Antibodies: Timeline of key events

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Waldmann is an immunologist who demonstrated how monoclonal antibodies could induce tolerance to foreign proteins and transplanted tissues. He and his team developed the first humanised monoclonal antibody (alemtuzumab) which is now used for combating leukaemia, preventing transplant rejection and treating autoimmune disorders such as multiple sclerosis and vasculitis. 1945-02-27T00:00:00+0000Together with Cesar Milstein, Kohler 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. 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+0000In 1978 Birndorf, along with Ivor Royston, helped found Hybritech, America's first biotechnology company dedicated to monoclonal antibodies. Birndorf went on to found other companies including: Gen-Probe, IDEC Pharmaceuticals (which merged with Biogen to form Biogen-Idec), Ligand, Gensia (Sicor), Neurocrine Biosciences, FastTraQ and Nanogen. 1950-02-21T00:00:00+0000Schoemaker was co-founder and first Chief Executive Officer of Centocor, an American biotechnology company that pioneered the commercialisation of monoclonal antibody diagnostics and therapeutics. After Centocor was sold to Johnson & Johnson for $5.2 billion in 1999, Schoemaker founded Neuronyx to develop cellular therapies. One of the treatments pioneered by Neuronyx was the use of stem cells from bone marrow to help regenerate heart tissue damaged by heart attacks. 1950-03-23T00:00:00+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+0000A pioneer of protein engineering, Winter invented techniques to both humanise and later to make fully human antibodies for therapeutic uses. Today his technology is used in over two-thirds of antibody drugs on the market, including Humira, a treatment for rheumatoid arthritis and other autoimmune conditions, which in 2012 was listed as the top selling drug in the world. He is also the founder of three biotechnology companies: Cambridge Antibody Technology, Domantis and Bicycle Therapeutics. 1951-03-31T00:00:00+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+0000A pioneer of antibody engineering, Neuberger developed some of the first techniques for the generation of chimeric and humanised antibodies. He also helped create the first transgenic mice for the production of human monoclonal antibodies. His work paved the way for the generation of safer and more effective monoclonal antibody drugs. 1953-11-02T00:00:00+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+0000Originally developed to measure insulin levels, the radioimmunoassay (RIA) provides a highly sensitive means of measuring incredibly low concentrations of many different substances in solutions. It does this by taking advantage of the antigen-antibody reaction and radioactive materials. The technique is now used for a variety of purposes, including screening for the hepatitis virus in blood, determining effective dosage levels of drugs and antibiotics, detecting foreign substances in the blood and correcting hormone levels in infertile couples. RS Yalolw, SA Berson, 'Assay of plasma in human subjects by immunological methods', Nature, 184 (1959), 1648-49. 1959-11-21T00:00:00+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+0000Bordet was a Belgian physician, immunologist and microbiologist who won the 1919 Nobel Prize for his discovery of two components in the blood - antibodies and complement proteins. The two components help destroy invading bacteria by rupturing the cell walls of the bacteria, a process known as bacteriolysis. Bordet made the discovery in 1895. Three years later Bordet observed that red blood cells from one animal species injected into another get destroyed by haemolysis - a process analogous to bacteriolysis. His finding led to the development of diagnostic tests that hunt for antibodies in the blood to detect infectious agents. The first one was for typhoid, developed in 1896. 1961-04-06T00:00:00+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+0000The medium was first described by John Littlefield in work he did to characterise four cell lines. He published this in JW Littlefield, 'Selection of hybrids from matings of fibroblasts in vitro and their presumed recombinants,' Science 145 (1964), 709–10.The HAT meidum has the advantage that it can inhibit unfused myeloma cell proliferation. This is particularly important for the growth of monoclonal antibodies. 1964-08-14T00:00:00+0000
Date Event People Places Sciences
27 Feb 1945Herman Waldmann was born in LebanonWaldmannCambridge University, Oxford UniversityImmunology, Monoclonal antibodies
17 Apr 1946Georges Kohler was born in Munich, GermanyKohlerLaboratory of Molecular BiologyMonoclonal antibodies
1948Antibody production found in plasma B cellsFagraeusKarolinska InstitutetAntibodies
1949Immune tolerance concept developedBurnet, FennerWalter and Eliza Hall InstituteAntibodies
21 Feb 1950Howard Birndorf was born in Detroit, Michigan, USABirndorfHybritechMonoclonal antibodies
23 Mar 1950Hubert Schoemaker was born in Deventer, The NetherlandsSchoemakerDeventer, The NetherlandsMonoclonal antibodies, Stem cells
1951Myeloma cells found to resemble normal antibodiesKunkelRockefeller UniversityAntibodies
31 Mar 1951Gregory Winter was born in Leicester, UKWinterLaboratory of Molecular BiologyMonoclonal antibodies
1953Immune tolerance theory proved in experimentsMedawar, Billingham, BrentUniversity College LondonAntibodies
2 Nov 1953Michael Neuberger was born in London, United KingdomNeubergerLondonMonoclonal antibodies
1955 - 1959Clonal selection theoryJerne, Talmage, BurnetDanish National Serum Institute, Walter and Eliza Hall InstituteAntibodies
1958The cell is confirmed responsible for antibody productionJoshua Lederberg, NossalUniversity of Wisconsin, Walter and Eliza Hall InstituteAntibodies
21 Nov 1959Rosalyn Yalow and Soloman Berson published the radioimmunoassay method opening up a new era in immunology and diagnosticsYalow, BersonVeterans Administration HospitalAntibodies, Diagnostics
1960Cellular fusion technique formulatedBarski, Sorieul, CarnefertInstitut Gustave RoussyMonoclonal antibodies
6 Apr 1961Jules Bordet diedBordetPasteur InstituteAntibodies, Immunology, Diagnostics
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
14 Aug 1964HAT medium introduced for cell selectionLittlefieldHarvard UniversityCell culture, Monoclonal antibodies

27 Feb 1945

Herman Waldmann was born in Lebanon

17 Apr 1946

Georges Kohler was born in Munich, Germany


Antibody production found in plasma B cells


Immune tolerance concept developed

21 Feb 1950

Howard Birndorf was born in Detroit, Michigan, USA

23 Mar 1950

Hubert Schoemaker was born in Deventer, The Netherlands


Myeloma cells found to resemble normal antibodies

31 Mar 1951

Gregory Winter was born in Leicester, UK


Immune tolerance theory proved in experiments

2 Nov 1953

Michael Neuberger was born in London, United Kingdom

1955 - 1959

Clonal selection theory


The cell is confirmed responsible for antibody production

21 Nov 1959

Rosalyn Yalow and Soloman Berson published the radioimmunoassay method opening up a new era in immunology and diagnostics


Cellular fusion technique formulated

6 Apr 1961

Jules Bordet died


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

14 Aug 1964

HAT medium introduced for cell selection

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