Antibodies: Timeline of key events

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The American biomedical scientists Michael Heidelberger, Forrest Kendall and Elvin Kabat demonstrate antibodies to be proteins.1935-01-01T00:00:00+0000Swedish chemists Theodor Svedberg and Arne Tiselius and the American biomedical scientist Elvin Kabat start using new biochemical techniques, notably ultracentrifugation and electrophoresis, to investigate the structure of antibodies.1939-01-01T00:00:00+0000Tonegawa discovered how the immune system genetically changes the body's antibodies to counter different foreign invaders.1939-09-06T00:00:00+0000Linus Pauling, an American chemist, puts forward the notion of a template underlying antibody formation, echoing Ehrlich's earlier vision of antibodies and antigens working together like a lock and a key.1940-01-01T00:00:00+0000Albert Coons, an American physician and immunologist, develops the immunofluorescence technique using antibodies coupled with fluorophore. This allowed for microscopic visualisation of antibodies helping to launch the clinical disciplines of diagnostic immunofluorescence microscopy for bacteriology and immunology, immunocytology, and immunohistochemistry in anatomic pathology.1941-01-01T00:00:00+0000Kohler co-pioneered the first monoclonal antibodies which today are a major component in diagnostics and blockbuster drugs.1946-04-17T00:00:00+0000Astrid Fagraeus, a Swedish immunologist, publishes her doctoral thesis demonstrating plasma B cells produce antibodies. 1948-01-01T00:00:00+0000Macfarlane Burnet and Frank Fenner develop the concept that organisms can discriminate between self and non-self. Defined as immune tolerance this helped explain how the body fails to mount an attack against its own antigens and against certain external antigens. This theory inspired greater investigation into antibodies and unravelling the mechanism underlying autoimmunity, laying the foundation for organ transplants. 1949-01-01T00:00:00+0000Henry Kunkel, an American immunologist, while studying the blood of patients with myeloma (a type of cancer that develops from plasma cells in the bone marrow) unexpectedly discovers myeloma proteins to resemble normal antibodies.1951-01-01T00:00:00+0000Peter Medawar, Brazilian-British biologist, Rupert Billingham, British-American scientist, and Leslie Brent, German-British immunologist, confirm the theory of immune tolerance through skin gafting experiments with mice. The work helped shift immunologists focus away from efforts to manage the fully developed immune mechanism towards altering the immunity mechanism itself, such the immune suppression to prevent the body's rejection of organ transplants.1953-01-01T00:00:00+0000Niels Jerne, a Danish immunologist, David Talmage, and Ameican immunologist, and Macfarlane Burnet, an Austrialian immunologist, independently develop the clonal selection theory. This proposes that the cell is repsonsible for making antibodies and that a small number of antibodies can distinguish between a larger number of antigen determinants. 1955-01-01T00:00:00+0000The American molecular geneticist Joshua Lederberg and the Austrian-Australian biologist Gustav Nossal publish results from experiments confirming one cell is responsible for the production of just one type of antibody. This confirms the clonal selection theory. 1958-01-01T00:00:00+0000Georges Barski, Serge Sorieul and Francine Cornefert, French scientists at the Institut Gustave Roussy, spot cellular fusion occurs when two different tumour cell lines, taken from two different inbred strains of mice, are grown as a cell mixture in tissue cultures. This observation lays the basis for the development of new techniques for cellular fusion. 1960-01-01T00:00:00+0000Independently Rodney Porter, a British scientist, and Gerald Edelman, an American biologist, determine the structure of antibodies to consist of heavy and light protein chains, which join together to form three sections yielding a molecule shaped like the letter Y.1962-01-01T00:00:00+0000Niels Jerne, Danish immunologist, and Albert Nordin develop a plaque test which allows for the first time scientists to visualise and determine the number of antibody-producing cells with the naked eye. 1963-01-01T00:00:00+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+0000Funded by the multinational pharmaceutical company F. Hoffman La Roche, the Basel Institute of Immunology was designed to keep the pharmaceutical company keep ahead of developments in biology, cell biology and biochemistry. It rapidly became the world's largest centres for immunological research and antibody investigation.1969-01-01T00:00:00+0000Joseph Sinkovics, a Hungarian clinical pathologist and laboratory clinical virologist, successfully develops a cell line of antibodies with known specificity that could be grown indefinitely by fusing antibody-producing plasma cells with lymphoma cells.1969-01-01T00:00:00+0000
Date Event People Places Sciences
1935 - 1936Antibodies shown to be proteinsHeidelberger, Kendall, KabatColumbia UniversityAntibodies
1939Antibodies start to be investigated using quantitative immunochemistrySvedberg, Tiselius, KabatUniversity of UppsalaAntibodies
6 Sep 1939Susumu Tonegawa was born in Nagoya, JapanTonegawaMassachusetts Institute of TechnologyAntibodies, Immunology
1940Concept of antibody templates proposedPaulingCalifornia Institute of Technology Antibodies
1941Immunofluorescence technique introducedCoonsHarvard UniversityAntibodies
17 Apr 1946Georges Kohler was bornKohlerLaboratory of Molecular BiologyMonoclonal antibodies
1948Antibody production found in plasma B cellsFagraeusKarolinska InstitutetAntibodies
1949Immune tolerance concept developedBurnet, FennerWalter and Eliza Hall InstituteAntibodies
1951Myeloma cells found to resemble normal antibodiesKunkelRockefeller UniversityAntibodies
1953Immune tolerance theory proved in experimentsMedawar, Billingham, BrentUniversity College LondonAntibodies
1955 - 1959Clonal selection theoryJerne, Talmage, BurnetDanish National Serum Institute, Walter and Eliza Hall InstituteAntibodies
1958The cell is confirmed responsible for antibody productionLederberg, NossalUniversity of Wisconsin, Walter and Eliza Hall InstituteAntibodies
1960Cellular fusion technique formulatedBarski, Sorieul, CarnefertInstitut Gustave RoussyMonoclonal antibodies
1962Antibodies discovered to have structure like a 'Y'Porter, EdelmanNational Institute for Medical Research, Rockefeller University Antibodies
1963Plaque test allows visualisation of antibodiesJerne, NordinUniversity of PittsburghAntibodies
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
1969Basel Institute of Immunology foundedJerneBasel Institute of ImmunologyAntibodies
1969First antibodies with known specificity grownSinokovicsMD Anderson Cancer CenterAntibodies

1935 - 1936

Antibodies shown to be proteins


Antibodies start to be investigated using quantitative immunochemistry

6 Sep 1939

Susumu Tonegawa was born in Nagoya, Japan


Concept of antibody templates proposed


Immunofluorescence technique introduced

17 Apr 1946

Georges Kohler was born


Antibody production found in plasma B cells


Immune tolerance concept developed


Myeloma cells found to resemble normal antibodies


Immune tolerance theory proved in experiments

1955 - 1959

Clonal selection theory


The cell is confirmed responsible for antibody production


Cellular fusion technique formulated


Antibodies discovered to have structure like a 'Y'


Plaque test allows visualisation of antibodies


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


Cesar Milstein publishes his first paper on antibodies

Jul 1966

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


Basel Institute of Immunology founded


First antibodies with known specificity grown