A Century of Crystallography: the Braggs Legacy

Nothing is more seductive than a hidden world that is just out of reach. This is the story of how scientists learn to look deep inside the invisible structure of everything around us. Developing a technique so powerful that whenever something new drops out of the blue, you'll probably want to give it to a crystallographer. Like Anna. Anna spends her days exploring everyday things at the atomic level. She does it using the largest science machine that the UK has ever built. The Diamond Light Source. Medical breakthroughs, ever-shrinking machines, new wonder materials. The knowledge that flows from machines like Diamond is vital to our understanding of how our world works. 28 Nobel Prizes have been awarded to the Masters of the Science of Crystallography. Why have so many crystallographers won Nobel Prizes? Well, because the work is so important. You do something and you're the first person to truly understand it. Looking at these incredible images. Every day we see huge advances with that, new insights on the world in which we live. I've formed a company, I'm making cancer medicines, I'm still doing my basic crystallography. Many people say that when they choose crystallography, it's actually crystallography has chosen them. And to satisfy their needs, we have built ever more extreme machines. None of this would be possible without the pioneering efforts of a father and son team working together 100 years ago. I have been asked to say something to you of modern scientific discoveries. We all like to hear of the very large or the very small. Why do we value a diamond so? It's got no colour, generally, it's just a transparent little crystal. As you know, we value it so because it sparkles. This just illustrates the extraordinary property of a diamond, the sparkling. Neither fried, poached, boiled or scrambled, this egg is about to be crystallised. The diamond light source represents the latest chapter in a story that spans a century. It is a story of brilliant inspiration, ingenious invention, blood and tears. It's to do with the beauty of crystals, really, even today, many, many years later. If I look at a little crystal under the microscope and it has nice shiny faces and colours, I still get very excited by that. Warwick University in August 2013. I'm Professor Mike Glazer and I am a crystallographer and have been since the age of eight. This is a public exhibition devoted to the lives and work of William Henry Bragg and his son, William Lawrence Bragg. The Braggs inspired countless young scientists. And here I am in the audience in 1958 at the age of 15. Mike Glazer helped organise this exhibition along with Professor Pam Thomas of Warwick University and the Royal Institution. What are the odds of that, out of 200,000 school children going through there? That just says something about me because it means I was obviously a bit of a nerd and going there quite often. One of the great things about crystallography is not only that crystals are beautiful, but the people are beautiful. And we began with the Braggs. Well there were two Braggs, father and son, and 100 years ago they set up a whole new scientific discipline which we today call X-ray crystallography. Son with the original theoretical understanding and father with the experimental technique to make the most of it. An expertise in experiment, I should say, that father had learnt in Australia. I have never forgotten the warmth of my welcome, nor the kindness of the friends that I made during the 23 years of my stay in Adelaide. 23 happy years in which he married a local painter, Gwendolyn, and started a family. Their first son, William Lawrence, was born in 1890. Though a mathematician by training, William Henry taught himself physics and became a skilled maker of scientific instruments. He was fascinated by the mysterious new science of X-rays and gave lectures in the subject for students and the general public alike. The Adelaide population flocked along to Professor Bragg's lectures. Word of his expertise spread and in 1908 he was appointed Cavendish Professor of Physics at the University of Leeds. Leaving the clean air and sunny climes of Australia for the cold and smoke of Leeds might have dampened William Henry's spirits were it not for the emerging brilliance of his eldest son, William Lawrence. Very handsome, very upright. He was a shy man and a shy young man, but you would have noticed him nevertheless. William Lawrence Bragg had accompanied his parents to England and enrolled at the University of Cambridge to study for his second degree. He graduated in 1912 and immediately began research in the Cavendish Laboratory. It's difficult to realise how it was in those days because of our present knowledge of everything. Nothing was certain for them. I mean, X-rays were mysterious. Most of the people in Europe believed that they were waves, but some people believed in particles. In Munich that same year, physicist Max von Laue had been considering the burning question of the day. Were X-rays made of waves or particles? This puzzle had long been solved for visible light. When shone through sets of narrow slits, it would cast a pattern of dots. The dots could only be explained by the waves of light cancelling or reinforcing each other as they came together, forming a diffraction pattern. Laue knew that if X-rays were waves, then they should do something similar. But it could only work with a set of impossibly narrow slits. Where to find them? It's a rather lovely crystal of alum, a beautifully regular one with a top rather like... Sir William Lawrence Bragg's boyish enthusiasm for crystals is evident at the Royal Institution in 1959. He was by this time a grand old man of science, much loved by colleagues and the general public alike. It was at the very beginning of his career, aged just 22, that he founded the science of X-ray crystallography. What is it really that makes a thing a crystal? It's its inside arrangement. It's the fact that the molecules or atoms in it are in an absolutely regular pattern, like soldiers on parade or like the pattern of a wallpaper. At the heart of crystallography, it's this what we call translational symmetry, this repeating pattern of molecules that really defines what a crystal is. And Laue obtained the first photographs showing spots. When Laue's colleagues, Friedrich and Knipping, shone a beam of X-rays through crystals, a pattern of spots was recorded on the photographic plate behind them. First of copper sulphate, then of zinc blend. So in the summer of 1912, William Bragg here, he received a letter from a colleague called Lars Wegard informing him about this experiment of Laue's. Laue had even given Wegard a photograph of the pattern which was enclosed. And Lawrence goes back to Cambridge now with a wonderful research project, namely to try and understand the German experiment better than the Germans themselves. He pored over von Laue's pictures. There had to be some connection between the symmetrical array of spots and the invisible arrangement of matter in the crystals. In a brilliant flash of inspiration, Lawrence realised... Symmetry and pattern. The space lattice hypothesis. Their forms are very beautiful externally. The morphology of crystals. The beauty of the regularity. Must be related to a three-dimensional arrangement. And that external form reflects, and one might use the word reflecting in the context of reflecting light and reflecting X-rays. These spots are actually an image in Fourier space, in reciprocal space of the dispersion of atoms. And people had no way of understanding that. So you get external forms that are beautiful and then you get scattering of radiation, like X-radiation, that are equally beautiful. And the underlying common element of all of that is symmetry and pattern. Everything about the diffraction patterns could be explained precisely. They were really understood by Lawrence Bragg's work, which really explained them very clearly using diffraction by a set of lattice planes. Reflection of X-rays from planes of atoms in the crystal. Crystals have lots of planes. Parallel sheets of atoms that repeat regularly. They go from top to bottom, left to right, front to back, and through all the possible diagonals in between. Lawrence's genius was to recognise that each spot on the Lowy photographs was a single reflection from each set of these crystal planes. And the reflection, rather like a mirror, except that the X-rays going out tended to interfere with one another to produce constructive and destructive interference, to produce a pattern of spots. Lawrence quickly condensed all his measurements and calculations into one simple formula. N lambda equals 2d sin theta. This is now one of the most famous equations in all of science. It is called Bragg's law. Bragg was doing something that had never been done, never been thought of, and he just comes up with this idea of how it works. Such a simple concept, but it's so elegant. Bragg's law and the Bragg contribution to crystallography is something that is part of our DNA, you know what I mean? A 22-year-old student had succeeded by all the best brains in Europe had failed. His prediction of the pattern that would be produced by a zinc blend was spot on. Writing to his father about the discovery, Lawrence's excitement was evident. Lowy's thing was the equivalent to reflection, but, of course, he didn't see it, and it's great fun getting it straight off, isn't it? His father very quickly realised that his son had got something here, and that's when William Bragg had the spectrometers designed by his assistant C.H. Jenkinson. This is one of the most important inventions of the 20th century. So in front of me here we have one of the original spectrometers used by William Bragg and Lawrence Bragg together in 1913. The whole idea of this is that you put a crystal on the central turntable and you have X-rays striking the crystal. The crystal splits the beam into a bloom of new rays. Each of these new rays projects a single spot outwards. Lowy's photograph had captured many of these spots at once, whereas William Henry's machine could only study them one at a time. But it could do so with exquisite precision. Zooming down to the scale of atoms and a set of crystal planes heaves into view. The beam of X-rays passes straight through the crystal. Just a little is reflected off each plane. And nothing happens. This crystal, like all crystals, must obey Bragg's law. The reflected waves have each travelled slightly further than the one before, but in doing so they have fallen out of step. The peaks do not line up. The waves simply cancel each other out. Darkness. At certain special angles, however, a bright spot shines out from the crystal. The reflections are travelling further by exactly the right amount to fall back into step. d, the distance between atoms, to be solved with simple trigonometry. Understanding this law of nature had been Lawrence's brilliant deduction, but it was now his father's machine that fed Bragg's law with data. The ionisation chamber detects each spot and generates a current, and that is measured by observing through a microscope at the base of the instrument the deflection of a slender gold leaf. And then do this many, many times until you've traced through all the possible angles. And it's these peaks of intensity which you need to have if you want to solve the crystal structure that's causing the diffraction. Bragg the father collected the data, while Bragg the son did the analysis. So the father and son worked together closely throughout 1913 and early 1914, plundering the field of crystallography, looking at lots of structures. One of the ones that's very important, that really began all of this, was the structure of common salts. Salt. Here's a salt cellar with crystals in it. It's very trendy now to have rock salt on your table, and these crystals are of sodium chloride. And we have the original model of sodium chloride here in the exhibition. This is one of the first structures, and I think that's interesting because people sort of knew, had an idea about the cubic nature, but these are the first thing that really opened people's eyes that you can use the X-rays to see atoms. The Braggs did salt. Big deal. Everybody knows salt. Not then they didn't know salt, because at that time most scientists thought salt was a molecule, like a water molecule, which is usually represented for high school students as the Mickey Mouse faced with the two ears. So they thought that sodium and chloride were together in a vapor phase and that they were a molecule of sodium chloride. So the crystal structure was a surprise. This was something the chemists didn't like at all, and it was highly controversial. In fact, the professor of chemistry at Leeds, Smithles, actually tried to get Lawrence Bragg to move the chlorine and the sodium slightly together to form a molecule rather than have equally spaced atoms. Even after it's clear what salt is, some people still think that salt is a molecule and that that crystallography is rubbish. But, of course, it turned out that Lawrence Bragg was right, the chemists were wrong. It's hard to go against that kind of thing, but it's the only way you make real change. In celebration of a hundred years of Bragg's law, Professor Pam Thomas of the University of Warwick decided to recreate their salt result. So we did the experiment on our modern diffractometer. It's not running with x-rays at the moment, otherwise I wouldn't be standing here with the doors open. Very similar to the Bragg's original ionisation spectrometer, the crystal is in the beam of x-rays and produces a set of diffractive beams, which are captured. And here's the modern electronic equivalent of photographic film. So it collects the reflections and allows us to measure their intensity and position. So the end result is an image like this one, looking down the fourfold axis of the structure in sodium chloride. And so you can see that the spots have a fourfold symmetry about the centre. And indeed, if you were to solve the structure of salt from these data, you would get the same result as the Braggs got from their experiment a hundred years ago. I take a crystal, a crystal of rock salt, and cunningly give this a nick in just the right direction. You see how beautifully it breaks? Absolutely regularly. And we can go on carving it up in a cubical way forever. There it goes again. So this is one reason why diffraction crystallography is still a powerful method if you want to know where the atoms are and what are their neighbours. Nobody can beat that today. Today, the diamond light source represents the state-of-the-art of the Braggs legacy. It is a huge particle accelerator called a synchrotron and is designed to be one of the brightest lights on Earth. There are X-ray labs all the way round. The past century of Braggs' law has seen crystallographers solve ever-larger structures through a menagerie of chemical compounds to the very machinery of life, the proteins, enzymes and even viruses in our cells. If they can be crystallised, then diamond can help solve their structure, leading to new treatments and a better understanding of biology. Have you ever wondered why eggs seem to last so long before they go bad, even when they aren't refrigerated? It's because they contain a bacteria-fighting enzyme called lysozyme, which keeps them fresh. The structure of lysozyme was solved by a team of crystallographers working for five years in the 1960s. Diamond is up for the same challenge today. OK, so what we're going to do is we first have to crystallise the lysozyme. And how we do that is we have two different solutions. What we have in here is a solution of our lysozyme. Here, ethylene glycoside. Put that into the same well. That will continue to slowly diffuse into the well, changing the concentration and helping to form crystals over a few hours, a few days or a few weeks. One of the greatest challenges faced by protein crystallographers is growing the crystal in the first place. It is very difficult. Some people take years to get to a point where they have crystals suitable to study with X-ray diffraction. Large biological molecules are hard to purify, and often fragile or floppy. They would never exist as crystals in nature. So finding the unusual set of conditions required to force them into an ordered array can take years. In order to grow a crystal, you need to have what we call a seed. Now that's a little bit of crystal, something that's already ordered. So here is my seed. You'll notice it is the bottom half of an octahedron. And if you look from the top here, you see all of the marbles in a nice regular array. So that is a bit of crystal. What I'm going to do is I'm going to add the other atoms or marbles randomly to this and see what happens. So this is the magical bit which I hope will work, and we'll see what happens. Magically, what's happened, we've formed the other side of the octahedron. If you start with some order, then the crystal continues to grow in an ordered fashion. The egg lysozyme has formed into perfect crystals. Well, when I started, we practised with sugar crystals before we were allowed to test on real crystals. They're quite fragile, so it takes quite a lot of time before you get used to doing it. OK, so we take this over to the microscope to mount the crystals. I'm going to look for the most beautiful-looking crystals, so that's one that has really nice edges. It's not got any of the crystals stuck to it, so we want a single crystal. So I'm going to have a look under the microscope and see which ones look best. It takes a steady hand to mount the vanishingly small crystal on the tip of a pin. Yes, definitely steady hand. Lots of practice. So I've frozen the crystal now, and I'm going to place that into the puck. So that's now in there. And then we just need to place on the base plate for it to go into the robot. What happens is the atoms, when they form a crystal, they bond together. They want to maximise their density and at the same time maintain symmetry in order to produce a stable structure. In this way, they minimise their energy, and the crystal grows. So crystal growing very often is done in this way. You start with a seed, and you create a growth. For example, this is an artificial crystal of quartz. And when we hold it up to the light, one can see a band through the middle of it, and that is the original seed plate that this crystal was grown from. Good evening. A little crystal, exactly like the one we were trying to copy. It was at the front that William Lawrence Bragg received a telegram. Nobel Prize for Physics, 1915, awarded to you and your father. This is the only time that the Nobel Prize has been awarded jointly to a father and son team. And Lawrence Bragg remains its youngest ever recipient. He was just 25. I'm Patience Thompson, and my father was Lawrence Bragg, and my grandfather, William Bragg, and together they started crystallography. As we go along the scale, we come to number five. That's a mineral called apatite there, which, strangely enough, is the stuff which our teeth are made of. He was a teacher. He was an absolutely born teacher. These are so arranged that each scratches the next. This one scratches that, that scratches that. Talc is the stuff we use for baby powder. Babies, apparently, are slightly more than one on the hardness scale. It was such fun to be with. I mean, I remember we went to a sans-lumiere, and there they were spouting about the historical stories, and he said, By Jove, everybody, there's an otter in the moat. He was more of a wild lover than a historian. But he always said what he loved to see was a pattern and purpose in life. Now, if you live that long, you really do see the pattern of crystallography development from its raw beginnings, as you might say, to the complexity of DNA, and I think he thought himself immensely lucky to have dropped into this field at the right moment and have the right sort of three-dimensional mind to solve these problems, which is very important, I think. The right sort of three-dimensional mind, the right stuff, as it were, was something that both Braggs sought to nurture. It was all there waiting for us. The Braggs were very inclusive. There were a wonderful group of colleagues who then created a family. With all the Nobel Prizes, of course, it's a family with some glamour. The family tree of crystallography. William Henry Bragg created one of the world's leading X-ray crystallography labs at the Royal Institution in 1923. Under his guidance, many great scientists were nurtured. Brilliant Irishman J.D. Bernal, along with his PhD student Dorothy Hodgkin, was the first to see a protein diffraction pattern when he placed a hydrated pepsin crystal in front of his beam. This was the first glimpse into the molecular world that underlies living things. At the time, however, it wasn't possible to solve the structure from the pattern. Then, of course, there were no computers, but soon after, the beaver's lips and strips were invented. When I began research as a PhD student in London in Kathleen Lonsdale's lab, one of the first things she asked us to do was to use beaver's lips and strips like this to do a very simple map of the structure that she had solved back in the 1920s. And we laid out all the bits of paper and did all the calculations, and to get one very simple map, that took a week. All the calculations that mattered were done with beaver's lips and strips. Dorothy Hodgkin, Nobel Prize winner... I thought I'd better begin with some small molecules. ..and one of the most successful and famous crystallographers of all time. One of these small molecules was penicillin, just the right size for a beginner. That penicillin, you see, that structure, is the reason why we have all the antibiotics we need. Dorothy went on to solve vitamin B12, and after many years of work, insulin as well. Insulin was solved by Dorothy Hodgkin after 30-plus years of work, when she was working in Oxford with the Dodsons and Tom Blundell. Dorothy Hodgkin had spent 30 years really working on the insulin structure. I was lucky to be there. These things are very, very important, extremely important. The world would be a very different place if Bragg hadn't done his work. Now we're flying faster than Mach 1. Faster than sound. Lawrence Bragg compared her B12 success to a sonic boom. As for the first time, X-ray analysis beat the chemists to the solve. For this achievement, she was awarded the Nobel Prize in Chemistry. In 1937, William Lawrence Bragg was invited to be head of the Cavendish Laboratory in Cambridge, and he went there and encouraged a whole generation of crystallographers. So he had Kendrew, Perutz, Watson, Crick. When Jim Watson first came to the Cambridge lab, at the very beginning, he was not working with Francis Crick on DNA. He was working with me on myoglobin. And we were working on lampreys, a very slimy fish. Dissecting lampreys is not easy. So after about three weeks of this, Jim Watson decided this was not for him, and went off to what seemed to him an easier assignment, which was to think about DNA. I couldn't think about anything else than DNA. You could say I was helped in Cambridge, because there were no girls. And I didn't do sports, so it was just DNA out there. DNA. Now, everybody knows about the structure of DNA and Crick and Watson. That was published in a famous book called The Double Helix, and Lawrence Bragg was asked to write the foreword for the book. Why did you get Lawrence Bragg to do the foreword to your book? Well, because he knew the story very well, and it was my way of really saying I respect you. Wilkins, Crick and Watson shared the Nobel Prize. Now, Maurice Wilkins was working in King's College. Also working in King's College at the time was another pioneering woman of crystallography, Rosalind Franklin. There, she produced one of the most famous X-ray diffraction patterns of all time, photo 51 of DNA fibres. What role did crystallography play in helping you do that discovery? Oh, it told us it was going to be a helix. In the very early 1950s, my colleague Francis Crick gave a lecture in the Cavendish entitled What Mad Pursuit? Kendrew and Perutz, of course, were trying to do proteins, even though everybody at the time thought they were really a bit crazy to try. Because everybody thought we'd never saw a structure as complex a molecule as this. Max Perutz and John Kendrew, the pioneers of protein crystallography, worked under the attentive guidance of Lawrence Bragg. Kendrew, after 12 years of research, produced the first 3D map of a protein, myoglobin, in 1957. And there it is on the right. And you see on the left is a piece of modern sculpture. We were thinking of putting the myoglobin model into a modern art exhibition. I think we might have won a prize. Bragg didn't think of it that way. He thought the myoglobin model was... The word he used was obscene. LAUGHTER Crystallography is a very visual subject. We have very, very beautiful models, very beautiful structures. Now, this model is the original model for the structure of haemoglobin. Suddenly saw this thing, you know, which I'd been working on for 22 years, and it was a fantastically exciting moment. I always say it was like reaching the top of a mountain after a very hard climb and falling in love at the same time. Most of you crystallographers are romantics, and so you will certainly know that this is a quotation from a poem by Keats. I used to carry on with my X-ray pictures day and night. What men or gods are these? What maiden's loaf? Every two hours, I would get up, turn my crystal, restart the X-ray tube, take another photograph and so on. What mad pursuit? What struggle to escape? The other research students in the lab thought I was crazy to take this on. What pipes and timbrels? What wild ecstasy? Intensity of joy and jubilation and admiration, which perhaps you find only in science, when nature reveals one of its great secrets. So that was marvellous. The result of this was that in 1962, Kendrew and Perutz obtained the Nobel Prize for this work. As crystallography grew and grew, its reach stretched beyond the scientific domain. With ever more complex structures emerging, their beautiful patterns inspired the worlds of art and fashion. This dress was worn by Lady Alice Bragg, Lawrence Bragg's wife, at an international meeting of crystallographers in 1951. Its delicate lacework shows one of her husband's souls, the mineral beryl, composed of intricate hexagonal crystals. In the same year, the patterns of crystallography were celebrated at the Festival of Britain. Carpets, curtains, plates and even food menus were inspired by the beautiful images generated by the science. Insulin, myoglobin and haemoglobin, among many others. The visual science of crystallography had captured the public's imagination. The exhibition was organised by crystallographer Helen McGaw. Crystallographers are often very good at visualising things in three dimensions. I can tell you a little story. I used to work for a lady called Helen McGaw in Cambridge who had been a student of J.D. Bernal, who had been a student of W.H. Bragg, William Bragg. In fact, she worked on this particular structure as well. And I could go to her and I could say, what does the structure of quartz look like if it's down some funny direction? And she'd think about it for a few moments, take a piece of paper out and a pen and draw it for me. She never used computers. In those times, by doing things by hand, you would understand better what was going on, you know. When I started, we still had open X-ray tubes. So this is really going way back. It's a very much weaker source of X-rays than we have today with modern synchrotrons. In those days, it was slightly different to diamond and modern technology. If someone entered the room smoking a cigarette, the signal would be much wider than the signal due to the X-rays. Quite glad that I had that bad experience. You know, it gave me, I think, more insight into the real things that were going on. We punched each reflection that you measured from the crystal on a punch card. The mathematics, the physics behind what you're doing. Sent that off to a University of London computer centre. I had to write my own computer programme. And got one job back in a week. Nowadays, you just press a button, you get the result. Things have speeded up. Things have speeded up. But by how much? Back at the diamond light source, we're about to find out. It's like a giant thermos flask. The crystals are stored in liquid nitrogen at minus 196 degrees Celsius. So all the time we're trying to make sure we don't have our samples out of the liquid nitrogen for too long. Because otherwise our crystals will die. The crystal will be picked up and placed in front of the X-ray beam by the robot arm. And the X-rays will come out of this small hole here, hit our crystal as it rotates, and the diffraction that comes off will be detected on our detector here. But before the experiment can begin, the rule must be cleared. This X-ray source is 100 billion times brighter than the bulbs used by the Braggs a century ago. Anna makes her final checks before sealing the room. Yep, so it's moving now. The lid's going to open. Now that's finished, it should be ready. You can see our crystal positioned within the centre of that mesh. So the crosshairs here, that signifies where the X-ray beam is. We should see everything moving into place up here, and then the data collection will start. So our images are coming in now. Just rotating the crystal 0.1 degrees between images. So, since you set that going, it's already finished. So the whole data collection is complete. As soon as the crystal stops spinning, the computer takes over. Quickly scanning through the hundreds of diffraction images, the system reads the position and brightness of thousands of Braggs spots. Solving lysozyme the first time in the 1960s took David Phillips and his team at the Royal Institution five years. This is the actual model at the time, a complex model for its period. At the back of the exhibit, around the corner here, we have a line drawing done by Lawrence Bragg at the time of lysozyme. And you can see that he really understood this structure very well, even though he wasn't the person that actually was working on it directly. Graduate student Louise Johnson is credited as co-discoverer of this, the first enzyme ever to be solved. Louise later became Director of Life Sciences at Diamond Light Source and was instrumental in making the machine the perfect tool for probing biological structures. She passed away in September 2012. It was my job to clear her office out recently, and I was really awed by her... I was awed by how much information she'd collected and what's more how much she clearly understood and remembered. Now, using the very machine that Louise helped to build, Anna is solving her enzyme lysozyme again. A nice 3D picture of where all our atoms are located. And it's already finished. If I zoom out, we end up having a whole image. The lysozyme that's present in the white of this egg, we've now got the atomic structure of that material, and we can then use this 3D information to work out how that lysozyme functions within the egg. Obviously, the experiment itself only takes a few minutes, but it will have taken years for scientists to have got to this point where they can get data like this. From five years in the 1960s to less than five minutes today, this is extraordinary progress. But with all the computers crunching data, robots lending a hand, and pure synchrotron light shining on the crystals, isn't it all a bit too easy? It definitely helps having a synchrotron, but I wouldn't say it was easy. I think crystallography has become more routine for protein crystallographers, but that's opened up new possibilities of tackling even more challenging problems. And I think if you ask Venki Ramakrishnan if it was easy solving the ribosome, you would see that he pushed all the techniques that we've developed to their absolute limit to solve this fantastically enormous and important machine. The advances in crystallography over the past 100 years can be seen in the size and complexity of the structures we have now solved. From the Braggs' early experiments with salt, to the several thousand atoms in the egg white lysozyme, to the vast molecular machine that is the ribosome... ..we've come a long way. We're still on a steeply rising curve. The machine you see behind us is constantly being developed. The source, the optical components, the detectors are all being improved at an incredible rate. So that experiment you saw today, you come back in a few years' time and not only will you be able to do that experiment much more quickly, but you'll be able to do completely new types of experiments that are currently not possible. And trying to work out new ways that we can use diamond to understand these complex systems. So we just moved on a bit, but still the X-ray crystallography and the real crystals are critical. We don't do anything unless we can get them. You know, some 30 years ago, people, mostly chemists, would say, oh, crystallography is a dead science. It's so easy to solve crystal structure. And nowadays, we are contributing to biology, to chemistry, to physics, and to everything. And things are going on at the same pace, I think. Why do I still love protein crystallography? Because we've just spent four years, two years to get the protein, two years to solve a structure from which we only got one crystal, which is a tuberculosis protein, which may be a help in finding a drug target in tuberculosis. And to see that structure for the first time is still the most fantastic thing. Crystallography will continue to play a vital, vital role for a hundred years more. Bragg's legacy continues. And to my viewers, I'd like to say that I hope I succeeded my aim of showing you what a deep interest there is in the science of everyday things.