Antibodies: Timeline of key events

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A 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+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+0000Bordet was a Belgian physician, immunologist and microbiologist. He is best known for winning the 1919 Nobel Prize for his discovery of two components in the blood - antibodies and complement proteins - that help destroy invading bacteria. They do this by rupturing the cell walls of the bacteria, a process known as bacteriolysis. Bordet made the discovery in 1895. He subsequently found, in 1898, that red blood cells from one animal species injected into another get destroyed by haemolysis - a process analogous to bacteriolysis. His research laid the foundation for the development of diagnostic tests that looked 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+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+0000Norman 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+0000
Date Event People Places Sciences
31 Mar 1951Gregory Winter was born in EnglandWinterUnited KingdomMonoclonal antibodies
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
6 Apr 1961Jule 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
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
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

31 Mar 1951

Gregory Winter was born in England

1953

Immune tolerance theory proved in experiments

1955 - 1959

Clonal selection theory

1958

The cell is confirmed responsible for antibody production

1960

Cellular fusion technique formulated

6 Apr 1961

Jule Bordet died

1962

Antibodies discovered to have structure like a 'Y'

1963

Plaque test allows visualisation of antibodies

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

1969

Basel Institute of Immunology founded

1969

First antibodies with known specificity grown

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