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C OMMENTARY C sar Milstein the father of modern immunology Timothy A Springer Center for Blood Research Harvard Medical School Boston MA 02115 USA springeroffice cbr med harvard edu C sar Milstein was born in 1927 at Bahia Blanca Argentina to immi 1959 Gerald Edelman described dissociation into heavy and light chains enabling the modern view of antibodies as Y shaped molecules grants from Russia involved in the secular intellectual Jewish culture with two Fab fragments and one Fc fragment to emerge in the early of the time C sar was an adventurous youth who went to college in 1960s The question of whether antibody diversity was a consequence Buenos Aires where he majored in chemistry and was active in poliof sequence variation had become a soluble problem tics It was through politics that he met his lifelong love Celia and Milstein first approached this problem by determining the after graduation and marriage the couple hitchhiked through Europe sequence of disulfide bonded peptides in Bence Jones light chains on a year long honeymoon and obtained evidence for both variable and constant sequences After returning C sar carried out enzyme research under Stoppani Milstein also defined the inter heavy chain disulfide bridges that for his Doctor en Qu mica degree at the Universidad de Buenos Aires characterize each immunoglobulin Ig subclass Milstein became an while he and Celia scraped together just enough money to support advocate of somatic mutation and with Sydney themselves by moonlighting as clinical bioBrenner published a paper on this topic in chemists In 1958 C sar received a prestigious 1966 As is often the case the advocates of the British Council fellowship and sailed with Celia opposing schools of germline diversity and to England Milstein published papers on kinetics somatic mutation both turned out to be right on his own and on the amino acid sequence of with a combined mechanism far more complex enzyme active sites with Fred Sanger and received than



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