The 100th anniversary of Wassermann-Neisser-Bruck reaction

August Paul von Wassermann (1866-1925), German bacteriologist, together with Albert Neisser (1855-1916), German dermatologist and venereologist, and Carl Bruck (1879-1944), German dermatologist and venereologist, developed the first serologic test for the diagnosis of syphilis. They published their first article about it on May 10, 1906 (Dtsch Med Wochenschr 1906;32:745). They made use of the idea of the complement fixation test of Jules Bordet (1870-1961) and Octave Gengou (1875-1957), so the Wassermann reaction is sometimes called Bordet-Wassermann reaction. The study was done at the Berlin Institute of Infectious Diseases (Berliner Institut für Infektionskrankheiten) and at the Breslau (Wroclaw) Department of Dermatology. The Wassermann reaction was used in the diagnosis of syphilis. The antigen used in it was prepared empirically. Originally, the so-called antigens were extracts of human or monkey tissue rich in Treponema pallidum. The most active one was a liver extract of a syphilitic fetus. Later on, the active substance, referred to as cardiolipin, was found in normal nonsyphilitic tissues, including the heart (usually bovine heart). Karl Landsteiner (1868-1943) identified the antigen involved in the Wassermann reaction as a lipoid substance, which finally was identified as diphosphatidylglycerol. Wassermann antibodies, produced in the course of syphilis infection, are reactive with cardiolipin in the presence of lecithin and cholesterol. The antigen-antibody reaction produces immune complexes, which results in complement fixation via the classic pathway; this may be used to determine the serum level of antibodies (if <1 microg/mL). In the final step, indicator cells (erythrocytes) together with a subagglutinating amount of antibodies (antierythrocyte antibodies) are added to the mixture. If there remains any complement left, these cells will be lysed; if it has been consumed by immune complexes, the amount of the remaining complement will be insufficient to produce the lysis of the red cells. In the first experiment of Wassermann et al, the reaction was positive exclusively with the sera of patients with syphilis, but it was soon discovered that some other diseases gave positive results in nonsyphilitic individuals. First such cases were reported in 1909. With the discovery of new and more specific tests for syphilis, the complement fixation tests of Wassermann type gradually went into oblivion. A new era in venereology was started with the discovery of T pallidum by Fritz Schaudinn (1871-1906) and Erich Hoffmann (1868-1954) in 1905, and the development of serology of syphilis by Wassermann, Neisser, and Bruck in 1906. Although the Wassermann reaction is no longer in use now, it should be emphasized that it was one of the very first serodiagnostic tests ever used in medical practice. Carl Bruck said in the 1920s: "This fortunate and unique mistake constituted the basis of a very important discovery, whose significance was both theoretical and practical."