Are Phage Viruses the Forgotten Cure for Superbugs? [Excerpt]

A new book follows a crop of biotech start-ups as they race to turn tiny bacteriophage viruses into a new weapon against antibiotic resistance















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Unlike antibiotics, bacteriophages make more of themselves as they work, eventually outnumbering and eradicating the bacteria they are sent to destroy. But, while antibiotics are effective against a wide variety of bacteria, each phage is specific, meaning that microbiologists must spend days and sometimes weeks in the lab identifying the bacteria in a patient's tissue sample and finding a phage that will eradicate it. 

The diagnostic center at the Eliava Institute determined that Fred's infection was caused by two types of bacteria, Pseudomonas aeruginosa and Staphylococcus aureus, and Alavidze and her coworkers set to work. They grew up bacteria from Fred's wound in a series of petri dishes, each containing two cloudy stripes of a single germ. Alavidze keeps her pseudomonas phages, of which she has around 20, in small glass bottles capped with eye droppers. A coworker of hers placed one drop of the first phage on the left side of one of the pseudomonas stripes. The next phage she dripped over the opposite end of the stripe, and so on. Each bacterial stripe got two different phages, four per plate. Then, she put the plates in an incubator for 18 hours, to allow the phages to reproduce and do their job. The next morning, they read the results.

Some phages did not work at all. In these areas, the stripe was as cloudy and opaque as it had been the day before. Others had left patchy circles—small areas where some of the bacteria had been eaten away. Only one phage had worked perfectly: where Nino had dripped it, it had eaten away a clear circle where the foggy bacterial growth had been. This is the one they would use for Fred. They performed a similar experiment on Fred's strain of staph bacteria, and then mixed, multiplied, sterilized their phage solution and poured it into a set of small glass vials that were sealed shut over a Bunsen burner. The process took 10 days.

In the meantime, the Bledsoes were getting to know their neighbors at the hospital. In a room across the hall from them lived a family of refugees from Abkhazia, one of Georgia's two breakaway provinces. The two simmering conflicts had uprooted 10 percent of the country's population, and there was not enough housing for all of them. The hospital had given the family a room where they installed a makeshift kitchen and made themselves at home. They frequently invited Fred and Saharra across the hall for lunch and dinner. The matriarch of the family had a small loom on which she wove handicrafts to sell on the streets. She made Fred and Saharra each a pair of socks and a small tapestry with an illustration of Georgia woven into it.

When Fred's phage preparation was ready, doctors doused his foot with it. Three times a day, a nurse would come, take two glass vials of phage out of a cardboard box, cut the tip of the vial off with a razor blade, transfer its contents into a syringe and squeeze it over Fred's toe. Physicians also put him on a low-sugar, low-fat diet and administered electrical stimulation to improve the circulation in his leg. After 30 days, his wound healed—and he had lost 19 pounds on his diet. What was once a gaping hole that would not close had become a large but benign callus. Fred had arrived on crutches and left on his feet.
***
Bledsoe's case exposes deadly gaps in one of the world's most advanced medical systems. After penicillin was first mass-produced in the mid-1940s, wealthy nations enjoyed decades of relative peace of mind when it came to infectious diseases. Pharmaceutical companies pumped a steady stream of antibiotics into the marketplace, drugs that tamed once-fatal diseases like pneumonia and strep throat. But, as patents have expired and germs seem to have been bowed into submission, that once fertile pipeline has dried up. Major drug companies have turned their attention toward newer, more profitable areas, like the diseases of aging:  hypertension, heart disease, and diabetes. Patients take these drugs for life, while a typical course of antibiotics lasts a few days.



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  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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