Rodney Porter Memorial Lectures

Rodney Porter

Rodney Porter was the perfect example of a scientist in the right place at the right time. In 1939 after graduation from Liverpool he started work there for his Ph.D but in 1940 this had to be given up when he voluntarily joined the Army and served with the RASC until 1945 when he was discharged with the rank of Major. At the suggestion of Sam Perry, a fellow graduate and life-long friend, they both went to Cambridge where Professor Chibnall appointed Fred Sanger as Porter's supervisor. Sanger was then working on the structure of insulin and its amino acid sequence, for which he obtained the first of his Nobel Prizes. It was during this period in Cambridge that Porter became interested in immunochemistry through reading Landsteiner's "The Specificity of Serological Action" and "The Production of Antibodies" by Macfarlane Burnett and Fenner.

Having completed his doctorate Porter joined the scientific staff of the National Institute for Medical Research at Mill Hill, then directed by Sir Charles Harrington. Here he collaborated with A.J.P.Martin (also to become a Nobel Laureate). Martin was also concerned with structural analysis and this may have confirmed Porter's conviction that he was a protein chemist working in the field of immunology. It was during his time at Mill Hill that he initiated the work that was to uncover the basic structure of antibody molecules. Their protein nature had already been established but their structure was puzzling. In Cambridge Porter had worked with Sanger on the determination of the N-terminal amino acids in protein sequences. On the basis of analyses on immunoglobulins (IgGs) Porter first believed antibodies had a single peptide chain and that their different specificities might be generated by differential folding. Using the proteolytic enzyme papain Porter found rabbit IgG was cleaved into three similarly sized pieces. Two of these, the Fab fragments, retained their original antibody specificity but surprisingly the third portion, Fc, crystallized. Papain had to be activated by cysteine; Porter would recall how for quite some time he had tipped the Fc crystals down the sink, believing them to be crystals of cystine and an artefact of the method.

That peptide chains within IgG molecules were linked by disulphide bridges was shown by Edelman,1959-61. The bridges are both inter- and intra-chain. By adapting techniques used to reduce SS bonds so that the interchain links were preferentially reduced Porter found there were four chains in each antibody molecule, two identical larger chains, the heavy chains, and two identical smaller ones, the light chains. In 1962 therefore he proposed the 4-chain model for IgG molecules, with two light and two heavy chains. By the time Porter arrived in Oxford in 1967, to take up the Whitley Chair, the structure was firmly established. His group, including Betty Press, who had worked with him at St Mary's, Paddington, was joined by Ken Reid, now Director of the MRC Immunochemistry Unit. They started to work on the complement system in blood where antigen/antibody complexes activate an intricate, cascading series of protein reactions to mobilise cells in the immune system and eliminate the foreign, antibody bearing, material. In 1972 Rodney Porter and Gerald Edelman were jointly awarded the Nobel Prize for Physiology and Medicine for their work on the structure of the immunoglobulin molecule.

By the early 1980s both the classical and the alternate pathways for complement activation had been clarified and the Unit now turned to the identification of the genes involved in programming the proteins concerned. During 1980-81 Porter therefore ensured that he and his group started to learn the techniques in molecular genetics which would be essential for the next stage of their programme. He planned to continue these studies after his retirement in September 1985 but his tragic death in a road accident prevented his full participation in this programme. It was however continued in the Unit to the end of the century, focussing on genes in the major histocompatibility complex (MHC), class III region which includes some of those of the complement system.