The history of the tetracyclines.

The history of the tetracyclines involves the collective contributions of thousands of dedicated researchers, scientists, clinicians, and business executives over the course of more than 60 years. Discovered as natural products from actinomycetes soil bacteria, the tetracyclines were first reported in the scientific literature in 1948. They were noted for their broad spectrum antibacterial activity and were commercialized with clinical success beginning in the late 1940s to the early 1950s. The second-generation semisynthetic analogs and more recent third-generation compounds show the continued evolution of the tetracycline scaffold toward derivatives with increased potency as well as efficacy against tetracycline-resistant bacteria, with improved pharmacokinetic and chemical properties. Their biologic activity against a wide spectrum of microbial pathogens and their uses in mammalian models of inflammation, neurodegeneration, and other biological systems indicate that the tetracyclines will continue to be successful therapeutics in infectious diseases and as potential therapeutics against inflammation-based mammalian cell diseases.

From mercury to malaria to penicillin: the history of the treatment of syphilis at the Mayo Clinic--1916-1955.

Between 1916 and 1955 the Mayo Clinic became recognized as one of the premier institutions specializing in the treatment of syphilis. First under the direction of John H. Stokes (1916-1924) and later Paul A. O'Leary (1924-1953), its Department of Dermatology and Syphilology, together with the members of the Clinical Cooperative Study Group, oversaw the establishment of standardized methods for the administration of the existing arsenicals and the introduction of new therapies. Malaria therapy, heat therapy, penicillin, and oxytetracycline each represented important advances in the treatment of syphilis and were extensively evaluated. Two important ancillary benefits of syphilis treatment were the development of routine intravenous techniques, which would later prove invaluable for the administration of antibiotics and cancer drugs, and the establishment of large cooperative clinical trials, the first of their kind. Under the leadership of Stokes and O'Leary the department produced a stream of pivotal clinical research that contributed to the effective management of syphilis in the United States.