COMMERCIAL PRODUCTION OF PHAGES
D'Herelle's commercial laboratory in Paris produced at least five phage preparations against various bacterial infections. The preparations were called Bacté-coli-phage, Bacté-rhino-phage, Bacté-intesti-phage, Bacté-pyo-phage, and Bacté-staphy-phage, and they were marketed by what later became the large French company L'Oréal (68). Therapeutic phages were also produced in the United States. In the 1940s, the Eli Lilly Company (Indianapolis, Ind.) produced seven phage products for human use, including preparations targeted against staphylococci, streptococci, Escherichia coli, and other bacterial pathogens. These preparations consisted of phage-lysed, bacteriologically sterile broth cultures of the targeted bacteria (e.g., Colo-lysate, Ento-lysate, Neiso-lysate, and Staphylo-lysate) or the same preparations in a water-soluble jelly base (e.g., Colo-jel, Ento-jel, and Staphylo-jel). They were used to treat various infections, including abscesses, suppurating wounds, vaginitis, acute and chronic infections of the upper respiratory tract, and mastoid infections. However, the efficacy of phage preparations was controversial (20, 26), and with the advent of antibiotics, commercial production of therapeutic phages ceased in most of the Western world. Nevertheless, phages continued to be used therapeutically—together with or instead of antibiotics—in Eastern Europe and in the former Soviet Union. Several institutions in these countries were actively involved in therapeutic phage research and production, with activities centered at the Eliava Institute of Bacteriophage, Microbiology, and Virology (EIBMV) of the Georgian Academy of Sciences, Tbilisi, Georgia, and the Hirszfeld Institute of Immunology and Experimental Therapy (HIIET) of the Polish Academy of Sciences, Wroclaw, Poland.
EIBMV.
TheEliavaInstitute(
Yahoo! GeoCities: Get a web site with easy-to-use site building tools. /hotsprings/spa/5386) was founded in 1923 by Giorgi Eliava, a prominent Georgian bacteriologist, together with Felix d'Herelle. D'Herelle spent several months in Georgia collaborating with Eliava and other Georgian colleagues, and he intended to move to Tbilisi permanently (a cottage built for his use still stands on the Institute's grounds). However, in 1937 Eliava was arrested by Stalin's NKVD (the predecessor of the KGB), pronounced a “People's Enemy,” and executed. Frustrated and disillusioned, d'Herelle never returned to Georgia. Nonetheless, the Institute survived and later became one of the largest facilities in the world engaged in the development of therapeutic phage preparations. The Institute, during its best times, employed approximately 1,200 researchers and support personnel and produced phage preparations (often several tons a day) against a dozen bacterial pathogens, including staphylococci, Pseudomonas, Proteus, and many enteric pathogens. Most of the Soviet studies reviewed in this article involved phages developed and produced at the EIBMV.
HIIET.
The Hirszfeld Institute (
http://surfer.iitd.pan.wroc.pl/index1.htm) was founded in 1952, and its staff has been actively involved in phage therapy research since 1957, when therapeutic phages were used to treat Shigella infections (B. Weber-Dabrowska, personal communication). The bacteriophage laboratory of the Institute was instrumental in developing and producing phages for the treatment of septicemia, furunculosis, and pulmonary and urinary tract infections and for the prophylaxis or treatment of postoperative and postraumatic infections. In many cases, phages were used against multidrug-resistant bacteria that were refractory to conventional treatment with antibiotics. The most detailed studies published in English on the use of phages in clinical settings have come from this institute (52–58).
