Phages and Precision Medicine

Bacteriophages target specific bacterial cells and destroy them leaving all other cells unharmed. These organisms have been used for phage therapy - a treatment for disease that involves administering the specific bacteriophage corresponding to a given bacterial infection in order to treat it. Now that the continuous use of broad spectrum antibiotics has resulted in superbugs with high levels of antibiotic resistance, phage therapy might be the precision medicine solution that we need. This will require us to overhaul our current thinking about pharmaceuticals and adopt more localised manufacture.

This article was first published in The Mint. You can read the original at this link.

I have long been intrigued by the notion of precision medicine: the idea that treatments should be bespoke, carefully tailored to the specific circumstances of each infection. Given how unique we all are—from our genetic make-up down to the composition of our individual microbiome—this should, intuitively, have been the way to go. And yet our treatment protocols remain more or less standardized. Medicines are designed to address the widest possible segment of the population. And while this has meant that drugs are more widely available than ever before, it is unclear whether our outcomes have been optimal.

A Protective Substance

In his most recent book, Invisible Empire, Pranay Lal introduced me to an aspect of the history of modern medicine that I was unaware of. In the late 1800s, British bacteriologist Ernest Hankin noticed that there was surprisingly little bacterial contamination in the Ganga despite the fact that so many people bathed in it, discarded waste in its waters and cremated the dead on its banks.

While this phenomenon has long been given a mythical explanation, Hankin, through a process of scientific investigation, identified a “protective substance" in the water that was small enough to pass through filters but was so potent that it destroyed all the cholera bacteria suspended in it. In 1896, he published his findings on the antibacterial properties of the river’s water, but his research remained largely unheeded.

Over the following decades, other scientist began to notice similar phenomena—invisible agents seemingly capable of attacking and destroying a range of different bacteria with high efficiency.

Phage Therapy

These tiny killers, or ‘bacteriophages’ as they would later be called, were found to be viruses that targeted specific bacterial cells, multiplying within them till they ultimately killed their hosts before moving on to the next cell. Among the many striking features of these viruses is the fact that they are host-specific, each only invading the specific strains of the bacterium with which they are associated, leaving every other one untouched. For instance, viruses that attacked the bacteria that caused paratyphoid fever left all other gut bacteria unharmed.

The discovery of these organisms led to the development of phage therapy, a treatment protocol that involved the administration of specific bacteriophage viruses to persons suffering from identified bacterial diseases. Early experiments proved successful against a range of diseases, from bubonic plague to cholera and dysentery.

While phage therapy was somewhat popular before World War II, since then—largely fuelled by the military-industrial complex that invested heavily in developing these treatments for the war effort—antibiotics have become our preferred method of treatment. Unlike bacteriophages that are specific, antibiotics are effective across a broad spectrum of infections, making them easy to administer even if the exact pathogen has not been identified. Today, they are used for a wide range of purposes, from curing disease to speeding up the growth of livestock, while work on phage therapy is restricted to a few countries and generally viewed with mistrust.

Antibiotic Resistance

As useful as antibiotics have been in improving the quality of health around the world, our over-reliance on them is starting to have extremely serious consequences. The phenomenon of antibiotic resistance is now such a serious concern that the World Health Organization has had to establish a global action plan on antimicrobial resistance. A report by the US Centres for Disease Control suggests that in the US alone, more than 2.8 million antibiotic-resistant infections occur each year, resulting in more than 35,000 deaths. In India, antibiotic resistance has led to the rise of superbugs, diseases seemingly resistant to multiple drugs (or in some cases all known antibiotics).

There has never been a better time to restart active research into phage therapy. Given the targeted effectiveness of bacteriophages, these treatments have relatively fewer side-effects and almost always result in a cure. Thanks to advances in genetic sequencing, it is now easier than ever before to identify infection-causing pathogens. Other advances in bacterial technology have made it possible for us to harvest phages from cured patients, giving us a relatively unlimited supply of therapeutic material.

Re-thinking Pharma

The problem with switching to phage therapy is that it will require us to completely overhaul our current thinking about pharmaceuticals. Phage treatments need to be developed locally, as a virus that is effective against one strain of a disease in Europe could well be ineffective against another strain of the same illness in India. This in turn means that the massive centralised facilities that we currently rely on to manufacture medicines for supply around the world will be of little use if we start using bacteriophages for therapy.

Instead we will need to build decentralised repositories of bacteriophages that work most effectively against local disease strains. This will require us to re-train medical professionals to focus on accurately diagnosing specific pathogens, so that the specific phage that corresponds to that particular strain of bacteria can be identified and administered.

Over the millennia, viruses have developed specialised weapons to take down bacteria. For all we know, there is a virus capable of targeting and destroying every bacteria that exists on the planet.

It is time to use them to our advantage.