Antibodies: Timeline of key events

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Norman Klinman, an American immunologist, devises a splenic fragments culture technique for growing antibodies.1969-01-01T00:00:00+0000Brigette Askonas, a Canadian biochemist, Alan Williamson, a British immunologist, and Brian Wright clone B cells in vivo using spleen cells from mice immunised with haptenated carrier antigen.1970-01-01T00:00:00+0000The American geneticist Leonard Herzenberg creates the flueorcence-activated cell sorter, or FACS, an invaluable tool for studying cell structure and function. Coupled later with monoclonal antibodies the FACS is today a vital not only for basic research but medical diagnosis. 1970-01-01T00:00:00+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+0000Sera-Lab is established in Crawley-Down, UK, to commercially supply serum reagents to the scientific community. Sera-Lab was to become the first company to commercialise monoclonal antibodies. 1971-01-01T00:00:00+0000Niels Jerne, Danish immunologist, electrifies research into antibodies with his proposition that within the body there are a vast number of immune responses going on all the time and that antibodies form not only to external antigens but also in response to internal antigens within the body. 1973-01-01T00:00:00+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+0000Swiss-born immunologist Walter Gerhard cultivates single antibodies with known specificity against influenza viruses using Klinman's splenic fragment technique.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+0000The idotype marker was found by Freda and George Stevenson at the Tenovus Research Laboratory, Southampton University during their investigations of leukaemia in guinea-pigs. The marker was only present on cancer cells. This enabled the very precise targeting of cancer with antibodies.1975-04-25T00:00:00+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+0000G. 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+0000EA Carswell, LJ Old, RL Kassel, S Green, N Fiore, B Williamson, 'An endotoxin-induced serum factor that causes necrosis of tumors', Proc Natl Acad Sci USA, 72/9 (1975), 3666-70.1975-09-01T00:00:00+0000The experiments use antibodies generated by in sheep with chronic lymphocytic leukaemia cells taken from humans. The research is carried out by Freda and George Stevenson at the Tenovus Research Laboratory, Southampton University.1976-01-01T00:00:00+0000Koprowski uses myeloma cells from Milstein's laboratory to generate monoclonal antibodies against tumour antigens. This work forms the basis of the first patent later awarded for monoclonal antibodies.1976-09-01T00:00:00+0000The British National Research Development Corporation executives indicate that they will not pursue a patent the technique for producing monoclonal antibodies because they cannot see what diagnostic application it can be used for or any industrial end-products.1976-10-01T00:00:00+0000American geneticist and biochemist, Leonard Herzenberg and Argentinian biochemist, Cesar Milstein, devise monoclonal antibodies for use on an automatic fluorescence-activated cell sorter, FACS. This improves the reliability of the FACS allowing the instrument to go on to become a major tool not only for cell sorting and cellular biology but the diagnosis of disease. The work is done in collaboration with the American geneticist and immunologist Leonore Herzenberg and Vernon Oi, then a graduate student in genetics at Stanford University. 1977-01-01T00:00:00+0000
Date Event People Places Sciences
1969Splenic fragment technique devised for growing antibodiesKlinmanWistar InstituteMonoclonal antibodies
1970 - 1972Means developed for cloning B cells that produce single antibodies with known specificityAskonas, Williamson, WrightNational Institute for Medical ResearchMonoclonal antibodies
1970Fluorescence activated cell sorter createdHerzenbergStanford UniversityAntibodies
Jul 1970Cesar Milstein launches experiments to determine whether somatic mutation underlies antibody diversityCotton, Milstein, SecherLaboratory of Molecular BiologyAntibodies
1971Sera-Lab foundedMurray Monoclonal antibodies
1973Antibody network theoryJerneBasel Institute of ImmunologyAntibodies
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
1975Short-lasting antibodies against influenza virus devisedGerhardWistar InstituteMonoclonal antibodies
1975 - 1979First monoclonal antibody created to target a neurotransmitter peptideMilstein, CuelloLaboratory of Molecular Biology, MRC Neurochemical Pharmacology Unit, Oxford UniversityMonoclonal antibodies
Apr 1975Unique marker, known as an idiotypic determinant, discovered on the surface of proteins in cancer cells, providing a new target for treating cancerStevensonSouthampton UniversityAntibodies
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 paper outlining a technique for producing limitless monoclonal antibodiesKohler, MilsteinLaboratory of Molecular BiologyMonoclonal antibodies
Sep 1975Tumour necrosis factor (TNF) was discovered. It was the first immune molecule shown to kill cancer cellsCarswell, Old, Kassel, Green, Fiore, WilliamsonMemorial Sloan Kettering Cancer CenterImmunology, Cancer immunotherapy, Oncology, Monoclonal antibodies
Jan 1976Experiment in guinea-pigs with anti-idiotype antibodies shown to slow down leukaemiaStevensonSouthampton UniversityAntibodies
Sep 1976Cesar Milstein supplies myeloma cells to Hilary Koprowski at the Wistar Institute for producing monoclonal antibodiesKoprowski, MilsteinLaboratory of Molecular Biology, Wistar InstituteMonoclonal antibodies
Oct 1976British government declines to patent monoclonal antibodiesMilsteinLaboratory of Molecular BiologyMonoclonal antibodies
1977Monoclonal antibodies developed for automatic fluorescence-activated cell sorter Milstein, Herzenberg, OiLaboratory of Molecular Biology, Stanford University Medical School, University of TorontoMonoclonal antibodies

1969

Splenic fragment technique devised for growing antibodies

1970 - 1972

Means developed for cloning B cells that produce single antibodies with known specificity

1970

Fluorescence activated cell sorter created

Jul 1970

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

1971

Sera-Lab founded

1973

Antibody network theory

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

Short-lasting antibodies against influenza virus devised

1975 - 1979

First monoclonal antibody created to target a neurotransmitter peptide

Apr 1975

Unique marker, known as an idiotypic determinant, discovered on the surface of proteins in cancer cells, providing a new target for treating cancer

Aug 1975

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

7 Aug 1975

Cesar Milstein and Georges Kohler published their paper outlining a technique for producing limitless monoclonal antibodies

Sep 1975

Tumour necrosis factor (TNF) was discovered. It was the first immune molecule shown to kill cancer cells

Jan 1976

Experiment in guinea-pigs with anti-idiotype antibodies shown to slow down leukaemia

Sep 1976

Cesar Milstein supplies myeloma cells to Hilary Koprowski at the Wistar Institute for producing monoclonal antibodies

Oct 1976

British government declines to patent monoclonal antibodies

1977

Monoclonal antibodies developed for automatic fluorescence-activated cell sorter