Obituary

Lord Phillips of Ellesmere KBE, FRS (1924-1999)

[David Phillips] Photo: W. L. Duax.
David Phillips was an outstanding scientist, one of the founding fathers of structural biology and an influential figure in science and government. He was Founder President of the British Crystallographic Association (1982-1984) and the spread of the Association's activities mirrored David’s career in crystallography. He moved from intensity statistics and small molecule crystallography, to protein crystallography and instrument design. Protein crystallography led to proposals for structure/function relationships, homology modelling, fundamental understanding of thermal motion, and protein molecules of pharmaceutical interest. It is for his work with lysozyme that he will be most widely remembered. In 1966 he and the team working at the Royal Institution in London, solved the first structure of an enzyme, lysozyme and put forward proposals for its catalytic activity. The work opened the way to the explosion in the numbers of protein structures that are now being determined with modern technology and for the insights that these structures provide for the benefit of fundamental research, medicine and agriculture.

David was awarded a first class war-time degree in Physics, Mathematics and Electrical Communications (1942-1944; 1947-1948) at U. College Cardiff. The degree course was interrupted (1944-1947) for service in the RNVR. He remained at Cardiff for his Ph.D. and began work in crystallography under the supervision of A.J.C. Wilson. After a post doctoral period at the NRL, Ottawa (1951-1955), David came to the Royal Inst. of Great Britain in London in 1956 to join Uli Arndt in the design and construction of an automated diffractometer.

The solution of the 2 Å resolution structure of lysozyme in 1965 showed the complete path of the polypeptide chain folded into both alpha helices, that had previously been recognised in myoglobin, and beta sheet, a structure that had been predicted by Linus Pauling but not hitherto observed.

The inhibitor binding studies were extended to 2 Å resolution by early 1966. Data collection was laborious; a data set took 14 crystals and required nearly 3 weeks. A lysozyme-tri-N-acetylchitotriose complex led to a detailed interpretation of the lysozymeinhibitor complex and the key elements of recognition at the catalytic site and a proposal for the way in which a hexasaccharide  substrate must bind. With C. Vernon's insights into mechanisms of glycoside hydrolysis, it was possible to make proposals for the catalytic mechanism. This was the first time that structure had provided an explanation of how an enzyme speeded up a chemical reaction. The extrapolation from inhibitor binding to the substrate binding was a remarkable leap of deductive reasoning, achieved in three days. David described these three days as the most rewarding that he had ever spent. David was awarded the Feldberg Prize, the CIBA Medal, the Royal Medal of the Royal Society, the Charles Leopold Meyer Prize of the French Academy of Sciences, the Wolf prize, the Aminoff medal of the Royal Swedish Academy of Sciences and many honorary doctorates.

In 1966, David was appointed Professor of Molecular Biophysics in Oxford U. In an article published in Scientific American (1966), Phillips showed how knowledge of the lysozyme structure could predict possible folding pathways that the protein might adopt as it was being synthesised on the ribosome. In another first, he, T. North and W. Browne used homology modelling to show how a protein distantly related in amino acid sequence (a-lactalbumin) might adopt the same structure as lysozyme. With graduate students (A. Bloomer, D. Banner, G. Petsko and I. Wilson) he solved the structure of glycolytic enzyme, triose phosphate isomerase, the first example of an 8-fold α/β barrel protein.

David was elected to the Royal Society in 1967. From 1976-1983 he was Biological Secretary and Vice President at the Royal Society and was instrumental in introducing the Royal Society University Research Fellowships to promote the independent careers of gifted individuals. In his 1991 Bernal lecture, David put forward his view that scientific research must be organised so that 'combined with the provision of the necessary infrastructure, it can release individual scientists to display their critically important gifts of spontaneity and originality'. From 1983-1993 he was Chairman of the Advisory Board for the Research Councils (ABRC). His skills in committee were characterised by honesty, oratory and a gift for friendships.

His time at ABRC was not without controversy. On the one hand he needed to satisfy the increasing demands for funding from scientists faced with the growth of scientific opportunities, the need for more complex apparatus and facilities; the growing importance of interdisciplinary science, and the need for different organisations within which research can be conducted most effectively. On the other hand he fought to persuade Government to deliver more money while recognising the necessarily limited resources and pressures for concentration. He won the respect of both sides, emphasising that only the best science should be funded.

David was made Knight Batchelor in 1979, Knight Commander, Order of the British Empire (KBE) in 1989 and appointed in 1994 to a Life Peerage as Baron Phillips of Ellesmere (his birthplace). He joined the House of Lords Select Committee on Science and Technology and became Chairman in 1997 contributing to a report on Resistance to Antibiotics.

In the last years of his life he was ill with cancer but took a keen scientific interest in the treatment that held the disease at bay and he completed the final draft of a manuscript on how the lysozyme molecule was solved. He once listed among his interests 'talking to children'. He had a simplicity and directness that was equally effective with children and with the most august members of his committees. Many have commented on his great wisdom and on how they have benefited from his guidance and support. He was a special person who moved from academia to wider aspects of science policy, guided by a strong appreciation of history. He is much missed.

Louise N. Johnson
BCA Crystallography News, June 1999