In 1919 several children in a hospital in central Paris were suffering from severe dysentery,
caused by a bacterial infection of the intestines and resulting in severe diarrhoea.
However, a microbiologist, Félix d'Herelle, was ready to trial a new treatment.
Three years prior, in 1916, d'Herelle, was an unpaid, self-taught volunteer at the Pasteur
Institute and searching for a discovery to place his name in the history books alongside Pasteur himself.
He isolated bacteriophages, viruses that attack bacteria,
from the filtrates of dysentery fluids from soldiers.
He immediately speculated that his discovery could explain the recovery of patients from the disease.
And in early 1919, he had began conducting trial experiments on animals,
isolating phage from chicken faeces and successfully treating a plague of chicken typhus.
With that success he was now ready to begin human trials.
His treatment of several children at the hospital was successful
and promised to herald the beginning of a new medical revolution.
But today, few bacterial infections are treated with Phage Therapy,
instead physicians turn to antibiotics, but with the rise of superbugs resistant to many antibiotics
perhaps bacteriophages could be useful.
So then why did they fall out of use in the first place?
The short answer as to why antibiotics became preferred over Phage is one of convenience, and money.
Phage are specific, targeting only a few bacterial species
and while this can be beneficial in leaving beneficial bacterial species untouched,
a board spectrum antibiotic, wiping clean all species of bacteria can cure an infection
regardless of what specific species is the culprit;
thus allowing for presumptive treatment, prior to the identification of the pathogen.
And the new Sulfonamide antibiotics of the 1930s were easy to use by solo general practitioners,
without the access to expensive bacteriological laboratories needed for the diagnosis
and complex support necessary for effective phage therapy.
Off-the-shelf medications were simple and effective.
And naturally occurring phage, cannot be patented,
so pharmaceutical companies naturally followed the money;
rather than endeavour to isolate new phages faster than bacteria evolved resistance.
But while we can summarise that the wide-spread availability of antibiotics
after the Second World War has reduced the use of phage therapy,
the issues faced began at the moment of discovery.
Even the very nature of phage was the subject of debate.
In 1919, the same year d'Herelle first treated patients with phage,
Jules Bordet was awarded the Nobel Prize for his work on immunity
based on lysis of bacteria by antibodies, not phage.
d'Herelle boldly challenged Bordet's work, and with that an academic rivalry was born.
Bordet and his protégé, Andre Gratia, responded by challenging both his conception
of phage as a virus - arguing that bacterial lysis was induced by enzyme -
and his status as discoverer, noting that Frederick Twort, a British microbiologist had observed
“transmissible glassy transformation” of bacteria, but failed to follow up on his original observations,
D’Herelle fought back as best he could, but with no formal scientific education
and lacking the standings of a Nobel Prize, he couldn’t persuade the scientific community
that phage was a virus and not a self-perpetuating lytic enzyme.
Nevertheless, the medical results couldn’t be ignored
and doctors across Western Europe successfully tested Phage Therapy it against a variety of diseases.
And in 1924 d'Hérelle received an honorary doctorate of the University of Leiden,
as well as the Leeuwenhoek medal, placing him alongside his idol Louis Pasteur.
But it was not until the electron microscopy was developed in Germany in 1939 that d’Herelle’s
viral conception of phage would be vindicated, and even then World War II limited the distribution
of scientific literature out of Germany.
And the then known status of phage as a virus led to a marketing issue.
Scientists and the public alike were intrigued by the virus “at the edge of life”,
but patients could be off put by a treatment involving a living agent.
Regardless, by this point D’Herelle had left the West, to help establish an institute
to study phage and phage therapy in the Soviet Republic of Georgia in 1934.
Without the profit requirements of capitalism, Phage therapy was widely employed in the Soviet Union
who also lacked access to the antibiotics being developed in the west.
This operation became large, employing 1200 people and producing two tons of phage each week,
mostly for use by the Soviet military.
However this resulted in another marketing issue.
In the aftermath of World War II, with the cold war governing international relations,
all things “communist” became suspect in the West.
This included Soviet Science, and phage therapy was now Soviet Science.
As Gunther Stent, one of the early bacteriophage biologists and Graduate Professor at the University
of California in Berkeley wrote as phage therapy was fading into obscurity:
“… as late as World War II, bacteriophages were said to have found employ in the medical
services of the German and Japanese armies, and even today the medical use of bacteriophages
still persists in some out-of-the-way places”.
Being associated with America’s enemy’s, especially the out of the way places understood at the
time to be the Soviet Union, resulted in phage therapy becoming something to be quickly dismissed.
But now with the rise of superbugs interest in phage therapy is increasing.
Phage not only provide an opportunity as an alternative treatment for antibiotic resistant bacteria
but modified viruses could turn the CAS9 protein the bacteria normally uses to defend itself
againced the bacteria to make modifications to the bacteria’s own genome - with CRISPR
potentially solving the problem of bacterial resistance to the phage, as well as allowing patents.
And speaking of CRISPR, my wife made a video on that the medical uses of this technique
over on her channel, Crazy Little Things, so go check it out, links in all the usual places.