00:05

[Music]

00:10

what is life that’s going to be the

00:15

question that I’m going to consider this

00:18

evening it’s one of the most fundamental

00:21

questions in biology I think many would

00:24

argue it is the most fundamental

00:26

question in bio biology I’m going to

00:30

talk mostly about life on planet Earth

00:34

but the question also makes us think

00:37

about life elsewhere in the universe

00:39

should it exist perhaps built in

00:43

different ways from that on our own

00:45

planet before I begin I want to strength

00:50

stress something living things are

00:53

extraordinary they are completely

00:56

extraordinary they are entities that can

01:00

maintain themselves they can grow they

01:04

can organize themselves construct

01:06

themselves reproduce into two identical

01:10

copies or close to identical copies they

01:14

pass on their characteristics to their

01:16

progeny they are also extremely diverse

01:21

and it so happens which is why this

01:25

lecture is difficult is that life is

01:28

very difficult to define now the

01:33

approach I’m going to use is to examine

01:36

some of the great ideas of biology five

01:40

great ideas of biology which

01:43

characterize the attributes of life I’m

01:46

going to give you a little history of

01:48

where those ideas came from and then I’m

01:52

going at the end or towards the end of

01:55

my lecture to derive from those five

01:58

great ideas some core principles with

02:02

the hope of getting closer to defining

02:05

what life is I hope you noticed the

02:09

careful way I said that sentence

02:12

clothes hope of getting closer rather

02:15

than actually answering the question now

02:18

of course I’m not the first to ask this

02:22

question it’s been wrestled with by

02:25

scientists over the ages and my first

02:28

slide here was is the first page of a

02:31

very influential contribution published

02:34

by scrolling her heel the uncertainty

02:37

principle a physicist who dabbled in

02:42

biology in his later life and published

02:45

a book this book here in 1944 it’s a

02:49

75th anniversary of this book based on

02:53

lectures he gave in Dublin in 1943 he

02:58

was particularly concerned with how

03:01

living organisms maintained order as a

03:06

physicist he was particularly interested

03:08

in the second law of thermodynamics and

03:11

he wanted to know how life could escape

03:15

the decay into chaos that is of course

03:19

enshrined in that particular law and how

03:22

to do it across generations this is two

03:26

quotes I’ve taken from that 1944 book

03:30

which actually is quite a good read I I

03:34

still read it occasionally and in fact

03:37

it’s on my kitchen table because of this

03:39

talk at this very moment the first there

03:44

an organism’s astonishing gift of

03:47

controlling a stream of order on itself

03:50

and thus escaping the decay into atomic

03:53

chaos the second law as I just said he’s

03:57

also interested in how this order

03:58

displays the power of maintaining itself

04:01

and producing orderly events and this is

04:05

what I’m going to be talking about in

04:08

the rest of this lecture I’m going to

04:11

start it with the cell the cell as the

04:16

basic unit of life as I said I’m going

04:20

to give a some background to this some

04:23

history

04:25

the soul was first observed by Robert

04:29

Hooke in and who he published his

04:32

observations in 1665 and you’ll see here

04:36

on the left the black and white picture

04:38

of what he saw he took a piece of cork

04:42

cut it with a razor put it under a

04:44

microscope similar to the one you see in

04:46

this picture behind me and saw lots of

04:50

little boxes I put on the right there

04:54

a modern scanning e/m picture it’s

04:58

pretty similar really not too much

05:01

advancing 350 years what he saw there

05:05

were rows of boxes he called themselves

05:08

after the Latin cellar for small cubicle

05:12

and soon after him a Dutch Draper Lowen

05:18

Hooke lived in Delft quite a humble man

05:21

made even better microscopes then then

05:26

hook and he scraped between his teeth

05:30

and put it under one of his microscopes

05:33

and what did he see he saw bacteria the

05:38

very first observations of single-celled

05:42

microbial life the charming pictures

05:45

here can you see

05:46

I think it’s Figure B obviously they

05:49

were swimming around and did a

05:50

loop-the-loop there as you can see lone

05:54

hook was a bit disturbed by this because

05:56

he’s rather proud of his clean teeth and

05:59

I think was disturbed at discovering all

06:02

this life in between his his teeth he

06:07

sent all his observations to the Royal

06:09

Society as a thousand letters they’re

06:11

describing his observations we don’t

06:16

have a reliable portrait of him but he

06:21

was the neighbor of Vermeer the famous

06:25

Delft painter and Vermeer and usually

06:28

did two paintings of a scientists at

06:32

you’re a geographer and an astronomer

06:34

and I like to think this might be loan

06:37

hook that

06:37

looking at here I should say as I am a

06:40

scientist there’s not one ounce of

06:42

evidence in favor in favor of that

06:47

now although cells were observed just

06:52

before the beginning of the 18th century

06:56

science developed over quite a long time

06:59

and a couple of centuries in fact and

07:03

eventually led to two concepts the first

07:07

concept was stated here by Theodor

07:11

Schwann a German zoologist he published

07:14

in German this is a translation here

07:16

from 1839 we have seen that all

07:19

organisms are composed essentially of

07:22

like parts namely of cells in other

07:25

words the cell is the basic structural

07:28

unit of life very critical the second

07:32

observation the second concept I want

07:34

you to be aware of a few years later

07:36

another German Rudolf Birkhoff

07:38

politician and scientists founder of

07:41

pathology by the way he stated it’s a

07:44

little different every animal appears as

07:47

a sum of vital units living units each

07:49

of which bears in itself the complete

07:52

characteristics of life in other words

07:55

the cell is also the basic functional

07:58

unit of life all growth and development

08:02

of life is in fact based on the cell

08:04

here’s a fertilized mammalian egg with

08:08

the sperm bashing on the door of the of

08:11

the egg and if I haven’t inspired an

08:15

interest in you yet let me remind you

08:18

all that you once all looked like this

08:21

you were once all a single cell through

08:25

growth and repeated reproduction of

08:28

cells we produce here I mammalian embryo

08:31

and then eventually ourselves now what

08:34

do we learn by cell from from from this

08:36

discussion about cells about life and

08:39

what it is this is a modern multicolored

08:43

version of cells well a couple of

08:45

conclusions the first point is as I have

08:50

just said

08:51

as the basic structural and functional

08:52

unit of life it is the simplest entity

08:56

which exhibits the characteristics of

08:59

life it can maintain itself it can grow

09:02

it can self-organize it reproduces and

09:04

it has heredity what this means is if we

09:08

try and simplify the discussion that if

09:12

we can understand cells then we’re very

09:15

close to understanding life because it

09:17

is the simplest entity that has the

09:19

characteristics of life and that means

09:21

cells are going to figure quite a lot in

09:23

this talk but what I say about cells

09:26

applies to living organisms as well

09:28

including ourselves the second point is

09:32

that the cell is bounded it’s separate

09:36

from its environment

09:38

you saw that obviously with the

09:40

microbial cells the bacteria but it’s

09:42

also the case for all our cells which

09:45

are all surrounded by a membrane and

09:50

separate from the rest of the

09:52

environment why is that important it’s

09:55

important because it allows order to be

09:59

generated within the cell giving rise to

10:01

complexity without contravening the

10:05

second law of thermodynamics it’s an

10:08

isolated system which creates order as a

10:12

consequence of further disorder in the

10:14

environment so in fact the problems with

10:17

second law of thermodynamics that

10:18

physicists always worry about simply

10:21

isn’t an issue because of the cell as a

10:23

bounded entity although it’s a bounded

10:27

intimate entity it has to be in

10:30

communication with the environment it’s

10:34

semi permeable the membrane is is

10:37

literally semi permeable and it builds

10:40

up within itself components that it

10:43

takes from outside in its environment it

10:47

produces Monteux it takes them off a

10:54

concentration gradient it requires

10:56

energy to do that but the important

10:59

point is that being isolated from the

11:02

environment

11:03

complexity can arise so we don’t have to

11:05

worry about the problem that certainly

11:09

was of great interest for Schrodinger

11:12

however he said something a little more

11:15

he was interested in how that orders

11:18

maintained generation after generation

11:20

and he came up with the idea that maybe

11:25

there was a code script and this is

11:28

another quote from that little book

11:30

these chromosomes we kind of come to

11:35

chromosomes in a moment containing some

11:36

kind of code script the entire pattern

11:39

of the individuals future development in

11:42

function is related to a code script and

11:44

he goes on to speculate that it may be

11:47

what he called an a periodic solid it

11:51

was trying to explain how order could

11:53

persist and he speculated that that code

11:57

script underpinned the development and

11:59

function of the living organism now this

12:02

is essentially the second great idea of

12:07

biology I want to talk about which is

12:08

the gene as the basis of heredity now

12:13

this came about from work from the abbot

12:17

of a monastery in Bruno now the Czech

12:22

Republic he was a monk when he did what

12:25

I’m about to describe but then became

12:27

the abbot he was trained as a physicist

12:33

and he got very interested in doing

12:36

crosses with plants to try and

12:40

understand heredity and how

12:42

characteristics were transferred down

12:45

over the generations I visited it in

12:48

1981 at the height of the Cold War I

12:51

took this photograph of his garden

12:54

actually it was quite a big gun wasn’t

12:57

used for growing things to eat it was

13:00

used for growing his plants for his

13:02

experiments and next door to it was a

13:04

greenhouse unfortunately dismantled of

13:06

similar size I mean frankly there was

13:09

major investment from the Justinian

13:12

monastery in scientific research quite

13:15

extreme

13:16

ordinary in the 1860s and from that

13:19

research he came up with the laws of

13:22

genetics and he did that and he was

13:25

successful where many others had failed

13:27

for several reasons he did trial crosses

13:31

with a range of plants and decided only

13:34

to work on those which he could make

13:35

sense of you could say that he was

13:38

cheating in some ways but actually in

13:40

biology which is so complex you have to

13:44

choose material and problems that you

13:46

can solve remember science is the art of

13:49

the soluble and it’s no point wandering

13:52

around if you can make no sense of it

13:53

and he ended up choosing the P and he

13:56

chose the P because it was easy to

13:58

characterize the the different traits of

14:01

the plants I’ll show you some in a

14:04

moment and because he was a physicist he

14:07

counted what he saw he was quantitative

14:09

so you can see here some of the

14:12

different characteristics here we have

14:14

flowers of different colors we have tall

14:16

plants short plants we have seeds that

14:19

are not shown here which are rough or

14:22

smooth now because he worked on peas and

14:27

these different characteristics the

14:30

differences were decided by single genes

14:33

it became easy for him to analyze what

14:37

they produce for the very simple ratios

14:39

that you may have read about in school

14:41

like three to one one to one nine three

14:45

three to one and what you need to take

14:48

home from that is simply that he could

14:51

explain it all if what was the basis of

14:54

this were particles particles that were

14:57

being segregated during the during the

15:01

crosses that he was carrying out these

15:04

particles a particular model for

15:07

inheritance of what we’d know as genes

15:09

today interestingly nobody sublime

15:13

didn’t notice of what he published it

15:17

lay there for 35 years and then it was

15:21

discovered by three geneticists at

15:26

roughly the same time who got the same

15:28

results

15:29

they weren’t always so generous in

15:32

acknowledging their predecessor and

15:34

there’s a story around that but I’m not

15:37

going to sully science by telling you

15:39

about it all you have to conclude is

15:42

that they’re human beings just like we

15:43

are today and we’re not perfect then it

15:47

was taken very seriously why we don’t

15:50

really know but several things happened

15:52

between 1865 and 1900 1900 and – the

15:57

first is that chromosomes were

15:59

discovered this is a late 19th century

16:02

picture of chromosomes in onion root tip

16:07

cells which is where I first saw cells

16:10

when I was at school in Northwest London

16:13

did a squash and saw these these

16:15

chromosomes here and these chromosomes

16:19

were postulated to be the place where

16:23

genes were located which were being

16:26

separated every time a cell underwent

16:28

division then of course that led

16:31

subsequently to the idea in fact the

16:35

fact that these chromosomes and genes

16:37

were made of nucleic acid DNA that was

16:43

discovered by Avery working in the

16:46

Rockefeller Institute in New York which

16:49

I led for eight years from years ago

16:51

actually and that showed that DNA was

16:55

the chemical basis of heredity did a

17:00

beautiful experiment took a DNA from a

17:03

pneumococcus a bacterium of a not of a

17:06

virulent strain basically dropped it on

17:09

a non violent strain and transferred

17:13

virulence from one to the other and it

17:15

was DNA that contained that and that’s

17:17

what showed it was DNA was the

17:20

hereditary material and then of course

17:23

what we see here is the double helix the

17:25

famous double helix structure involving

17:29

Crick and Watson based on the

17:31

experiments of of Franklin and and

17:36

others like Wilkins and

17:39

we know and I shall refer to it again a

17:42

bit later that this is the basis of

17:45

heredity and finally Crick himself

17:50

postulated what he called the central

17:54

dogma of molecular biology where the

17:58

information which I shall talk about

18:00

more stored in DNA is transcribed into

18:05

another nucleic acid RNA and then

18:07

translated into protein and that’s going

18:10

to form a central part of what I shall

18:11

say this is the basis of Schrodinger’s

18:15

code script it explains the permanence

18:18

of the heredity because it’s replicated

18:22

every time a cell and therefore organism

18:25

divides so living organisms and now we

18:29

have to think about principles are based

18:32

at least on earth on nucleic acids

18:36

nucleic acids and encode information and

18:40

they can be precisely copied because of

18:44

pairing between bases that make them up

18:48

and again I shall say a little more

18:49

about it before we do that though this

18:52

discussion has introduced two new

18:55

concepts that I want to introduce to you

18:58

the first is chemistry the chemical

19:03

aspects of living organisms are critical

19:06

for understanding life life as chemistry

19:09

the second concept is the importance of

19:13

information encoded in those molecules

19:16

and these are the two ideas are going to

19:18

discuss next and I’m going to start with

19:21

life as chemistry basically life is

19:26

based on chemistry and physics

19:29

it’s the mechanistic basis of life I

19:32

have to stress that because for many

19:36

years actually a couple of thousand

19:37

years I’m starting with Aristotle

19:41

scientists thought that the complexity

19:44

of life was so great that it could not

19:47

be explained by the laws of chemistry in

19:49

physics they proposed

19:51

vitalism that there were vital laws that

19:54

weren’t based on chemistry and physics

19:55

and that were necessary to explain that

19:59

complexity it took work by French

20:04

chemists to overturn this initially

20:07

Lavoisier although his work was

20:10

terminated because he was guillotine

20:12

because unfortunately as well as being a

20:14

scientist he was a tax collector for the

20:16

ancient regime so he lost his head and

20:20

then it was taken over by Pasteur the

20:23

famous Louis Pasteur who was working on

20:26

an applied project on why sugar beet

20:29

fermentation went wrong came to the

20:32

conclusion that it was all to do with

20:34

chemical products being made during

20:36

fermentation and came to the following

20:39

conclusion that fermentation was a

20:42

physiological act yielding chemical

20:45

products for the cell and he could then

20:48

advise the sugar be fermenters as to how

20:51

to do it and then he made a general

20:53

conclusion chemical reactions are an

20:56

expression of the life of the cell in

20:59

other words he was postulating if we

21:01

want to understand life we have to

21:03

understand the chemistry that goes on in

21:06

life I can summarize that in a different

21:09

way which is that living cells back to

21:12

cells again can be considered as a

21:14

chemical machine a complex chemical

21:19

machine including also physical

21:22

processes as well however it is a very

21:26

special sort of chemistry that we see in

21:29

living cells on this planet this

21:33

chemistry is based on carbon carbon is

21:37

made inside stars

21:39

it’s the fourteenth most common element

21:42

in the universe we are basically based

21:45

on stars sort of rather interesting idea

21:50

now what’s important is that each carbon

21:53

atom can form four chemical bonds

21:56

linking it to other atoms and it can use

21:59

two of those bonds to link to other

22:01

carbon atoms to make up chains

22:05

a sort of polymer you can see that here

22:07

there’s a backbone of carbon that makes

22:10

up a linear polymer but then it has to

22:17

free bombs which can form bonds with

22:23

other atoms such as oxygen hydrogen

22:28

carbon itself and this means that

22:31

there’s a variety of different

22:33

chemistry’s that can be put on top of

22:36

this basic polypeptide chain and that’s

22:39

because it’s made of a chain of amino

22:44

acids which are of carbon and connected

22:47

by nitrogen and there’s 20 different

22:50

amino acids that are used by life and

22:53

they had different chemical

22:54

characteristics some of them are bulky

22:56

some of them are small some of them are

22:59

siddik some of them are basic that is

23:01

their negative or positive charges

23:03

some of them like water some of them

23:05

don’t like water and all of this can

23:08

lead to a wide variety of chemical

23:10

properties and because you can build up

23:14

extremely long carbon chains

23:17

maybe I mean thousands of thousands long

23:22

then you can produce very complex

23:25

structures which can also fold up into a

23:29

three-dimensional structure now there’s

23:32

a lot going on here that is really

23:34

important to emphasize because what we

23:37

heard see here starting off with a

23:39

simple carbon polymer made up of

23:42

different amino acids you can make

23:44

elaborate molecular structures with a

23:47

variety of different chemistry’s that

23:50

can be put there that leads to a huge

23:52

variety of chemical machines and these

23:57

are the basic workhorse of life these

24:02

make up the enzymes that change other

24:04

chemicals into different chemicals they

24:07

can build up molecules they can break

24:11

down molecules

24:12

that’s as part of metabolism which in

24:17

critical for the functioning of life and

24:20

these chemical machines are so efficient

24:22

that they can operate in very gentle

24:25

conditions we sometimes try and mimic it

24:28

in rather more extreme conditions in for

24:31

example industrial chemical plants where

24:34

we have high temperatures and high

24:35

pressures and an extreme conditions but

24:39

these can operate in very gentle

24:41

conditions why is that important it’s

24:44

important because it means that within a

24:47

cell a tiny cell many hundreds in fact

24:50

thousands of chemical reactions can be

24:53

occurring in a very restricted space

24:57

because you’re not having to have high

24:58

temperatures or pressures you can have

25:00

very gentle conditions however these

25:04

reactions can only occur if there’s

25:07

different chemical micro environments so

25:12

if we look a metabolic map here each of

25:15

those dots on this map I had to learn

25:17

this as an undergraduate that’s why I

25:19

took all the names of but all these dots

25:23

are different chemical reactions and

25:24

they’re all occurring simultaneously in

25:28

the tiny structure of the cell and if

25:31

you now look at a cell you’ll see it’s

25:35

extremely complex and but what I want to

25:38

try and convince you is that actually

25:41

this complexity represents the micro

25:46

compartments of different chemistries

25:48

that are occurring on in the cells it’s

25:50

not how it’s normally explained and

25:51

that’s brought about by the proteins

25:54

themselves with different folds making

25:57

little compartments where a certain

25:59

chemistry can go on assembly of those

26:01

enzymes which result in components being

26:05

passed and molecules being passed from

26:08

one enzyme to another different membrane

26:10

components compartments as you see here

26:13

in the cell and even different colloidal

26:16

structures what we now call phase

26:18

separations so when you look at the

26:21

complexity of the cell I want you to

26:23

imagine it as many hundreds in fact

26:27

thousands of little chemical

26:30

microenvironments carrying out specific

26:32

chemical reactions adjacent to each

26:35

other connected to each other but

26:37

separate and that is needed to generate

26:40

the chemical complexity of life now

26:44

there’s a consequence of this is that

26:46

this intricate spatial organization of

26:49

the cell of these different chemistry’s

26:52

must be able to communicate across the

26:56

cell because if they don’t communicating

26:58

with each other you can’t get order so

27:01

you need compartment ation and

27:03

separation that you need also

27:06

communication what contributes to that

27:09

and that comes from physics is that

27:12

there is a skeleton within the cell made

27:15

up a different like tramway raised or

27:18

railway tracks connecting different

27:20

parts of the cell and there’s little

27:21

motors working their way through the

27:24

cell transporting different components

27:26

from one place of the cell to other

27:28

places in the cell and all of these did

27:32

need energy and in fact to maintain the

27:35

cell needs energy and there’s little

27:38

batteries in the cell as well like our

27:40

chemical batteries charged hydrogen

27:42

atoms can accumulate behind some of

27:44

these membranes and active batteries are

27:47

transferred through the membrane the

27:50

protons are charged atoms and that

27:55

produces high energy chemical bonds

27:58

which are stored for use elsewhere

28:04

communication then is critical and

28:07

communication between all these

28:09

components is dependent upon information

28:12

and the transfer of information and

28:15

that’s my next great idea in biology

28:18

that I want to explain to you as the

28:21

basis of life and that is that

28:23

biological entities are complex systems

28:27

and the information management is

28:30

crucial to understanding how they work

28:34

it won’t surprise you that this idea has

28:38

grown a lot of prominence in the age of

28:40

computing because obviously information

28:43

and the man

28:44

if information it’s critical in

28:46

computing and so there was much

28:49

discussion of this from the 1940s 1950s

28:52

and 1960s onwards but it may surprise

28:56

you to learn that the idea that light is

28:59

a complex system with these properties

29:01

has his origins with the philosopher

29:04

Kant Immanuel Kant around 1800 I found

29:09

this a big surprise he wrote a book on

29:12

on moral philosophy and for some reason

29:16

got completely distracted into talking

29:19

about the complexity of life in talking

29:22

about moral philosophy in fact although

29:29

biology can be described in terms of

29:32

chemistry as I’ve just done it often

29:34

only makes sense biologically when that

29:38

description is translated into the

29:41

management of information that sounds a

29:44

bit abstract but it’s important that you

29:46

get this for understanding life and

29:48

there’s two examples I want to use to

29:51

illustrate that and why it’s important

29:54

and the first is to go back to DNA

29:58

now I’ve already explained that DNA is

30:03

made of DNA of course but is the

30:07

hereditary material it encodes

30:10

information implicitly Mendel by the way

30:13

it was information showing the use the

30:16

word code stripped but the only made

30:18

sense back in 1865 if you saw it that

30:21

way now the double helix of DNA and you

30:24

see here being copied and because of the

30:28

DNA is like a ladder of bases there’s

30:32

four different bases and G base G will

30:36

bind to the base C and base a will bind

30:39

with base T so that if you pull that

30:41

apart you can get a perfect copy it’s a

30:44

beautiful thing and I want you to note

30:46

that those bases are all on the inside

30:49

of the polymer that sort of protected

30:52

there and that’s going to be important

30:54

in a moment now as I said we can do

30:57

describe it as I just did in terms of

30:59

chemistry but it makes sense

31:01

biologically when you recognize that

31:04

actually it’s a digital information

31:07

storage device I mean that’s what we’re

31:10

looking at here a digital information

31:12

storage device now there’s more to it

31:17

than just that because it’s organized as

31:21

a linear script now we often nearly

31:26

always order information as linear

31:30

scripts think of reading a sentence it’s

31:33

a linear script think of listening to me

31:36

talk to you they are linear scripts

31:39

think of computer code it’s a linear

31:42

script think of a polymer it’s a linear

31:46

script it is no accident that life is

31:49

built on a polymer because it is the

31:51

perfect way of storing information which

31:55

is critical for biology it’s critical

31:57

for information storage also as I

32:02

explained it gets better because the

32:05

linear DNA molecule is very stable

32:07

because the backbone is on the outside

32:10

it is not chemically reactive the

32:12

chemical reactive parts are on the

32:14

inside and are protected one with

32:16

another so it’s a very stable way of

32:18

storing that information however it

32:23

can’t do anything because it’s so stable

32:26

it cannot do anything but remember the

32:30

central dogma you go from DNA to RNA and

32:33

then you go to protein and remember what

32:36

I said about protein and I’m going to

32:38

just show you the same slides again now

32:40

you still have a polymer it still

32:43

reflects information each of those amino

32:45

acids what you put in there and the

32:47

order is determined by the base sequence

32:50

in the DNA but now everything is facing

32:53

outwards and all the chemistry is facing

32:56

the environment so you have oxygen you

32:59

have nitrogen your positive charge

33:00

negative charge much less stable but now

33:04

it can carry out chemical reactions so

33:06

what you do is you are turn

33:10

stored information in nucleic acid into

33:13

chemical actions in protein which are

33:16

needed for life so you have a storage

33:19

device which is stable and you have a

33:21

protein which are reactive and carry out

33:25

the chemistry of life this is really

33:27

fundamental in understanding life

33:30

because you can solve the problem of

33:31

information storage and you can solve

33:33

the problem also of chemical action

33:37

second example relevant for information

33:40

and making sense of biology and

33:43

information is seen with gene regulation

33:47

this was shown by Jacob Amano

33:51

who I knew at least a new couple quite

33:54

well and they did it by doing beautiful

33:57

genetics with bacteria looking at sugar

34:00

metabolism in bacteria and what they did

34:04

by abstract genetics is discovered

34:07

negative feedback control what is

34:10

negative feedback control well this is a

34:14

governor from a steam engine now you may

34:17

be like me I sort of understand most

34:19

machines built before 1900 and almost

34:23

nothing built after 1900 I took a

34:26

picture of this in New Zealand actually

34:29

it was in a steamship and I went down

34:32

and photographed it because it was such

34:34

a beautiful thing it was found on

34:36

originally on James Watts his steam

34:38

engines and we understand it the spindle

34:41

rotates the balls are thrown out they

34:45

lift a valve and that closes steam off

34:48

from going into the engine so it slows

34:50

down then the balls go back in again and

34:53

they let steam back into it and it

34:56

speeds up and this is essentially

34:58

homeostatic s– it’s maintaining a

35:01

certain in this particular case rotation

35:04

of the particular spindle and what

35:08

Jacques will mano did was to use this

35:11

principle to describe regulation and

35:14

here we’re looking at something in fact

35:18

not to do with gene regulation but it’s

35:20

the same principle

35:22

what they described where we have a

35:25

chemical AE turned into chemical be

35:27

turned into chemical see there’s enzymes

35:30

which are the green arrow and as C

35:32

accumulates it switches off the enzyme

35:35

that is catalyzing a into B and

35:38

therefore you inhibit making B you

35:42

inhibit making C and then C drops in

35:45

level you lose the inhibition up comes

35:48

the enzyme between a and B and you’ll go

35:50

back again what this is doing is

35:52

maintaining by negative feedback a

35:55

constant source of material if we look

35:58

at the bottom one we have positive

36:00

feedback loop which is the complete

36:02

opposite when you accumulate C it

36:04

switches on the enzyme going from A to B

36:07

so once you’ve started this it turns

36:09

into a switch and you cannot go back you

36:12

get the principal and life’s metabolism

36:15

and gene regulation is built on these

36:17

simple principles of this type of

36:20

feedback control now you can put them

36:22

together in all sorts of complicated

36:24

ways and a metaphor is an electronic

36:27

circuit that you see here and these

36:29

circuits which we find in life can

36:32

produce negative and positive feedback

36:34

switches timers toggles oscillators all

36:38

of which are playing a role in life now

36:43

it’s rather special just like the

36:45

chemistry is special this is special

36:47

because when we think of for example

36:50

computing which is of course the same

36:52

principle you have hardware and software

36:55

yes but hardware can’t change the

36:58

software you can make the hardware

37:00

operate in different ways but the

37:03

hardware is wired in in biology it’s

37:07

cleverer it was used the term was used

37:10

by Dennis Breyers assistants biologists

37:13

he used the word wetware rather than

37:16

hardware because the communication

37:19

between the different regulatory steps

37:22

is carried out by molecules diffusing

37:25

through water and this means you can

37:28

rewire the hardware by directing the

37:32

chemicals to go to different places so

37:34

not only

37:35

can you reprogram it through if you like

37:38

changes in software you can also change

37:40

it to changes in hardware we do not yet

37:43

begin to understand this complexity but

37:46

it’s in it’s important now networks and

37:50

be very complex we see at the top here

37:53

how we like to think about things or to

37:56

be more precise how men like to think

37:59

about things which is linear pathways

38:03

going from A to Z but the truth is in

38:06

biology it’s much more complex and

38:09

whereas we all intuitively understand

38:12

what’s happening at the top there we

38:13

don’t at the bottom it’s just too

38:15

difficult that is because of the next

38:18

idea I shall talk about that of

38:21

evolution by natural selection simply

38:23

means that you add things on to

38:25

something and make it just more complex

38:27

not necessarily the simplest way to do

38:30

something but simply a way of actually a

38:34

way of actually doing it but I want to

38:37

mention one more thing that we don’t

38:38

often think about in these pathways but

38:41

if we introduced dynamics into a pathway

38:44

that is changes in time it becomes much

38:47

richer and this is a simple example of

38:51

it we have a single at the bottom their

38:53

pathway and now we’re pulsing

38:56

information down and either frequently

38:59

or infrequently and the output can be

39:02

different depending on the oscillation

39:05

the frequency this has already been seen

39:07

why am i stressing this well I’ll tell

39:09

you why here we see a metaphor for it

39:12

can you see the traffic light if it’s a

39:15

simple on-off signal it’s either green

39:17

or red not a lot of information if you

39:20

introduce dynamics you can produce the

39:22

Morse code that you’re pulsing

39:25

information and now you can write the

39:27

works of Shakespeare now I’m not

39:29

suggesting the cell is writing the works

39:31

of Shakespeare but I am suggesting that

39:34

we haven’t got to beginning to the

39:36

bottom of how this is all operating in

39:39

cells they are absolutely extraordinary

39:42

and are the basis of how living things

39:46

work so what I’ve explained to you is

39:48

that the

39:49

where it’s working is through chemistry

39:50

plus physics and then management of

39:53

information and that’s key to

39:55

understanding what life is now my final

39:59

idea I can’t stop it this is the most

40:03

beautiful idea in biology evolution by

40:07

natural selection it’s got two aspects

40:12

life evolves and a major mechanism of it

40:17

is natural selection it’s a beautiful

40:22

idea which we mostly associate with

40:26

Charles Darwin who you see on the right

40:30

but actually the idea of evolution that

40:35

is of living organisms changing over

40:37

time was not Charles as I idea it had

40:41

been talked about for a century before

40:44

by French scientists like like Lamarck

40:49

for example but also erasmus darwin

40:52

who’s shown there on the left who was

40:55

his grandfather of charles now erasmus

40:58

is a rather entertaining character so

41:01

I’m just going to entertain you with one

41:03

of two things about erasmus he he was a

41:08

poet and he published most of his

41:10

science in blank verse I have a number I

41:15

collect books from this time and I have

41:18

a number of books published in the late

41:20

18th century and it’s all written there

41:22

in poetry with it with actually very

41:26

interesting science there as well he was

41:29

a dr. George the third asked him to be

41:33

his physician more than once but he was

41:36

a Republican and wouldn’t do it he was

41:39

in favor of female education and he set

41:43

up a girl school and wrote a book on how

41:47

women should be taught it’s the first

41:49

female school in in the UK so I’m told

41:55

he got into trouble with his local Dean

42:01

he lived in Litchfield for some of his

42:03

life in the Cathedral closed and he had

42:05

on his coach the motto everything from

42:10

Cheryl’s what did that mean if you open

42:13

up a shell you see you would see a sort

42:16

of formless blob in it yeah and what he

42:19

was arguing is all life came from

42:21

formless blobs but the Dean didn’t like

42:24

it very much

42:25

and told his richer patients that they

42:29

shouldn’t go to this rather eccentric

42:33

doctor and because he actually only

42:35

charged rich patients he didn’t charge

42:38

poor patients he had to paint it out

42:41

anyway very interesting character and he

42:45

wrote a number of verses about life

42:51

changing evolution but he had no

42:53

mechanism and that was led to his

42:56

grandson Charles over there who gathered

42:59

enormous evidence first of all the fact

43:02

that based on fossil evidence that there

43:05

had been evolution and secondly during

43:09

his voyage on the Beagle and secondly

43:12

that he proposed a mechanism and the

43:15

mechanism was natural selection and it

43:18

goes a bit like this actually completely

43:21

like this I don’t mean a bit like this

43:22

within a species there are variants they

43:27

have differences these are due to

43:30

inheritable differences they’re not ones

43:32

where if you grow a plant in the Sun or

43:35

not in the Sun they are inherited

43:37

differences those variants genetically

43:41

inherited ones which are most successful

43:44

reproduce more therefore pass on more

43:48

genes to the next population in the next

43:51

generation and therefore there is

43:53

selection for changes in characters and

43:56

over time that will lead to speciation

44:00

and therefore evolution and it also

44:03

accounts for why you can get exquisite

44:06

at that

44:08

and that we see here he studied these

44:11

finches in the Galapagos and came to the

44:14

conclusion that they were beautifully

44:17

adapted to weather they fed on insects

44:21

or broke nuts and I put up there a

44:23

series of tools which are also perfectly

44:26

adapted for what they do so two things

44:31

he argued that there was evolution so

44:34

all life was related this is the one

44:37

figure in the Origin of Species related

44:41

by descent and secondly there is

44:44

beautiful adaption and the reason why

44:48

this is controversial is because it can

44:52

lead to apparently purposeful behaviors

44:55

and if you have purposeful behavior

44:59

normally it’s easier to describe that

45:02

because somebody’s made it and there’s

45:04

the famous story of the Reverend William

45:07

Paley finding a watch on the path and

45:10

when he saw the watch he said this had

45:12

to be created and it when you see

45:15

animals and plants perfectly adapted he

45:18

argued therefore they had to be created

45:20

but what Darwin’s idea of natural

45:23

selection showed is that you could

45:25

evolve by natural selection

45:28

apparently purpose without having to

45:31

postulate a creator it would come

45:33

naturally from that now how can it

45:37

actually occur well it occurs because

45:42

life reproduces it has a hereditary

45:45

system based on genes which determine

45:48

what life is like and it has variability

45:51

upon which natural selection can work

45:53

and there I’ve turned this into single

45:56

cells and what you see here is a cell I

45:59

hope it’s visible behind me which starts

46:02

being orange and ends up being red at

46:05

least on the right hand side you see

46:07

that okay the idea is this that you have

46:10

genes they’re replicated you pick up an

46:14

alteration what we’d call a mutation and

46:16

that leads

46:18

to the coat of the cell being read

46:21

rather than orange and red cells have a

46:24

reproductive advantage so over time you

46:27

replace the orange population with a red

46:29

one okay so that’s a simple evolution by

46:33

natural selection and what we have here

46:35

is everything you need to evolve you

46:39

have and that scene in cells you have

46:41

genes are the hereditary system they

46:44

show variation because I’m not copied

46:46

completely precisely or they’re damaged

46:48

by external fourth x-rays or sunlight

46:53

and then that can lead to evolution by

46:58

natural selection I want to finish this

47:00

part with a quote this is the old

47:04

Charles Darwin the one that we tend to

47:07

think of and it’s a bit it’s the last

47:09

sentence of the Origin of Species

47:11

because he wanted to show that he could

47:14

produce laws in biology just like Newton

47:17

could do it in physics and he states

47:20

whilst his planet has been gone cycling

47:22

on according to the fixed law of gravity

47:26

obviously reflecting Newton from so

47:29

simple a beginning endless forms most

47:32

beautiful and most wonderful have been

47:35

and are being evolved it’s a beautiful

47:39

ending to a book I wish I could write

47:43

like that but if I did it would be

47:45

edited out as being pompous or or not

47:49

entirely relevant I get it all the time

47:54

of course no I’ve told you about some

48:00

ideas which are relevant and I’m about

48:02

to do a sort of synthesis of them to sum

48:06

up but before I do that I just want to

48:09

make one or two comments about some life

48:12

forms which are difficult to know

48:14

whether are alive or not alive of course

48:18

there’s no simple answers here but

48:19

viruses are the critical one this is a

48:23

bacteriophage which is a virus that

48:25

lives inside bacteria but we have

48:27

viruses in us as well

48:30

viruses have a nucleic acid genome it

48:34

can be based on DNA or RNA both work and

48:38

they contain that genome genes encoding

48:42

components of the virus they undergo

48:45

evolution by natural selection we see

48:47

that with for example how the flu virus

48:50

changes all the time every generation so

48:53

that undergoing evolution by natural

48:55

selection which you could argue is a

49:01

very important principle for defining

49:04

life it was one that was actually

49:07

proposed by Hermann Muller he was a 19

49:12

genesis in the middle 99 20th century

49:16

because he defined life as living things

49:19

have properties which allow them to

49:21

undergo natural selection and therefore

49:24

do evolve he simply took Darwin’s idea

49:26

and turned it into a sort of a principle

49:30

oh I should have said darling wasn’t the

49:33

first person to think of natural

49:35

selection should have said that it was

49:37

published in 1831 by a man called

49:40

Matthews who was writing a book about

49:43

ships timbers and how to grow it it was

49:46

only one side so it was nothing like

49:48

Darwin but he did have the he did have

49:52

the principle and he wrote to Darwin

49:56

after Origin of Species and said you

49:58

might be interested in reading this and

50:00

Darwin in the second edition actually

50:02

acknowledged this and of course the

50:05

story of him also Alfred Wallace who had

50:08

the same idea when in a malarial fever

50:10

is well known back to viruses virus is

50:15

evolved by natural selection so they

50:17

pass if you like them will err tests but

50:20

they can only reproduce themselves where

50:22

it they when they’re in the side the

50:25

cells of other living things they’re

50:27

completely dependent upon it and they do

50:30

so by hijacking the cells molecular

50:32

machinery to copy the virus’s genome and

50:36

to copy and to make the components that

50:38

in case that virus so this means a virus

50:41

cannot operate separately for

50:44

another living being its host it’s

50:46

completely dependent upon another living

50:49

entity so is it truly alive or isn’t it

50:53

well it’s not a clear there’s no clear

50:56

answer about this but I want to say

50:58

something that generally isn’t discussed

51:00

in thinking about this it’s important to

51:02

remember that other life forms are also

51:05

to greater or lesser extent often

51:08

dependent on other living things it’s

51:11

not just viruses that have such a

51:13

dependency we have many parasites that

51:16

live inside the cells of bodies or

51:19

animals or plants or fungi which are

51:21

living and depending upon them this

51:25

dependency is less total than it is for

51:28

a virus but it’s in the same direction

51:30

even ourselves we cannot make all the

51:34

chemicals we need we get them from some

51:37

other living organisms we can’t make

51:39

certain amino acids efficiently we have

51:42

to eat them and we eat them from plants

51:45

and animals that actually do make them

51:48

so we are also not entirely independent

51:52

of other living organisms even free

51:55

living microbes are dependent on

51:57

molecules made by other living organisms

52:00

bacteria fungi and so on and require

52:04

glucose ammonia generally made from

52:07

other living organisms particularly

52:09

plants which use the energy of the Sun

52:12

to make biomolecules from simple

52:15

chemicals including from the carbon

52:18

dioxide in the air or nitrogen which is

52:22

in turn actually made by bacteria found

52:25

in the roots of certain plants what I’m

52:28

trying to stress here and as I said it’s

52:31

not normally sort of recognised what we

52:34

really have is a graded spectrum of

52:36

living organisms from viruses which are

52:39

obviously utterly dependent through two

52:42

plants which are almost completely

52:44

independent on a wide range in before in

52:47

the case of the virus the dependency is

52:50

strong in other it’s weak

52:53

but they all share attributes of life

52:57

and we

52:57

you want to draw the line it’s up to you

53:00

and it depends really on your psychology

53:04

are you in your taxonomy do you like

53:06

splitting things up or do you like

53:08

putting them together I like putting

53:11

them together and saying they’re all

53:13

life but some require other life forms

53:16

to fully operate but actually all life

53:19

on the earth is fundamentally connected

53:23

it’s also fundamentally related as a

53:26

result of evolution there is a great

53:28

interdependency of all living forms on

53:31

our planet now I’m going to finish with

53:36

principles and I’m going to describe six

53:39

principles which I think are important

53:42

for thinking about life the first one is

53:46

simply really a description I’ve

53:48

discussed all of these things before

53:50

it’s just really to try and put it

53:52

together living organisms have these

53:55

properties they maintain themselves they

53:58

grow they can organize themselves

54:00

they’re exquisite doing that

54:02

self-organization they can reproduce

54:04

make precise copies of themselves they

54:06

have heredity and they’re highly diverse

54:08

this is what we have to explain these

54:12

are the attributes of life secondly life

54:16

and this is critical this is the Muller

54:19

statement life evolves by natural

54:22

selection through reproduction heredity

54:25

and the variability of the heredity

54:29

system now by doing this they acquire

54:34

purpose they are entities that can build

54:38

and maintain themselves and they have

54:40

these attributes that allows them to

54:42

actually do that and therefore to evolve

54:45

but it’s the way purposeful behavior can

54:48

arise without having to invoke a creator

54:51

so it’s critical the third one the cell

54:54

is the basic unit of life separate from

54:57

the environment but in communication

54:59

with the environment this is clearly

55:02

required to cope with the second law of

55:04

thermodynamics and you have a bounded

55:07

entity that can make complex

55:10

a complex entity to produce the things

55:15

that you see on that slide principles

55:20

for life is based on carbon Pullip

55:24

polymer chemistry we have lipid

55:27

membranes built on carbon that separates

55:30

the cells hereditary material built on

55:33

carbon polymers that makes DNA makes RNA

55:36

we have enzymes built on protein carbon

55:40

polymers which easily give rise to

55:44

chemical reactions so polymer chemistry

55:48

can give rise to complex chemical

55:51

reactions once nucleic acids store

55:55

information in linear chains of DNA

55:59

bases integrating all these functions

56:03

together is needed and what a living

56:09

organism does is to gather information

56:12

on inputs from within itself and from

56:14

outside itself processes them stores

56:17

them uses it to instruct the cells to

56:21

behave in particular ways all of this is

56:24

generated by polymer chemistry and I

56:29

don’t need to repeat it but the beauty

56:32

of it the stable chemical structure of

56:34

nucleic acid chemically inactive

56:36

beautiful for storing information so

56:39

easily translated into the chemically

56:42

reactive proteins that we see there in

56:46

living things final point life is

56:49

related and to everything else on the

56:53

planet and it’s highly interconnected

56:56

and we are dependent to varying extents

56:59

upon all other life-forms on the planet

57:01

we are all part of an ecosystem I didn’t

57:06

put it up here but just to stress all

57:08

life has to use energy to organize

57:12

itself their energy ultimately comes

57:15

mostly from the Sun through light and

57:18

photosynthesis generating high energy

57:22

compound

57:23

but it can also come from heat from

57:25

geothermal sources where there’s

57:27

life-forms that depend upon that so this

57:31

is what I want you to think about in

57:33

principles underlying life but I want to

57:36

end with something a little bit more

57:38

almost philosophical I think those

57:44

principles we’ve talked about here are

57:46

likely to be found in other life forms

57:50

should they exist um in somewhere else

57:54

in the universe I think in particularly

57:57

important is polymers because of the way

58:00

it connects information to chemical

58:03

reactions and I think that’s something

58:04

that we is really quite profound if you

58:07

think about it but if we go to if we

58:10

consider our planet it is of course the

58:12

only corner of the universe where we

58:15

know for certain at the moment at least

58:17

that life exists and we know as I

58:20

started that it is extraordinary is

58:23

extraordinarily diverse and we can make

58:27

sense of it and making sense of it by

58:29

the way is fun it’s it’s rather central

58:32

to our culture and our civilization I

58:35

mean we have to know it I mean it’s

58:38

important to us we know that we’re

58:41

related to the rest of life on the

58:42

planet we also know we’re deeply

58:45

connected to the rest of life on the

58:48

planet as far as we are aware we are the

58:52

only life-forms on this planet who can

58:54

see this deep connectivity and reflect

58:57

on what it means I would also argue we

59:02

have a particular responsibility because

59:05

of all of this for life on this planet

59:07

it’s made up of our relatives some of

59:10

them quite distant but they are all in

59:12

some sense our relatives and it we are

59:17

interconnected with it I want to leave

59:20

you with this thought we need to care

59:22

about life we need to care about it and

59:27

we need to care for it and to do that we

59:30

need to understand it and I hope you

59:32

understand it a bit better at the end of

59:34

this talk and at the beginning

59:36

thank you very much

59:37

[Applause]