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The first report about what we now recognize as bacteriophage was published more than a century ago. In 1896, Hankin reported that something in the waters of the Ganges and Jumna rivers in India had marked antibacterial action and could pass through a very fine porcelain filter. However, it was another 20 years before a British bacteriologist, Frederick Twort, actually isolated filterable entities capable of destroying bacterial cultures and producing small cleared areas on bacterial lawns (1915). Twort did not further explore his finding. Two years after Twort's discovery, Felix d’Herelle, a French Canadian microbiologist working at the Pasteur Institute in Paris, reported the same phenomenon. For d’Herelle, 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'Herelle called the virus bacteriophage or bacteria-eater (from the Greek phago meaning to eat). Therapeutic use of phages in clinical settings In the period after his discovery, D’Herelle
promoted the use of phages as therapeutic agents for the treatment of
infectious diseases. The first reported application of phages to
treat infectious diseases of humans came from Bruynoghe and Maisin in
France in 1921, who used bacteriophages to treat staphylococcal skin
disease. Phages have been used, since that time, for prophylaxis
and therapy in the United States (early 1930s) and, for the last five
decades, in eastern Europe and in the Soviet Union. Therapeutic use of phages in animals One of the most detailed reports (in the English literature) of the use of phages in veterinary medicine comes from H. W. Smith and R. B. Huggins in Great Britain. In one of their early papers published in the Journal of General Microbiology, the authors reported the successful treatment of experimental E. coli infections in mice using phages, and noted the general superiority of phages over antibiotics. In subsequent studies, the authors demonstrated that a single dose of specific E. coli phage was sufficient to reduce, by many orders of magnitude, the number of target bacteria in the alimentary tract of calves, lambs and piglets infected with a diarrheagenic E. coli strain, and to stop the associated fluid loss; all animals treated with phage survived the infection. The authors also showed that diarrhea could be prevented in calves by simply spraying the litter in the calf rooms with an aqueous phage suspension, or by keeping the calves in uncleaned rooms previously occupied by calves whose E. coli infections had been treated with phage. Another group of investigators in England performed several experiments in which they demonstrated the utility of phages in preventing/treating experimental infections with P. aeruginosa and Acinetobacter in mice and guinea pigs. The ability of Salmonella and E. coli phages to reduce colonization in/prevent death of experimentally-infected chickens also has been described. During the long history of using phages as
therapeutic agents throughout eastern Europe and the former Soviet Union
(and, before the antibiotic era, in the United States), there have been
virtually no reports of serious complications associated with their use.
In the United States, phages have been used safely for monitoring humoral
immune function in adenosine deaminase-deficient patients, and for
analyzing the importance of cell surface-associated molecules in
modulating the immune response in humans. In the later study, the
phage was injected intravenously into healthy volunteers, without apparent
side effects. "For well over half
a century, the most active center of research on phages as antibiotics
was the G. Eliava Institute of Bacteriophage, Microbiology, and
Virology, part of Georgian Academy of Sciences, Tbilisi, in the
former Soviet republic of Georgia." The historical background of the institute is
interesting. George Eliava (after whom the institute is currently
named), observed the bactericidal action of the water of the Mtkvari (Kura)
river in Tbilisi in the 1910s. However, he could not explain this
phenomenon until d’Herelle’s work on phages was published.
Eliava spent 1920-1921 at the Pasteur Institute where he became
acquainted with, and became a personal friend of, Felix d’Herelle.
The two friends had a dream to establish a phage research center in
Tbilisi. This dream, however, remained unfulfilled for over a
decade, until d’Herelle visited Georgia and he and Eliava went forward
with their idea. The long-dreamed-of institute soon became a
reality because of the strong support of Sergo Orjonikidze, the
People’s Commissar (read: minister) of Heavy Industry in Stalin’s
government. The Bacteriophage Institute was established in Tbilisi
in 1923, and a large campus on the Mtkvari river soon was Currently, the
Bacteriophage institute is a part of the Georgian |
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allocated for
its expansion. D’Herelle spent several months in Tbilisi
collaborating with Eliava and other Georgian colleagues (photo above), and intended to move to Tbilisi permanently
(a cottage built for his use still stands on the Institute’s grounds;
photo below, right). However, in 1937, Eliava was arrested by
“Cheka” (the predecessor of the KGB), pronounced a “People’s
Enemy,” and executed. Frustrated and disillusioned,
D’Herelle
never returned to Georgia. However, the Institute survived and
soon became a leader in developing therapeutic phage preparations in
Eastern Europe, and possibly in the world.