Bacteriophage - Phage Therapy

Phage Therapy

Phages were discovered to be antibacterial agents and were used in the United States and Europe during the 1920s and 1930s for treating bacterial infections. They had widespread use, including treatment of soldiers in the Red Army. However, they were abandoned for general use in the West for several reasons:

• Medical trials were carried out, but a basic lack of understanding of phages made these invalid.

• Phage therapy was seen as untrustworthy, because many of the trials were conducted on totally unrelated diseases such as allergies and viral infections.

• Antibiotics were discovered and marketed widely. They were easier to make, store and to prescribe.

• Former Soviet research continued, but publications were mainly in Russian or Georgian languages, and were unavailable internationally for many years.

• Clinical trials evaluating the antibacterial efficacy of bacteriophage preparations were conducted without proper controls and were methodologically incomplete preventing the formulation of important conclusions

Their use has continued since the end of the Cold War in Georgia and elsewhere in Eastern Europe. Globalyz Biotech is an international joint venture that commercializes bacteriophage treatment and its various applications across the globe. The company has successfully used bacteriophages in administering Phage therapy to patients suffering from bacterial infections, including: Staphylococcus (including MRSA), Streptococcus, Pseudomonas, Salmonella, skin and soft tissue, gastrointestinal, respiratory, and orthopedic infections.

The first regulated randomized, double blind clinical trial was reported in the Journal of Wound Care in June 2009, which evaluated the safety and efficacy of a bacteriophage cocktail to treat infected venous leg ulcers in human patients. The study was approved by FDA as Phase I clinical trial. Study results satisfactorily demonstrated safety of therapeutic application of bacteriophages, however it did not show efficacy, which authors explain by the use of certain chemicals that are part of the standard wound care (e.g. lactoferrin, silver) that may have interfered with bacteriophages viability in the wound. Another regulated clinical trial in Western Europe (treatment of ear infections caused by Pseudomonas aeruginosa) was reported shortly after in the journal Clinical Otolaryngology in August 2009. The study concludes, that bacteriophage preparations were safe and effective for treatment of chronic ear infections in humans. Additionally, there have been numerous animal and other experimental clinical trials evaluating the efficacy of bacteriophages for various diseases, such as infected burns and wounds, and cystic fibrosis associated lung infections, among others. Meanwhile, Western scientists are developing engineered viruses to overcome antibiotic resistance, and engineering the phage genes responsible for coding enzymes which degrade the biofilm matrix, phage structural proteins and also enzymes responsible for lysis of bacterial cell wall.

Independently, French-Canadian microbiologist Félix d'Hérelle, working at the Pasteur Institute in Paris, announced on 3 September 1917, that he had discovered "an invisible, antagonistic microbe of the dysentery bacillus". For d’Hérelle, there was no question as to the nature of his discovery: "In a flash I had understood: what caused my clear spots was in fact an invisible microbe ... a virus parasitic on bacteria." D'Hérelle called the virus a bacteriophage or bacteria-eater (from the Greek phagein meaning to eat). He also recorded a dramatic account of a man suffering from dysentery who was restored to good health by the bacteriophages.

In 1923, the Eliava Institute was opened in Tbilisi, Georgia, to research this new science and put it into practice.

In 1969, Max Delbrück, Alfred Hershey and Salvador Luria were awarded the Nobel Prize in Physiology and Medicine for their discoveries of the replication of viruses and their genetic structure.