Professor David Blow

Pioneer of protein crystallography at Cambridge and Imperial College, London

David Blow was an early pioneer of protein crystallography, a superbly productive method which, over the last 40 years, has revealed the detailed atomic structures of thousands of proteins, all of them important in biology or medicine.

David Mervyn Blow, protein crystallographer: born Birmingham 27 June 1931; staff, MRC Unit for Study of Molecular Biological Systems, Cambridge 1959-62; staff, MRC Laboratory of Molecular Biology, Cambridge 1962-77; Fellow, Trinity College, Cambridge 1969-77; FRS 1972; Professor of Biophysics, Imperial College, London 1977-94 (Emeritus), Dean, Royal College of Science 1981-84, Head, Department of Physics 1991-94, Senior Research Fellow 1994-2004; President, British Crystallographic Association 1984-87; married 1955 Mavis Sears (one son, one daughter); died Appledore, Devon 8 June 2004.

David Blow was an early pioneer of protein crystallography, a superbly productive method which, over the last 40 years, has revealed the detailed atomic structures of thousands of proteins, all of them important in biology or medicine.

Using his mathematical skills and unique ability to organise the many developments needed on a broad front, Blow made key contributions to the theory and practice of protein crystallography while simultaneously solving the structure of a number of important proteins. He trained many students and continued to produce lucid articles and books right up to his death.

Born in Birmingham in 1931, the second son of a Methodist minister, David Blow had a somewhat nomadic education prior to attending Kingswood School, Bath, where he and his brother Ralph developed their interest in physics. Ralph went to Oxford but David won an open scholarship to Corpus Christi College, Cambridge, where he was an undergraduate and graduate student, delayed only by National Service with the RAF, where he learned to fly gliders, met Ronnie Corbett and Jim Biddulph, and had the occasional brush with early death.

As a young scientist graduating in Physics from the Cavendish Laboratory at Cambridge in 1954, he was looking for an exciting area of research when a friend told him about an Austrian scientist, Max Perutz, working in the Cavendish, who was good at getting money. Blow was thrilled to learn about the work Perutz was doing and immediately accepted the offer to become his student. Perutz, having been a student of Desmond Bernal and Lawrence Bragg, now headed a small Medical Research Council Unit for the Study of the Molecular Structure of Biological Systems with funds for a research student.

Twenty years earlier, Perutz had been inspired by Bernal's statement that the secret of life lay in the structure of proteins and the only way to find the structure was by using X-ray crystallography. When Blow joined the unit in late 1954, there was still no sign of any protein structure and opinion among many was that the task was impossible. Perutz himself had commented that attempting to analyse the structure of a protein seemed on the face of it about as promising as a journey to the moon.

As it happened, the protein Perutz had chosen to study, on which Blow joined him, was haemoglobin, the oxygen carrier in the blood, whose atomic structure was eventually determined in 1968, a year before man first landed on the moon. Blow therefore began his research career by learning to purify and crystallise horse, pig, dog and rabbit haemoglobin, and to characterise the crystals.

In 1953, Perutz had recognised that the "isomorphous replacement" method might be able to solve the structure of protein crystals. This involved attaching chemically, to precise positions in the protein, one or two atoms of a heavy metal such as mercury which would scatter X-rays strongly, producing small changes to the intensities of X-ray beams. In principle, these small changes were exactly what was needed to solve the crystal structure, but in practice a great deal of theory was still required and it was this challenge that Blow found exciting.

Blow came up with a rigorous general method for data analysis, implemented it on the Edsac I computer and used it to determine the projection structure of horse haemoglobin. He discussed his approach with Francis Crick, with whom he shared an office, leading to a famous paper on the treatment of errors by Blow and Crick ("The Treatment of Errors in the Isomorphous Replacement Method", 1959). By the end of his PhD work in 1957, the foundations of protein crystallography had been laid and the first three-dimensional images of the protein myoglobin had been obtained by John Kendrew and his colleagues. The method has been used to solve the vast majority of new protein structures ever since.

Blow then spent two rather unproductive years as a Fulbright scholar with Alex Rich in the United States, at NIH (the National Institute of Health, Bethesda) and MIT, learning that it was better to work on crystals than fibres. Meanwhile the atomic structure of myoglobin and the three-dimensional structure of haemoglobin were worked out by the group he left behind in Cambrdige. Perutz and Kendrew were to be awarded the 1962 Nobel Prize for Chemistry. Blow had become one of the earliest contributors to a revolution in biology based on understanding the structure of proteins and nucleic acids, a field now called structural molecular biology or biophysics.

Towards the end of his American postdoctoral work, influenced by the missionary zeal of his Methodist parents and elder brother, he considered teaching in what is now Zimbabwe. However, surprised and delighted to be offered a post back in the MRC Unit, he immediately agreed to return to Cambridge to work in the rapidly developing field of protein crystallography, and began a remarkable collaboration with another young scientist with whom he shared an office, Michael Rossmann. Their success was due to their completely complementary personalities. Rossmann was tremendously enthusiastic and would go roaring off at the least idea whereas Blow would reflect, thinking about it more analytically, and in that way they formed a tremendously effective and very positive working relationship.

During the next five years, they pioneered "molecular replacement" - the second major approach to solving protein structures. They published a series of classic papers defining the mathematics of rotation and translation functions in the 1960s which laid the foundations of the molecular replacement method. Nowadays, this method can be used to solve a new crystal structure very quickly by using existing knowledge of similar structures to bootstrap to a solution.

After these initial methodological successes, Blow decided he needed to branch out from simply helping with Perutz's work on haemoglobin. He resolved to tackle the structure determination of another protein and chose a digestive enzyme from the gut, chymotrypsin. Brian Hartley, whom he had met several years before in the nearby Biochemistry Department, had worked on the mechanism of chymotrypsin for years, and had already tried to interest the crystallographers in it. Perutz meanwhile had persuaded MRC to build a new laboratory, on a site now shared with Addenbrooke's NHS Trust, to bring together the Cavendish Unit with another MRC-funded group led by Fred Sanger, and Sanger had recruited Hartley, also fresh from two years in America. As a result, Blow and Hartley found themselves together in what became a long-term association at the MRC Laboratory of Molecular Biology when it was opened by the Queen in 1962.

There, Blow built up an enthusiastic team including two outstanding colleagues, Brian Matthews and Paul Sigler, who succeeded in determining the atomic structure of chymotrypsin by 1967. It was only the third or fourth protein structure to be determined. Thus, at 36, Blow had helped develop the two methods which form the backbone of protein crystallography and had led the team which solved the structure of chymotrypsin.

With Hartley and others, he went on to work out the mechanism of action of chymotrypsin and solved the structure of many other enzymes and enzyme complexes initially in Cambridge and later at Imperial College, London, where in 1977 he moved to set up the Biophysics group in the Physics Department.

In Cambridge and London, he had a strong commitment to teaching and trained many PhD students. This led him first to take up a teaching fellowship at Trinity College, Cambridge, in 1969, and then a Professorship of Biophysics at Imperial College in 1977, forming a cross-departmental alliance, unusual in universities at that time, with Hartley, who moved to Imperial two years earlier as Professor of Biochemistry.

Blow's students and colleagues found him to be generous, modest, kind, fair, far-sighted and persuasive. He was especially skilful at matching problems to people. Thus he was in great demand, first as Dean of the Royal College of Science at Imperial College, then to oversee the introduction of teaching assessment. As Head of the Physics Department from 1991, he helped rescue the astronomy group from likely extinction.

He earned many scientific honours, being elected FRS in 1972 aged 40, and winning the CIBA prize of the Biochemical Society, the Charles Léopold Meyer prize of the French Academy and the Wolf Prize for Chemistry, Israel's most prestigious scientific award. These last two were awarded to Blow jointly with David Phillips ("the two Davids") for their work on the structures of the first two enzymes, lysozyme and chymotrypsin.

After retiring with a serious heart problem in 1994, Blow continued working part-time at Imperial College, writing and ensuring projects he had started were properly concluded. His excellent book Outline of Crystallography for Biologists (2002) displayed his long experience and many contributions to the field. During the last year, whilst coping courageously with lung cancer, he continued to write, producing a biographical memoir of his mentor Perutz (to be published by the Royal Society: he had written his obituary for The Independent in 2002); a prehistory of the British Crystallographic Association that he helped to found in 1982; and even a short novel.

Many of his colleagues travelled to visit him in Appledore, where he had settled in 1994 with his wife Mavis, returning to his roots in a village his great-grandfather had lived in and where he could enjoy walking and sailing. He and Mavis became enthusiastic members of the local community, Mavis as secretary and euphonium player in the Appledore Brass Band and David as band roadie and architect of a Lottery grant to purchase new brass instruments, and as chairman of the Torridge branch of the Campaign to Protect Rural England.

Richard Henderson

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