Cesar Milstein: Timeline of key events

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Milstein was an Argentinian biochemist. Together with Georges Kohler, Milstein developed the first unlimited supply of long-lasting monoclonal antibodies. Their technique now underpins the development and application of many diagnostics and therapeutics. Kohler and Milstein devised the method as part of their search for a tool to investigate how the immune system can make so many different kinds antibodies, each able to bind to a highly specific receptor on foreign substances that invade the body. 1927-10-08T00:00:00+0000Cesar Milstein studies at the University of Buenos Aires.1945-01-01T00:00:00+0000Milstein investigates the enzyme dehydrogenase for his doctorate under the supervision of Andres Stoppani in the Department of Medicine, University of Buenos Aires1954-01-01T00:00:00+00001957-01-01T00:00:00+0000Milstein's first publication is C. Milstein, and A.O.M. Stoppani, 'Sensibilidad de aldehido deshidrogenasas para reactivos de tioles', An. Asoc. Quimica Argentina, 45 (1957), 33-51.1957-01-01T00:00:00+0000Milstein studies the enzyme phosphoglucomutase under the supervision of Malcolm Dixon and Edwin Webb at the Sir William Dunn School of Biochemistry.1958-01-01T00:00:00+00001961-01-01T00:00:00+0000Milstein heads up the newly-created Department of Molecular Biology, part of the National Institute of Microbiology within the Instituto Malbran.1961-01-01T00:00:00+0000Milstein decides to leave Argentina when the director of the Instituto Malbran and his supporters are dismissed in the wake of the tumoil created by a military coup led by General Raul Poggi.1962-01-01T00:00:00+0000Milstein is awarded a three-year MRC contract, arranged by Fred Sanger, to work at the Laboratory of Molecular Biology.1963-01-01T00:00:00+0000C.M. Milstein, 'Disulphide bridges and dimers of Bence-Jones Protein,' Journal of Molecular Biology, 9 (1964), 836-8.1964-01-01T00:00:00+0000S. Brenner, C. Milstein, 'Origin of antibody variation', Nature, 211 (1966), 242-3.1966-07-16T00:00:00+0000Milstein working with his doctoral student, David Secher, and post-doctoral researcher Dick Cotton, start their hunt for somatic mutants among antibodies. Reported in R.G.H. Cotton, D.S. Secher, C. Milstein, 'Somatic mutation and the origin of antibody diversity, Clonal variability of the immunoglobulin produced by MOPC21 cells in culture', European Journal Immunology, 3 (1973), 135-40. 1970-07-01T00:00:00+0000Kohler hears Milstein present work on myeloma cellular fusions and asks to join Milstein's team in Cambridge1973-01-01T00:00:00+0000Milstein and Cotton's create hybrid cell to study allelenic exclusion in antibodies. Reported in R.G.H. Cotton, C. Milstein, 'Fusion of two immunoglobulin-producing myeloma cells', Nature 244 (1973), 42-3. This work lays the foundation for the later development of monoclonal antibodies.1973-07-06T00:00:00+0000The investigation into somatic mutation lays the basis for the hunt for an antibody which has known specificity for particular antigens.1974-06-01T00:00:00+0000Cesar Milstein, an Argentinian scientist, and Georges Kohler, a German scientist, develop the first long-lasting monoclonal antibodies as part of their basic research project to investigate the mechanism behind the diversity of antibodies. 1975-01-01T00:00:00+0000The Argentinian born scientists Claudio Cuello and Cesar Milstein generate a monoclonal antibody against substance P, a peptide involved in the neurotransmission of pain. This marks the first application of monoclonal antibodies to neuroscience paving the way to an explosion of research into the brain the central nervous system bringing with it better understandings of neurological disease and neuropharmacological intervention. The work is published in A.C. Cuello, G. Galfre, C. Milstein, 'Detection of substance P in the central nervous system by a monoclonal antibody', Proceedings of the National Academy Science, USA, 76 (1979), 3532-6. 1975-01-01T00:00:00+0000Cesar Milstein, with the help of Tony Vickers, submits the monoclonal antibody technique to the British National Development Corporation for patenting,1975-08-07T00:00:00+0000Providing a means to produce limitless quantities of antibodies for the first time, Milstein and Kohler's technique was a major breakthrough. It provided a major tool for unravelling disease pathways, and brought major changes to diagnosis and the treatment of over 50 major diseases. The technique was published in G. Kohler, C. Milstein, 'Continuous cultures of fused cells secreting antibody of predefined specificity', Nature 256 (1975), 495-7. Article highlighted that monoclonal antibodies could be invaluable for medical and industrial purposes. By 1993 the paper had been cited in more than 6,905 publications.1975-08-07T00:00:00+0000
Date Event People Places Sciences
8 Oct 1927Cesar Milstein was born in Bahia Blanca, ArgentinaMilsteinLaboratory of Molecular BiologyAntibodies, Monoclonal antibodies, Immunology
1945 - 1952Cesar Milstein studies for a chemistry degreeMilsteinUniversity of Buenos Aires  
1954 - 1958Cesar Milstein pursues his first doctorate in biochemistryMilstein, StoppaniUniversity of Buenos Aires 
1957The Associacion Quimica Argentina awards Milstein a prize for the best doctoral thesis in chemistry that yearMilsteinUniversity of Buenos Aires 
1957 - 1959Cesar Milstein publishes papers from his doctorate with his supervisor Andres StoppaniMilsteinUniversity of Buenos Aires 
1958 - 1961Cesar Milstein takes up a British Council Scholarship at Cambridge UniversityMilstein, Dixon, WebbSir William Dunn School of Pathology 
1961Cesar Milstein is awarded a second doctorate in biochemistry at Cambridge UniversityMilsteinSir William Dunn School of Pathology 
1961Cesar Milstein takes up a position at the Instituto Malbran, Buenos AiresMilsteinInstituto Malbran 
1962An Argentinian military coup throws Cesar Milstein's academic work into disarrayMilsteinInstituto Malbran 
1963Cesar Milstein returns to Cambridge and begins researching the structure and diversity of antibodiesMilsteinLaboratory of Molecular BiologyMonoclonal antibodies
1964Cesar Milstein publishes his first paper on antibodiesMilsteinLaboratory of Molecular BiologyAntibodies
Jul 1966Cesar Milstein and Sydney Brenner publish theory attributing antibody diversity to somatic mutationBrenner, MilsteinLaboratory of Molecular BiologyAntibodies
Jul 1970Cesar Milstein launches experiments to determine whether somatic mutation underlies antibody diversityCotton, Milstein, SecherLaboratory of Molecular BiologyAntibodies
1973Cesar Milstein meets Georges Kohler at the Basel Institute of ImmunologyKohler, MilsteinBasel Institute of ImmunologyAntibodies
Jul 1973Cesar Milstein and Dick Cotton report the successful fusion of two different myeloma cell lines, one from a mouse and the other from a ratCotton, MilsteinLaboratory of Molecular BiologyMonoclonal antibodies
Jun 1974Georges Kohler joins Cesar Milstein's research team to investigate somatic mutation and antibody diversityKohler, MilsteinLaboratory of Molecular BiologyMonoclonal antibodies
Jan 1975Unlimited long-surviving monoclonal antibodies createdMilstein, KohlerLaboratory of Molecular BiologyMonoclonal antibodies
1975 - 1979First monoclonal antibody created to target a neurotransmitter peptideMilstein, CuelloLaboratory of Molecular Biology, MRC Neurochemical Pharmacology Unit, Oxford UniversityMonoclonal antibodies
Aug 1975First step taken to patent Kohler and Milstein's monoclonal antibodiesMilsteinLaboratory of Molecular BiologyMonoclonal antibodies
7 Aug 1975Cesar Milstein and Georges Kohler published their technique for monoclonal antibodiesKohler, MilsteinLaboratory of Molecular BiologyMonoclonal antibodies

8 Oct 1927

Cesar Milstein was born in Bahia Blanca, Argentina

1945 - 1952

Cesar Milstein studies for a chemistry degree

1954 - 1958

Cesar Milstein pursues his first doctorate in biochemistry

1957

The Associacion Quimica Argentina awards Milstein a prize for the best doctoral thesis in chemistry that year

1957 - 1959

Cesar Milstein publishes papers from his doctorate with his supervisor Andres Stoppani

1958 - 1961

Cesar Milstein takes up a British Council Scholarship at Cambridge University

1961

Cesar Milstein is awarded a second doctorate in biochemistry at Cambridge University

1961

Cesar Milstein takes up a position at the Instituto Malbran, Buenos Aires

1962

An Argentinian military coup throws Cesar Milstein's academic work into disarray

1963

Cesar Milstein returns to Cambridge and begins researching the structure and diversity of antibodies

1964

Cesar Milstein publishes his first paper on antibodies

Jul 1966

Cesar Milstein and Sydney Brenner publish theory attributing antibody diversity to somatic mutation

Jul 1970

Cesar Milstein launches experiments to determine whether somatic mutation underlies antibody diversity

1973

Cesar Milstein meets Georges Kohler at the Basel Institute of Immunology

Jul 1973

Cesar Milstein and Dick Cotton report the successful fusion of two different myeloma cell lines, one from a mouse and the other from a rat

Jun 1974

Georges Kohler joins Cesar Milstein's research team to investigate somatic mutation and antibody diversity

Jan 1975

Unlimited long-surviving monoclonal antibodies created

1975 - 1979

First monoclonal antibody created to target a neurotransmitter peptide

Aug 1975

First step taken to patent Kohler and Milstein's monoclonal antibodies

7 Aug 1975

Cesar Milstein and Georges Kohler published their technique for monoclonal antibodies

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