1 00:00:04,500 --> 00:00:10,260 In 1953, scientists discovered the structure of DNA, 2 00:00:10,260 --> 00:00:12,700 and changed for ever our understanding of genetics, 3 00:00:12,700 --> 00:00:14,220 of heredity, 4 00:00:14,220 --> 00:00:16,100 and even of life itself. 5 00:00:19,100 --> 00:00:21,380 It was the beginning of a revolution in biology 6 00:00:21,380 --> 00:00:25,660 that led eventually to the sequencing of the human genome, 7 00:00:25,660 --> 00:00:28,860 the genetic code of life that defines our species. 8 00:00:31,420 --> 00:00:34,300 But this was a revolution with a difference. 9 00:00:34,300 --> 00:00:37,860 'These critical scientific discoveries were among the first 10 00:00:37,860 --> 00:00:41,260 'to be documented on television and radio.' 11 00:00:41,260 --> 00:00:43,380 Dr Wilkins, what do you actually do? 12 00:00:43,380 --> 00:00:47,500 The main thing in my kind of scientific work is to be able to 13 00:00:47,500 --> 00:00:50,820 fiddle with a thing, go on fiddling with it and fiddle, fiddle, 14 00:00:50,820 --> 00:00:52,700 until everyone else has given up. 15 00:00:54,700 --> 00:00:59,140 'In an era before spin doctors and PR, the scientists were prepared to 16 00:00:59,140 --> 00:01:03,020 'talk about their work - and each other - with extraordinary candour.' 17 00:01:03,020 --> 00:01:06,020 She came toward me and I thought she was going to hit me! 18 00:01:06,020 --> 00:01:08,700 Oh, God! Who hit who?! 19 00:01:08,700 --> 00:01:11,860 Their stories, buried in the BBC archives, 20 00:01:11,860 --> 00:01:15,220 reveal the people behind the science. 21 00:01:15,220 --> 00:01:18,460 In few moments, through television you will be able to meet them 22 00:01:18,460 --> 00:01:21,540 and judge for yourselves what manner of men they are. 23 00:01:21,540 --> 00:01:24,180 Passionate, ambitious men and women, 24 00:01:24,180 --> 00:01:28,260 driven by intense, sometimes bitter rivalries. 25 00:01:28,260 --> 00:01:30,420 Scientists sat back and got fat and happy 26 00:01:30,420 --> 00:01:32,220 getting tens of millions of dollars, 27 00:01:32,220 --> 00:01:34,420 and I put John in that category. 28 00:01:34,420 --> 00:01:38,260 We have already released two thirds of the human genome 29 00:01:38,260 --> 00:01:42,100 into the public domain, and he's released nothing at all. 30 00:01:42,100 --> 00:01:44,660 The archive reveals that truly to understand 31 00:01:44,660 --> 00:01:46,140 how the discoveries were made, 32 00:01:46,140 --> 00:01:49,460 it's essential first to understand the people who made them. 33 00:01:50,740 --> 00:01:53,100 This is the story of those scientists, 34 00:01:53,100 --> 00:01:57,060 of the men and women who set out to crack the code of life... 35 00:01:57,060 --> 00:01:58,660 Happy days! 36 00:01:59,740 --> 00:02:01,860 ..told in their own words. 37 00:02:16,100 --> 00:02:18,380 Do electrons think? 38 00:02:20,380 --> 00:02:24,140 Electrons are charged particles, 39 00:02:24,140 --> 00:02:29,340 the minutest we find in analysing the ultimate constitution of matter. 40 00:02:30,820 --> 00:02:36,660 To think that such a particle can think is so absurd... 41 00:02:36,660 --> 00:02:39,700 that I might give the answer, no, and have my talk over. 42 00:02:40,820 --> 00:02:42,100 However... 43 00:02:42,100 --> 00:02:45,100 This is one of very few recordings made of a man called 44 00:02:45,100 --> 00:02:46,180 Erwin Schrodinger. 45 00:02:47,380 --> 00:02:50,460 Schrodinger had served in the Austrian army in the First World War 46 00:02:50,460 --> 00:02:53,740 and later made a name for himself in physics 47 00:02:53,740 --> 00:02:55,820 as the inventor of a theoretical cat. 48 00:02:59,420 --> 00:03:01,900 The odd thing is that here is Schrodinger, 49 00:03:01,900 --> 00:03:05,980 a world famous physicist, musing on a biological problem - 50 00:03:05,980 --> 00:03:09,780 the nature of consciousness, of what it means to be human. 51 00:03:11,220 --> 00:03:15,660 Mind per se cannot play the piano. 52 00:03:15,660 --> 00:03:19,380 Mind per se cannot move a finger of a hand. 53 00:03:20,540 --> 00:03:26,140 This leaves us with the outlook that our body is as automatic or 54 00:03:26,140 --> 00:03:30,540 non-automatic as any inanimate piece of matter... 55 00:03:30,540 --> 00:03:33,740 only infinitely more complicated than even the most 56 00:03:33,740 --> 00:03:35,340 ingenious man-made machine. 57 00:03:37,620 --> 00:03:42,380 Schrodinger is a name in physics to conjure with. 58 00:03:42,380 --> 00:03:46,140 I think even members of a quite broad general public would hear 59 00:03:46,140 --> 00:03:50,380 the name Schrodinger, associate it with Einstein, it goes with... 60 00:03:50,380 --> 00:03:54,860 tough physics, it goes with quantum physics, and the fact 61 00:03:54,860 --> 00:04:01,420 that in 1944 Schrodinger published a book called "What Is Life?" 62 00:04:01,420 --> 00:04:08,100 about biology, and how biology would yield to scientific attention, 63 00:04:08,100 --> 00:04:12,540 that physics could unpack biology. 64 00:04:12,540 --> 00:04:17,260 That was a light bulb moment for physicists. 65 00:04:17,260 --> 00:04:19,460 I think it's a universal among all biologists 66 00:04:19,460 --> 00:04:21,740 that they've got physics envy. 67 00:04:21,740 --> 00:04:24,500 Um, they really wish they were physicists, 68 00:04:24,500 --> 00:04:26,260 but they know they're not clever enough. 69 00:04:26,260 --> 00:04:28,460 I know I'm not clever enough to be a physicist. 70 00:04:28,460 --> 00:04:31,820 As Lord Rutherford once said, "There is only physics. 71 00:04:31,820 --> 00:04:34,660 "Everything else is stamp collecting." 72 00:04:34,660 --> 00:04:37,420 In writing "What Is Life?", Schrodinger helped 73 00:04:37,420 --> 00:04:41,500 shake off biology's stamp collecting image and launched a period 74 00:04:41,500 --> 00:04:43,740 that would bring it to the forefront of science. 75 00:04:45,140 --> 00:04:49,860 What I think was really useful about that book was the was the rigour of 76 00:04:49,860 --> 00:04:52,620 physical thinking, the thinking of a physicist, 77 00:04:52,620 --> 00:04:56,020 which allowed the question to be properly framed. 78 00:04:56,020 --> 00:04:59,460 What he emphasised was the importance of thinking 79 00:04:59,460 --> 00:05:03,780 about the transmission of information from one generation to another, 80 00:05:03,780 --> 00:05:06,860 that was essentially the nature of heredity, 81 00:05:06,860 --> 00:05:11,380 and how you might think about coding information in molecules. 82 00:05:14,540 --> 00:05:17,540 During the Second World War, Erwin Schrodinger was 83 00:05:17,540 --> 00:05:20,780 head of Theoretical Physics at Trinity College, Dublin, 84 00:05:20,780 --> 00:05:24,580 and it was here, in neutral Ireland, that he set about unleashing 85 00:05:24,580 --> 00:05:27,700 the rigour of physics on the messy business of life. 86 00:05:29,860 --> 00:05:33,180 Schrodinger talks about life in physical terms, 87 00:05:33,180 --> 00:05:38,260 about life being an islands of order in a sea of disorder, and that's 88 00:05:38,260 --> 00:05:40,580 perhaps the best definition of life I can think of, 89 00:05:40,580 --> 00:05:45,060 and he also pointed out that it was a kind of twofold process, 90 00:05:45,060 --> 00:05:49,100 a living creature itself will die and return to disorder, 91 00:05:49,100 --> 00:05:53,380 but will have passed on its information in a molecule, 92 00:05:53,380 --> 00:05:57,300 which, at that time, wasn't known, so there was a code involved too. 93 00:05:57,300 --> 00:06:01,020 So, those two things - entropy and the code - both of which are 94 00:06:01,020 --> 00:06:03,820 physical ideas, really, mathematical ideas, I think, 95 00:06:03,820 --> 00:06:06,980 formed a lot of modern biology. 96 00:06:06,980 --> 00:06:08,780 The same laws of physics 97 00:06:08,780 --> 00:06:12,980 and physical chemistry hold within the living body as outside. 98 00:06:14,420 --> 00:06:16,980 The simplest spontaneous bodily movement... 99 00:06:18,060 --> 00:06:20,060 ..say, the lifting of my arm, 100 00:06:20,060 --> 00:06:23,900 would require the planned collaboration of billions 101 00:06:23,900 --> 00:06:28,220 of single atoms in their undetermined swerves 102 00:06:28,220 --> 00:06:31,060 if they should bring about the integrated action. 103 00:06:35,500 --> 00:06:39,180 Science had started to make inroads into the secrets of life 104 00:06:39,180 --> 00:06:41,580 in the previous century. 105 00:06:41,580 --> 00:06:45,300 Charles Darwin had proposed his theory of evolution, 106 00:06:45,300 --> 00:06:49,300 and Gregor Mendel had worked out the principle of how characteristics 107 00:06:49,300 --> 00:06:54,220 were passed from one generation to the next biologically through genes, 108 00:06:54,220 --> 00:06:57,740 though he had no idea what genes actually were or how they worked. 109 00:06:59,060 --> 00:07:00,460 Then things went wrong. 110 00:07:02,340 --> 00:07:05,700 The way that these ideas were misapplied is perhaps 111 00:07:05,700 --> 00:07:10,620 the clearest example ever of two rights making one colossal wrong. 112 00:07:12,020 --> 00:07:16,220 As demonstrated by leading British biologist Professor Julian Huxley. 113 00:07:17,700 --> 00:07:21,660 What is the bearing of the laws of heredity upon human affairs? 114 00:07:21,660 --> 00:07:24,420 Eugenics provides the answer. 115 00:07:24,420 --> 00:07:28,140 Eugenics was a 19th century idea that spawned a movement whose 116 00:07:28,140 --> 00:07:32,340 aim was to ensure that only the fittest survive. 117 00:07:32,340 --> 00:07:35,340 An attempt at biological engineering. 118 00:07:35,340 --> 00:07:38,820 Breeding out those deemed to be a drain on society. 119 00:07:38,820 --> 00:07:42,780 People labelled at the time as defective. 120 00:07:42,780 --> 00:07:44,380 Here is a man who, 121 00:07:44,380 --> 00:07:47,540 although normal, comes from a mentally defective family. 122 00:07:47,540 --> 00:07:50,900 Here is his wife who is also normal. 123 00:07:50,900 --> 00:07:52,380 They have had 17 children. 124 00:07:53,940 --> 00:07:55,980 Let us examine the pedigree of these children. 125 00:07:55,980 --> 00:08:00,020 Five of them died in infancy, three are still too young 126 00:08:00,020 --> 00:08:04,500 for an opinion to be formed of their mental state, a boy and two girls. 127 00:08:04,500 --> 00:08:08,860 Only two of the remaining children are normal, a man and a girl. 128 00:08:08,860 --> 00:08:12,020 The remaining seven children are all mental defectives. 129 00:08:13,540 --> 00:08:16,540 The people who set up the eugenics movement, 130 00:08:16,540 --> 00:08:19,940 who were studying human heredity, in retrospect knew nothing, 131 00:08:19,940 --> 00:08:23,020 and I mean nothing, possibly less than nothing, 132 00:08:23,020 --> 00:08:25,580 because what they did know was simply wrong, 133 00:08:25,580 --> 00:08:29,500 but that didn't stop them from going into these dreadful practices. 134 00:08:31,580 --> 00:08:34,500 In institutions such as this all over the country, 135 00:08:34,500 --> 00:08:36,020 mental defectives are cared for. 136 00:08:37,220 --> 00:08:41,820 Once such children have been born we must do the best we can for them. 137 00:08:41,820 --> 00:08:44,180 But it would have been better by far, for them 138 00:08:44,180 --> 00:08:47,300 and for the rest of the community, if they had never been born. 139 00:08:50,620 --> 00:08:54,980 I think that...before World War II, 140 00:08:54,980 --> 00:08:58,500 biology was somewhat of a backwater, not least because the 141 00:08:58,500 --> 00:09:01,180 interwar period is a period of 142 00:09:01,180 --> 00:09:05,380 frenetic development of military hardware. 143 00:09:05,380 --> 00:09:06,860 The scientific community, 144 00:09:06,860 --> 00:09:14,060 which was growing in stature was regarded now as the great hope. 145 00:09:14,060 --> 00:09:19,420 It was what was going to defend Europe, defend the United States. 146 00:09:19,420 --> 00:09:23,940 The biological sciences were really, I think... 147 00:09:25,220 --> 00:09:26,700 ..on the back burner. 148 00:09:26,700 --> 00:09:28,220 The bright, young men - 149 00:09:28,220 --> 00:09:33,060 and I use the term advisedly - went into physics and chemistry. 150 00:09:34,300 --> 00:09:36,980 Three...two...one. 151 00:09:36,980 --> 00:09:37,980 And go. 152 00:09:41,380 --> 00:09:42,620 The irony was that 153 00:09:42,620 --> 00:09:47,100 while Schrodinger used physics to explain what it means to be alive, 154 00:09:47,100 --> 00:09:49,540 most of his "bright, young colleagues" 155 00:09:49,540 --> 00:09:52,740 were using physics as a means of snuffing life out 156 00:09:52,740 --> 00:09:54,340 on an apocalyptic scale. 157 00:09:55,580 --> 00:09:59,700 In the course of World War II, literally every 158 00:09:59,700 --> 00:10:02,740 able and eminent scientist was working for the war effort, 159 00:10:02,740 --> 00:10:04,140 and I think that out of that 160 00:10:04,140 --> 00:10:08,060 came a thoughtfulness about the meaning of life on the part 161 00:10:08,060 --> 00:10:11,380 of physicists, that they maybe thought more about philosophy, 162 00:10:11,380 --> 00:10:14,420 and I do think it characterises the men of this generation. 163 00:10:14,420 --> 00:10:18,060 And coming out of the war into a time of promise and peace, 164 00:10:18,060 --> 00:10:20,820 wouldn't you then want to go where those thoughts had taken you? 165 00:10:20,820 --> 00:10:22,220 And THAT was biology. 166 00:10:28,940 --> 00:10:32,980 One such scientist was Maurice Wilkins, an English physicist who'd 167 00:10:32,980 --> 00:10:36,820 spent much of the war at Los Alamos developing the atomic bomb. 168 00:10:37,980 --> 00:10:41,860 Certainly, the atomic bomb business was a stimulus for getting 169 00:10:41,860 --> 00:10:44,380 out of physics and into something else, 170 00:10:44,380 --> 00:10:48,820 and I think the immense destructive forces which were 171 00:10:48,820 --> 00:10:54,860 discovered in the atomic bomb were rather appalling, and so I felt 172 00:10:54,860 --> 00:11:00,980 that I wanted to work on things which were living and growing for a change. 173 00:11:00,980 --> 00:11:03,340 Dr Wilkins, what do you actually do? 174 00:11:03,340 --> 00:11:05,940 I mean, what do you actually do in your work? 175 00:11:05,940 --> 00:11:09,740 The main thing in my kind of scientific work is to be able 176 00:11:09,740 --> 00:11:12,700 to fiddle with a thing, go on fiddling with it and 177 00:11:12,700 --> 00:11:15,820 fiddle, fiddle until everyone else has given up. 178 00:11:18,380 --> 00:11:21,900 Wilkins settled into academic life at King's College, London, 179 00:11:21,900 --> 00:11:25,380 where he began fiddling with crystallography in a bid to 180 00:11:25,380 --> 00:11:28,460 shed some light on the mechanism of genetics, 181 00:11:28,460 --> 00:11:31,420 on how what Schrodinger called a code might work. 182 00:11:33,340 --> 00:11:34,540 Crystallography, 183 00:11:34,540 --> 00:11:38,820 the idea that you could shoot x-rays at a copper sulphate crystal 184 00:11:38,820 --> 00:11:40,620 or common salt crystals, 185 00:11:40,620 --> 00:11:43,220 and by looking at the way they bounced off, you could 186 00:11:43,220 --> 00:11:46,900 reconstitute what the structure of the atoms in the crystal were. 187 00:11:46,900 --> 00:11:49,580 That was pretty astounding stuff 188 00:11:49,580 --> 00:11:52,420 and he made enormous advances in physics, 189 00:11:52,420 --> 00:11:54,180 and then somebody had the idea - 190 00:11:54,180 --> 00:11:56,060 Wilkins was one of the somebodies - 191 00:11:56,060 --> 00:11:58,300 of using that on the much messier system 192 00:11:58,300 --> 00:12:01,340 which is biology, and to everybody's great surprise, 193 00:12:01,340 --> 00:12:05,180 it turned out that some molecules were really quite amenable to 194 00:12:05,180 --> 00:12:07,820 being treated in this way, and one of those molecules, which is 195 00:12:07,820 --> 00:12:11,060 very abundant in the body, is DNA. 196 00:12:11,060 --> 00:12:13,300 It was initially called the stupid molecule 197 00:12:13,300 --> 00:12:16,860 because it seemed to be everywhere, you know, it was in all cells, 198 00:12:16,860 --> 00:12:18,500 and yet it didn't seem to do anything. 199 00:12:22,940 --> 00:12:27,340 Then, in 1944, a group in America performed an experiment, 200 00:12:27,340 --> 00:12:31,140 which showed that DNA wasn't quite as stupid as everyone had thought. 201 00:12:36,380 --> 00:12:37,660 They took strains of a pneumococcus bacterium 202 00:12:37,860 --> 00:12:38,780 They took strains of a pneumococcus bacterium 203 00:12:38,780 --> 00:12:43,220 and the two strains differed - one was smooth, one was rough - 204 00:12:43,220 --> 00:12:48,060 and what they did is they extracted DNA from one of those strains, 205 00:12:48,060 --> 00:12:50,220 sprinkled it on the other, 206 00:12:50,220 --> 00:12:53,820 and transformed the character of that into the previous one, 207 00:12:53,820 --> 00:12:57,180 and therefore concluded that it was the DNA that conveyed that 208 00:12:57,180 --> 00:12:59,860 information, it wasn't protein, it wasn't lipid, 209 00:12:59,860 --> 00:13:03,220 it wasn't the other components - it was DNA. 210 00:13:03,220 --> 00:13:06,540 DNA was the source of Schrodinger's code. 211 00:13:06,540 --> 00:13:09,060 It was where inheritance was written. 212 00:13:09,060 --> 00:13:12,060 So, now the race was on to discover how it worked. 213 00:13:13,660 --> 00:13:17,060 It was already known that the DNA was made of simple sugars, 214 00:13:17,060 --> 00:13:18,980 some phosphate groups, and just 215 00:13:18,980 --> 00:13:21,140 four other chemical structures - 216 00:13:21,140 --> 00:13:23,780 the so-called bases of adenine, 217 00:13:23,780 --> 00:13:26,420 thymine, cytosine and guanine. 218 00:13:27,460 --> 00:13:30,180 But how they all fitted together was a mystery... 219 00:13:31,420 --> 00:13:34,060 ..and the relationship between DNA and genes, 220 00:13:34,060 --> 00:13:36,900 the conceptual carriers of characteristics from one generation 221 00:13:36,900 --> 00:13:38,260 to the next, was another. 222 00:13:39,500 --> 00:13:42,500 These problems were what Maurice Wilkins was trying to solve 223 00:13:42,500 --> 00:13:43,780 with his X-rays. 224 00:13:52,820 --> 00:13:56,180 But Wilkins wasn't the only physicist in the game. 225 00:13:56,180 --> 00:13:59,300 In Cambridge, another out of work weapons designer was 226 00:13:59,300 --> 00:14:00,060 casting his eye over the same problem. 227 00:14:00,300 --> 00:14:01,980 casting his eye over the same problem. 228 00:14:01,980 --> 00:14:04,540 His name was Francis Crick. 229 00:14:04,540 --> 00:14:09,220 But, unlike Wilkins, Crick was not motivated by the horror of war. 230 00:14:09,220 --> 00:14:10,700 He just fancied a change. 231 00:14:14,500 --> 00:14:18,460 After the war, I was, of course, in the Admiralty, but I really didn't 232 00:14:18,460 --> 00:14:22,100 want to go on being a scientific civil servant, as I was, for 233 00:14:22,100 --> 00:14:26,500 the rest of my life, so I decided, "Well, what a marvellous opportunity. 234 00:14:26,500 --> 00:14:30,460 "Here you are at the age of 30, you can go into what you like." 235 00:14:30,460 --> 00:14:33,260 But the problem was, what did I like? 236 00:14:33,260 --> 00:14:34,700 I noticed that I was telling some of my young naval officer friends things, 237 00:14:35,100 --> 00:14:38,220 I noticed that I was telling some of my young naval officer friends things, 238 00:14:38,220 --> 00:14:41,060 I remember one about antibiotics, and it occurred to me 239 00:14:41,060 --> 00:14:43,780 one day that, "You don't know anything about antibiotics! 240 00:14:43,780 --> 00:14:45,540 "You're just gossiping about it." 241 00:14:45,540 --> 00:14:47,980 So, I decided that the gossip test is a good one, 242 00:14:47,980 --> 00:14:51,980 that what you're really interested in is what you gossip about. 243 00:14:51,980 --> 00:14:54,980 So, I looked at what I was gossiping to people about in science 244 00:14:54,980 --> 00:14:58,140 and it boiled down really to two regions - one was the 245 00:14:58,140 --> 00:15:01,220 borderline between the living and the non-living, 246 00:15:01,220 --> 00:15:04,220 and the other was the way the human brain worked. 247 00:15:04,220 --> 00:15:06,420 I knew nothing about either of the subjects. 248 00:15:06,420 --> 00:15:08,700 I decided it had better be molecular biology, 249 00:15:08,700 --> 00:15:11,020 it was nearer to what I knew. 250 00:15:11,020 --> 00:15:14,460 And so that's how I decided to work on molecular biology. 251 00:15:15,580 --> 00:15:17,380 Well, I have to declare an interest, 252 00:15:17,380 --> 00:15:21,220 which is I knew Francis Crick from my childhood. 253 00:15:21,220 --> 00:15:25,900 He, as a young man, during World War II had been allocated, 254 00:15:25,900 --> 00:15:29,580 as a very brilliant, young physicist, 255 00:15:29,580 --> 00:15:34,820 had been allocated a key role in charge of a section that was 256 00:15:34,820 --> 00:15:40,300 developing deep sea mines to blow up enemy shipping. 257 00:15:41,980 --> 00:15:45,820 And he, being the kind of man he was, a numbers man, 258 00:15:45,820 --> 00:15:50,100 decided that he didn't want to do mines that blew up all of shipping. 259 00:15:50,100 --> 00:15:51,380 He wanted to develop a mine 260 00:15:51,380 --> 00:15:54,260 that would only explode under minesweepers 261 00:15:54,260 --> 00:15:58,300 and he did indeed do that, he did it successfully and there are those who 262 00:15:58,300 --> 00:16:01,300 say that he helped win the war at sea because knocking out 263 00:16:01,300 --> 00:16:03,860 the minesweepers was exactly what was needed. 264 00:16:03,860 --> 00:16:05,540 Admiralty never came round to it. 265 00:16:05,540 --> 00:16:11,260 Admiralty thought of him as an uppity, uncontrollable, 266 00:16:11,260 --> 00:16:13,940 difficult young man who wouldn't take orders. 267 00:16:13,940 --> 00:16:19,260 He ran his section with great authority... 268 00:16:19,260 --> 00:16:22,260 So, here's this young man who's been given lots of authority, 269 00:16:22,260 --> 00:16:24,860 way ahead of what he would have got in a lab, 270 00:16:24,860 --> 00:16:27,860 and also has learned to challenge authority and get away with it, 271 00:16:27,860 --> 00:16:30,860 and indeed be able to say he was right. 272 00:16:30,860 --> 00:16:32,460 'So, he comes out of the war 273 00:16:32,460 --> 00:16:36,380 'and he's a very different kettle of fish from Wilkins.' 274 00:16:36,380 --> 00:16:38,420 Amazingly... 275 00:16:38,420 --> 00:16:44,020 links up really fortuitously with a madcap young man from America 276 00:16:44,020 --> 00:16:48,340 who went to university at 16 and never toed the line. 277 00:16:48,340 --> 00:16:52,020 They form an intellectual...couple. 278 00:16:52,020 --> 00:16:54,540 I don't want to say collaboration, they don't collaborate. 279 00:16:54,540 --> 00:16:57,580 They're a sort of, you know, couple. 280 00:16:57,580 --> 00:17:00,580 The madcap American was Jim Watson, 281 00:17:00,580 --> 00:17:03,980 a brilliant biochemist at the start of his career who'd recently 282 00:17:03,980 --> 00:17:07,780 received his PhD at the unlikely age of 22. 283 00:17:07,780 --> 00:17:10,780 'My first couple of months in Cambridge were terribly chaotic. 284 00:17:11,020 --> 00:17:11,340 'My first couple of months in Cambridge were terribly chaotic. 285 00:17:12,620 --> 00:17:15,780 'I went to the digs Max had helped get me at Park Place, 286 00:17:15,780 --> 00:17:20,460 'a dismal place where the landlady wanted me to take off my shoes 287 00:17:20,460 --> 00:17:22,420 'when I came in at night and didn't want me 288 00:17:22,420 --> 00:17:24,900 'to flush the toilet after ten in the evening. 289 00:17:24,900 --> 00:17:27,980 'After a rather short while, I wasn't very sympathetic 290 00:17:27,980 --> 00:17:29,420 'and she threw me out.' 291 00:17:29,420 --> 00:17:32,420 But I think the main thing was that none of these things bothered me 292 00:17:32,420 --> 00:17:33,660 because I'd met Francis. 293 00:17:33,660 --> 00:17:34,020 MUSIC: "Je T'Aime...Moi Non Plus" by Serge Gainsbourg & Jane Birkin 294 00:17:34,260 --> 00:17:37,460 MUSIC: "Je T'Aime...Moi Non Plus" by Serge Gainsbourg & Jane Birkin 295 00:17:43,740 --> 00:17:46,860 'Jim was certainly our first American visitor and' 296 00:17:46,860 --> 00:17:51,220 as soon as we met, we found that, although we had very 297 00:17:51,220 --> 00:17:54,780 different backgrounds, we had a lot of things in common. 298 00:17:54,780 --> 00:17:57,260 Neither of us were trained for what really interested us. 299 00:17:57,260 --> 00:17:59,940 We both wanted to find the gene, we weren't organic chemists, 300 00:17:59,940 --> 00:18:02,700 we weren't anything else. We just wanted to do the best... 301 00:18:02,700 --> 00:18:05,180 To do the most sensible thing. 302 00:18:05,180 --> 00:18:08,220 Francis Crick was a wild man, 303 00:18:08,220 --> 00:18:11,300 a man who encouraged wild behaviour around him. 304 00:18:11,300 --> 00:18:14,900 I was a student at Cambridge when I got to know the family well, 305 00:18:14,900 --> 00:18:18,140 and it was a big joke that 306 00:18:18,140 --> 00:18:20,780 if you stayed out overnight as an undergraduate in those 307 00:18:20,780 --> 00:18:23,900 ancient days, you had to stay with an MA of the university, 308 00:18:23,900 --> 00:18:25,860 so, you could go to one of Crick's 309 00:18:25,860 --> 00:18:27,300 insanely wild parties 310 00:18:27,300 --> 00:18:29,140 and stay the night because he was an 311 00:18:29,140 --> 00:18:31,060 MA of the University of Cambridge, 312 00:18:31,060 --> 00:18:34,820 but I'm telling you, I shouldn't have been at those parties aged 18! 313 00:18:36,580 --> 00:18:42,020 And the thing about Jim Watson was that he was a prude 314 00:18:42,020 --> 00:18:46,780 and he was hopeless with girls and he just tagged along with Francis. 315 00:18:46,780 --> 00:18:49,340 He just always wanted Francis to somehow get him 316 00:18:49,340 --> 00:18:51,260 into the thick of it, but he never did cos 317 00:18:51,260 --> 00:18:54,900 he was sort of somehow too pusillanimous himself. 318 00:18:54,900 --> 00:18:57,980 Crick and Watson's intellectual common ground was 319 00:18:57,980 --> 00:19:02,460 in the idea that they might be able to determine the structure of DNA. 320 00:19:02,460 --> 00:19:05,020 That challenge was something Jim Watson had first heard 321 00:19:05,020 --> 00:19:09,100 described by Maurice Wilkins at a conference he'd attended in Vienna. 322 00:19:11,140 --> 00:19:14,780 Then I suddenly became aware there existed someone... 323 00:19:14,780 --> 00:19:18,980 who actually was trying to solve the structure of DNA, which... 324 00:19:18,980 --> 00:19:21,940 seemed to be the likely candidate for the gene. 325 00:19:21,940 --> 00:19:26,100 But Maurice was serious, deadly serious, and... 326 00:19:26,100 --> 00:19:27,300 I tried to talk to him, 327 00:19:27,300 --> 00:19:32,300 but Maurice is English, he doesn't talk much to strangers, 328 00:19:32,300 --> 00:19:36,860 and so I left and sort of had a vague feeling that it would be nice 329 00:19:36,860 --> 00:19:42,180 if I could work with Maurice, but it wasn't...it wasn't the sort of... 330 00:19:42,180 --> 00:19:44,700 obvious coming together of like minds. 331 00:19:44,700 --> 00:19:46,180 That's a carbon atom... 332 00:19:46,180 --> 00:19:50,140 'Crick and Watson's approach to the problem was to try to imagine 333 00:19:50,140 --> 00:19:54,860 'how all the known parts might fit together, build scale models, 334 00:19:54,860 --> 00:19:56,020 'and talk about them.' 335 00:19:56,020 --> 00:20:01,500 Well, Francis likes to talk...it's his dominant quality, I think. 336 00:20:01,500 --> 00:20:04,580 He doesn't stop unless he gets tired or he thinks the idea is no good 337 00:20:04,580 --> 00:20:08,780 and so, since we hope to solve the structure by talking our way 338 00:20:08,780 --> 00:20:12,660 through it, Francis was the ideal person to do it. 339 00:20:14,060 --> 00:20:16,580 In London, Maurice Wilkins and the King's group 340 00:20:16,580 --> 00:20:19,020 were actually doing something about the problem. 341 00:20:20,100 --> 00:20:23,460 Ray Gosling was a research student at King's at the time 342 00:20:23,460 --> 00:20:26,100 and helped with the X-ray crystallography experiments. 343 00:20:28,500 --> 00:20:32,580 This is the original camera that we... 344 00:20:32,580 --> 00:20:36,100 took the first DNA specimens on in this lab. 345 00:20:36,100 --> 00:20:41,180 And we had a fairly weak X-ray beam so that we needed 346 00:20:41,180 --> 00:20:44,460 lots of material in the beam to get a diffraction pattern. 347 00:20:44,460 --> 00:20:46,660 Now, you see there... 348 00:20:46,660 --> 00:20:51,740 a specimen made with 30 to 40 fibres of DNA wrapped around this 349 00:20:51,740 --> 00:20:55,460 little metal jig there, and we place that in front of the X-ray set... 350 00:20:58,460 --> 00:21:02,060 ..and after about a day, we had a diffraction pattern. 351 00:21:03,260 --> 00:21:05,260 The data the experiments produced 352 00:21:05,260 --> 00:21:08,220 was found in these fuzzy photographs - 353 00:21:08,220 --> 00:21:11,420 pictures of how the X-rays were scattered by the DNA crystals. 354 00:21:13,380 --> 00:21:14,860 These, it was hoped, 355 00:21:14,860 --> 00:21:18,340 would provide the crucial evidence for DNA's elusive structure. 356 00:21:21,180 --> 00:21:24,100 But the results they were getting were disappointing. 357 00:21:24,100 --> 00:21:25,660 The pictures were too fuzzy. 358 00:21:27,180 --> 00:21:29,900 So, because none of the group were expert in the technique, 359 00:21:29,900 --> 00:21:31,700 an expert was hired. 360 00:21:32,940 --> 00:21:38,700 In 1951, Rosalind Franklin arrived to help sharpen up the photos. 361 00:21:38,700 --> 00:21:40,620 Or so they thought. 362 00:21:40,620 --> 00:21:43,540 She actually arrived while Wilkins was away, which was 363 00:21:43,540 --> 00:21:47,380 probably about the most unfortunate mishap in the whole story. 364 00:21:47,380 --> 00:21:49,940 Wilkins was away, he was expecting her, 365 00:21:49,940 --> 00:21:53,260 but she had come much later than she was supposed to come 366 00:21:53,260 --> 00:21:57,340 because her work took longer to finish in Paris than she'd expected. 367 00:21:57,340 --> 00:21:59,860 And she arrived in the laboratory, 368 00:21:59,860 --> 00:22:02,900 she decided what she wanted to do, she'd decided who she was 369 00:22:02,900 --> 00:22:06,620 going to work with, indeed, who was going to be her graduate student. 370 00:22:06,620 --> 00:22:09,900 When she came first to the lab, Wilkins was in America and 371 00:22:09,900 --> 00:22:13,580 the interview took place in Professor Randall's office 372 00:22:13,580 --> 00:22:17,300 between Alex Stokes, myself meeting Rosalind for the first time. 373 00:22:17,300 --> 00:22:21,300 And I can remember my own feelings at that interview, 374 00:22:21,300 --> 00:22:23,740 it was very clear that, as a research student, 375 00:22:23,740 --> 00:22:27,340 I was being formally passed from one to the other and that, 376 00:22:27,340 --> 00:22:30,740 not only was she being given the problem, she was being given 377 00:22:30,740 --> 00:22:33,540 an assistant to work with her on the problem. 378 00:22:33,540 --> 00:22:36,460 Rosalind didn't see herself as collaborating with Maurice, 379 00:22:36,460 --> 00:22:38,980 but there was always this tension between the two. 380 00:22:38,980 --> 00:22:41,740 I think Maurice, uh... 381 00:22:41,740 --> 00:22:45,020 when he brought Rosalind in, afterwards he regretted he'd 382 00:22:45,020 --> 00:22:47,540 given away his problem, that is, he thought he needed help, 383 00:22:47,540 --> 00:22:50,180 brought in someone who was a trained crystallographer 384 00:22:50,180 --> 00:22:52,620 and then discovered that it wasn't his problem any more. 385 00:22:52,620 --> 00:22:54,380 So, it was a catastrophe. 386 00:22:54,380 --> 00:22:56,540 She didn't share and he didn't share, 387 00:22:56,540 --> 00:22:59,900 and I have no idea whether she was a sharing person or not, 388 00:22:59,900 --> 00:23:03,020 but certainly the conditions under which she was working meant 389 00:23:03,020 --> 00:23:06,220 that putting her arm over her work was absolutely, 390 00:23:06,220 --> 00:23:07,900 you know, the starting point. 391 00:23:07,900 --> 00:23:10,900 She certainly wasn't going to let Wilkins have what she was doing. 392 00:23:10,900 --> 00:23:13,180 But how did you get on with Rosalind? 393 00:23:13,180 --> 00:23:15,180 Terrible! Ha, ha! 394 00:23:15,180 --> 00:23:17,820 You make out, Jim, you're sort of some male chauvinist pig, 395 00:23:17,820 --> 00:23:20,220 but I think the real thing was, it wasn't that, it was 396 00:23:20,220 --> 00:23:23,020 the fact that she didn't think you knew much crystallography. 397 00:23:23,020 --> 00:23:25,700 To which she was totally correct. 398 00:23:25,700 --> 00:23:28,460 Rosalind was rather prepared to discount them 399 00:23:28,460 --> 00:23:32,020 as being very serious competitors. I think there was 400 00:23:32,020 --> 00:23:34,980 a general impression in the scientific community 401 00:23:34,980 --> 00:23:37,060 at that time that they were, uh... 402 00:23:38,060 --> 00:23:40,500 ..like butterflies, they were... 403 00:23:40,500 --> 00:23:45,460 flipping around with lots of brilliance, but not much solidity. 404 00:23:45,460 --> 00:23:52,620 And, obviously, in retrospect, this was a sort of ghastly misjudgement. 405 00:23:52,620 --> 00:23:55,700 It was a ghastly misjudgement because the Cambridge butterflies 406 00:23:55,700 --> 00:23:59,020 were actually getting somewhere by building their models, 407 00:23:59,020 --> 00:23:59,620 talking, and perhaps more importantly, listening. 408 00:23:59,900 --> 00:24:02,660 talking, and perhaps more importantly, listening. 409 00:24:05,020 --> 00:24:06,500 In those days, there was 410 00:24:06,500 --> 00:24:10,420 a brilliant young theoretical chemist in Cambridge called John Griffith. 411 00:24:10,420 --> 00:24:13,020 He died quite recently. 412 00:24:13,020 --> 00:24:18,060 And he'd found that adenine stacked nicely on top of thymine 413 00:24:18,060 --> 00:24:19,780 and guanine on top of cytosine. 414 00:24:19,780 --> 00:24:22,660 He'd been thinking along those lines at the time, but I didn't know 415 00:24:22,660 --> 00:24:25,700 that, so I said to him, "That's all right, that's perfect. 416 00:24:25,700 --> 00:24:28,820 "That's all we need for our replication scheme." 417 00:24:28,820 --> 00:24:32,500 The relative amount of the four bases in DNA had been worked 418 00:24:32,500 --> 00:24:35,460 out by a nucleic acid chemist called Erwin Chargaff, 419 00:24:35,460 --> 00:24:38,220 a few years before this time. 420 00:24:38,220 --> 00:24:41,540 And it happened he was passing through Cambridge 421 00:24:41,540 --> 00:24:43,500 and he told us about his results, 422 00:24:43,500 --> 00:24:49,020 which were that the amount of adenine equalled the amount of thymine, 423 00:24:49,020 --> 00:24:53,020 and the amount of guanine equalled the amount of cytosine in all 424 00:24:53,020 --> 00:24:55,260 sorts of DNA, wherever he looked. 425 00:24:55,260 --> 00:24:58,580 Although the other ratios were all over the place. 426 00:24:58,580 --> 00:25:02,820 Well, the effect on me was electric because I saw immediately 427 00:25:02,820 --> 00:25:06,660 that this is what you'd expect from a scheme like John Griffith's. 428 00:25:07,780 --> 00:25:10,940 So, I was very excited. I didn't mention it to Chargaff at the time, 429 00:25:10,940 --> 00:25:13,500 because it was work I was doing with John Griffith, 430 00:25:13,500 --> 00:25:17,260 but when we checked it all out, we could see the two fitted together. 431 00:25:24,500 --> 00:25:27,140 Crick and Watson now got word from the US 432 00:25:27,140 --> 00:25:29,940 that the legendary chemist Linus Pauling was 433 00:25:29,940 --> 00:25:31,820 also working on the DNA problem. 434 00:25:33,140 --> 00:25:37,020 Armed with a draft copy of Pauling's soon to be published ideas, 435 00:25:37,020 --> 00:25:40,260 Watson went to King's to discuss them with Wilkins. 436 00:25:42,260 --> 00:25:44,540 Maurice read it and, in his usual way, 437 00:25:44,540 --> 00:25:47,020 didn't convey sort of enthusiasm one way or the other, 438 00:25:47,020 --> 00:25:49,460 but I guess he sort of said he didn't think Linus 439 00:25:49,460 --> 00:25:51,460 was going to get the right structure. 440 00:25:51,460 --> 00:25:54,980 At the same time however, he sort of let loose the bombshell, at least 441 00:25:54,980 --> 00:25:59,900 to me, when he said there was two types of DNA X-ray photographs. 442 00:25:59,900 --> 00:26:03,100 There was the form which I knew about called the A-form, which gave this 443 00:26:03,100 --> 00:26:06,700 crystalline pattern, but there was this second from called the B-form. 444 00:26:06,700 --> 00:26:09,140 He opened a drawer, took out a photograph and, boy, 445 00:26:09,140 --> 00:26:12,180 I could hardly believe it! It was a perfect helix. 446 00:26:12,180 --> 00:26:15,100 It was a cross-like pattern and the told me that they 447 00:26:15,100 --> 00:26:18,380 repeated it and that meant there was a helix. 448 00:26:18,380 --> 00:26:21,940 I thought also that I should go and see Rosalind. 449 00:26:21,940 --> 00:26:25,900 It was clear that she was annoyed at my trying to tell her something about 450 00:26:25,900 --> 00:26:27,900 crystallography, and she came toward me 451 00:26:27,900 --> 00:26:30,340 and I thought she was going to hit me, so I quickly got out, 452 00:26:30,340 --> 00:26:33,780 at which point Maurice was coming around and she almost hit Maurice! 453 00:26:33,780 --> 00:26:35,780 Oh, God! Who hit who?! 454 00:26:35,780 --> 00:26:38,100 I don't think anybody hit anybody, actually. 455 00:26:38,100 --> 00:26:39,460 Some people may have thought 456 00:26:39,460 --> 00:26:41,700 someone was going to hit somebody, 457 00:26:41,700 --> 00:26:43,300 but, um... 458 00:26:43,300 --> 00:26:44,460 there certainly weren't 459 00:26:44,460 --> 00:26:45,580 very friendly feelings. 460 00:26:47,780 --> 00:26:51,260 Watson escaped back to Cambridge in one piece, carrying with him 461 00:26:51,260 --> 00:26:54,500 the memory of the B-form photograph that Franklin had taken 462 00:26:54,500 --> 00:26:56,580 and Wilkins had shown him. 463 00:26:58,380 --> 00:27:00,980 Straightaway, he started a new model. 464 00:27:00,980 --> 00:27:03,220 So, I cut some things out of cardboard 465 00:27:03,220 --> 00:27:06,220 and made the right shapes and then pasted things on, which would 466 00:27:06,220 --> 00:27:09,340 indicate hydrogen atoms, and then I think I went off and played tennis. 467 00:27:09,340 --> 00:27:12,300 I would do maybe three hours a day. 468 00:27:12,300 --> 00:27:15,220 It was hard to get at it in the morning, but... 469 00:27:15,220 --> 00:27:17,860 Because by the time you get in there was morning coffee, 470 00:27:17,860 --> 00:27:20,500 then you'd go for lunch, have a walk, and then I'd come back 471 00:27:20,500 --> 00:27:22,300 and build the model and, sort of, 472 00:27:22,300 --> 00:27:24,500 Francis was working on his thesis... 473 00:27:24,500 --> 00:27:28,580 I would look over my shoulder to try and see what Jim was doing. 474 00:27:28,580 --> 00:27:31,180 I guess it's awfully hard to give up an idea of your own, so 475 00:27:31,180 --> 00:27:33,260 I started putting the phosphates in the centre, 476 00:27:33,260 --> 00:27:35,740 maybe because it was sort of like a Pauling structure. 477 00:27:35,740 --> 00:27:38,380 Maybe, if we would have used ions we'd get somewhere, 478 00:27:38,380 --> 00:27:40,700 but Francis really wasn't comfortable with this, 479 00:27:40,700 --> 00:27:44,020 and told me, why don't I try putting the phosphates on the outside? 480 00:27:44,020 --> 00:27:47,500 I can't really remember why you said that, Francis. 481 00:27:47,500 --> 00:27:49,820 Well, it's because, I think, Jim, that, you know, 482 00:27:49,820 --> 00:27:51,580 you were obsessional about having them 483 00:27:51,580 --> 00:27:56,420 on the inside and you produced a lot of phony arguments as to why 484 00:27:56,420 --> 00:27:59,540 basic groups from protamines had to go in, 485 00:27:59,540 --> 00:28:02,100 and in all collaboration, it's very important 486 00:28:02,100 --> 00:28:05,740 when one person has an idea, that the 487 00:28:05,740 --> 00:28:09,380 other person criticises it as they were the devil's advocate, 488 00:28:09,380 --> 00:28:12,420 so, just for the very reason that Jim was keen on having 489 00:28:12,420 --> 00:28:14,060 the phosphates on the inside, 490 00:28:14,060 --> 00:28:16,180 I thought he ought to try on the outside. 491 00:28:16,180 --> 00:28:18,980 And suddenly I could put together A and T, and G and C. 492 00:28:18,980 --> 00:28:20,340 I could hardly believe it. 493 00:28:20,340 --> 00:28:22,780 Francis came in almost immediately and saw this. 494 00:28:22,780 --> 00:28:26,140 Something came out of the model building that Jim had done, 495 00:28:26,140 --> 00:28:27,540 which he hadn't put in, 496 00:28:27,540 --> 00:28:30,620 and that's always the sign that you feel you're on the right lines. 497 00:28:30,620 --> 00:28:30,660 When something begins to click, which you hadn't actually 498 00:28:30,900 --> 00:28:34,020 When something begins to click, which you hadn't actually 499 00:28:34,020 --> 00:28:36,940 put in, in your thinking, which you knew was there. 500 00:28:36,940 --> 00:28:40,860 But, even more important, Francis, by using these rules, A and T 501 00:28:40,860 --> 00:28:43,900 and G and C, we understood how the molecule replicated. 502 00:28:43,900 --> 00:28:46,540 Everything from then on was clear. 503 00:28:46,540 --> 00:28:50,100 Everything was finished except the hard work, that's to say, 504 00:28:50,100 --> 00:28:52,380 producing an accurate model. 505 00:28:52,580 --> 00:28:52,700 producing an accurate model. 506 00:28:52,700 --> 00:28:57,380 I worked continuously for about four days and, uh... 507 00:28:57,380 --> 00:28:57,580 then came the point where we saw that everything fitted, 508 00:28:57,900 --> 00:29:00,980 then came the point where we saw that everything fitted, 509 00:29:00,980 --> 00:29:03,940 and I was so tired I went straight home and went to bed. 510 00:29:08,540 --> 00:29:11,340 The structure of DNA had been found. 511 00:29:12,740 --> 00:29:16,700 A pair of sugar chains, linked by the A, G, C and T bases, 512 00:29:16,700 --> 00:29:19,540 twisted into a double helix. 513 00:29:19,540 --> 00:29:22,780 But, more than that, its structure made it immediately obvious 514 00:29:22,780 --> 00:29:26,500 how DNA could make copies of itself. 515 00:29:26,500 --> 00:29:30,300 If the strand of DNA is split apart, identical copies can be 516 00:29:30,300 --> 00:29:35,020 reassembled because each base can only pair up with its base partner. 517 00:29:37,220 --> 00:29:38,860 There before us 518 00:29:38,860 --> 00:29:40,940 was the answer to one of the 519 00:29:40,940 --> 00:29:43,700 fundamental problems in biology - 520 00:29:43,700 --> 00:29:45,540 how do genes replicate? 521 00:29:45,540 --> 00:29:47,580 And it was very simple... 522 00:29:47,580 --> 00:29:49,860 and you couldn't miss it. 523 00:29:49,860 --> 00:29:52,940 The great paper that was published in the early 1950s with 524 00:29:52,940 --> 00:29:57,140 the structure of DNA is actually a masterpiece and beautifully 525 00:29:57,140 --> 00:30:02,220 understated, ending with what I'm sure must have been a Crick 526 00:30:02,220 --> 00:30:07,300 sentence about the significance of this structure has not escaped us. 527 00:30:07,300 --> 00:30:10,660 We used to occasionally, just...Jim and I, just sit 528 00:30:10,660 --> 00:30:15,180 and look at the molecule and think how beautiful it was. 529 00:30:15,180 --> 00:30:16,700 And I remember on occasion 530 00:30:16,700 --> 00:30:20,500 when Jim gave a talk to a little biophysics club we had. 531 00:30:20,500 --> 00:30:23,220 It's true, they gave him one or two drinks before dinner. 532 00:30:23,220 --> 00:30:26,340 It was rather a short talk because all he could say at the end was, 533 00:30:26,340 --> 00:30:30,260 "Well, you see, it's so pretty. It's so pretty." 534 00:30:30,260 --> 00:30:33,780 The twin successes of the discovery of the structure of DNA and 535 00:30:33,780 --> 00:30:39,580 the mechanism for its replication was a critical moment in science. 536 00:30:39,580 --> 00:30:44,620 I was a student in Edinburgh and, rather cleverly, my tutor told me 537 00:30:44,620 --> 00:30:48,780 to go to the library and to find the most important paper in biology. 538 00:30:48,780 --> 00:30:50,060 I thought, "This man is mad. 539 00:30:50,060 --> 00:30:51,180 "How am I going to do this?" 540 00:30:51,180 --> 00:30:53,180 I walked in, and remember, these were the days 541 00:30:53,180 --> 00:30:55,340 when everything was bound into big volumes, 542 00:30:55,340 --> 00:30:59,060 and I walked past the journal Nature, bound in green, 543 00:30:59,060 --> 00:31:02,940 covered in dust, until you got to the 1953 issue, 544 00:31:02,940 --> 00:31:05,940 and it was battered, it was torn, the back of the cover was come off... 545 00:31:05,940 --> 00:31:08,900 You opened it up and two pages fell out which were black with the 546 00:31:08,900 --> 00:31:13,060 grease of many scientists' fingers, and that was the Watson-Crick paper. 547 00:31:19,060 --> 00:31:22,500 The paper may have rocked the scientific world, but, so far as 548 00:31:22,500 --> 00:31:28,260 the public were concerned, 1953 was a year remembered for bad weather... 549 00:31:28,260 --> 00:31:30,540 The waters rose with the wind... 550 00:31:30,540 --> 00:31:33,900 ..the coronation, and the conquering of Mount Everest. 551 00:31:35,020 --> 00:31:38,500 Edmund Hillary, beekeeper from New Zealand... 552 00:31:38,500 --> 00:31:40,300 Tenzing Norgay... 553 00:31:40,300 --> 00:31:45,180 Sherpa from Nepal, conquerors of Everest, May 29th 1953. 554 00:31:45,180 --> 00:31:48,860 The structure of DNA doesn't even get a mention. 555 00:31:48,860 --> 00:31:52,300 Biology really wasn't on the agenda, certainly not on the public agenda or 556 00:31:52,300 --> 00:31:56,420 the press agenda, that was not what they were going to get excited about. 557 00:31:56,420 --> 00:31:59,180 The public were still in love with physics and chemistry, 558 00:31:59,180 --> 00:32:02,460 and they were, so, if you look at the South Ken exhibition 559 00:32:02,460 --> 00:32:06,300 for the Festival Of Britain in 1951, 560 00:32:06,300 --> 00:32:08,340 it's all physics and chemistry. 561 00:32:08,340 --> 00:32:12,740 All the excitement of molecules and then the excitement of radar 562 00:32:12,740 --> 00:32:15,580 and the excitement...not bombs, of course, nothing about bombs. 563 00:32:16,980 --> 00:32:21,220 But biology, toughened up by physics, was on the march. 564 00:32:21,220 --> 00:32:24,900 New vaccines and medicines had whetted the public's appetite 565 00:32:24,900 --> 00:32:28,820 and in 1962, when Crick and Watson, together with Maurice Wilkins, 566 00:32:28,820 --> 00:32:31,460 were awarded the Nobel Prize for Medicine, 567 00:32:31,460 --> 00:32:35,180 the double helix DNA had well and truly arrived. 568 00:32:37,420 --> 00:32:40,380 'The BBC even commissioned this special programme 569 00:32:40,380 --> 00:32:42,380 'about the prize winners.' 570 00:32:42,380 --> 00:32:45,660 This is to be a personal programme about these men. 571 00:32:45,660 --> 00:32:48,420 In a few moments, through television, you will be able to meet them 572 00:32:48,420 --> 00:32:52,100 and judge for yourselves what manner of men they are. 573 00:32:52,100 --> 00:32:55,020 'Biology was now at the forefront of science. 574 00:32:55,020 --> 00:32:57,260 'The possibilities seemed endless.' 575 00:32:58,500 --> 00:33:02,260 I think one can reasonably predict that within the next 20, 30, 576 00:33:02,260 --> 00:33:05,740 50 years, there will be an immense increase of knowledge 577 00:33:05,740 --> 00:33:08,500 about the higher nervous system and about ourselves, 578 00:33:08,500 --> 00:33:10,820 and I think, myself, as a personal belief, 579 00:33:10,820 --> 00:33:14,580 it will radically change the way we think about ourselves as persons 580 00:33:14,580 --> 00:33:16,700 and also, eventually, as people in society. 581 00:33:18,340 --> 00:33:22,220 The old rivalries were put aside, at least for a while. 582 00:33:23,580 --> 00:33:26,060 'Though, since the Nobel Prize was awarded, 583 00:33:26,060 --> 00:33:28,860 'the public memory has been of Crick and Watson, 584 00:33:28,860 --> 00:33:31,620 'and not of the others who helped them over the line.' 585 00:33:31,620 --> 00:33:34,260 But, of course, the Watson-Crick breakthrough was... 586 00:33:34,260 --> 00:33:35,460 ..as I've said many times, 587 00:33:35,460 --> 00:33:36,940 a little sort of pinnacle built 588 00:33:36,940 --> 00:33:40,260 on an immense basis of chemistry, 589 00:33:40,260 --> 00:33:43,740 biochemistry, genetics and so on. 590 00:33:43,740 --> 00:33:48,100 Essential work which people like Todd and Chargaff 591 00:33:48,100 --> 00:33:50,980 and many others had to work through 592 00:33:50,980 --> 00:33:51,060 before I was able to put 593 00:33:51,300 --> 00:33:52,980 before I was able to put 594 00:33:52,980 --> 00:33:57,220 the three-dimensional structure of DNA on top. 595 00:34:00,980 --> 00:34:04,900 Perhaps least celebrated of all was Rosalind Franklin... 596 00:34:04,900 --> 00:34:07,780 who'd provided the crucial evidence in the form of the B-form 597 00:34:07,780 --> 00:34:11,420 diffraction pattern that provided the final part of the jigsaw. 598 00:34:14,020 --> 00:34:18,660 Franklin had developed ovarian cancer and died in 1958, 599 00:34:18,660 --> 00:34:23,020 and so never knew about the prize or the public excitement around DNA. 600 00:34:24,980 --> 00:34:28,300 It's often said she was unjustly overlooked, 601 00:34:28,300 --> 00:34:31,340 but the Nobel Prize is not awarded posthumously, 602 00:34:31,340 --> 00:34:34,060 so the truth is less clear. 603 00:34:34,060 --> 00:34:37,940 I sometimes wonder what would have happened had Rosalind Franklin 604 00:34:37,940 --> 00:34:40,860 been alive when that Nobel Prize was given. 605 00:34:40,860 --> 00:34:44,420 I don't really know what the outcome of that would have been. 606 00:34:44,420 --> 00:34:47,620 The Nobel Prize is only given to three individuals. 607 00:34:47,620 --> 00:34:53,100 Crick and Watson would have been clear. Um, I suspect... 608 00:34:53,100 --> 00:34:57,620 that Franklin might have trumped Wilkins. 609 00:34:57,620 --> 00:34:58,140 Um, I don't know that for sure. 610 00:34:58,300 --> 00:34:59,980 Um, I don't know that for sure. 611 00:34:59,980 --> 00:35:04,180 But that, I think, would have been a definite possibility. 612 00:35:04,180 --> 00:35:06,820 'Though many contributed to the discovery, 613 00:35:06,820 --> 00:35:10,020 'it was ultimately Crick and Watson who made it, 614 00:35:10,020 --> 00:35:12,580 'and they have their own views as to why.' 615 00:35:14,340 --> 00:35:17,140 We weren't in the least afraid of being very candid 616 00:35:17,140 --> 00:35:19,460 to each other, to the point of being rude, 617 00:35:19,460 --> 00:35:22,020 and if you don't have constant interchange 618 00:35:22,020 --> 00:35:25,180 and chatting together and saying what you think about the other people's 619 00:35:25,180 --> 00:35:29,220 ideas to their face, I don't think you can solve problems of this kind. 620 00:35:29,220 --> 00:35:31,900 We sort of pooled the way we looked at things. 621 00:35:31,900 --> 00:35:35,380 We didn't leave it that Jim did the biology and I did the physics. 622 00:35:35,380 --> 00:35:39,620 We both did it together and switched roles and criticised each other, 623 00:35:39,620 --> 00:35:43,100 and this gave us a great advantage over the other people who were 624 00:35:43,100 --> 00:35:44,380 trying to solve it. 625 00:35:44,380 --> 00:35:47,020 You see, what I think is interesting is that Crick and Watson 626 00:35:47,020 --> 00:35:49,540 do insist on how collaborative their own work 627 00:35:49,540 --> 00:35:54,220 was between the two of them, but I don't kind of regard two as much 628 00:35:54,220 --> 00:36:00,660 of a collaboration, and I think it was more of an intense relationship. 629 00:36:00,660 --> 00:36:02,300 Scientific relationship. 630 00:36:02,300 --> 00:36:05,820 And the fact that they absolutely knew that they needed one another. 631 00:36:05,820 --> 00:36:10,740 They each needed the expertise from the other's discipline. 632 00:36:10,740 --> 00:36:14,900 They were absolutely not collaborative scientists outside. 633 00:36:14,900 --> 00:36:21,580 Not in the least. For them, it was a game of who you could beat. 634 00:36:21,580 --> 00:36:24,420 Um, in my hearing, 635 00:36:24,420 --> 00:36:27,580 I heard them laughing about Linus Pauling 636 00:36:27,580 --> 00:36:30,740 and not showing something to Linus Pauling 637 00:36:30,740 --> 00:36:33,180 because otherwise his lab might get there first. 638 00:36:33,180 --> 00:36:34,820 It was all about who'd get there first. 639 00:36:34,820 --> 00:36:36,820 That's not collaborative science. 640 00:36:36,820 --> 00:36:40,500 Maurice Wilkins seems to have been all too willing to collaborate. 641 00:36:40,500 --> 00:36:43,260 He was, perhaps, a naive idealist 642 00:36:43,260 --> 00:36:46,020 and something of a victim of his understated demeanour. 643 00:36:47,220 --> 00:36:50,500 Wilkins was an active Communist in his youth. 644 00:36:50,500 --> 00:36:54,140 He was a spiky, spunky man. 645 00:36:54,140 --> 00:36:59,140 We have no knowledge of that, partly because, presumably, such 646 00:36:59,140 --> 00:37:03,620 activities as he was engaged in, he didn't exactly trumpet abroad. 647 00:37:03,620 --> 00:37:06,500 The only reason I know that he was that kind of man is 648 00:37:06,500 --> 00:37:10,180 because his MI5 file was released in 2010. 649 00:37:10,180 --> 00:37:13,620 And it is clear from there that he was regarded as a threat. 650 00:37:13,620 --> 00:37:17,620 'Uh, Wilkins must have been a much gutsier man in his youth than' 651 00:37:17,620 --> 00:37:21,820 the bits of film that we see of him, would lead one to believe. 652 00:37:21,820 --> 00:37:23,260 Are you interested in music? 653 00:37:24,380 --> 00:37:26,220 Well... 654 00:37:26,220 --> 00:37:30,500 I used to be, but I'm not so interested now. 655 00:37:30,500 --> 00:37:32,980 The reason we think of Maurice Wilkins as this irritable 656 00:37:32,980 --> 00:37:35,580 and actually, irritating man, 657 00:37:35,580 --> 00:37:38,620 when my view is that as a young man he was probably quite dashing 658 00:37:38,620 --> 00:37:42,980 and exciting and Communist and non-aligned, um, 659 00:37:42,980 --> 00:37:47,140 is because of his behaviour around the fact that Rosalind Franklin 660 00:37:47,140 --> 00:37:50,500 just wouldn't play ball, wouldn't be a member of a collaborative lab, 661 00:37:50,500 --> 00:37:53,460 and I'm sure, in Paris, had not been expected to be. 662 00:37:53,460 --> 00:37:56,020 She didn't get it, she didn't sign up for it, 663 00:37:56,020 --> 00:37:57,500 she hadn't signed up for it. 664 00:37:57,500 --> 00:38:01,020 The fact she wasn't allowed in the common room at King's, London, 665 00:38:01,020 --> 00:38:04,580 because women weren't allowed in it, really didn't help. 666 00:38:04,580 --> 00:38:08,900 Um, and therefore Wilkins' collaborative endeavour 667 00:38:08,900 --> 00:38:13,180 embraced everybody outside, but broke down in his own lab. 668 00:38:13,180 --> 00:38:15,140 And, looking back on it, of course, 669 00:38:15,140 --> 00:38:16,420 it's quite clear that 670 00:38:16,420 --> 00:38:18,420 if you regard sort of getting 671 00:38:18,420 --> 00:38:20,420 a structure of DNA as a race, 672 00:38:20,420 --> 00:38:23,780 that we'd lost the race very early on, 673 00:38:23,780 --> 00:38:26,140 because we didn't find it 674 00:38:26,140 --> 00:38:28,580 possible to work together. 675 00:38:29,940 --> 00:38:34,700 Regardless of who won or lost, learning the structure of DNA 676 00:38:34,700 --> 00:38:37,740 and finding out how it might replicate were huge 677 00:38:37,740 --> 00:38:40,580 Nobel Prize winning discoveries. 678 00:38:40,580 --> 00:38:44,980 But knowing these things revealed nothing about how DNA actually 679 00:38:44,980 --> 00:38:50,260 turns mindless chemicals into trees, frogs, parrots and people. 680 00:38:50,260 --> 00:38:54,980 How our genes, now realised to be discrete sections of DNA, give us 681 00:38:54,980 --> 00:39:00,140 unique anatomies and personalities, making each of us who we are. 682 00:39:00,140 --> 00:39:03,140 This became known as the coding problem. 683 00:39:03,140 --> 00:39:06,380 So, the next important problem was the coding problem. 684 00:39:06,380 --> 00:39:09,220 Um, of great interest to Crick. 685 00:39:09,220 --> 00:39:12,500 By this time, Watson had left, gone back to the United States 686 00:39:12,500 --> 00:39:15,060 and Sydney Brenner turned up. 687 00:39:15,060 --> 00:39:18,300 'Sydney Brenner was a reluctant doctor from South Africa 688 00:39:18,300 --> 00:39:21,500 'who'd hung up his stethoscope in favour of research 689 00:39:21,500 --> 00:39:23,220 'as soon as he possibly could.' 690 00:39:25,460 --> 00:39:29,060 'When I grew up in a small town in South Africa, 691 00:39:29,060 --> 00:39:31,460 'where my father was a shoemaker... 692 00:39:31,460 --> 00:39:36,380 'uh, at the age of 15, I went to university and' 693 00:39:36,380 --> 00:39:40,700 I was strongly advised that, for the subject I was interested in, 694 00:39:40,700 --> 00:39:45,340 which people thought was biological chemistry or whatever, 695 00:39:45,340 --> 00:39:49,300 the only jobs existed in medical schools. 696 00:39:49,300 --> 00:39:51,660 And so, I was told, you've got to get a medical degree 697 00:39:51,660 --> 00:39:54,900 because no-one will employ you in a medical school without 698 00:39:54,900 --> 00:39:57,060 a medical degree, which I did. 699 00:39:57,060 --> 00:39:59,020 It was another four years. 700 00:39:59,020 --> 00:40:00,780 It was actually four and a half years 701 00:40:00,780 --> 00:40:03,660 because I failed my finals 702 00:40:03,660 --> 00:40:06,500 in Medicine by diagnosing 703 00:40:06,500 --> 00:40:08,980 one lady as having an acute attack of 704 00:40:08,980 --> 00:40:11,220 the use of Macleans toothpaste, 705 00:40:11,220 --> 00:40:13,220 rather than something else. 706 00:40:13,220 --> 00:40:15,300 I was right, she had actually used 707 00:40:15,300 --> 00:40:16,740 Macleans toothpaste. 708 00:40:16,740 --> 00:40:18,940 I was told to smell her breath and 709 00:40:18,940 --> 00:40:21,540 that's all I could smell. However... 710 00:40:21,540 --> 00:40:23,540 But I did return and did the other 711 00:40:23,540 --> 00:40:25,580 six months and finally passed. 712 00:40:27,100 --> 00:40:32,100 It is a very difficult experience doing science, I think, 713 00:40:32,100 --> 00:40:35,780 in a provincial atmosphere. 714 00:40:37,780 --> 00:40:44,060 All this changed for me when I came to England to work for a PhD. 715 00:40:44,060 --> 00:40:46,740 If I laid out all those great scientists who I had 716 00:40:46,740 --> 00:40:51,580 the privilege of knowing as a child, Sydney Brenner was the funniest one. 717 00:40:51,580 --> 00:40:54,260 Sydney Brenner was just damn funny. 718 00:40:54,260 --> 00:40:58,460 And comfortable to be around. He was a sort of... 719 00:40:58,460 --> 00:41:00,540 very gregarious, 720 00:41:00,540 --> 00:41:02,980 very open... 721 00:41:02,980 --> 00:41:07,060 open-faced, open everything...man. 722 00:41:07,060 --> 00:41:09,460 He rode a huge motorbike, you know. 723 00:41:09,460 --> 00:41:15,780 He was...but he was very sort of stocky and together, and, eh... 724 00:41:15,780 --> 00:41:18,660 I suspect I thought he was quite glamorous. 725 00:41:18,660 --> 00:41:22,060 Now, Sydney Brenner, another one of these brilliant characters 726 00:41:22,060 --> 00:41:24,500 who's also extremely witty and humorous. 727 00:41:24,500 --> 00:41:27,900 I perhaps know Sydney the best of all the characters, 728 00:41:27,900 --> 00:41:31,620 perhaps together with Jim Watson, 729 00:41:31,620 --> 00:41:34,980 and I always seek him out if there's a dinner so I can sit next 730 00:41:34,980 --> 00:41:38,860 to him, cos I will be highly entertained throughout dinner. 731 00:41:38,860 --> 00:41:41,780 Just like humour, you put different things together, you 732 00:41:41,780 --> 00:41:47,180 juxtapose different sorts of ideas and thinking, and they're funny. 733 00:41:47,180 --> 00:41:50,100 It's the way he also carried out his science, he would put different 734 00:41:50,100 --> 00:41:53,780 things together and see how things could emerge from it. 735 00:41:53,780 --> 00:41:57,260 I think they were related - the creativity of humour, 736 00:41:57,260 --> 00:42:02,220 I see also was in his creativity of tackling the coding problem. 737 00:42:02,500 --> 00:42:02,740 I see also was in his creativity of tackling the coding problem. 738 00:42:02,740 --> 00:42:06,340 Now, the coding problem was enormously attractive, 739 00:42:06,340 --> 00:42:08,780 because, in a sense... 740 00:42:08,780 --> 00:42:13,060 it looked possible that you could crack it, solve it... 741 00:42:13,060 --> 00:42:14,900 without doing any work at all. 742 00:42:14,900 --> 00:42:20,420 There would be something in the sequence that you could then 743 00:42:20,420 --> 00:42:22,580 sit down and write down the code. 744 00:42:22,580 --> 00:42:29,500 Once again, we have a collaboration. This time it's Crick with Brenner. 745 00:42:29,500 --> 00:42:31,740 Watson's gone back to the United States. 746 00:42:31,740 --> 00:42:36,940 During the period that Brenner and Crick were working together, 747 00:42:36,940 --> 00:42:40,860 there was one of the greatest experiments of all time to 748 00:42:40,860 --> 00:42:45,940 determine what's called the triplet nature of the genetic code, 749 00:42:45,940 --> 00:42:49,420 because the problem was this - in DNA, 750 00:42:49,420 --> 00:42:52,740 you have a language made up of four letters... 751 00:42:52,740 --> 00:42:56,060 and in proteins, the language is made up of 20 letters, 752 00:42:56,060 --> 00:43:00,260 so, you can't encode for 20 different letters by 4 alone. 753 00:43:00,260 --> 00:43:05,260 They have to be read either in twos or threes or fours, 754 00:43:05,260 --> 00:43:10,820 and the key experiment was what the number was. 755 00:43:10,820 --> 00:43:14,940 And there was an absolutely genius experiment done, 756 00:43:14,940 --> 00:43:18,460 where the...and Crick explains this, 757 00:43:18,460 --> 00:43:23,260 that he introduced mutations 758 00:43:23,260 --> 00:43:27,580 and if you introduce one mutation then you destroy function, 759 00:43:27,580 --> 00:43:30,020 if you introduce two, you would destroy function, 760 00:43:30,020 --> 00:43:33,660 if you introduce three...you've got the function back again, 761 00:43:33,660 --> 00:43:39,700 because all you did was lose one amino acid and then the rest was OK. 762 00:43:39,700 --> 00:43:43,020 And this is a brilliant piece of abstract reasoning which came 763 00:43:43,020 --> 00:43:45,100 to a concrete conclusion. 764 00:43:45,100 --> 00:43:48,140 'We had discovered that the dye, proflavine, 765 00:43:48,140 --> 00:43:53,940 'does cause additions and deletions of bases in DNA.' 766 00:43:53,940 --> 00:43:58,620 DNA consists of a one-dimensional sequence of 767 00:43:58,620 --> 00:44:01,300 four different building blocks - the bases. 768 00:44:04,380 --> 00:44:08,820 The proteins consist of another language, the amino acids, 769 00:44:08,820 --> 00:44:10,740 of which there are 20. 770 00:44:12,060 --> 00:44:17,020 You need more than one nuclear type to correspond to an amino acid 771 00:44:17,020 --> 00:44:20,820 because there are only four of the first and 20 of the latter. 772 00:44:20,820 --> 00:44:22,780 Indeed, you need at least three, 773 00:44:22,780 --> 00:44:26,380 so we suspected the code was a triplet one. 774 00:44:26,380 --> 00:44:27,900 We also suspected that it was 775 00:44:27,900 --> 00:44:31,660 read from one end, three at a time. 776 00:44:31,660 --> 00:44:37,260 Imagine a gene being composed of the triplet CAT, C-A-T. 777 00:44:37,260 --> 00:44:40,700 So, we have CAT, CAT, CAT, CAT, CAT, CAT, CAT. 778 00:44:41,820 --> 00:44:45,780 You can see that if you delete one of these nucleotides, 779 00:44:45,780 --> 00:44:50,060 beyond the deletion, it's converted into gibberish - ATC, ATC, and so on. 780 00:44:52,900 --> 00:44:55,500 If you delete yet another nucleotide, 781 00:44:55,500 --> 00:45:00,420 you will see you get the second form of gibberish - TCA, TCA. 782 00:45:01,700 --> 00:45:04,700 But if you delete a third nucleotide, 783 00:45:04,700 --> 00:45:06,140 you convert it back to the 784 00:45:06,140 --> 00:45:09,300 original message - CAT, CAT, CAT. 785 00:45:10,380 --> 00:45:12,340 It absolutely worked. 786 00:45:12,340 --> 00:45:14,900 It proved that the code was non-overlapping 787 00:45:14,900 --> 00:45:19,260 and a triplet one, and then, as a joke, we later called 788 00:45:19,260 --> 00:45:25,100 the triplet a codon - the unit corresponding to one amino acid. 789 00:45:25,100 --> 00:45:28,380 So, this was an example of the sort of thinking, the brilliance 790 00:45:28,380 --> 00:45:34,260 of the thinking, that was tackling problems in rather simple ways. 791 00:45:34,260 --> 00:45:37,740 Not fantastically sophisticated equipment and so on, 792 00:45:37,740 --> 00:45:40,460 but brilliant logical reasoning. 793 00:45:41,980 --> 00:45:43,980 What had been accomplished as a result of 794 00:45:43,980 --> 00:45:45,540 Crick and Brenner's discovery, 795 00:45:45,540 --> 00:45:48,580 had opened the door to the ultimate possibility - 796 00:45:48,580 --> 00:45:51,820 that DNA was the book of life. 797 00:45:51,820 --> 00:45:54,180 That the units of inheritance, the genes, 798 00:45:54,180 --> 00:45:59,660 were simply specific sequences of A, C, G and T held in the DNA... 799 00:45:59,660 --> 00:46:02,180 and that it could all be read in its entirety. 800 00:46:03,540 --> 00:46:07,020 But before the final assault on the stuff of life could begin, 801 00:46:07,020 --> 00:46:08,860 another problem needed solving. 802 00:46:10,700 --> 00:46:14,540 Even though the structure of DNA was known, and it had been shown that 803 00:46:14,540 --> 00:46:16,900 DNA coded for proteins, 804 00:46:16,900 --> 00:46:21,140 actually reading the exact order of the bases was proving impossible. 805 00:46:25,740 --> 00:46:29,220 Enter Fred Sanger who, like Crick and Brenner, 806 00:46:29,220 --> 00:46:31,860 was from the Molecular Biology lab in Cambridge. 807 00:46:32,980 --> 00:46:39,940 Fred Sanger, who I also know a little bit, is... 808 00:46:39,940 --> 00:46:45,100 a very humble man, somebody you hardly would notice, you know, 809 00:46:45,100 --> 00:46:49,460 you'd think he was the gardener, I'm sure, in Cambridge rather than, 810 00:46:49,460 --> 00:46:52,900 you know, one of the greatest scientists of his time. 811 00:46:54,180 --> 00:46:56,020 Fred Sanger had already received 812 00:46:56,020 --> 00:46:57,820 a Nobel Prize for discovering 813 00:46:57,820 --> 00:47:00,260 the structure of proteins. 814 00:47:00,260 --> 00:47:03,700 Now, he turned his attention to how to read or sequence 815 00:47:03,700 --> 00:47:06,620 DNA's elusive code. 816 00:47:06,620 --> 00:47:10,940 For Sanger, there was a useful similarity between proteins and DNA. 817 00:47:12,020 --> 00:47:15,540 One became much more interested in nucleic acids. 818 00:47:15,540 --> 00:47:19,340 Again, it was a long chain molecule similar to the proteins. 819 00:47:20,780 --> 00:47:23,860 So, that there was a similar problem there. 820 00:47:23,860 --> 00:47:27,980 And I thought maybe my abilities would be 821 00:47:27,980 --> 00:47:31,860 useful in that field, and we might be able to do something in sequencing 822 00:47:31,860 --> 00:47:37,020 them because, clearly, the sequence was the important thing about them. 823 00:47:37,020 --> 00:47:39,460 I think Fred Sanger, 824 00:47:39,460 --> 00:47:43,420 who really pioneered the notion of sequencing DNA, 825 00:47:43,420 --> 00:47:46,380 using what in retrospect was a clumsy method, 826 00:47:46,380 --> 00:47:48,780 but was the only one that was then available. 827 00:47:48,780 --> 00:47:52,660 Um, he's again a rather forgotten figure by the general public, 828 00:47:52,660 --> 00:47:56,900 and he set out to do something which certainly, when I was a... 829 00:47:56,900 --> 00:48:00,180 student of genetics and I was doing my PhD in genetics, and even 830 00:48:00,180 --> 00:48:01,900 when I started my career in genetics, 831 00:48:01,900 --> 00:48:04,020 seemed fundamentally impossible, 832 00:48:04,020 --> 00:48:06,980 the idea that you could read off a complete genome 833 00:48:06,980 --> 00:48:09,300 just seemed completely out of the window, 834 00:48:09,300 --> 00:48:12,260 let alone that you could read off the human genome. 835 00:48:12,260 --> 00:48:16,540 But Sanger started the job with this method of labelling the bases 836 00:48:16,540 --> 00:48:19,700 one at a time and chipping them off and separating them, 837 00:48:19,700 --> 00:48:23,980 and just reading them ploddingly slowly from one end to another, 838 00:48:23,980 --> 00:48:28,660 and he played a central part in the technical change, 839 00:48:28,660 --> 00:48:33,500 which turned genetics into the modern day equivalent of anatomy. 840 00:48:44,340 --> 00:48:47,260 Fred Sanger's work earned him another Nobel Prize 841 00:48:47,260 --> 00:48:51,260 and opened the door to a tantalising prospect - 842 00:48:51,260 --> 00:48:55,780 that the DNA of an entire species, its genome, could be read. 843 00:48:55,780 --> 00:48:58,260 That its genetic code could be solved. 844 00:49:03,660 --> 00:49:06,500 John Sulston is the archetypal, left-leaning, 845 00:49:06,500 --> 00:49:10,460 Guardian-reading, muesli-eating scientist. 846 00:49:10,460 --> 00:49:12,500 I like muesli, you know? 847 00:49:12,500 --> 00:49:16,180 I'm not doing it for any particular reason, I suppose that's what I mean. 848 00:49:16,180 --> 00:49:17,500 CAT MEOWS 849 00:49:17,500 --> 00:49:20,020 Sulston is a man with a very clear idea of what is 850 00:49:20,020 --> 00:49:22,380 important in life and what is not. 851 00:49:23,900 --> 00:49:27,300 Um, I suppose simple... 852 00:49:27,300 --> 00:49:30,740 rampant, anti-consumerist, well, non-consumerist is the point, 853 00:49:30,740 --> 00:49:34,700 but, on the whole, the presumption is that one is not going to buy 854 00:49:34,700 --> 00:49:38,020 things rather than that you are, if you see what I mean. 855 00:49:38,020 --> 00:49:40,740 Um, what do you want, really? I mean, it's... 856 00:49:41,980 --> 00:49:45,740 It's thinking and reading and talking and all of that that matters, 857 00:49:45,740 --> 00:49:47,820 not actually having stuff, unless the stuff's there for a purpose. 858 00:49:48,020 --> 00:49:49,700 not actually having stuff, unless the stuff's there for a purpose. 859 00:49:49,700 --> 00:49:53,020 His low-key domestic arrangements give few clues 860 00:49:53,020 --> 00:49:54,980 to his standing in the academic world. 861 00:49:56,860 --> 00:49:59,620 Like Sanger, Wilkins, Watson and Crick, 862 00:49:59,620 --> 00:50:01,540 John Sulston has a Nobel Prize. 863 00:50:03,500 --> 00:50:05,820 It was awarded for cataloguing the development of 864 00:50:05,820 --> 00:50:08,580 every single cell in the nematode worm. 865 00:50:09,820 --> 00:50:14,700 Years of research culminating in 18 months of intensive observation. 866 00:50:14,700 --> 00:50:18,940 Eight hours every day looking at worm cells through his microscope. 867 00:50:20,260 --> 00:50:23,420 I think it's rather fun, really. You know, it's a job of work. 868 00:50:23,420 --> 00:50:26,540 You don't have to worry about what you're going to do the next day, 869 00:50:26,540 --> 00:50:27,900 you know what you're going to do - 870 00:50:27,900 --> 00:50:30,060 you're going to watch some more cells divide. 871 00:50:31,980 --> 00:50:35,780 What he did next was even more tedious. 872 00:50:35,780 --> 00:50:38,780 To work out exactly why the cells behaved as they did, 873 00:50:38,780 --> 00:50:41,660 Sulston needed to understand their genes. 874 00:50:43,900 --> 00:50:44,620 And to do that meant sequencing them. 875 00:50:44,860 --> 00:50:46,860 And to do that meant sequencing them. 876 00:50:46,860 --> 00:50:47,860 All of them. 877 00:50:49,420 --> 00:50:52,740 Before we began, people said, "Oh, it's not worth doing that. 878 00:50:52,740 --> 00:50:54,100 "What you ought to be doing is to study real biological problems. 879 00:50:54,340 --> 00:50:55,500 "What you ought to be doing is to study real biological problems. 880 00:50:55,500 --> 00:50:58,540 "Look, John, you've done all this cell linaging. You ought to be 881 00:50:58,540 --> 00:51:01,500 "getting mutants and finding out how the cell linage works." 882 00:51:01,500 --> 00:51:04,420 And I said, "Hmm, I'm not sure. I think it's more complicated 883 00:51:04,420 --> 00:51:06,980 "than that. We really need to get at all the genes." 884 00:51:06,980 --> 00:51:10,100 And so I started this business of looking 885 00:51:10,100 --> 00:51:13,140 directly at the genome as a whole. 886 00:51:13,140 --> 00:51:17,020 The nematode worm genome was the proof of concept. 887 00:51:17,020 --> 00:51:20,420 Now, the way was clear for the ultimate prize. 888 00:51:20,420 --> 00:51:23,340 The mild-mannered worm scientist found himself running 889 00:51:23,340 --> 00:51:27,260 the British part of a global effort to read the human genome. 890 00:51:30,020 --> 00:51:33,460 From its outset, Sulston believed that the Human Genome Project 891 00:51:33,460 --> 00:51:36,860 was a noble undertaking for the benefit of everyone. 892 00:51:36,860 --> 00:51:40,900 All the labs met in Bermuda, and we met in Bermuda precisely because it's 893 00:51:40,900 --> 00:51:44,940 a rock in the middle of the Atlantic, so it's a sort of neutral place. 894 00:51:44,940 --> 00:51:47,420 It was in the off season, I should add. 895 00:51:47,420 --> 00:51:52,180 So, we were there and we...I remember standing at the board there, 896 00:51:52,180 --> 00:51:54,900 trying to construct with the assembled labs 897 00:51:54,900 --> 00:51:58,460 a statement to the effect that all of us would release 898 00:51:58,460 --> 00:52:02,420 all of our data all the time and we would not try to take patterns. 899 00:52:02,420 --> 00:52:05,860 And we came out with what have been called the Bermuda Principles 900 00:52:05,860 --> 00:52:11,060 and have actually informed quite a lot of endeavour since. 901 00:52:11,060 --> 00:52:13,300 It was all done in a very gentlemanly 902 00:52:13,300 --> 00:52:16,620 and gentlewomanly way, and everybody was very nice 903 00:52:16,620 --> 00:52:19,340 and decent and I would say rather British about it. 904 00:52:19,340 --> 00:52:23,220 And then suddenly into this calm, Cambridge environment came 905 00:52:23,220 --> 00:52:27,500 a bombshell, this chap called Craig Venter. 906 00:52:32,380 --> 00:52:36,860 Craig Venter had been the team leader of one of the genome groups 907 00:52:36,860 --> 00:52:39,620 in the US, but had decided to go it alone. 908 00:52:39,620 --> 00:52:43,340 There was, he decided, money to be made in the human genome. 909 00:52:48,340 --> 00:52:51,860 There were lots of bio-tech companies that viewed 910 00:52:51,860 --> 00:52:53,900 genes as commodities. 911 00:52:53,900 --> 00:52:57,020 People started assuming you got a patent on a human gene, 912 00:52:57,020 --> 00:52:58,980 you would get a billion-dollar drug. 913 00:53:00,420 --> 00:53:03,820 This went against everything Sulston believed. 914 00:53:03,820 --> 00:53:08,140 Human genes should be owned by the public, not owned by any 915 00:53:08,140 --> 00:53:11,660 particular person or even corporation or even government. 916 00:53:11,660 --> 00:53:12,820 They are publicly owned. 917 00:53:12,820 --> 00:53:15,740 John Sulston now found himself 918 00:53:15,740 --> 00:53:18,700 as the reluctant defender of the people's genome. 919 00:53:20,140 --> 00:53:21,740 He was now in a race. 920 00:53:21,740 --> 00:53:23,180 Every gene that he identified 921 00:53:23,180 --> 00:53:26,380 and published was one that couldn't be patented by Venter. 922 00:53:27,660 --> 00:53:31,140 He secured extra funding to ensure his UK group could complete 923 00:53:31,140 --> 00:53:34,780 a third of the genome, and jetted to America to stiffen 924 00:53:34,780 --> 00:53:37,780 the resolve of the National Institute of Health, who were 925 00:53:37,780 --> 00:53:43,460 on the brink of cutting a deal with their former employee's new company. 926 00:53:43,460 --> 00:53:46,540 I think it did turn things around, because NIH were in fact 927 00:53:46,540 --> 00:53:49,420 making moves to compromise, because they thought they were dead. 928 00:53:49,420 --> 00:53:51,700 They thought Congress would just say, all right, 929 00:53:51,700 --> 00:53:55,260 now you've got a company doing it, you're not allowed to compete. 930 00:53:55,260 --> 00:53:57,900 But by us coming in and saying, well, the Brits are going to do 931 00:53:57,900 --> 00:54:00,740 a third publicly, it really stiffened their backs. 932 00:54:00,740 --> 00:54:02,660 You could see the moral force it had. 933 00:54:02,660 --> 00:54:07,700 Not for the first time in the story of DNA, things got nasty. 934 00:54:07,700 --> 00:54:10,340 John wanted to sequence the human genome. 935 00:54:10,340 --> 00:54:12,300 I wanted to sequence the human genome. 936 00:54:12,300 --> 00:54:14,860 I can't fault him for wanting to do that. 937 00:54:14,860 --> 00:54:17,340 But it was more important to him 938 00:54:17,340 --> 00:54:19,220 to be the one to do it than to 939 00:54:19,220 --> 00:54:21,460 enable it to get done quickly. 940 00:54:21,460 --> 00:54:24,140 I suppose I am anti-capitalist to the point where 941 00:54:24,140 --> 00:54:27,060 I feel that companies are completely unnecessary, yes, that's right. 942 00:54:27,060 --> 00:54:28,580 I think we'd get on very well 943 00:54:28,580 --> 00:54:30,940 if we did all that discovery in universities, frankly. 944 00:54:30,940 --> 00:54:34,340 They gave him the Nobel Prize for counting cells in a worm, right? 945 00:54:34,340 --> 00:54:36,700 The absolutely debilitating diseases - AIDS - 946 00:54:36,700 --> 00:54:40,620 of Africa and other developing countries, they cannot be dealt with 947 00:54:40,620 --> 00:54:43,580 on a capitalist basis, because there is no market, there is no money. 948 00:54:43,580 --> 00:54:47,460 So, you now have two programmes going in parallel. 949 00:54:47,460 --> 00:54:52,140 One, a public programme, set up for the public good, 950 00:54:52,140 --> 00:54:53,980 a second, a private programme, 951 00:54:53,980 --> 00:54:56,180 ultimately leading to the public good, 952 00:54:56,180 --> 00:54:58,460 but in the meantime going to make a lot of money. 953 00:54:58,460 --> 00:55:03,060 Our efforts are at least equally important, if not more so, 954 00:55:03,060 --> 00:55:05,060 because it forced them to get going 955 00:55:05,060 --> 00:55:07,900 and get off their butts and actually do something. 956 00:55:07,900 --> 00:55:10,220 Ah, yes, "I lit a fire under the human genome." 957 00:55:10,220 --> 00:55:11,780 They always like that image! 958 00:55:11,780 --> 00:55:15,700 But I think objectively the facts speak against it. 959 00:55:15,700 --> 00:55:18,260 I really don't think that it was helpful. 960 00:55:18,260 --> 00:55:21,620 I think we'd have finished pretty much next year anyway. 961 00:55:21,620 --> 00:55:24,060 And without all the fuss. 962 00:55:24,060 --> 00:55:27,420 Sulston is a much, much more traditional scientist, 963 00:55:27,420 --> 00:55:30,780 much more of the Maurice Wilkins type, the sharing, 964 00:55:30,780 --> 00:55:33,940 collaborative, making the world a better place. 965 00:55:33,940 --> 00:55:37,140 I wouldn't have thought it would have crossed his mind that he 966 00:55:37,140 --> 00:55:38,860 could make his fortune. 967 00:55:38,860 --> 00:55:41,700 I think Venter saw very early on he could make his fortune. 968 00:55:41,700 --> 00:55:44,020 I don't think it's a bad thing, but he saw it. 969 00:55:44,020 --> 00:55:48,660 Well, Venter was simply, you know, he was... How can I summarise it? 970 00:55:48,660 --> 00:55:52,060 Venter was an American. Sulston was British. 971 00:55:52,060 --> 00:55:54,580 That, I think, summarises the entire problem. 972 00:55:59,860 --> 00:56:03,500 But, ultimately, it was politicians - British and American - 973 00:56:03,500 --> 00:56:06,700 who came down on the side of the people's genome. 974 00:56:06,700 --> 00:56:10,820 ..Genome science and its benefits will be directed toward making life 975 00:56:10,820 --> 00:56:15,300 better for all citizens of the world, never just a privileged few. 976 00:56:16,420 --> 00:56:18,380 In 2000, Bill Clinton 977 00:56:18,380 --> 00:56:22,460 and Tony Blair announced that the race was effectively over 978 00:56:22,460 --> 00:56:26,260 and that no-one would be making any money by patenting genes. 979 00:56:26,260 --> 00:56:28,620 When the public project guys, 980 00:56:28,620 --> 00:56:31,380 ie, you and everyone else, got Tony Blair 981 00:56:31,380 --> 00:56:34,420 and Bill Clinton to make that announcement early last year, 982 00:56:34,420 --> 00:56:37,420 when they said they would like to see unencumbered access 983 00:56:37,420 --> 00:56:43,220 to this data, it wiped $150 off Venter's company's share price. 984 00:56:43,220 --> 00:56:45,620 It's a natural thing that that would drop. 985 00:56:45,620 --> 00:56:48,300 But it must have made you smile, put a smile on your face. 986 00:56:48,300 --> 00:56:50,700 HE CHUCKLES Well, it has now! 987 00:56:50,700 --> 00:56:55,380 Well, yes, but the trouble is, at the same time - it's true, I smile, 988 00:56:55,380 --> 00:57:00,420 but these are minor victories or skirmishes in the whole thing. 989 00:57:03,140 --> 00:57:07,140 Much has been made of the importance of the reading of the human genome, 990 00:57:07,140 --> 00:57:11,460 of the medical benefits that will emerge from its now cracked code. 991 00:57:11,460 --> 00:57:15,540 That maybe it even holds the secret of life itself. 992 00:57:15,540 --> 00:57:19,620 We cannot understand what life is without understanding 993 00:57:19,620 --> 00:57:23,660 the genome, but it is only one part of the problem. 994 00:57:23,660 --> 00:57:28,660 And we need also to understand how living organisms work, 995 00:57:28,660 --> 00:57:32,140 how cells work, how tissues and organs work. 996 00:57:32,140 --> 00:57:36,860 Without the human genome sequence, we can hardly address the problem. 997 00:57:36,860 --> 00:57:40,100 It is crucial, but it is not the only thing we need to know. 998 00:57:43,540 --> 00:57:46,140 Since the middle of the last century, 999 00:57:46,140 --> 00:57:49,140 the murky business of inheritance has been dragged out 1000 00:57:49,140 --> 00:57:52,460 of an age of near witchcraft to one where individual groups 1001 00:57:52,460 --> 00:57:55,940 of atoms, in what was once considered the "stupid molecule", 1002 00:57:55,940 --> 00:57:58,780 are now recognised as agents of heredity. 1003 00:58:00,060 --> 00:58:04,820 Crick and Watson's identification of DNA structure, 1004 00:58:04,820 --> 00:58:09,220 informed by the crystallography done by the King's group, 1005 00:58:09,220 --> 00:58:12,420 Sydney Brenner's solution to the coding problem, 1006 00:58:12,420 --> 00:58:16,100 Fred Sanger's work on sequencing, and the global effort to read 1007 00:58:16,100 --> 00:58:18,340 the human genome, has revealed what some might call the code of life. 1008 00:58:18,620 --> 00:58:21,580 the human genome, has revealed what some might call the code of life. 1009 00:58:21,580 --> 00:58:24,420 But, in reality, DNA, 1010 00:58:24,420 --> 00:58:29,700 coding and genomics is only the start of the next chapter.