Phage therapy

Phage therapy or viral phage therapy is the therapeutic use of bacteriophages to treat pathogenic bacterial infections. Phage therapy has many potential applications in human medicine as well as dentistry, veterinary science, and agriculture. If the target host of a phage therapy treatment is not an animal, the term 'biocontrol' (as in phage-mediated biocontrol of bacteria) is usually employed, rather than 'phage therapy'. Phage therapy or viral phage therapy is the therapeutic use of bacteriophages to treat pathogenic bacterial infections. Phage therapy has many potential applications in human medicine as well as dentistry, veterinary science, and agriculture. If the target host of a phage therapy treatment is not an animal, the term 'biocontrol' (as in phage-mediated biocontrol of bacteria) is usually employed, rather than 'phage therapy'. Bacteriophages are much more specific than antibiotics. They are typically harmless not only to the host organism, but also to other beneficial bacteria, such as the gut flora, reducing the chances of opportunistic infections. They have a high therapeutic index, that is, phage therapy would be expected to give rise to few side effects. Because phages replicate in vivo (in cells of living organism), a smaller effective dose can be used. This specificity is also a disadvantage: a phage will kill a bacterium only if it matches the specific strain. Consequently, phage mixtures ('cocktails') are often used to improve the chances of success. Alternatively, samples taken from recovering patients sometimes contain appropriate phages that can be grown to cure other patients infected with the same strain. Phages tend to be more successful than antibiotics where there is a biofilm covered by a polysaccharide layer, which antibiotics typically cannot penetrate. In the West, no therapies are currently authorized for use on humans. Phages are currently being used therapeutically to treat bacterial infections that do not respond to conventional antibiotics, particularly in Russia and Georgia. There is also a phage therapy unit in Wrocław, Poland, established 2005, the only such centre in a European Union country. The discovery of bacteriophages was reported by the Englishman Frederick Twort in 1915 and the French-Canadian Felix d'Hérelle in 1917. D'Hérelle said that the phages always appeared in the stools of Shigella dysentery patients shortly before they began to recover. He 'quickly learned that bacteriophages are found wherever bacteria thrive: in sewers, in rivers that catch waste runoff from pipes, and in the stools of convalescent patients'. Phage therapy was immediately recognized by many to be a key way forward for the eradication of pathogenic bacterial infections. A Georgian, George Eliava, was making similar discoveries. He travelled to the Pasteur Institute in Paris where he met d'Hérelle, and in 1923 he founded the Eliava Institute in Tbilisi, Georgia, devoted to the development of phage therapy. Phage therapy is used in Russia, Georgia and Poland. In Russia, extensive research and development soon began in this field. In the United States during the 1940s commercialization of phage therapy was undertaken by Eli Lilly and Company. While knowledge was being accumulated regarding the biology of phages and how to use phage cocktails correctly, early uses of phage therapy were often unreliable. Since the early 20th century, research into the development of viable therapeutic antibiotics had also been underway, and by 1942 the antibiotic penicillin G had been successfully purified and saw use during the Second World War. The drug proved to be extraordinarily effective in the treatment of injured Allied soldiers whose wounds had become infected. By 1944, large-scale production of Penicillin had been made possible, and in 1945 it became publicly available in pharmacies. Due to the drug's success, it was marketed widely in the U.S. and Europe, leading Western scientists to mostly lose interest in further use and study of phage therapy for some time. Isolated from Western advances in antibiotic production in the 1940s, Russian scientists continued to develop already successful phage therapy to treat the wounds of soldiers in field hospitals. During World War II, the Soviet Union used bacteriophages to treat many soldiers infected with various bacterial diseases e.g. dysentery and gangrene. Russian researchers continued to develop and to refine their treatments and to publish their research and results. However, due to the scientific barriers of the Cold War, this knowledge was not translated and did not proliferate across the world. A summary of these publications was published in English in 2009 in 'A Literature Review of the Practical Application of Bacteriophage Research'.