Future Challenges

"Take Two Phage and Call Me in the Morning''

ore and more bacteria are becoming resistant to an ever greater number of antibiotics, and so the effectiveness of these medications has been greatly reduced. One novel approach to treating infectious diseases is to use phage to kill the disease-causing bacteria. This is not a new idea. Felix d'Herelle, the co-discoverer of phage, believed that they were mainly responsible for natural immunity. He also claimed that phages would be a universal prophylaxis and therapy. So convinced was he that while he was a Professor of Bacteriology at Yale, he also owned a commercial laboratory in Paris that produced preparations of phage that he sold to the pharmaceutical industry. After leaving Yale, he went to the Bacteriophage Research Institute in the USSR state of Georgia. Today, much of the work on the possible use of phage as therapeutic agents is being carried out in this same Institute.

Although in theory the use of phage sounds attractive, in practice many problems are associated with this technology. First, a specific phage will only infect a single species or only a specific strain of a given species. Since it would take too long to isolate the causative infectious bacterium and isolate a phage that could attack it, "cocktails" containing many different phages must be used. Thus, to treat intestinal diseases, a "cocktail" of 17 different phages that attack intestinal pathogens has been developed. To treat burns that may be subject to infection by Pseudomonas, a kind of bandage saturated with a cocktail of 5 to 9 different phages

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has been employed. Whether phages are present that will attack all of the bacteria responsible for the disease, however, is questionable.

Another concern is that great care must be taken in purifying the phage before the preparation is administered. When phages lyse bacteria, a great deal of debris from the lysed cells is mixed in with the phage. This material could be very dangerous if it got into the bloodstream.

A third problem that must be overcome is that phages are recognized as foreign by the body's immune system, and therefore they are quickly eliminated. Some success has been achieved in increasing the time the phages stick around by altering the phage coat.

The fourth hurdle that must be overcome is the need for in-depth animal testing and human trials. No clinical trials involving human patients have been carried out but studies from England have reported that mice, calves, and chickens could be protected from disease-causing strains ofE. coli. Enough statements of success have been made in the use of phage in Russia and countries in the former Soviet Union, that phages are now being seriously considered as therapeutic agents in Western countries. It is the only therapy that increases in amount as it successfully carries out its job.

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