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Milstein, César

antibody antibodies cells mca

(1927–2002) [mil stiyn] Argentinian–British molecular biologist: co-discoverer of monoclonal antibodies.

Born and educated in Argentina, Milstein was a chemistry student, research student and staff member in Buenos Aires before his first stay in Cambridge from 1958. Back in Buenos Aires in 1961, he returned to Cambridge in 1963 to join on the Medical Research Council staff. There he worked on the structure of an immunoglobulin (an antibody) and then on a corresponding m-RNA, which led him towards monoclonal antibodies (MCAs). An MCA is a single, specific and chemically pure antibody produced in cloned cells, ie cells that are genetically identical, by a method devised in 1975 by Milstein and G Köhler (1946–95). Such MCAs are of great value in diagnosis and testing – for example they are now routinely used in the UK for typing of blood before transfusion–and they are potentially valuable in therapy, eg an MCA against Rhesus-D antigen (anti-D) can now be used for mothers who are Rh-negative and have just given birth to Rh-positive children.

To make an MCA, formation of the required antibody is first induced in an experimental animal by injection of an antigen. After a few weeks, antibody-rich B-lymphocytes are taken from its spleen. These cells are then fused with a malignant cell line (such as a myeloma cell). In some cases the resulting cell, a hybridoma, combines the lymphocyte’s ability to produce a pure antibody with the cancerous cell’s immortality, so that after selection and cloning it can be grown in culture indefinitely in laboratory conditions; in this way the antibody (which is normally present in serum only in trace amounts and mixed with other antibodies) can be produced in quantity.

The discovery of MCAs promises a revolution in biological research and in clinical diagnosis, and possibly in treatment for a variety of diseases, including some cancers. Milstein, Köhler and N Jerne (1911–94) shared a Nobel Prize in 1984. Jerne, an immunological theorist, had proposed in 1955 the first selection theory of antibody formation, which was then expanded by , who proposed the clonal selection theory. This states that each antibody is produced by a lymphocyte and that the effect of antigen is just to increase the number of cells producing specific antibodies. Later G Nossal (1931–) showed that, as predicted, individual lymphocytes produce only one kind of antibody, a necessary result for success in producing useful hybridomas.

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