In Our Time: Crystallography

Crystallography is a technique that uses the diffraction patterns created by passing x-rays through a crystallised substance to determine the structure of the substance. It was first described in 1912 & has become very important to many scientific disciplines since then. The experts who discussed it on In Our Time were Judith Howard (University of Durham), Chris Hammond (University of Leeds) and Mike Glazer (University of Oxford and University of Warwick).

The programme opened with a brief description of crystallography & its wide-ranging uses in the sciences and then moved on to discuss the history of the technique. X-rays were discovered by chance at the end of the 19th Century, and were given the name “x-ray” because they were unknown rays. One of the questions physicists were trying to answer about these new rays was “are they particles or waves?”. As I understand it the modern physicist’s answer to this would be “yes.” but at the turn of the 20th Century they were still trying to categorise things as one or the other. A German physicist called Laue figured out an experiment to look at this – light waves split and are diffracted if passed through a diffraction grating, but the holes in these are far too wide to do the same at the sorts of wavelengths that x-rays have. So when he learnt about crystals – that they are regular arrangements of atoms or molecules – he realised these might act as diffraction gratings for x-rays. As he was a theoretician he got his students to do the actual experiment (I thought Hammond was quite sarcastic about this as he was telling us about it) – which neatly showed both that x-rays act like light waves when you use a fine enough diffraction grating and that crystals have this regular structure.

The next step on the way to using crystallography to determine the structures of molecules was done by a father & son team called William Henry Bragg & William Lawrence Bragg. Glazer told us a bit about the family – that they came from Wigton, Cumbria (just like Melvyn Bragg, in fact) and William senior moved out to Australia where he met his wife & had children (including William Lawrence). The family moved back to England, where William senior became a professor of physics at Leeds University & Lawrence became a student at Cambridge University. And they both worked on x-rays & x-ray diffraction through crystals. It was Lawrence who figured out the formula (Bragg’s Law) that describes the way that x-rays pass through the crystal structure & how the interactions between the different wavelengths and the differing spaces between the parallel planes of atoms produce a particular configuration of spots on the photographic plate. This formula is now used to work out the structure of a molecule from knowing the wavelengths of X-rays that are put in, and analysing the diffraction patterns that come out.

William senior in parallel was developing the X-ray spectrometer which provides a quantitative measure of the diffraction patterns. The original set up for these experiments was to shine a beam of X-rays through a crystal onto a photographic plate, and then look at the intensities of the spots to work out what structure would’ve generated that pattern. And for simple structures this works out OK, but as it gets more complicated you have a much more complex pattern where differing dots of differing densities might be hard to tell apart. So William developed a technique & machine that shone different wavelengths of x-rays through the crystal at a variety of angles sequentially rather than simultaneously, and then passed the diffracted beam into an ionising chamber to measure the intensity. This was initially a slow & laborious process, but essentially the same principle is used in today’s crystallography experiments – just the advent of computers & more refined technology has made the whole process much easier.

The first structures solved were simple ones – the very first was that of salt, NaCl. People then moved on to slightly more complex molecules (such as the benzene ring). And from there to much more complicated things, like proteins which consist of hundreds of thousands of atoms. The first of these to be published was the structure of haemoglobin, which was solved by Max Perutz – I think I once went to a lecture given by Perutz (but about 20 years ago so I can’t really remember it). The most famous is the structure of DNA, the discovery of which was published by Watson & Crick but relied heavily on data from Rosalind Franklin (which she wasn’t aware had been given to the other two, and she wasn’t credited for her work at the time).

During the programme the conversation went off on some interesting tangents. The first of these was that there is a relatively large number of women working in crystallography at all levels, and has been since the early days of the science. Howard said that this was down to both the newness of the field (relatively speaking) and the attitudes of the initial founders. Both Braggs welcomed anyone who could do the work into their groups, and didn’t discriminate based on gender, and there weren’t previous entrenched attitudes about the “place of women” in the field to overcome.

They also briefly discussed the way that modern science funding would’ve stifled some of the pioneering work in the field. I shan’t get up on my soapbox here, but it’s something I’m in agreement with. The examples from this discussion include the discovery of both x-rays themselves, and the technique of crystallography, which revolutionised several scientific fields and wouldn’t’ve happened if the scientists had had to figure out in advance why it was worth spending the money on that research. And some of the initial work solving structures was incredibly long term by modern standards – it took Perutz 25 years to be able to publish the structure of haemoglobin, no direct pay off in a 3 year project that’s easy to point to when you’re writing a grant application. You need some blue skies research and long term projects, as well as the more directed and more obviously relevant stuff – that’s how you expand the boundaries of knowledge & find out truly new things.

And they discussed how crystallography is a multi-disciplinary field – and that’s one of it’s strengths. People come from different scientific backgrounds, and collaborate across the boundaries of these fields.