Excerpted from The Forgotten Cure: The Past and Future of Phage Therapy, by Anna Kuchment. (Copernicus Books, 2011. Reprinted by permission of Springer Science+Business Media)

In April 2002, Fred Bledsoe was doing construction work on his parents' lake house near Fort Wayne, Indiana, when he stepped on a rusty nail that bore through his shoe and lodged in the sole of his foot. Bledsoe cleaned up the wound and drove to a nearby hospital where doctors gave him a tetanus shot. Case closed, he thought.

One week later, his foot swelled up, and the wound began oozing pus. Bledsoe, a burly, quiet man with a graying goatee, was a one-time factory worker out on disability leave and battling diabetes. He decided to pay an office visit to his brother, Larry, a general practitioner, who prescribed a 10-day course of antibiotics. That seemed to do the trick; Fred felt much better. But in August, the infection came back with a vengeance. His foot tripled in size—"it looked like a football," said his sister, Saharra—and a new infection site appeared at the base of his big toe. He couldn't wear normal shoes, much less walk. Larry had his brother hospitalized, and doctors started him on a heavy course of IV antibiotics. They also implanted Gentamicin, an antibiotic that looks like a small string of pearls, near Bledsoe's big toe so that a high concentration of medicine could be delivered directly to the site of the infection. But diabetes had damaged the circulation in Bledsoe's foot, making it more difficult for the antibiotics to penetrate deeply enough and for his body's own white blood cells to help beat back the invading organisms. Though the wound seemed to improve on the surface, the bacteria had taken up residence near the bone, where the Gentamicin could no longer reach them. Nine weeks later, Bledsoe's physicians gave up. "My doctor told me I'd have a good quality of life without my toes," he says.

A short time later Bledsoe's sister, Saharra, caught an episode of the CBS news program "48 Hours." An episode called "Silent Killers" discussed the increasing incidence of antibiotic-resistant infections. After reporting on two scary cases—a woman whose paper cut turned into a blood infection, an 18 month old girl who nearly died from an ear infection—the story turned to a case that was eerily similar to Fred's. Alfred Gertler, a jazz musician from Toronto, Canada, had developed an infection in his ankle after fracturing it while hiking in Costa Rica. As with Fred, doctors had advised him to have his foot amputated.

Gertler refused to listen to his physicians. Desperate for an alternative, he had scoured the medical literature until he came upon a magazine article describing a treatment called "bacteriophage therapy." Practiced in the United States until the 1940s and still used in parts of Eastern Europe, it pits tiny viruses—bacteriophages, or phages for short—against disease-causing bacteria. These viruses, the most ubiquitous organisms on earth, are bacterial parasites: they reproduce by attacking and destroying deadly germs.

The world's oldest institute dedicated to the study and practice of phage therapy is in Tbilisi, the capital of the former Soviet Republic of Georgia. Unable to find a cure in the state-of-the-art hospitals of Canada, Gertler bought himself a plane ticket to the Third World. There, doctors infused his wound with an amber-colored broth teeming with the invisible creatures. After three days of treatment, he reported, his infection was gone. Though it recurred later, after he returned to Canada, it was in a mild enough form that doctors could finally fuse together his anklebones.

10 Comments

1. 1. AllanRBrewer 11:59 AM 8/31/12

   "Meat and seafood companies are spraying the viruses on their equipment to protect consumers from foodborne illness."
   
   That's exactly the sort of overuse/misuse which has led to so much antibiotic resistance - those bacteria which are susceptible to that specific phage mix will perish and leave the food for other bacteria which are not susceptible to that specific phage mix.

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2. 2. Acoyauh2 01:39 PM 8/31/12

   Speaking of overuse/misuse: Can you say "I Am Legend"? Let's keep playing with bugs...
   

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3. 3. Laroquod 06:06 PM 8/31/12

   Alarmists aside, Phages are inherently a superior solution to antibiotics because they are at least theoretically capable of co-evolving in order to counter the increased resistance of their target bacteria. Whereas antibiotics require billions of dollars of funding and a monolithic industry in order to keep up with the arms race between humans and little critters, phages could conceivably keep up essentially for free -- provided the scientists are paying attention.

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4. 4. Acoyauh2 in reply to Laroquod 07:24 PM 8/31/12

   I agree with you, and even can see other advantages. What really worries me, though, is that we won't resist the itch to 'improve' the viruses and/or change them for use in other areas. Once we find a good idea, we do tend to abuse it - push it until some damage is done, somewhere. And even then, if it's already a good enough business, not back up again. Plenty of examples in today's world, right? Plastic? Fishing? Oil and coal? Antibiotics!
   
   Great idea alright, but a bit scary if you think beyond what it CAN do, and into what we USUALLY do...

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5. 5. bottom quark in reply to AllanRBrewer 10:50 PM 8/31/12

   The alarm is unwarranted. Currently there are no known bacterium that are resistant to phage viruses. I use "currently" loosely to all but eliminate all future instances of phage resistant bacterium. I am afraid to say it will never happen, in the same way most people say cold fusion will never happen.

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6. 6. AllanRBrewer 07:18 AM 9/1/12

   You misunderstand my point and resistance. Phages are extremely specific to which bacterial strains they will infect, so if a phage mix is overused as in the example, although the target bacteria will be wiped out, it simply opens the door for other bacteria, not targeted by the phage to take over that niche. If you want to look at it as developing resistance, OK, it only takes a few mutations to turn one bacterial strain into another which would not be targeted by the same phage.

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7. 7. Phathisani 02:26 PM 9/5/12

   AllanRBrewer is spot on. The phages are specific, but are not perfect killers. Sometimes the DNA packets are transferred to a bacterium which then gives the resulting bacteria new facets. The VTEC E.coli seem to be an example. Let us use viruses, but also learn from the antibiotic lessons and also bear in mind that the use on animals has implications for humans. We need a scientifically based approvals system for proper use by the proper people. Now is the time to do something, not when the first problems appear. Phages offer a great opportunity; don't let us waste it.

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8. 8. Safety-by-Nature 07:31 PM 9/5/12

   A couple of points worth mentioning: 1. The battle between bacteria and phage has been going on for the last 3 ½ billion years, without any know diminishment of bacteria or phage. Yes, they do co-evolve. 2. The idea that phage treatment on food will actually eliminate a serotype is fanciful. A serotype could develop resistant, but since food producers constantly monitor production for pathogens, efficacy is restored by swapping out one or more monophages in the cocktail. Regulatory approval of the FDA’s first phage-based food additive, ListShield™, specifically permits replacing monophages to sustain efficacy. I should note that since ListShield’s production began in 2006, not one case of resistance has been reported by its users. 3. We ingest phages all the time. Every fresh salad, glass of spring water, of food exposed for any appreciable amount of time contains or is covered by phage. Unfortunately, they are randomly specific and usually cannot ward off an attack by food borne pathogens. 4. Transferring DNA packets only apply to lysogenic phages, which will not be approved by regulatory authorities. Food safety phages are composed of lytic phages. 5. Finally, rather than chemical sanitizers, phages are safe and natural. Products in use today are kosher, halal and OMRI (Organic Materials Research Institute) listed and they substantially reduce the use of water in food processing facilities.

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9. 9. roleednc in reply to AllanRBrewer 07:23 PM 3/24/13

   Good points about overuse. Thoughtless and indiscriminate use of anything is not wise. One possible counter to that argument is that "excessive" use can create new phages that are deadly to the new bacteria. We shall see. I think our best best is balance and moderation in whatever course we take, including our own relationship with our personal biota.

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10. 10. FanOPhage 06:57 PM 5/5/13

    The only comment here that seems to come from someone who knows more about phages that only what's written in this article is the one from Safety-by-Nature.

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