in the early 20th century physicists and chemists unlocked secrets of the atom that changed the world forever but life remained a profound mystery among life's deepest secrets were was inheritance everyone knew that traits like the shape of a peep pod or the color of eyes and hair were passed on from generation to generation but no one knew how such information was stored or transmitted scientists were convinced that there had to be a biological molecule at the heart of the process and that molecule had to have some pretty special qualities the three-dimensional arrangement of atoms in those molecules had to explain the stability of life so that traits were passed Faithfully from generation to generation and Al the mutability of life you have to have change in order for evolution to happen the challenge of solving this mysterious arrangement of atoms this fundamental secret of life was taken up in 1951 by two unknown scientists less than 18 months later they would make one of the great discoveries of the 20th [Music] century they met and joined forces at the Cavendish Laboratory in Cambridge England one was a 23-year-old American named James Watson he had a crew cut when he first came to Cambridge and that was very rare in Cambridge in those days he liked to wear what I call gym shoes and leave the laces untied and things like that he was quite anant I would say but behind that of course was his extreme intense love of science right from his early years and his determination the other wasn't Englishman named Francis Crick trained as a physicist his academic career had been interrupted by the outbreak of the second world war it wasn't until 1949 that he got back into academic science he was anxious to make up for lost time and now interested in biology Crick and Watson connected instantly when they met in 1951 they both loved to talk science Francis and I both liked ideas and as long as I could talk talk to Francis I you know felt every day was worthwhile Crick was always ready to share his thoughts though he rarely did so quietly any room he was in he was going to make more noise than anyone else they would constantly throw crazy ideas at each other dismiss them have another idea follow that a little further dismiss that but then something comes out of left field so it's kind of this give and take we did have different backgrounds but we had the same interest we we both thought that finding the structure of the gene was the key problem the idea of the gene dates back to Gregor mle's experiments with P plants in the 1860s by the 1920s genes had been convincingly located inside the nucleus of cells and associated with structures called chromosomes it was also known that chromosomes are made of proteins and a nucleic acid deoxy ribonucleic acid or DNA that meant that genes had to be made of either DNA or protein but which was it protein seemed the better bet there are lots of different kinds of them and they do lots of different stuff inside the cell in contrast DNA didn't seem very interesting it's just repeated units of a sugar linked to a phosphate and any of four bases the Readiness to dismiss DNA was so entrenched that it persisted even after Oswalt Avery showed that it can carry genetic information Avery had isolated a substance that conveyed a trait from one bacterium to another and this transforming Principle as he called it he showed that it was not destroyed by a protein digesting enzyme but was destroyed by a DNA digesting enzyme Watson and Crick were among the few who found Aver's work persuasive they thought genes were made of DNA they also thought that solving the molecular structure of the molecule would reveal how genetic information is stored and passed on at the time a powerful technique for solving molecular structure was being perfected x-ray crystallography at its best x-ray crystallography can determine the position of every single atom in the molecule that you're analyzing with respect to every other single atom not that it's easy the picture you end up with is a defraction pattern and to make sense of it to work out where the atoms are involves interpreting lengthy calculations and in the 1950s the equipment was primitive and difficult to maintain the X-ray sources weren't very bright and on top of that DNA is not an easy molecule to work with basically you picture snot it's kind of hard to pick it up and do stuff with it and analyze it um polymers are not fun to work with from that point of view the Cavendish was famous for x-ray crystallography but the director of the lab didn't want his staff x-raying DNA he knew that a group at King's College in London was already doing that and he didn't want to be seen as competing it just wasn't uh good manners the King's College scientist who had initiated the work on DNA was Morris Wilkins like Crick he was trained as a physicist and had only recently become interested in biological questions though he was drawn to the problem of the gene Wilkins lacked Watson and crick's burning urgency to find a solution complicating things for Wilkins was his relationship ship with his colleague Rosalyn Franklin she was a talented crystallographer but when she joined the team at Kings she believed that she would be leading its DNA research she had the notion that this was her project he had the notion it was his project and if anything she should help him in his effort to solve this structure and so this is a recipe for disaster the times and their personalities worked against an effective partnership this was a time when it was very very hard for women in science to to be taken seriously and so I would imagine that rosn Franklin had to be perhaps quite assertive she certainly asserted her independence Wilkins by all accounts a shy man reluctantly agreed that they would work separately London is only 75 miles from Cambridge that means the Watson and Crick could easily keep tabs on the work being done at Kings but another potential competitor was was thousands of miles away in California lonus Pauling was renowned as the greatest physical chemist of his generation he was widely admired for his ability to build accurate models of complex molecules Watson and Crick were convinced that it was just a matter of time before Pauling used this technique to solve DNA biological molecules come in a variety of shapes Pauling and Watson and Crick suspected DNA might be a helix of some kind but if so how were the sugar the phosphate and the bases arranged early in his collaboration with Watson Crick had worked out mathematically what the X-ray defraction pattern of a helical molecule should look like shortly afterwards Watson went to London to hear Franklin report on some of her recent work when he got back he told Crick what he remembered of her talk and they decided to build a model in a few days they had one it was a helix with three sugar phosphate chains on the inside and the bases sticking out at that time only interesting thing about the DNA molecule is the basis and so it made perfect sense I mean only an idiot would put them inside because then they're hidden they invited Wilkins and Franklin to come and take a look unfortunately Watson had misremembered some of her key measurements Franklin saw this immediately and quickly and derisively missed their effort she went on to craft a mocking announcement for the death of DNA as a helix it was an embarrassment that did not sit well with the Cavendish leadership we were forbidden in a sense to work on DNA the failure of the first model was painful but it can also be seen as just part of the scientific process I would actually maintain that um in order to arrive at the right solution you have to put out a couple of wrong on and that's just the nature of Discovery and um if you're afraid of making a mistake um you're going to fail in this business through 1952 Watson and Crick read and talked over anything and everything that could prove relevant for their ongoing but now underground quest to discover the structure of DNA to me there was only one way I could be happy or two ways you know Sol DNA or get a girlfriend you know and I didn't get a girlfriend so it was solv DNA the year ended with Watson and Craig thinking about DNA Franklin taking pictures of DNA Wilkins avoiding Franklin and Pauling a distant but worrisome presence then in January 1953 everything changed news came that Pauling was indeed preparing a paper on the structure of DNA Watson secured a copy of the manuscript and found to his great relief the Pauling was proposing a triple helix it was very similar to the one that he and Crick had been shamed into abandoning the previous year relieved he headed to London to share the news that the race for DNA wasn't over only to find that rosn Franklin wasn't particularly interested what he had to say following his departure from Rosen Franklin's room he encountered Wilkins and Wilkins took him into his room and then took out of a drawer a picture which had been taken by Rosen Franklin that picture would become one of the most famous images in all biology Franklin's photo 51 Jim Watson recognized the defraction pattern immediately it was a helix and based on this Watson thought it might have just two chains a double helix about the same time Francis Crick was shown a report on Franklin's work that included an observation on the symmetry of DNA this led Crick to a crucial Insight that Franklin had missed the two backbones had to run in opposite directions that led him to the conclusion that the sugar phosphate backbones had to be on the outside with the bases inside so Watson started to build models again he experimented with pairing like with like adenine with adenine thyine with thyine and so on that would make each chain identical Watson thought that could explain how genetic information is stored he thought he had the solution but then a Cambridge colleague told him that the bases could not pair with themselves in that way and Crick pointed out that the model didn't take account of something else that was known about DNA a few years earlier another chemist interested in DNA DNA o and charf had reported a puzzling fact about the molecule he analyzed the chemical composition of DNA in different species and what he found is that the amount of a the base edinin and the amount of Base T's was always the same and G's and C's were always the same but no one including CHF had figured out what those base ratios meant with Cha's data in mind Jim Watson went alone to the lab one Saturday morning and started playing with cardboard cutouts I began moving them around and I wanted an arrangement you know where I had a big and a small molecule and uh so how did you do it somehow you had to to form link bonds so here is h a and here's T and I wanted this hydrogen to point directly at this nitrogen so I had something like this oh so then I went to the the pair and one of this nitrogen point to this one I went like this boom they look the same and you can put one right on top of the [Music] other we knew we could just you know even if we go up to the ceiling we were building a tiny fraction of a mcle hundred of million of these base pairs in one mark all fitting into this wonderful symmetry which we saw you the morning of February 28th 1953 the model fit the measurements both from the X-ray defraction pictures and from Char's data but most important of all the arrangement of the bases immediately revealed how DNA works the key aspect of the structure was the complementary nature of the bases if you had a big one on this side you had to have a particular small one on this side or vice versa and so on all the way up so it meant that you could easily make by separating the two chains you could then easily make a new complimentary copy by just obeying these pairing rules of which one went with what and that solved in one blow the whole idea of how you replicate a gene the structure immediately revealed two things how genetic information is stored and how changes or mutations happen the information is stored by the sequence of the bases mutations occur when the sequence is changed it's a simpler and better answer than we ever DED hope for I remember an occasion when Jim gave a talk it's true they gave him one or two drinks before dinner he it 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 I think everyone just took joy in it because the field needed it but on the other hand you know the biochemistry Department didn't invite us to give a seminar on it when the structure of the double helix was revealed most by biologists instantly recognize the power of the explanation before them here was this beautiful molecule that could explain both the stability of Life over huge amounts of time and its mutability in evolution that Triumph was reporter in the journal Nature it made headlines around the world and was celebrated 9 years later with a Nobel Prize that's kind of what every scientist Dre dreams about to make a discovery that has this kind of impact for biologists the discovery of the double helix opened up a whole new world it was a passport to all the mysteries of Life Mysteries that biologists have been decoding ever [Music] since [Music] [Music]