Life Story

BBC Horizon - The Race for the Double Helix

14,662 views  Premiered on 15 Mar 2022  #NOVA #BBC #Horizon

 Author Isaac Asimov joins NOVA in the retelling of the remarkable story of the discovery of the structure of DNA. James Watson and his ex-colleague Francis Crick exchange memories of the events which led to their winning the race for the structure of the gene.

#NOVA #BBC #Horizon #Documentary

Music] why does a calf look like its mother well for that matter why do cows always produce calves and not rabbits or camels i suppose you could say it's because they always do but that's really not a scientific explanation a scientist wants to know the details of inheritance [Music] this straw contains bull sperm each straw contains 25 million sperm and yet one of those sperm is enough to fertilize a cow and produce a new individual a new individual with four legs ahead all the details right and different from any other cow all that information or at least half of it has to be contained in the head the minute head of these very tiny sperm that shows that it must be written in a very minute language it must be written in some way in a chemical language not only that when the egg has been fertilized it divides into two into four into eight produces millions of cells in each one of those cells there's a copy a precise copy of all that genetic information when i left physics 25 years ago it seemed to me that these two problems how you store genetic information in such a small space and how you copied it exactly every time a cell divided they seem to me the two most important problems in biology at that time a young american james watson from harvard and two englishmen francis crick from cambridge and morris wilkins from london were awarded the 1962 nobel prize for medicine they discovered the nature of the inheritance chemical dna or deoxyribonucleic acid doing the research that led to this nobel prize needed outstanding imagination but before the moment of elation there were blunders frustration insights personal conflicts between colleagues a sense of competition [Music] this film is the story of the process of discovery [Music] cambridge in the early 1950s was the setting for watson and crick's part in the dna story cambridge after the war was rather an exciting place because a lot of us young and not so young had come back to do biological research i myself was doing cell biology there were a lot of other people in that general area there was a lot of interest in the chemistry of life and foremost amongst the characters around the place was of course francis crick and jim watson on the face of it francis crick and james watson were a rather improbable pair to solve what was then the most important problem in biology because crick was already about 35 he hadn't even finished his own doctoral thesis though i can't say i remember he was remarkably good at giving advice on to other people on solving their doctoral thesis um and watson was a very bright young man american who hadn't done a great deal and crick was a physicist he didn't know very much about biology and watson didn't know very much about molecules and officially at least they never really collaborated on dna but informally unofficially they argue with each other and in a really rather dramatic way uh did solve what i think one must call the problem of the century jim was certainly our first american visitor when i got home that evening my wife said to me you know max was round with a rather strange young american geneticist and you know what she said he had no hair that's because he had a crew cut in those days and uh as soon as we met we found uh that although we had very different backgrounds we had a lot of things in common neither of us were trained for what really interested us now we both wanted to find the gene we weren't organic chemists we weren't anything else we just wanted to do the best we wanted to do the most sensible thing i've been self-taught i was stuck in cambridge there weren't that number of people who i could communicate with so that when i met you it was you were the first person in the outside world what is it in living cells that carries the genetic information from generation to generation what specifies how an organism grows at one level chromosomes are the answer and within the chromosomes the genes but how does a gene work and what is it made of by the end of the 1940s it was becoming clear that dna was the most likely candidate professor john randall had set up a group at king's college london to investigate the processes in living cells in randall's king's college group maurice wilkins was working on dna i was a physicist who'd worked during the war on on the atom bomb and uh i was rather disgusted by the way in which science had been misapplied and so i want to get out of physics and i thought there were bigger potentiality for uh using science in a sort of beneficial way in biology wilkins work on genetic material took him on a visit to naples early in 1951 while there he gave a talk on dna in the audience was jim watson and then i suddenly became aware there existed someone who actually was trying to solve the structure of dna which seemed to be the likely candidate for the gene but morris was serious and deadly serious and i tried to talk to him but morris i feel you know he's english and doesn't talk much to strangers and so i left and sort of vague feeling that would be nice if i could work with morris but it wasn't it wasn't a sort of obvious coming together of like minds jim watson realized that england was the ideal place to pursue his dna interest by a lucky accident he managed to obtain a place at cambridge there the medical research council had an ambitious program of research on biological molecules my first couple months in cambridge were terribly chaotic when i went up i went to the digs and max had helped get me on park place and dismal place where the landlady wanted me to take off my shoes when i came in at night and didn't want me to flush the toilet after 10 in the evening and after a rather short while i wasn't very sympathetic and she threw me out but i think the main thing was that none of these things bothered me because i met francis and it was a tremendous change before that i had been with lots of bright people which was very useful and i couldn't agree with any of them i guess both of us at that time our thoughts were somewhat dominated by linus pauling might have been dominated for a long while because he was sort of the symbol of caltech greatness and he was the great chemist who was going to solve biology and uh had you met lymeless by this time he smiled he smiled at you once i remember it very clearly because we were uh walking in the the washroom of the athenian the sort of faculty club of caltech and linus looks down at me and smiles at me and i think a strange place for this to happen linus pauling then professor of chemistry at the california institute of technology is one of the most eminent chemists of this century he was awarded the nobel prize for his work on the chemical bond he came to public notice recently through his suggestion that vitamin c could fend off the common cold in the late 1940s brilliant insight enabled pauling to work out an important element in the structure of proteins the so-called alpha helix one day when i was eastman professor at oxford in the spring of 1948 to april 1948 i caught a cold it was before the vitamin c days i caught a cold and after a day or two in bed reading science fiction and detective stories i got tired of that and i thought why don't i discover the alpha helix or thought something like that i took a piece of paper much like this piece and i drew on it to a representation of an extended polypeptide chain with the distances approximately right and the angles right except that one angle does not have did not have the right to value i still have that original piece of paper by the way this is the bond angle at the alpha carbon atom that didn't have the right value so i folded the paper actually it took several trials i folded it along several parallel lines through the successive alpha carbon atoms and finally i found a way by folding the paper i can make this bond angle have the value 110 degrees and i finally found a way of folding such that a hydrogen bond which held the helical structure together and had just the right dimensions it was the combination of deep chemical insight and brilliant inspiration that made linus pauling a potential threat would he now solve dna in the same manner of course linus pauling was a genius at this sort of thing he was capable of taking shortcuts he knew how to take a small part of the data use the rules of model building erect some general theoretical postulate and from out of that would become one or small number of models which would fit the data and what we decided really was that we'd try and use the same sort of method that he used on the alpha helix in trying to solve the structure of dna watson and crick hoped that by working out the molecular structure of dna deoxyribonucleic acid they'd get the insight as to how the hereditary mechanism is stored and duplicated in living cells and they decided that the linus pauling method was the right one for them they wanted to do it by thought and not by a lot of laborious experiment and that perhaps is rather the key to it because that was their style how did they set about it well the chemists had already shown that dna was made up of a lot of subunits the subunits consisted of sugars and phosphates and bases and it was known that there were four sorts of bases there was adenine there was thymine cytosine guanine and all these were put together in what were very long molecules it was known that there were hundreds of subunits in these dna molecules so that there undoubtedly were millions of possible combinations and one needed to know which was the right one well now how could they exclude all the irrelevant and the impossible combinations and for that one needed some hard experimental data on dna uh and the only place where that was coming from at the time was the group at king's college london raymond gosling was a phd student at king's college in professor randall's team uh professor randle was using the electron microscope to look for the genetic structure in ram sperm and as a junior research student at the time i was given the job of persuading a whole heap of brand sperm to lie down in an orderly fashion and try and get an x-ray diffraction photograph of them not getting a very clear picture i went to morris wilkins who was looking at extracted dna and had find that you could pull it into fibers so that i use these fibers to make a specimen to give me a dna pattern that i could compare with the ram sperm pattern of course pulling fibers isn't quite as easy as it sounds you take some of the pure material and put a little on the microscope slide add just enough water to make the gel and then you can use a glass fiber stuck on the side of the microscope with a piece of plasticine which you lower into the gel and you need the lamp on the side to see the fibers which when they come are very very tiny indeed and here we go persuade some of it to stick to the end of the rod like this and then gently raise it up out of the jelly until you get a column like that from which the fiber will run if you're lucky ah so back to square one it seems rather more difficult after 20 years than i in fact remembered this is the original camera that we took the first dna specimens on in this lab and we had a fairly weak x-ray beam so that we needed lots of material in the beam to get a diffraction cap and you see there a specimen made with 30 to 40 fibers of dna wrapped around this little metal jig there and we placed that in front of the x-ray set and after about a day we had a diffraction pattern what we realized we wanted was a much more intense beam that would let us look at single dna fibers this is the camera that we use to take photographs of single fibers you can see it's a very simple affair the single fiber is placed straight across the hole there defining the small beam of x-rays the film is in the back of the camera in this half they simply go together like that and you mount the camera in front of this x-ray set which had just been developed at the time and it was really the coming together of these three things being able to have a single strand a camera which would look at that strand with a very fine very intense beam of x-rays that previously hadn't been available and that enabled us to get diffraction photographs from a small crystalline region within one single fiber deciding what these pictures said about dna's structure needed specialist know-how rosalind franklin brought this expertise to the king's college group i first met rather than franklin late 1953 at birkbeck college where we both came to work on problems of virus structure i was perhaps her closest and certainly her last scientific colleague until her death four years later and got to know pretty well she would sometimes talk about dna and was very clear she'd been engaged by randall to put some teeth into the dna effort at kings when she came first to the lab wilkins was in america and the interview took place in professor randall's office between alex stokes myself meeting rosalind for the first time and i can remember my my own feelings at that interview it was very clear that as a research student i was being formally passed from one to the other and that not only was she being given the problem she was being given an assistant to work with her on the problem within a short time of her arrival at kings although she had known nothing about dna beforehand she uh rather transformed the problem and from the kind of murky pictures they had before she got excellent clear pictures which could be used for quantitative analysis scientifically the king's college work was going well but personal relationships between rosalind franklin and maurice wilkins had become rather strained well of course roslyn franklin was a professional crystallographer she'd done crystallography before and i think she always regarded morris as being less so and i think this was part of the the trouble between them rosney wanted to take over the problem and do it all herself and um while didn't see herself as collaborating with morris but there was always this tension between the two it was the days before a woman's live but she felt it was long do and women were badly discriminated against i think at king's college and uh i think morris uh when he brought roslyn in uh sort of afterwards regretted he'd given away his problem that is he thought he needed help brought in someone who's a trained crystallographer and then discovered that it wasn't his problem anymore i was a sort of general physical molecular biologist and i hadn't at all specialized in x-ray diffraction methods and so rosalind franklin was brought into this work uh because she was an experienced very able uh x-ray diffraction sort of specialist professional and uh looking back on it of course it's quite clear that if you regard sort of getting the structure of dna as a race that we'd lost the race very early on because we didn't find it possible to work together morris was and still is i think a reserved person rosslyn i don't think was so reserved she was shy so that she was intense morris wilkins was rather withdrawn and so they were really just about as different as you could get but how did you get on with roslyn terrible you make out jim you're sort of some male chauvinist pig but i think the real thing was it wasn't that it was the fact that she didn't think you knew much crystallography to which he was totally correct rosalind was rather prepared to discount them as being very serious competitors i think there was a general impression in the scientific community at that time that they were like butterflies they are flipping around with lots of lots of brilliance but not much solidity and obviously in retrospect this was a ghastly misjudgment by now rosalind franklin's pictures were good enough to analyze and she presented her results at a meeting which jim watson attended it was in kings which was next to somerset house it was a very old sort of place and it was almost dick in the slack and uh not many people really cared about what roslyn said it was a small audience and uh i didn't well i made this terrible mistake because well you're only a newborn crystallography how are you tonight the difference between the unit 7 the asymmetric unit but anyways i got the water wrong by a factor of 24 or something what what jim essentially reported was that in the way in the terms he uses was that it was a dry structure actually the facts were was extremely wet but this was due to the misunderstanding of two technical terms so we had an abortive attempt trying to solve the structure as if it were dry and we even got so far when we got back to cambridge to build models and i got very excited do you remember all that jim i was very excited probably because francis was excited it was our first dna model it wasn't very pretty but it was our first model so i guess we're pleased with it it did look like a sort of cylinder of things didn't it just tell them with things sticking out roughly speaking so we called up people with kings and said we solved it and would they like to see the answer and they came up because scared to death that we might have because they've been working on it and probably also skeptical that you couldn't have really guessed it without seeing the pictures but anyways the really especially roslyn because she was sort of a trained crystallographer knew how she thought you should solve it in a semi-logical fashion and uh here we were disobeying all the rules we didn't care much about the evidence we were going to sort of try and build a pretty structure and one which obeyed chemical rules and she didn't really think it was going to work but when she got up and we started explaining things she immediately asked you know where was the water and i said that there wasn't any you said that of course she said i didn't say that and i felt rather stupid and uh we all felt rise to you i think the housing was a complete flop and they were stumped back to london and got confident that we made assets ourselves of course the cambridge model really was an embarrassment to us to see these highly intelligent um cambridge chaps turning up with something which was obviously so crazily wrong it's uh i mean the whole thing was inside out i mean it's intuitively seen to us quite wrong that the phosphate said to be in the inside like that and the bases were on the outside and what the hell were they doing there but it had the effect that uh it was sort of a crying wolf and uh whereas up to then you know if we'd ask them some data they would have said uh sure this is what it is because they didn't think we were that interested now they knew we were deadly interested in in what they sort of had a long-range program maybe it'd take you another five ten years uh and we'll come up with the answer the fiasco over the model with the king's college group irritated sir lawrence bragg who was the head of the cavendish laboratory and as a matter of fact crick didn't always endear himself to brag i remember bragg once saying to me that crick's extremely penetrating voice made his head bars at 10 rate this last trouble wasn't the only one because some months earlier there'd been a problem over scientific priority as far as i could tell francis had just told the professor he'd stolen his ideas and of course when you tell your professor you're a thief someone has to give either you or the professor well you always had an exaggerated view of that jim the the plain fact of the matter was that i'd had a an idea of a of the crystallographic sort of idea and i discussed it with perez and kendra and as it turned out i'd even given it to the small cloak in which bragg was present but you know uh lots of ideas are mentioned you don't always take it up and actually what had happened was braggart had it independently but when bragg said isn't a nice idea and so on so forth i was you know young and naive and i couldn't resist saying yes it's it's very good but it's of course exactly what i was saying six months ago and nobody likes to be told that and he told me afterwards he didn't want to go to the tea room because he'd have to hear francis's voice which just meant that you know remind him of this thing and maybe he actually did pinch the idea you know it's very difficult because uh you know you hear someone's idea and maybe you you don't listen to him and he says something and then afterwards you think about it and god you know you've discovered independently and someone calls you a thief and so the border line between stealing someone else's idea and arriving at it independently is not always as clean cut as you think and since your memory is often you know it's hard to do it anyways it was a sort of tricky situation because i think from that moment on break had well you know a lot of ambitions chiefs they'd understand proteins but one of his minor ambitions certainly was that francis should leave the lab bragg wanted crick to stop talking so much and get on with his phd thesis and so he actually ordered francis to stop working on dna well now bragg and randall were two very powerful important figures and you might say that they rarely carved up the territory between themselves because bragg's lab at cambridge it was agreed would work on proteins and randall's lab in london it was agreed would work on dna so that francis by keeping on working on dna was in braggsville rocking the boat and protocol in those days and maybe even today as a matter of fact is really rather important so that you know dna was randall's territory and not bragg's but of course those sort of restraints didn't apply to linus pauling in fact linus uh wrote a letter or someone surprised me who said he was going to come to europe and hoped he could talk to me about francis and my work on dna pauling really was interested in everything sort of someday he was going to hit on dna and we kept telling morris yes we kept trying to frighten him just like the the mothers in the time of napoleon used to try and send their children to sleep by saying if you don't come to sleep boney will come we used to say tomorrow if you don't solve the structure you know lioness pauling will solve it you see didn't move morris he wanted to put the sound way and not be bullied by us morris had told us that linus in fact had asked them for their data that is to look at their x-ray photographs and i think by morris thought well i don't want to send linus our data until we've had enough time ourselves to look at it i wrote to wilkins at king's college asking if i could have prints of the photographs that he had obtained but i my effort was not successful so that i continued to work on the basis of these poor poorer photographs and of course this this was in part responsible for my failure to find the structure well it's really a matter of etiquette in these things so there is a convention which i think is very right in science that when you've done a lot of work and got some experimental data you have that should have the first chance of interpreting it you're not supposed to sit on it for years because the whole essence of science is communication but if you've done the work you should have the first go so i think was quite reasonable for morris not to give out his data before he'd done it at the time linus pauling wanted to come to england the mccarthy purges were at their height in america because of pauling's pacifist sympathies his passport was withdrawn some news of linus's scientific progress reached the cavendish through letters to his son peter my father wrote me a letter saying that he had uh had an idea for the structure of dna and we're going to publish it in the proceedings of the national academy of sciences which my father being a member he didn't have to have it refereed they'd publish it automatically he asked me whether i wanted a manuscript copy of it this was something that would be published within a month but did i want it sooner so i wrote back and said yes please and it came of course we're upset and the question was could it be right and we knew that linus didn't have a good x-ray photograph so could he have thought it through without any of the king's data as i recall jim peter didn't know at the time what the structure was he just knew that there was a structure so we were really on tenterhooks now in those days i had no idea what a gene was no idea what dna was uh in fact as i remember i had no idea what anything was and this paper came and i didn't know what any of this meant so i gave it to these two men one on my right hand side jim watson and one on my left hand side francis crick who seemed to have some idea they seemed to be interested peter came in with a big grin on his face and said he had his father's manuscript or even his magic princess actually about tore it from him to read what it was and quickly went through it it certainly wasn't confidential information this was just a preprint manuscript so i gave it to them and they looked at it and they seemed to understand it according to jim not only did i not know what nucleic acids were but my father didn't know either in fact he decided that dna was a deoxyribonucleic acid wasn't in effect an acid it wasn't charged it was using these hydrogen atoms sort of to form hydrogen bonds and it was a three stranded structure and we just couldn't believe it so the question was why did he do this why did he say that a nucleic acid wasn't an acid we didn't know and i rushed around cambridge showing it to people asking could he be right and they all said no it's an acid and as the afternoon wore on i was you know feeling a great relief that we still had a chance that the problem hadn't been solved by uh lioness we was born in the great release gym we were hilarious i'm sorry to say the thing we must have embarrassed poor peter because it wasn't absolutely i would say transparent it was wrong but we at least formed the opinion it was highly probable my father did the structure of mica and sodalite and a lot of other things and to him dna was just another chemical well it's nice using this particular method actually the stochastic method of of trying to determine the truth by conjecture in other words guessing you get so excited and interested that it's nice to get the right answer out and it's also nice to get the right answer out first but it's more important to get the right answer rather than be first now in his case he got the wrong answer well of course linus pauling really had terribly bad luck he had poor x-ray pictures but even worse than that they were misleading they were really two x-ray pictures on top of one another so the data that he used to get produce his structure didn't correspond to anything at all it isn't too surprising he got it wrong now at kings they had much better x-ray pictures an x-ray picture is not a simple picture like a photograph and to understand what you expect from a helix you have to work out a mathematical theory which shows you what the diffraction pattern would be and the mathematical theory of x-ray diffraction which was worked out for helix by several of us says that there will be a strong spot on the x-ray pattern in this direction here right angles of this line such as there on the pattern which has its center there and you can equally see that waves coming up this way here will also be strongly diffracted so you'll get that one up there and by symmetry one down there and one down there now it's also true that if you have shorter waves you get the same result you can have the waves going like this and so on and that will correspond to something in the same direction but a sort of second harmonic out like that and you may get the third harmonic it depends on the exact nature of the structure so what you'll get is a cross like that and the angle of the cross will depend on the angle of the helix and when jim went to kings with the erroneous structure of linus pauling in his pocket he was familiar with this x-ray diffraction theory morris read it and in his usual way didn't convey sort of enthusiasm one way or the other but i guess sort of said yes he didn't think linus was going to get the right structure at the same time however he sort of let loose the bombshell at least to me was that actually there were two types of dna x-ray photographs there was the form which i knew about called the a forum which gave this crystalline pattern but there was a second form called the b form and he opened the drawer and took out a photograph and boy i could hardly believe it it was a perfect it was a cross-like pattern and he told me that it repeated the 34 angstroms and that meant there was a helix in so i said morris you've got to build models of morrow yes he should build models but and trouble was with miss franklin but he thought the thing was coming under control and soon he would be able to build models but i tried to impress adam that really lioness wasn't going to wait someone at caltech was bound to tell linus that was wrong and uh so i thought also though i should go in and see uh roslyn and so i went in and told her here's a copy of the pog manuscript uh would you like to see it it was clear that she was sort of annoyed at my trying to tell her something about crystallography and she came toward me i thought she was going to hit me so i quickly got out at which point morris was coming around and she almost hit morris oh god who hit who i don't think anybody anybody actually some people may have thought someone was going to hit somebody but um there certainly weren't very friendly feelings rosalind was under some strain uh possibly she was going to be leaving kings in a few months time in any case she was working very hard on the analysis of the dna structures both forms and the way watson couldn't possibly know and i think she simply regarded him as an intruder by now braggart heard of linus pauling's attempts to work out the structure of dna and you have to remember that linus pauling had beaten the british scientist to it in working out the alpha helical structure of protein when albrecht wanted dna to be a british success so he agreed that jim watson could start working on dna again by now of course the chemists knew exactly the chemical content of dna it was realized that there must be some sort of helical structure but why wasn't the structure entirely obvious and why build models the easiest way to answer this is to look at a little bit of the molecule such as the one i have here and you can see that we already know quite a bit these balls represent atoms the rods represent the bonds between atoms and we know from the study of small molecules in crystals this distance for example to about one percent all the other distances we know all the angles so it is true that we do know the shape of that little bit that's a base and it's connected to a sugar but it's connected by a single bond the sugar is fairly rigid too but what isn't rigid is this bond here you can get free rotation about it and there are other places in the molecule where there's free rotation several along the backbone so there's a very large number of ways given the chemical formula that you can actually build a model i would do it maybe three hours a day i mean it was hard to get at it in the morning but because by the time you'd get in there was morning coffee and then go for lunch we'd have our walk and then i'd come back and build the motto and sort of francis was working on his thesis and i would look over my shoulder to try and see what what jim was doing i guess it's awfully hard to give up an idea of your own so i started putting the phosphates in the center maybe because it was sort of like a polling structure maybe if we wouldn't use ions we'd get somewhere but francis really wasn't comfortable with this and told me why don't i try putting the phosphates on the outside i can't really remember why you said that francis well it's because i think jim that you know you were obsessional about having them on the inside and you produced a lot of phony arguments as to why basic groups from protamines had to go in and in all collaboration it's very important when one person has an idea that the uh other person criticizes it and as it were the devil's advocate so just for the very reason that jim was keen on having the phosphates on the inside i thought he ought to try on the outside and i remember this conversation was happening in the the um my dining room of our house and i said to jim well why don't you try a model with the phosphates on the outside and jim said it would be too easy meaning of course that you could build too many of them and i said well if it's too easy why don't you do it francis may have been playing the devil's advocate in telling jim to try the phosphates on the outside but indeed there were very good reasons for doing so and rosalind had said so at a colloquium in november 51 which watson attended but he had not understood and therefore hadn't taken the news back to francis so i cut some things out of cardboard and sort of made the right shapes and then pasted things on which would indicate hydrogen atom then i think i went off and played tennis and it wasn't until the following morning i came in i started to put them together in pairs because this tie stage we decided well two a two chain structure is simpler than three chain and why shouldn't we try it well there were complicated technical reasons whether it was two or three but by that time the balance was strongly in favor of two i think so but but still it was easier to do and i always choose the easier so by now it was obvious that dna consisted of two strands wound helically around each other it was obvious that the phosphates were on the outside but where exactly were the bases and how did they fit together and it was francis who spotted the first vital clue in those days there was a brilliant young theoretical chemist in cambridge called john griffith he died quite recently and one evening we were sitting in a pub and talking about biological replication and i said to him perhaps the secret is that the bases attract each other in pairs but like would like adenine going with adenine stacked on top of each other like this and guanine going with guanine and so on and i said could he work out work it out to see if calculations would support that he was good at that sort of thing i met him a little later in the tq at the cavendish and he told me he'd done a few scribbles on the back of an envelope and he'd found that not like would like but that adenine stacked nicely on top of thymine and guanine on top of cytosine he'd been thinking along those lines at the time that i didn't know that so i said jim well that's all right that's perfect that's all we need for a replication scheme the relative amount of the four bases in dna had been worked out by a nucleic acid chemist called owen chagaf a few years before this time and it happened he was passing through cambridge and we were chatting to him in john kendra's rooms in peter house and we asked him what had come of all this nucleic acid work and he told us about his results which were that the amount of adenine equal the amount of thymine and the amount of guanine equal the amount of cytosine in all sorts of dna wherever he looked although the ra other ratios were all over the place well the effect on me was electric because i saw immediately that this is what you'd expect from a scheme like john griffice's so i was very excited i didn't mention it to charge at the time because it was work i was doing with john griffis but when we checked it all out we could see the two fitted together and looking back on it i find it extremely surprising that nobody else pointed this out because anybody who knows about the history of science knows that when you have one-to-one ratios it means that things go together i knew chargeff and was aware of his uh analyses one-to-one ratios and the whole thing is in retrospect it's easy enough to see that one-to-one ratios uh suggested that things were connected in pairs but but at the time it was very different the idea of deducing structural characteristics from analytical data is really quite a big and in some cases unjustifiable leap and but in my case it uh the the penny dropped on this one really very late and too late in relation to any of our model building the second clue came when watson started playing with cardboard models of the bases he knew that adenine should go with thymine and that guanine should go with cytosine but exactly how in march 1953 watson suddenly saw that when a went with t in this way it formed the same shape pair as when c went together with g this was the second crucial inside now the pairs of bases could fit easily inside the two helical backbones and suddenly i could put together a and t and g and c could hardly believe it and francis came in almost immediately and saw this and he you remember something came out of the model building that jim had done which he hadn't put in and that's always the sign that you feel you're on the right lines when something begins to click which you hadn't actually put in in your thinking of the subject which you knew was there but even more important francis by using these rules a and t and g and c we understood how the molecule replicated everything from then on was clear everything was finished except the hard work that's to say producing an accurate model jim wasn't much good at that sort of thing the models tended to flop about in his hands so he left it to me we didn't work with a great big model we worked with a small piece just a sugar a phosphate and half a base pair and i had to get it so that the bond distances and angles were reasonable he joined on to the next one and it was at the right sort of radius and so on sometimes the time jim would come rather nervously up and see what i was doing hoping that everything was all right we were in a funny situation psychologically we could we knew we were home but we weren't quite certain we were in it's as if we could see the port in the distance but we still had to navigate our way into the harbor it was a lot of hard work i worked continuously for about four days and uh then came the point where we saw that everything fitted and i was so tired i went straight home and went to bed the pairs of bases lay flat across the molecule suspended between the two backgrounds here was the key to replication as the backbones unwind the pairs of bases split apart each separated base has to be complemented by its partner base a with t and c with g each unwan chain was a template for two identical copies this is how the genetic material is copied as cells divide into two into four and so on all the time we were working on the structure i didn't think i worried too much about what the structure might tell us i just thought we ought to find out that when we had found out of course it struck us with a tremendous impact just how beautiful and exciting it was because there before us was the answer to one of the fundamental problems in biology how do genes replicate and it was very simple and you couldn't miss it we used occasionally just jim and i just sit and look at the molecule and think how beautiful it was and i remember an occasion when jane jim gave a talk to a little biophysics club we had it's true they gave him one or two drinks before dinner he was rather a short talk because all he could say at the end was well you see he's so pretty he's so pretty [Music] people said we were terribly clever for thinking of this idea of replication i mean we had to be sort of a five-year-old not to see it wasn't clever at all it was sort of a bonus which you could say made it's terribly famous we had nothing to do with it at all it was the molecule itself which did it undoubtedly it was a major turning point but of course the watson creek breakthrough was a said many times a little sort of pinnacle built on an immense wide basis of chemistry by chemistry and genetics and so on essential work which people like todd and um chargaff and many others um had to work through before and was able to put that little thing the three-dimensional structure of dna on top in jim's mind pauline was a great rival but in his rather perfunctory context with rosalind he hadn't got the measure of her at all indeed he didn't know that she was only one or two steps away from the solution and she showed in a very short while that there were two helices the double helix of phosphate sugar chains and she was trying to fit in the bases looking back on it all it's very clear that one of her difficulties was that she didn't have a collaborator with whom she could discuss problems very very closely and she was one person against this very very powerful combination of two extraordinary people i think this is the most important discovery in the field of biology that has been made in the last 100 years we owe a great deal to watson and crick for having made this discovery when the thing had come out of course we were tremendously excited about it we wanted to tell it to everybody every time a visitor came they would get this account of how this model explained so easily and beautifully the replication until jim got so sick of my explaining to people he just went out of the room every time i brought a visitor in but there again we didn't realize i think how widely it was going to spread i remember going home and telling odile that you know we made what looked like an important discovery and she told me after i didn't leave a word of it that i was always saying that they didn't always turn out and so it only came rather more gradually and as for having anything about prizes and so forth although the impression i got from jim is that he realized at the time it wasn't until a year or two later in america actually frank putnam said something to me about a prize and it suddenly struck me for the first time this is the sort of work which you give a prize for because uh to get a nobel prize it has to have a certain character and i was astonished to notice that this piece of work had exactly that character now what was the secret of qriken watson's success it was i think a unique collaboration between two people of entirely different backgrounds very different personalities uh different scientific abilities and yet sharing an identical very deep curiosity about the fundamental processes of life the dna story is without doubt one of the greatest success stories in the history of science but i'm not sure it's an altogether typical one of the way science is done because it can't be often that two comparative newcomers to a field make such a major discovery so quickly francis do you think we were lucky to have solved it or was it real brain work well i guess we were certainly lucky and of course you give the impression your book jim we didn't really do too much thinking but uh we were lucky i think for two reasons we we were thinking about the problem at the right time and then the two of us by collaborating when one of us got on the wrong track the other one could get us out of it when if if i thought there were three chains at one stage you were sure there were two if you thought that the phosphates had to be in the middle then i would be the devil's advocates and say put them on the outside and i think this is very important in solving structures of this kind because the difficulty is that you've got to give several logical steps one after the other if you get go wrong you get one person gets too fond of their own ideas i think another thing that which helped us in our collaboration was we weren't at least afraid of being very candid to each other at the point of being rude and if you don't have constant interchange and chatting together and saying what you think of the other people's ideas to their face i don't you can solve problems of this kind i've often had a thought with that in a slightly different way that if either of us you know we're either two years older or two years younger at least in my case i would have never solved it yes we had to be there just at that particular time we sort of pulled the way we looked at things we didn't leave it the gym did the biology and i did the physics we both did it together and switched roles and criticized each other and this gave us a great advantage over the other other people who are trying to solve it not [Music]