As infections become harder to treat because of drug resistance, creating so-called superbugs, scientists are once again enlisting help from the oldest enemy of bacteria: viruses. Though researchers have used bacteriophages (Latin for “bacteria eaters”) to treat people for a century, these biological agents have been largely ignored in much of the world since antibiotics became available. That’s changing.
1. Where did bacteriophages come from?
“Phages” are among the most abundant living entities on Earth. The natural enemies of bacteria, these viruses have been hunting down, attacking and killing bacteria for hundreds of millions of years. They were discovered by scientists early last century and soon after fashioned into lotions, potions and pills to treat a variety of bacterial diseases by laboratories owned by companies including Eli Lilly & Co. and L’Oreal SA. Phage therapy has been used continuously in some former Soviet republics, such as Georgia, where it’s routinely offered as a treatment for everything from acne and bronchitis to cystic fibrosis and intestinal infections. It fell out of favor in the Western world in the 1930s and ’40s when penicillin and other antibiotics became a more reliable and easier-to-use alternative.
2. How do phage treatments work?
Specific phages are isolated -- often from raw sewage -- for their ability to target unwanted bacteria. Once the phage has latched onto a germ, it hijacks the organism’s cellular machinery to make more phages and to cause the host cell to explode in a cloud of new viral particles. These viral explosions spread exponentially throughout a bacterial colony, eventually destroying all the susceptible disease-causing cells.
3. Why is phage therapy of renewed interest?
An estimated 700,000 people die annually worldwide from antibiotic-resistant infections, and the number is projected to increase to 10 million by 2050. Resistance occurs when bacteria adapt to the drugs being used against them and change to ensure they survive. The need for alternative treatments is pushing doctors and scientists across the globe to investigate phage therapy. For instance, it’s being studied in Paris, Brussels and Lausanne, Switzerland, as a treatment for infections in burn patients. Researchers in Bordeaux, France, plan to test whether it can fight staphylococcal infections in diabetic foot ulcers. Some successful, well-publicized cases have heightened interest in phage therapy.
4. Like what?
Tom Patterson, an American HIV researcher who got sick while on vacation in Egypt in 2015, is a good example. He developed an infection in his pancreas that eventually poisoned his blood. At home in California, despite multiple antibiotic courses over four months, he was in a coma, suffering multiple organ failure. When he was close to death, his wife, Steffanie Strathdee, associate dean of global health sciences at the University of California, San Diego School of Medicine, urged his doctors to give him an experimental phage therapy produced with the help of Texas A&M University, the U.S. Navy and AmpliPhi Biosciences Corp. Within days, Patterson’s infection was halted and he woke from his coma. Months later, he returned to work.
5. What advantages do phages offer?
Phages are highly specific. They often target single strains or subtypes of bacteria without disturbing other germs, including those in the gastrointestinal tract that support digestion, vitamin production and the immune system. These “friendly bacteria” often become collateral damage with antibiotic use. Phages are even able to make bacteria sensitive to antibiotics to which they were previously resistant.
6. What are the minuses?
Because bacteria mutate to evade phage attack, multiple phages often need to be administered to overcome or slow the development of resistance. The preparation of such cocktails can be delayed by the need to identify the correct phages to use. Research shows that phage-bacteria interactions can be unpredictable and influenced by such things as concurrently taking antibiotics or eating soy sauce. Phages need to be propagated under controlled conditions and carefully purified to remove any toxins. And while they produce few or no side effects, there are concerns that there could be some dangerous consequences if quality-control procedures for phage selection aren’t established. For example, phages could carry antibiotic resistance genes and transfer them to bacteria infecting the body.
7. How effective is phage therapy?
The center in Tbilisi, Georgia, that’s treated the most patients with phage therapy over eight decades has reported success rates varying from 67 percent in patients with lung infections to 100 percent for bone infections. Researchers in other countries have found these results difficult to evaluate because often the data weren’t collected as part of randomized, controlled trials -- the gold standard for assessing medical treatments. While it’s reasonable to say that the phage therapy used on Tom Patterson saved his life, there’s insufficient clinical data for the treatment to be approved for routine use by regulators, such as the U.S. Food and Drug Administration and the European Medicines Agency.
8. What’s next?
Biotechnology companies making phage products and doctors and scientists researching them are working on or planning more than a dozen clinical trials in the U.S., Australia, France, Georgia and Italy to collect data on whether phages are effective and, if so, how best to apply them. The Phage Therapy Center in Tbilisi, Georgia, counts more than a dozen companies involved in phage research and development.
The Reference Shelf
- Watch Steffanie Strathdee’s TedXNashville talk about how sewage saved her husband’s life and a mini documentary prepared by UC San Diego Health.
- Listen to infectious diseases physician Robert ‘Chip’ Schooley discuss the Patterson case with the Journal of the American Medical Association.
- The Naval Medical Research Center and the University of California San Diego School of Medicine explain their phage research.
- The scientific journal Nature details why researchers are returning to phage therapy.
- Researcher Eric Keen chronicles the history of phage research.
- U.S. and Georgian scientists review past efforts and the future prospects for the use of phages in medicine.