The Code of Life: Great Scientists in their Own Words

In 1953, scientists discovered the structure of DNA,

and changed for ever our understanding of genetics,

of heredity,

and even of life itself.

It was the beginning of a revolution in biology

that led eventually to the sequencing of the human genome,

the genetic code of life that defines our species.

But this was a revolution with a difference.

'These critical scientific discoveries were among the first

'to be documented on television and radio.'

Dr Wilkins, what do you actually do?

The main thing in my kind of scientific work is to be able to

fiddle with a thing, go on fiddling with it and fiddle, fiddle,

until everyone else has given up.

'In an era before spin doctors and PR, the scientists were prepared to

'talk about their work - and each other - with extraordinary candour.'

She came toward me and I thought she was going to hit me!

Oh, God! Who hit who?!

Their stories, buried in the BBC archives,

reveal the people behind the science.

In few moments, through television you will be able to meet them

and judge for yourselves what manner of men they are.

Passionate, ambitious men and women,

driven by intense, sometimes bitter rivalries.

Scientists sat back and got fat and happy

getting tens of millions of dollars,

and I put John in that category.

We have already released two thirds of the human genome

into the public domain, and he's released nothing at all.

The archive reveals that truly to understand

how the discoveries were made,

it's essential first to understand the people who made them.

This is the story of those scientists,

of the men and women who set out to crack the code of life...

Happy days!

..told in their own words.

Do electrons think?

Electrons are charged particles,

the minutest we find in analysing the ultimate constitution of matter.

To think that such a particle can think is so absurd...

that I might give the answer, no, and have my talk over.

However...

This is one of very few recordings made of a man called

Erwin Schrodinger.

Schrodinger had served in the Austrian army in the First World War

and later made a name for himself in physics

as the inventor of a theoretical cat.

The odd thing is that here is Schrodinger,

a world famous physicist, musing on a biological problem -

the nature of consciousness, of what it means to be human.

Mind per se cannot play the piano.

Mind per se cannot move a finger of a hand.

This leaves us with the outlook that our body is as automatic or

non-automatic as any inanimate piece of matter...

only infinitely more complicated than even the most

ingenious man-made machine.

Schrodinger is a name in physics to conjure with.

I think even members of a quite broad general public would hear

the name Schrodinger, associate it with Einstein, it goes with...

tough physics, it goes with quantum physics, and the fact

that in 1944 Schrodinger published a book called "What Is Life?"

about biology, and how biology would yield to scientific attention,

that physics could unpack biology.

That was a light bulb moment for physicists.

I think it's a universal among all biologists

that they've got physics envy.

Um, they really wish they were physicists,

but they know they're not clever enough.

I know I'm not clever enough to be a physicist.

As Lord Rutherford once said, "There is only physics.

"Everything else is stamp collecting."

In writing "What Is Life?", Schrodinger helped

shake off biology's stamp collecting image and launched a period

that would bring it to the forefront of science.

What I think was really useful about that book was the was the rigour of

physical thinking, the thinking of a physicist,

which allowed the question to be properly framed.

What he emphasised was the importance of thinking

about the transmission of information from one generation to another,

that was essentially the nature of heredity,

and how you might think about coding information in molecules.

During the Second World War, Erwin Schrodinger was

head of Theoretical Physics at Trinity College, Dublin,

and it was here, in neutral Ireland, that he set about unleashing

the rigour of physics on the messy business of life.

Schrodinger talks about life in physical terms,

about life being an islands of order in a sea of disorder, and that's

perhaps the best definition of life I can think of,

and he also pointed out that it was a kind of twofold process,

a living creature itself will die and return to disorder,

but will have passed on its information in a molecule,

which, at that time, wasn't known, so there was a code involved too.

So, those two things - entropy and the code - both of which are

physical ideas, really, mathematical ideas, I think,

formed a lot of modern biology.

The same laws of physics

and physical chemistry hold within the living body as outside.

The simplest spontaneous bodily movement...

..say, the lifting of my arm,

would require the planned collaboration of billions

of single atoms in their undetermined swerves

if they should bring about the integrated action.

Science had started to make inroads into the secrets of life

in the previous century.

Charles Darwin had proposed his theory of evolution,

and Gregor Mendel had worked out the principle of how characteristics

were passed from one generation to the next biologically through genes,

though he had no idea what genes actually were or how they worked.

Then things went wrong.

The way that these ideas were misapplied is perhaps

the clearest example ever of two rights making one colossal wrong.

As demonstrated by leading British biologist Professor Julian Huxley.

What is the bearing of the laws of heredity upon human affairs?

Eugenics provides the answer.

Eugenics was a 19th century idea that spawned a movement whose

aim was to ensure that only the fittest survive.

An attempt at biological engineering.

Breeding out those deemed to be a drain on society.

People labelled at the time as defective.

Here is a man who,

although normal, comes from a mentally defective family.

Here is his wife who is also normal.

They have had 17 children.

Let us examine the pedigree of these children.

Five of them died in infancy, three are still too young

for an opinion to be formed of their mental state, a boy and two girls.

Only two of the remaining children are normal, a man and a girl.

The remaining seven children are all mental defectives.

The people who set up the eugenics movement,

who were studying human heredity, in retrospect knew nothing,

and I mean nothing, possibly less than nothing,

because what they did know was simply wrong,

but that didn't stop them from going into these dreadful practices.

In institutions such as this all over the country,

mental defectives are cared for.

Once such children have been born we must do the best we can for them.

But it would have been better by far, for them

and for the rest of the community, if they had never been born.

I think that...before World War II,

biology was somewhat of a backwater, not least because the

interwar period is a period of

frenetic development of military hardware.

The scientific community,

which was growing in stature was regarded now as the great hope.

It was what was going to defend Europe, defend the United States.

The biological sciences were really, I think...

..on the back burner.

The bright, young men -

and I use the term advisedly - went into physics and chemistry.

Three...two...one.

And go.

The irony was that

while Schrodinger used physics to explain what it means to be alive,

most of his "bright, young colleagues"

were using physics as a means of snuffing life out

on an apocalyptic scale.

In the course of World War II, literally every

able and eminent scientist was working for the war effort,

and I think that out of that

came a thoughtfulness about the meaning of life on the part

of physicists, that they maybe thought more about philosophy,

and I do think it characterises the men of this generation.

And coming out of the war into a time of promise and peace,

wouldn't you then want to go where those thoughts had taken you?

And THAT was biology.

One such scientist was Maurice Wilkins, an English physicist who'd

spent much of the war at Los Alamos developing the atomic bomb.

Certainly, the atomic bomb business was a stimulus for getting

out of physics and into something else,

and I think the immense destructive forces which were

discovered in the atomic bomb were rather appalling, and so I felt

that I wanted to work on things which were living and growing for a change.

Dr Wilkins, what do you actually do?

I mean, what do you actually do in your work?

The main thing in my kind of scientific work is to be able

to fiddle with a thing, go on fiddling with it and

fiddle, fiddle until everyone else has given up.

Wilkins settled into academic life at King's College, London,

where he began fiddling with crystallography in a bid to

shed some light on the mechanism of genetics,

on how what Schrodinger called a code might work.

Crystallography,

the idea that you could shoot x-rays at a copper sulphate crystal

or common salt crystals,

and by looking at the way they bounced off, you could

reconstitute what the structure of the atoms in the crystal were.

That was pretty astounding stuff

and he made enormous advances in physics,

and then somebody had the idea -

Wilkins was one of the somebodies -

of using that on the much messier system

which is biology, and to everybody's great surprise,

it turned out that some molecules were really quite amenable to

being treated in this way, and one of those molecules, which is

very abundant in the body, is DNA.

It was initially called the stupid molecule

because it seemed to be everywhere, you know, it was in all cells,

and yet it didn't seem to do anything.

Then, in 1944, a group in America performed an experiment,

which showed that DNA wasn't quite as stupid as everyone had thought.

They took strains of a pneumococcus bacterium

and the two strains differed - one was smooth, one was rough -

and what they did is they extracted DNA from one of those strains,

sprinkled it on the other,

and transformed the character of that into the previous one,

and therefore concluded that it was the DNA that conveyed that

information, it wasn't protein, it wasn't lipid,

it wasn't the other components - it was DNA.

DNA was the source of Schrodinger's code.

It was where inheritance was written.

So, now the race was on to discover how it worked.

It was already known that the DNA was made of simple sugars,

some phosphate groups, and just

four other chemical structures -

the so-called bases of adenine,

thymine, cytosine and guanine.

But how they all fitted together was a mystery...

..and the relationship between DNA and genes,

the conceptual carriers of characteristics from one generation

to the next, was another.

These problems were what Maurice Wilkins was trying to solve

with his X-rays.

But Wilkins wasn't the only physicist in the game.

In Cambridge, another out of work weapons designer was

casting his eye over the same problem.

His name was Francis Crick.

But, unlike Wilkins, Crick was not motivated by the horror of war.

He just fancied a change.

After the war, I was, of course, in the Admiralty, but I really didn't

want to go on being a scientific civil servant, as I was, for

the rest of my life, so I decided, "Well, what a marvellous opportunity.

"Here you are at the age of 30, you can go into what you like."

But the problem was, what did I like?

I noticed that I was telling some of my young naval officer friends things,

I remember one about antibiotics, and it occurred to me

one day that, "You don't know anything about antibiotics!

"You're just gossiping about it."

So, I decided that the gossip test is a good one,

that what you're really interested in is what you gossip about.

So, I looked at what I was gossiping to people about in science

and it boiled down really to two regions - one was the

borderline between the living and the non-living,

and the other was the way the human brain worked.

I knew nothing about either of the subjects.

I decided it had better be molecular biology,

it was nearer to what I knew.

And so that's how I decided to work on molecular biology.

Well, I have to declare an interest,

which is I knew Francis Crick from my childhood.

He, as a young man, during World War II had been allocated,

as a very brilliant, young physicist,

had been allocated a key role in charge of a section that was

developing deep sea mines to blow up enemy shipping.

And he, being the kind of man he was, a numbers man,

decided that he didn't want to do mines that blew up all of shipping.

He wanted to develop a mine

that would only explode under minesweepers

and he did indeed do that, he did it successfully and there are those who

say that he helped win the war at sea because knocking out

the minesweepers was exactly what was needed.

Admiralty never came round to it.

Admiralty thought of him as an uppity, uncontrollable,

difficult young man who wouldn't take orders.

He ran his section with great authority...

So, here's this young man who's been given lots of authority,

way ahead of what he would have got in a lab,

and also has learned to challenge authority and get away with it,

and indeed be able to say he was right.

'So, he comes out of the war

'and he's a very different kettle of fish from Wilkins.'

Amazingly...

links up really fortuitously with a madcap young man from America

who went to university at 16 and never toed the line.

They form an intellectual...couple.

I don't want to say collaboration, they don't collaborate.

They're a sort of, you know, couple.

The madcap American was Jim Watson,

a brilliant biochemist at the start of his career who'd recently

received his PhD at the unlikely age of 22.

'My first couple of months in Cambridge were terribly chaotic.

'I went to the digs Max had helped get me at Park Place,

'a dismal place where the landlady wanted me to take off my shoes

'when I came in at night and didn't want me

'to flush the toilet after ten in the evening.

'After a rather short while, I wasn't very sympathetic

'and she threw me out.'

But I think the main thing was that none of these things bothered me

because I'd met Francis.

MUSIC: "Je T'Aime...Moi Non Plus" by Serge Gainsbourg & Jane Birkin

'Jim was certainly our first American visitor and'

as soon as we met, we found that, although we had very

different backgrounds, we had a lot of things in common.

Neither of us were trained for what really interested us.

We both wanted to find the gene, we weren't organic chemists,

we weren't anything else. We just wanted to do the best...

To do the most sensible thing.

Francis Crick was a wild man,

a man who encouraged wild behaviour around him.

I was a student at Cambridge when I got to know the family well,

and it was a big joke that

if you stayed out overnight as an undergraduate in those

ancient days, you had to stay with an MA of the university,

so, you could go to one of Crick's

insanely wild parties

and stay the night because he was an

MA of the University of Cambridge,

but I'm telling you, I shouldn't have been at those parties aged 18!

And the thing about Jim Watson was that he was a prude

and he was hopeless with girls and he just tagged along with Francis.

He just always wanted Francis to somehow get him

into the thick of it, but he never did cos

he was sort of somehow too pusillanimous himself.

Crick and Watson's intellectual common ground was

in the idea that they might be able to determine the structure of DNA.

That challenge was something Jim Watson had first heard

described by Maurice Wilkins at a conference he'd attended in Vienna.

Then I suddenly became aware there existed someone...

who actually was trying to solve the structure of DNA, which...

seemed to be the likely candidate for the gene.

But Maurice was serious, deadly serious, and...

I tried to talk to him,

but Maurice is English, he doesn't talk much to strangers,

and so I left and sort of had a vague feeling that it would be nice

if I could work with Maurice, but it wasn't...it wasn't the sort of...

obvious coming together of like minds.

That's a carbon atom...

'Crick and Watson's approach to the problem was to try to imagine

'how all the known parts might fit together, build scale models,

'and talk about them.'

Well, Francis likes to talk...it's his dominant quality, I think.

He doesn't stop unless he gets tired or he thinks the idea is no good

and so, since we hope to solve the structure by talking our way

through it, Francis was the ideal person to do it.

In London, Maurice Wilkins and the King's group

were actually doing something about the problem.

Ray Gosling was a research student at King's at the time

and helped with the X-ray crystallography experiments.

This is the original camera that we...

took the first DNA specimens on in this lab.

And we had a fairly weak X-ray beam so that we needed

lots of material in the beam to get a diffraction pattern.

Now, you see there...

a specimen made with 30 to 40 fibres of DNA wrapped around this

little metal jig there, and we place that in front of the X-ray set...

..and after about a day, we had a diffraction pattern.

The data the experiments produced

was found in these fuzzy photographs -

pictures of how the X-rays were scattered by the DNA crystals.

These, it was hoped,

would provide the crucial evidence for DNA's elusive structure.

But the results they were getting were disappointing.

The pictures were too fuzzy.

So, because none of the group were expert in the technique,

an expert was hired.

In 1951, Rosalind Franklin arrived to help sharpen up the photos.

Or so they thought.

She actually arrived while Wilkins was away, which was

probably about the most unfortunate mishap in the whole story.

Wilkins was away, he was expecting her,

but she had come much later than she was supposed to come

because her work took longer to finish in Paris than she'd expected.

And she arrived in the laboratory,

she decided what she wanted to do, she'd decided who she was

going to work with, indeed, who was going to be her graduate student.

When she came first to the lab, Wilkins was in America and

the interview took place in Professor Randall's office

between Alex Stokes, myself meeting Rosalind for the first time.

And I can remember my own feelings at that interview,

it was very clear that, as a research student,

I was being formally passed from one to the other and that,

not only was she being given the problem, she was being given

an assistant to work with her on the problem.

Rosalind didn't see herself as collaborating with Maurice,

but there was always this tension between the two.

I think Maurice, uh...

when he brought Rosalind in, afterwards he regretted he'd

given away his problem, that is, he thought he needed help,

brought in someone who was a trained crystallographer

and then discovered that it wasn't his problem any more.

So, it was a catastrophe.

She didn't share and he didn't share,

and I have no idea whether she was a sharing person or not,

but certainly the conditions under which she was working meant

that putting her arm over her work was absolutely,

you know, the starting point.

She certainly wasn't going to let Wilkins have what she was doing.

But how did you get on with Rosalind?

-Terrible!

-Ha, ha!

You make out, Jim, you're sort of some male chauvinist pig,

but I think the real thing was, it wasn't that, it was

the fact that she didn't think you knew much crystallography.

To which she was totally correct.

Rosalind was rather prepared to discount them

as being very serious competitors. I think there was

a general impression in the scientific community

at that time that they were, uh...

..like butterflies, they were...

flipping around with lots of brilliance, but not much solidity.

And, obviously, in retrospect, this was a sort of ghastly misjudgement.

It was a ghastly misjudgement because the Cambridge butterflies

were actually getting somewhere by building their models,

talking, and perhaps more importantly, listening.

In those days, there was

a brilliant young theoretical chemist in Cambridge called John Griffith.

He died quite recently.

And he'd found that adenine stacked nicely on top of thymine

and guanine on top of cytosine.

He'd been thinking along those lines at the time, but I didn't know

that, so I said to him, "That's all right, that's perfect.

"That's all we need for our replication scheme."

The relative amount of the four bases in DNA had been worked

out by a nucleic acid chemist called Erwin Chargaff,

a few years before this time.

And it happened he was passing through Cambridge

and he told us about his results,

which were that the amount of adenine equalled the amount of thymine,

and the amount of guanine equalled the amount of cytosine in all

sorts of DNA, wherever he looked.

Although the other ratios were all over the place.

Well, the effect on me was electric because I saw immediately

that this is what you'd expect from a scheme like John Griffith's.

So, I was very excited. I didn't mention it to Chargaff at the time,

because it was work I was doing with John Griffith,

but when we checked it all out, we could see the two fitted together.

Crick and Watson now got word from the US

that the legendary chemist Linus Pauling was

also working on the DNA problem.

Armed with a draft copy of Pauling's soon to be published ideas,

Watson went to King's to discuss them with Wilkins.

Maurice read it and, in his usual way,

didn't convey sort of enthusiasm one way or the other,

but I guess he sort of said he didn't think Linus

was going to get the right structure.

At the same time however, he sort of let loose the bombshell, at least

to me, when he said there was two types of DNA X-ray photographs.

There was the form which I knew about called the A-form, which gave this

crystalline pattern, but there was this second from called the B-form.

He opened a drawer, took out a photograph and, boy,

I could hardly believe it! It was a perfect helix.

It was a cross-like pattern and the told me that they

repeated it and that meant there was a helix.

I thought also that I should go and see Rosalind.

It was clear that she was annoyed at my trying to tell her something about

crystallography, and she came toward me

and I thought she was going to hit me, so I quickly got out,

at which point Maurice was coming around and she almost hit Maurice!

Oh, God! Who hit who?!

I don't think anybody hit anybody, actually.

Some people may have thought

someone was going to hit somebody,

but, um...

there certainly weren't

very friendly feelings.

Watson escaped back to Cambridge in one piece, carrying with him

the memory of the B-form photograph that Franklin had taken

and Wilkins had shown him.

Straightaway, he started a new model.

So, I cut some things out of cardboard

and made the right shapes and then pasted things on, which would

indicate hydrogen atoms, and then I think I went off and played tennis.

I would do maybe three hours a day.

It was hard to get at it in the morning, but...

Because by the time you get in there was morning coffee,

then you'd go for lunch, have a walk, and then I'd come back

and build the model and, sort of,

Francis was working on his thesis...

I would look over my shoulder to try and see what Jim was doing.

I guess it's awfully hard to give up an idea of your own, so

I started putting the phosphates in the centre,

maybe because it was sort of like a Pauling structure.

Maybe, if we would have used ions we'd get somewhere,

but Francis really wasn't comfortable with this,

and told me, why don't I try putting the phosphates on the outside?

I can't really remember why you said that, Francis.

Well, it's because, I think, Jim, that, you know,

you were obsessional about having them

on the inside and you produced a lot of phony arguments as to why

basic groups from protamines had to go in,

and in all collaboration, it's very important

when one person has an idea, that the

other person criticises it as they were the devil's advocate,

so, just for the very reason that Jim was keen on having

the phosphates on the inside,

I thought he ought to try on the outside.

And suddenly I could put together A and T, and G and C.

I could hardly believe it.

Francis came in almost immediately and saw this.

Something came out of the model building that Jim had done,

which he hadn't put in,

and that's always the sign that you feel you're on the right lines.

When something begins to click, which you hadn't actually

put in, in your thinking, which you knew was there.

But, even more important, Francis, by using these rules, A and T

and G and C, we understood how the molecule replicated.

Everything from then on was clear.

Everything was finished except the hard work, that's to say,

producing an accurate model.

I worked continuously for about four days and, uh...

then came the point where we saw that everything fitted,

and I was so tired I went straight home and went to bed.

The structure of DNA had been found.

A pair of sugar chains, linked by the A, G, C and T bases,

twisted into a double helix.

But, more than that, its structure made it immediately obvious

how DNA could make copies of itself.

If the strand of DNA is split apart, identical copies can be

reassembled because each base can only pair up with its base partner.

There before us

was the answer to one of the

fundamental problems in biology -

how do genes replicate?

And it was very simple...

and you couldn't miss it.

The great paper that was published in the early 1950s with

the structure of DNA is actually a masterpiece and beautifully

understated, ending with what I'm sure must have been a Crick

sentence about the significance of this structure has not escaped us.

We used to occasionally, just...Jim and I, just sit

and look at the molecule and think how beautiful it was.

And I remember on occasion

when Jim gave a talk to a little biophysics club we had.

It's true, they gave him one or two drinks before dinner.

It was rather a short talk because all he could say at the end was,

"Well, you see, it's so pretty. It's so pretty."

The twin successes of the discovery of the structure of DNA and

the mechanism for its replication was a critical moment in science.

I was a student in Edinburgh and, rather cleverly, my tutor told me

to go to the library and to find the most important paper in biology.

I thought, "This man is mad.

"How am I going to do this?"

I walked in, and remember, these were the days

when everything was bound into big volumes,

and I walked past the journal Nature, bound in green,

covered in dust, until you got to the 1953 issue,

and it was battered, it was torn, the back of the cover was come off...

You opened it up and two pages fell out which were black with the

grease of many scientists' fingers, and that was the Watson-Crick paper.

The paper may have rocked the scientific world, but, so far as

the public were concerned, 1953 was a year remembered for bad weather...

The waters rose with the wind...

..the coronation, and the conquering of Mount Everest.

Edmund Hillary, beekeeper from New Zealand...

Tenzing Norgay...

Sherpa from Nepal, conquerors of Everest, May 29th 1953.

The structure of DNA doesn't even get a mention.

Biology really wasn't on the agenda, certainly not on the public agenda or

the press agenda, that was not what they were going to get excited about.

The public were still in love with physics and chemistry,

and they were, so, if you look at the South Ken exhibition

for the Festival Of Britain in 1951,

it's all physics and chemistry.

All the excitement of molecules and then the excitement of radar

and the excitement...not bombs, of course, nothing about bombs.

But biology, toughened up by physics, was on the march.

New vaccines and medicines had whetted the public's appetite

and in 1962, when Crick and Watson, together with Maurice Wilkins,

were awarded the Nobel Prize for Medicine,

the double helix DNA had well and truly arrived.

'The BBC even commissioned this special programme

'about the prize winners.'

This is to be a personal programme about these men.

In a few moments, through television, you will be able to meet them

and judge for yourselves what manner of men they are.

'Biology was now at the forefront of science.

'The possibilities seemed endless.'

I think one can reasonably predict that within the next 20, 30,

50 years, there will be an immense increase of knowledge

about the higher nervous system and about ourselves,

and I think, myself, as a personal belief,

it will radically change the way we think about ourselves as persons

and also, eventually, as people in society.

The old rivalries were put aside, at least for a while.

'Though, since the Nobel Prize was awarded,

'the public memory has been of Crick and Watson,

'and not of the others who helped them over the line.'

But, of course, the Watson-Crick breakthrough was...

..as I've said many times,

a little sort of pinnacle built

on an immense basis of chemistry,

biochemistry, genetics and so on.

Essential work which people like Todd and Chargaff

and many others had to work through

before I was able to put

the three-dimensional structure of DNA on top.

Perhaps least celebrated of all was Rosalind Franklin...

who'd provided the crucial evidence in the form of the B-form

diffraction pattern that provided the final part of the jigsaw.

Franklin had developed ovarian cancer and died in 1958,

and so never knew about the prize or the public excitement around DNA.

It's often said she was unjustly overlooked,

but the Nobel Prize is not awarded posthumously,

so the truth is less clear.

I sometimes wonder what would have happened had Rosalind Franklin

been alive when that Nobel Prize was given.

I don't really know what the outcome of that would have been.

The Nobel Prize is only given to three individuals.

Crick and Watson would have been clear. Um, I suspect...

that Franklin might have trumped Wilkins.

Um, I don't know that for sure.

But that, I think, would have been a definite possibility.

'Though many contributed to the discovery,

'it was ultimately Crick and Watson who made it,

'and they have their own views as to why.'

We weren't in the least afraid of being very candid

to each other, to the point of being rude,

and if you don't have constant interchange

and chatting together and saying what you think about the other people's

ideas to their face, I don't think you can solve problems of this kind.

We sort of pooled the way we looked at things.

We didn't leave it that Jim did the biology and I did the physics.

We both did it together and switched roles and criticised each other,

and this gave us a great advantage over the other people who were

trying to solve it.

You see, what I think is interesting is that Crick and Watson

do insist on how collaborative their own work

was between the two of them, but I don't kind of regard two as much

of a collaboration, and I think it was more of an intense relationship.

Scientific relationship.

And the fact that they absolutely knew that they needed one another.

They each needed the expertise from the other's discipline.

They were absolutely not collaborative scientists outside.

Not in the least. For them, it was a game of who you could beat.

Um, in my hearing,

I heard them laughing about Linus Pauling

and not showing something to Linus Pauling

because otherwise his lab might get there first.

It was all about who'd get there first.

That's not collaborative science.

Maurice Wilkins seems to have been all too willing to collaborate.

He was, perhaps, a naive idealist

and something of a victim of his understated demeanour.

Wilkins was an active Communist in his youth.

He was a spiky, spunky man.

We have no knowledge of that, partly because, presumably, such

activities as he was engaged in, he didn't exactly trumpet abroad.

The only reason I know that he was that kind of man is

because his MI5 file was released in 2010.

And it is clear from there that he was regarded as a threat.

'Uh, Wilkins must have been a much gutsier man in his youth than'

the bits of film that we see of him, would lead one to believe.

Are you interested in music?

Well...

I used to be, but I'm not so interested now.

The reason we think of Maurice Wilkins as this irritable

and actually, irritating man,

when my view is that as a young man he was probably quite dashing

and exciting and Communist and non-aligned, um,

is because of his behaviour around the fact that Rosalind Franklin

just wouldn't play ball, wouldn't be a member of a collaborative lab,

and I'm sure, in Paris, had not been expected to be.

She didn't get it, she didn't sign up for it,

she hadn't signed up for it.

The fact she wasn't allowed in the common room at King's, London,

because women weren't allowed in it, really didn't help.

Um, and therefore Wilkins' collaborative endeavour

embraced everybody outside, but broke down in his own lab.

And, looking back on it, of course,

it's quite clear that

if you regard sort of getting

a structure of DNA as a race,

that we'd lost the race very early on,

because we didn't find it

possible to work together.

Regardless of who won or lost, learning the structure of DNA

and finding out how it might replicate were huge

Nobel Prize winning discoveries.

But knowing these things revealed nothing about how DNA actually

turns mindless chemicals into trees, frogs, parrots and people.

How our genes, now realised to be discrete sections of DNA, give us

unique anatomies and personalities, making each of us who we are.

This became known as the coding problem.

So, the next important problem was the coding problem.

Um, of great interest to Crick.

By this time, Watson had left, gone back to the United States

and Sydney Brenner turned up.

'Sydney Brenner was a reluctant doctor from South Africa

'who'd hung up his stethoscope in favour of research

'as soon as he possibly could.'

'When I grew up in a small town in South Africa,

'where my father was a shoemaker...

'uh, at the age of 15, I went to university and'

I was strongly advised that, for the subject I was interested in,

which people thought was biological chemistry or whatever,

the only jobs existed in medical schools.

And so, I was told, you've got to get a medical degree

because no-one will employ you in a medical school without

a medical degree, which I did.

It was another four years.

It was actually four and a half years

because I failed my finals

in Medicine by diagnosing

one lady as having an acute attack of

the use of Macleans toothpaste,

rather than something else.

I was right, she had actually used

Macleans toothpaste.

I was told to smell her breath and

that's all I could smell. However...

But I did return and did the other

six months and finally passed.

It is a very difficult experience doing science, I think,

in a provincial atmosphere.

All this changed for me when I came to England to work for a PhD.

If I laid out all those great scientists who I had

the privilege of knowing as a child, Sydney Brenner was the funniest one.

Sydney Brenner was just damn funny.

And comfortable to be around. He was a sort of...

very gregarious,

very open...

open-faced, open everything...man.

He rode a huge motorbike, you know.

He was...but he was very sort of stocky and together, and, eh...

I suspect I thought he was quite glamorous.

Now, Sydney Brenner, another one of these brilliant characters

who's also extremely witty and humorous.

I perhaps know Sydney the best of all the characters,

perhaps together with Jim Watson,

and I always seek him out if there's a dinner so I can sit next

to him, cos I will be highly entertained throughout dinner.

Just like humour, you put different things together, you

juxtapose different sorts of ideas and thinking, and they're funny.

It's the way he also carried out his science, he would put different

things together and see how things could emerge from it.

I think they were related - the creativity of humour,

I see also was in his creativity of tackling the coding problem.

Now, the coding problem was enormously attractive,

because, in a sense...

it looked possible that you could crack it, solve it...

without doing any work at all.

There would be something in the sequence that you could then

sit down and write down the code.

Once again, we have a collaboration. This time it's Crick with Brenner.

Watson's gone back to the United States.

During the period that Brenner and Crick were working together,

there was one of the greatest experiments of all time to

determine what's called the triplet nature of the genetic code,

because the problem was this - in DNA,

you have a language made up of four letters...

and in proteins, the language is made up of 20 letters,

so, you can't encode for 20 different letters by 4 alone.

They have to be read either in twos or threes or fours,

and the key experiment was what the number was.

And there was an absolutely genius experiment done,

where the...and Crick explains this,

that he introduced mutations

and if you introduce one mutation then you destroy function,

if you introduce two, you would destroy function,

if you introduce three...you've got the function back again,

because all you did was lose one amino acid and then the rest was OK.

And this is a brilliant piece of abstract reasoning which came

to a concrete conclusion.

'We had discovered that the dye, proflavine,

'does cause additions and deletions of bases in DNA.'

DNA consists of a one-dimensional sequence of

four different building blocks - the bases.

The proteins consist of another language, the amino acids,

of which there are 20.

You need more than one nuclear type to correspond to an amino acid

because there are only four of the first and 20 of the latter.

Indeed, you need at least three,

so we suspected the code was a triplet one.

We also suspected that it was

read from one end, three at a time.

Imagine a gene being composed of the triplet CAT, C-A-T.

So, we have CAT, CAT, CAT, CAT, CAT, CAT, CAT.

You can see that if you delete one of these nucleotides,

beyond the deletion, it's converted into gibberish - ATC, ATC, and so on.

If you delete yet another nucleotide,

you will see you get the second form of gibberish - TCA, TCA.

But if you delete a third nucleotide,

you convert it back to the

original message - CAT, CAT, CAT.

It absolutely worked.

It proved that the code was non-overlapping

and a triplet one, and then, as a joke, we later called

the triplet a codon - the unit corresponding to one amino acid.

So, this was an example of the sort of thinking, the brilliance

of the thinking, that was tackling problems in rather simple ways.

Not fantastically sophisticated equipment and so on,

but brilliant logical reasoning.

What had been accomplished as a result of

Crick and Brenner's discovery,

had opened the door to the ultimate possibility -

that DNA was the book of life.

That the units of inheritance, the genes,

were simply specific sequences of A, C, G and T held in the DNA...

and that it could all be read in its entirety.

But before the final assault on the stuff of life could begin,

another problem needed solving.

Even though the structure of DNA was known, and it had been shown that

DNA coded for proteins,

actually reading the exact order of the bases was proving impossible.

Enter Fred Sanger who, like Crick and Brenner,

was from the Molecular Biology lab in Cambridge.

Fred Sanger, who I also know a little bit, is...

a very humble man, somebody you hardly would notice, you know,

you'd think he was the gardener, I'm sure, in Cambridge rather than,

you know, one of the greatest scientists of his time.

Fred Sanger had already received

a Nobel Prize for discovering

the structure of proteins.

Now, he turned his attention to how to read or sequence

DNA's elusive code.

For Sanger, there was a useful similarity between proteins and DNA.

One became much more interested in nucleic acids.

Again, it was a long chain molecule similar to the proteins.

So, that there was a similar problem there.

And I thought maybe my abilities would be

useful in that field, and we might be able to do something in sequencing

them because, clearly, the sequence was the important thing about them.

I think Fred Sanger,

who really pioneered the notion of sequencing DNA,

using what in retrospect was a clumsy method,

but was the only one that was then available.

Um, he's again a rather forgotten figure by the general public,

and he set out to do something which certainly, when I was a...

student of genetics and I was doing my PhD in genetics, and even

when I started my career in genetics,

seemed fundamentally impossible,

the idea that you could read off a complete genome

just seemed completely out of the window,

let alone that you could read off the human genome.

But Sanger started the job with this method of labelling the bases

one at a time and chipping them off and separating them,

and just reading them ploddingly slowly from one end to another,

and he played a central part in the technical change,

which turned genetics into the modern day equivalent of anatomy.

Fred Sanger's work earned him another Nobel Prize

and opened the door to a tantalising prospect -

that the DNA of an entire species, its genome, could be read.

That its genetic code could be solved.

John Sulston is the archetypal, left-leaning,

Guardian-reading, muesli-eating scientist.

I like muesli, you know?

I'm not doing it for any particular reason, I suppose that's what I mean.

CAT MEOWS

Sulston is a man with a very clear idea of what is

important in life and what is not.

Um, I suppose simple...

rampant, anti-consumerist, well, non-consumerist is the point,

but, on the whole, the presumption is that one is not going to buy

things rather than that you are, if you see what I mean.

Um, what do you want, really? I mean, it's...

It's thinking and reading and talking and all of that that matters,

not actually having stuff, unless the stuff's there for a purpose.

His low-key domestic arrangements give few clues

to his standing in the academic world.

Like Sanger, Wilkins, Watson and Crick,

John Sulston has a Nobel Prize.

It was awarded for cataloguing the development of

every single cell in the nematode worm.

Years of research culminating in 18 months of intensive observation.

Eight hours every day looking at worm cells through his microscope.

I think it's rather fun, really. You know, it's a job of work.

You don't have to worry about what you're going to do the next day,

you know what you're going to do -

you're going to watch some more cells divide.

What he did next was even more tedious.

To work out exactly why the cells behaved as they did,

Sulston needed to understand their genes.

And to do that meant sequencing them.

All of them.

Before we began, people said, "Oh, it's not worth doing that.

"What you ought to be doing is to study real biological problems.

"Look, John, you've done all this cell linaging. You ought to be

"getting mutants and finding out how the cell linage works."

And I said, "Hmm, I'm not sure. I think it's more complicated

"than that. We really need to get at all the genes."

And so I started this business of looking

directly at the genome as a whole.

The nematode worm genome was the proof of concept.

Now, the way was clear for the ultimate prize.

The mild-mannered worm scientist found himself running

the British part of a global effort to read the human genome.

From its outset, Sulston believed that the Human Genome Project

was a noble undertaking for the benefit of everyone.

All the labs met in Bermuda, and we met in Bermuda precisely because it's

a rock in the middle of the Atlantic, so it's a sort of neutral place.

It was in the off season, I should add.

So, we were there and we...I remember standing at the board there,

trying to construct with the assembled labs

a statement to the effect that all of us would release

all of our data all the time and we would not try to take patterns.

And we came out with what have been called the Bermuda Principles

and have actually informed quite a lot of endeavour since.

It was all done in a very gentlemanly

and gentlewomanly way, and everybody was very nice

and decent and I would say rather British about it.

And then suddenly into this calm, Cambridge environment came

a bombshell, this chap called Craig Venter.

Craig Venter had been the team leader of one of the genome groups

in the US, but had decided to go it alone.

There was, he decided, money to be made in the human genome.

There were lots of bio-tech companies that viewed

genes as commodities.

People started assuming you got a patent on a human gene,

you would get a billion-dollar drug.

This went against everything Sulston believed.

Human genes should be owned by the public, not owned by any

particular person or even corporation or even government.

They are publicly owned.

John Sulston now found himself

as the reluctant defender of the people's genome.

He was now in a race.

Every gene that he identified

and published was one that couldn't be patented by Venter.

He secured extra funding to ensure his UK group could complete

a third of the genome, and jetted to America to stiffen

the resolve of the National Institute of Health, who were

on the brink of cutting a deal with their former employee's new company.

I think it did turn things around, because NIH were in fact

making moves to compromise, because they thought they were dead.

They thought Congress would just say, all right,

now you've got a company doing it, you're not allowed to compete.

But by us coming in and saying, well, the Brits are going to do

a third publicly, it really stiffened their backs.

You could see the moral force it had.

Not for the first time in the story of DNA, things got nasty.

John wanted to sequence the human genome.

I wanted to sequence the human genome.

I can't fault him for wanting to do that.

But it was more important to him

to be the one to do it than to

enable it to get done quickly.

I suppose I am anti-capitalist to the point where

I feel that companies are completely unnecessary, yes, that's right.

I think we'd get on very well

if we did all that discovery in universities, frankly.

They gave him the Nobel Prize for counting cells in a worm, right?

The absolutely debilitating diseases - AIDS -

of Africa and other developing countries, they cannot be dealt with

on a capitalist basis, because there is no market, there is no money.

So, you now have two programmes going in parallel.

One, a public programme, set up for the public good,

a second, a private programme,

ultimately leading to the public good,

but in the meantime going to make a lot of money.

Our efforts are at least equally important, if not more so,

because it forced them to get going

and get off their butts and actually do something.

Ah, yes, "I lit a fire under the human genome."

They always like that image!

But I think objectively the facts speak against it.

I really don't think that it was helpful.

I think we'd have finished pretty much next year anyway.

And without all the fuss.

Sulston is a much, much more traditional scientist,

much more of the Maurice Wilkins type, the sharing,

collaborative, making the world a better place.

I wouldn't have thought it would have crossed his mind that he

could make his fortune.

I think Venter saw very early on he could make his fortune.

I don't think it's a bad thing, but he saw it.

Well, Venter was simply, you know, he was... How can I summarise it?

Venter was an American. Sulston was British.

That, I think, summarises the entire problem.

But, ultimately, it was politicians - British and American -

who came down on the side of the people's genome.

..Genome science and its benefits will be directed toward making life

better for all citizens of the world, never just a privileged few.

In 2000, Bill Clinton

and Tony Blair announced that the race was effectively over

and that no-one would be making any money by patenting genes.

When the public project guys,

ie, you and everyone else, got Tony Blair

and Bill Clinton to make that announcement early last year,

when they said they would like to see unencumbered access

to this data, it wiped 150 off Venter's company's share price.

It's a natural thing that that would drop.

But it must have made you smile, put a smile on your face.

-HE CHUCKLES

-Well, it has now!

Well, yes, but the trouble is, at the same time - it's true, I smile,

but these are minor victories or skirmishes in the whole thing.

Much has been made of the importance of the reading of the human genome,

of the medical benefits that will emerge from its now cracked code.

That maybe it even holds the secret of life itself.

We cannot understand what life is without understanding

the genome, but it is only one part of the problem.

And we need also to understand how living organisms work,

how cells work, how tissues and organs work.

Without the human genome sequence, we can hardly address the problem.

It is crucial, but it is not the only thing we need to know.

Since the middle of the last century,

the murky business of inheritance has been dragged out

of an age of near witchcraft to one where individual groups

of atoms, in what was once considered the "stupid molecule",

are now recognised as agents of heredity.

Crick and Watson's identification of DNA structure,

informed by the crystallography done by the King's group,

Sydney Brenner's solution to the coding problem,

Fred Sanger's work on sequencing, and the global effort to read

the human genome, has revealed what some might call the code of life.

But, in reality, DNA,

coding and genomics is only the start of the next chapter.