For some peculiar reason, I have viruses on my mind a lot lately. (I live in New York State. ‘nough said.) As I walked from my kitchen to my office, and back again, and again and again and again, like a caged animal, I decided that perhaps a better use of my time would be to read an article I’d downloaded weeks ago entitled The Forgotten Tale of Brazilian Phage Therapy.[i] Firstly, as you know, I am fascinated by the very idea of phage therapy as it simply uses the body’s natural defense system against bacterial infection and overgrowth. Secondly, the article sounded like a ripping yarn, and who doesn’t love a good story? (It did turn out to be a great read, by the way!) Thirdly, since the worldwide lock-down and the closure of universities, there hasn’t been a huge amount of new and interesting biome research published. It’s COVID-19 and more COVID-19. And I think we all could use a mental break from it.
A quick refresher first: phages, short for bacteriophages, are viruses that attack only bacteria. The word actually means “bacteria eater.” The biome is full of them, comprising what is now known as the virome. Each is specific to only one kind of bacteria, so can theoretically be used in a highly targeted way as an alternative to antibiotics. They keep our bacterial microbiome healthy. Alterations to the virome is now associated with the development of disease. (You can read a couple of my posts on this here and here.)
Phages were discovered in the early part of the 1900s, and researchers immediately saw their potential value. Back then, the bulk of research was going on in Eastern Europe and, as it turns out, Brazil. Unfortunately, much of the South American research has been lost…but what the authors of this article managed to dig up is pretty fascinating.
Dr. Jose da Costa Cruz was a leader in the field in the early part of the 20th century, and began to treat, very successfully, dysentery (an often fatal bacterial infection of the intestines that causes massive, sometimes bloody, diarrhea). In 1923, Cruz wrote in the medical literature that “…anyone who sees the in vitro activity of phages is ‘filled with hope that a new therapeutic against infectious disease will immediately appear’.” The first attempt to treat Sigella dysenteriae, a bacteria that causes dysentery, was not successful but the second testing later that year, on 24 patients, showed improvement within 4-5 hours after the start of the therapy: “It was concluded that phages were recommended for dysentery for being easy to administer, innocuous for the patients, and efficient in patients for whom other treatments had failed.”
In 1924, 10,000 vials of these phages were produced and showed positive results throughout the country, ameliorating symptoms within hours, curing the disease within a day or two.
In 1929, at a Brazilian medical conference, another physician, Dr. Oscar Pereira, pointed out that phage therapy was also important because it cleared stool of live bacteria, thus alleviating it has a potential carrier of disease. He also presented a successful case of using phages to treat E.coli; 9 cases of pyodermitis (bacterial infections of the skin including impetigo); and 32 cases of furunculosis (boils on the skin) on people treated with anti-staph phages. These doctors were not only safely giving phages orally, but also using them topically and by injection. By the late 1930s, Dr. Cruz was treating septic patients with phages: “Mortality was lower than predicted in phage-treated patients”
So what happened to continued use and research into phages? The short answer – antibiotics: “The first half of the 1940s was marked by an increase in publications about other antibacterial substances.” The authors describe a kind of slow fade out in the use of phages, as antibiotics became more and more de rigueur. It’s not that there were any publications denouncing their use, nor were any regulations passed preventing doctors from acquiring or prescribing them. It was simply another case of out-with-old-in-with-the-new, even though there were tremendous benefits to the old. As I mentioned earlier, because phages are targeted to only one kind of bacteria, they do not wipe out the microbiome – nor do they cause antibiotic resistance.
And thus, an interest in using phages began a resurgence in the 1980s, and is escalating now, as resistance to antibiotics – and our understanding of the dangers of overusing antibiotics – grows: “Many research groups and modern clinical trials have focused on this subject of growing importance…” In 2010, there were 188 million cases of dysentery in the world cause by shigella, and this was the second leading cause of death by diarrhea. Staph infections are still a major problem, and are becoming dangerous because of antibiotic resistance. As these authors write, “The safe and efficient use of phages against these targets, as suggested by the Brazilian experience shown in this Historical Review, can be taken as a guideline to develop modern phage therapy trials and shape phage use in our time…this Historical Review might serve as an inspiration to look into a successful past and aim for a better future.”
It always strikes me as a shame that the wisdom of the past is all too often disregarded, as though simply by being new, something is by definition, better.
[i] Almeida GMF, Sundberg LR. The forgotten tale of Brazilian phage therapy [published online ahead of print, 2020 Mar 23]. Lancet Infect Dis. 2020;S1473-3099(20)30060-8. doi:10.1016/S1473-3099(20)30060-8