Sunday, March 1, 2009

Phage Therapy Pt. 1

Phage therapy, the method of treating infection by Bacteriophage (bacteria eating virus) has been around since the beginning of the 20th century. In 1896, Ernest Hanbury Hankin found that the waters of the river Ganges had some mysterious healing power upon the causative agent of cholera, Vibrio cholerae. Bacteriophage are known to inhabit sewer waters frequently so it is thought that this must have been the origin of the anti-cholera effect. Further progress was made when Frederick W. Twort noted the existence of "ultramicroscopic viruses" that could kill bacteria in solution. However, the credit for the discovery of phage and their potential for treatments is given to Felix d'Herelle, a Canadian scientist who, while working at the Pasteur Institute, applied the phage to the treatment of dysentery by isolating the dysentery pathogen and inoculating it with bacteriophage. The result was profound. Bacteriophage were naturally occurring elements that could kill bacteria.

A Georgian scientist, George Eliava, showed great interest in d'Herelle's work and in 1926 invited d'Herelle to his laboratory in Tbilisi. By the mid-1930s, d'Herelle agreed and began further work with bacteriophage in Georgia. The work of d'Herelle gained Stalin's attention which afforded d'Herelle a great amount of support for his work in the years to come. The 1925 publication of Arrowsmith by Sinclair Lewis, a novel about a scientist/physician had further proliferated the methods of phage therapy in its passages on an outbreak of the bubonic plague in the West Indies. The notoriety of phage therapy grew in spite of inconsistent trials. Pharmaceutical companies began investing, most notably Eli Lilly. However, back in Georgia, the ties with Stalin were less fortuitous for d'Herelle's partner George Eliava as he fell in love with the same woman Lavrenti Beria, head of the NKVD (Soviet secret police) had. This was a death sentence for Eliava. After Eliava was shot, d'Herelle left Georgia and never returned.

After a brief honeymoon of investment and promise, 1928 would be the year marking the downfall of phage therapy. While the accidental discovery of penicillin did not reach public markets until 1940 when Ernst Chain, Norman Heatley and Howard Florey were able to isolate, concentrate and produce the antibiotic for further testing. The reliable success of penicillin (especially its use in World War II) and later streptomycin by Albert Schatz pushed phage therapy to the side while antibiotics enjoyed integration into clinical practices around the world.

In reality science and medicine were not ready for phage therapy in the early twentieth- century. Knowledge of bacteriophage was not nearly advanced enough until molecular biology arrived in the late 1940s. The "Phage Group" founded in 1940 by Max Delbruck was a network of scientists dedicated to studying bacterial genetics. Delbruck was originally a member of the T.H. Morgan Caltech fly lab but decided to study bacteriophage instead of Drosophila. The Phage Group marks the return of bacteriophage study and its new connections with molecular biology. The Hershey-Chase experiment of 1944 that earned its leaders a Nobel Prize and suggested that DNA was the central hereditary material of living organisms, was facilitated by bacteriophage study.
Although bacteriophage were used in many important biological experiments, their medical importance was overlooked until the 1970s. Until then, the mechanisms of phage therapy and its inherent inconsistency were unknown.


to be continued...

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