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Crystallography - feature - feature

STRUCTURAL BIOLOGY, GEOLOGY, , CHEMISTRY, . BRAGG’S LAW. SPECTROMETERS. DIFFRACTOMETERS. PIONEERING DONE AT LEEDS A CENTURY AGO STILL FEEDS INTO MUCH OF MODERN . THIS IS HOW IT STARTED

The birth of X-ray crystallography For their achievements, William at Leeds in 1912-1913 through the and were awarded work of Sir Bragg the 1915 in Physics. In and his son Sir W. Lawrence Bragg 2013, the Braggs’ work was named was one of the culminating episodes the third most important British in arguably the most extraordinary innovation of the in an three decades in the physical . online vote of 80,000 people. Between 1890 and the end of Yet research on crystallography the First World , X-rays and had not even begun when the Braggs radioactivity were discovered, the arrived in England from Australia theories of relativity and six years before the Nobel award. developed, and the Such immediate recognition is rare constitution of first explained. for Nobel Prizes, and it testifies both During this period Marconi to the importance of their work and developed radio telecommunication, the clarity with which they explained the Wright brothers made their first and demonstrated its potential in flights and proposed many areas of science. quantum theory. These were, in Cumbrian-born William came other words, the formative decades to Leeds from the University of of the modern age. , Australia, where he had It is not often appreciated established a international how important to that incipient reputation for his work on modernity the Braggs’ work was. radioactivity and the of the William and Lawrence paved the new invisible ‘emanations’ from way to countless scientific and : X-rays, gamma rays and technological breakthroughs by alpha particles. As of revealing the arrangement of atoms Physics and , William in crystals. Although it had been long had found in Adelaide a meagre suggested that crystals were made laboratory, so he set about making up of a regular pattern of atoms and his own equipment by apprenticing molecules, there was previously no himself to a local instrument maker. way of knowing precisely how these When Leeds needed a new were arranged. Cavendish Professor of Physics in X-ray crystallography is the 1907, the English Frederick chemist’s most reliable tool Soddy recommended William to the for deducing the shapes and University, saying that, when he had arrangements of molecules. It tells visited Adelaide, “I was much struck us about the nature of terrestrial with the spirit he has created around and extra-terrestrial minerals. him.” William was offered and Through an understanding of crystal accepted the post. THE BIRTH OF Sir structures, it became possible to In January 1909 William and explains the theory of develop new and better materials. his family – wife Gwendoline, sons reflecting by prisms When applied to the molecules of Lawrence and Robert and daughter BY PHILIP BALL to school children at life, it ushered in the age of molecular Gwendy – boarded the coal-fired a 1931 lecture at the biology and genetics – most famously Watarah for the journey to England, . as the technique that revealed the arriving in Plymouth in March. Photo © Hutton-Deutsch structure of DNA to They rented a house in fashionable CRYSTALLOGRAPHY Collection/CORBIS and in 1953. Headingley as well as a weekend

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AFTER ONLY SIX YEARS THE BRAGGS WERE AWARDED A NOBEL PRIZE FOR THEIR WORK. NOT EVERYONE RECOGNISED THE IMPORTANCE OF BRAGG EXPLAINED THE IDEA OF THEIR WORK HOWEVER. “I WAS SO SHEETS OR PLANES OF ATOMS WITH A PLAQUE OUTSIDE THE PARKINSON EXCITED THAT I HAD TO TELL MY BRAGG X-RAY SPECTROMETER REFERENCE TO THE ROWS OF VINES BUILDING COMMEMORATES THE WORK AUNT ABOUT IT, WITH INDIFFERENT ENGLAND, 1910-1926 IN A VINEYWARD OF THE BRAGGS AT LEEDS SUCCESS,” WROTE LAWRENCE

father was supreme at handling X-ray align and you can see them stretching gathering of Europe’s top physical A LEEDS GRADUATE: tubes and ionization chambers. You away in parallel formation. – was a particularly must find it hard to realize these days On this , Lawrence worked prestigious platform, and at the FROM LEEDS TO MARS what brutes X-ray tubes then were.” out how the reflection angles of the 1913 meeting on “The Structure At Leeds, William had rather better spots depend on the distances between of Matter” William discussed his Would the Braggs ever have looked technical support than Lawrence did sheets and the wavelength of the work with and Marie up at Mars and imagined that, one in Cambridge, which still pursued X-rays. He expressed this in a formula Curie, along with several scientists, day, an X-ray spectrometer would PHOTO: a “sealing wax and string” approach now known as ‘Bragg’s law,’ which such as Leon Brillouin and Frederick W. LAWRENCE BRAGG, be there, gathering data on the to experimentation. William, in first appeared in a paper presented to Lindemann, who went on to make WHO WORKED WITH planet’s surface? Although only the contrast, enjoyed the services of the Cambridge Philosophical Society important contributions to the HIS FATHER AT LEEDS size of a tin can, the Alpha Particle WHILST A STUDENT AT an excellent workshop led by head in and was reported understanding of and CAMBRIDGE X-ray Spectrometer (APXS), mechanic C H Jenkinson. in Nature in December. Here he also crystal structure. developed by the Canadian It was Jenkinson who built, from showed that, by assuming a particular Late in 1914, William wrote CREDIT: Agency (CSA), MDA robotics and SCIENCE & SOCIETY William’s design, a revolutionary kind of arrangement of atoms in a long letter to the Leeds Vice- PICTURE LIBRARY Professor Ralf Gellert’s science instrument that could be used crystals of zinc sulphide, he could Chancellor Michael Sadler, pointing team at University of Guelph, both to measure X-ray account perfectly for the X-ray pattern. out the University’s pre-eminence Canada, is sending an enormous (the technique of X-ray The Braggs’ crucial realisation was in X-ray diffraction. “The practical amount of data about the geology spectrometry) and to measure that, if the X-ray diffraction pattern applications are likely to be of no of Mars back to Earth. Attached reflections from crystal plains could be accurately predicted from a less importance than the theoretical,” by an arm to NASA’s Curiosity (X-ray diffraction). The instrument, crystal structure, then one could also he wrote. Although his request rover, the instrument determines used both as a spectrometer and a work backwards, deducing from the for funds was supported, Leeds the chemical composition of the diffractometer, partly superseded experimentally measured pattern, the couldn’t match the offer in early rocks and soil in the red planet’s Laue’s photographic technique in structure of the crystal itself. 1915 of a professorship from wealthy Gale Crater. that it enabled precise measurements Of all the crystals whose structures University College (UCL). CSA’s mission for of the angles and intensities of the were worked out principally during William at first refused the offer, but Curiosity is a who diffracted beams. 1913 (sodium chloride, potassium by the he accepted their second studied at Leeds. Vicky Hipkin Adhering to William’s ‘corpuscular’ chloride, calcium fluoride, zinc offer he had decided he needed to (PhD Atmospheric Physics 2000), view of X-rays, the Braggs at first sulphide and diamond) it was the be in London at the centre of the Senior Program Scientist, Planetary sought to interpret Laue’s bright structure of iron sulphide which gave war effort. Exploration, says “Curiosity’s X-ray spots on the basis that X-ray Lawrence “the greatest thrill,” as he William’s departure was not APXS is amazingly sensitive given AT THE 1913 MEETING ‘particles’ were being channelled recorded long afterwards. This was the necessarily the tragedy for Leeds ON “THE STRUCTURE its small size. William Henry along ‘avenues’ between rows of first structure in which the positions of that it might have seemed at the OF MATTER” WILLIAM Bragg’s spectrometer at Leeds has atoms, an idea they described in a the (sulphur) atoms were determined time. The Braggs’ seminal work BRAGG DISCUSSED been miniaturised using modern HIS WORK WITH paper published in October 1912 in from the intensity (brightness) of the here inevitably left a legacy. In 1929 ALBERT EINSTEIN AND technologies – the drift the journal Nature. reflections. Lawrence recalled that “I William’s student , detector and sensitive electronic cottage near Bolton Abbey 20 miles Given this interest, the Braggs, But later that month, shortly worked it out in the drawing room of who worked with him at UCL circuitry for pulse detection. north of the city. Lawrence enrolled, father and son, were fascinated by PHOTO: after his return to Cambridge for our house in Leeds and was so excited and later at the Royal Institution APXS data are very important as his father had 28 years earlier, at news of work in by Max WILLIAM HENRY the Michaelmas term, Lawrence hit that I had to tell my aunt who was in London, came to Leeds as a to geochemists on the Curiosity BRAGG WITH HIS Trinity College, Cambridge. Laue, a student of Max Planck. Laue SPECTROMETER, on a novel explanation. “The idea sitting in a corner all about it, with ‘textile physicist.’ Textiles was the team. Ratios of trace abundances William was deeply interested in found that when a narrow beam of C1910. WILLIAM suddenly leapt into my mind,” he indifferent success.” manufacturing base on which Leeds of soluble elements like chlorine the nature of X-rays. At the time X-rays was directed at a crystal, the ENJOYED THE later wrote, “that Laue’s spots were The collaboration between father had grown prosperous, and the and bromine can tell us about the SERVICES OF AN a vigorous debate raged among scattered rays formed a geometric EXCELLENT WORKSHOP due to the reflection of X-ray pulses and son continued throughout the hope was that research on wool water history of Mars, and ratios about whether X-rays were pattern of bright spots on a AT LEEDS, LED BY by sheets of atoms in the crystal.” whole of 1913 and until the outbreak and other economically important of sodium, potassium and silicon ‘corpuscles’ or ‘pulses’ – particles or photographic plate placed behind the HEAD MECHANIC What Lawrence understood was of war in 1914. Lawrence spent part fibres might one day improve the oxides can be used to understand – the latter widely believed to sample. Laue attempted to interpret CH JENKINSON that the beam behaves as though it of the spring and summer terms in manufacturing process. rocks of volcanic origin.” travel through an invisible medium the pattern but could not account CREDIT: has been reflected by these sheets, or 1913 at Cambridge but the rest of X-ray crystallography had been called the ether. Although William for all the spots. Lawrence, still at © E.O. HOPPÉ/CORBIS layers, as light is reflected by a mirror. the year at Leeds. The Braggs’ work, initially applied to inorganic crystals, preferred the particle interpretation, Cambridge, recalled that he and William explained the idea of for which they jointly were awarded and the challenge of applying the X-rays are in electromagnetic his father discussed Laue’s findings sheets or planes of atoms in 1915 the Nobel Prize, was published in a same technique to the study of the waves, like light, but of a very much intensely “when we were on holiday in the Leeds student magazine The series of papers by the Royal Society large biological molecules found in smaller wavelength. Yet Albert at Cloughton on the Yorkshire coast.” Gryphon with reference to the in London, marking the birth of fibres was considerable. Yet Astbury Einstein argued in 1905 that light Over the summer and autumn rows of vines in a vineyard – not X-ray crystallography. met the challenge and, thanks to a can also be considered to be like a of 1912, William and Lawrence an obvious Yorkshire reference, but William delivered talks on this series of breakthrough papers on stream of particles, called : collaborated in the Leeds Physics wine had been made in the Adelaide new science around the country, the structure of proteins and to his this ‘wave-particle duality’ was laboratory. Writing in 1961, Hills since the early nineteenth at the British Association and in energetic proselytising, Leeds became one of the first fruits of the nascent Lawrence pointed out how adept century. As you walk through the particular at the . famous as the “X-ray Vatican” and quantum theory. William was in the laboratory. “My rows of vines, every so often they The conference – a roughly triennial the home of molecular biology.

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A LEEDS GRADUATE: Thomas is part of an Astbury Centre modern devices such as , team of structural biologists and medical ultrasound, fuel injection A LEEDS GRADUATE: STILL LEADING THE WAY virologists that recently discovered valves and parking sensors. Without SAVING LIVES WITH X-RAY how the Schmallenberg virus, which using X-ray diffraction to inspecting A leading pioneer in causes birth defects and still births in the atomic structure in piezoelectric SPECTROMETRY microscopy, Ondrej Krivanek some animals, could be targeted by materials, researchers would be FRS (BSc Physics 1971) is anti-viral drugs. They deciphered the unable to observe the results of The study of the structure of developing a new generation of 3-D shape of the Schmallenberg virus their atomic manipulation and protein receptors in cancer cells electron microscopes and other nucleocapsid protein and saw the engineering efforts. and how they react to drugs is electron-optical instruments. proteins bind together in a ring-like Because current commercial at the heart of how one Leeds Nion, a company he co-founded structure, held together by contacts piezoelectric materials only work graduate has saved women’s lives 15 years ago near Seattle, USA, between the protein units, a bit like well up to around 200°C, their around the world. makes the world’s leading people holding hands in a circle. development has been limited. Ionix V Craig Jordan OBE (BSc scanning transmission electron Thomas says: “We are now designing Advanced Technologies, a spin-out Pharmacy and Pharmacology microscopes, which are able to small molecules that could block company based on work done in the 1969, PhD Pharmacology 1973, focus a beam of on one ring formation and could therefore Institute of Materials Research by Dr DSc 1985, DMed 2001), an at a time to determine its become an effective antiviral drug.” Tim Stevenson and Dr Tim Comyn, is eminent specialist in drugs for chemical type, its precise location creating novel piezoelectric materials breast cancer treatment and in a complex structure and its that can operate at high temperatures prevention, is known as “the atomic environment. MATERIALS ENGINEERING and in extreme environments. If these Father of Tamoxifen” after doing Both the Bragg apparatus and materials could be used in valves his PhD on the oestrogen receptor the use a and transducers for cars and aero- (ER) binding with oestrogen radiation with a wavelength short Professor Rik Brydson leads the engines at temperatures in excess or antioestrogen. enough so that individual atoms Leeds Electron Microscopy and of 500°C, they would enable the Today, Craig is Scientific can be distinguished. Compared Centre (LEMAS) as development of cleaner, more efficient Director and Vice Chairman to the X-rays used in the Bragg In 1938 one of Astbury’s research the University to understand the well as coordinating the National transport systems. of Oncology at the Lombardi instrument, the electrons used PHOTO: students, Florence Bell, produced the molecular basis of life, and much Facility for Electron Microscopy Comprehensive Cancer A HIGH RESOLUTION in electron microscopes have an EMISSION GUN first X-ray diffraction image of ND A, of this work is based on X-ray (SuperSTEM). Based at Daresbury Center, Georgetown University, additional advantage: they can SCANNING ELECTRON a crucial step that led in 1953 to one crystal structures. Laboratories in Cheshire, SuperSTEM Washington, DC. He uses be focused into a beam that’s MICROSCOPE IN THE of the most important discoveries of Thomas Edwards, Deputy houses the UK’s best electron CENTENARY BRAGG CHAIR conformational analysis of IN BIOLOGY, narrower than a single atom. Such LEEDS ELECTRON the 20th century: the double-helical Director of the Centre, uses X-ray microscopes (see Ondrej Krivanek molecules binding to the ER to MICROSCOPY AND STRUCTURE IS precise focusing requires highly SPECTROSCOPY structure of DNA. crystallography in much the same sidebar) and was formed by a A FUNCTION. BY To mark the Braggs’ achievements, understand breast cancer cell death. perfected electron lenses. These CENTRE Astbury’s work is one example way as the Braggs, but on a vastly consortium of five universities and SEEING THE SHAPE the University is creating a new “With conformational analysis OF A PROTEIN, WE have only become available due to of the significance of the Braggs’ different scale. Instead of using four collaborating partners. UNDERSTAND BETTER Professorial post (the Centenary we’re still applying the Braggs’ and a recent breakthrough in electron research not only within the confines diffraction to determine the structure The diffraction and scattering of HOW IT WORKS, Bragg Chair) in collaboration with Astbury’s X-ray crystallography, called correction, of crystallography, but more broadly of sodium chloride (which has two high electrons rather than OR IN SOME CASES, the Royal Academy of Engineering, this time to see how one shape a technique pioneered by Nion. across science, engineering and atoms), the lab team is working with X-rays makes it possible to actually DOESN’T Diamond Light Source and Infineum of the complex causes survival Nion’s instruments have societal boundaries. It has been biological molecules made up of directly image the planes of atoms that UK. This aims to advance engineering and another death” says Craig. many other features such as fundamental to the development hundreds of thousands of atoms. give rise to the reflection or diffraction applications of crystallography “This knowledge will help us an unprecedented stability that of various scientific fields within They determine the 3-D structure of the electron or X-ray waves. using one of the most intense X-ray help patients.” allows them to keep the beam industry, including microelectronics, of proteins that perform normal SuperSTEM has contributed to sources in the world – the Diamond Craig’s new book Estrogen centred on each single atom for pharmaceuticals, aerospace and tasks within living organisms, and an atomic level understanding of Synchrotron – for studying changes , SERMs and Women’s several minutes. They are found power generation. can identify how this is different to the structure of many advanced in the structural arrangements Health (Imperial College in only a few laboratories around THE BRAGGS’ CRUCIAL The influence of William Bragg’s a protein that causes disease. “In materials used in electronics, of atoms in crystals in the Press) includes a chapter on the world. Two are located at the REALISATION WAS time at Leeds continues to resonate at biology, structure is function,” says chemical catalysis and in the manufacture and use of engineering X-ray crystallography. THAT, IF THE X-RAY UK SuperSTEM laboratory, based DIFFRACTION PATTERN the forefront of science a century later. Thomas. “By seeing the shape of a application of nanotechnology to materials. — (l.) at a very stable vibrational site in COULD BE ACCURATELY protein, we understand better how it healthcare. Notably it has made Cheshire. Bragg’s diffractometer PREDICTED FROM A works or, in some cases, doesn’t.” a significant contribution to the CRYSTAL STRUCTURE, showed that matter is made of THEN ONE COULD ALSO LEEDS TODAY Developing drugs to stop understanding of the new material atoms, and led to figuring out WORK BACKWARDS, malfunctioning proteins, Thomas called graphene (a single layer of how the atoms are arranged. DEDUCING FROM THE says, is “a bit like a lock needing hexagonally bonded carbon atoms) EXPERIMENTALLY SuperSTEM is now able to image MEASURED PATTERN, a key. Once we see the shape of for which researchers at the individual atoms and analyse THE STRUCTURE OF MOLECULAR BIOLOGY the lock, we’ll look for a small received the Nobel Prize for Physics them one atom at a time. THE CRYSTAL ITSELF molecule that will fit into it.” Using in 2010. The Astbury Centre of Structural crystallography to find the exact Piezoelectric ceramics are all Molecular Biology brings together shape of the lock can up drug around us in sensors and actuators around 250 researchers from across design by five to ten years. and are the irreplaceable heart of

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