César Milstein (1927–2002) | Nature

Access through your institution Buy or subscribe Milstein was born into a Jewish family in Bahía Blanca, Argentina, and graduated from the University of Buenos Aires with a thesis on

aldehyde dehydrogenase. In 1958, he won a scholarship to work at the University of Cambridge in Britain, where he did a second PhD, again in enzymology. There he met Fred Sanger, who had

just won his first Nobel prize for determining the structure of insulin. Meeting Sanger was critical for Milstein's career. He returned to Argentina in 1961, but soon became

dissatisfied with the political climate and, in 1963, took up Sanger's invitation to join the Medical Research Council's Laboratory of Molecular Biology (LMB), which had already

attracted other top scientists from abroad such as Max Perutz, Aaron Klug and Sydney Brenner. It was on Sanger's advice that Milstein then began to study antibody structure and

diversity: this was to be his life's work, with LMB in Cambridge his scientific home. Milstein's hope was that the structural comparison of different antibodies would reveal the

secret of antibody diversity. But things turned out to be more complicated. Soon after his arrival in Cambridge, it was discovered that antibody molecules contained variable (_V_) and

constant (_C_) regions and the 'two genes, one polypeptide' hypothesis was proposed. According to this idea, separate genes encode _V_ and _C_ regions, and there are thousands of

_V_ genes in the germ line — the set of genes inherited by offspring. This was shockingly unorthodox, and other ideas were put forward. Among them, in 1966, was Brenner and Milstein's

proposal of a mechanism that introduces 'somatic' (non-germline) mutations selectively into _V_ segments of antibody genes. This proposal proved inadequate to explain primary

antibody diversity. But it later became a leading model for the diversification of antibodies in immune responses, the main subject of Milstein's research for the latter part of his

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AFFILIATIONS * the Center for Blood Research, Harvard Medical School, 200 Longwood Avenue, Boston, 02115, Massachusetts, USA Klaus Rajewsky Authors * Klaus Rajewsky View author publications

You can also search for this author inPubMed Google Scholar CORRESPONDING AUTHOR Correspondence to Klaus Rajewsky. RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE

THIS ARTICLE Rajewsky, K. César Milstein (1927–2002). _Nature_ 416, 806 (2002). https://doi.org/10.1038/416806a Download citation * Issue Date: 25 April 2002 * DOI:

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