:05

causation at different levels, what I hear you

24:07

saying is that as you move from bacteria

24:10

to more complex you coyotes and multicellular organisms

24:12

you get a shift in the the sort

24:14

of Los I have causation and the Los

24:16

I have agency. So for example antibacterial level

24:19

you might think of the lack opera on

24:21

and Nikolai as a sort of a gentle

24:23

circuit right said in a road very real

24:26

sense is making decisions about what sorts of

24:28

sugars are available and what sorts. Of

24:30

ways it should retool it's biochemical machinery

24:32

to use that sort of cigarettes a

24:34

very generic kind of based. Locus

24:37

of Causation. And I think what you're saying

24:39

is that as you get more complex animals

24:41

like us, those Los I a current other

24:43

levels. so maybe let's just be more specific

24:46

about that. What levels to be a crowd

24:48

and what prophecies are you talking about? Yeah.

24:51

Whoop. This was another kind of

24:53

penny dropping when I was in

24:55

a struggling to figure out what

24:57

the structure, what the general theme

24:59

of this book was. The issue

25:01

of causation, I think is an

25:04

absolutely crucial one. And there's this

25:06

idea that has been talked about

25:08

for a long time, but often

25:10

in very vague ways. the notion

25:12

of emergence and you know, emergent

25:14

systems. and it's often illustrated with

25:16

reference to things like flocks of

25:18

starlings or even road traffic. Where

25:20

you get structures. And patterns that

25:22

can't be deduced by looking at the

25:25

individual components of the system. You can

25:27

only see them as they emerge at

25:29

some higher levels. And this is something

25:31

that I say it's familiar in physics

25:34

is being familiar for a long time.

25:36

In a sense, what we call phase

25:38

transitions are examples of emergence. That's there

25:41

is nothing in a water molecule that

25:43

will tell you the water has three

25:45

different phases gas, liquid and solid and

25:47

that their as jobs switches between them.

25:50

These are cooperatives things. That happen between

25:52

many water molecules. Phase transitions are

25:54

emergence and ominous. So it's a

25:56

real thing that happens is certainly

25:58

in nature. We see it

26:01

also in organic nature in life, but

26:03

it's very hard to sort of pin

26:05

down. But one of the aspects of

26:08

that notion of emergence is what some

26:10

people to talk about as causal emergence.

26:12

And here again it's become possible to

26:15

quantify this to get series to understand

26:17

this, that there are some complex systems

26:19

and we seem to be one of

26:22

them and things like the brain or

26:24

also one of them were. It turns

26:26

out that that never ways you can

26:29

measure the amount. Of causation that's happening

26:31

in a complex system at different levels,

26:33

at different levels of magnification if you

26:35

like. And it turns out that there

26:38

are some systems where the causes of

26:40

the overall behavior of the system are

26:42

located much more in the higher levels

26:45

of the system, the bigger scale things,

26:47

and in the smaller scale things as

26:49

this is the idea of course, on.

26:53

Of this seems to be remade it's

26:55

it's be measured in living things at

26:57

it seems that they're absolutely is a

26:59

degree of causal emergence. In living

27:01

things At once again, there's

27:03

a difference between simple living

27:06

things are bacteria and complex

27:08

organisms. Air is more as

27:10

he would probably intuitively expect,

27:12

but you can quantify. there

27:14

is more quarterly migrants and

27:16

complex creatures White House which

27:18

means the causes of our

27:20

behavior are located at higher

27:22

levels organization than for example,

27:24

the genome. So. There are

27:26

many things that that happened where

27:28

you cannot say can't point to

27:30

a gene or even two or

27:32

three jeans and say these of

27:34

the causes of this is what

27:37

we've known as certainly in Juno

27:39

makes for a long time that

27:41

it's that. The notion for example

27:43

that if you try to identify

27:45

which genes or was gene variants

27:47

are correlated with particular trait like

27:49

height or like intelligence or like

27:51

obesity for example if we're thinking

27:53

about either did he did you

27:55

find out. That as most of the

27:57

genome, right? Absolutely Yes. So a hit

27:59

us all. Regina, what does that

28:01

may? Well, you know. one way of

28:03

thinking about it is well people say

28:05

was that all the genes are somehow

28:07

causes but that doesn't really tell you

28:09

anything that doesn't sort of mean anything.

28:12

I think all that's really telling us

28:14

is that the truth causes for those

28:16

kinds of traits. Happen at

28:18

a higher level and what you

28:20

can see and that the genes

28:22

are still affecting them, influencing them

28:24

in some way but always seeing

28:26

in as genomic carnations all the

28:28

echoes is rarely of causation happening

28:30

at higher levels. Miss any means

28:32

that if you want to make

28:34

interventions as we want to in

28:37

medicine that there were plenty of

28:39

friends that have some fanatic component

28:41

thanks to spend every time we

28:43

have or something that compartment but

28:45

this cannot be fundamentally cannot be

28:47

addressed or intervened. In the genetic

28:49

level, not just because they're too many

28:51

genes involved at because that's not where

28:53

the causation lies in a we see

28:56

this a lot for example with Cozad

28:58

that actually you know the problematic cases

29:00

of cove it what seem to be

29:03

happening to cause problems wasn't something genetic

29:05

even though some people seem to have

29:07

more of a genetic propensity to have

29:10

a bad rash. And to go with

29:12

the my case the level of the

29:14

immune system. and in fact you know

29:17

Tanzania and this is something that has

29:19

been had been a recognized for a

29:21

long time and biomedicine. The immune system

29:23

is such a locus of causation for

29:26

so much that happens to us, even

29:28

things it doesn't seem obviously connected to

29:30

information and immune response, it's a massive

29:33

locus of causation. and so if we

29:35

want to intervene in those sorts of

29:37

conditions that we shouldn't be looking to

29:40

find a genetic target or a protein

29:42

target for a drug to hit, we

29:44

got to find a way of intervening

29:47

that is going. To alter the way

29:49

the immune system does stuff. so we

29:51

need to intervene at a higher level

29:53

of causation. So that's what I mean

29:56

by cause, will emergence and also why

29:58

I think it's an important. The

30:00

biology and buy medicine. And

30:11

it will circle back to her five medical

30:14

implications of the book in a bit. Being

30:16

a bit of an immunologist and especially intrigued

30:18

to talk about these kinds of things the

30:20

before we leave it enters Touch on Agency

30:23

is are brought up. What do you think

30:25

about the selfish Gene concept as I want?

30:27

I want to talk about your book in

30:29

the context of evolutionary theory or. You.

30:32

Know modern understanding of how life works,

30:34

what it means, for how we think

30:36

evolutionarily? How does the self esteem concept?

30:40

Where I'd always have this struggle with

30:42

the notion of selfish genes because you

30:44

know it's clear I think to to

30:46

every who hunted by him as he

30:48

that our genes have to operate cooperatively

30:50

in order to be a part are

30:52

not going to say to build because

30:55

then static us right way to look

30:57

at it. But to be a part

30:59

of you know an organism that enables

31:01

the evolution to happen at all. So

31:03

to be viable they have to cooperate.

31:05

They have to do all their respective

31:07

jobs at the right place and time.

31:10

You know in relation to one another. And

31:12

in fact the whole selfish gene idea isn't

31:14

about what the genes the during, it's about

31:17

what different variants of particular James the doing

31:19

important different alliums A doing so. There is

31:21

a meaningful sense if you think about population

31:23

by with you there is a meaningful sense

31:26

in which we can think of different

31:28

alley, a list of a given g as

31:30

being in competition with one another you know.

31:32

and if you like being selfish because you

31:35

know it is a bit of a zero

31:37

sum game that you have one of

31:39

those alley. Else is fucking if

31:41

he likes it. To put it

31:43

that's remotely is trying to outdo

31:45

the others so I I totally

31:47

understand. You know why that picture

31:50

make sense. In terms of evolutionary

31:52

population biology, it doesn't make sense.

31:54

It is incoherent from the point

31:56

of view of thinking about genetics

31:58

from a different. Mental Defective and

32:01

developmental biologists have felt this way forever.

32:03

Rarely you know bank. Certainly banks don't

32:05

know what into this has been us

32:07

a problem that they have. So one

32:09

thing that I talked about in the

32:12

book is that there is this at

32:14

least as conceptual difference between the notion

32:16

of a gene in evolutionary biology and

32:18

in developmental biology and is always been

32:20

hard to reconciled as to an insight.

32:23

Perhaps I can't be reconciled because we're

32:25

talking about genes in different contexts that

32:27

way. but what I wanted to try

32:29

to do here I kind of am

32:31

sensing at it would have been easy

32:34

in a way to have simply attacked

32:36

the notion of a selfish gene. from

32:38

this point of view of enough you

32:40

think about it about mentally it makes

32:43

has since But I i thought well

32:45

it really is a useful idea to

32:47

evolutionary in a to desist of use

32:49

it all the time. So what is

32:51

it really expressing. And a it

32:53

seems to me that it's. Not a

32:56

metaphor for what genes are of

32:58

what foods do, It's a metaphor

33:00

for the models they used in

33:03

evolutionary biology to understand that particular

33:05

aspect. And those models don't? I

33:08

mean, you know, I've spoken to

33:10

Evolution Policies who sets a says

33:12

models don't really recognize organisms as

33:15

such at all, and either Richard

33:17

Dawkins talks about the organism is

33:19

simply a vehicle for the genes.

33:22

That notion, it seems nice, almost

33:24

antithetical to. Eat a one star

33:27

with is trying to do to

33:29

understand organisms in there and right

33:31

into some respect. Organism said, there

33:34

are right, but it is a

33:36

viable enough picture if you're thinking

33:38

about populations of different alley ales

33:41

and how those in a chain

33:43

three to three times south. Really

33:45

the selfish gene notion? It's a

33:48

metaphor for the models that evolutionary

33:50

genetics uses to understand how populations

33:52

of different alley or change over

33:55

time. So that's fine, but it's

33:57

really important I thanks to recognize

33:59

that the. What It's doing.

34:01

It's not a metaphor for what

34:03

seems all of a what Genes

34:05

do. It's a metaphor for that

34:07

particular model of evolutionary biology. And.

34:10

I never thought of it that way. Others

34:12

Really interesting. Another word that we've already said

34:14

multiple times here is agency and I think

34:16

it's worth maybe being also a little more

34:19

explicit about what you mean by this word

34:21

agency, which we hear increasingly in the scientific

34:23

literature. It feels like sort of an interesting

34:25

moment for this as an idea, but to

34:27

you, what is That was an important. Well.

34:30

I, I think I'd give a

34:32

definition of agency as opposed to

34:34

life. I'd say something along the

34:36

lines that an agent is an

34:38

entity that is able to act

34:40

on itself and on it environment

34:42

in order to achieve. Self.

34:45

Directed of self determined guns. So

34:47

an agent is some entity that

34:49

has goals for a start. and

34:51

there goes that. I mean, there

34:53

are various ways that they could

34:56

be set. You know. I I

34:58

think goals for organisms are set

35:00

by evolution is so either evolution

35:02

is a process that produces goal

35:04

oriented things. Evolution itself. the process

35:06

of evolution, as far as we

35:08

know, has no goal. There's no

35:10

obvious reason why we should think

35:13

of evolution as having us I

35:15

target. Or at direction or anything.

35:17

Some people have argued that either

35:19

they're always a week. That might

35:21

be the case. I that's an

35:23

interesting debates.we don't particularly need to

35:26

get into that to understand agents.

35:28

it's simply that evolution create goal

35:30

oriented entities. And it's it's It's

35:32

amazing To uncontroversial it we have

35:34

no problem with the fact that

35:36

we are goal oriented beings and

35:39

the goals that we have a

35:41

often We kind of here that

35:43

if we admit that living. Things

35:45

have goals, their survival and reproduction. and

35:47

you know that I often. that's the

35:50

case. that pseudo that gets you a

35:52

long way, but there's no way that

35:54

we can explain everything that we do.

35:57

In those terms other than

35:59

with some kind of evolutionary

36:01

psychological you know just says

36:03

story with sometimes happens. Here

36:06

I mean, if is like you know, I mean

36:08

one way to get around that is to say

36:10

you know there's his prime goals which our survival

36:12

and reproduction. and then there's a bunch of subsidiary

36:15

goals that contribute to that. And. You know,

36:17

life is an elaboration of a lot of

36:19

those subsidiary goals I wanted to ask a

36:21

been like to me that idea. The agency

36:23

becomes really interesting when we think about. Agency.

36:26

Occurring at different levels simultaneously.

36:28

So, for example, Large.

36:30

Multi cellular animals like myself? How. Golf.

36:33

And purposes. I'm an agent, but each of

36:35

my cells also you could think of as

36:38

being an agent, right? So we have sort

36:40

of nested levels of agency, right? And and

36:42

I guess that bronze out this idea of

36:44

agency and an interesting way. And it is,

36:47

or a sort of general way to think

36:49

about agency across all of those levels simultaneously.

36:52

I. Think the simplest the that

36:54

is if there isn't ours does that.

36:56

I don't know it, but I think

36:59

that that is as a really important

37:01

and interesting question. You know, add one

37:03

that informs all sorts of other questions.

37:06

Or how is it that if

37:08

we recognize that every and I would

37:10

argue that every living cell is an

37:12

agent? In some sense even bacteria have

37:15

a kind of agency. How is

37:17

it that multi cellular creatures are viable?

37:19

It's all in a rather than just

37:21

being. Torn apart by the agency

37:23

evil their part of a you could

37:26

say this is Richard Dawkins is talked

37:28

about the paradox of the organism that

37:30

he's talked about that from a gene

37:32

centric view which I find harder to

37:34

understand but certainly if we think about

37:36

it and from the the the point

37:38

of view of cells, the agents and

37:40

there is a sort of paradox as

37:42

you know how that works but it

37:44

is one that I think either we

37:46

can think about and start to understand

37:48

but it of we are collective agents.

37:51

narration see as corrective. In a big

37:53

part of our agency of course comes

37:55

from our complex commission and eat. A

37:57

One thing that I've argued a factor

37:59

they argue dated my previous book in

38:02

the book of mine's is that are

38:04

you know I would say I mean

38:06

aren't you talked about of having it

38:08

out and this of overarching goals, reproduction

38:10

and survival and then we should have

38:13

do other things and racing to that?

38:15

I would argue that minds ah, we

38:17

have minds because we are as complex

38:19

creatures. There is no way that we

38:21

can predict what we going to face

38:24

tomorrow or in the next moment. Our

38:26

behavior and our environments is just too

38:28

complex to have any sort. Of hard

38:30

wired solution to everything that we

38:32

might face. Bacteria are much simpler

38:34

and that can have a more

38:37

automated response although even they don't

38:39

have any toilet and I think

38:41

brains are evolution solution to that.

38:43

That instead of giving us some

38:45

you know hardwired response to every

38:47

situation or even instead of giving

38:49

us some computer because I don't

38:51

think the brain meaningfully as a

38:53

computer that kind of some have

38:55

computes what we have to do

38:57

next. It wouldn't have the time.

39:00

To do that it's no guns that

39:02

uses rules of thumb rarely Yeah to

39:04

do to do something that we have

39:07

found through trial and error, through experience

39:09

and through some degree of and eight

39:11

nests to be usually good enough to

39:14

be good enough to two hours to

39:16

get by and. What that

39:18

ends up doing is giving us

39:20

more innocent, more cognitive capacity. The

39:22

we would seem to really have

39:25

any need for steps. What is

39:27

they? Evolutionary of function of being

39:29

able to devices? Theory of General

39:31

Relativity? Why on earth do we

39:33

do that will? It's because in

39:35

order to have these brains that

39:37

can function well enough in our

39:39

environment to give it says it's

39:42

capacity as doing these things that

39:44

seem to have no evolutionary benefits

39:46

and in fact some things. That

39:48

seem to be counterproductive. Get a

39:50

non adaptive and that's just what

39:52

minds are like. But I think

39:54

in arguing the book that actually

39:56

when we start to think about

39:58

what agency rarely is. One agency

40:00

requires it requires things like

40:02

memory. It requires things like

40:04

having some sort of internal

40:07

representation of your environment so

40:09

that you can anticipate what

40:11

you might find when we

40:13

start to think about it.

40:15

That way, we have to

40:17

start thinking of every living

40:19

thing, down to single celled

40:21

organisms as innocent cognitive agents,

40:23

not just stimulus response machines.

40:25

That own life is cognitive.

40:28

At agreed and in of that sort

40:30

of foreshadows are questions to you about

40:32

Mike Levin's work, but let's hold off

40:34

on those for just a second and

40:36

stick in the spaces in a why

40:38

agency. And then I think you've articulated.

40:40

Some. About the utility of

40:42

agency but what are they

40:44

come from? So you know, art

40:47

raised the issue of conflicts across levels.

40:49

but where did it start? Added a

40:51

got going: Is it heritable that even

40:53

makes sense to ask that question? Is

40:55

it sort of variable among individuals and

40:57

a population Is our way to merge

40:59

these concepts of these the sort of

41:01

frameworks really? Yeah. And

41:03

these are absolutely the questions that

41:05

should motivate Having a theory of

41:07

agency said that we can get

41:09

some handle on them on a

41:12

where did it come from? I

41:14

think that actually eight correlates completely

41:16

with with living things. and actually

41:18

I don't think anything can be

41:20

truly alive if he doesn't have

41:22

agency. I don't think necessarily the

41:24

converse is true. I think that

41:26

we may end up making genuine

41:29

agent show machines A I basically

41:31

might already have some. Degree of Asian

41:33

say it might already be setting his home

41:35

goes to some degree. so you know I

41:37

don't think the only living things can be

41:40

agents although at the moment I suspect of

41:42

living things are are genuine agents. But that

41:44

may change the future. But I do think

41:46

that know living thing cannot be an agent

41:49

that everything in life has been. I did

41:51

so we have. What that means is that

41:53

in order to I'm in the origin of

41:55

life is complex enough already. Okay without introducing

41:58

agency. but I would hope that I. We

42:00

by introducing agencies we can focus like

42:02

Christian a bit more because you know

42:04

so often discussions about the to the

42:06

the origin of life they they might

42:08

start of listing various things, that living

42:10

thing, how to be any good and

42:12

to get a reproduce have to be

42:14

metabolized. it's just that a certain kind

42:16

of shopping list that you know if

42:18

it no one agrees on and that

42:20

might see more or less arbitrary but

42:22

I think that the to have a

42:24

genuine living fake you have to have.

42:27

Created. In some way, agency

42:29

and so fully understand what is needed

42:31

for agency. And you know, as I

42:33

say, I've mentioned some of them, I

42:35

think it does need some sort of

42:38

memory. They're out of physical series that

42:40

suggests the. Only by

42:42

having memory and by using that to

42:44

create some for representation of the environment

42:47

only systems right? That can be some

42:49

a dynamically efficient. Otherwise, I made

42:51

it through the speaking at even literally

42:53

speaking. Otherwise you just bumping into stuff

42:56

all the time because you're not anticipating

42:58

what's coming into. That's very inefficient.

43:00

So we can start by thinking about

43:02

what agency is and what it requires.

43:05

Breaking it down, we can start to

43:07

formulate some questions about what would have

43:10

been required for life to begin. That

43:12

it outside the normal ones? Have

43:14

you know have you made replicating

43:16

molecules? howdy my dna and settles.

43:18

Yeah. Do you think that

43:21

agency is something that we can

43:23

directly measure? Or is it one

43:25

of these more abstract kind of

43:27

things like fitness that we know

43:29

is really important but takes lots

43:31

and lots of different forms and

43:33

is context dependent and mean. Will

43:36

we ever had an agent amateur

43:38

Fat Yeah. Great question and I

43:40

can't answer that with confidence. I

43:42

do think that it will be

43:44

possible to. An atomizer agency

43:46

to say was this is you know,

43:49

as I should have hinted that Asians

43:51

have to have these particular characteristics. I

43:53

don't expect any kinda versions on exactly

43:55

what those need debates, and I think

43:58

it's quite reason suppose that things will

44:00

have degrees of agency in much the

44:02

same way as we imagine living things

44:05

have degrees of sentence, but I think

44:07

there has to be some agency as

44:09

I say for it to be alive

44:12

did. Over there, different degrees of agency

44:14

would probably also different types of agency

44:16

in much the same way as I

44:18

think we need to stop thinking of

44:21

consciousness as a single thing, like a

44:23

single you know fluid that we have

44:25

more or less all have different organisms.

44:28

I think there are different dimensions. To

44:30

consciousness I think there will be to

44:32

Agency says that some agents will be

44:34

very good at doing particular things. I

44:37

might have been a particularly good memories

44:39

for example, some agents might be particularly

44:41

good at actuating thanks. a lot of

44:43

been home to move of being able

44:45

to sense in certain ways so you

44:47

know I think we could break it

44:49

down and an atomizer. but whether we

44:52

could I ever really sort of quantify

44:54

that I'm agnostic about at this point

44:56

is why we need a theory to

44:58

to help us. Yeah. I've

45:00

been enough. understandable and it's also great. The

45:02

here caution You know the did not want

45:04

to go too far but as these ideas

45:06

had been and ass off for a long

45:08

time and and just started to come around

45:11

as we intend to formalize and you've used

45:13

the word a couple of times it's sort

45:15

of as conflicts with of the we're talking

45:17

about a minute ago or you I guess

45:19

youth implied that agency may be decomposed bull.

45:21

Is that what you mean A minute? If it

45:24

is sort is what Is it? A substrate of

45:26

emerges causalities to go back to what we are

45:28

talking about before any net raises the bar for

45:30

of measurement, doesn't it? Had we put these two

45:33

things together. Yeah well it does

45:35

except that I would hope that if we

45:37

can decompose the i feel we probably can

45:39

then perhaps we can quantify it a bit

45:42

better because I'm we can start to even

45:44

think about the individual components and again you

45:46

know I'm using memory because it said of

45:48

for as familiar wonder you we can kind

45:51

of measure the amount of memory that something

45:53

has and I should say in fact that

45:55

of better discussion than I'm going to be

45:57

a to give of what of how the

46:00

to and optimize agency and you know how

46:02

to think about eight in Tibet a discussion

46:04

is you can find it it in a

46:07

book called free Agents by the Irish Here

46:09

scientists Kevin Mitchell which I'd really recommend of

46:11

which I it's you know drill on for

46:13

quite a bit for my discussions of agency

46:16

we totally agree we just had Cabin on

46:18

and that a month ago process is a

46:20

great bus fare very good but yes so

46:22

I think we probably can't and atomizer. One

46:25

thing though I would mean this is Pat

46:27

scared to sad. More controversial is that's as

46:29

lied. To the notion of agency and

46:32

to the recognition that agents have purpose.

46:34

I think we need to be able

46:36

to start talking about meaning. And.

46:38

Living Systems and that that will send

46:40

a lot of people scuffling a fighter.

46:42

I know because assess as a spot.

46:45

Here's what I made by that because

46:47

I have the start of the.i say

46:49

that I think one way to think

46:51

about living things is that they are

46:53

creators of meanings. And what I mean

46:55

by that is that any living thing.

46:58

Is going to inhabit this environment

47:00

that is full of stuff happening,

47:02

full of what we might think

47:04

of his information. We know that

47:06

that that's the case. We have

47:08

all the sensory inputs coming towards

47:10

us. What a living thing has

47:12

to be able to do is

47:14

to celta that information to figure

47:16

out what matters for survival. it

47:19

as first and foremost of what

47:21

doesn't and different organisms have made

47:23

different assistance of our that so

47:25

that it as for us. Vision

47:27

is really important. Because that's in

47:29

the nature of our environments It as

47:31

for don't smell laser really important thing

47:33

for lots of creatures in the seats.

47:36

Didn't have a deep ocean vision isn't

47:38

gonna get very far because it's just

47:40

to.down as a it's have other senses

47:42

but they have different ways of filtering

47:45

that information but not as filtering it

47:47

but giving it some kind of valence

47:49

it out. How much attention do I

47:51

have to pay to this information? How

47:53

worried? If you like to put a

47:56

anthropomorphic they have where he should. I

47:58

be that I've just had this thing. Well

48:00

that signal how interested should I be

48:02

in it? So I think that this

48:05

is so that Living Systems games they

48:07

don't necessarily know those the doesn't have

48:09

to be any awareness, any conscious awareness

48:12

of that happening that they have to

48:14

have some system for creating a surveillance

48:16

to their response And that's what I

48:18

mean by meaning and enough they have

48:21

to be able to do that in

48:23

order to not be overwhelmed that in

48:25

order to not cannot promote of information

48:28

on store old that isn't going. To

48:30

be any use to them because

48:32

again, as inefficient how that is

48:34

very specific sense. I think living

48:37

things do create meaning from what

48:39

I experience. Great!

48:41

I have a question from the skeptics

48:43

corner and this comes from party Whether

48:45

other couples ten damper on I I

48:48

I sort of has. you'd ask this

48:50

question itself, but he's asked me and

48:52

Marty several times some hard questions about

48:55

what we mean by agency and his

48:57

take on it is. there is no

48:59

clear necessarily what the differences between agency

49:02

and just plain old phenotypic plasticity which

49:04

he spent a lot of time thinking

49:06

about, Lot of time studying and I

49:08

think you could argue that. You

49:10

know what are the systems that

49:13

instantiate this idea of phenotypic plasticity?

49:15

Their complex systems that are sensing

49:17

the world. And. Making decisions about

49:20

how the altar phenotypes across different spatial

49:22

and temporal scales from very rapidly to

49:24

very long term development on kinds of

49:26

changes and you know it's hard for

49:29

me to come back to camp and

49:31

say, well, I think agency is something

49:33

else and that so would you say

49:35

something different about that. Yeah.

49:38

That is very good question. I

49:40

guess it's not. Clear

49:42

to me. Where

49:44

if with simply thinking in

49:46

terms of phenotypic plasticity. Were

49:49

in that picture, were going to get notions

49:52

of purpose and goals It may be in

49:54

there may be the right is that I'm

49:56

not familiar enough with that way of thinking

49:58

to know that. But I. I feel

50:00

like that's the key thing that we

50:03

have to recognize with agents. We have

50:05

to think about them as having some

50:07

sort of goals that it internally set

50:09

and you know one reflection of that

50:12

is even for be different. Need some

50:14

sort of bank here and I suspect

50:16

roses the bacteria we can give look

50:19

look to be an identical population of

50:21

South. And. Identical stimulus and

50:23

I want or responded the same

50:25

way because I'm in now Be

50:27

Some to Cast is Dns. Some

50:29

of that will be random, but

50:32

some of that will be purposeful

50:34

in the sense that because I

50:36

had different histories they will have

50:38

different internal settings, little conditions, the

50:40

response that they give and I

50:42

think it's meaningful to talk about

50:44

that is those bacteria having different

50:46

goals which you know rationalize is

50:49

the different responses are they will

50:51

have so it seems. To me

50:53

that that's something that goes beyond

50:55

simply recognizing phenotypic plasticity in the

50:58

sense of recognizing will I can

51:00

be these differences Maybe it's really

51:02

about asking me why is that

51:05

what is driving in of causes

51:07

of those different responses and that

51:09

has to come down to some

51:12

notion of the system and making

51:14

a decision ready making decisions that

51:16

that are related to interview you

51:19

only make decisions if you Goals.

51:37

So we'd such done a consequences

51:39

of agency and assorted systems thinking

51:41

for how we should think about

51:43

problems and issues. and in medicine,

51:45

I think it's a good point

51:47

just to return to that. and

51:49

the point you're making it the

51:51

very beginning of our conversation was

51:53

that you know it's hard often

51:55

to trace particular medical situations to

51:57

particular Los I. And that's because

51:59

these. Los I of causation ertl was

52:01

I have agency or spread out across the

52:03

body Maybe let's talk about that in the

52:06

context of cancer. Yes I'm quite interesting things

52:08

that you say about cancer and you know

52:10

if we just or a step back and

52:12

say well what is cancer. It's

52:15

effectively cells that. Are.

52:17

Going rogue is in the sense

52:19

that they're giving up on this

52:21

common project of running an operating

52:23

a multi slater body and they

52:25

strike off on their own and

52:27

they become selfish. It becomes about

52:29

them and I think one way

52:31

to conceive of that is that

52:33

something about their a general decisions

52:35

their purposes have changed. So what

52:38

is it about writing this book

52:40

that influence in our other sort

52:42

a new horizons for how we

52:44

should think about the origins and

52:46

possible treatments of. Cancer. Yeah.

52:48

I think they're absolutely are. And I

52:50

think that one of the things that

52:53

seems to me to have happened again

52:55

over the past maybe ten twenty years

52:57

is that that picture that you've just

52:59

presented about the way to think about

53:01

cancer that that I think to has

53:03

changed. So this notion that is the

53:05

cancer cell is a rogue sound is

53:07

it has become selfishness during its and

53:10

things clearly cancer cells are in a

53:12

sense if you like and not cooperating

53:14

with the rest of the body but.

53:16

They aren't total individualists. It's

53:18

really, really striking that now

53:20

that we have the technologies

53:22

to be able to have

53:24

a single cell basis, look

53:26

at what is really going

53:28

on inside a tumor. We

53:30

find that actually, rather than

53:33

just being this undifferentiated mass

53:35

of proliferating cells, each of

53:37

them an individualist, it's more

53:39

like. And I use

53:41

this phrase. I think it is.

53:43

I have this phrase from Brad

53:45

Bernstein originally that it's more like

53:48

it rains recapitulation of development stuff.

53:50

Actually, to must have some characteristics

53:52

of organ. Sit there at different

53:54

types of cel within them and

53:57

they seem to be operating more

53:59

like a kind go crazy organ

54:01

than just a you know, a

54:04

massive individuals and even to the

54:06

extent that we see. Team.

54:08

As a Killer. Getting healthy

54:10

cells and including healthy cells

54:12

within the two months to

54:14

do things for that tumor

54:16

and do doing things. That.

54:19

They sort of do normally be to make

54:21

them to be developing in of blood surprise

54:23

for example you know the skin or as

54:25

a ton of the Dubai is really important

54:28

and that's one of these the things that

54:30

is often our tax to drive your tank

54:32

the demon. So I think the view of

54:34

cancer or you know has has changed in

54:37

that regard that it's perhaps better to see

54:39

it as a an aberrant form of development

54:41

rather than as in our on a Single

54:43

Help and his. But I also kind of.

54:46

I think it's more useful to see at

54:48

not as. So much as cells

54:50

that have totally gone rogue but

54:52

that south of have acquired one

54:55

of the many different possible state

54:57

that ourselves can form that it's

54:59

I think about it more in

55:02

terms of Waddington Screen this landscape

55:04

of possibilities. Time salute the the

55:06

way that Silva now being thought

55:09

of in terms of how they

55:11

find their fate sits on a

55:13

landscape which era face value seems

55:16

to be a landscape of enormous

55:18

complexity. Of multi dimensional complexity if

55:20

you think of how many it of

55:22

jeans we haven't habit a different types

55:25

of regulatory system we have that the

55:27

the possibilities for cel seem endless and

55:29

yet there seem to be only a

55:32

few different states have a for relatively

55:34

few and they seem to find them

55:36

quite sort of reliably and some of

55:38

those states will be ones corresponding to

55:41

to cancel like states and cells can

55:43

flip over into those and eat at

55:45

this is being sort of and analyze

55:48

now innocent. Of dynamical systems framework where

55:50

we think of in a one

55:52

of the different collective states as

55:54

the d network can form of one

55:56

of them have some of them

55:58

corresponds to these. The that we

56:01

we can go with cancer cells

56:03

and thinking about it that way.

56:05

I mean I his first saw

56:07

it. I think it creates more

56:09

realism about cancer because I think

56:11

drugs or is just a consequence

56:13

of being multicellular organisms. You know

56:15

every organism has some organisms, right?

56:18

Whales have better defenses against it

56:20

so they have less cancer. but

56:22

it's something that old multicellular organisms

56:24

are going to be vulnerable to

56:26

just as misfolded protein states that

56:28

give rise to things. Right in

56:30

a near degenerative diseases are attacks

56:32

against is having protein. This is

56:34

just something the proceeds will do.

56:36

and this means that we need

56:38

to think about cancer treatment listeners

56:40

something to be eradicated which is

56:42

just not possible for it. Instead,

56:44

if if we think about it

56:47

is wanting to guide ourselves to

56:49

stay on track to stay one

56:51

of these healthy valleys, adults go

56:53

over to one of the others.

56:55

And even to the extent that there are.

56:57

Now these approaches to treating Canseco differentiation

56:59

therapy were what you're trying to do

57:02

is instead of just blasting them and

57:04

tried to kill off as many as

57:06

you can without telling over healthy stuff

57:09

as well. It's more along the lines

57:11

are thinking about it in terms of

57:13

sell reprogramming with were doing for other

57:15

purposes but reprogramming cancer cells to bring

57:18

them back on track to bring them

57:20

back into a healthy state. or perhaps

57:22

programming them in a way where they

57:24

get stuck in a dead end where

57:27

they. Tom proliferate aware that kind

57:29

of sitting ducks for chemotherapy.

57:31

so he does it. Hopefully

57:33

this way of thinking about

57:35

cancer as a sort of

57:37

dynamical systems sort of take

57:39

just that. This that might

57:41

lead to other approaches to

57:43

attacking. While. And you know

57:46

one thing that dissemination them anything

57:48

to things thirst. Do you think

57:50

that tumors may be used to

57:52

sort of these quasi agents to

57:54

understand the composition algae of agency?

57:56

Because if they're sort of organs

57:58

of a sort. They're not quite

58:00

and the some composite of things that

58:02

have it existed before but they do

58:04

have agency and away have a mic.

58:07

Maybe tumors could be a useful model

58:09

of understand the agency. Well I

58:11

think he hasn't Really interesting I thinking

58:13

that the I certainly think that. Thinking

58:16

about to move from an agent for

58:18

point of view makes a lot of

58:20

sense because either them we need to

58:22

ask what manner of agents all about

58:24

what all that goals and as I

58:26

say you know that goes now seem

58:28

no longer to base well I'm just

58:30

gonna go proliferate as much as possible.

58:33

It's much more that they have club

58:35

active again so goals you know to

58:37

develop his ways it as meat silly

58:39

supporting within a tumor and that make

58:41

use of some of the agency that

58:43

healthy cells have club as also sort

58:45

of motivated. To think about that because I

58:47

know you read a lot about Mike Levin's work

58:49

with frog embryos my son amazing work with that

58:52

on the shelves many times that one of the

58:54

things that you emphasize or his you know bots.

58:56

So I wonder as you talk with Mike about

58:58

sort of. Combinations of frog

59:00

embryos cells to produce a variety

59:03

is seeding tumors and sort of

59:05

understanding their behavior. And a

59:07

searched understand cancer. Is it something that he's progressing?

59:10

It absolutely is. I've I've talked to a lot

59:12

to Mike over the years. You know for this

59:14

book and for other things in front of. When

59:16

I was in Boston when I was at Harvard

59:19

I visited Mike in the lab and that was

59:21

when I first. Woke. Up

59:23

to just on a new Every time I

59:25

speak to my A seems like he has

59:27

had new ideas have an answer to your

59:29

best and amongst those he's absolutely now and

59:32

as you know it he's gone public about

59:34

this already so I can say he's it

59:36

versus of of for me to start up

59:38

companies to make use of the word that

59:40

he's done on the scene about systems to

59:42

to find applications for them and it Of

59:44

by Medicine is absolutely going to be one

59:47

that they're going to be looking and it's

59:49

very early days whether it's going to pan

59:51

out or not I don't think. My nose

59:53

and alone anyone else. but you know,

59:55

Eight absolutely seems to be a sensible

59:57

way to to proceed. Yes, oh his.

1:00:00

Work on cedar box. It was another sort

1:00:02

of. I guess is

1:00:04

a you know trigger for getting me

1:00:06

to really think about what the broader

1:00:08

concepts of this book all because one

1:00:10

of that things that is the seem

1:00:13

to. Jump. Have from

1:00:15

the idea of thinking about cells

1:00:17

as these complex systems that have

1:00:20

it of a landscape of different

1:00:22

possibilities. Once you start thinking about

1:00:24

that, it seems I think pretty

1:00:27

inevitable that it's unlikely that evolution

1:00:29

has explored all the possible states

1:00:31

that ourselves half. I think it's

1:00:34

if it's very unlikely the road.

1:00:36

So what else is out there?

1:00:38

What? What This tissue types might?

1:00:41

cells be able to form that.

1:00:43

We haven't seen because you know evolution

1:00:46

just hasn't got there, hasn't had a

1:00:48

need for them. It seems utterly incredible

1:00:50

to think that is what evolution has

1:00:53

found. His exhaustive of all the possibilities

1:00:55

ourselves could do any more than evolution

1:00:57

will have exhausted all the possible proteins

1:01:00

that exists. Still, you know the possible

1:01:02

gene sequences. so what else is out

1:01:04

there in this is a in ah

1:01:07

solidity, what might is doing all this

1:01:09

other states of in his case you

1:01:11

know. He started with from sales. Other

1:01:14

states at these cells can have that

1:01:16

can be liberated that we can find

1:01:18

our way to and he found his

1:01:21

way to these ones that he causes

1:01:23

About Switzer didn't have collections of cells

1:01:25

are they're absolutely homeless. that a forms.

1:01:28

They're not just individual cells doing that.

1:01:30

it it offends the things. That are

1:01:32

formed that seem to. Be collective agents

1:01:34

of some sort and that has

1:01:36

as far as we can say

1:01:38

they don't correspond to anything that

1:01:40

we find in nature. I made

1:01:42

we've seen. You know that there

1:01:44

are observations going way back beyond

1:01:46

Mike's work for structures of this

1:01:48

sort that that frog cells in

1:01:51

particular seem to be able to

1:01:53

form but by by looking at

1:01:55

those rather than seeing those as

1:01:57

get updates of tissue that have

1:01:59

just started. Them loose or whatever.

1:02:01

Looking at them as potential agent

1:02:03

and seeing what they do if

1:02:05

left to their own devices ear

1:02:07

the A revealed all this kind

1:02:09

of behavior that had. presumably.

1:02:12

Been overlooked before. How advanced? Absolutely

1:02:14

the kind of thing that Mike's

1:02:16

experiments in a got me thinking

1:02:18

about. And of course he was

1:02:20

have way before me. Insane. What

1:02:22

else can sounds month that know

1:02:24

haven't made? Oregon? And you

1:02:27

know that leads us into

1:02:29

whole area's soft tissue engineering

1:02:31

and is straight biotechnology for

1:02:33

multi cellular biotechnologies. One else

1:02:35

can we build with cells?

1:02:38

And I guess I should mention that why

1:02:41

we called him a genuine i prefer Sudden

1:02:43

as a general is that the Duchess conglomeration

1:02:45

to sell that sit in a dish. Me:

1:02:47

these are new entity isn't entity that never

1:02:49

existed in evolutionary past As the conglomerations they

1:02:51

are different frogs but these are different kinds

1:02:54

of cells are you put them in mazes

1:02:56

with resource gradients and they can use the

1:02:58

sillier. Had thera. Follow. These resource

1:03:00

gradients and in that's what makes it a gentle.

1:03:02

they're not dying. As long as you're giving the

1:03:04

resources they're behaving. You're doing. And. To

1:03:07

me, I think you know one of

1:03:09

the mind blowing take away his here's

1:03:11

the agency of Emerges Re nationally when

1:03:13

you put cells together and to agglomerations,

1:03:15

right? It doesn't take some magic evolutionary

1:03:17

want that operates over a long period

1:03:19

of time, but rather the samosas capacity

1:03:21

of cells to form higher level agents

1:03:23

just directly when they come into contact

1:03:25

with one another either gets kind of

1:03:27

amazing. It is because it's not at

1:03:29

all obvious that they should do that.

1:03:31

Perfect. You know, even if we admit

1:03:33

that individual cells are Asians. How

1:03:36

do they collectively? In

1:03:38

of decide on the some some sort

1:03:40

of group of activists your life. you

1:03:42

know I should say that there are

1:03:44

people who say of my work well

1:03:47

what we're saying in this behavior it's

1:03:49

not actually purposefully so. Goal directed is

1:03:51

not a really I didn't so it's

1:03:53

just you know the playing out of

1:03:55

the things that the cells to share

1:03:57

the waving about of silly i would

1:03:59

happen to create this sort of motion

1:04:01

that isn't emotions you know with any

1:04:04

sort of goal or purpose. so there

1:04:06

are you know that there are people

1:04:08

a sort of pushed back on that

1:04:10

idea but I think it seems to

1:04:12

me hard to understand some of the

1:04:14

things that might have seen Xena bullets

1:04:16

do unless we. Bring and

1:04:18

a gentle picture to it. Now

1:04:22

hundred traits. Well, we're getting pretty close

1:04:24

to the end of our time. That

1:04:26

of will be guy wanted to ask

1:04:28

you about some really interesting thing, but

1:04:30

you had just of the very end

1:04:32

of your buck. You had this sort

1:04:34

of extended box at the end of

1:04:36

the last chapter and in it you

1:04:38

start to explore some of the consequences

1:04:40

or even just a question of are

1:04:42

there are consequences for how we understand

1:04:44

evolution of agency And this is quite

1:04:46

interesting. Of course, in light of this

1:04:48

ongoing controversy over the past couple of

1:04:50

decades about. What should the scope of

1:04:52

modern evolutionary theory be? How much of an

1:04:54

overhaul does it need? How inclusive and it

1:04:57

be of new ideas? I guess I just

1:04:59

want to. But the question to you directly,

1:05:01

like after having written or spoken thought a

1:05:03

lot about agency, Do you think it changes

1:05:06

in any fundamental way? How we should understand

1:05:08

the evolutionary process? Yeah

1:05:10

oh I would say on that is

1:05:12

it might do have a nice I'd.this

1:05:14

question naughty for view earlier idea of

1:05:16

what does have a revolution? it's and

1:05:18

I do tuck it in the book.

1:05:20

It is to some extent as well

1:05:23

because as you say I leave notice

1:05:25

this box at the end. Other two

1:05:27

reasons for that one it is that

1:05:29

I think I know enough about evolutionary

1:05:31

theory to know how little I know

1:05:33

about it and to know how vast

1:05:35

my ignorance of it is and also

1:05:37

to know how suffer ladies so I

1:05:39

don't. Feel I am well informed

1:05:41

enough about evolutionary theory to be

1:05:44

confident as a meeting about that.

1:05:46

But the other reason perhaps a

1:05:48

better reason for me being circumspect

1:05:51

about that is I don't think

1:05:53

anyone knows well enough at the

1:05:55

moment what these new perspectives on

1:05:58

biology are going to imply. For

1:06:00

evolutionary theory, I think it's

1:06:02

absolutely conceivable that when we

1:06:04

start to think of organisms

1:06:06

as agents that have their

1:06:09

own purposes and goals, including

1:06:11

ones that enable them to

1:06:13

change themselves and to change

1:06:15

their i make up in

1:06:17

some ways. the question of

1:06:19

is that going to impact

1:06:21

standard near Darwinian evolutionary theory

1:06:23

that was predicated previously on

1:06:26

seeing Morgan is of justice.

1:06:28

If you like passenger vehicles,

1:06:30

For jeans, you know they're no longer

1:06:32

passive. They're actually it's top down control

1:06:34

agents. Is that going to change the

1:06:36

theories it seems at entirely reasonable in

1:06:39

fact and an unavoidable question to ask.

1:06:41

but I don't think we know the

1:06:43

answer to that at the moment and

1:06:45

sites in our you you mentioned that

1:06:47

there are some people who are gonna

1:06:49

push back on some. The thing to

1:06:52

this book says I absolutely anticipated that

1:06:54

and absorbed into see more of it.

1:06:56

but I think of myself as quite

1:06:58

conservative and these respects because. I'm totally

1:07:00

it's agnostic about whether we need

1:07:03

something like this new evolutionary, extended

1:07:05

evolutionary sense as as or whether

1:07:07

you know we just need to

1:07:09

tweak standard near darwinian theory. A

1:07:11

Whether in fact, a lot of

1:07:13

these things are already in there,

1:07:16

a Weather's Nice Construction already incorporates

1:07:18

his idea, as you know, a

1:07:20

gentle behavior from organisms. I'm totally

1:07:22

on the fence about that because

1:07:24

I don't think I understand the

1:07:26

issues well enough to decide, but

1:07:28

also has a. Anyone does I thank

1:07:31

you? Probably spend a dentist was about

1:07:33

this. Dennis is a fantastic book we

1:07:35

have. Yes, yep, yep. You know I

1:07:37

think he makes a great case for

1:07:39

why weeds really do need to revise

1:07:41

the lots of our ideas and evolutionary

1:07:43

theories. You know, it's a really interesting

1:07:46

case that as I say, I'm agnostic

1:07:48

about how much of that is needed

1:07:50

or how much is understood at the

1:07:52

moment. but these are. Definitely.

1:07:54

Questions that this new sort

1:07:56

of perspective on living things

1:07:59

as aging, That definitely questions

1:08:01

that that perspective raises. Yeah, okay, last question,

1:08:03

sort of. Last question the first. I appreciate.

1:08:05

You know, the sort of caution that that's

1:08:07

really refreshing to hear because for a long

1:08:10

time we did hear there's a need for

1:08:12

It's an extended Everly Shards synthesis and that

1:08:14

just lead to a lot of arguments. It

1:08:16

feels like people talking past each other so

1:08:19

that that take was a fresh in your

1:08:21

book. Very much can say that perspective. One

1:08:23

of the other things that it says is

1:08:26

that in a we should maybe look for

1:08:28

or provide better metaphors besides agency. I. Think

1:08:30

you're clearly behind agency is one of

1:08:32

those, but the have other said mind

1:08:34

or the have specific ways that you

1:08:37

think that agency can be a useful

1:08:39

metaphor. Yeah, well. the notion of metaphors

1:08:41

in biology is is also pretty central

1:08:44

to what I talk about in this

1:08:46

book because it became clear to me

1:08:48

it's first of all how much everything

1:08:50

we say depends on metaphor. Idol language

1:08:53

spends. A metaphor for the everything in

1:08:55

science depends on that. But I think

1:08:57

the life sciences are particularly reliant on

1:09:00

metaphor because. Life is such

1:09:02

a complex thing and so that's

1:09:04

essential. It's necessary. It's useful. But

1:09:06

he's also dangerous because these metaphors

1:09:09

become so strong. The blueprints. you

1:09:11

know for the genome. the selfish

1:09:13

gene. We introduce him for a

1:09:16

reason, but then they get still.

1:09:19

And they become what is often called dead

1:09:21

metaphors which means not the they're actually get

1:09:23

a not use. That means that we forget

1:09:25

the they're metaphors and we just months. This

1:09:28

is how the way things are and then

1:09:30

that's when they become really dangerous. And

1:09:32

there's no good way for aren't

1:09:34

rooted metaphors We know. How to deal

1:09:36

with series we tested against experiment. You

1:09:38

know if the ferry gives wrong prediction

1:09:40

that eventually they get jumped out So

1:09:42

we know about that. But metaphors. There's

1:09:44

no mechanism inside syrup rooting them. and

1:09:47

I think that that's a real problems.

1:09:49

So I really wanted to push back

1:09:51

on some of the metaphors we used

1:09:53

the machine matter for in you know,

1:09:55

it bows he to I really wanted

1:09:57

to say knows, they're very good arguments

1:09:59

I think. Showing now that that's

1:10:01

not a good way to think about

1:10:03

living things, nor is it good to

1:10:05

to bring in computer metaphors. too much

1:10:08

so. yeah, we need new metaphors and

1:10:10

I don't yet know what some of

1:10:12

that is. All but one thing that

1:10:14

did become I felt clear to me

1:10:16

in the course of this book is

1:10:19

that perhaps life needs to be. Living

1:10:21

systems need to be that own metaphor.

1:10:23

Biology needs to be the source of

1:10:25

it's a metaphor rather than during a

1:10:27

metaphor. For math technologies. we don't have

1:10:30

any technology. That works in the

1:10:32

way life does none and so we

1:10:34

need to get rid of those have

1:10:36

some is metaphors and for example yeah

1:10:38

I talked about this wasn't my idea

1:10:40

either that how. The combinatorial systems

1:10:43

that we see working

1:10:45

in gene regulation. Where I

1:10:47

you know talked about all these committees

1:10:49

of molecules working together in some fashion.

1:10:52

A great metaphor for that is the

1:10:54

way our own factory system works. Where

1:10:56

we have you know, justice kind of

1:10:58

few hundred sensory receptors. Or

1:11:00

we have millions and millions of

1:11:03

different into significant for those because.

1:11:05

I grew up combinatorial and so

1:11:07

there's you know, a metaphor where

1:11:09

we could use one living system

1:11:11

to refer to another. The whole

1:11:13

notion of living systems as cognitive

1:11:15

beings don't move agents, comforted systems

1:11:17

that is out in a sense

1:11:19

a metaphor that comes from cognition

1:11:21

Council. the way our brains worth

1:11:23

a maybe something more than that

1:11:25

but certainly again. I think it's

1:11:27

a a this say to a

1:11:29

set of more useful matter for

1:11:32

than a sort of machine bags

1:11:34

metaphor. So that's. As much as

1:11:36

I can offer this stage that actually

1:11:38

into get good metaphor for living systems

1:11:40

look for other living systems to draw

1:11:43

them from. That makes sense. Now.

1:11:46

Well. That's just a beautiful and of I got

1:11:48

the great place to stop so ball thanks so

1:11:50

much for the conversation has been a total delight.

1:11:52

We always ask our guess at the very end

1:11:54

as as anything else you'd like to say the

1:11:56

thing we didn't cover that is like to have

1:11:58

last word on. I think you've tried

1:12:01

have gone. It's got in my mind from

1:12:03

the start to the finish of my book

1:12:05

so I think I have happened. If you're

1:12:07

a very debris and civic during that we

1:12:09

want to the appendix sorry that into their

1:12:11

defending said there is nothing I feel at

1:12:14

a to add scientists so but both of

1:12:16

us been fantastic talking d. Thanks.

1:12:18

Phil Thanks a lot that you. Listening:

1:12:35

If you like what you hear, let. Us know

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