Phages are highly specific, naturally occurring agents that invade bacteria and destroy them
Phages attach to their targets through specific sites (receptors) on the bacterial surface and inject their DNA (genetic material) into the bacteria. The phage DNA redirects the bacterial cell's biosynthetic machinery to produce hundreds of new phages in a short time (30 – 60 Minutes). The new progeny phages are released by breaking down the bacterial cell wall and invade other susceptible bacteria in the vicinity and the process is repeated until all the bacteria are eliminated.
Phages can be developed to eradicate any bacterial infection since they specifically target only bacteria. They cannot be used to treat viral infections.
There are two classes of phages - lytic and lysogenic; only lytic phages are useful as therapeutic agents. GangaGen products are all lytic phages. Phages are generally found in nature wherever bacteria are present. They have co-evolved with bacteria over the last 3.5 billion years.
Therapeutic phages have been used extensively in Eastern Europe and the former Soviet Union since the nineteen thirties without significant side effects. Minor side effects such as liver pain are attributed to the therapeutic process of killing bacteria and antibiotics elicit the same side effects also.
The first observation of phage was made in India in1896 when E. Hankin demonstrated that the waters of the Indian rivers Ganga(Ganges) and Yamuna (Jumna) contained a biological principle( that could pass through filters capable of retaining bacteria), which destroyed cultures of cholera bacteria. Twenty years later Frederick Twort in England, and Felix d'Herelle from Canada, working at the Pasteur Institute in Paris, reported isolating similar filterable entities capable of destroying bacterial cultures. It was d'Herelle who named these ultra microbes, "bacteriophages" (bacteria eaters) and pioneered the use of phages for treating Shigella dysentery in rural France. His success stimulated the commercial production of phages for treating a variety of bacterial infections both in Europe and the United States in the 1920's and 1930's.
Yes. Felix d'Herelle came to India in 1927 and demonstrated the efficacy of anti-cholera phage in reducing the mortality rate in Punjab from 63% in the untreated group to 8% for the phage-treated group. Encouraged by these results, Morison, Director of the King Edward VII Pasteur Institute in Assam, tried phage therapy with impressive success. Whereas 300 to 500 people died during the cholera epidemics in 1925 - 1928, following the use of phage in 1929, the death rates fell to less than ten per year in the period 1930 - 1935, the duration of the study(Transactions of the Royal Society of Tropical Medicine & Hygiene, Volume 28, pp 563 -570, 1935).
Yes. Whereas Felix d'Herelle was highly successful in treating dysentery in rural France and cholera in India, other early attempts to treat infections with phage gave mixed results. A review of phage therapy commissioned by the Council on Pharmacy and Chemistry of the American Medical Association concluded in 1934 that the "evidence for the therapeutic value of lytic filtrates is for the most part contradictory" (Eaton,M.D. and Stanhope, B-J, Journal of the American Medical Association, Volume 103, pp. 1769 - 1776; 1847 - 1853;1934 - 1939). The use of the phrase "lytic filtrates" in place of phage reflects the Commission's bias that the nature of phage was not yet known. This assessment had adverse effects on further exploration of phage therapy in the United States and the advent of antibiotics later in that decade effectively stopped the development of phage therapy except in the former Soviet Union and Eastern Europe.
The major problem was the poor understanding of the nature, heterogeneity and specificity of both phages and their bacterial hosts. Lack of proper diagnosis of the pathogen responsible for the infection and using the appropriate phage for the specific pathogen(s), led to the controversies referred to in section 8. D'Herelle himself avoided these pitfalls by isolating phages from naturally recovering patients and used these stocks to generate phages for the treatment of a large number of patients in the area of the epidemic. This strategy enabled him to use the appropriate phage even in the absence of proper diagnosis. Unfortunately, other practitioners of phage therapy did not use d'Herelle's strategy. Furthermore, the lack of quality control led to the use of ineffective phage prepared by inappropriate methods, preservatives, and storage procedures. Other factors were the use of single phages in infections caused by more than one bacterial pathogen and the failure to neutralize gastric acidity prior to oral phage administration.
Phages are highly specific. Phages against cholera or dysentery causing bacteria will target and eliminate only those pathogens and will not harm the beneficial bacteria normally present in the intestines. Antibiotics, in general, attack both the pathogen as well as the "good" bacteria in the gut and this bacterial imbalance leads to secondary infections involving resistant bacteria.
Phages will destroy antibiotic-resistant bacteria that are threatening the health of large populations both inside and outside the hospital.
Phages are self-replicating and self-limiting. Phages multiply as long as the sensitive bacterial host is around and are eliminated once the sensitive bacteria are destroyed. Antibiotics have to be administered repeatedly, over many days.
Yes. However, new phages active against the resistant bacteria can be isolated and developed very quickly at a modest cost. Development of new antibiotics takes years and is very expensive. There are no reports of resistance development in the areas where phages have been used in the past
No. Phages have great potential in controlling and eliminating bacterial pathogens in the environment, animals, and plants. Phages provide an eco-friendly approach for hospital and workplace hygiene(e.g. in food processing), as well as in control of harmful bacteria like E.coli, Listeria and Salmonella, which cause periodic outbreaks of food poisoning around the world. Leaf blight and other plant diseases caused by bacteria can also be controlled with phage.
Foreseeing a critical need and a strong market for the treatment of infectious disease in September of 2000, Dr. J Ramachandran brought together an experienced and committed team of professionals in a state-of-the-art laboratory to work on bacteriophages as a therapy for bacterial infections. Thus were sown the first seeds towards the creation of GangaGen Inc.