Discovered in WWI, bacterial viruses may be our allies in a post-antibiotic age

As we again reflect on the sacrifices our Anzac soldiers, nurses and doctors made during the first world war, another centenary goes by unnoticed by most Australians.

It celebrates a scientific discovery made behind the Western Front, one that might soon affect the health and life of many Australians. Bacteriophages (viruses that attack bacteria) – described by Felix d'Herelle in 1917 – may now be the answer to a world where antibiotics are losing effectiveness.

Dysentery in the trenches

Historians record WWI as the first conflict in which more military deaths were attributable to hostile action than disease. But the filthy nature of trench warfare on battlefronts like Gallipoli allowed infectious diseases like dysentery to spread widely among troops.

Only twice during the Gallipoli campaign did the proportion of Anzac troops being evacuated with wounds exceed those being taken off due to some form of illness.

The situation was scarcely better on the Western Front. In August 1915, ten infantrymen in the French army had contracted severe haemorrhagic dysentery – described as diarrhoea with heavy blood loss.

Investigation of this outbreak was assigned to a young French-Canadian scientist Felix d'Herelle. Working in Paris at the prestigious Institut Pasteur, he quickly isolated and identified the Shigella bacterium as the cause of the infantrymen’s dysentery.

At this critical time during the war, many researchers at the Institut Pasteur practically lived in the laboratory, often working through the night on important scientific pursuits. D’Herelle would sneak in inquisitive side experiments during his rare moments of free time. And it was in these moments he made his great discovery.

Invisible agents

D’Herelle had a hunch. Previous research had suggested the possibility an invisible agent (possibly a virus) could kill bacteria. To investigate this, he decided to mix filtered (bacteria-free) faeces from dysentery-infected soldiers with a layer of Shigella bacteria he grew in a petri dish.

A day later, d’Herelle saw saw evidence his invisible virus appeared to be killing the bacteria. In 1917, d’Herelle published an article in the proceedings of the French Academy of Sciences. Its title translated from French was “On an invisible microbe antagonistic to dysentery bacilli”.

Suspecting a virus but unable to prove these agents killed the bacteria, d’Herelle gave the antagonistic agents the name bacteriophage (from the Greek “phagein”, meaning to eat).

The rise and fall of bacteriophage therapy

Before antibiotics were developed in 1945, bacterial infections such as pneumonia and tuberculosis were among the leading causes of death in industrialised societies.

D’Herelle pioneered bacteriophage (phage) therapy in the 1920s and 1930s to successfully treat a range of bacterial infections. These included skin and eye infections, septicaemia and intestinal diseases. The therapy was administered to patients orally, by injection or even through the general water supply.

But the use of phage therapy did not persist. Scientific understanding of bacteriophages and biology at the time was limited. Perhaps the most notable problem was that viruses remained invisible to human eyes until the electron microscope was developed in the late 1930s.

It was also speculated D’Herelle’s work on bacteriophages did not achieve greater prominence as he was regarded as a scientific outsider who allegedly had a tendency for hostility rather than persuasion.

Nevertheless, from the 1940s, d'Herelle’s bacteriophage techniques were used to unravel many molecular processes of genetics, leading to multiple Nobel prizes. But with the meteoric rise of antibiotics in treating bacterial diseases from 1945 onwards, use of bacteriophages to treat bacterial infections was largely forgotten.

The post-antibiotic era

We have now entered a new era in which the World Health Organisation has declared antibiotic resistance a global health priority. Antibiotics can no longer be relied on to halt the spread of bacterial infections.

The Australian government’s Antimicrobial Resistance Strategy recognises “the single most powerful contributor to resistance is the global unrestrained use of antibiotics”.

As antibiotic resistance continues to spread, we are seeing the emergence of the century-old infections and diseases suffered by Anzac troops during WWI.

Bacterial infections routinely prescribed and treated with antibiotics are transforming into superbugs that threaten to send us back to a pre-antibiotic era. In recent years, strains of Shigella bacteria have re-emerged with broad-spectrum antibiotic resistance in industrialised societies such as Australia and the United States.

It’s worth noting that in the world’s poorest communities – where access to clean water and basic sanitation is lacking – dysentery was never defeated. Shigella infects hundreds of millions of people each year, and thousands die.

Making a comeback

But the future is not altogether bleak. Easy access to DNA sequencing technology is expanding our understanding of the microbial worlds that surround us. And there is a renewed interest in bacteria’s most ancient enemy, and d’Herelle’s important discovery, the bacteriophage.

Some of the original phage therapy techniques he developed have been maintained in the former Soviet republic of Georgia, to treat recalcitrant infections such as Golden Staph caused by the bacterium Staphylococcus aureus.

These bacteriophage preparations can be imported into Australia for personal use. Yet we previously had little use for them because antibiotics worked, and worked well.

This is changing as scientists, doctors and businesses are leveraging decades of bacteriophage research in a renewed attempt to combat antibiotic-resistant superbugs.

Australia is a growing hotspot for bacteriophage research, investment and biotech companies. Scientists at Flinders University are already using bacteriophages to combat bacterial diseases, including Golden Staph.

My laboratory is expanding on a 2013 discovery which described the role bacteriophage viruses play in protecting our bodies from disease-causing bugs.

This unlikely symbiotic partnership is explained for a mainstream audience in a graphic novel (which I co-authored) called The Invisible War. It is set in the trenches of the first world war, featuring dysentery-ridden nurses, warring microbes and heroic viruses.

Lest we forget

Scientists from all over the world are gathering this week at Paris’s Institut Pasteur to commemorate the 100-year anniversary of the discovery of bacteriophages, made behind the Western Front.

So when remembering our troops, doctors and nurses this Anzac Day, consider also tipping your hat or your glass to the vital role bacteriophages play in our world. One day our health might just depend on them.

This article was co-written with Dr Gregory Crocetti from Scale Free Network.

Jeremy J. Barr receives funding from the Australia Research Council and is a member of the Australian Society for Microbiology.