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Back to the Future

While most of the attention and competition is focused on creating new antibiotics and rescuing those now on the market, a few researchers advocate returning to the anti-infection remedies used before the introduction of antibiotics in the 1940s. One such treatment is bacteriophage. Commonly known as phage, this is a virus that grows in bacteria until it finally pops out and kills its host.

Phage treatments used in the ’20s and ’30s often failed.

At the time scientists didn’t understand that each kind of phage is highly specific; only one type will attack a particular species-and even strain-of bacteria. Re-ports of the treatment in journals were lacking in controls and filled with anecdotes, and many scientists looking at the studies today say they are not professionally acceptable.

But Carl R. Merril, chief of the Laboratory of Biochemical Genetics at the National Institute of Mental Health, is enthusiastic about the potential for using phage therapy to treat serious infectious diseases in humans. Merril, who reported in the April 1996 Proceedings of the National Academy of Sciences (PNAS) that he had successfully used phage therapy in mice, says several procedures must be followed for phage treatments in people to be successful. First, the bacterium causing the infection must be cultured to determine the exact type and strain. Next, the strain has to be tested against different phage to find the one phage specific to that strain. Then a mutant phage must be grown in a manner that ensures that the patient’s body will not see the virus as foreign and remove it. Finally the phage needs to be purified to eliminate any toxic bacterial fragments left after bursting free of its bacterial host. Merril says he has found that spinning phage in a centrifuge separates out bacterial particles.

Merril is collaborating with Exponential Biotherapies, a start-up biotech firm in New York, to develop phage therapies for use in people with major infectious diseases. Richard Carlton, a psychiatrist, founded the firm after meeting Merril and becoming impressed with his work. Carlton says that the first therapy the company hopes to market aims to kill a strain of vancomycin-resistant enterococcus called VREf, which causes skin, bloodstream, wound, and heart-valve infections.

At least one other American company reports that it is pursuing phage treatments. Formed in the fall of 1996, Phage Therapeutics is trying first to develop a treatment against resistant Staphylococcus aureus, according to Richard Honour, a microbiologist and the company’s president and chief executive officer.

Because of the lack of rigorous scientific proof that phage treatment works against infectious diseases, the companies hoping to market it in the United States have taken on a big selling job.

Last November, Elizabeth Kutter, a biophysics professor, visited the Eliava Institute of Bacteriophage, Microbiology, and Virology in Tbilisi in the Republic of Georgia, where phage therapy is heavily used. She says the institute’s clinicians most often administer phage treatment topically to treat wounds and burns, or orally for intestinal disorders and some other infections. “What I’ve seen is enough good data to make me think it’s definitely worth further exploration,” says Kutter, of Evergreen State College in Olympia, Wash.

Honour, whose company has a relationship with the Eliava Institute, says the work of researchers and doctors in Tbilisi and other parts of eastern Europe is not readily transferable to the United States. “They’ve saved thousands of lives, but you could never take those products or techniques and submit them to Western regulators,” he says. When a treatment “works, it works well, but when it doesn’t work, they don’t know why.”

Other Western experts are even more skeptical. Bruce Levin, a population and evolutionary biologist at Emory University who has conducted some successful animal experiments with phage therapy, says its main drawback for human use is its specificity. Identifying the particular species and strain of an infecting bacterium before treating patients could be a problem, he suggests. Also, he says, researchers have not yet proven that phage treatment works throughout the body. But despite his skepticism, Levin says that given the potential crisis antibiotic-resistant bacteria could cause, researchers should examine phage therapy in light of modern scientific knowledge.

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Tagged: Biomedicine

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