Prior to the discovery and widespread use of antibiotics, it was suggested that bacterial infections could be prevented and/or treated by the administration of bacteriophages. Although the early clinical studies with bacteriophages were not vigorously pursued in the United States and Western Europe, phages continued to be utilized in the former Soviet Union and Eastern Europe. The results of these studies were extensively published in non-English (primarily Russian, Georgian, and Polish) journals and, therefore, were not readily available to the western scientific community. In this minireview, we briefly describe the history of bacteriophage discovery and the early clinical studies with phages and we review the recent literature emphasizing research conducted in Poland and the former Soviet Union. We also discuss the reasons that the clinical use of bacteriophages failed to take root in the West, and we share our thoughts about future prospects for phage therapy research.

Bacteriophages or phages are bacterial viruses that invade bacterial cells and, in the case of lytic phages, disrupt bacterial metabolism and cause the bacterium to lyse. The history of bacteriophage discovery has been the subject of lengthy debates, including a controversy over claims for priority. Ernest Hankin, a British bacteriologist, reported in 1896 on the presence of marked antibacterial activity (against Vibrio cholerae) which he observed in the waters of the Ganges and Jumna rivers in India, and he suggested that an unidentified substance (which passed through fine porcelain filters and was heat labile) was responsible for this phenomenon and for limiting the spread of cholera epidemics. Two years later, the Russian bacteriologist Gamaleya observed a similar phenomenon while working with Bacillus subtilis, and the observations of several other investigators are also thought to have been related to the bacteriophage phenomenon. However, none of these investigators further explored their findings until Frederick Twort, a medically trained bacteriologist from England, reintroduced the subject almost 20 years after Hankin's observation by reporting a similar phenomenon and advancing the hypothesis that it may have been due to, among other possibilities, a virus. However, for various reasonsincluding financial difficulties Twort did not pursue this finding, and it was another 2 years before bacteriophages were "officially" discovered by Felix d'Herelle, a French-Canadian microbiologist at the Institut Pasteur in Paris.

The emergence of pathogenic bacteria resistant to most, if not all, currently available antimicrobial agents has become a critical problem in modern medicine, particularly because of the concomitant increase in immunosuppressed patients. The concern that humankind is reentering the "preantibiotics" era has become very real, and the development of alternative antiinfection modalities has become one of the highest priorities of modern medicine and biotechnology.