ResearchPod Summary
This collection of reports details the seminal discovery of the helical structure of deoxyribonucleic acid (DNA). By analyzing X-ray diffraction images of DNA fibers, researchers in the Cavendish Laboratory (Watson and Crick) and King's College, London (Wilkins, Stokes, Wilson, Franklin, and Gosling) identified a consistent, regular molecular configuration across various biological samples.
The researchers observed that DNA fibers produce X-ray diffraction patterns characteristic of a helical structure. The patterns indicated a repeating unit along the fiber axis of approximately 34 angstroms, with a diameter of about 20 angstroms. Mathematical modeling using Bessel functions confirmed that this configuration is consistent with a series of phosphate groups arranged on the outer portion of a helix, while the nitrogenous bases are oriented inward toward the central axis. This structure, which the authors compare to a spiral staircase, appears to be consistent regardless of the species from which the DNA was extracted.
Before these studies, the molecular complexity of nucleic acids was well-recognized, yet the underlying geometric organization remained elusive. By identifying this helical arrangement—and specifically placing the phosphate groups on the exterior—the researchers provided a structural foundation for understanding how genetic material might pack into cells and interact with other biological components. The work demonstrated that despite the biological diversity of DNA across different organisms, its physical building block follows a universal, highly ordered geometric form.
Alex: A smudged X-ray pattern can reveal a molecule's shape without showing a single atom. In 1953, patterns like that showed DNA is a helix, about twenty angstroms wide, with its phosphates on the outside and its bases stacked inside.
Sam: An angstrom being a tenth of a nanometre. Before the shape itself, place this for me. Whose work is it, and what kind of document am I hearing about?
Alex: It's two short experimental letters from King's College London, printed in Nature in April 1953. One is by Maurice Wilkins, Alexander Stokes and Herbert Wilson. The other, right after it, is by Rosalind Franklin and Raymond Gosling. They appeared in the same issue as Watson and Crick's model.
Sam: Most people know the model and have never read these. Why should someone outside structural biology care about them now?
Alex: Because the model was a proposal built from chemistry and reasoning. These letters are the measurements it had to agree with. They show which parts of the double helix the data actually supported, and how firmly. So we'll cover what the patterns are, the one idea that turns spots into dimensions, and where the evidence stops.
Sam: Start with the samples. What were they shining X-rays at?
Alex: Fibres of DNA, where the long molecules are pulled into rough alignment. That's fibre diffraction: X-rays scattered by aligned molecules. Franklin and Gosling describe two forms. A drier, crystalline form they call structure A. And a wetter, less ordered form, structure B, which appears at higher humidity and persists over a wide range.
Sam: Which form matters here, and why that one?
Alex: Structure B. Going from A to B, the fibre takes up water and gets about thirty per cent longer. Franklin and Gosling argue that in B, each molecule sits in its own sheath of water. So it's free to take its preferred shape, independent of its neighbours. That's the shape you'd want to know about.
Sam: Water-soaked fibres in a lab are still a long way from a cell. Did they look at anything closer to living material?
Alex: Wilkins and colleagues did, and it's one of their stronger points. They say the structure is the same in all species, even though the ratios of bases vary a lot. They got similar photographs from sources ranging from calf thymus and wheat germ to human tissue and a bacterial virus. Then they looked at intact systems. Centrifuged trout semen gave the same pattern as earlier sperm-head samples. Wet pellets of T2 phage, sealed between mica windows, showed the main features of structure B.
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Sam: And the transforming principle? That's the DNA that can pass heritable traits between bacteria.
Alex: Yes. Working with Harriett Ephrussi-Taylor, they found that active transforming DNA, dried at about sixty per cent humidity, had the same crystalline structure as certain samples of purified DNA. So the shape isn't an artefact of extraction.
Sam: Now the central idea. How do you get a helix out of a pattern of spots?
Alex: A helix scatters X-rays in a recognisable way. The spots fall on horizontal rows, called layer lines. Their spacing is set by the length of one full turn, the pitch. The innermost spots on each row line up along a diagonal, forming a cross. The angle of that cross tells you how steeply the helix winds, and so its diameter. And the region straight up the fibre axis is empty. Wilkins and colleagues say that empty zone immediately suggests a helix.
Sam: So the spacing gives you the pitch, the angle gives you the width, and the blank stripe says "helix."
Alex: That's it. Here's the example that makes it concrete. The repeat along the fibre is about thirty-four angstroms. There's a very strong spot at three point four angstroms. And it sits exactly on the tenth layer line. Ten steps of three point four make one turn of thirty-four. So Franklin and Gosling conclude there are very probably exactly ten residues per turn.
Sam: Earlier work had already seen that three point four spacing, I assume. What's actually new here?
Alex: Astbury had read the three point four spot as the distance between nucleotides along the fibre. Wilkins and colleagues agree with that. What they add is that the longer thirty-four angstrom rows aren't a repeating chemical sequence. They come from the coil itself. And the sequence of bases along the chain isn't visible at all.
Sam: Then where are the pieces sitting? A width doesn't tell you what's on the outside.
Alex: Franklin and Gosling measure the positions of those innermost spots on several layer lines. All give a radius of about ten angstroms. Since that diagonal is one of the strongest features, something heavy and regular must lie on that circle. They argue it can only be the phosphate groups. Check the spacing too: ten phosphates around that circle puts neighbours about seven angstroms apart. That matches a fully extended chain.
Sam: Which would put them at odds with Pauling.
Alex: Directly. Pauling and Corey had proposed a structure with the phosphates forming a dense core. These data put them outside. Franklin and Gosling add independent chemistry. Earlier titration work found the groups on the bases are inaccessible in solution, while the phosphates are fully accessible. And the phosphate groups are the part that soaks up water, which fits fibres swelling into a gel and then a solution.
Sam: And the bases, then, are inside.
Alex: Wilkins and colleagues find the three point four spacing cleanly divides only the central region. The outer parts blur into a continuous helix. That suggests the bases are stacked like a pile of pennies in the middle.
Sam: The famous claim is two chains. If density were the only argument, I'd want to know how tight it is.
Alex: It isn't tight, and Franklin and Gosling say so. A cylinder that size, at dry DNA density, would hold about thirty-two nucleotides. That fits three chains of ten better than two. But if neighbouring units interpenetrate a little, the effective radius shrinks, and you could get down to twenty. So density alone can't decide.
Sam: Then what tips it to two?
Alex: Two indirect arguments. First, an analysis of the crystalline form A found only two chains per repeating cell, and since A turns into B reversibly, regrouping into threes seems unlikely. Second, the chains can't be equally spaced along the axis. Three equally spaced chains would imply a helix around sixty angstroms wide, which they call absurdly large. Three unequally spaced chains would be non-equivalent, which also seems unlikely. So two chains, offset by about three-eighths of a turn, which accounts for a missing fourth layer line.
Sam: So how much should a listener trust all this?
Alex: The helix dimensions and phosphates outside rest on several independent lines, and I'd call that strong. The two-chain conclusion is a reasoned inference, not a measurement. And both letters hedge. Franklin and Gosling say the X-ray evidence cannot yet be taken as direct proof of a helix. They don't attempt a complete interpretation, and some outer streaks aren't easily explained. Wilkins and colleagues say parts of their discussion are not without ambiguity. Both conclude only that their data are consistent with the Watson and Crick model.
Sam: So who should sit down with the full letters, and where should they start?
Alex: Structural biologists, and anyone who teaches diffraction or the history of molecular biology. Start with Franklin and Gosling's argument that the phosphates lie outside, then their case for two chains. Then read Wilkins and colleagues' section on diffraction by helices, a clear physical picture of why a helix makes that cross.
Sam: And for everyone else, the one thing to carry around?
Alex: The double helix was a model. These letters are the measurements that held it to account, and they said exactly how sure they were.
Sam: Careful hedging, on one of the biggest results in biology.