Phage therapy--history from Twort and d'Herelle through Soviet experience to current approaches.

Felix d'Herelle proposed the use of bacteriophages for the therapy of human and animal bacterial infections at the beginning of the 20th century. This approach, however, was not widely accepted in the West. After the emergence of antibiotics in 1940s, phage research was diverted to a more fundamental level. At the same time, phage therapy was widely practiced in the Soviet Union due to collaboration of Felix d'Herelle with his Georgian colleagues. The majority of the articles dedicated to this subject are from the 1930s and 1940s. The old Soviet literature indicates that phage therapy was used extensively to treat a wide range of bacterial infections in the areas of dermatology (Beridze, 1938), ophthalmology (Rodigina, 1938), urology (Tsulukidze, 1938), stomatology (Ruchko and Tretyak, 1936), pediatrics (Alexandrova et al., 1935; Lurie, 1938), otolaryngology (Ermolieva, 1939), and surgery (Tsulukidze, 1940, 1941). These articles were published in Russian and thus were not readily available to Western scientists. The Western skepticism toward phage therapy itself was again followed by renewed interest and reappraisal, mainly due to the emergence of drug-resistant bacteria. Often the experiments described in the old Soviet articles were not designed properly: the use of placebos and the coding of preparations were absent from most of the studies, number of patients in the experimental and control groups was unequal or missing, sometimes no control groups were used at all, or patients treated previously unsuccessfully with antibiotics were employed as an experimental group and as control. The results obtained and the efficiency of phage prophylaxis were estimated by comparing with results obtained in previous years. In most publications, phage titers and descriptions of methods used for evaluation of the results are not specified. Nevertheless, past experience indicates some effectiveness of phage therapy and prophylaxis. Therefore, these clinical results should not be neglected when designing any future studies.