A well-known cause of many human diseases, bacteria have played a key role in our history. In the 14th century, the Black Death reduced the world’s population by at least 50 million (1), leaving terror and confusion in its wake. Recently, it has been estimated that one in every three people suffers from tuberculosis (2). Bacteria are also responsible for the decease of renowned figures in human history; Cholera managed to defeat Tchaikovsky, tuberculosis ended the life of Emily Bröntsubmie and Karl Max, and Gustave Flaubert and Al Capone succumbed to syphilis (3). For many of us today, it is hard to imagine that a dog bite, a spot or a paper cut could be lethal. The discovery of penicillin and antibiotic mass production have allowed us to live in a world in which we feel relatively safe and protected. However, a recent report from the World Health Organization stated that resistance to these antibiotics “is no longer a prediction for the future, it is happening right now in every region of the world. Common infections and minor injuries which have been treatable for decades can once again kill” (4). This poses a huge challenge for humanity; we’re becoming vulnerable to bacterial attack again and we need to come up with imaginative antibacterial alternatives. And we need to do it quickly.
Of course, bacteria are not the only ones causing us trouble. Humanity constantly faces the risk of noxious viral infections. Viruses are exceptional creatures inhabiting the edges of life. They wander around with a sophisticated, protective protein coat that shields their treasured genetic material. Ebola, HIV, Smallpox; to us they embody evil and constitute a dreadful threat. However, in this extremely anthropocentric view of the world, the potential of viruses is totally underrated.
Viruses are big. Big in numbers and big in diversity. Let’s take flu as an example. Every single year, hundreds of thousands of people experience uncomfortable sore throats and runny noses. The ability of influenza viruses to multiply within our lungs is truly outstanding. A few days after infection, we are filled with more than a 100 trillion viral particles – 10,000 times more viruses within a single person than the total number of people on Earth (5). If we were to examine all the different viruses on the planet, we would come up with something like 1031 viral particles, which is 10 million times more viruses than stars in the universe (6). These enormous numbers arise because viruses can infect all sorts of living creatures. Humans, owls, bees, carnations, mushrooms and bacteria; nothing is safe. However, could we turn this potential threat into a source of inspiration, using this natural rivalry between viruses and bacteria to our advantage? Could we make two of our greatest enemies fight against each other? Could it be that, just beneath our noses, nature is providing us with a longed for solution to antibiotic resistance?
Bacteriophages (or “phages” for short) are viruses that infect bacteria. They were first discovered in the 1910s by two independent microbiologists, Félix d’Hérelle and Frederick W. Twort. This is how d’Hérelle described his groundbreaking finding:
“The next morning, on opening the incubator, I experienced one of those rare moments of intense emotion …all the bacteria had vanished, they had dissolved away like sugar in water…I had understood: what caused my clear spots was in fact an invisible microbe (7).”
And phages remained invisible until 1940, when electron microscopy allowed, for the very first time, the visualization of these beautiful, geometrical creatures with powerful antibiotic abilities.
Because of their viral nature, phages are intrinsically parasitic. They float around looking for a susceptible host and, like a sophisticated spacecraft, land on bacterial surfaces. Once they are comfortably anchored, they accurately position themselves for the delivery of their precious genetic material inside the target cell. The fatal exploitation can now begin. The phage will hijack the bacterial biochemical machinery to build a factory for the mass production of viral particles. At a certain point, the bacterial wall will be ruptured and all the newly conceived phages will be released. As soon as that happens, each new phage will start searching for its next victim.
The phages’ potential use in antimicrobial treatments was something that d’Hérelle foresaw and successfully applied, giving rise to what is known as phage therapy. His work was controversial and deeply shrouded in criticism. Detractors claimed conflicting experimental observations and poorly controlled clinical applications (8). However, we must acknowledge the political tensions of the time. D’Hérelle’s findings were embraced in Eastern Europe under the Soviet Union, but were largely ignored by Western scientists, keen to demonstrate the efficacy of the Western antibiotic approach. Now that we have lived the golden era of antibiotics and phages have almost been forgotten, it is perhaps time for their resurrection.
Some of the intrinsic features of phages make them an effective and elegant tool for fighting pathogenic bacteria. In contrast to antibiotics, they are abundant and relatively easy to find. Omnipresent, they reside wherever bacteria exist, including soil, rivers and animal intestines. Sea water is one of their favourite habitats, each millilitre hosting about 9·108 of them (9).
3. Weissfeld A,. Infectious Diseases and Famous People Who Succumbed to Them. Clinical Microbiology Newsletter. Vol. 31, No. 22. 2009.
7. Dublanchet A and Bourne S. The epic of phage therapy. Can J Infect Dis Med Micriobiol. 2007 Jan;18(1):15-8.
8. Larckum N. Bacteriophage in clinical medicine. J. Lab. Clin. Med.17, 675. 1932.
9. Overview of Bacterial Viruses (https://www.boundless.com)