César Milstein | |
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| Born | (1927-10-08)8 October 1927 Bahía Blanca, Argentina |
| Died | 24 March 2002(2002-03-24) (aged 74) Cambridge, England |
| Nationality | Argentine, naturalised as British |
| Education | |
| Known for | Receiving Nobel Prize "for theories concerning the specificity in development and control of theimmune system and the discovery of the principle for production ofmonoclonal antibodies" |
| Spouse | [2] |
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| Scientific career | |
| Fields | Biochemistry |
| Doctoral advisor | Andrés O.M. Stoppani[1] |
César Milstein,CH,FRS[3] (8 October 1927 – 24 March 2002) was anArgentinebiochemist in the field ofantibody research.[4][5][6][7][8] Milstein shared theNobel Prize in Physiology or Medicine in 1984 withNiels Kaj Jerne andGeorges J. F. Köhler for developing thehybridoma technique for the production ofmonoclonal antibodies.[9][10][11][12][1][13][14]
Milstein was born inBahía Blanca, Argentina. His parents were Máxima (Vanarks) and Lázaro Milstein, a Jewish Ukrainian immigrant.[15] He graduated from theUniversity of Buenos Aires and obtained a PhD under Professor Stopani[16] (Professor ofBiochemistry). Later he became a member of the Medical Research Council Laboratory of Molecular Biology, Cambridge, England; he acquired British citizenship and haddual British-Argentinian nationality.[17] In 1956, he received an award from the Sociedad Argentina de Investigation eon Bio Quimica (SAIB) for his work onenzyme kinetics with theenzymealdehyde dehydrogenase. In 1958, funded by theBritish Council, he joined theBiochemistry Department at theUniversity of Cambridge to work for a PhD underMalcolm Dixon on the mechanism of metal activation of the enzymephosphoglucomutase.[18] During this work, he collaborated withFrederick Sanger, whose group he joined with a short-termMedical Research Council appointment.
Science will only fulfill its promises when the benefits are equally shared by the really poor of the world
— César Milstein
The major part of Milstein's research career was devoted to studying the structure of antibodies and the mechanism by which antibody diversity is generated. It was as part of this quest that, in 1975, he worked withGeorges Köhler (a postdoctoral fellow in his laboratory) to develop thehybridoma technique for the production ofmonoclonal antibodies—a discovery recognized by the award of the 1984Nobel Prize for Physiology or Medicine. This discovery led to an enormous expansion in the exploitation of antibodies in science and medicine. The termhybridoma was coined byLeonard Herzenberg during his sabbatical in Milstein's laboratory between 1976 and 1977.[19]
Milstein himself made many major contributions to improvements and developments in monoclonal antibody technology—especially in the use ofmonoclonal antibodies to provide markers that allow distinction between different cell types. In collaboration with Claudio Cuello, he helped lay the foundation for the use of monoclonal antibodies as probes for the investigation of the pathological pathways in neurological disorders as well as many other diseases.[20] These advances in biology and clinical medicine would take several years to realize their potential.[21] Milstein and Cuello's work also enabled the use of monoclonal antibodies to enhance the power of immuno-based diagnostic tests.[22] In addition, Milstein foresaw the potential wealth of ligand-binding reagents that could result from applying recombinantDNA technology to monoclonal antibodies and inspired the development of the field of antibody engineering, which was to lead to safer and more powerful monoclonal antibodies for use as therapeutics.
Milstein's early work on antibodies focused on their diversity at the amino acid level, as well as on the disulfide bonds by which they were held together. Part of this work was done in collaboration with his wife, Celia. The emphasis of his research then shifted towards the mRNA encoding antibodies, where he was able to provide the first evidence for the existence of a precursor for these secretedpolypeptides that contained asignal sequence.[23] The development of thehybridoma technology coupled to advances in nucleic acid sequencing allowed Milstein to chart the changes that occurred in antibodies following antigen encounter. He demonstrated the importance ofsomatic hypermutation of immunoglobulin V genes in antibodyaffinity maturation. In this process, localized mutation of the immunoglobulin genes allows the production of improvedantibodies, which make a major contribution to protective immunity and immunological memory. Much of his work in later years was devoted to characterizing this mutational process with a view to understanding its mechanism. He contributed a manuscript[24] for publication on this topic less than a week before he died.
Quite apart from his own achievements, Milstein acted as a guide and inspiration to many in the antibody field, as well as devoting himself to assisting science and scientists in less developed countries. Milstein patented the production of monoclonal antibodies,[25] and held three other patents.
In addition to the Nobel Prize in 1984, Milstein was elected aFellow of the Royal Society (FRS) in 1975,[3] was a fellow ofDarwin College, Cambridge, from 1980 to 2002, awarded theLouisa Gross Horwitz Prize fromColumbia University in 1980, he was awarded theWolf Prize in Medicine in 1980, he won theCopley Medal in 1989, and became aMember of the Order of the Companions of Honour in 1995. In 1993, the ArgentinianKonex Foundation granted him the DiamondKonex Award, one of the most prestigious cultural awards of Argentina, as the most important scientist in the last decade of his country.
Milstein married Celia Prilleltensky in 1953.
Milstein died early on 24 March 2002, inCambridge, England, at age 74, as a result of a heart condition that he had suffered from for many years.[26][27][28][29][30] His wife died in 2020 aged 92.
The filmUn fueguito, la historia de César Milstein was released in 2010. Directed by Ana Fraile, the film was awarded Best Documentary by the Academy of Film in Argentina.[citation needed]
The term hybridoma was proposed by Len Herzenberg during a sabbatical in my laboratory in 1976/1977. At a high-table conversation at a Cambridge College, Len was told by one of the dons that hybridoma was garbled Greek. By then, however, the term was becoming popular among us, and we decided to stick to it.
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