In Our Time - Crystallography

Episode Date: November 28, 2012

Melvyn Bragg and his guests discuss the history of crystallography, the study of crystals and their structure. The discovery in the early 20th century that X-rays could be diffracted by a crystal revo...lutionised our knowledge of materials. This crystal technology has touched most people's lives, thanks to the vital role it plays in diverse scientific disciplines - from physics and chemistry, to molecular biology and mineralogy. To date, 28 Nobel Prizes have been awarded to scientists working with X-ray crystallography, an indication of its crucial importance. The history of crystallography began with the work of Johannes Kepler in the 17th century, but perhaps the most crucial leap in understanding came with the work of the father-and-son team the Braggs in 1912. They built on the work of the German physicist Max von Laue who had proved that X-rays are a form of light waves and that it was possible to scatter these rays using a crystal. The Braggs undertook seminal experiments which transformed our perception of crystals and their atomic arrangements, and led to some of the most significant scientific findings of the last century - such as revealing the structure of DNA. With:Judith Howard Director of the Biophysical Sciences Institute and Professor of Chemistry at the University of DurhamChris Hammond Life Fellow in Material Science at the University of LeedsMike Glazer Emeritus Professor of Physics at the University of Oxford and Visiting Professor of Physics at the University of WarwickProducer: Natalia Fernandez.

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Starting point is 00:00:00 This BBC podcast is supported by ads outside the UK. Every Sunday, we talk about the week's tech news on this week in tech. Hi, this is Leo Leport. Inviting you to join me this week with Lisa Schmeiser, Dan Patterson, and Yanko Rekkers. We're going to talk about the new 49 megabyte web page. It's the standard, you know. We'll also talk about Elon Musk. You've got some spleenin to do and the Yassify filter, new from Nvidia.
Starting point is 00:00:28 That's this week on this week in tech. You'll find it at Twitter. or wherever you get your podcasts. Thank you for downloading this episode of In Our Time. For more details about in our time, and for our terms of use, please go to BBC.co.com.uk slash radio four. I hope you enjoy the program. Hello, in a letter to a colleague,
Starting point is 00:00:48 the Nobel Prize-winning chemist Max Perutz tried to convey the crucial importance of crystallography to our understanding of the world. Perutz wrote that the technique explains why blood is red and grass is green, why diamond is hard and wax is soft why graphite writes on paper and silk is strong why glaciers flow and iron gets hard when you hammer it
Starting point is 00:01:11 crystallography is the study of the structure of solids and for centuries our knowledge of crystal structures was based on little more than their physical appearance but 100 years ago in 1912 the father and son team of Lawrence and William Bragg developed x-ray crystallography a technique which uses x-rays to work out the precise arrangements of atoms within a crystal. The ramifications of their discovery
Starting point is 00:01:35 revolutionized molecular analysis across scientific disciplines and since then, 28 Nobel Prizes have been awarded for work related to X-ray crystallography, including one of the most important breakthroughs in the history of science, the discovery of the structure of DNA in 1953.
Starting point is 00:01:52 With me to discuss crystallography are Judith Howard, Professor of Chemistry at the University of Durham, Chris Hammond, Life Fellow in Materials, science at the University of Leeds and Mike Glazer, Emeritus Professor of Physics at the University of Oxford and visiting Professor of Physics at the University of Warwick. Julius Howard, before we go into the history of crystallography
Starting point is 00:02:12 and explore its many achievements, could you explain what it is? Thank you, Madam. Yes, I mean, crystal logarithy, apart from being an enormously fascinating, colourful and exciting subject, which I think is what appeals to most of us that work in it, it's really the science that examines the arrangement of atoms in a solid. That's the small, short explanation. Modern x-ray crystallography, of course, enables chemists, biochemists, biologists, material scientists to examine in extreme detail the material in which they're interested
Starting point is 00:02:45 and so they can look at the properties or relate the properties to the structure. And we're using two, in x-ray crystallography, obviously we're using x-rays but we can also use the same methodology using neutrons and electrons. Can you tell listeners how you do that and what, just be a, can you unravel a bit more what you're looking for and how you're looking for it? The technique uses a fine beam of x-rays, which are generated mostly in the laboratory these days, it then impinges on a small crystal. And the reflected beams, the diffraction beams are then measured in one of many ways. I mean, we can go back into the history or the modern way, but that's the fundamental.
Starting point is 00:03:26 What we collect an enormous number of these reflections. These are then processed these days in the computer, and the structure of the material you're looking at is then unraveled in a mathematical sense. But the, I mean, I don't want to go into all the mathematical detail right now, but what we're looking for is the detail of the atomic arrangement, which atoms are connected to which, in what order in three dimensions. So these may be a simple structure like sodium chloride, salt, common sense. they may be something as complicated as you mentioned DNA, but the techniques we use are common to all of these applications. And again, just to sort of go, as it were, to an end result. This mathematical and extremely, as it seems, sort of closed system of science
Starting point is 00:04:19 has led to in the life sciences, for instance, maybe it can give us one of two examples of how it's benefited that area, among many others. Yes, the impact of crystallography is, is huge economically and of course of fundamental science because of course the nature we're examining materials that come from the areas that I mentioned so that for example in the life science is not just the enormous discovery, the fantastic discovery of DNA
Starting point is 00:04:45 but in terms of if you're looking at economics, pharmaceutical compounds we're looking also in the agrochemicals, food industry ceramics and many areas in which crystallography is applied and if you would want one example going back a long time, the discovery of the structure of penicillin in the time of the Second World War, this led, of course, then, knowing the structure, knowing the atomic arrangement, it was then possible for the chemist to synthesize this very important and very new drug structure.
Starting point is 00:05:19 And it is still true that if we can determine the structure of the materials that we're interested in, then there's an opportunity to synthesize those. And originally, of course, many of these materials were derived from nature, the natural products, or in case of penicillin from mould. But then once we, as I say, have the atomic arrangement in detail, the chemist can go back to the bench and synthesise it. So there is the impact. Chris Hammond, there's always been interesting crystallographer for a long time.
Starting point is 00:05:50 And we can go back to Kepler and then Hook but the modern idea arrived when the in 1895, when the German physicist Rentgen discovered X-rays, that seems to be the big breakthrough. Yes, it was. His discovery was, in a sense, he might call it serendipity in science. Rantan wasn't looking for X-rays.
Starting point is 00:06:13 He didn't know they existed. When he did discover them, he wasn't able to describe exactly what they were. But that doesn't belittle his great achievement, for which he got the first Nobel Prize in Physics, later. Brantgoe was carrying out some... Before then, the way to find
Starting point is 00:06:30 things out was to look through a microscope. Oh yes, yes, yes. So it was a massive change. Yes, yes, yes, yes. He was... In the discovery of x-rays, he was carrying out some experiments with discharge tubes. This was a very old sort of experiments where
Starting point is 00:06:45 he passed high voltages through electrodes and looked at the rays emit of the, what were called cathode rays then, electrons. And for some reason, and he never divulged what the reason was, he enclosed the discharge tube in a light-tight cardboard box, and he dimmed the lights in his laboratory. He worked entirely on his own, very reticent man.
Starting point is 00:07:05 And he noticed, when the discharge she went through the tube, a piece of paper coated with barry and plateau cyanide lit up on the bench a few feet from him. He realized some rays were being emitted from the tube, which penetrated the paper. If he'd been looking another way or the liberatory had not been dark and sufficient, he would have missed this observation.
Starting point is 00:07:28 So it's really fortuitous. And a feverish bout of work, he established that these rays were more heavily absorbed by more dense materials than light ones. They blackened photographic plates. He took the first radiograph just before Christmas 1895, with his wife and a beautiful photograph
Starting point is 00:07:47 showing the bones and the gold ring which had all the X-rays. And of course, that was the beginning of the major medical technique of radiology. But he tried reflecting the beams, focusing with lenses, diffracting them, bending them, all without success.
Starting point is 00:08:02 So he called them X-rays, unknown rays. And curious, it's a word which we still have today, even though we know what their nature is. As you say, got the first Nobel Prize in physics in 19001. It lay around for a while, and at this puzzle of x-rays,
Starting point is 00:08:19 didn't it? But it was taken up by another German physicist, Max Lauer. Can you say what he brought to the... Yes, yes. There was a controversy, of course, and often physicists moved into two camps. Were these raised particles or their waves? Why was it important? Because it was important,
Starting point is 00:08:37 because if they were waves, they could be defracted. Just as light, say, is defracted. Say, when a light passes through a pinhole, it spreads or through a diffraction grating, it spreads, and you can see defracted beams. Lowy realized from Maxwell's equations, the actual magnetic theory, if x-rays were waves, they would be light-light, but have wave-rays million times smaller than that of light,
Starting point is 00:09:02 and that trying to defracting them with ordinary diffraction gratings, it was impossible, with ordinary defracting radius, this was far too large, but he was in conversation with the young student who told him about crystals. Lloyd didn't know about crystals at all, and ever the young student told him that crystals raised of rows of atoms regularly arranged,
Starting point is 00:09:19 And now he had the intuition, well, perhaps these atoms in crystals, there rose on them, regular arrangement, could also defract x-rays, just as gratings defract light. So he got two assistants to do the experiments for him. He's a theoretician. He didn't do experiments himself, of course. Paul Nipping and Walter Friedrich. And they carried that experiment, a very simple experiment,
Starting point is 00:09:44 a simple experiment which Einstein called, one of the most beautiful in physics, because they simply shone a beam of x-rays that some crystals of copper sulfite and zinc sulfide got a beautiful pattern of diffraction spots, which clearly showed the very first time that the atoms were indeed regularly arranged inside crystals. An x-ray diffraction revealed that for the very first time.
Starting point is 00:10:06 Can you just go over that again, so that people know exactly what you're talking about. An x-ray diffraction revealed that the way that atoms were regularly organized in crystals. In fact, the mark of a crystal is that the atoms are regularly organised, that's one thing, that is the thing that is. That is the mark. The criticism. In suspective, an external form, but this was the very first time that the atom, the
Starting point is 00:10:28 regularity, revealed itself through diffraction. In one case, it was called, like a chessboard. Yes, that's neatly done. Yes, yes, yes, yes. Yes. Yes. Well, Mike will be describing a little bit more about the, but Lowy, we should say that Lowy, he'd received the Nobel Prize. I think his assistant should have received the Nobel Prize. prize too, but things were very hierarchical
Starting point is 00:10:50 with the Nibel Foundation. He tried to interpret these spots. He tried to work out actually where the atoms were from the spots, but failed. He didn't have the sort of, if we might call, geometrical intuition that the Braggs had that might all be described later on.
Starting point is 00:11:08 Well, we can start with Mike as well now. Mike Leiser, two of the principal figures in this X-ray crystallography story, and you and Yon, I would say, key figures really, the father and son team, most unusual, William and Lawrence Bragg. Could you tell us something about them? Okay. I'll start with William Bragg, who was born in 1862 in Cumbria near Wigton,
Starting point is 00:11:32 an area where the name Bragg is very common, I understand. Not that common. Well, it's interesting that we're here with the Bragg program. So he's born 1862, and to cut the story short, he goes to Cambridge, and reads mathematics and does very well. It's a first-class degree. And very quickly after this, he acquires a position in Adelaide in Australia
Starting point is 00:11:58 as the professor of experimental physics and mathematics. And he goes there. He knows very little physics and has to teach himself. And while he's there, he meets a very important family, the Todd family. Charles Todd had been sent out there by the government as the government astronomer and superintendent of telegraphy. And is responsible for setting up the first telegraph system in Australia.
Starting point is 00:12:25 His wife, Alice, is the person who gave the name to Alice Springs. So this was a very distinguished family. And he makes friends with the family and eventually marries one of Charles Todd's daughters, Gwendolyn. And he has children, one of whom is William Lawrence Bragg. So we have William Henry Bragg, William Lawrence Bragg, which is little confused. using the similarity of the names. So I think the best way to do this is to call the father, William, and I'll try and call the son Lawrence,
Starting point is 00:12:54 just so that we can distinguish between them. So Lawrence is educated in Adelaide in school, and William hears about Ronkin's discovery of x-rays, decides he wants to get interested in this, and he builds his own x-ray system there in Adelaide, and this is the time when Lawrence gets his first exposure to x-rays. I mean, literally, a frightening experience at the time with the sort of apparatus they were using. Anyway, in, I think it's 1908, the family moved to Britain,
Starting point is 00:13:28 and William took up the position of Professor of Physics at the University of Leeds. It must have been a very tough of Gwendolyn to come from Sunny Australia, find herself in Leeds. Which can be sunny too, but let's, he got the sense. So that's the background, these people. That's very good note. That's exactly what we need. And he worked in it there, and he seized on this idea of the x-ray diffraction, and started to work in it. And so most unusually did an undergraduate at Cambridge at that, his son, both of them in different ends, worked on this. Yeah, there was a problem, and that was that William believed that the x-rays were particles.
Starting point is 00:14:07 This was part of the argument at the time. And they heard about Lowey's discovery and set about trying to show that Lowry's experiment actually, actually was not to do with waves and diffraction, but could be explained by particles travelling down through avenues and the crystal. And they tried experiments and those failed. And then Lawrence, when he was in Cambridge, was walking around and he had an idea
Starting point is 00:14:28 that he could explain Lowell's experiment. And so what I need to do now is really to explain the importance of that. And this is when he was 22. He was 22 years old and he had it published in the Cambridge Philosophical Society on the 11th of November, 19th, 12, so just over 100 years ago.
Starting point is 00:14:47 And this paper really, I think, is the one that's fundamentally changed the world of certainly crystallography and a lot of other science. His idea was very simple when it came to it. First of all, if you think about a crystal consisting of regular arrays of atoms in all directions,
Starting point is 00:15:06 if you look at it, what you find is that the atoms all lie on parallel planes. And every direction you look at through the crystal, you find these planes. of different spacing. Lawrence's idea which he got from normal physical optics was imagine that the beam striking a set of planes is reflected as if the planes were mirrors.
Starting point is 00:15:29 But unlike mirrors, the rays that are reflected now interfere with one another. And that means that if one ray has its peaks of a wave coinciding with another one, they will add together and give intensity. If not, they will cancel out. allowed. And he comes up with a very simple formula which relates the wavelength of the x-rays to the spacing of the planes and the angle at which the x-rays come in. And this formula is now known as Bragg's Law and it's widely used to the present day and the future in all kinds of
Starting point is 00:16:02 areas, not just in crystallography but in physics of optics and so on. This formula is very important because the problem that Lowy had was that he tried to to explain his patterns in terms of a fixed wavelength, single wavelength, and eventually he tried five different wavelengths and still couldn't get it to work. Bragg realized that the beam must be a white beam. In other words, a beam consisting of all wavelengths incident on the crystal. And this is something that Lowy didn't understand. Even the following year, he was still saying that if you had a white beam, you would get uniform blackening on the film. Braggslaw shows that you have to satisfy these three conditions, spacing, wavelength and angle in order to get this diffraction.
Starting point is 00:16:48 And that's the reason why you don't get diffraction all over the film, but it in spots. The next thing that he did was, and this is the real second breakthrough here, was that he was able to explain Lowey's patterns precisely and actually find the crystal structure of zinc sulphide. By showing that with zinc sulfide, and the way the atoms were distributed in the crystal, all the spots could be explained, and not only all the spots, but all the ones that were missing that should have been there, which Lowy was having trouble with. This was the first case of the determination of a crystal structure,
Starting point is 00:17:25 and it's this which has launched the whole of the modern science. This is the reason we know structures of proteins and DNA, penicillin that Judas has talked about, materials, silicon, all these things. that stems from that very first experiment and the very first, rather the explanation that the young Lawrence came. 22 years old, not bad, eh? Well, it was brilliantly explained,
Starting point is 00:17:49 so at the moment, everybody listening, including me, knows what you're talking about. I hope so. Let's hope we can hold it. Right, Judith Howard, his father, working in Leeds, and they were working simultaneously in different aspects of this,
Starting point is 00:18:02 invented a machine called an X-ray spectrometer to assist him and to insist his son, which is still good signs today, as I understand. Can you tell us about that and why it was important? Yes, before the invention of Bragg's ionisation spectrometer, the way to record the pattern that we've just been hearing about, this pattern of spots, which is peculiar to the sample you're irradiating, the method was on photographic plate, and in that way you collected a lot of information in one go, but it was hard to determine accurately the difference in the intensity. So you'd have a dark spot, a light spot, sort of stronger and weaker
Starting point is 00:18:43 intensities recorded on the film. What Thurmbrag did was to create an instrument which had a mechanism of producing of fine beam of x-rays. This was then bounced off a monochromator so that you could extract just one wavelength that you needed from the white beam that Mike's been talking about. The crystal was situated on a rotatable platform, so that it could be oriented in one or another direction or in several directions, and the defracted beams were then sent to an ionization chamber, and that was the way of detecting x-rays at that time. What this instrument did was enable you to measure accurately the intensities of the diffracted beams, and that's the first time this was ever done. What, of course, it meant was that you were actually measuring one,
Starting point is 00:19:32 one defracted beam at a time, unlike a photograph which took many, but over a different time scale. And what was the consequence of that? You were able to extract detail of the structure in a sort of more quantitative way. Although Bragg did say that because of the measurement of only one diffracted beam at a time, whereas you've got a lot of information faster in a way by photography, if you couldn't at that time it was very laborious taking measurements with the ionisation spectrometer
Starting point is 00:20:06 and he did say that if you reserved it just for the more complicated structures which you couldn't solve with photographic methods but it was rather more like a battering ram than the sort of lighter approach of the photographs but it meant that there was a quantitative measure for the first time of the intensities
Starting point is 00:20:22 of the diffracted beams so in place as Mike Laser pointed out the system which He's in place then, isn't it? Within a few months, these two working, Cambridge and Leeds, but working together. Chris Hammond, how was there...
Starting point is 00:20:40 They got a Nobel Prize bridge in 1915. Lawrence got his notice of it when he was on the front, doing some sounding, trying to work out where the German guns were placed by the sounds that were coming up. But how were their achievements met in the world of chemistry? Not very well, actually. The chemists were rather upset,
Starting point is 00:20:58 because in the case of, say, sodium chloride, one of the simplest crystals, as long as Bradg pointed out, the sodium chlorine atoms simply ran like a chessboard. And you couldn't identify any NACL molecule as such. And this upset chemist, who thought in terms of molecules, even Brad's close colleague at the University of Leeds, Arthur Smith said, surely, surely, surely, Lawrence, couldn't you make two of these atoms just a little bit closer
Starting point is 00:21:24 so he can see them paired off rather than being uniformly distributed? and even as late as 1927, Henry Armstrong, a very distinguished chemist, fellow of the Royal Society, wrote a letter in nature which he called Poor Common Salt. He begins this letter, quoting Robert Burns, Some books are lies from end to end, and he says that Professor Bragg assert some sodium chloride. There are no molecules, a chessboard, he says. This is a statement repugnant to common sense. Worst criticism, it's not chemical cricket.
Starting point is 00:22:00 Observe the end of degree, and so he goes on. So I thought when I read this, that surely this was written with a pinch of souls, it's a poem song, simply being whimsical. But John Muri Thomas, a former professor of chemistry at Cambridge, says, not at all. Armstrong was not a man given to whimsicality at all. In this letter, even as late as 1927,
Starting point is 00:22:20 was written in a deadly earnest. But I think that must have been the swan song of the objection, and after the chemist realized that in a solid state, you cannot identify individual molecules, or rather the whole crystal is one great big molecule with thousands of sodiums and thousands of chlorine atoms altogether. Mike Glazer, as I said,
Starting point is 00:22:41 they were rewarded the Nobel Prize in 2015 jointly. What did they go on to do after that? Because that was just the beginning for them, wasn't it, for both of them? Well, after the war, there was, first of all, the question of the, Nobel Prize ceremony, which was an issue because they decided to hold the ceremony. They couldn't hold it in the war, so they had the ceremony for Lowy, and they invited the two Braggs to come to that. They didn't go. And as W.H. Briggs, William Bragg said, there'll be
Starting point is 00:23:10 Germans there, because this was the strength of feeling. They lost, William had lost one of his sons, Bob, during the war, so there was bad feeling. And in fact, he never went to the Nobel ceremony. Lawrence went two years later. Anyway, Lawrence, takes up a position in Manchester, in the physics department there, runs the department, sets up a research group, and William goes to the University College, London, and then later on to the Royal Institution,
Starting point is 00:23:38 sets up a research group. The two of them decide to partition up the subject slightly, so that William would deal with organic crystals, mainly, whereas Lawrence would deal with metals and inorganic materials. That was the decision they jointly came to. There was this question of, of overlap, the two of them doing possibly the same things,
Starting point is 00:24:00 and it did cause a little bit of problems between them, not serious really, it's been over-exaggerated in the literature. The two of them were very devoted to each other. They were always writing letters to each other, explaining what they were doing. But you can see that Lawrence was a little upset because William Bragg was the person who was well-known in the science community, and it was William that tended to get invited to meetings and so on.
Starting point is 00:24:25 So, for example, there was the famous Solvay meeting, the second one in Brussels, where all the great physicists attended. Williams was invited, Lawrence was not invited. And this certainly caused a bit of an issue between them. But one can overstate that. They actually worked together quite a lot, quite closely. And were they pushing forward? Can you give the list of some idea of working as wanting,
Starting point is 00:24:47 but working at what and with what effect? Okay, so William's group, a large group he established, was doing a lot of work on organic crystals. For example, my old PhD supervisor, Kathleen Lonsdale was one of his students, and she was working on a problem which is well known in chemists whether the benzene ring, which is a six-membered carbon ring, is flat or not, which is an essential thing to know for chemists. And she was able to do a crystal structure of hexamethyl benzene
Starting point is 00:25:14 in very early days and showed that indeed it was flat, which is a great relief to many chemists. So this is the kind of thing that they were involved in. Lawrence, on the other hand, was doing more work on metals and on more inorganic materials while he was at Manchester. And this continued both at the University College, Royal Institution and Manchester between them were doing all this work in the 20s, 1920s period.
Starting point is 00:25:42 Judith Hart, Mike Glazier mentioned Kathleen Lonselder, and it is a rather almost a unique factor I wouldn't go that far in crystallography. that there are such a high proportion of female crystallographers. At one stage, William had 18 people working with him, and 11 of them were women, and Lawrence had a big proportion of women in his laboratories as well. What's going on there?
Starting point is 00:26:06 I think because it was a new subject, going back, obviously 100 years, there wasn't any sort of a feeling of exclusion. I mean, the early fathers, if you like, of the subject, there were the Braggs in the period we were talking about later on. There was J.D. Bernal and other great leaders, but they were not jealously guarding their corners, their area of subjects. And they were very generous in inviting any able students into their groups.
Starting point is 00:26:36 And it just so happened that women were being allowed to do more science. It had been a difficult period before then, so women going into science was limited. And I think the reason that we have still so many women in the suburb, It dates from the beginning, the generosity of the male scientists who were the research group leaders, and then setting up an atmosphere in which everybody was welcome. It's a very sharing community, and it still is. It's a very interdisciplinary community.
Starting point is 00:27:05 People come in from all sorts of basic subjects into crystallography. You could be a physicist, chemist, whatever, and you share your knowledge, and that's always been the case. And these founding fathers were very generous about that, and they didn't exclude anybody on the grounds of, well, you know, it was their subject already and they were jealously guarding it. And the women went to the top level, didn't it? Like Dorothy Hodgkin, who got a Nobel Prize. As you mentioned earlier, actually, for a work on Penicillian,
Starting point is 00:27:32 like as you were to come in. I was just going to say that William actually said on one occasion, women are rather good at crystallography. So he really appreciated having them in the lab. Do you think there was something different about the way, that women do crystallography, different from that way, which men do crystallography? was it being cheerful?
Starting point is 00:27:48 Doing crispography is getting the answer right, doing the subject well. The fact that women have maybe an appreciation of symmetry and appreciation of the order of things could be argued, but I mean that's a very odd view in my opinion. No, women do crystallography because they like it and if they're good at it, they go on doing crystallography
Starting point is 00:28:12 and doing it well. Yeah, I rather agree with that. Chris Hammond, Lawrence Bragg moved on to Cambridge, to Camdish, where he had a famously successful run there with the people he supervised, among whom was Max Perutz. Could you tell us a bit about him and his work under Bragg on the structure of proteins and how that carried the story of crystallography forward?
Starting point is 00:28:33 Max Perutz was an Austrian refugee who came to Cambridge in 1936 and began to work with Desmond Benal. He started work on hemoglobin. Bernal moved to Birkbeck College, in London, but Perutz was left behind, and he went to see Bragg to explain to him his project, and it was a wildly impossible project. At that time, 1937, the most complicated crystal structure then solved had 40 atoms or so. Hemoglobin, which Perutz wanted to solve, have 5,000 atoms. It seemed in a ridiculous project, but Bragg,
Starting point is 00:29:11 Bragg was a man to take chances, and he thought this was something which could crown his career as it were, by supporting Pruts. And he supported Pruts through the Medical Research Council and Graz right through to what was in fact an odyssey. It took Pruts 25 years to eventually solve the problem. Enormous amount of hard work,
Starting point is 00:29:31 absolute determination and not to give up. And for which you can receive the Nobel Prize in 1962. It was an odyssey. It makes the Greek myth sort of paling comparison with it. It also makes the case if ever and it needs to be made again and again that research going at an area
Starting point is 00:29:49 for which you cannot write one side of paper saying this will result in that happening in a few years. Somebody does not apply. 25 years he was supported by the Cavendish and other people there and so on and he came up with this solution to this problem which has had enormous consequences for all of us
Starting point is 00:30:07 and every day and increasingly and that was just by doing research for the sake of research finding things out and just hope that somebody is listening don't you? Having false act of faith, yeah. Absolutely. Can I just point out, Melvin,
Starting point is 00:30:21 that Dorothy Hodgkin took her first photographs of insulin in 1934, and the structure was the more refined high-resolution structure was published in 1969, and again she was devoted to solving that structure. It is an interesting point, and I wasn't making a part of a political point, I meant a cross-part of political point, that some of these things have taken an enormously long time by present-day standards.
Starting point is 00:30:46 But what they've delivered has been colossal for humanity. We're not talking about being good at winning Nobel Prizes, although crystallographers have been exceptionally good at winning Nobel Prizes. What is delivered, Judith? I think I would just say that, of course, at the time the first photographs were taken, and that was exciting enough to see diffraction spots
Starting point is 00:31:02 from a protein structure, and they did prove it really was a protein structure. The crystal they were looking at. I mean, the instrumentation has come on in leaps and bounds. The spectrometer, that I described just now, the fundamental parts of that were the rotating states, with the crystals, something to detect the x-rays and the x-ray beam. Those are still the fundamental parts of our instruments,
Starting point is 00:31:20 but of course the beams have got brighter, the detectors have got better, the computer programmes have improved in speed and everything else. So really we're looking at advances that have been incremental in some place, at some times rather, and leaps at other times.
Starting point is 00:31:37 They laid the foundation of all this. Mike Glazer, at the same time the Pritz was working on him, at the Cavendish. It was going full steam then. I mean, there was some wonderful scientists, some wonderful results. And at that period, enormous.
Starting point is 00:31:52 It was about 20 and a bar prize winners came out in crystallography alone. But Watson and Crick were there, supervised by Lauren Sprague, and there was Rosalind Franklin at UCL who played a very big part in this. At King's College. Sorry, King's College. Can you tell us about how that
Starting point is 00:32:10 developed? It's not my particular area, but I'll try and that. It's a long story and we'll have to cut that short obviously. Could we? Yes. Keep out all the salient points. It's a difficult one but anyway I'll try. We start off
Starting point is 00:32:24 with Watson and Crick in Cambridge. Jim Watson coming from the United States working with Francis Crick. Getting interested in the structure of DNA, which is the essence of genetics. Just prior to that, Morris Wilkins in
Starting point is 00:32:42 King's College had started a program under John Randolph, the head of department, looking at the structure of DNA, and they were starting to do some x-ray diffraction experiments, but none of these people, Kings, had any real experience in crystallography. They took on an assistant, Rosalind Franklin, who had a bit more experience. He's been working in the crystallography of carbon in graphite and coal. And she was given the task of really doing the experiments
Starting point is 00:33:12 to measure, to produce decent, three photographs of DNA. It was very divisive. There were problems at King's College. She fell out with Morris Wilkins. The communication between the two was very difficult. Some people say it was her fault, her attitude. Others say
Starting point is 00:33:29 that there was a very sexist attitude in King's College, and we don't really know the full story of exactly what happened there. What's a matter of conjecture? So Crickon Watson from Cambridge went to King's College, started at a collaboration, but it came very clear. It was very difficult because Rosalind was being uncommunicative some of the times, or rather they stumbled into a kind of mini-war that was going on in Kings. And so it was rather fraught. The cut the story short, on a visit
Starting point is 00:34:01 by Jim Watson to King's College, Morris Wilkins shows him a photograph that Rosalind Franklin had done without her knowledge, the famous photograph number 51. And Jim Watson seeing that, realizes that, in fact, this gives the clue. Now, I have to understand that Rosalynne Franklin wanted to do a really good scientific job on this, proper crystallography job. But people like the great Linus Pauling in the United States were very close to finding the solution, who already had published a triple helix. And so the race was on.
Starting point is 00:34:35 Watson and Crick had no time for that. So they spent their time building models, which initially Rosling and Franklin didn't approve of. eventually they produced the model, the famous model we've all seen and they sent that for publication into nature and the rest is history. Very good. And Rosalind Franklin's story remains out there but is becoming told more and more strongly and her influence and impact is being increasingly recognised, though not at the time. Not at the time but certainly now, and it does raise the question had she lived to see it
Starting point is 00:35:10 whether she would have been a recipient of the Nobel Prize. Yes. Can we, what, that is a big, I think, I can't remember who said, one of your, one of your company said it was one of the, perhaps the greatest invention that had ever been, the year. Einstein said that, yes, yes.
Starting point is 00:35:28 Did he? I wasn't thinking of Einstein, but Einstein will do, in this point. Is there any sense in which, because those amateurs like myself, like things to move on, like to be a story. Has there any sense in which it moved on from there? Judith?
Starting point is 00:35:46 Moved on from... What has gone on since the DNA discovery? What has moved... Where has Christopher... Oh, fantastic. Because as we've mentioned, the number of years that it took to solve a protein structure
Starting point is 00:35:58 in the old-fashioned methods and there wasn't any choice, of course, and the computer programs weren't there. And the computers weren't there. So the moving on, if you like, has come from the technology that we've been able to exploit and in fact even inventable, as you could say,
Starting point is 00:36:13 so the crystal officers have pushed off from the technology and so we're moving on such that instead of the years it took to solve a protein structure, we're now able to collect the data on a synchrotron on very, very tiny crystals, much smaller than we could have used in the past, and we're able to solve protein structures in next to no time at all.
Starting point is 00:36:32 I'd just like to add to that, that the great revolution has happened in the biological side, is that we can now solve structure, or the vacant soil structures with thousands of thousands of atoms almost immediately and we now have these major sources that Judas just mentioned,
Starting point is 00:36:47 synchrotron sources. For example, the diamond light source in Oxfordshire as well as the big neutron source they have their ISIS. This is revolutionising the way in which data's collected for these purposes. Now these are intensities of x-rays which were undreamed of in the time of
Starting point is 00:37:03 Bragg-winning. It took hours to get your data. Now it can be done in fractions of a second. Chris, Anne. And you can also see chemical process actually happening instead of things being fixed. You can actually see a chemical process in situ, which you could not have done with the old slow x-ray techniques, like
Starting point is 00:37:19 taking a running photograph, for example. That's revolutionised chemistry in a sense, too. You can see processes and the structural changes taking place as they take place with this rapid x-ray synchristral techniques. So there's a deepening and a spreading of research in this area, which is why it keeps appearing
Starting point is 00:37:34 in Annabelle Prize list, why other scientists are recognising it for the breakthrough science it is and it's influencing sciences right across the board, isn't it? Chris Hammondy. That's right. The crystallography has to be understood is an interdisciplinary subject and so you find not only in the biological site but in
Starting point is 00:37:51 metals, all sorts of material science and so on. So it has a very, very wide application and it's the way the reason that we can design new materials for the future by knowing the structures and understanding how they go. Oh, for example, in my own field I'm interested in materials which we call Piazoelectric. So these are
Starting point is 00:38:09 these materials which you can apply an oscillating electric field on create sound waves with them, or you can make timing devices with them. And there's a lot of interest at the moment in finding new materials which do not contain lead, which is a dangerous element. Most of the commercial material contains lead. So there's a race on around the world to find new materials. The only way you're going to do that was two ways you can do that. One is to try everything, the bucket and spade method.
Starting point is 00:38:34 Or you can be a scientist and try to understand why it works in the materials, have and then use that to develop the new materials. Judith? I think the evolution of structure with change of temperature of instant radiation and so on and so forth, I mean change of pressure. So structure evolution with an external device
Starting point is 00:38:52 is what we're interested in these days and we are able to do more experiments because we can do them faster. Because then we know that a material has a property but the property may not be useful at the temperature at which this phenomenon occurs. We can have a phase transition so it can become conducting, superconducting
Starting point is 00:39:09 at a temperature which isn't a useful temperature because it's so much below normal zero. If we can see what the structure is and we can make modifications and then bring that temperature transition into the ambient range which becomes therefore useful. That's just one example.
Starting point is 00:39:26 I mean the relationship between material properties and the internal structure was suspected a very long time ago before anybody could actually see inside the crystal but of course now we can tweak the chemistry or tweak the physics to make these materials more useful in the particular area that we're focused on. Chris Hammond, we talked at the beginning of the program
Starting point is 00:39:48 about the way that scientific research in this area has led to massive improvements in many areas in the life sciences. Are you able to give us some indication of that? In the life sciences? Yes. Always, I think the structures of say the proteins, and we most recently, lysosine, an enzyme.
Starting point is 00:40:11 In fact, we know that the structure. We know how these proteins actually operate, how lysosine and enzymes operate without this structural information arrived at from crystallography. They wouldn't know that. And so it's actually a revolutionized medicine in some ways too. I should say probably another thing about crystallography in general is that because it's interdisciplinary, it brings together people of all sorts of
Starting point is 00:40:33 different backgrounds, which is rather refreshing. You don't just meet, say, metallurphyxia. or biochemists who meet all sorts of different people. And that's very refreshingness. There's this cross-linking which goes on between crystallographers. It's one of the sources of inspiration, I think. Mike Lozor. We're very lucky to have our own international union,
Starting point is 00:40:51 and we hold meetings, international meetings, with crystallographers. And at those meetings, you can meet not only men and women, but you can meet metallurgies, mathematicians, physicists, chemists, a lot. All gathered together. So there's an enormous amount of cross-feeding that goes on between these different communities and it's unique to crystallography this.
Starting point is 00:41:11 So you think that crystallography is going to eat up every other science? There's only going to be one science in the world and it's yours. I wish we could. I think you already have in some ways. No, because we need the fundamental science in the first place. So the people who are trained in one discipline come into crystallography from those disciplines and meet together. But I think we do spark off each other
Starting point is 00:41:31 and I think those interactions are vital because a physicist may well know what his final aim is, but not be able to get there. The same with a biologist. Originally, biologists were not people who built machines. They were built by the physicists, chemists, maybe, a physical chemist. And so the developments there have been
Starting point is 00:41:48 from a mixture of disciplines. We've talked about the quite an outstanding success of the Cavendish laboratory. Is cutting edge, sorry about that work, still being done in this country, Mike Loza? Yes, I would say, so it's a little bit more difficult because of funding problems with it all
Starting point is 00:42:05 scientists have at the moment, but Yes, there's still a very active crystallography community doing cutting of research around the country. We are the second largest crystallography community in the world, the United States being first. Got to go. Mike Glazer, Judy Howard, Chris Hammond. Thank you very much, Bertrand Russell next week. There are many more Radio 4 arts and discussion programs to download for free. Find these on the website at BBC.co.uk slash radio 4.

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