Bacteriophage Therapy as a last resort in treating Antibiotic Resistant Bacteria

Deep behind the Iron Curtain, during the height of the Cold War, Soviet Scientists experimented on the patients of a children’s hospital by injecting them with a living virus.    

                But the pathogen was completely harmless, to human cells at least. It was a bacteriophage: deadly only to the bacteria that infected the children. During much of the Cold War, the Soviet Union didn’t have access to antibiotics. Though common place now, penicillin was a secret weapon for the United States in World War II. Reading accounts of battle field medicine will show how devastating infection of minor wounds could be. Antibiotics allowed for the rapid redeployment of troops that were wounded or ill.  Throughout the history of war more lives were lost to disease than any battle. Plague and disease were the dread of any army or navy. During World War II and the subsequent Cold War, the United States had antibiotics in her armory. But in the Soviet Union scientist had to be a little more creative.

                A Bacteriophage is a virus that infects bacteria. These viruses are specific pieces of machinery that recognizes surface molecules unique to the host organism. A virus that could utterly wipe out a population of bacteria would bounce hopelessly off the alien molecules of a human cell. Because of its specificity the Soviet Doctors sought to clear infection using bacteriophages as a targeted attack.

                Many of these experiments were carried out in children’s hospitals. Certainly, the ethics of experimenting on children are questionable. But the real sin of the researchers was poor experimental design and record keeping. They lacked control groups and precise protocol. Most of the accounts of bacteriophage therapy are anecdotal. But we shouldn’t neglect the potential of phage therapy. According to the Center for Disease Control, as of 2013, two million Americans were infected by antibiotic resistant bacteria, and 23,000 succumbed to these infections. I myself have worked in a hospital and seen first-hand the burden of these infections. Not only do patients suffer, but it is a massive cost to the hospitals to sustain proper protocol. Many biologists fear we are on the edge of a post antibiotic era. Life without antibiotics is just as terrifying a prospect as nuclear war or global warming. A slow death by consumption, a sure death from wound infection, a risk every surgery: these are the old faces of disease born again in antibiotic resistance.

                Many studies are now being conducted to look into the validity of phage therapy. Unlike the Cold War experiments these have good design and reliable data. An experiment conducted at the National Institute of Health in Maryland used mice to show the efficacy of phage therapy. Mice were infected with Vancomycin resistance Enterococcus Faecium. Vancomycin is the last resort when treating infections resistant to all other antibiotics. The mice were infected with the resistant E. Faecium and after different intervals of time were then administered the bacteriophage. Mice infected with E. Faecium that received the dosage of Bacteriophage 5 hours later all recovered back to normal health. Of mice given the phage dosage after 18 hours 60% survived, after 24 hours 40% survived. In the 24-hour group all of the mice seemed bound for death, but those that did survive managed to recover completely after only one dosage of bacteriophage.  The mice that received no dosage all succumbed to the E. Faecium infection.

This experiment highlights the effective potential of phage therapy. But treating a disease in human patients is an order of magnitude more complicated than treating it in mice. There are many other barriers as well to effective phage treatment. The specificity of the virus that keeps it from infecting the patient also makes it a very specific cure. Just because a phage is effective against E. Faecium doesn’t mean it will have any effect on Staphylococcus Aureus or Clostridium Difficile infections. Different strains would need their own specific bacteriophage. Viruses are not easy to culture and grow, they require a large sample of the host cell, and a great deal of expense goes into their manufacture and storage. The bacteriophage also might be cleared by our immune system. The virus might not be specific to human cells, but our immune system will attack it regardless. However, since many patients with antibiotic resistant infections are immunocompromised the virus might have a better chance of hitting its target. 

These hurdles should not prevent us from further investigating the usefulness of phage therapy. Even if it is only used as a last resort, it could still be of tremendous benefit to patients who have exhausted all other options. The only way we can know if bacteriophage therapy will be a useful treatment for dire antibiotic infection is to further study it. The desperation of the Soviet Scientists during the Cold War may have given us a helpful tool in the fight against antibiotic resistance. Maybe with bacteriophage therapy as a weapon we can give infectious bacteria a dose of their own medicine.

References:

Chanishvili, N. Phage Therarpy: History from Twort and d’Herelle Through Soviet Experience to Current Approaches. Bacteriophages, Laboratory for Genetics of Microorganisms and Bacteriophages, Eliava Institute of Bacteriophage, Microbiology & Virology, Tbilisi, GA, USA.  2012

U.S. department of Health and Human Services, Antibiotic Resistance Threats in the United States, Center for Disease Control and Prevention

Biswas, B., Bacteriophage Therapy Rescues Mice Bacteremic from a Clinical Isolate of Vancomycin-Resistant Enterococcus faecium, Infection and Immunity, 2002