the drug heavily in medical journals, eventually spending twice as much on marketing as it did to discover and develop terramycin. Still, it turned Pfizer, then a small company, into a pharmaceutical giant. The Pfizer group, led by Francis A. Hochstein, in loose collaboration with and Robert Burns Woodward, determined the structure of oxytetracycline, enabling Lloyd H. Conover to successfully produce tetracycline itself as a synthetic product. In 1955, Conover discovered that hydrogenolysis of aureomycin gives a deschloro product that is just as active as the original product. This proved for the first time that chemically modified antibiotics could have biological activity. Within a few years, a number of semisynthetic tetracyclines had entered the market, and now most antibiotic discoveries are of novel active derivatives of older compounds. Other tetracyclines were identified later, either as naturally occurring molecules, e.g., tetracycline from S. aureofaciens, S. rimosus, and S. viridofaciens and dimethyl-chlortetracycline from S. aureofaciens, or as products of semisynthetic approaches, e.g., methacycline, doxycycline, and minocycline. Research conducted by anthropologist George J. Armelagos and his team at Emory University showed that ancient Nubians from the post-Meroitic period (around AD 350) had deposits of tetracycline in their bones, detectable through analyses of cross-sections through ultraviolet light – the deposits are fluorescent, just as are modern ones. Armelagos suggested that this was due to ingestion of the local ancient beer (very much like the Egyptian beer), made from contaminated stored grains. Development Tetracyclines 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 platform towards derivatives with increased potency as well as efficacy against tetracycline-resistant bacteria, with improved pharmacokinetic and chemical properties. Shortly after the introduction of tetracycline therapy, the first tetracycline-resistant bacterial pathogen was identified. Since then, tetracycline-resistant bacterial pathogens have continued to be identified, limiting tetracycline's effectiveness in treatment of bacterial disease. Glycylcyclines and fluorocyclines are new classes of antibiotics derived from tetracycline. These tetracycline analogues are specifically designed to overcome two common mechanisms of tetracycline resistance, namely resistance mediated by acquired efflux pumps and/or ribosomal protection. In 2005, tigecycline, the first member of a new subgroup of tetracyclines named glycylcyclines, was introduced to treat infections that are resistant to other antimicrobials. Although it is structurally related to minocycline, alterations to the molecule