Milstein, César, 1927-2002

Csar Milstein was born in Baha Blanca, Argentina, on 8 October 1927, the middle boy of three sons. His father was a Ukrainian Jewish immigrant and his mother, a teacher, was also Jewish but born in Argentina, although her family had originally emigrated from Lithuania. As a child Milstein developed an interest in biology at an early age. In an interview in 1998 he recounted that it stemmed from a holiday visit made by his cousin, a chemistry graduate student from the University of Buenos Aires, when he was just over seven years old: 'Her explanations of how she removed venom from snakes and used it to prepare antiserum to treat people bitten by poisonous snakes had a profound impact on me and awakened my interest in biology'.

After schooling at the Colegio Nacional in Baha Blanca, Milstein studied chemistry at the University of Buenos Aires. Here he was active in student politics and met his future wife, Celia Prilleltensky. They married in 1953, taking a one-year honeymoon trip travelling around Europe and Israel. Returning to the Instituto de Quimica Biologica at the University of Buenos Aires, Milstein studied for his doctorate under the direction of the eminent biochemist A.O.M. Stoppani, Professor of Biochemistry at the Medical School. To support themselves during this period both he and his wife worked part-time as clinical analysts, Milstein for Laboratorios Liebeschutz. He obtained his Ph.D. in 1957, for a kinetic analysis of the enzyme aldehyde dehydrogenase and on its completion Milstein was awarded a British Council Fellowship to go to Cambridge to work in the Department of Biochemistry under Malcolm Dixon, studying the mechanism of metal activation of the enzyme phosphoglucomutase. There he met Fred Sanger, with whom he formed a lifelong association, and completed a second doctorate. In 1961 he returned to Argentina as Head of Division de Biologia Molecular, Instituto Nacional de Microbiologia in Buenos Aires to continue his research into enzymes.

Upon returning to Argentina, the Milsteins found the political climate very different from before. Following a military coup '...political persecution of liberal intellectuals and scientists manifested itself as a vendetta against the director of the institute where I was working', Milstein later wrote. The situation was intolerable and in 1963 Milstein left Argentina for the second time and returned to Cambridge to rejoin Sanger at the newly established MRC Laboratory of Molecular Biology. Here he was to remain for the rest of his career, Head of the Protein Chemistry Subdivision 1969-1980, Joint Head of the Division of Protein and Nucleic Acid Chemistry 1981-1995 and from 1988 to retirement in 1995 serving as Deputy Director of the Laboratory. He became a Fellow of Darwin College, Cambridge in 1980 (Emeritus Fellow 1995, Honorary Fellow 2002) and an Honorary Fellow of Fitzwilliam College in 1982.

At the Laboratory of Molecular Biology, on the advice of Sanger, Milstein switched from enzymology to immunology and work on antibodies, proteins produced by the cells of the immune system in response to attacks by foreign bodies (antigens). His research focused on the genetic study of antibody diversification, how antibodies acquire their ability to fight specific antigens and the means by which pure antibodies could be produced in the laboratory. Milstein's research group was a lively one and many young scientists from all over the world, in later years especially from Spanish-speaking countries, came to research under him. It was with a German visiting researcher, Georges Kr, who came from the Basel Institute for Immunology (Ph.D. University of Freiburg), that in 1975 Milstein invented the hybridoma technique for the production of monoclonal antibodies. By fusing antibody-producing cells with tumour cells, Milstein and Kr were able to produce a hybridoma, which could then continuously synthesize antibodies that were identical to those produced by the antibody-producing cell before it was fused. Used as research tools, monoclonal antibodies revolutionised the way in which biologists viewed living systems, but monoclonal antibody production also opened the way for the commercial development of new types of drugs and diagnostic tests in fields as diverse as cancer, the prevention of transplant rejection, pregnancy testing and the treatment of arthritis. In 1984 Milstein and Kr received the Nobel Prize for Medicine for their work, along with N.K. Jerne, who had done theoretical work on the human immune system. Milstein and his research group continued to work in this field, improving and developing monoclonal antibody technology right up to his death, aged 74, on 24 March 2002. He was survived by his wife Celia.

Milstein won very many honours and awards. He was elected FRS in 1975 (Wellcome Medal 1980, Royal Medal 1982, Copley Medal 1989, Croonian Lecture 1989) and in 1981 was made a Foreign Associate of the US National Academy of Sciences. He received the Avery-Landsteiner Prize of the Society for Immunology in 1979, the Wolf Prize in Medicine in 1980, the Robert Koch Prize (Germany) and Karl Landsteiner Award of the American Association of Blood Banks, both in 1982, and the Albert Lasker Basic Medical Research Award in 1984. These awards culminated with the award of the Nobel Prize in 1984. In 1995 Milstein was made a Companion of Honour for services to molecular biology and in 2000 the MRC awarded him its first Millennium Medal. After the fall of the military government in Argentina in 1983 Milstein received many invitations to visit his native country and was accorded many honours, including in 1985 Honorary Membership of the Associacion Argentina de Alergia e Immunologia, in 1988 Honorary Fellowship of the National Academy of Sciences of Argentina and Honorary Membership of the Sociedad Cientifica Argentina and in the year 2000 the Presidential Medal of Merit for Scientific Excellence. The same year he was made a Corresponding Member of the Academia de Ciencias de Am?ca Latina.