ABSTRACT
Introduction .................................................................................................................................... 713 Early History .................................................................................................................................. 714
Early Attempts at Commercialization ................................................................................ 716 Specic Problems of Early Phage Therapy Work .............................................................. 716
Phages and the Immune System .................................................................................................... 717 Clinical Application: Phage Therapy Work in the Age of Antibiotics .......................................... 719
Institute of Immunology and Experimental Medicine, Polish Academy of Sciences ........ 719 Eliava Institute of Bacteriophage, Microbiology and Virology, Tbilisi, Georgia .............. 721 Recent Work in the West .................................................................................................... 723
Phage and Bacterial Pathogenicity ................................................................................................724 Phage Therapy with Well-Characterized, Professionally Lytic Phages ........................................ 725 Safety Issues ................................................................................................................................... 726 Conclusion ...................................................................................................................................... 726 References ...................................................................................................................................... 727
Bacteriophages — specic kinds of viruses that can only replicate in bacteria — have been discussed in much detail in the previous chapter. The art of using these phages to kill pathogenic microorganisms was rst developed early in the last century; but because chemical antibiotics became available in the 1940s, phage therapy has been little used in the West. Today, however, the growing incidence of bacteria that are resistant to most or all available antibiotics is leading to widespread, renewed interest in the possibilities of phage therapy.1-11 This overview is designed to put phage therapy into historical and ecological context; to briey explore some of the most interesting and extensive applications carried out in eastern Europe, conducted primarily in a clinical rather than controlled-research mode; and to look at the original decline and current renaissance of phage therapy work in the West. Ironically, this renaissance takes full advantage of the advances in molecular biology that were themselves made possible by fundamental work with bacteriophages beginning in the 1940s under the leadership of Max Delbrück. The rapidly increasing emergence of multiantibiotic-resistant pathogenic bacteria has rekindled the interest of the Western scientic community, industry, and the general public in this almost century-old approach — as documented by the number of new phage therapy-related publications in the Western peer-reviewed and popular literature and the formation of new biotechnology rms commercializing phage-based technology in the West. Detailed discussions of phage therapy for both human and agricultural applications can
be found in Kutter and Sulakvelidze,7 along with chapters on related technologies, such as the use by Vincent Fischetti, Dan Nelson, and co-workers of phage lysin to kill Streptococcus pneumoniae, which holds promise for application in accessible places such as nasal passages. Recent work also suggests potential for phage lysin use in at least some systemic infections and even in biolms.12
