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Pathogens & People: Bacteriophage: The invisiblemicrobe
By EDWARD McSWEEGAN, For The CapitalPublished 07/05/09
If antibiotics disappeared tomorrow, would we be at the mercy ofevery stray germ? Would every cut and scratch be a potential deathsentence? Would life become little more than survival of theimmunologically fittest? No, but life would be different, and perhapsmore complicated.
 
Decades before Alexander Fleming picked up a mold-speckled Petridish and discovered penicillin, other scientists had discovered amysterious entity that also could kill bacteria. In 1896, a man namedHankin found that filtered, bacteria-free river water would kill Vibriocholerae, the agent of cholera. Two years later, another physiciannamed Gamaleya discovered a similar filtered water sample thatwould kill Bacillus subtilis, a cousin of the anthrax bacillus. It wasn'tuntil 1917 that a French-Canadian microbiologist named Felixd'Herelle systemically studied this bacteria-killing phenomenon andput it to good use.D'Herelle thought the mysterious bacteria killer was a virus: an"invisible microbe" too small to be seen with the microscopes of theday. He couldn't see these "bacteria eaters" or bacteriophage, but hecould grow them, study them, store them and test them. He thought ifthey could kill bacteria in a test tube, maybe they could kill bacteria inanimals and people.He was right, of course. His bacteriophages were viruses. Many of
 
them look like a cross between a lunar lander and a long-neckedspider. Yet, they act more like syringes; injecting their DNA into abacteria cell in order to take over the cell's genetic machinery andmass-produce more copies of themselves. The newly made viruseseventually burst the cell to escape into the environment in search ofmore hosts.D'Herelle's first test subjects were chickens infected with a salmonellaspecies that caused typhoid, and rabbits infected with a shigellaspecies that caused dysentery. D'Herelle gave his test animalsinjections or oral doses of his phages and then infected them withbacteria. Most of the recipients of the phage therapy lived. He hadsimilar results treating a highly fatal bloodstream infection in waterbuffalo. It seemed all he had to do was find a particular phage thatwould lyse or break open a particular bacterial pathogen, and give itto the infected animal.He needed some human subjects to be sure. After drinking andinjecting various phage preparations - and asking friends and familymembers to do the same - he decided the phages were safe forhuman use.In Alexandria, Egypt, he got a chance to test some anti-plaguepreparations on four people with bubonic plague. All four lived. Thatcaught the attention of the medical world, and d'Herelle was invited toIndia to try phage therapy on cholera patients. It seemed to workthere too. (Fifty years later in Pakistan, a study of phages versustetracycline antibiotics showed the two treatments to be about equalagainst cholera.)D'Herelle's work with plague in Egypt would later become one of thesubplots in Sinclair Lewis' Pulitzer Prize-winning novel "Arrowsmith."
 
Yet even as phage therapy was making its way into hospital wards,pharmaceutical companies and the popular culture, it was about to besidelined by two unexpected discoveries. The first was a simpleantibacterial chemical called sulfanilamide discovered in the 1930s.The second was the discovery and mass production of penicillin inthe 1940s. Unlike the finicky, bacteria-specific phages, penicillin andsulfanilamide were two "generic" drugs that could kill a wide variety ofbacteria. Other such "broad-spectrum" antibiotics were discoveredand commercialized in the '50s and '60s. It was the end of d'Herelle,Arrowsmith and phagotherapy in the West.But not in the East. In an obscure corner of the Caucasus, in Tbilisi,Georgia, d'Herelle's work lived on. The George Eliava Institute ofBacteriophage, Microbiology and Virology has been producingphages and treating patients for decades. In 2005, the institutecreated the Phage Therapy Center to commercialize its phagetherapies, and recently merged with the American company PhageInternational.After a long absence, phages may be creeping back into the U.S. In2006, USA Today carried a story titled, "U.S. needs to open eyes to'phage therapy.' " Maybe we have. Evergreen State College inWashington is holding its 18th biennial International Phage Biologymeeting. Other American researchers are studying ways to reducebacterial contamination of beef and poultry products with phages.Intralytix Inc. in Baltimore is developing commercial phage productsfor use in food safety, environmental clean-up, and the treatment ofantibiotic-resistant infections.D'Herelle would be pleased to know his invisible microbes continue tointrigue scientists and save patients.
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