Antibodies: 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+0000Fibiger published the first randomisation method for a clinical trial. The aim of the trial, conducted in 1898, was to investigate the effect of serum therapy on diphtheria. Fibiger would later go on to win the 1926 Nobel Prize for Medicine for demonstrating a roundworm could cause stomach cancer in rats and mice. Following his death researchers showed that the roundworm could not cause cancer and were due to vitamin deficiency and that Fibiger had mistakenly confused non-cancerous tumours for cancerous tumours in his experiments.1928-01-30T00:00:00+0000E Witebsky, 'Disponibilitiit und Spezifitat alkoholloslicher Strukturen von Organen und bosartigen Geschwulsten', Zeitschrift fur Imrnunitaetsforschung, Allergie und Klinische Immunologie' 62 (1929), 35-73. 1929-01-01T00:00:00+0000Edelman was a biologist renowned for his research on antibodies. His research helped determine the chemical structure of antibodies in the early 1960s. It showed that antibodies were made up of two light and heavy chains linked together by disulfide bonds. The breakthrough immediately galvanised feverish activity in all fields of immunological science, paving the way to the development of antibodies for both diagnostics and therapy. Edelman was awarded the Nobel Prize for Medicine in 1972 for his work.1929-07-01T00:00:00+0000Michael Smith shared the 1993 Nobel Prize for Chemistry for a technique that enables researchers to introduce specific mutations into genes and, thus, to the proteins that they encode. He developed the method, known as site-directed mutagenesis, in the 1970s, in collaboration with Fred Sanger and Clyde A Hutchinson III. The advantage of the technique was that it allowed comparisons to be made of different protein molecules and provided a means to deliberately alter a specific gene thereby making it possible to modify the characteristics of an organism. His work opened up a new chapter for studying and treating genetic diseases. Site-directed mutagenesis is a pivotal tool today in genetic and protein research and engineering and at the forefront of the development of monoclonal antibody drugs. 1932-04-26T00:00:00+0000John Marrack, a British chemical pathologist, proposes the biochemical forces which underly the bond between antibodies and antigens. 1934-01-01T00:00:00+0000The American biomedical scientists Michael Heidelberger, Forrest Kendall and Elvin Kabat demonstrate antibodies to be proteins.1935-01-01T00:00:00+0000Klinman was an immunologist who developed the splenic focus assay, a tool that allowed analysis of antibody production derived from single clones of B cells. He used the tool to analyse immune tolerance and immune responses to influenza. In additon he invented the splenic fragment system, a technique that helped generate some of earliest monoclonal antibodies against viral antigens and cancer. 1937-03-23T00:00:00+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+0000Waldmann 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+0000
Date Event People Places Sciences
8 Oct 1927Cesar Milstein was born in Bahia Blanca, ArgentinaMilsteinLaboratory of Molecular BiologyAntibodies, Monoclonal antibodies, Immunology
30 Jan 1928Johannes Fibiger diedFiber Antibodies, Oncology, Clinical trial
1929First molecular marker, antigen, identified on a tumour, laying foundation for use of antibodies to diagnose and treat cancerWitebsky University of HeidelbergImmunology, Cancer immunotherapy, Oncology, Monoclonal antibodies
1 Jul 1929Gerald M Edelman was born in New York NY, USAEdelmanRockefeller UniversityAntibodies, Immunology
26 Apr 1932Michael Smith was born in Blackpool, United KingdomSmithUniversity of British ColumbiaGene editing, Genetics, Monoclonal antibodies
1934 - 1938Antigen-antibody binding hypothesis formulatedMarrackLondon UniversityAntibodies
1935 - 1936Antibodies shown to be proteinsHeidelberger, Kendall, KabatColumbia UniversityAntibodies
23 Mar 1937Norman Klinman was born in Philadelphia, Pennsylvania, USAKlinmanWistar Institute, University of PennsylvaniaAntibodies, Monoclonal antibodies, Immunology
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
27 Feb 1945Herman Waldmann was born in United KingdomWaldmannUnited KingdomImmunology, 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 EnglandWinterUnited KingdomMonoclonal antibodies

8 Oct 1927

Cesar Milstein was born in Bahia Blanca, Argentina

30 Jan 1928

Johannes Fibiger died

1929

First molecular marker, antigen, identified on a tumour, laying foundation for use of antibodies to diagnose and treat cancer

1 Jul 1929

Gerald M Edelman was born in New York NY, USA

26 Apr 1932

Michael Smith was born in Blackpool, United Kingdom

1934 - 1938

Antigen-antibody binding hypothesis formulated

1935 - 1936

Antibodies shown to be proteins

23 Mar 1937

Norman Klinman was born in Philadelphia, Pennsylvania, USA

1939

Antibodies start to be investigated using quantitative immunochemistry

6 Sep 1939

Susumu Tonegawa was born in Nagoya, Japan

1940

Concept of antibody templates proposed

1941

Immunofluorescence technique introduced

27 Feb 1945

Herman Waldmann was born in United Kingdom

17 Apr 1946

Georges Kohler was born in Munich, Germany

1948

Antibody production found in plasma B cells

1949

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

1951

Myeloma cells found to resemble normal antibodies

31 Mar 1951

Gregory Winter was born in England