Articles, Blog

Why don’t we use Viruses to Fight Diseases for Us?

December 14, 2019


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.

12 Comments

  • Reply mafarmerga June 29, 2018 at 4:02 pm

    Excellent review of phage therapy. The other advantage is that phage, like their target bacteria, can evolve. So even without CRISPR modifications nature should allow us to select for those phage strains that are most effective at targetting specific pathogens.

  • Reply 45rpm June 30, 2018 at 6:24 pm

    I saw a TV program years ago about phage medicine in Russia. They where collecting the phages from a sewer if I remember correctly but in the end the centre ran out of money and the refrigerators stopped running and all their phages where lost. Quite sad.

  • Reply The real MacGyver July 22, 2018 at 3:22 pm

    how much is bacterial resistance to phages a problem? phages do evolve too or they just phish for another type of phages.
    patents are not the solution rather less to no regulation to phages that way it can be sold as a unique cure just as a massage.

  • Reply Zain Syed December 15, 2018 at 11:45 am

    the funny thing is humans are just too different for phages to infect and besides phages have been with us since the start of humanity if they wanted to evolve they could've done it back then lol on top of that in order for bacteria to be phage immune they have to give up antibiotic resistance we already pretty much won.

  • Reply firefrostcat62 January 13, 2019 at 7:41 am

    lol any inspiration from Kurzgegast?
    Edit: it’s probably the other way round

  • Reply TransistorSnack April 4, 2019 at 1:59 am

    your smoke detector needs new batteries

  • Reply Prairie Climber April 14, 2019 at 5:38 pm

    My buddy is working on this right now actually, I hope he succeeds

  • Reply Burt Burt May 12, 2019 at 11:09 pm

    Reply to this comment for a new subscriber.

  • Reply teddy Field June 26, 2019 at 10:01 pm

    Antibiotics age 37 rating 95 potential 95 going down

    Phages age 17 rating 83 potential 99 going up greatly

  • Reply Jordan Resendiz July 4, 2019 at 5:51 pm

    before i hear the answer i wanna guess because they're unreliable and could mutate at any second

  • Reply weirdintro 9 September 2, 2019 at 12:46 pm

    So if someone is gonna die from e. Coil they and they can't do anything but phages they won't ingect them with phages?

  • Reply RHN October 1, 2019 at 3:46 pm

    The guy who found penicillin is such a fraud, man found it by accident.

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