Antibody Structure and the Antibody Workshop 1958-1965

ANTIBODY STRUCTURE AND THE ANTIBODY WORKSHOP 1958-1965 R. R. PORTER* By 1950, rapid progress was being made in solving the chemical structure of proteins based on developments in chromatography pioneered by Martin and Synge [I]. These were used by Sanger [2] and then Edman [3] to work out a method for N-terminal amino acid assay and then to obtain the amino acid sequences of peptides and by Moore and Stein for accurate amino acid microanalysis. This was a prerequisite for the study of antibody structure. However, one very important step, taken more than 10 years earlier, was perhaps the first most striking example of international collaboration in the field of antibody structure. I am referring to the visits, financed by the Rockefeller Foundation, of Michael Heidelberger and of Elvin Rabat to Uppsala before World War II. They took antisera and purified antibodies to Sweden to use the powerful physical techniques of ultracentrifugation [4] and electrophoresis which had been developed there [5]. They were able, with Pederson and Tiselius, to show that antibodies were discrete, though complex, proteins, with two distinct molecular weight fractions contained in a single though rather broad electrophoretic fraction [6]. The importance of this work becomes clear if the second edition of J. R. Marrack's classic monograph on "The Chemistry of Antigens and Antibodies " (1938) is reread [7]. In the chapter on the nature of antibodies, Marrack considered it necessary to present the evidence that antibodies were indeed proteins. Over the next 10 years, three observations were made which were the basis of important subsequent work. First, Oudin at the Pasteur Institute discovered the existence of inherited variants of rabbit antibodies—the allotypes [8]. Independently, Grubb made a similar finding with human *Professor, Department of Biochemistry, Oxford University, South Parks Road, Oxford OXl 3QU, United Kingdom.© 1986 by The University of Chicago. All rights reserved. 003 1-5982/86/2932/$0 1 .00 Perspectives in Biology and Medicine, 29, 3, Part 2 ¦ Spring 1986 \ S161 antibodies [9]. Edelman showed that the molecular weight of antibodies fell on reduction and that they therefore must be multichain proteins [10]; I found that splitting with papain gave two fragments retaining the power to combine with antigen and a third, which crystallised [H]. All three fragments were of similar molecular weight. Correlation of the identification of the peptide chains with the products of limited proteolysis gave the four-chain structure [12] and the first evidence of domains with different functions in antibodies. The discovery of allotypes opened up possibilities of investigating the structural genes of immunoglobulins , a topic still being pursued vigorously at the molecular level. The breaking down ofantibody molecules together with the recognition that myeloma proteins were homogeneous immunoglobulins made possible the eventual solution of the structure of antibodies— including the crystal structure. It was in 1958, as these key findings were being made, that E. S. Lennox, together with Mel Cohn, had the idea of creating an antibody workshop for frequent meetings of the small number of interested people to discuss informally the rapid progress in antibody structure and genetics which wasjust starting. It was modelled on the Phage Workshop meetings initiated by Delbrück some years earlier, which were intended to speed the research on bacteriophage by quick exchange of techniques and ideas and much argument. There were no formal program and no publication of the discussions. This was the post-Sputnik era when, in the United States, science funding was increasing rapidly. Lennox contrived to invite Singer, Eisen, Karush, Cohn, and myself to a meeting of the American Biophysical Society in February 1959. There we met and agreed on the idea of a continuing Workshop on Antibody Synthesis and Characterisation. An application for a grant was prepared subsequently and sent to the National Science Foundation to cover travel and meetings costs. Some nine meetings were held between 1959 and 1966, most in the United States, but also one in London, one in Royaumont, France, and one at the Weizmann Institute at Rehovot, Israel. With about 10 people at the first preliminary meeting at Woods Hole inJune 1959, efforts were made to invite anyone active in the field. The popularity grew quickly and the...