Phage

Phage (pronounced feyj)

In microbiology & virology, a virus parasitic towards bacteria; a truncation of bacteriophage.

1917: from the Ancient Greek φάγος (phágos) (eater), from φαγ (phag), aorist (the tense of Greek verbs that most closely corresponds to the simple past in English) stem of ἐσθίω (esthíō) & ἔδω (édō) (to eat, to consume) and thus a combining form meaning “a thing that devours,” used in the formation of compound words, especially the names of phagocytes.  The noun bacteriophage (virus that parasitizes a bacterium by infecting it and reproducing inside it) was adopted in English in 1921, from the 1917 French original bactériophage, the construct being bacterio- (a combining form of bacteria) + -phage.

Some viruses can be helpful: A depiction of phages phaging.

Not all viruses are bad like SARS-CoV-2.  A bacteriophage, known almost always as a phage, is a virus which infects and replicates within bacteria.  Phages are composites of proteins that surround a DNA or RNA genome and may encode any number of genes from a handful to many hundreds.  Phages replicate within the bacterium following the injection of their genome into the target cytoplasm.  Phages exist naturally in the environment and are among the most common and diverse entities on earth.  Serious research began in several parts of Europe during the late nineteenth century and have been used for almost a century as anti-bacterial agents the former USSR and Central Europe.  In the West, phage therapy (using specific viruses to fight difficult bacterial infections) has been of interest for some time, attention heightened as the problem of antibiotic-resistant bacteria (superbugs in the popular imagination) began to grow in severity (the US Centers for Disease Control and Prevention (CDC) attributes one death every 15 minutes in the US to superbugs).  Since the discovery of penicillin, antibiotics have been used as a reliable cure for those suffering from once lethal bacterial infections but, over decades, a handful (compared with the trillions and trillions killed) of bacteria have proved resistant to antibiotics and as these survivors multiply, new infections emerge.  Historically this had prompted the development of revised or new antibiotics but the biological arms race has reached the point where some infections caused by called antibiotic resistant bacteria cannot be treated and for many other serious infections, the number of potent “last resort” antibiotics is dwindling.

Hence the interest in phages, a type of “friendly virus” which can be weaponized to fight even the most virulent and persistent bacterial infections.  Phages work as well as they do because viruses like the tiresome SARS-Cov-2 that makes humans sick, phages can infect only bacteria and are selective about which they target, a vital aspect of their role in medicine because human survival depends on the billions of bacteria in our bodies.  These phages are far from rare, existing in the natural environment almost everywhere on the planet and scientists conducting research find dirty waterways or damp, aerated, warm, decaying soil (both areas where high bacterial growth might be expected) are good places to collect samples.  The advantages phages offer are well known but there are also drawbacks and indeed some of the features of phages manifest as both.  For example, the great specificity of phages helpful in that they can be administered safely with the knowledge that no other organisms will be harmed but this can be a practical disadvantage in clinical medicine when it’s not known exactly which bacteria need to be targeted, which is why broad-spectrum antibiotics proved so effective at scale.  Being wholly natural, the shelf-life of phages is highly variable and there’s little experience in their administration beyond some communities in Eastern Europe where they’ve been part of medical practice for over a century.  Additionally, bacteria can develop resistance even to phages and one practical impediment to deployment not well recognized until recent years is that compared to chemical molecules, phages are quite big and there are sites in the human body which will be inaccessible.

Potential phage research subject:  In 2014, while on holiday in French Polynesia, Lindsay Lohan was infected with chikungunya, a virus spread by mosquitoes which causes debilitating joint pain and flu-like symptoms.  The World Health Organization (WHO) notes it was first identified in Africa in the 1950s and has since spread to the Indian Ocean region, southeast Asia and the Pacific islands, cases emerging for the first time in the Caribbean in 2013 while a small number have been reported in the US and Europe, mostly in travelers from affected areas.  The role of climate change in the geographical spread of Chikungunya has not been discounted and the symptoms include severe joint pain, headache, fever, nausea, fatigue and rash.  There is no cure or vaccine, and the illness can last from several days to as long as a few weeks, Ms Lohan advising all in susceptible regions to use bug spray and posted on Instagram a photo from the beach, captioned "I refuse to let a virus effect (sic) my peaceful vacation."

However, looming over the treatment of bacteriological infection is the economics of the pharmaceutical business (the big-pharma).  It was the ability in the twentieth century of the industry to mass-produce antibiotics at scale and at astonishingly low cost which meant what little research on phages was being undertaken was quickly abandoned; antibiotics truly were miracle drugs.  However, the economics which made antibiotics attractive to the public health community meant they added comparatively little to the profits of big-pharma compared with something lucrative like a blood-pressure drug which a patient would be required to take every day for the rest of their lives.  A cheap antibiotic, needed disproportionately in low-income countries was a less attractive path for the billions of dollars (and usually years of trials) required to bring a new drug to market.  What the industry likes are drugs which can be mass-produced to treat the “curse of plenty” diseases of first world customers.  Unless there’s some sort of molecular breakthrough (presumably at the level of DNA), phages seem likely for the foreseeable future to remain a niche treatment.

Little killing machines: Matt Cirigliano's graphical depiction of phages in action.