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The history of immunology in Cambridge

cin Nuttall 150pxcin parasitology building 150pxcinCoombs tests 300px An entry in the New York Times in April 1904 relates how the Californian born biologist, George Nuttall "has collected the researches he made in the Pathological Laboratory of Cambridge University during 1902 into a volume entitled 'Blood Immunity and Blood Relationships Among Animals by Means of the Precipitin Test for Blood' ". Nuttall was a pioneer of immunology in Cambridge over a century ago when it was merely considered as a branch of another subject, such as bacteriology. During his time at Cambridge he founded the Molteno Institute for Parasitological Research, which still undertakes parasitology research today, as part of the Department of Pathology.

The subject got into its stride after the Second World War in the Pathology Department with Robin Coombs, with the Coombs Test which he introduced in 1945 continuing to have global impact. As related in every immunology textbook, the Coombs test has been instrumental in diagnosing haemolytic disease in newborns, where anti-rhesus antibodies from the mother cause destruction of the red blood cells in a rhesus positive baby. As a graduate student, Coombs addressed the problem of why, unlike the situation with ABO blood typing, anti-rhesus antibodies did not cause red cell agglutination. He arrived at an ingenious solution whilst returning to Cambridge on a dimly-lit wartime train, realizing that a second bridging antibody might make the red cells agglutinate. This formed the basis of the diagnostic test that transformed transfusion medicine, almost eliminating the problem of transfusion reactions and aiding management of rhesus incompatibility. The Coombs Test remains a standard test in all transfusion laboratories. Robin Coombs' other major contribution to British Immunology was his role in establishing the British Society of Immunology in November 1956, convening the first meeting at Trinity College, Cambridge.cinC Milstein 150px

 

 

The study of antibodies has continued to be a success story for Cambridge. Its zenith was the Nobel Prize in Medicine awarded to George Kohler and Cesar Milstein of the MRC Laboratory for Molecular Biology in 1984 for the development of monoclonal antibodies, which revolutionised medicine. Their key idea was to use a continuously growing line of myeloma cells that no longer secreted antibodies. These cells were fused with healthy antibody producing B-cells from an immunised mouse. Finally, clones of fused cells producing antibodies of the chosen specificity were selected.

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Techniques of humanizing monoclonal antibodies to minimise their adverse reactions in patients were also developed in Cambridge. Therapeutic monoclonals were championed by Herman Waldmann at a time when drug companies showed little interest, in favour of small molecules. The first fully-humanised antibody from this research programme, Campath-1, is now licensed as alemtuzumab, and is effective in the treatment of chronic lymphocytic leukemia and multiple sclerosis. It is currently licensed to Genzyme Oncology.

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Cambridge has also made major contributions in the field of transplantation. Foremost among these is the introduction of ciclosporin into clinical practice. Ciclosporin was isolated from the rare fungus Tolypocladium inflatum by Sandoz, who found it had immunosuppressive properties in vitro and in animal models. In 1978 Professor Sir Roy Calne commenced initial trials in renal transplant recipients at Addenbrooke’s hospital. Ciclosporin was found to be effective at inhibiting rejection, initial problems with nephrotoxicity and over-immunosuppression were overcome, and it was found that ciclosporin with a combination of steroids gave better control of rejection, preserved renal function, and decreased morbidity. In 1983, ciclosporin was approved by the US Food and Drug administration for prevention of transplant rejection. Ciclosporin has resulted in a 20% increase in one year renal allograft survival, and transplantation of organs which had previously been experimental due to poor success rates became possible (e.g. heart, lung and combined heart lung transplants). Ciclosporin, and its newer relative tacrolimus, remain central players in modern immunosuppression.
Today, immunology is a core subject that impinges on most branches of biomedical research in Cambridge. Immunologists are to be found in many different Departments within the University, and working closely with those in other local institutes, such as the Babraham Institute and the MRC Laboratory of Molecular Biology. The success story with antibodies continues with research into the role of AID in antibody diversification, but there is strength and depth across a wide range of research areas, including autoimmunity, cellular immune responses, clinical and translational immunology, immunity, immunogenetics, and molecular and structural immunology. Further information on each of these areas can be found on our research pages.