Bacteriophages, or phages, are viruses that specifically infect and destroy bacterial cells. They are the most abundant life form on Earth and play a crucial role in regulating bacterial populations in various environments, including the human gut. Phages have significant potential in treating bacterial infections, especially in the context of antibiotic resistance, and have been instrumental in advancing our understanding of molecular biology and genetics.
The phenomenon of bacteriophages was first observed in the late 19th century. In 1896, Ernest Hankin noted that cholera bacteria in the Ganges River were being lysed by something in the water. Frederick William Twort in 1915 and Félix d’Herelle in 1917 independently identified and studied these lytic agents. Twort observed a glassy dot that could destroy bacteria, while d’Herelle coined the term 'bacteriophage' and demonstrated their ability to infect and kill bacteria.
Bacteriophages played a pivotal role in uncovering the nature of DNA. In 1952, Alfred Hershey and Martha Chase used phages to demonstrate that DNA, not protein, is the genetic material. This experiment, known as the 'blender experiment,' showed that phages inject DNA into bacterial cells, leading to the replication of the phage. This discovery was foundational for the later elucidation of the DNA double helix structure by James Watson and Francis Crick.
The rise of antibiotic resistance has spurred renewed interest in bacteriophages as a potential treatment for bacterial infections. With millions of people dying annually from infections that antibiotics can no longer treat, phages offer a promising alternative. Advances in genomic tools now allow researchers to better understand and tailor phages for specific bacterial targets, making them a viable option in modern medicine.
Developing phage-based treatments is challenging due to their specificity. Each phage targets a specific strain of bacteria, requiring precise identification of the pathogen. Additionally, phages must be carefully selected to avoid lysogenic cycles where they integrate into bacterial DNA rather than killing the host. Regulatory and patent issues also complicate their development and commercialization, as phages do not fit neatly into existing drug development models.
Bacteriophages are used in environmental monitoring to detect fecal contamination in water. Unlike traditional indicator bacteria, phages can identify the source of contamination (e.g., human vs. animal). They are also used to study the behavior of other enteric viruses, such as norovirus, in water systems. Phages are highly abundant in wastewater and can persist longer than bacteria, making them effective tools for water quality assessment.
Bacteriophages and bacteria engage in a constant evolutionary arms race. Phages infect and kill bacteria, but bacteria can evolve resistance mechanisms. This dynamic regulates bacterial populations and drives genetic diversity. Phages can also transfer genetic material between bacteria through lysogeny, where phage DNA integrates into the bacterial genome, potentially conferring new traits such as antibiotic resistance or virulence factors.
In the Soviet Union, bacteriophages were extensively used for treating bacterial infections, particularly during the 1920s and 1930s. George Eliava, a Georgian scientist, collaborated with Félix d’Herelle to establish the Eliava Institute in Tbilisi, which became a center for phage research and therapy. Phages were used to treat diseases like typhoid, diphtheria, and the plague, but their use declined with the advent of antibiotics.
Bacteriophages are considered a treasure trove of genetic diversity because they are the most abundant biological entities on Earth, with trillions of unique phages. Their genomes contain vast amounts of undiscovered genetic information, much of which is unlike anything previously known. This diversity makes phages a rich resource for understanding microbial ecosystems, developing new therapies, and advancing biotechnology.
Bacteriophages can be used alongside antibiotics to enhance their effectiveness. Phages can target and destroy biofilms, which often protect bacteria from antibiotics, allowing the antibiotics to reach their target. Additionally, phages can be used to treat infections caused by antibiotic-resistant bacteria, providing a dual approach to combating bacterial infections. Studies have shown that combining phages with antibiotics can eradicate infections that are otherwise untreatable.
Melvyn Bragg and guests discuss the most abundant lifeform on Earth: the viruses that 'eat' bacteria. Early in the 20th century, scientists noticed that something in their Petri dishes was making bacteria disappear and they called these bacteriophages, things that eat bacteria. From studying these phages, it soon became clear that they offered countless real or potential benefits for understanding our world, from the tracking of diseases to helping unlock the secrets of DNA to treatments for long term bacterial infections. With further research, they could be an answer to the growing problem of antibiotic resistance.
With
Martha Clokie Director for the Centre for Phage Research and Professor of Microbiology at the University of Leicester
James Ebdon Professor of Environmental Microbiology at the University of Brighton
And
Claas Kirchhelle Historian and Chargé de Recherche at the French National Institute of Health and Medical Research’s CERMES3 Unit in Paris.
Producer: Simon Tillotson
In Our Time is a BBC Studios Audio Production
Reading list:
James Ebdon, ‘Tackling sources of contamination in water: The age of phage’ (Microbiologist, Society for Applied Microbiology, Vol 20.1, 2022)
Thomas Häusler, Viruses vs. Superbugs: A Solution to the Antibiotics Crisis? (Palgrave Macmillan, 2006)
Tom Ireland, The Good Virus: The Untold Story of Phages: The Mysterious Microbes that Rule Our World, Shape Our Health and Can Save Our Future (Hodder Press, 2024)
Claas Kirchhelle and Charlotte Kirchhelle, ‘Northern Normal–Laboratory Networks, Microbial Culture Collections, and Taxonomies of Power (1939-2000)’ (SocArXiv Papers, 2024)
Dmitriy Myelnikov, ‘An alternative cure: the adoption and survival of bacteriophage therapy in the USSR, 1922–1955’ (Journal of the History of Medicine and Allied Sciences 73, no. 4, 2018)
Forest Rohwer, Merry Youle, Heather Maughan and Nao Hisakawa, Life in our Phage World: A Centennial Field Guide to Earth’s most Diverse Inhabitants (Wholon, 2014)
Steffanie Strathdee and Thomas Patterson (2019) The Perfect Predator: A Scientist’s Race to Save Her Husband from a Deadly Superbug: A Memoir (Hachette Books, 2020)
William C. Summers, Félix d`Herelle and the Origins of Molecular Biology (Yale University Press, 1999)
William C. Summers, The American Phage Group: Founders of Molecular Biology (University Press, 2023)