Among researchers, 2015 is known as the year of the phage. It marks the 100th anniversary of the discovery of bacteriophage. Bacteriophage are viruses that infect bacteria and look, for the most part, like variations of video game space invaders or real life lunar modules.
The Evergreen International Phage Meeting held at the Evergreen State College in Olympia, Washington, has been a go-to event for phage researchers for the past 40 years. Every other year, researchers from around the world gather to present work in phage ecology, phage-based biotech, agricultural and environmental applications, phage therapy, and phage-host interactions. In August 2015, I attended Evergreen to celebrate 100 years of phage.
Phage research has been incredibly significant over the past 10 decades, but phage have been around much longer than that—much, much longer, in fact. Phage have likely been around since the beginning of life on Earth some 3.8 billion years ago.
Phage in the Ecosystem
Phage play a critical role in ecology. They are nearly ubiquitous, extremely diverse, and prolific, with an estimated 1031 in the biosphere. Following infection, lytic phage burst open bacteria, releasing into the ecosystem nutrients and biological components (including carbon and nitrogen). This activity is most prominent in the oceans where phage density on average is an astonishing 107 phages per milliliter, outnumbering bacteria and archaea by a ratio of at least 10 to 1. Phage activity critically contributes to the biogeochemical cycle and to an ecosystem that can support life on Earth.
Bacteria are absurdly copious multipliers that adapt relatively quickly to environmental changes. Adaptation occurs primarily through horizontal gene transfer, conjugation, and phage mediated transduction, and less frequently through accrual of simple point mutations. Phage help maintain microbial diversity and balance within Earth’s biosphere. Phage are thought to turn over 20–50 percent of the biomass in Earth’s oceans daily! In the absence of these microbial predators it is hard to imagine how our planet would ever sustain life beyond mere microbes. The planet would be covered with microbial competition specialists, sequestering all of Earth’s resources necessary for advanced life. If not for bacterial predation via phage, bacteria would certainly dominate life to the exclusion of advanced organisms.
One of the amazing things about phage (and other viruses) is their diversity in structure, molecular components, and host range. Phage, like all other viruses, require a living host cell in order to replicate. They depend on the metabolic energy, molecular machinery, and molecular resources of the host cell in order to produce more phage. In other words, phage are obligate intracellular pathogens. Since phage cannot precede living bacteria in their respective origins there is good reason to consider them part of God’s providential creation, either created directly and simultaneously with life or as an engineered adaptive mechanism emerging early from life in order to help drive and sustain diversity and balance in Earth’s ecosystem.
Phage Combating Bacteria
Yet, phage are even more amazing. They have the ability to target and kill specific bacteria. Since the 1920s, researchers have studied and employed phage as a therapeutic treatment to counteract harmful bacterial infections in humans. Although largely abandoned for human therapy in the United States due to the advent of antibiotics in the 1940s, various phage have gained FDA approval, including phage cocktails (mixes of various phage in solution) specific for Listeria, E. coli, and Salmonella bacterial species. However, over the past 20 years, fueled by growing concern over antibiotic-resistant bacteria, interest in phage therapy for humans has been renewed. Many of the presentations at this year’s Evergreen meeting reflected this, covering research challenges and advancements as well as technical and regulatory issues in using phage in anti-bacterial treatments.
Although bacteria can also become resistant to phage, phage have the ability to overcome resistance. So the long-term potential for phage therapy and modification may be much greater and relatively easier than developing new and effective antibiotics. Due to the specificity of phage for bacterial cells, use in humans and other animals is considered extremely safe. This is reflected by current applications in food safety, animal health, probiotics, and additional human therapeutics. In fact, phage therapy for use in humans was never abandoned in Russia and the former Soviet republic of Georgia. Many of the phage experts at Evergreen have had ties to the Eliava Institute in Tbilisi, Georgia, where phage research in treating human disease has been studied continuously since 1923. On rare occasions, phage therapy—using phage cocktails characterized and provided by the Eliava Institute—has been employed in human treatment in the United States.
Phage Exemplify God’s Providence
The year of the phage is a great time to thank God for phage and for the diversity and complexity of this creation. We can also thank God for his providence in both sustaining life and in providing resources for our stewardship and well-being. I am thankful for ongoing discoveries of the diversity and complexity of phage and for the advances that scientists are making. We continue to gain insight into how we can best use phage for creation care and human health. Happy year of the phage to all!