0:00:04 > 0:00:09In 1953, scientists discovered the structure of DNA,
0:00:09 > 0:00:12and changed for ever our understanding of genetics,
0:00:12 > 0:00:13of heredity,
0:00:13 > 0:00:15and even of life itself.
0:00:18 > 0:00:21It was the beginning of a revolution in biology
0:00:21 > 0:00:25that led eventually to the sequencing of the human genome,
0:00:25 > 0:00:28the genetic code of life that defines our species.
0:00:31 > 0:00:33But this was a revolution with a difference.
0:00:33 > 0:00:37'These critical scientific discoveries were among the first
0:00:37 > 0:00:41'to be documented on television and radio.'
0:00:41 > 0:00:43Dr Wilkins, what do you actually do?
0:00:43 > 0:00:47The main thing in my kind of scientific work is to be able to
0:00:47 > 0:00:50fiddle with a thing, go on fiddling with it and fiddle, fiddle,
0:00:50 > 0:00:52until everyone else has given up.
0:00:54 > 0:00:58'In an era before spin doctors and PR, the scientists were prepared to
0:00:58 > 0:01:02'talk about their work - and each other - with extraordinary candour.'
0:01:02 > 0:01:05She came toward me and I thought she was going to hit me!
0:01:05 > 0:01:08Oh, God! Who hit who?!
0:01:08 > 0:01:11Their stories, buried in the BBC archives,
0:01:11 > 0:01:14reveal the people behind the science.
0:01:14 > 0:01:18In few moments, through television you will be able to meet them
0:01:18 > 0:01:21and judge for yourselves what manner of men they are.
0:01:21 > 0:01:23Passionate, ambitious men and women,
0:01:23 > 0:01:27driven by intense, sometimes bitter rivalries.
0:01:27 > 0:01:30Scientists sat back and got fat and happy
0:01:30 > 0:01:31getting tens of millions of dollars,
0:01:31 > 0:01:34and I put John in that category.
0:01:34 > 0:01:37We have already released two thirds of the human genome
0:01:37 > 0:01:41into the public domain, and he's released nothing at all.
0:01:41 > 0:01:44The archive reveals that truly to understand
0:01:44 > 0:01:45how the discoveries were made,
0:01:45 > 0:01:49it's essential first to understand the people who made them.
0:01:50 > 0:01:52This is the story of those scientists,
0:01:52 > 0:01:56of the men and women who set out to crack the code of life...
0:01:56 > 0:01:58Happy days!
0:01:59 > 0:02:01..told in their own words.
0:02:15 > 0:02:18Do electrons think?
0:02:20 > 0:02:23Electrons are charged particles,
0:02:23 > 0:02:29the minutest we find in analysing the ultimate constitution of matter.
0:02:30 > 0:02:36To think that such a particle can think is so absurd...
0:02:36 > 0:02:39that I might give the answer, no, and have my talk over.
0:02:40 > 0:02:41However...
0:02:41 > 0:02:44This is one of very few recordings made of a man called
0:02:44 > 0:02:45Erwin Schrodinger.
0:02:47 > 0:02:50Schrodinger had served in the Austrian army in the First World War
0:02:50 > 0:02:53and later made a name for himself in physics
0:02:53 > 0:02:55as the inventor of a theoretical cat.
0:02:59 > 0:03:01The odd thing is that here is Schrodinger,
0:03:01 > 0:03:05a world famous physicist, musing on a biological problem -
0:03:05 > 0:03:09the nature of consciousness, of what it means to be human.
0:03:10 > 0:03:15Mind per se cannot play the piano.
0:03:15 > 0:03:19Mind per se cannot move a finger of a hand.
0:03:20 > 0:03:25This leaves us with the outlook that our body is as automatic or
0:03:25 > 0:03:30non-automatic as any inanimate piece of matter...
0:03:30 > 0:03:33only infinitely more complicated than even the most
0:03:33 > 0:03:35ingenious man-made machine.
0:03:37 > 0:03:42Schrodinger is a name in physics to conjure with.
0:03:42 > 0:03:45I think even members of a quite broad general public would hear
0:03:45 > 0:03:50the name Schrodinger, associate it with Einstein, it goes with...
0:03:50 > 0:03:54tough physics, it goes with quantum physics, and the fact
0:03:54 > 0:04:01that in 1944 Schrodinger published a book called "What Is Life?"
0:04:01 > 0:04:07about biology, and how biology would yield to scientific attention,
0:04:07 > 0:04:12that physics could unpack biology.
0:04:12 > 0:04:16That was a light bulb moment for physicists.
0:04:16 > 0:04:19I think it's a universal among all biologists
0:04:19 > 0:04:21that they've got physics envy.
0:04:21 > 0:04:24Um, they really wish they were physicists,
0:04:24 > 0:04:25but they know they're not clever enough.
0:04:25 > 0:04:28I know I'm not clever enough to be a physicist.
0:04:28 > 0:04:31As Lord Rutherford once said, "There is only physics.
0:04:31 > 0:04:34"Everything else is stamp collecting."
0:04:34 > 0:04:37In writing "What Is Life?", Schrodinger helped
0:04:37 > 0:04:41shake off biology's stamp collecting image and launched a period
0:04:41 > 0:04:43that would bring it to the forefront of science.
0:04:44 > 0:04:49What I think was really useful about that book was the was the rigour of
0:04:49 > 0:04:52physical thinking, the thinking of a physicist,
0:04:52 > 0:04:55which allowed the question to be properly framed.
0:04:55 > 0:04:59What he emphasised was the importance of thinking
0:04:59 > 0:05:03about the transmission of information from one generation to another,
0:05:03 > 0:05:06that was essentially the nature of heredity,
0:05:06 > 0:05:11and how you might think about coding information in molecules.
0:05:14 > 0:05:17During the Second World War, Erwin Schrodinger was
0:05:17 > 0:05:20head of Theoretical Physics at Trinity College, Dublin,
0:05:20 > 0:05:24and it was here, in neutral Ireland, that he set about unleashing
0:05:24 > 0:05:27the rigour of physics on the messy business of life.
0:05:29 > 0:05:32Schrodinger talks about life in physical terms,
0:05:32 > 0:05:37about life being an islands of order in a sea of disorder, and that's
0:05:37 > 0:05:40perhaps the best definition of life I can think of,
0:05:40 > 0:05:44and he also pointed out that it was a kind of twofold process,
0:05:44 > 0:05:48a living creature itself will die and return to disorder,
0:05:48 > 0:05:53but will have passed on its information in a molecule,
0:05:53 > 0:05:56which, at that time, wasn't known, so there was a code involved too.
0:05:56 > 0:06:00So, those two things - entropy and the code - both of which are
0:06:00 > 0:06:03physical ideas, really, mathematical ideas, I think,
0:06:03 > 0:06:06formed a lot of modern biology.
0:06:06 > 0:06:08The same laws of physics
0:06:08 > 0:06:12and physical chemistry hold within the living body as outside.
0:06:14 > 0:06:16The simplest spontaneous bodily movement...
0:06:17 > 0:06:19..say, the lifting of my arm,
0:06:19 > 0:06:23would require the planned collaboration of billions
0:06:23 > 0:06:27of single atoms in their undetermined swerves
0:06:27 > 0:06:30if they should bring about the integrated action.
0:06:35 > 0:06:38Science had started to make inroads into the secrets of life
0:06:38 > 0:06:41in the previous century.
0:06:41 > 0:06:44Charles Darwin had proposed his theory of evolution,
0:06:44 > 0:06:48and Gregor Mendel had worked out the principle of how characteristics
0:06:48 > 0:06:53were passed from one generation to the next biologically through genes,
0:06:53 > 0:06:57though he had no idea what genes actually were or how they worked.
0:06:58 > 0:07:00Then things went wrong.
0:07:02 > 0:07:05The way that these ideas were misapplied is perhaps
0:07:05 > 0:07:10the clearest example ever of two rights making one colossal wrong.
0:07:11 > 0:07:16As demonstrated by leading British biologist Professor Julian Huxley.
0:07:17 > 0:07:21What is the bearing of the laws of heredity upon human affairs?
0:07:21 > 0:07:24Eugenics provides the answer.
0:07:24 > 0:07:27Eugenics was a 19th century idea that spawned a movement whose
0:07:27 > 0:07:31aim was to ensure that only the fittest survive.
0:07:31 > 0:07:34An attempt at biological engineering.
0:07:34 > 0:07:38Breeding out those deemed to be a drain on society.
0:07:38 > 0:07:42People labelled at the time as defective.
0:07:42 > 0:07:44Here is a man who,
0:07:44 > 0:07:47although normal, comes from a mentally defective family.
0:07:47 > 0:07:50Here is his wife who is also normal.
0:07:50 > 0:07:52They have had 17 children.
0:07:53 > 0:07:55Let us examine the pedigree of these children.
0:07:55 > 0:07:59Five of them died in infancy, three are still too young
0:07:59 > 0:08:04for an opinion to be formed of their mental state, a boy and two girls.
0:08:04 > 0:08:08Only two of the remaining children are normal, a man and a girl.
0:08:08 > 0:08:11The remaining seven children are all mental defectives.
0:08:13 > 0:08:16The people who set up the eugenics movement,
0:08:16 > 0:08:19who were studying human heredity, in retrospect knew nothing,
0:08:19 > 0:08:22and I mean nothing, possibly less than nothing,
0:08:22 > 0:08:25because what they did know was simply wrong,
0:08:25 > 0:08:29but that didn't stop them from going into these dreadful practices.
0:08:31 > 0:08:34In institutions such as this all over the country,
0:08:34 > 0:08:35mental defectives are cared for.
0:08:36 > 0:08:41Once such children have been born we must do the best we can for them.
0:08:41 > 0:08:43But it would have been better by far, for them
0:08:43 > 0:08:47and for the rest of the community, if they had never been born.
0:08:50 > 0:08:54I think that...before World War II,
0:08:54 > 0:08:58biology was somewhat of a backwater, not least because the
0:08:58 > 0:09:00interwar period is a period of
0:09:00 > 0:09:05frenetic development of military hardware.
0:09:05 > 0:09:06The scientific community,
0:09:06 > 0:09:13which was growing in stature was regarded now as the great hope.
0:09:13 > 0:09:19It was what was going to defend Europe, defend the United States.
0:09:19 > 0:09:23The biological sciences were really, I think...
0:09:24 > 0:09:26..on the back burner.
0:09:26 > 0:09:27The bright, young men -
0:09:27 > 0:09:32and I use the term advisedly - went into physics and chemistry.
0:09:34 > 0:09:36Three...two...one.
0:09:36 > 0:09:37And go.
0:09:41 > 0:09:42The irony was that
0:09:42 > 0:09:46while Schrodinger used physics to explain what it means to be alive,
0:09:46 > 0:09:49most of his "bright, young colleagues"
0:09:49 > 0:09:52were using physics as a means of snuffing life out
0:09:52 > 0:09:54on an apocalyptic scale.
0:09:55 > 0:09:59In the course of World War II, literally every
0:09:59 > 0:10:02able and eminent scientist was working for the war effort,
0:10:02 > 0:10:03and I think that out of that
0:10:03 > 0:10:07came a thoughtfulness about the meaning of life on the part
0:10:07 > 0:10:11of physicists, that they maybe thought more about philosophy,
0:10:11 > 0:10:14and I do think it characterises the men of this generation.
0:10:14 > 0:10:17And coming out of the war into a time of promise and peace,
0:10:17 > 0:10:20wouldn't you then want to go where those thoughts had taken you?
0:10:20 > 0:10:21And THAT was biology.
0:10:28 > 0:10:32One such scientist was Maurice Wilkins, an English physicist who'd
0:10:32 > 0:10:36spent much of the war at Los Alamos developing the atomic bomb.
0:10:37 > 0:10:41Certainly, the atomic bomb business was a stimulus for getting
0:10:41 > 0:10:44out of physics and into something else,
0:10:44 > 0:10:48and I think the immense destructive forces which were
0:10:48 > 0:10:54discovered in the atomic bomb were rather appalling, and so I felt
0:10:54 > 0:11:00that I wanted to work on things which were living and growing for a change.
0:11:00 > 0:11:03Dr Wilkins, what do you actually do?
0:11:03 > 0:11:05I mean, what do you actually do in your work?
0:11:05 > 0:11:09The main thing in my kind of scientific work is to be able
0:11:09 > 0:11:12to fiddle with a thing, go on fiddling with it and
0:11:12 > 0:11:15fiddle, fiddle until everyone else has given up.
0:11:18 > 0:11:21Wilkins settled into academic life at King's College, London,
0:11:21 > 0:11:25where he began fiddling with crystallography in a bid to
0:11:25 > 0:11:28shed some light on the mechanism of genetics,
0:11:28 > 0:11:31on how what Schrodinger called a code might work.
0:11:33 > 0:11:34Crystallography,
0:11:34 > 0:11:38the idea that you could shoot x-rays at a copper sulphate crystal
0:11:38 > 0:11:40or common salt crystals,
0:11:40 > 0:11:42and by looking at the way they bounced off, you could
0:11:42 > 0:11:46reconstitute what the structure of the atoms in the crystal were.
0:11:46 > 0:11:49That was pretty astounding stuff
0:11:49 > 0:11:52and he made enormous advances in physics,
0:11:52 > 0:11:53and then somebody had the idea -
0:11:53 > 0:11:55Wilkins was one of the somebodies -
0:11:55 > 0:11:57of using that on the much messier system
0:11:57 > 0:12:01which is biology, and to everybody's great surprise,
0:12:01 > 0:12:04it turned out that some molecules were really quite amenable to
0:12:04 > 0:12:07being treated in this way, and one of those molecules, which is
0:12:07 > 0:12:10very abundant in the body, is DNA.
0:12:10 > 0:12:12It was initially called the stupid molecule
0:12:12 > 0:12:16because it seemed to be everywhere, you know, it was in all cells,
0:12:16 > 0:12:18and yet it didn't seem to do anything.
0:12:22 > 0:12:26Then, in 1944, a group in America performed an experiment,
0:12:26 > 0:12:30which showed that DNA wasn't quite as stupid as everyone had thought.
0:12:36 > 0:12:38They took strains of a pneumococcus bacterium
0:12:38 > 0:12:42and the two strains differed - one was smooth, one was rough -
0:12:42 > 0:12:47and what they did is they extracted DNA from one of those strains,
0:12:47 > 0:12:49sprinkled it on the other,
0:12:49 > 0:12:53and transformed the character of that into the previous one,
0:12:53 > 0:12:56and therefore concluded that it was the DNA that conveyed that
0:12:56 > 0:12:59information, it wasn't protein, it wasn't lipid,
0:12:59 > 0:13:02it wasn't the other components - it was DNA.
0:13:02 > 0:13:06DNA was the source of Schrodinger's code.
0:13:06 > 0:13:08It was where inheritance was written.
0:13:08 > 0:13:11So, now the race was on to discover how it worked.
0:13:13 > 0:13:16It was already known that the DNA was made of simple sugars,
0:13:16 > 0:13:18some phosphate groups, and just
0:13:18 > 0:13:20four other chemical structures -
0:13:20 > 0:13:23the so-called bases of adenine,
0:13:23 > 0:13:26thymine, cytosine and guanine.
0:13:27 > 0:13:29But how they all fitted together was a mystery...
0:13:31 > 0:13:33..and the relationship between DNA and genes,
0:13:33 > 0:13:36the conceptual carriers of characteristics from one generation
0:13:36 > 0:13:38to the next, was another.
0:13:39 > 0:13:42These problems were what Maurice Wilkins was trying to solve
0:13:42 > 0:13:43with his X-rays.
0:13:52 > 0:13:55But Wilkins wasn't the only physicist in the game.
0:13:55 > 0:13:58In Cambridge, another out of work weapons designer was
0:13:58 > 0:14:01casting his eye over the same problem.
0:14:01 > 0:14:04His name was Francis Crick.
0:14:04 > 0:14:08But, unlike Wilkins, Crick was not motivated by the horror of war.
0:14:08 > 0:14:10He just fancied a change.
0:14:14 > 0:14:18After the war, I was, of course, in the Admiralty, but I really didn't
0:14:18 > 0:14:21want to go on being a scientific civil servant, as I was, for
0:14:21 > 0:14:26the rest of my life, so I decided, "Well, what a marvellous opportunity.
0:14:26 > 0:14:30"Here you are at the age of 30, you can go into what you like."
0:14:30 > 0:14:32But the problem was, what did I like?
0:14:32 > 0:14:37I noticed that I was telling some of my young naval officer friends things,
0:14:37 > 0:14:40I remember one about antibiotics, and it occurred to me
0:14:40 > 0:14:43one day that, "You don't know anything about antibiotics!
0:14:43 > 0:14:45"You're just gossiping about it."
0:14:45 > 0:14:47So, I decided that the gossip test is a good one,
0:14:47 > 0:14:51that what you're really interested in is what you gossip about.
0:14:51 > 0:14:54So, I looked at what I was gossiping to people about in science
0:14:54 > 0:14:57and it boiled down really to two regions - one was the
0:14:57 > 0:15:00borderline between the living and the non-living,
0:15:00 > 0:15:03and the other was the way the human brain worked.
0:15:03 > 0:15:06I knew nothing about either of the subjects.
0:15:06 > 0:15:08I decided it had better be molecular biology,
0:15:08 > 0:15:10it was nearer to what I knew.
0:15:10 > 0:15:14And so that's how I decided to work on molecular biology.
0:15:15 > 0:15:17Well, I have to declare an interest,
0:15:17 > 0:15:20which is I knew Francis Crick from my childhood.
0:15:20 > 0:15:25He, as a young man, during World War II had been allocated,
0:15:25 > 0:15:29as a very brilliant, young physicist,
0:15:29 > 0:15:34had been allocated a key role in charge of a section that was
0:15:34 > 0:15:40developing deep sea mines to blow up enemy shipping.
0:15:41 > 0:15:45And he, being the kind of man he was, a numbers man,
0:15:45 > 0:15:49decided that he didn't want to do mines that blew up all of shipping.
0:15:49 > 0:15:51He wanted to develop a mine
0:15:51 > 0:15:53that would only explode under minesweepers
0:15:53 > 0:15:57and he did indeed do that, he did it successfully and there are those who
0:15:57 > 0:16:00say that he helped win the war at sea because knocking out
0:16:00 > 0:16:03the minesweepers was exactly what was needed.
0:16:03 > 0:16:05Admiralty never came round to it.
0:16:05 > 0:16:10Admiralty thought of him as an uppity, uncontrollable,
0:16:10 > 0:16:13difficult young man who wouldn't take orders.
0:16:13 > 0:16:18He ran his section with great authority...
0:16:18 > 0:16:21So, here's this young man who's been given lots of authority,
0:16:21 > 0:16:24way ahead of what he would have got in a lab,
0:16:24 > 0:16:27and also has learned to challenge authority and get away with it,
0:16:27 > 0:16:30and indeed be able to say he was right.
0:16:30 > 0:16:32'So, he comes out of the war
0:16:32 > 0:16:36'and he's a very different kettle of fish from Wilkins.'
0:16:36 > 0:16:38Amazingly...
0:16:38 > 0:16:43links up really fortuitously with a madcap young man from America
0:16:43 > 0:16:48who went to university at 16 and never toed the line.
0:16:48 > 0:16:51They form an intellectual...couple.
0:16:51 > 0:16:54I don't want to say collaboration, they don't collaborate.
0:16:54 > 0:16:57They're a sort of, you know, couple.
0:16:57 > 0:17:00The madcap American was Jim Watson,
0:17:00 > 0:17:03a brilliant biochemist at the start of his career who'd recently
0:17:03 > 0:17:07received his PhD at the unlikely age of 22.
0:17:07 > 0:17:11'My first couple of months in Cambridge were terribly chaotic.
0:17:12 > 0:17:15'I went to the digs Max had helped get me at Park Place,
0:17:15 > 0:17:20'a dismal place where the landlady wanted me to take off my shoes
0:17:20 > 0:17:22'when I came in at night and didn't want me
0:17:22 > 0:17:24'to flush the toilet after ten in the evening.
0:17:24 > 0:17:27'After a rather short while, I wasn't very sympathetic
0:17:27 > 0:17:29'and she threw me out.'
0:17:29 > 0:17:32But I think the main thing was that none of these things bothered me
0:17:32 > 0:17:33because I'd met Francis.
0:17:33 > 0:17:37MUSIC: "Je T'Aime...Moi Non Plus" by Serge Gainsbourg & Jane Birkin
0:17:43 > 0:17:46'Jim was certainly our first American visitor and'
0:17:46 > 0:17:50as soon as we met, we found that, although we had very
0:17:50 > 0:17:54different backgrounds, we had a lot of things in common.
0:17:54 > 0:17:56Neither of us were trained for what really interested us.
0:17:56 > 0:17:59We both wanted to find the gene, we weren't organic chemists,
0:17:59 > 0:18:02we weren't anything else. We just wanted to do the best...
0:18:02 > 0:18:04To do the most sensible thing.
0:18:04 > 0:18:07Francis Crick was a wild man,
0:18:07 > 0:18:10a man who encouraged wild behaviour around him.
0:18:10 > 0:18:14I was a student at Cambridge when I got to know the family well,
0:18:14 > 0:18:17and it was a big joke that
0:18:17 > 0:18:20if you stayed out overnight as an undergraduate in those
0:18:20 > 0:18:23ancient days, you had to stay with an MA of the university,
0:18:23 > 0:18:25so, you could go to one of Crick's
0:18:25 > 0:18:26insanely wild parties
0:18:26 > 0:18:28and stay the night because he was an
0:18:28 > 0:18:30MA of the University of Cambridge,
0:18:30 > 0:18:34but I'm telling you, I shouldn't have been at those parties aged 18!
0:18:36 > 0:18:41And the thing about Jim Watson was that he was a prude
0:18:41 > 0:18:46and he was hopeless with girls and he just tagged along with Francis.
0:18:46 > 0:18:49He just always wanted Francis to somehow get him
0:18:49 > 0:18:50into the thick of it, but he never did cos
0:18:50 > 0:18:54he was sort of somehow too pusillanimous himself.
0:18:54 > 0:18:57Crick and Watson's intellectual common ground was
0:18:57 > 0:19:02in the idea that they might be able to determine the structure of DNA.
0:19:02 > 0:19:04That challenge was something Jim Watson had first heard
0:19:04 > 0:19:08described by Maurice Wilkins at a conference he'd attended in Vienna.
0:19:10 > 0:19:14Then I suddenly became aware there existed someone...
0:19:14 > 0:19:18who actually was trying to solve the structure of DNA, which...
0:19:18 > 0:19:21seemed to be the likely candidate for the gene.
0:19:21 > 0:19:25But Maurice was serious, deadly serious, and...
0:19:25 > 0:19:26I tried to talk to him,
0:19:26 > 0:19:32but Maurice is English, he doesn't talk much to strangers,
0:19:32 > 0:19:36and so I left and sort of had a vague feeling that it would be nice
0:19:36 > 0:19:41if I could work with Maurice, but it wasn't...it wasn't the sort of...
0:19:41 > 0:19:44obvious coming together of like minds.
0:19:44 > 0:19:45That's a carbon atom...
0:19:45 > 0:19:49'Crick and Watson's approach to the problem was to try to imagine
0:19:49 > 0:19:54'how all the known parts might fit together, build scale models,
0:19:54 > 0:19:55'and talk about them.'
0:19:55 > 0:20:01Well, Francis likes to talk...it's his dominant quality, I think.
0:20:01 > 0:20:04He doesn't stop unless he gets tired or he thinks the idea is no good
0:20:04 > 0:20:08and so, since we hope to solve the structure by talking our way
0:20:08 > 0:20:12through it, Francis was the ideal person to do it.
0:20:13 > 0:20:16In London, Maurice Wilkins and the King's group
0:20:16 > 0:20:18were actually doing something about the problem.
0:20:19 > 0:20:23Ray Gosling was a research student at King's at the time
0:20:23 > 0:20:25and helped with the X-ray crystallography experiments.
0:20:28 > 0:20:32This is the original camera that we...
0:20:32 > 0:20:35took the first DNA specimens on in this lab.
0:20:35 > 0:20:40And we had a fairly weak X-ray beam so that we needed
0:20:40 > 0:20:44lots of material in the beam to get a diffraction pattern.
0:20:44 > 0:20:46Now, you see there...
0:20:46 > 0:20:51a specimen made with 30 to 40 fibres of DNA wrapped around this
0:20:51 > 0:20:55little metal jig there, and we place that in front of the X-ray set...
0:20:58 > 0:21:01..and after about a day, we had a diffraction pattern.
0:21:02 > 0:21:04The data the experiments produced
0:21:04 > 0:21:07was found in these fuzzy photographs -
0:21:07 > 0:21:11pictures of how the X-rays were scattered by the DNA crystals.
0:21:13 > 0:21:14These, it was hoped,
0:21:14 > 0:21:18would provide the crucial evidence for DNA's elusive structure.
0:21:20 > 0:21:23But the results they were getting were disappointing.
0:21:23 > 0:21:25The pictures were too fuzzy.
0:21:26 > 0:21:29So, because none of the group were expert in the technique,
0:21:29 > 0:21:31an expert was hired.
0:21:32 > 0:21:38In 1951, Rosalind Franklin arrived to help sharpen up the photos.
0:21:38 > 0:21:40Or so they thought.
0:21:40 > 0:21:43She actually arrived while Wilkins was away, which was
0:21:43 > 0:21:47probably about the most unfortunate mishap in the whole story.
0:21:47 > 0:21:49Wilkins was away, he was expecting her,
0:21:49 > 0:21:52but she had come much later than she was supposed to come
0:21:52 > 0:21:57because her work took longer to finish in Paris than she'd expected.
0:21:57 > 0:21:59And she arrived in the laboratory,
0:21:59 > 0:22:02she decided what she wanted to do, she'd decided who she was
0:22:02 > 0:22:06going to work with, indeed, who was going to be her graduate student.
0:22:06 > 0:22:09When she came first to the lab, Wilkins was in America and
0:22:09 > 0:22:13the interview took place in Professor Randall's office
0:22:13 > 0:22:16between Alex Stokes, myself meeting Rosalind for the first time.
0:22:16 > 0:22:20And I can remember my own feelings at that interview,
0:22:20 > 0:22:23it was very clear that, as a research student,
0:22:23 > 0:22:27I was being formally passed from one to the other and that,
0:22:27 > 0:22:30not only was she being given the problem, she was being given
0:22:30 > 0:22:33an assistant to work with her on the problem.
0:22:33 > 0:22:36Rosalind didn't see herself as collaborating with Maurice,
0:22:36 > 0:22:38but there was always this tension between the two.
0:22:38 > 0:22:41I think Maurice, uh...
0:22:41 > 0:22:44when he brought Rosalind in, afterwards he regretted he'd
0:22:44 > 0:22:47given away his problem, that is, he thought he needed help,
0:22:47 > 0:22:49brought in someone who was a trained crystallographer
0:22:49 > 0:22:52and then discovered that it wasn't his problem any more.
0:22:52 > 0:22:54So, it was a catastrophe.
0:22:54 > 0:22:56She didn't share and he didn't share,
0:22:56 > 0:22:59and I have no idea whether she was a sharing person or not,
0:22:59 > 0:23:02but certainly the conditions under which she was working meant
0:23:02 > 0:23:05that putting her arm over her work was absolutely,
0:23:05 > 0:23:07you know, the starting point.
0:23:07 > 0:23:10She certainly wasn't going to let Wilkins have what she was doing.
0:23:10 > 0:23:12But how did you get on with Rosalind?
0:23:12 > 0:23:14- Terrible!- Ha, ha!
0:23:14 > 0:23:17You make out, Jim, you're sort of some male chauvinist pig,
0:23:17 > 0:23:19but I think the real thing was, it wasn't that, it was
0:23:19 > 0:23:22the fact that she didn't think you knew much crystallography.
0:23:22 > 0:23:25To which she was totally correct.
0:23:25 > 0:23:28Rosalind was rather prepared to discount them
0:23:28 > 0:23:31as being very serious competitors. I think there was
0:23:31 > 0:23:34a general impression in the scientific community
0:23:34 > 0:23:36at that time that they were, uh...
0:23:37 > 0:23:40..like butterflies, they were...
0:23:40 > 0:23:45flipping around with lots of brilliance, but not much solidity.
0:23:45 > 0:23:52And, obviously, in retrospect, this was a sort of ghastly misjudgement.
0:23:52 > 0:23:55It was a ghastly misjudgement because the Cambridge butterflies
0:23:55 > 0:23:58were actually getting somewhere by building their models,
0:23:58 > 0:24:02talking, and perhaps more importantly, listening.
0:24:04 > 0:24:06In those days, there was
0:24:06 > 0:24:10a brilliant young theoretical chemist in Cambridge called John Griffith.
0:24:10 > 0:24:12He died quite recently.
0:24:12 > 0:24:17And he'd found that adenine stacked nicely on top of thymine
0:24:17 > 0:24:19and guanine on top of cytosine.
0:24:19 > 0:24:22He'd been thinking along those lines at the time, but I didn't know
0:24:22 > 0:24:25that, so I said to him, "That's all right, that's perfect.
0:24:25 > 0:24:28"That's all we need for our replication scheme."
0:24:28 > 0:24:32The relative amount of the four bases in DNA had been worked
0:24:32 > 0:24:35out by a nucleic acid chemist called Erwin Chargaff,
0:24:35 > 0:24:37a few years before this time.
0:24:37 > 0:24:41And it happened he was passing through Cambridge
0:24:41 > 0:24:43and he told us about his results,
0:24:43 > 0:24:48which were that the amount of adenine equalled the amount of thymine,
0:24:48 > 0:24:52and the amount of guanine equalled the amount of cytosine in all
0:24:52 > 0:24:54sorts of DNA, wherever he looked.
0:24:54 > 0:24:58Although the other ratios were all over the place.
0:24:58 > 0:25:02Well, the effect on me was electric because I saw immediately
0:25:02 > 0:25:06that this is what you'd expect from a scheme like John Griffith's.
0:25:07 > 0:25:10So, I was very excited. I didn't mention it to Chargaff at the time,
0:25:10 > 0:25:13because it was work I was doing with John Griffith,
0:25:13 > 0:25:17but when we checked it all out, we could see the two fitted together.
0:25:24 > 0:25:26Crick and Watson now got word from the US
0:25:26 > 0:25:29that the legendary chemist Linus Pauling was
0:25:29 > 0:25:31also working on the DNA problem.
0:25:32 > 0:25:36Armed with a draft copy of Pauling's soon to be published ideas,
0:25:36 > 0:25:39Watson went to King's to discuss them with Wilkins.
0:25:41 > 0:25:44Maurice read it and, in his usual way,
0:25:44 > 0:25:46didn't convey sort of enthusiasm one way or the other,
0:25:46 > 0:25:49but I guess he sort of said he didn't think Linus
0:25:49 > 0:25:51was going to get the right structure.
0:25:51 > 0:25:54At the same time however, he sort of let loose the bombshell, at least
0:25:54 > 0:25:59to me, when he said there was two types of DNA X-ray photographs.
0:25:59 > 0:26:02There was the form which I knew about called the A-form, which gave this
0:26:02 > 0:26:06crystalline pattern, but there was this second from called the B-form.
0:26:06 > 0:26:08He opened a drawer, took out a photograph and, boy,
0:26:08 > 0:26:11I could hardly believe it! It was a perfect helix.
0:26:11 > 0:26:14It was a cross-like pattern and the told me that they
0:26:14 > 0:26:18repeated it and that meant there was a helix.
0:26:18 > 0:26:21I thought also that I should go and see Rosalind.
0:26:21 > 0:26:25It was clear that she was annoyed at my trying to tell her something about
0:26:25 > 0:26:27crystallography, and she came toward me
0:26:27 > 0:26:29and I thought she was going to hit me, so I quickly got out,
0:26:29 > 0:26:33at which point Maurice was coming around and she almost hit Maurice!
0:26:33 > 0:26:35Oh, God! Who hit who?!
0:26:35 > 0:26:37I don't think anybody hit anybody, actually.
0:26:37 > 0:26:39Some people may have thought
0:26:39 > 0:26:41someone was going to hit somebody,
0:26:41 > 0:26:43but, um...
0:26:43 > 0:26:44there certainly weren't
0:26:44 > 0:26:45very friendly feelings.
0:26:47 > 0:26:50Watson escaped back to Cambridge in one piece, carrying with him
0:26:50 > 0:26:54the memory of the B-form photograph that Franklin had taken
0:26:54 > 0:26:56and Wilkins had shown him.
0:26:58 > 0:27:00Straightaway, he started a new model.
0:27:00 > 0:27:02So, I cut some things out of cardboard
0:27:02 > 0:27:05and made the right shapes and then pasted things on, which would
0:27:05 > 0:27:09indicate hydrogen atoms, and then I think I went off and played tennis.
0:27:09 > 0:27:11I would do maybe three hours a day.
0:27:11 > 0:27:14It was hard to get at it in the morning, but...
0:27:14 > 0:27:17Because by the time you get in there was morning coffee,
0:27:17 > 0:27:20then you'd go for lunch, have a walk, and then I'd come back
0:27:20 > 0:27:22and build the model and, sort of,
0:27:22 > 0:27:24Francis was working on his thesis...
0:27:24 > 0:27:28I would look over my shoulder to try and see what Jim was doing.
0:27:28 > 0:27:30I guess it's awfully hard to give up an idea of your own, so
0:27:30 > 0:27:32I started putting the phosphates in the centre,
0:27:32 > 0:27:35maybe because it was sort of like a Pauling structure.
0:27:35 > 0:27:38Maybe, if we would have used ions we'd get somewhere,
0:27:38 > 0:27:40but Francis really wasn't comfortable with this,
0:27:40 > 0:27:43and told me, why don't I try putting the phosphates on the outside?
0:27:43 > 0:27:47I can't really remember why you said that, Francis.
0:27:47 > 0:27:49Well, it's because, I think, Jim, that, you know,
0:27:49 > 0:27:51you were obsessional about having them
0:27:51 > 0:27:56on the inside and you produced a lot of phony arguments as to why
0:27:56 > 0:27:59basic groups from protamines had to go in,
0:27:59 > 0:28:01and in all collaboration, it's very important
0:28:01 > 0:28:05when one person has an idea, that the
0:28:05 > 0:28:09other person criticises it as they were the devil's advocate,
0:28:09 > 0:28:12so, just for the very reason that Jim was keen on having
0:28:12 > 0:28:13the phosphates on the inside,
0:28:13 > 0:28:15I thought he ought to try on the outside.
0:28:15 > 0:28:18And suddenly I could put together A and T, and G and C.
0:28:18 > 0:28:20I could hardly believe it.
0:28:20 > 0:28:22Francis came in almost immediately and saw this.
0:28:22 > 0:28:25Something came out of the model building that Jim had done,
0:28:25 > 0:28:27which he hadn't put in,
0:28:27 > 0:28:30and that's always the sign that you feel you're on the right lines.
0:28:30 > 0:28:33When something begins to click, which you hadn't actually
0:28:33 > 0:28:36put in, in your thinking, which you knew was there.
0:28:36 > 0:28:40But, even more important, Francis, by using these rules, A and T
0:28:40 > 0:28:43and G and C, we understood how the molecule replicated.
0:28:43 > 0:28:46Everything from then on was clear.
0:28:46 > 0:28:49Everything was finished except the hard work, that's to say,
0:28:49 > 0:28:52producing an accurate model.
0:28:52 > 0:28:57I worked continuously for about four days and, uh...
0:28:57 > 0:29:00then came the point where we saw that everything fitted,
0:29:00 > 0:29:03and I was so tired I went straight home and went to bed.
0:29:08 > 0:29:11The structure of DNA had been found.
0:29:12 > 0:29:16A pair of sugar chains, linked by the A, G, C and T bases,
0:29:16 > 0:29:19twisted into a double helix.
0:29:19 > 0:29:22But, more than that, its structure made it immediately obvious
0:29:22 > 0:29:26how DNA could make copies of itself.
0:29:26 > 0:29:30If the strand of DNA is split apart, identical copies can be
0:29:30 > 0:29:34reassembled because each base can only pair up with its base partner.
0:29:36 > 0:29:38There before us
0:29:38 > 0:29:40was the answer to one of the
0:29:40 > 0:29:43fundamental problems in biology -
0:29:43 > 0:29:45how do genes replicate?
0:29:45 > 0:29:47And it was very simple...
0:29:47 > 0:29:49and you couldn't miss it.
0:29:49 > 0:29:52The great paper that was published in the early 1950s with
0:29:52 > 0:29:56the structure of DNA is actually a masterpiece and beautifully
0:29:56 > 0:30:01understated, ending with what I'm sure must have been a Crick
0:30:01 > 0:30:07sentence about the significance of this structure has not escaped us.
0:30:07 > 0:30:10We used to occasionally, just...Jim and I, just sit
0:30:10 > 0:30:14and look at the molecule and think how beautiful it was.
0:30:14 > 0:30:16And I remember on occasion
0:30:16 > 0:30:20when Jim gave a talk to a little biophysics club we had.
0:30:20 > 0:30:22It's true, they gave him one or two drinks before dinner.
0:30:22 > 0:30:26It was rather a short talk because all he could say at the end was,
0:30:26 > 0:30:29"Well, you see, it's so pretty. It's so pretty."
0:30:29 > 0:30:33The twin successes of the discovery of the structure of DNA and
0:30:33 > 0:30:39the mechanism for its replication was a critical moment in science.
0:30:39 > 0:30:44I was a student in Edinburgh and, rather cleverly, my tutor told me
0:30:44 > 0:30:48to go to the library and to find the most important paper in biology.
0:30:48 > 0:30:49I thought, "This man is mad.
0:30:49 > 0:30:50"How am I going to do this?"
0:30:50 > 0:30:52I walked in, and remember, these were the days
0:30:52 > 0:30:55when everything was bound into big volumes,
0:30:55 > 0:30:58and I walked past the journal Nature, bound in green,
0:30:58 > 0:31:02covered in dust, until you got to the 1953 issue,
0:31:02 > 0:31:05and it was battered, it was torn, the back of the cover was come off...
0:31:05 > 0:31:08You opened it up and two pages fell out which were black with the
0:31:08 > 0:31:12grease of many scientists' fingers, and that was the Watson-Crick paper.
0:31:18 > 0:31:22The paper may have rocked the scientific world, but, so far as
0:31:22 > 0:31:27the public were concerned, 1953 was a year remembered for bad weather...
0:31:27 > 0:31:30The waters rose with the wind...
0:31:30 > 0:31:33..the coronation, and the conquering of Mount Everest.
0:31:34 > 0:31:38Edmund Hillary, beekeeper from New Zealand...
0:31:38 > 0:31:39Tenzing Norgay...
0:31:39 > 0:31:44Sherpa from Nepal, conquerors of Everest, May 29th 1953.
0:31:44 > 0:31:48The structure of DNA doesn't even get a mention.
0:31:48 > 0:31:51Biology really wasn't on the agenda, certainly not on the public agenda or
0:31:51 > 0:31:56the press agenda, that was not what they were going to get excited about.
0:31:56 > 0:31:58The public were still in love with physics and chemistry,
0:31:58 > 0:32:02and they were, so, if you look at the South Ken exhibition
0:32:02 > 0:32:06for the Festival Of Britain in 1951,
0:32:06 > 0:32:08it's all physics and chemistry.
0:32:08 > 0:32:12All the excitement of molecules and then the excitement of radar
0:32:12 > 0:32:15and the excitement...not bombs, of course, nothing about bombs.
0:32:16 > 0:32:20But biology, toughened up by physics, was on the march.
0:32:20 > 0:32:24New vaccines and medicines had whetted the public's appetite
0:32:24 > 0:32:28and in 1962, when Crick and Watson, together with Maurice Wilkins,
0:32:28 > 0:32:31were awarded the Nobel Prize for Medicine,
0:32:31 > 0:32:34the double helix DNA had well and truly arrived.
0:32:37 > 0:32:40'The BBC even commissioned this special programme
0:32:40 > 0:32:42'about the prize winners.'
0:32:42 > 0:32:45This is to be a personal programme about these men.
0:32:45 > 0:32:48In a few moments, through television, you will be able to meet them
0:32:48 > 0:32:51and judge for yourselves what manner of men they are.
0:32:51 > 0:32:54'Biology was now at the forefront of science.
0:32:54 > 0:32:57'The possibilities seemed endless.'
0:32:58 > 0:33:01I think one can reasonably predict that within the next 20, 30,
0:33:01 > 0:33:0550 years, there will be an immense increase of knowledge
0:33:05 > 0:33:08about the higher nervous system and about ourselves,
0:33:08 > 0:33:10and I think, myself, as a personal belief,
0:33:10 > 0:33:14it will radically change the way we think about ourselves as persons
0:33:14 > 0:33:16and also, eventually, as people in society.
0:33:18 > 0:33:22The old rivalries were put aside, at least for a while.
0:33:23 > 0:33:25'Though, since the Nobel Prize was awarded,
0:33:25 > 0:33:28'the public memory has been of Crick and Watson,
0:33:28 > 0:33:31'and not of the others who helped them over the line.'
0:33:31 > 0:33:33But, of course, the Watson-Crick breakthrough was...
0:33:33 > 0:33:35..as I've said many times,
0:33:35 > 0:33:36a little sort of pinnacle built
0:33:36 > 0:33:39on an immense basis of chemistry,
0:33:39 > 0:33:43biochemistry, genetics and so on.
0:33:43 > 0:33:47Essential work which people like Todd and Chargaff
0:33:47 > 0:33:50and many others had to work through
0:33:50 > 0:33:52before I was able to put
0:33:52 > 0:33:57the three-dimensional structure of DNA on top.
0:34:00 > 0:34:04Perhaps least celebrated of all was Rosalind Franklin...
0:34:04 > 0:34:07who'd provided the crucial evidence in the form of the B-form
0:34:07 > 0:34:11diffraction pattern that provided the final part of the jigsaw.
0:34:13 > 0:34:18Franklin had developed ovarian cancer and died in 1958,
0:34:18 > 0:34:22and so never knew about the prize or the public excitement around DNA.
0:34:24 > 0:34:27It's often said she was unjustly overlooked,
0:34:27 > 0:34:31but the Nobel Prize is not awarded posthumously,
0:34:31 > 0:34:33so the truth is less clear.
0:34:33 > 0:34:37I sometimes wonder what would have happened had Rosalind Franklin
0:34:37 > 0:34:40been alive when that Nobel Prize was given.
0:34:40 > 0:34:44I don't really know what the outcome of that would have been.
0:34:44 > 0:34:47The Nobel Prize is only given to three individuals.
0:34:47 > 0:34:52Crick and Watson would have been clear. Um, I suspect...
0:34:52 > 0:34:57that Franklin might have trumped Wilkins.
0:34:57 > 0:34:59Um, I don't know that for sure.
0:34:59 > 0:35:03But that, I think, would have been a definite possibility.
0:35:03 > 0:35:06'Though many contributed to the discovery,
0:35:06 > 0:35:09'it was ultimately Crick and Watson who made it,
0:35:09 > 0:35:12'and they have their own views as to why.'
0:35:14 > 0:35:16We weren't in the least afraid of being very candid
0:35:16 > 0:35:19to each other, to the point of being rude,
0:35:19 > 0:35:21and if you don't have constant interchange
0:35:21 > 0:35:24and chatting together and saying what you think about the other people's
0:35:24 > 0:35:28ideas to their face, I don't think you can solve problems of this kind.
0:35:28 > 0:35:31We sort of pooled the way we looked at things.
0:35:31 > 0:35:35We didn't leave it that Jim did the biology and I did the physics.
0:35:35 > 0:35:39We both did it together and switched roles and criticised each other,
0:35:39 > 0:35:42and this gave us a great advantage over the other people who were
0:35:42 > 0:35:44trying to solve it.
0:35:44 > 0:35:46You see, what I think is interesting is that Crick and Watson
0:35:46 > 0:35:49do insist on how collaborative their own work
0:35:49 > 0:35:53was between the two of them, but I don't kind of regard two as much
0:35:53 > 0:36:00of a collaboration, and I think it was more of an intense relationship.
0:36:00 > 0:36:01Scientific relationship.
0:36:01 > 0:36:05And the fact that they absolutely knew that they needed one another.
0:36:05 > 0:36:10They each needed the expertise from the other's discipline.
0:36:10 > 0:36:14They were absolutely not collaborative scientists outside.
0:36:14 > 0:36:21Not in the least. For them, it was a game of who you could beat.
0:36:21 > 0:36:24Um, in my hearing,
0:36:24 > 0:36:27I heard them laughing about Linus Pauling
0:36:27 > 0:36:30and not showing something to Linus Pauling
0:36:30 > 0:36:32because otherwise his lab might get there first.
0:36:32 > 0:36:34It was all about who'd get there first.
0:36:34 > 0:36:36That's not collaborative science.
0:36:36 > 0:36:40Maurice Wilkins seems to have been all too willing to collaborate.
0:36:40 > 0:36:42He was, perhaps, a naive idealist
0:36:42 > 0:36:45and something of a victim of his understated demeanour.
0:36:46 > 0:36:50Wilkins was an active Communist in his youth.
0:36:50 > 0:36:53He was a spiky, spunky man.
0:36:53 > 0:36:58We have no knowledge of that, partly because, presumably, such
0:36:58 > 0:37:03activities as he was engaged in, he didn't exactly trumpet abroad.
0:37:03 > 0:37:06The only reason I know that he was that kind of man is
0:37:06 > 0:37:09because his MI5 file was released in 2010.
0:37:09 > 0:37:13And it is clear from there that he was regarded as a threat.
0:37:13 > 0:37:17'Uh, Wilkins must have been a much gutsier man in his youth than'
0:37:17 > 0:37:21the bits of film that we see of him, would lead one to believe.
0:37:21 > 0:37:23Are you interested in music?
0:37:24 > 0:37:25Well...
0:37:25 > 0:37:30I used to be, but I'm not so interested now.
0:37:30 > 0:37:32The reason we think of Maurice Wilkins as this irritable
0:37:32 > 0:37:35and actually, irritating man,
0:37:35 > 0:37:38when my view is that as a young man he was probably quite dashing
0:37:38 > 0:37:42and exciting and Communist and non-aligned, um,
0:37:42 > 0:37:46is because of his behaviour around the fact that Rosalind Franklin
0:37:46 > 0:37:50just wouldn't play ball, wouldn't be a member of a collaborative lab,
0:37:50 > 0:37:53and I'm sure, in Paris, had not been expected to be.
0:37:53 > 0:37:55She didn't get it, she didn't sign up for it,
0:37:55 > 0:37:57she hadn't signed up for it.
0:37:57 > 0:38:00The fact she wasn't allowed in the common room at King's, London,
0:38:00 > 0:38:04because women weren't allowed in it, really didn't help.
0:38:04 > 0:38:08Um, and therefore Wilkins' collaborative endeavour
0:38:08 > 0:38:12embraced everybody outside, but broke down in his own lab.
0:38:12 > 0:38:14And, looking back on it, of course,
0:38:14 > 0:38:16it's quite clear that
0:38:16 > 0:38:18if you regard sort of getting
0:38:18 > 0:38:20a structure of DNA as a race,
0:38:20 > 0:38:23that we'd lost the race very early on,
0:38:23 > 0:38:25because we didn't find it
0:38:25 > 0:38:28possible to work together.
0:38:29 > 0:38:34Regardless of who won or lost, learning the structure of DNA
0:38:34 > 0:38:37and finding out how it might replicate were huge
0:38:37 > 0:38:40Nobel Prize winning discoveries.
0:38:40 > 0:38:44But knowing these things revealed nothing about how DNA actually
0:38:44 > 0:38:49turns mindless chemicals into trees, frogs, parrots and people.
0:38:49 > 0:38:54How our genes, now realised to be discrete sections of DNA, give us
0:38:54 > 0:38:59unique anatomies and personalities, making each of us who we are.
0:38:59 > 0:39:02This became known as the coding problem.
0:39:02 > 0:39:06So, the next important problem was the coding problem.
0:39:06 > 0:39:08Um, of great interest to Crick.
0:39:08 > 0:39:12By this time, Watson had left, gone back to the United States
0:39:12 > 0:39:14and Sydney Brenner turned up.
0:39:14 > 0:39:17'Sydney Brenner was a reluctant doctor from South Africa
0:39:17 > 0:39:21'who'd hung up his stethoscope in favour of research
0:39:21 > 0:39:23'as soon as he possibly could.'
0:39:25 > 0:39:28'When I grew up in a small town in South Africa,
0:39:28 > 0:39:31'where my father was a shoemaker...
0:39:31 > 0:39:36'uh, at the age of 15, I went to university and'
0:39:36 > 0:39:40I was strongly advised that, for the subject I was interested in,
0:39:40 > 0:39:45which people thought was biological chemistry or whatever,
0:39:45 > 0:39:49the only jobs existed in medical schools.
0:39:49 > 0:39:51And so, I was told, you've got to get a medical degree
0:39:51 > 0:39:54because no-one will employ you in a medical school without
0:39:54 > 0:39:56a medical degree, which I did.
0:39:56 > 0:39:58It was another four years.
0:39:58 > 0:40:00It was actually four and a half years
0:40:00 > 0:40:03because I failed my finals
0:40:03 > 0:40:06in Medicine by diagnosing
0:40:06 > 0:40:08one lady as having an acute attack of
0:40:08 > 0:40:10the use of Macleans toothpaste,
0:40:10 > 0:40:12rather than something else.
0:40:12 > 0:40:15I was right, she had actually used
0:40:15 > 0:40:16Macleans toothpaste.
0:40:16 > 0:40:18I was told to smell her breath and
0:40:18 > 0:40:21that's all I could smell. However...
0:40:21 > 0:40:23But I did return and did the other
0:40:23 > 0:40:25six months and finally passed.
0:40:26 > 0:40:31It is a very difficult experience doing science, I think,
0:40:31 > 0:40:35in a provincial atmosphere.
0:40:37 > 0:40:43All this changed for me when I came to England to work for a PhD.
0:40:43 > 0:40:46If I laid out all those great scientists who I had
0:40:46 > 0:40:51the privilege of knowing as a child, Sydney Brenner was the funniest one.
0:40:51 > 0:40:53Sydney Brenner was just damn funny.
0:40:53 > 0:40:58And comfortable to be around. He was a sort of...
0:40:58 > 0:41:00very gregarious,
0:41:00 > 0:41:02very open...
0:41:02 > 0:41:06open-faced, open everything...man.
0:41:06 > 0:41:09He rode a huge motorbike, you know.
0:41:09 > 0:41:15He was...but he was very sort of stocky and together, and, eh...
0:41:15 > 0:41:18I suspect I thought he was quite glamorous.
0:41:18 > 0:41:21Now, Sydney Brenner, another one of these brilliant characters
0:41:21 > 0:41:24who's also extremely witty and humorous.
0:41:24 > 0:41:27I perhaps know Sydney the best of all the characters,
0:41:27 > 0:41:31perhaps together with Jim Watson,
0:41:31 > 0:41:34and I always seek him out if there's a dinner so I can sit next
0:41:34 > 0:41:38to him, cos I will be highly entertained throughout dinner.
0:41:38 > 0:41:41Just like humour, you put different things together, you
0:41:41 > 0:41:46juxtapose different sorts of ideas and thinking, and they're funny.
0:41:46 > 0:41:49It's the way he also carried out his science, he would put different
0:41:49 > 0:41:53things together and see how things could emerge from it.
0:41:53 > 0:41:56I think they were related - the creativity of humour,
0:41:56 > 0:42:02I see also was in his creativity of tackling the coding problem.
0:42:02 > 0:42:06Now, the coding problem was enormously attractive,
0:42:06 > 0:42:08because, in a sense...
0:42:08 > 0:42:12it looked possible that you could crack it, solve it...
0:42:12 > 0:42:14without doing any work at all.
0:42:14 > 0:42:20There would be something in the sequence that you could then
0:42:20 > 0:42:22sit down and write down the code.
0:42:22 > 0:42:29Once again, we have a collaboration. This time it's Crick with Brenner.
0:42:29 > 0:42:31Watson's gone back to the United States.
0:42:31 > 0:42:36During the period that Brenner and Crick were working together,
0:42:36 > 0:42:40there was one of the greatest experiments of all time to
0:42:40 > 0:42:45determine what's called the triplet nature of the genetic code,
0:42:45 > 0:42:49because the problem was this - in DNA,
0:42:49 > 0:42:52you have a language made up of four letters...
0:42:52 > 0:42:55and in proteins, the language is made up of 20 letters,
0:42:55 > 0:42:59so, you can't encode for 20 different letters by 4 alone.
0:42:59 > 0:43:04They have to be read either in twos or threes or fours,
0:43:04 > 0:43:10and the key experiment was what the number was.
0:43:10 > 0:43:14And there was an absolutely genius experiment done,
0:43:14 > 0:43:18where the...and Crick explains this,
0:43:18 > 0:43:22that he introduced mutations
0:43:22 > 0:43:27and if you introduce one mutation then you destroy function,
0:43:27 > 0:43:29if you introduce two, you would destroy function,
0:43:29 > 0:43:33if you introduce three...you've got the function back again,
0:43:33 > 0:43:39because all you did was lose one amino acid and then the rest was OK.
0:43:39 > 0:43:42And this is a brilliant piece of abstract reasoning which came
0:43:42 > 0:43:44to a concrete conclusion.
0:43:44 > 0:43:47'We had discovered that the dye, proflavine,
0:43:47 > 0:43:53'does cause additions and deletions of bases in DNA.'
0:43:53 > 0:43:58DNA consists of a one-dimensional sequence of
0:43:58 > 0:44:01four different building blocks - the bases.
0:44:04 > 0:44:08The proteins consist of another language, the amino acids,
0:44:08 > 0:44:10of which there are 20.
0:44:11 > 0:44:16You need more than one nuclear type to correspond to an amino acid
0:44:16 > 0:44:20because there are only four of the first and 20 of the latter.
0:44:20 > 0:44:22Indeed, you need at least three,
0:44:22 > 0:44:26so we suspected the code was a triplet one.
0:44:26 > 0:44:27We also suspected that it was
0:44:27 > 0:44:31read from one end, three at a time.
0:44:31 > 0:44:36Imagine a gene being composed of the triplet CAT, C-A-T.
0:44:36 > 0:44:40So, we have CAT, CAT, CAT, CAT, CAT, CAT, CAT.
0:44:41 > 0:44:45You can see that if you delete one of these nucleotides,
0:44:45 > 0:44:49beyond the deletion, it's converted into gibberish - ATC, ATC, and so on.
0:44:52 > 0:44:55If you delete yet another nucleotide,
0:44:55 > 0:45:00you will see you get the second form of gibberish - TCA, TCA.
0:45:01 > 0:45:04But if you delete a third nucleotide,
0:45:04 > 0:45:05you convert it back to the
0:45:05 > 0:45:09original message - CAT, CAT, CAT.
0:45:10 > 0:45:12It absolutely worked.
0:45:12 > 0:45:14It proved that the code was non-overlapping
0:45:14 > 0:45:18and a triplet one, and then, as a joke, we later called
0:45:18 > 0:45:24the triplet a codon - the unit corresponding to one amino acid.
0:45:24 > 0:45:28So, this was an example of the sort of thinking, the brilliance
0:45:28 > 0:45:33of the thinking, that was tackling problems in rather simple ways.
0:45:33 > 0:45:37Not fantastically sophisticated equipment and so on,
0:45:37 > 0:45:40but brilliant logical reasoning.
0:45:41 > 0:45:43What had been accomplished as a result of
0:45:43 > 0:45:45Crick and Brenner's discovery,
0:45:45 > 0:45:48had opened the door to the ultimate possibility -
0:45:48 > 0:45:51that DNA was the book of life.
0:45:51 > 0:45:53That the units of inheritance, the genes,
0:45:53 > 0:45:59were simply specific sequences of A, C, G and T held in the DNA...
0:45:59 > 0:46:01and that it could all be read in its entirety.
0:46:03 > 0:46:06But before the final assault on the stuff of life could begin,
0:46:06 > 0:46:08another problem needed solving.
0:46:10 > 0:46:14Even though the structure of DNA was known, and it had been shown that
0:46:14 > 0:46:16DNA coded for proteins,
0:46:16 > 0:46:20actually reading the exact order of the bases was proving impossible.
0:46:25 > 0:46:28Enter Fred Sanger who, like Crick and Brenner,
0:46:28 > 0:46:31was from the Molecular Biology lab in Cambridge.
0:46:32 > 0:46:39Fred Sanger, who I also know a little bit, is...
0:46:39 > 0:46:44a very humble man, somebody you hardly would notice, you know,
0:46:44 > 0:46:49you'd think he was the gardener, I'm sure, in Cambridge rather than,
0:46:49 > 0:46:52you know, one of the greatest scientists of his time.
0:46:53 > 0:46:55Fred Sanger had already received
0:46:55 > 0:46:57a Nobel Prize for discovering
0:46:57 > 0:46:59the structure of proteins.
0:46:59 > 0:47:03Now, he turned his attention to how to read or sequence
0:47:03 > 0:47:06DNA's elusive code.
0:47:06 > 0:47:10For Sanger, there was a useful similarity between proteins and DNA.
0:47:11 > 0:47:15One became much more interested in nucleic acids.
0:47:15 > 0:47:19Again, it was a long chain molecule similar to the proteins.
0:47:20 > 0:47:23So, that there was a similar problem there.
0:47:23 > 0:47:27And I thought maybe my abilities would be
0:47:27 > 0:47:31useful in that field, and we might be able to do something in sequencing
0:47:31 > 0:47:36them because, clearly, the sequence was the important thing about them.
0:47:36 > 0:47:39I think Fred Sanger,
0:47:39 > 0:47:43who really pioneered the notion of sequencing DNA,
0:47:43 > 0:47:46using what in retrospect was a clumsy method,
0:47:46 > 0:47:48but was the only one that was then available.
0:47:48 > 0:47:52Um, he's again a rather forgotten figure by the general public,
0:47:52 > 0:47:56and he set out to do something which certainly, when I was a...
0:47:56 > 0:47:59student of genetics and I was doing my PhD in genetics, and even
0:47:59 > 0:48:01when I started my career in genetics,
0:48:01 > 0:48:03seemed fundamentally impossible,
0:48:03 > 0:48:06the idea that you could read off a complete genome
0:48:06 > 0:48:08just seemed completely out of the window,
0:48:08 > 0:48:11let alone that you could read off the human genome.
0:48:11 > 0:48:16But Sanger started the job with this method of labelling the bases
0:48:16 > 0:48:19one at a time and chipping them off and separating them,
0:48:19 > 0:48:23and just reading them ploddingly slowly from one end to another,
0:48:23 > 0:48:28and he played a central part in the technical change,
0:48:28 > 0:48:33which turned genetics into the modern day equivalent of anatomy.
0:48:44 > 0:48:46Fred Sanger's work earned him another Nobel Prize
0:48:46 > 0:48:50and opened the door to a tantalising prospect -
0:48:50 > 0:48:55that the DNA of an entire species, its genome, could be read.
0:48:55 > 0:48:58That its genetic code could be solved.
0:49:03 > 0:49:06John Sulston is the archetypal, left-leaning,
0:49:06 > 0:49:10Guardian-reading, muesli-eating scientist.
0:49:10 > 0:49:12I like muesli, you know?
0:49:12 > 0:49:15I'm not doing it for any particular reason, I suppose that's what I mean.
0:49:15 > 0:49:17CAT MEOWS
0:49:17 > 0:49:19Sulston is a man with a very clear idea of what is
0:49:19 > 0:49:22important in life and what is not.
0:49:23 > 0:49:27Um, I suppose simple...
0:49:27 > 0:49:30rampant, anti-consumerist, well, non-consumerist is the point,
0:49:30 > 0:49:34but, on the whole, the presumption is that one is not going to buy
0:49:34 > 0:49:37things rather than that you are, if you see what I mean.
0:49:37 > 0:49:40Um, what do you want, really? I mean, it's...
0:49:41 > 0:49:45It's thinking and reading and talking and all of that that matters,
0:49:45 > 0:49:49not actually having stuff, unless the stuff's there for a purpose.
0:49:49 > 0:49:52His low-key domestic arrangements give few clues
0:49:52 > 0:49:54to his standing in the academic world.
0:49:56 > 0:49:59Like Sanger, Wilkins, Watson and Crick,
0:49:59 > 0:50:01John Sulston has a Nobel Prize.
0:50:03 > 0:50:05It was awarded for cataloguing the development of
0:50:05 > 0:50:08every single cell in the nematode worm.
0:50:09 > 0:50:14Years of research culminating in 18 months of intensive observation.
0:50:14 > 0:50:18Eight hours every day looking at worm cells through his microscope.
0:50:19 > 0:50:23I think it's rather fun, really. You know, it's a job of work.
0:50:23 > 0:50:26You don't have to worry about what you're going to do the next day,
0:50:26 > 0:50:27you know what you're going to do -
0:50:27 > 0:50:29you're going to watch some more cells divide.
0:50:31 > 0:50:35What he did next was even more tedious.
0:50:35 > 0:50:38To work out exactly why the cells behaved as they did,
0:50:38 > 0:50:41Sulston needed to understand their genes.
0:50:43 > 0:50:46And to do that meant sequencing them.
0:50:46 > 0:50:47All of them.
0:50:49 > 0:50:52Before we began, people said, "Oh, it's not worth doing that.
0:50:52 > 0:50:55"What you ought to be doing is to study real biological problems.
0:50:55 > 0:50:58"Look, John, you've done all this cell linaging. You ought to be
0:50:58 > 0:51:01"getting mutants and finding out how the cell linage works."
0:51:01 > 0:51:04And I said, "Hmm, I'm not sure. I think it's more complicated
0:51:04 > 0:51:06"than that. We really need to get at all the genes."
0:51:06 > 0:51:09And so I started this business of looking
0:51:09 > 0:51:12directly at the genome as a whole.
0:51:12 > 0:51:16The nematode worm genome was the proof of concept.
0:51:16 > 0:51:20Now, the way was clear for the ultimate prize.
0:51:20 > 0:51:23The mild-mannered worm scientist found himself running
0:51:23 > 0:51:27the British part of a global effort to read the human genome.
0:51:29 > 0:51:33From its outset, Sulston believed that the Human Genome Project
0:51:33 > 0:51:36was a noble undertaking for the benefit of everyone.
0:51:36 > 0:51:40All the labs met in Bermuda, and we met in Bermuda precisely because it's
0:51:40 > 0:51:44a rock in the middle of the Atlantic, so it's a sort of neutral place.
0:51:44 > 0:51:47It was in the off season, I should add.
0:51:47 > 0:51:51So, we were there and we...I remember standing at the board there,
0:51:51 > 0:51:54trying to construct with the assembled labs
0:51:54 > 0:51:58a statement to the effect that all of us would release
0:51:58 > 0:52:02all of our data all the time and we would not try to take patterns.
0:52:02 > 0:52:05And we came out with what have been called the Bermuda Principles
0:52:05 > 0:52:10and have actually informed quite a lot of endeavour since.
0:52:10 > 0:52:13It was all done in a very gentlemanly
0:52:13 > 0:52:16and gentlewomanly way, and everybody was very nice
0:52:16 > 0:52:19and decent and I would say rather British about it.
0:52:19 > 0:52:22And then suddenly into this calm, Cambridge environment came
0:52:22 > 0:52:27a bombshell, this chap called Craig Venter.
0:52:32 > 0:52:36Craig Venter had been the team leader of one of the genome groups
0:52:36 > 0:52:39in the US, but had decided to go it alone.
0:52:39 > 0:52:43There was, he decided, money to be made in the human genome.
0:52:48 > 0:52:51There were lots of bio-tech companies that viewed
0:52:51 > 0:52:53genes as commodities.
0:52:53 > 0:52:56People started assuming you got a patent on a human gene,
0:52:56 > 0:52:58you would get a billion-dollar drug.
0:53:00 > 0:53:03This went against everything Sulston believed.
0:53:03 > 0:53:07Human genes should be owned by the public, not owned by any
0:53:07 > 0:53:11particular person or even corporation or even government.
0:53:11 > 0:53:12They are publicly owned.
0:53:12 > 0:53:15John Sulston now found himself
0:53:15 > 0:53:18as the reluctant defender of the people's genome.
0:53:19 > 0:53:21He was now in a race.
0:53:21 > 0:53:22Every gene that he identified
0:53:22 > 0:53:26and published was one that couldn't be patented by Venter.
0:53:27 > 0:53:30He secured extra funding to ensure his UK group could complete
0:53:30 > 0:53:34a third of the genome, and jetted to America to stiffen
0:53:34 > 0:53:37the resolve of the National Institute of Health, who were
0:53:37 > 0:53:43on the brink of cutting a deal with their former employee's new company.
0:53:43 > 0:53:46I think it did turn things around, because NIH were in fact
0:53:46 > 0:53:49making moves to compromise, because they thought they were dead.
0:53:49 > 0:53:51They thought Congress would just say, all right,
0:53:51 > 0:53:54now you've got a company doing it, you're not allowed to compete.
0:53:54 > 0:53:57But by us coming in and saying, well, the Brits are going to do
0:53:57 > 0:54:00a third publicly, it really stiffened their backs.
0:54:00 > 0:54:02You could see the moral force it had.
0:54:02 > 0:54:07Not for the first time in the story of DNA, things got nasty.
0:54:07 > 0:54:10John wanted to sequence the human genome.
0:54:10 > 0:54:12I wanted to sequence the human genome.
0:54:12 > 0:54:14I can't fault him for wanting to do that.
0:54:14 > 0:54:17But it was more important to him
0:54:17 > 0:54:18to be the one to do it than to
0:54:18 > 0:54:21enable it to get done quickly.
0:54:21 > 0:54:23I suppose I am anti-capitalist to the point where
0:54:23 > 0:54:26I feel that companies are completely unnecessary, yes, that's right.
0:54:26 > 0:54:28I think we'd get on very well
0:54:28 > 0:54:30if we did all that discovery in universities, frankly.
0:54:30 > 0:54:34They gave him the Nobel Prize for counting cells in a worm, right?
0:54:34 > 0:54:36The absolutely debilitating diseases - AIDS -
0:54:36 > 0:54:40of Africa and other developing countries, they cannot be dealt with
0:54:40 > 0:54:43on a capitalist basis, because there is no market, there is no money.
0:54:43 > 0:54:47So, you now have two programmes going in parallel.
0:54:47 > 0:54:51One, a public programme, set up for the public good,
0:54:51 > 0:54:53a second, a private programme,
0:54:53 > 0:54:55ultimately leading to the public good,
0:54:55 > 0:54:58but in the meantime going to make a lot of money.
0:54:58 > 0:55:02Our efforts are at least equally important, if not more so,
0:55:02 > 0:55:04because it forced them to get going
0:55:04 > 0:55:07and get off their butts and actually do something.
0:55:07 > 0:55:09Ah, yes, "I lit a fire under the human genome."
0:55:09 > 0:55:11They always like that image!
0:55:11 > 0:55:15But I think objectively the facts speak against it.
0:55:15 > 0:55:17I really don't think that it was helpful.
0:55:17 > 0:55:21I think we'd have finished pretty much next year anyway.
0:55:21 > 0:55:23And without all the fuss.
0:55:23 > 0:55:27Sulston is a much, much more traditional scientist,
0:55:27 > 0:55:30much more of the Maurice Wilkins type, the sharing,
0:55:30 > 0:55:33collaborative, making the world a better place.
0:55:33 > 0:55:36I wouldn't have thought it would have crossed his mind that he
0:55:36 > 0:55:38could make his fortune.
0:55:38 > 0:55:41I think Venter saw very early on he could make his fortune.
0:55:41 > 0:55:43I don't think it's a bad thing, but he saw it.
0:55:43 > 0:55:48Well, Venter was simply, you know, he was... How can I summarise it?
0:55:48 > 0:55:51Venter was an American. Sulston was British.
0:55:51 > 0:55:54That, I think, summarises the entire problem.
0:55:59 > 0:56:03But, ultimately, it was politicians - British and American -
0:56:03 > 0:56:06who came down on the side of the people's genome.
0:56:06 > 0:56:10..Genome science and its benefits will be directed toward making life
0:56:10 > 0:56:15better for all citizens of the world, never just a privileged few.
0:56:16 > 0:56:18In 2000, Bill Clinton
0:56:18 > 0:56:22and Tony Blair announced that the race was effectively over
0:56:22 > 0:56:25and that no-one would be making any money by patenting genes.
0:56:25 > 0:56:28When the public project guys,
0:56:28 > 0:56:31ie, you and everyone else, got Tony Blair
0:56:31 > 0:56:34and Bill Clinton to make that announcement early last year,
0:56:34 > 0:56:37when they said they would like to see unencumbered access
0:56:37 > 0:56:42to this data, it wiped 150 off Venter's company's share price.
0:56:42 > 0:56:45It's a natural thing that that would drop.
0:56:45 > 0:56:47But it must have made you smile, put a smile on your face.
0:56:47 > 0:56:50- HE CHUCKLES - Well, it has now!
0:56:50 > 0:56:55Well, yes, but the trouble is, at the same time - it's true, I smile,
0:56:55 > 0:57:00but these are minor victories or skirmishes in the whole thing.
0:57:02 > 0:57:06Much has been made of the importance of the reading of the human genome,
0:57:06 > 0:57:11of the medical benefits that will emerge from its now cracked code.
0:57:11 > 0:57:15That maybe it even holds the secret of life itself.
0:57:15 > 0:57:19We cannot understand what life is without understanding
0:57:19 > 0:57:23the genome, but it is only one part of the problem.
0:57:23 > 0:57:28And we need also to understand how living organisms work,
0:57:28 > 0:57:31how cells work, how tissues and organs work.
0:57:31 > 0:57:36Without the human genome sequence, we can hardly address the problem.
0:57:36 > 0:57:39It is crucial, but it is not the only thing we need to know.
0:57:43 > 0:57:45Since the middle of the last century,
0:57:45 > 0:57:48the murky business of inheritance has been dragged out
0:57:48 > 0:57:52of an age of near witchcraft to one where individual groups
0:57:52 > 0:57:55of atoms, in what was once considered the "stupid molecule",
0:57:55 > 0:57:58are now recognised as agents of heredity.
0:57:59 > 0:58:04Crick and Watson's identification of DNA structure,
0:58:04 > 0:58:08informed by the crystallography done by the King's group,
0:58:08 > 0:58:12Sydney Brenner's solution to the coding problem,
0:58:12 > 0:58:15Fred Sanger's work on sequencing, and the global effort to read
0:58:15 > 0:58:21the human genome, has revealed what some might call the code of life.
0:58:21 > 0:58:24But, in reality, DNA,
0:58:24 > 0:58:29coding and genomics is only the start of the next chapter.