0014-2980/02/0707-1819$17.50+.50/0© WILEY-VCH Verlag GmbH, D-69451 Weinheim, 2002

Cesar Milstein(1927–2002)

Cesar Milstein was associated with the European Jour-nal of Immunology from the very first issue and served asan editor until his death. We are very grateful for his con-tinuous support and contributions to our journal.

Cesar Milstein died on the 24th of March. He was anextraordinary man. His death is a great loss for every-body who knew him. It is also a great loss for science.

Cesar grew up in Argentina and started his scientificcareer in the group of Stoppani at the University of Bue-nos Aires, where he obtained his doctorate in Chemistryfor work on yeast aldehyde dehydrogenase. In 1958 hewent to Cambridge to work in the Department of Bio-chemistry with the leading enzymologist M. Dixon. Hereceived a second doctorate for his studies on the heavymetal activation of the enzyme phospho-glucomutase.He returned to Buenos Aires for 2 years (1961-1963),after which he and his wife Celia decided to leave thecountry for political reasons. He took up Fred Sanger’soffer to work in the Division of Protein Chemistry of thenewly formed Medical Research Laboratory of MolecularBiology (LMB) in Cambridge. For the rest of his life hepursued one overriding question - the generation of anti-body diversity. The long series of fascinating publica-tions gives evidence of his great productivity and creativ-ity.

In 1966, together with Sydney Brenner, he published apaper describing a hypothetical genetic basis for anti-body diversity; 36 years later the error prone DNA repairmechanism, which they suggested, still provides one ofthe central heuristic paradigms of somatic V genehypermutation.

One of the methodologies that were extensively used tostudy the genetics of antibody production in Cesar’sgroup involved the fusion of different myeloma cell lines.When Georges Köhler joined the group he set up fusionsbetween a myeloma line and splenic B cells and suc-ceeded in establishing hybrid cell lines secreting anti-bodies of predefined specificity (1975). By allowing theimmortalization of antigen-specific B cells, the hybrid-oma technology provided a means to study the diversifi-cation of the antibody repertoire and - almost as a by-product - gave us powerful and specific tools with whichto examine and manipulate biological systems. Mono-clonal antibodies now play a central role in many areas offundamental research, in industry and in clinical medi-cine. This extraordinary discovery was honoured in 1984with the award of the Nobel Prize in Physiology or Medi-cine.

Together with George Brownlee’s group, then at theLMB, a modification of the Sanger sequencing techniquewas developed which allowed the direct determination ofthe mRNA sequence of the V-region genes of antibodiessecreted by hybridoma lines. I remember O. Mäkelä visit-ing the Basel Institute and reporting very excitedly on thenew results from Cesar’s lab, which, it was clear, wouldopen the way for a molecular analysis of the process ofaffinity maturation. These techniques were rapidlyadopted by other labs around the world and led to thepublication of a complete issue of ImmunologicalReviews (1986) devoted to the ”Role of somatic mutationin the generation of lymphocyte diversity”.

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Cesar’s research followed a continuous line. Jumpingfrom one hot subject to the next was not his way to doscience. ”Wait, wait”, he would say, followed by a longdrawn out ’ehmmm’. Things had to be thought through,thoroughly. But following one idea didn’t mean thatCesar’s thinking was rigid. He believed that, to get to thebottom of things, every aspect of a problem or an experi-ment had to be discussed carefully, so as not to overlookeven little details, which might be crucial. He loved anargument and fought for his point of view. He was persis-tent, but not stubborn. Discussions were a game in asense, but a very fruitful one. The only way to convinceCesar was to find a better argument. Discussions withhim were long - but it was never wasted time.

The people in Cesar’s lab were a colourful mixture. Inmost cases it seemed to be a rather spontaneous deci-sion as to who got a position in the group. In my case, itwas a telephone call lasting not longer than 10 min.Cesar just told me that he had heard that I was lookingfor a position in Cambridge and asked me whether Iwould like to work in his lab. I was so surprised that the

only word I could say was, ”Yes”, and I never regrettedthis quick decision. So began the best time in my scien-tific life.

Although science was the center of his life, he was a manof broad interests and curiosity. He loved cooking, hik-ing, visiting the theatre or meeting with friends. For yearshe had a small boat, with which he and his wife wouldslowly travel along the river, working their way throughthe sluices, having wonderful picnics at the riverside or agood glass of wine in one of the many old pubs along thewaterfront.

After official retirement he continued to work and theclose interactions with M. Neuberger and his group ledto many publications representing important steps forthe understanding of the process of hypermutation. Thefinal paper was submitted just a week before he died.

Its hard to accept that he is gone.

Claudia Berek

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