TOX and diphtheria: In the history of diphtheria diagnostics, three turning points might be identified: (i) the demonstration that DT is a major virulence factor of C. diphtheriae and development of the toxigenicity test using an animal model in 1888; (ii) the development of agar immunodiffusion assay for the detection of DT production in 1948, commonly called the Elek test; and (iii) the development of PCR in 1991, which enables the detection of the tox gene.