Tag Archives: X-ray crystallography

Celebrating Dorothy Hodgkin: Britain’s First Female Winner of a Nobel Science Prize

Rachel Boon, Content Developer, looks at the legacy of one of Britain’s most famous scientists, one of the stars of a new exhibition, Churchill’s Scientists, which opens in January 2015

Today marks exactly 50 years since Dorothy Crowfoot Hodgkin was awarded the Nobel Prize for Chemistry, on 10 December, 1964. Hodgkin won the prestigious prize “for her determinations by X-ray techniques of the structures of important biochemical substances”. She was only the third woman to win the prestigious prize – the crowning achievement of a 30 year career spent unravelling the structures of proteins, including insulin.

Dorothy Hodgkin was awarded the Nobel Prize for chemistry in 1964 for her studies using X-ray crystallography, with which she worked out the atomic structure of penicillin, vitamin B-12 and insulin. Image credit: Science Museum / SSPL

Dorothy Hodgkin was awarded the Nobel Prize for chemistry in 1964 for her studies using X-ray crystallography, with which she worked out the atomic structure of penicillin, vitamin B-12 and insulin. Image credit: Science Museum / SSPL

Hodgkin first found fame when she finally solved the structure of penicillin on Victory in Europe Day in 1945.

Alexander Fleming had identified the anti-bacterial properties of penicillium mould in 1928 but thought the substance was too unstable to isolate as a drug.  At Oxford University Howard Florey, Ernst Chain and Norman Heatley proved otherwise and successfully purified the antibiotic for human use in 1941.

Once the potential was realised, vast amounts of the drug were needed. Chain spoke of his excitement and challenged Hodgkin to find its structure, promising ‘One day we will have crystals for you.’

Penicillin saved many lives during the Second World War. Allied governments recognised the potential of the ‘wonder drug’ and the race was on to convert a laboratory discovery into a mass- produced drug.

Hodgkin unravelled the structure of penicillin using a method called X-ray crystallography - a technique used to identify the structure of molecules. Hodgkin had been fascinated by crystals from a young age and on her sixteenth birthday received a book about using X-rays to analyse crystals, which greatly inspired her.

You can see Hodgkin’s three dimensional atomic structure of penicillin in our new exhibition opening in January.

Molecular model of penicillin by Dorothy Hodgkin, c.1945. Image credit: Science Museum / SSPL

Molecular model of penicillin by Dorothy Hodgkin, c.1945. Image credit: Science Museum / SSPL

Another notable molecular structure Hodgkin tackled was that of vitamin B12, which she cracked with the help of Alan Turing’s Pilot ACE computer, which is on display in our Information Age gallery.

The Pilot ACE (Automatic Computing Engine), 1950. Image credit: Science Museum / SSPL

The Pilot ACE (Automatic Computing Engine), 1950. Image credit: Science Museum / SSPL

These achievements had an immense impact on chemistry, biochemistry and medical science, establishing the power of X-ray crystallography, and changing the practice of synthetic chemistry.

She was one of the first people in April 1953 to travel from Oxford to Cambridge to see the model of the double helix structure of DNA, constructed by Briton Francis Crick and American James Watson, based on data acquired by Rosalind Franklin, which can also be seen in the Museum’s  Making the Modern World gallery.

Crick and Watson's DNA molecular model, 1953. Image credit: Science Museum / SSPL

Crick and Watson’s DNA molecular model, 1953. Image credit: Science Museum / SSPL

Hodgkin was awarded the Order of Merit, only the second woman to be honoured in this way after Florence Nightingale. She was also the first woman to be awarded the Royal Society’s Copley medal, its oldest and most prestigious award.

She died in July 1994, aged 84. In her honour, the Royal Society established the prestigious Dorothy Hodgkin Fellowship for early career stage researchers.

The origins of the technique she used date back to when X-rays, one of the most remarkable discoveries of the late 19th century, had been shown to react strangely when exposed to crystals, producing patterns of spots on a photographic plate.

You can find out more about Dorothy Hodgkin in our new exhibition, Churchill’s Scientists, which opens on 23 January 2015. The exhibition will look at the triumphs in science during Churchill’s period in power, both in war and in the post-war era.

Strange objects give a feel for the origins of X-ray crystallography

A guest post by Stephen Curry, professor of structural biology at Imperial College.

The things and objects of history are important because they provide a tangible connection to the past. Seeing, or better yet holding and touching, the stuff that generations now dead made and worked with enlivens history, shucking us from the present and its endless clamour for our attention.

The Hidden Structures exhibition at the Science Museum trips us into the history of X-ray crystallography with a small but intriguing display of objects from the 1940s through to the 1970s. The exhibition commemorates the centenary of the development of the technique, by the father and son team of William and Lawrence Bragg who figured out how the scattering of X-rays by crystals could be analysed to reveal the atomic and molecular arrangements within, providing a vista of the structure of matter that had never been seen before.

The Braggs first applied the technique in 1913 to show how the patterns of X-rays diffracted onto photographic plates by table salt — sodium chloride — could be interpreted to reveal the organisation of the two atoms within its crystals. It was apparent from the beginning that the method was applicable to anything that could be induced to crystallise, even the most complex molecules of chemistry and biology. Soon structures composed of tens or hundreds or even thousands of atoms were emerging from UK labs, which established itself at the forefront of the technique thanks in no small part to the inspirational leadership of the younger Bragg.

Hidden Structures 1The first protein structures; left to right — myoglobin, perspex stack of electron density, haemoglobin

The artefacts in the Hidden Structures display come mainly from the first bloom of chemical and biological crystallography; there is Dorothy Hodgkin’s ball-and-stick model of penicillin, John Kendrew’s wormy brown representation of the oxygen-storage protein, myoglobin, Max Perutz’s black and white slabbed structure of haemoglobin, the oxygen-transporter from human blood, and in pride of place, Hodgkin’s huge model of the atomic structure of insulin.

These scientists had to be very hands-on at all stages of their work — growing crystals, carefully measuring X-ray diffraction patterns recorded on photographs, and printing out the electron density maps produced by their analysis. These three-dimensional maps (there is one for haemoglobin in the display, printed in sections on stacked sheets of perspex) show where the electrons are concentrated, so defining the positions of the atoms. The early models simply depict the contours of these maps and give the overall form of the protein molecule. Coming some years after X-rays had unveiled the elegant double-helix of DNA, their crude irregularity was at first a disappointment: “hideous and visceral” wrote Perutz.

But the resolving power of X-rays soon improved and those early crystallographers had to swap plastic and plasticene for intricate assemblies of rods, each representing a bond between two atoms, that were put together with loving attention to detail. Hodgkin’s insulin model from the early 1960s may not be beautiful, but it is mesmerising — and hugely informative.

Hidden Structures 2Hodgkin’s atomic structures: left, insulin; right, penicillin.

X-ray crystallography continues apace. Thousands of protein structures have been solved, providing a detailed understanding of the workings of biology at the molecular level. We see clearly now not just how hormones like insulin work, or how haemoglobin picks up and drops off its cargo of oxygen, but also how DNA is synthesised and decoded, how ion channels enable the transmission of nerve signals, how the immune system fights off infection. No pharmaceutical company works blind in the 21st Century; all use X-ray crystallography to reveal the molecular targets of therapy, whether from a virus or bacteria or a cancerous cell, as part of the quest for new drugs and vaccines.

But all the work of recording and analysing data and building models has now migrated to computers. For sure this has greatly accelerated the pace of research and discovery, but there are no more photographs or stacks of electron density or models made of stuff for future generations to pick up and wonder at. All the more reason therefore to cherish the crystallographic arcana on show at the Science Museum.

Stephen Curry is a professor of structural biology at Imperial College. He writes regularly about science at the Reciprocal Space and Occam’s Corner blogs.

William Henry Bragg and the Birth of Crystallography.

1910: The Birth of Crystallography

Each day as part of the Great British Innovation Vote – a quest to find the greatest British innovation of the past 100 years – we’ll be picking one innovation per decade to highlight. Today, from the 1910s, the birth of Crystallography.

William Henry Bragg and the Birth of Crystallography.

William Henry Bragg and the Birth of Crystallography. Image credit © Science Museum / Science & Society Picture Library

Science Museum curator, Boris Jardine, explains via an audioboo why he thinks Crystallography is the greatest British Innovation, and visitors to the Museum can see some examples of the work of X-ray crystallography in a new display case, Hidden Structures.

To paraphrase the great x-ray crystallographer Max Perutz: it’s even told us why blood is red and grass is green. ‘It is’ said Perutz ‘the key to the secret of life’.

Our understanding of the structure of compounds – from the ordered crystal structure of table salt and diamonds to the complex organic compounds that make up life – was only possible through the discovery of X-ray crystallography a century ago.

Father and son physicists William and Lawrence Bragg exposed crystals to X-rays, recording and interpreting the resulting image, the X-ray diffraction pattern, to predict the atomic structure of the crystal. For this, Bragg and his son won the Nobel Prize (at 25, Lawrence Bragg became the youngest ever Nobel Laureate) and X-ray crystallography remains to this day the most accurate method of determining the atomic structure of materials.

Crystallography has allowed innumerable advances in chemistry, physics and medicine, and it deserves your vote as the Greatest British Innovation. Click here to vote.