Matthew Cobb: What role did Rosalind Franklin really play in the discovery of the DNA double helix?

Matthew Cobb, image courtesy of Doug Vernimmen

"Click here to listen to the full podcast episode"

“What did Watson and Crick discover in 1953?”

“Rosalind Franklin’s notes!”

It’s a well-known joke that you’ve probably heard me tell before - but is it true? If you’ve listened to our previous episodes about the discovery of the double helix structure of DNA - that’s episode 16 from our first series, Genetics by Numbers, and episode 9 of season 3, Twisted History - you’ll be familiar with the story that James Watson and Francis Crick, who were working at the University of Cambridge, secretly got hold of information from Maurice Wilkins, Rosalind Franklin and Ray Gosling at Kings College London - including the infamous Photo 51 - which enabled them to figure out the structure and win a Nobel Prize, together with Wilkins. 

The way it’s usually told, Franklin was effectively ripped off and belittled by the Cambridge team, especially Watson, and has only recently been restored to her rightful place as one of the key discoverers of the double helix. It’s a dramatic narrative, with heroes, villains and a grand prize. But, as I found out when I sat down for a chat with Matthew Cobb, science author and Professor of Zoology at the University of Manchester, the real story is a lot more nuanced. 

Before we come to that, I wanted to start by setting the scene. Today, we’re all familiar with the idea of DNA as the instructions for life, and the iconic double helix, which appears everywhere from adverts to corporate logos (including hidden in our own here at First Create The Media). But as Matthew explains, back at the beginning of the 1950s, DNA just… wasn’t really a Thing.

Matthew: Everything that we think about this period is seen through modern eyes, through DNA being what genes are made of and all the rest of it. That wasn't the case in 1950. So DNA had been identified by Miescher in the late 19th century as nuclein, as this stuff you find in pus and was very soon identified in all sorts of cells and was clearly very important.

Matthew: Well important just 'cause it was widespread, right? So there's no function associated with it. And then by the time that chromosomes were identified as being the units of heredity in the 1910s, 1920s, 1930s, It becomes apparent that DNA is a major constituent of these chromosomes. However, so too is protein, and this is really the kind of the interpretative dilemma that scientists had for about 30 odd years.

Matthew: That is, we know that genes are apparently on chromosomes. What are chromosomes made of? Well, they're made up of DNA, which the analytical chemistry they had suggested was quite boring. That was actually a word that was used because it's simply made up of a kind of phosphate sugar element. And then these four things called bases, which are the A, C, T, G that everybody knows about, and that seemed kind of dull.

Matthew: If you've only got these four bases and phosphate sugars, how can that do what a gene does? 'Cause genes do anything, right? And that was fairly obvious from the early 1940s onwards, not only in principle that you could mutate a gene and it could do all sorts of weird things, but actually genes appeared to encode enzymes. This is what Beadle and Tatum discovered in the early 1940s.

Matthew: And then the idea was, well, they can do anything. So we've got this really boring stuff. But there's also proteins, and proteins we know can be any shape, size, do all sorts of stuff. So the implication was that probably most people's bet, if you'd taken a bet in the 1930s or early 1940s, people just said, well, if you make me decide, I think genes are made of proteins and that, that's kind of logical, right.

Matthew: Now there was a kind of more nuanced view, which was that in fact what they found was that the genes and the proteins tended to be bound up together. And so there's often a catch-all word that's used at the time, which is nucleoproteins. That is, there's something about these two kinds of molecule working together that is making genes do their stuff.

Matthew: The issue is what are genes made of? There's this kind of argument from boringness that it can't be DNA, but there's also Wendell Stanley's work. So Wendell Stanley wins the Nobel Prize in 1946 for his work he'd done in the 1930s, which showed that the tobacco mosaic virus was functional only if you had the protein component to it. So the proteins he argued were what was significant in causing the transmission of this virus. In other words, he actually had apparently experimental evidence for this, that the protein was the key thing. Now the change in this began in the mid 1940s with the work of Oswald Avery, who was working on pneumonia bacteria, and he'd studied them for decades.

Matthew: He'd been nominated for the Nobel Prize for his work 'cause before antibiotics. This was a major killer. And there's this weird phenomenon, which had been identified in the 1920s by a British public health official called Griffith. If you've got two kinds of pneumonia bacteria, sometimes they would be very infectious and therefore not very nice, and sometimes they would be not quite so infectious.

Matthew: And this corresponded to a different form. They were either rough or smooth, that you could see the colonises that these bacteria would form. And he noticed something really weird. That is that you could transform one of these kinds into the other kind by kind of sticking them together. If you had the two kinds together, then one of them would turn into the other and this would happen even if they were killed.

Matthew: So there was something in these bacteria that was transforming, as it became known, transforming the bacteria from one kind to another. And Avery got really interested in this and for about 15, 20 years, he was working aware that, trying to identify what he called the transforming principle. And eventually in 1944, he publishes an article, which he shows by a series of extractions and above all the use of enzymes to either metabolise, destroy DNA or protein, he shows that the transforming principle is made of DNA. Whoa. Well indeed. So this is really exciting. And in a, a letter to his brother, which he wrote in 1943, he said it looks like a gene and he uses in the letter to his brother. He's very excited about it in the article. He really isn't.

Kat: Classic scientist, just, you know, downplay it.

Matthew: Well, he was a very kind of conservative, quiet guy, and there's a lot of discussion amongst historians about why he wrote such a boring article. And it may be that he was conservative. It may be that the editors of the Journal of Experimental Medicine said, don't be quite so bold, please, but whatever the case, you had to kind of read between the lines to see exactly what he was getting at.

Kat: This does go to show that it's PR that's really important in science communication. Like how different would the world have been if Avery had actually had a decent press release about his paper?

Matthew: So there was a meeting, right? He did give a talk at the Rockefeller University describing his data, and in the traditional account of this, which I've repeated, there's a dead silence when he gives his talk.

Matthew: But that appears not to be true. There was a huge row, and the row was caused by one of Avery's colleagues called Mirsky. And Mirsky had heavily invested in the protein theory of genes, and in the idea that DNA was boring. So when Avery gets up and says, look, in this species at least, 'cause that's the only, you know, this is n equals one, and bacteria are weird- there's no necessary reason to think that bacteria are the same as eukaryotic organisms, for example - Mirsky says, “oh, no, no, no, no, no, no. Right. Your whole argument is based on the efficacy of your enzymes, so the DNAse that you've put in, which is deactivating the DNA. How do you know that it's as effective as you say? How do you know that in your pure DNA only sample. There isn't a tiny amount of protein?”

Kat: And that would be enough!

Matthew: Well, it would, right? It would, and the bizarre reason why we, we think it would is that we now know that Wendell Stanley's experiment where he showed that it was protein, that was the active ingredient in the tobacco mosaic virus, in fact, we know there were tiny traces of nucleic acid in there actually doing the business. So there was a lot of doubt. One of the reasons may have been that extraordinary claims require extraordinary evidence. Right? And so that's why there was this conservatism in the scientific community. It was also because Mirsky led a brutal campaign. He wrote review articles saying this was all rubbish and all the rest of it.

Kat: It's frustrating because you can see with protein, you've got 20 building blocks, these 20 amino acids. You've got so much diversity. You've got diversity in shapes and structures, and like you say, DNA is just this very boring, repeated four brick thing. But I guess what we didn't really have is any mechanistic insight for either DNA or protein. It wasn't clear how all these things work. So if it was DNA, how did that make life? Or if it was protein, how did that have the instructions for life?

Matthew: I. I've talked a lot with, uh, Nathaniel Comfort, my colleague who's writing a biography of Watson, and we've tried to get exactly this question. What did people, who advocated that genes were made of protein, what do they think they looked like? What were they? And I think the, I mean, this was never explicitly stated, right, but I think the idea that people had was that a protein gene will be something like a mould. So it's sitting there on the chromosome and basically it is like the thing you're gonna synthesise. And in some way that nobody knew, this mould, this shape, you can imagine it actually being a three-dimensional shape on the chromosome, would then be used to kind of stamp into the cellular gunk and produce another protein just like that. And that makes some kind of sense, right?

Kat: Like making like plaster of Paris moulds or something like that.

Matthew: Absolutely. Right. Or stamp, you know, pushing a, a coin into some blue tack and you can see the shape on the other side. So in that way, maybe a protein gene would be kinda like the negative of an actual protein. Right. On the other hand, the people who thought about, well maybe it is DNA, did actually start to think about, well, how could that work?

Matthew: And there were a series of meetings at Cold Spring Harbor after the war. These are annual, the Cold Spring Harbor Symposium on quantitative biology. And they're all oriented to trying to get to this idea about basically how genetics works. And I think it was in 1947. In one of the discussions about this question, a chap called Masson Gulland, who was a big DNA biochemist from the UK who tragically died about three months later in a railway accident in the north of England, and how history would've been different had he lived.

Matthew: Masson Gulland argued well, maybe it's something to do with the sequence of the bases. Maybe it's their order that is relevant if genes are made of DNA. So this idea was floating about, and people were talking about it. It wasn't completely unknown, but most people still thought that it was most likely that genes were made either of proteins or of nucleoproteins.

Matthew: So you've then got a problem. Well, how are we gonna work out what they look like? Right? So we've got this weird idea, which isn't explicit, but is implicit that maybe protein genes are some kind of negative form, and that might be true of a nucleoprotein as well, that there's some structural thing, you know, wibbly, wobbly, timey wimey stuff that works right?

Matthew: And the main way people had of thinking about or detecting molecular structure was this technique called X-ray crystallography, which had been developed by the Bragg's father and son. Lawrence Bragg, the son won the Nobel Prize at 25 in 1915 or something like that. I mean, he is still the youngest scientific Nobel Prize winner, and I don't suppose that crown will ever be taken away from him.

Matthew: And Bragg, by this stage was much older because this is now late 1940s, and he was running the Cavendish Laboratory in Cambridge and they had begun to use X-ray crystallography, this very, very complicated technique, which basically involves zapping an X -ray beam at a crystal, and then it diffracts. The beams bounce off, and if you leave it beaming away in front of a photographic plate for long enough, then you get nice, reliable images.

Matthew: The problem that you've then got is you've got a two dimensional image, and that reflects a three dimensional structure. So this is OK if you're looking at very simple molecules, but proteins in general are pretty complicated, although Dorothy Hodgkin had already used this on very short molecules in the late 1940s.

Matthew: So it was known that you could identify the structure of proteins in principle by using X-ray crystallography. But proteins are complicated, right? For all this, they are kind of bubbly, lumpy things, whereas DNA is a really stupid, simple molecule. So if you are gonna try and understand what a gene was made of, then probably using X-ray crystallography was the way to go.

Matthew: And maybe if you could find pure DNA and crystallise it, maybe that will be the thing you'd want to be looking at. And that is exactly what Maurice Wilkins at King's College London began doing in about 1948. But he was still, you know, he wasn't certain that DNA was what genes were made of. He was thought they were, nucleoproteins were still important. He built on some work by Asprey and Bell done before the war, which had made X-ray crystallographic images of DNA, and they'd suggested that the bases were kind of stacked up like a pile of pennies.

Matthew: So it was a very kind of vague structural thing, but they didn't know what the function of DNA was. It was just that it was a lot more doable than trying to get at all the myriad proteins that appeared to be in a chromosome. So it was kind of the easy, not the easy, but it was the thing that you could do. Whereas getting a protein was gonna be much more tricky.

Kat: Tractability, always.

Matthew: Absolutely.

Kat: So we're at a stage where we've got the crystallographers in Cambridge, and that's where the Watson and Crick connection comes in because they were both at Cambridge. And then we've got Wilkins and his team in London, and this is where we meet Rosalind Franklin and Ray Gosling, her PhD student. So what was the journey that brought Rosalind to London and particularly to Wilkins?

Matthew: Wilkins was the deputy head of the lab. The lab had been set up by John Randall with the support of the MRC, the Medical Research Council- not really because they were desperately interested in what was called biophysics at the time, but because they were engaged in a bizarre turf war with the other research councils and with the Royal Society over who should have control over treasury money of this. And Edward Mellanby, who was the head of the MRC kind of outmanoeuvred the others and ended up funding two units in 1947. First the King's unit under Randall, and then a very small group in Cambridge under Max Perutz, who are doing similar kinds of things. They're using the best techniques in physics to understand biology.

Matthew: And Rosalind Franklin was a chemist who had graduated from Newnham College, Cambridge in 1944, 5, and had then gone to Paris where she worked a while for the coal board, so she was using physical and chemical techniques to understand molecular structures. She went to Paris and there she learned X-ray crystallography. So she's not trained as a crystallographer, right? She's learned this effectively as a postdoctoral researcher, and she's again, studying coal.

Matthew: So she's got this really fantastic crystal, right? It's really hard stuff that she can then bombard with her X-rays and try and interpret this structure using various techniques. She eventually decided she wanted to leave Paris and she got a fellowship of her own that she could then basically take wherever she wanted. And she contacted Randall because he was doing this stuff and the initial plan was she was going to study proteins in solution, which was a very sexy kind of topic at the time, and posed lots of problems because these proteins clearly couldn't be crystallised in the same way. So it was gonna be an interesting problem.

Matthew: And that's what in 1950 she thought she was gonna do. And then she gets a letter from Randall saying, I have discussed with some of the other chaps here. We would like you to work on certain biological fibres that we are particularly interested in. And this was DNA. And my guess is, Franklin didn't know about that.

Matthew: She never worked on living material, right? She'd worked on coal and she no doubt understood the excitement eventually, but she didn't come thinking, I'm gonna study the structure of the gene. Right? That was not what either she was sold on or what to be honest, people thought at Kings.` They simply knew it was significant. They hadn't kind of taken sides in the Avery/Mirsky arguments, but it was gonna be a lot easier to understand the structure of DNA than it was to understand the structure of the proteins.

Matthew: So she comes to Kings and basically it's a disaster. She arrives when Wilkins is away. He's on holiday. Wilkins had a PhD student called Ray Gosling. He comes back and discovers that as deputy head of the lab, all of a sudden he no longer has a PhD student. And what was his topic, studying DNA has now been split, been also given to Rosalind Franklin.

Matthew: Now that maybe wouldn't matter. He didn't know any of this was gonna happen. We don't know why Randall did this. Maybe that wouldn't have mattered if he and Franklin could have got on. But I mean, chalk and cheese doesn't come into it. I mean, they really were completely different people. So Wilkins comes from New Zealand originally. He's very quiet, he's very reserved. He would look away when people talk to him. He hated confrontation, hated argument.

Matthew: And Franklin came from this very boisterous Jewish family, and her intellectual tradition was that you had a good old ding-dong and you'd sort things out. And that was also how you could develop new ways of thinking. And in Paris, the French will argue about anything. They'll argue about the taste of a croissant. Great. Let's have an argument now. Talk about Descartes and philosophy. And she had absolutely loved the lab atmosphere in Paris.

Matthew: She comes to London and it's very different. She said, well, there are no foreigners and no Jews here. She didn't like the atmosphere at Kings. She was, as a woman, excluded from the senior common room. I'm not sure that still goes on in universities, maybe in some of the stranger ones. But Randall had a very good record of employing women researchers and supporting them. So it wasn't that Randall was a bastard. I mean, he may have been, but certainly not particularly to Franklin.

Matthew: But the atmosphere was not good. And we now know from letters, she wrote that within months she was considering jumping and going back to Paris, where she'd been happy. She decided not to do that. I mean, this was because of these blazing rows that she had with Wilkins, and you can kind of imagine she's somebody who wants to get a response, right?

Matthew: That's part of the thing. Gosling said that she will always play the devil's advocate, so she's gonna take an extreme position and argue with you, and she wants you to push back, and that way you'll both get somewhere. And instead, poor old Maurice is going, oh my God, no, no, no. She's here again. No, no, I don't want to talk to her. I'm kind of running away. So he's terrified of her. She ends up, I think, kind of despising him as not having any gumption and every time she pushes at him it doesn't get anywhere. Maybe that's not entirely true 'cause Wilkins does also say he had lots of blazing rows with Randall. So maybe he did push back, but it wasn't in the right way.

Matthew: Whatever the case, this is a catastrophe and it is clearly obvious that had they worked together, had that magic gone OK, then we would not talk about Watson and Crick at all. We would talk about the Franklin Wilkins or Wilkins Franklin structure. And it's not only me that thinks that - lots of historians. I mean, Jim Watson has said it repeatedly that that was the problem in Kings.

Kat: So against this backdrop of conflict of Rosalind being brought into the lab to study these DNA Fibres, her and Ray Gosling, they're doing the stuff, they're doing their X-ray crystallography. They've made the famous photo, photo 51. That's we've seen all over the place on coins and in pictures. And so what's the journey from that to the structure of DNA and Crick and Watson. How does this story then develop from there?

Matthew: Well, it depends on whether you want the real version or the version that everybody knows, which is the version which comes from the Double Helix written by Jim Watson.

Kat: Let's start there.

Matthew: Yeah, well, that's the problem. So that's why we talk about photograph 51, which is a very pretty photograph. It's very clear and all the rest of it. And if you know the structure of DNA. You can see what it's telling you. Right? But that's the trick. That's the problem with x-ray crystallography is, as I said at the beginning, you're trying to turn a two dimensional image into a three dimensional structure, and more than one three dimensional structure can give a particular image.

Matthew: So you can't look at an image and say, oh, this tells me X, Y, and Z. You need lots of different images and you also need lots of analyses to try and come up with a structure that might give that particular image through X-ray diffraction. So part of the problem is that in the Double Helix by Jim Watson, everything revolves around photograph 51. He sees it, his pulse starts racing. He realises that DNA must be a helix of some kind, which is one of the arguments that they'd had with Franklin. And he then goes off with Crick and builds the double helix and hey presto, we've stolen her data. Haha.

Kat: Off to the pub we go!

Matthew: That's right. And all of that down to the going to the pub is all lies. It's all a dramatic device. It's a way of making the story more interesting for the reader because it is a bit hard going at times in reality. Plus, you know, it puts Jim Watson at the heart of the thing because he has seen this image.

Matthew: So what actually happens is that,for start, you've gotta realise that Crick and Wilkins were good friends. He ended up in Cambridge. And Watson gravitates there after having seen an X-ray image of DNA in 1951 he decides, my God, I've got to work on this stuff. But for some bizarre reason, he doesn't go and work at King's, which will be the obvious thing to do if you wanna work on the structure of DNA, go to the place that's studying it.

Matthew: Because Crick is not studying structure of DNA, he's working on protein structure, as is everybody else in the Cavendish unit at Cambridge. So DNA is not something that is on their agenda, partly because the King's group is doing it. You've got these two units funded by the MRC and they've got a division of labour.

Matthew: And what happens is that Wilkins and Crick talk all the time about what's going on, and Crick knows that he's working on DNA and Is knows he's got these ideas about it being helical and all the rest of it. But Wilkins is a bit slow, I mean for everybody's tastes, including for Randall, for Crick, he's taking a long time to do it.

Matthew: And Watson and Crick try making an initial structure of DNA, just because they're interested in it at the end of 1951. This is a complete, hopeless three helical structure. It's a disaster. Franklin takes one and look at it and laughs at it. And they're told to keep their hands off this topic because it's nothing to do with them, it's to do with Kings, which is actually true.

Matthew: So, the issue then comes at the beginning of 1953. Franklin has been trying to work on what was called the A-form, which is this very pure crystalline structure of DNA, and it produces these really precise images, which were hellish to interpret, in particular with the method that she chosen to adopt, called the Patterson function, which is basically lots and lots of sums, in a period when you do not have calculators. You may, if you're lucky, have a mechanical calculator for adding up, but you can't do anything complicated. It's all slide rules. So this is really, really hardcore maths that you've gotta crunch the numbers through.

Matthew: That was a mistake on Franklin's part. She was ill-advised to follow that, because for various complicated reasons, DNA is not the kind of molecule that you can use that for. There is too much blurring, partly because the sequences of the bases is not fixed. The molecule is not giving you precise images because it's not got a constant structure within it.

Matthew: And so Franklin's getting stuck on trying to interpret the A form, but she's really interested in that because she's a chemist and this is the crystal and that's what you need. And eventually she's already decided, I've had enough. I'm going to Birkbeck to work with JD Bernal because that's more interesting. And she's been told by Randall, OK, you can go, but you can't work on DNA. That's our baby.

Matthew: So she was having to finish everything up and she, like everybody else at the King's College Group, had had a meeting, a kind of end of year summary of what they were doing, in which heads of all the other MRC units came along. And listen, this is at the end of December 1952. And they all wrote a little summary of what they had done, and this was in an informal MRC report, which was handed round in order to let them know, all the other units, what we've been getting up to. And this is given also to Max Perutz, who's the head of the Cambridge group, and he then goes back to Cambridge with this little brochure in his hands.

Matthew: This is later shown to Watson and Crick and it contains that some key numbers. It doesn't contain photograph 51, it doesn't contain any mention of that, but it contains a handful of key numbers that Watson and Crick can now use as their starting point to uncover the structure. But the first thing you've got to realise is, well, why on earth were they?

Matthew: They were told to hands off 14 months earlier. How come they're now working on it? Well, the reason is that Linus Pauling, who was a chemist, started to get interest in this topic and the King's unit, both Bragg, who is in charge of the lab and Perutz, who was in charge of the MRC unit, they had history.

Kat: Oh, there's beef!

Matthew: Big beef. Big beef. He whooped their ass. Can't really say that. I don't think anybody did any of that kind of thing back then. He had beaten them in a real race, which was to uncover something called the alpha helix, which is a component of proteins, which is a little helix, a little wiggle. And they had used very different methods, very similar. Perutz and Bragg had used the data and they'd focused on using particular analytical methods and they'd explained everything in these X-ray crystallographic images of the alpha helix, and they had a particular model. And then Pauling came along and he said, "nah, you know what? We can be much cleverer because your model fits the data. But it's wrong because you've got obsessed by one particular little blob on your X-ray images. And I don't think that really matters. I don't think it's a relevant point. I'm gonna try and get the chemistry to fit the data and if the data aren't quite right, but the chemistry's OK then that's right."

Matthew: And he did that and he produced eight papers - eight papers! - one after another, explaining not only that Bragg and Perutz were wrong, but their whole approach was kind of leaden footed. And that made a great impression in particular on Francis Crick - never a man to want to have to do lots and lots of hard work if you could have a brilliant idea and work out how to do something.

Matthew: So the fact that Pauling was now interested in DNA led Bragg to think, OK, well, we're not letting him get away with this a second time. For the glory of Imperial British Science we're going to allow Watson and Crick to try and figure this out their way, which is basically copying what Pauling had done and doing what they called model building, which sounds really complicated and fancy.

Matthew: They later described it much more accurately as trial and error. So basically they're starting off with a chemical structure, which was known of DNA and trying to see can we find any way of fitting this that might look right and produce the kind of images, the basic data we can see. Now, what was that basic data? It was that which was in the MRC report and not photograph 51, is what was significant.

Kat: So what was that key data insight that helped them to fit all these pieces together in the right way?

Matthew: It's not so much that, it was more, the things that they accepted were that the distance between the bases was 3.4 Angstroms and that had been worked out in the 1930s,right. This is what was the pile of pennies that Asprey and Bell had suggested. And there was also the suggestion it was known Maurice Wilkins had shown that you could get two forms of DNA, the A and the B form. The drier, A form was a different size to the wetter squidgier B form. And the B form was about 34 Angstroms in a repetition and the A form was 28 Angstroms, so they're slightly different shapes, and this difference was significant. And in particular the 34 Angstroms. So that would suggest that if you've got 3.4 Angstroms between each base, you've either got 10, or maybe 20 even. Because 34 is just a repetition, right? So you could have it doubly repeating, you might have 20 bases per turn.

Matthew: You didn't actually know that, they couldn't be certain. So for a long time, Watson tried to cram 20 bases. So they actually discarded the 3.4 Angstroms and said, well, maybe it's 1.7 and you know, we just can't see it properly. So they're trying everything. Their starting point was that they knew that all the evidence - because Wilkins had chatted to them over and over again - suggested there were probably two phosphate chains. They knew from what Franklin had told them, that the phosphates were probably on the outside, but because they didn't want to get caught up in any particular data point, they abandoned those ideas too. They started off with three chains with the phosphates on the inside and the bases on the outside.

Matthew: So they're playing around basically with the chemistry and the things that we now know are significant, like for example, the fact that A binds with T and C binds with G, they had some inkling this might be the case. They knew that the ratios of those bases were one-ish. But they didn't use that at all. This wasn't a thing that they used. It was what suddenly appeared obvious at the very end.

Matthew: Basically they spend about six weeks fiddling around with bits of cardboard. So it's not bits of metal like you see in the pictures, bits of cardboard. This is still in two dimensions, and they're only really working on the link between one base and the phosphate chain. That's all they're doing. Just trying to see can we get the chemistry to fit. Will everything stick together? And strikingly, there was one bit of information that they were absolutely certain of, and that was that hydrogen bonds played no part.

Matthew: So the thing they actually relied on, they said, OK, there's no hydrogen bonding in here because the position of the hydrogen atoms in the bases isn't certain. It varies, there's variation. They knew this 'cause they'd read it in the textbooks and so on. And then they're told very later on in the process by their colleague Jerry Donahue, he looks at 'em and says, you know, you're using the wrong forms of the bases?

Matthew: And they go, no, what? And he says, yeah, that's all wrong. They are, in fact, quite constant. They don't have this variability, the hydrogen atoms are here and here. So Watson then makes new little cardboard bases, and then this is literally - they all three, Watson, Crick and Donahue tell the same story - that Watson on a Saturday morning turns one of these little silhouettes of a base over and he realizes that A combined with T, C combined with G, they produce exactly the same shape, so therefore there's a constant rung in between the two phosphate bits to form a ladder. And it's hydrogen bonding that's doing the business because they now know the correct shapes of the correct structures.

Matthew: And then they can say, OK, not only does it do that, we've got these ratios that now make perfect sense. And also a tiny crystallographic detail that Crick was obsessed by and Watson didn't get, that the two strands of DNA go in different directions. So there was nothing that gave them the structure of DNA, right. And none of Franklin's data gave them. And you know, if they could've done that, Franklin would've done it. I mean, she wasn't silly. She knew her stuff and we know from her notes that she was working through it. But we also know she too, was working with the wrong structures of the bases because she'd looked in the same textbooks as they had, and she didn't have a Jerry Donahue.

Matthew: So the only issue out of all this - photograph 51 played no part in it, Crick never saw it. But what about that report I mentioned? So they were shown this by Max Perutz and this in the 1960s when the Double Helix came out. 'cause Watson mentions it very, very briefly, half a sentence about it. Because it's all about photograph 51, according to his version.

Matthew: And this was picked up by some very astute reviewers, leading scientists who then caused a fuss in their reviews. And so there were letters in Science, Scientific American poor, old Max Perutz, trying to remember what on earth, "What did I do 15 years ago? I can't remember!" Trying to explain what he did and why he gave them the report and how sorry he was, and all the rest of it.

Matthew: And he should have asked, that's quite clear. But what's fascinating is that we discovered this little letter at the end of January, 1953. So Franklin is wrapping up, she's trying to work out all her results, and she gave a talk at King's, which was well known that she gave this talk. And there was a kind of invitation to Watson and Crick to go along if they wanted.

Matthew: But this was cancelled by Wilkins who said, no, we want it to be a private row. And he also wrote about, "don't worry chaps, the smell of witchcraft will soon be out of our eyes and we'll be able to get on with things."

Kat: Oh my God.

Matthew: Oh yes. She was a witch. Oh, so we knew about this little meeting. What's fascinating, this letter we found is, it's actually the invitation and it comes from Pauline Cowan, who was a PhD student at the time, who went on to become Pauline Harrison and a leading researcher on the structure of collagen, in fact. And she says to Crick, "Rosalind says that she and Raymond are giving a talk on the 28th. You can come along if you want." She gives the room details, but she says it's gonna be for a general audience, not very much crystallographic detail and that anyway, Perutz knows all about it already, so you might not think it's worthwhile coming.

Matthew: In other words, Franklin is saying, "look, I told Perutz all this. You might be interested in it. But if you really wanna know the details, why don't you ask Max? He can tell you." So, I mean, it's not saying, "Hey, use my data lads!" But it's not saying this is really private. You mustn't tell anybody. My God, you know all the things you might imagine somebody who's got the secret of life and now really, really wants to keep it secret. That wasn't what it was about. It was much more fluid and open. And this helps to explain why Franklin went on to be really good friends with the Cricks, in particular, Francis and his wife Odile. And even with Watson, they ended up both of them working on the structure of the tobacco mosaic virus in a kind of friendly competition.

Matthew: And she would write him letters showing her sketching her latest ideas. So she clearly didn't think that he was a bastard. Well, how wrong she was. She clearly didn't think that he was gonna steal her data, right? Because she was sharing this with him. She tried to go on a transcontinental car journey with him from Chicago to Pasadena. "I'd love to come if the dates match up" she wrote. So all this also explains why, to go back to your starting point, what was DNA? Most astonishing thing I found was a letter from Franklin to her best friend Anne Sayre, summing up what her life had been like in 1953. And she talked about all the hell of Kings and leaving Kings and going to Birkbeck, and it was much better, although Bernal was a bit of a git and she was having kind of problems with him, and she got this money from the coal board to carry on her work on coal, and she was now working on the viruses. "But the most interesting thing that happened to me in 1953 was going on holiday to Israel to a kibbutz, blah, blah, blah."

Matthew: Not one mention of DNA, not one mention of "I discovered the secret of life and those swines stole it from me." None of that. And all it says is that wasn't at the forefront of her mind at the beginning of 1954 because she'd moved on and because DNA wasn't as important as we now think it was.

Matthew: It was partly the double helix structure, which she had not only helped to discover but also had made the first public presentation of. This is the final thing that we found at the Royal Society's Conversazioni, which was what they used to call the summer exhibition. There was a presentation of the double helix, which was authored by the whole gang, both by Watson and Crick, by Gosling, by Wilkins, by Stokes, the other researcher at Kings, and was the first author, and it was presented by Rosalind Franklin. And she presents both the model, so the double helix, and the experimental data, which in fact have been published altogether in three articles under a common title in Nature. One from Watson and Crick, which is speculative, that's the theory. And then you've got two experimental articles, one from Wilkins and his colleagues, and one from Franklin and Gosling.

Matthew: So she knew what she'd done, but the actual significance of it was not yet clear. And it took another 10 years or so for everybody to finally be convinced that really DNA was what genes were made of. And it was only really with the cracking of the genetic code in 1961 that. I think the final opposition fell away.

Kat: So looking to the aftermath of this, obviously Watson writes his book, the Double Helix, where he tells this, what we now know to be somewhat of a fantasy about what happens. And then also we do know that Watson and Crick and Wilkins get awarded the Nobel Prize. What year was that in? 62. So this is after the cracking of the genetic code. So now DNA is a thing, and of course the name that's missing from that is Franklin.

Matthew: Well, she died in 1958. That's the main reason. The Nobel Prize rules about awarding prizes posthumously are complicated, but certainly it's very rarely happened. I think recently a guy got it because he died about a week before the announcement, and so they said, OK. But basically she died of ovarian cancer in 58. She was diagnosed in 56. She convalesced with the Cricks and it was all horrible. Now, would they have given her the prize? Well, they bloody well ought to have done. The other issue people sometimes say is, oh, well you can only have three people named on a prize. Well, you know what you'd have done? You'd have had two for chemistry and two for physiology or medicine. And so four of them, Watson Crick, Wilkins, and Franklin could easily have fitted that had the Nobel Prize Committee had the intelligence to do that.

Kat: So we now hold up Rosalind Franklin as this icon, this woman in science. There is the story about how she was robbed. We've got the joke about, what did Watson and Crick discover? Rosalind Franklin's notes. Ha ha. How should we think of her? How should we remember her and how should we put her in context?

Matthew: Well, I think actually stuff we haven't talked about is what she did next which people just don't know about, but very strikingly, for example, on her gravestone, it doesn't mention her work on DNA. It talks about her work on viruses. So she went on to work first on tobacco mosaic virus, and then on polio. What could be more important? This is at a time when the polio vaccine has just been rolled out, the Salk vaccine. So polio is still a massive problem around the world, and she's working on the structure of the virus. And I think her work in that respect when she's a fully independent researcher.

Matthew: Also, the things she wrote when she put in her grant applications and the vision that she had for what she and her colleagues, the postdocs that she had on these grants - because of course she, she didn't have a post, right? She's on soft money throughout this period. She never had a full-time job, a permanent post - I think those visions of what science can be and what it can do and the way you do it, that is really the most exciting thing. Yes, she did contribute essential work to the discovery, the structure of DNA, but really what she went on to do and how she went on to apply the things that she'd learnt in those two years at King's, two and a half years, and then with Bernal, I think those are the really interesting things of what she went on to do.

Matthew: She was a brilliant scientist. She was a lot of fun, which she wouldn't think from reading The Double Helix. She loved going out to the opera, she went out to the theatre with Odile Crick. She liked dressing up in fancy clothes. Yeah, she was very much a woman of the 1950s and she should be remembered in that respect. Somebody who did have to fight, but I'm not sure it's right to think of her as a feminist icon. And certainly her family and friends didn't think she would've thought of herself that way because she died in 1958, so she's growing up during the war and then in the 1950s, which was a very different time from what it is now. But, really significant.

Matthew: Should Watson and Crick have talked to her, have asked her? Oh yes, most definitely. They should have said, is it OK if we use your data, the handful of numbers? My guess is she would've said, "Well, duh. Yeah, Max has already got them. Well, aren't you doing that already?"

Matthew: But very strikingly, they did ask Maurice Wilkins, is it OK if we start modelling DNA? Because Pauling's out to get it. They didn't ask Franklin. On the other hand, they barely knew Franklin. They met her a couple of times. Maurice was best mates with Francis. It should also be said that when they did ask Maurice Wilkins, can we do it, they'd begun a week earlier.

Kat: That's asking for forgiveness rather than permission.

Matthew: Well, they didn't tell him that. They just said, is it all right if we start? And Wilkins felt a bit sick and said, oh, alright. But he didn't have the wit to say, no, I need to go and talk to Randall because this is our project. There are all sorts of ways he could've stalled them. It wouldn't have made any difference. They were gonna go ahead anyway. So yes, they were bad, but they're not bad in the way that most people thought they were.

Kat: I do find it interesting and a little frustrating that the public perception of Rosalind Franklin as someone who was hard done by, someone who didn't get recognized, as someone who didn't get her just rewards, has all come from Watson's perspective and Watson's story about her. She's been defined by a man's story because she never really got to tell her own.

Matthew: Absolutely. I mean, this is the irony is that, and one of the things that myself and Nathaniel Comfort, who wrote the article in Nature that kind of prompted our discussion, were keen to emphasise that even those people who want to advocate for Franklin's memory and for her genius and all the rest of it, they end up simply taking Watson's version of the story - photograph 51, they stole it - and flipping it on its head. That does a disservice to Franklin, it also does a disservice to science, which is actually a tremendously collaborative effort.

Matthew: And Crick in 1995, I think it was published, but it was for the 40th anniversary of the discovery of the structure, he called the article a collaborative discovery because Franklin wasn't collaborating with anybody, right? She couldn't collaborate with Wilkins and she wasn't collaborating with Watson and Crick because she wasn't supposed to be. But it was still all these people working on the same thing. And there were other people we haven't mentioned, there were chemists, there were all sorts of people who were involved in enabling this, in fact, to be discovered. It wasn't just either Franklin having the Secret of Life or Watson and Crick stealing it from her. For a start there was Wilkins who everybody forgets about, and there were lots of other people around there. And so we need to think about Franklin as being a very significant figure but it was not just for those two years, 18 months that she was working at Kings on this problem, but what she did afterwards. And people should take inspiration from that whole career, I think, and not simply only conclude that Jim Watson's account is kind of self-serving and one-sided, which it was, and actually use the more complex version I've tried to explain today to step away from that and think about the whole process.

Matthew: And rather than this being a deadly race, it's not always friendly, but it's a kind of competition. I mean, people working on the same problem today in different labs, sometimes it's awful and they won't talk to each other - postdocs and postgrads can be told, don't talk to people from that lab, you'll give something away. But that's bad, right? Everybody agrees that shouldn't happen. And it's generally due to the kind of crazed egos of the lab heads that that happens. The people who are actually involved in the work want to talk to somebody else. When you present a poster, your preliminary data, and somebody comes up and goes, "well, what about this, that, and that?" You go, "wow, that's good. Right? OK, yeah. I'll go away and think about that. "And that's much more what it was like. Much more relaxed than the cutthroat, desperate attempts to win a Nobel Prize, which is how Jim Watson presents it in the Double Helix. And I'm not sure that it actually was, that even for him at the time.

Matthew: I think this is a post hoc dramatisation because he is trying to make science interesting and exciting and human right. And so by injecting bad boys stealing data, I think that's one way that he thought he could do it. It tells the story, right? You know,it's a page turner. If listeners haven't read it, they really should because it's a cracking read. Just don't think that it's all true. That's all.

Thanks to Matthew Cobb for that fascinating and fun chat. As he mentioned, Matthew and Nathaniel Comfort have written a detailed article in the journal Nature looking at Rosalind Franklin’s role in the discovery of the double helix. And if you’re interested in learning more about the history of genetics, check out Matthew’s previous books including The Genetic Age, about the history of gene editing, Life’s Greatest Secret, about the race to crack the genetic code, and The Idea of the Brain, uncovering what we know - and what we don’t know - about the most mysterious object in the universe, the human brain.