Richard Nelson Perham (1937—2015)

Ricard Nelson PerhamCredit: Yvonne Burt

The world lost one of its most gifted biochemists Feb. 14 with the death of Richard Nelson Perham at the age of 77. An active, renowned member of the academic science community until the very end, Perham was distinguished for his work on the chemistry of proteins and the assembly of giant protein complexes and was a leader in bringing the power of protein-engineering approaches to problems of protein structure and function.

Perham pioneered the development of chemical tools to understand protein structure and function, revealing how enzymes generate energy from glucose (via the remarkable, massive 2-oxoacid dehydrogenase multienzyme complexes) and how viruses assemble capsid coats. Using protein redesign, he was the first to switch the co-enzyme requirement of an enzyme (altering glutathione reductase from using NADPH to NADH for catalysis and lipoamide dehydrogenase from NAD+ to NADP+). He also made outstanding contributions to our knowledge of the structure and assembly of filamentous bacteriophages and was among the first to use these phages to display foreign peptides on their surface, opening the door to their use for the production of novel vaccines.

Perham was born April 27, 1937, in the London borough of Hounslow West. He went on scholarship to Latymer Upper School, whose liberal outlook and broad curriculum including the arts and sport (both of which remained passions of his for life) inspired and nurtured the budding scientist. In 1955, Perham took the entrance exam for the University of Cambridge. The first of his family to go to university, he was awarded a place at St. John’s College.

At the time, the field of biochemistry was a hothouse of discovery and achievement. The structure of DNA had been solved in 1953. The first sequence of a protein (insulin) was determined in 1955. And the first three-dimensional structure of a protein (myoglobin/haemoglobin) was established in 1956. A whole new world was opening up.

A Ph.D. with double Nobel Laureate Fred Sanger was Perham’s next step. He worked on the structure and mechanism of glyceraldehyde 3-phosphate dehydrogenase under J. Ieuan Harris. Those two identified a key cysteine residue required for protein activity and went on to hold the world record in the mid-1960s for determining the longest amino acid sequence (more than 330 residues) of a protein. This work merited Perham’s first major article in Nature, which was published in 1968.

In 1965, Perham became demonstrator in the University of Cambridge Biochemistry department. At the same time, he was awarded a Helen Hay Whitney Fellowship to study at Yale University with Frederic Richards. There he met (over a shared electron microscope) gifted biologist Nancy Lane. The couple returned to Cambridge and married in 1969.

Perham made many significant contributions in his 50 years at Cambridge. In the late 1960s, he uncovered the importance of charge-charge interaction between protein subunits in the self-assembly of tobacco mosaic virus capsids, and later he elucidated the novel mechanism of protein–DNA charge interaction that governs the assembly of filamentous bacteriophage virions. He introduced a number of important techniques in chemical modification of proteins, in particular based on reversible amidination and trifluoroacetylation of lysine residues.

After some 30 years of effort, Perham and his team produced the first complete description of the structure and assembly pathway of the pyruvate dehydrogenase multienzyme complex (whose molecular mass is 10 MDa). He also uncovered a new mechanism of active-site cooperativity distinct from allostery in enzyme activity and elucidated unexpected mechanisms of active-site coupling in his multienzyme complexes based on motile protein domains.

Perham was a servant to the scientific community. He served as a councilor and trustee for the Novartis (formerly CIBA) Foundation, chaired the scientific advisory board of the Lister Institute of Preventive Medicine, and sat on the advisory committee and was vice-president of the Fondation Louis-Jeantet de Médicine in Geneva. In 1998, he took the helm of the European Journal of Biochemistry, reinventing it into what is now FEBS J, and served as editor until 2013.

Perham won election to the European Molecular Biology Organisation (1983) and the Academia Europaea (1992). He was a fellow of the Royal Society (1984) and the Academy of Medical Sciences (2005). He won the Max Planck Prize (1993), the Novartis Medal of the Biochemical Society (1998) and the Diplôme d'Honneur from the Federation of European Biochemical Societies (2011).

Perham was a truly exceptional scientist with an impressive knowledge of art, literature, history, sport and all types of music. He was an inspired teacher and mentor, loyal to his students, and passionate about the University of Cambridge and St. John’s College. He leaves a legacy of more than 350 scientific papers; an array of well-trained graduate biochemists; and family, friends and the scientific community proud of such a brilliant man.

A longer version of this article appeared in The Biochemist magazine.

Sheena E. Radford is a professor at the University of Leeds. Nigel S. Scrutton is a professor at the University of Manchester.