Immunohistochemistry began over 120 years ago when Von Behring discovered serum antibodies in 1890 and used them to cure diphtheria and tetanus. The precipitin test, developed by Dr. Kraus in 1897, demonstrated that these antitoxins reacted with antigens. In 1923, Dr. Michael Heidelberger quantified this reaction with the use of dyes attached to antigens and Dr. John Marrack visualized the reaction by attaching dyes to antibodies. Dr. Albert H. Coons developed the first fluorescent antibody labels, officially launching light microscopic (LM) immunohistochemistry in 1941. Immuno-electron microscopy (EM) was officially launched in 1959 when Dr. S.J. Singer attached ferritin to antibodies to detect viral surface antigens. Six years later, Drs. Stratis Avrameas and Paul Nakane reported the development of immunoperoxidase techniques, detecting antigens at LM and EM levels, with pioneering techniques developed by Drs. Graham and Karnovsky. Drs. Ludwig Sternberger and Sam Spicer modified the immunoenzyme protocol in 1969 with the use of antibody–antibody bridging, thus avoiding chemical conjugation. In 1970, Dr. Ludwig Sternberger developed soluble peroxidase–antiperoxidase (PAP) complexes, which increased sensitivity and efficiency. Doctors Gwen C. Moriarty and Nicholas S. Halmi demonstrated the feasibility of application of these PAP complexes at the EM level in 1972, encouraging its widespread use. Doctors Faulk and Taylor attached colloidal gold labels to antibodies in 1971 and Drs. Roth, Bendayan, and Orci modified this EM protocol in 1978 with the use of protein A. Colloidal gold became the immuno-EM technique, which is used widely today. In 1982, Dr. S.-M. Hsu added avidin–biotin linkages, which increased sensitivity and allowed the reliable detection of antigenic sites that were difficult to preserve.