Phage therapy in a post-antibiotics world
When Fleming discovered the first natural product antibiotic Penicillin in 1928, the discovery was groundbreaking for medicine. Antibiotics were a tool with brute force. Without knowing details about the illness from which a patient was suffering antibiotics allowed a doctor to fight illnesses due to bacteria.
Penicillin proved to be very useful for preventing wounds in the second World War from getting infected and research went into scaling up the production of it. After the war it came to be called a wonder drug. Economically, the fact that one antibiotica can be used for many different illnesses made it in the middle of the 20st century very profitable to patent new antibiotics and bring them to market.
Besides antibiotics phage therapy was another approach that was used a bit within the 1920s and 1930s. Phages cause a trillion trillion successful infections of bacteria per second. They destroy up to 40 percent of all bacterial cells in the ocean every day. Phage therapy is using the power of phages to kill viruses to fight bacteria in patients.
Phage therapy had the problem of being a solution that only targeted very specific bacterial species and sometimes only specific strains of bacteria. Frequently, phage therapy failed because it was not targeted towards the bacteria strain with which a patient was infected. It stopped being used in the West after antibiotics became a popular way to fight bacteria.
While Western health authorities managed to get a framework that allows new flu vaccines to be approved in a short time frame to react to a changing virus, we lack a regulatory system that allows new phage cocktails that are needed to deal with evolving bacteria to be approved without going through multiple years of clinical trials.
The property of being a very specific treatment has the drawback that it’s necessary to test the patient, to know which bacteria infects the patient, to be able to choose the right treatment. In the past it was both expensive and time consuming to test for the bacteria that causes an infection.
In Poland there’s the Phage Therapy Unit which provides Phage therapy for chronic drug-resistant bacterial infections but they operate under an exception for experimental procedures. They published a review titled Facing Antibiotic Resistance: Staphylococcus aureus Phages as a Medical Tool about using phage therapy for treating staphylococcus and argue in another paper that their way of treating patients might be more cost-effective than conventional treatment with antibiotics.
The cost of providing medical treatment matters a lot and causes our health care systems to spend more and more money. DNA sequencing is the one central technology that fell a lot in price in the last decades and while it doesn’t fall faster than Moore’s law anymore there is still hope that continued progress will allow it to be cheaper in the future. Whole-Genome Sequencing (WGS) can not only be used to sequence human DNA but can also be used to sequence bacteria DNA of infections. In several countries WGS-based pathogen typing is already in the trial phase for implementation as a routine tool for the monitoring and detection of multidrug-resistant bacteria pathogens.
As this sequencing becomes common place, doctors will have the relevant data to target specific strains in their patients with phage therapy. I predict that there will be a multi-billion dollar company that uses machine learning to pick the right phage cocktail to treat an infection based on the results from WGS-based pathogen typing.
Phage therapy will get around antibiotic resistance and it will only kill harmful bacteria, while not killing friendly bacteria the way antibiotics do. A company that uses machine learning to iterate on their phage cocktails will give us a more effective alternative to antibiotics.
2 cases that I’m aware of successfully treated with phage therapy: here and here. It’s a promising field.
Some historical info. (and a bit of an insight into medical discoveries/research’s ups and downs.)
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The overuse of antibiotics is shocking on a world-wide scale. From “growth promoters” and “disease prevention” in farm animals to the “just in case/covering my ass/the patient won’t fk-off without them” dispensing/being able to buy over-the-counter without a prescription.
I’ve seen infections spread and sepsis overwhelm animal patients within hours where the infection too fast for antibiotics to counter (euthanasia is only realistic clinical option).
I’ve often wondered what I’d do if infected with an antibiotic-resistant bacterial infection. My imaginary scenario starts local and external—where I’d use topical sodium chloride, freshly crushed garlic, colloidal silver (alternating or mixed I don’t know). With the phase “don’t fk about with debridement, just amputate” ready for anything that’s spreading. Whilst eating more fresh garlic and drinking high doses of tincture of Echinacea (potential to boost immune system and if not the alcohol component might be quite welcome during my final hours—partly said in jest also deadly serious.)
Anyway, an interesting post to share.
I think the usage of colloidal silver as antibiotic is interesting. It used to be used in the West as antibiotic before we had Penicillin.
Unfortunately, nobody run the necessary studies that are needed to see whether it’s a good treatment for antibiotic-resistant bacterial infection. The inability to patent the treatment seems to stop it from being studied.
It’s crazy that when people speak about the dangers of antibiotic resistance nobody funds the colloidal silver studies.
At the same time it’s a brute-force treatment that might turn your skin blue and phage therapy seems to be more promising for a future where we want better health outcomes and not just replace one antibiotica with a similar instrument.
I only know about colloidal silver as a topical treatment (a cream for wounds that I think I only ever prescribed twice). Are you talking about other usage methods? My fantasy flesh-eating multi-resistant infection is easily accessible—silver was a back-up thought after rushing to the kitchen for salt and garlic.
A bit of background info. about bacteriophages would be useful in your post. For general interest and understanding. The following is from the bottom of the case study here:
The potential for targeting individual bacterium in patients—fantastic.
The potential for patents on individual bacterium—frightening.
The thought that there’s all these ‘specific bacterial destroyers’ out there—weird and wonderful.
I really feel the need to hope in writing that phage therapy is something that’s developed in the spirit of co-operation and sharing. To treat patients with infections, not for generating profits at the expense of people who need help.
For better health outcomes we shouldn’t forget the basics: “Bugs” are ubiquitous. Strong immune systems to fight the baddies are more likely with healthy lifestyles in natural environments—unpolluted and full of all the other organisms we evolved encased in. If we’re all about the good bugs, the bad bugs can’t get established so easily.
I integrated information about phages from your link into my article.
Colloidal silver can also be ingested orally to fight bacteria and was used that way in the past in the 19th century. A friend of mine was into the topic of using silver for that purpose for a while but we lack good research that analyses which ways of using silver are useful.
https://www.healthline.com/nutrition/colloidal-silver#what-is-it gives you a summary about claims that are made about it.
If you create profits by giving people medical treatment that allows them to be healthy you aren’t earning those profits at the expense of people who need help but at their benefit.
It seems to me like there are strong network effect if you have one big company that develops algorithms for analyzing which virus to use in particular cases and which also constantly develops new viruses as new strains of viruses appear.
I think those are two separate important topics. On the one hand it’s a change that academia doesn’t research about how to strengthen the immune system.
Replacing bad bacteria with good bacteria is an exiting application. Combining probiotics with phage therapy to make the good bacteria out-compete the bad bacteria is exiting. It might lead to the ability to totally eliminate Streptococcus strains that cause caries out of our mouths.
I was unaware of phage therapy. Thanks for pointing it out, as I have been wondering what alternatives we might have in a future where we have many antibiotic resistant infections that have become more widespread.
How do phages interact with the host immune system? My naive model is the immune system would regard them as an infection and start to suppress.
In the normal state the human body has ten times as much bacteria cells and a bunch of phages that attack those bacteria.
Bacteria phages don’t infect human cells, which many part of the immune system do care about. Whether the immune system will start attacking some phages depends a lot on the context.
In many cases when fighting an infection you have the problem that the host immune system doesn’t effectively work.
In periodontitis for example periodontopathogens like Porphyromonas gingivalis, synergistically disarm host defence systems as a recent review paper on using phage therapy for it describes. In the paper they write about immune system interaction:
The paper seems to the conclusion that periodontitis seems like a good target for treating with phages given the success of existing studies but regulation makes it hard. It suggests in the end that one way to get around the regulation might be to focus first on veterinary medicine as there’s less regulation.
That’s really cool. Thanks for the pointer!
Are there any infections which are or could become resistant to this form of therapy? (Antibiotics are widely in use to day, and that’s why antibiotic resistant bacteria are well known.)
The great feature of viruses is that they evolve. If you have a bacteria where your existing viruses aren’t very effective you can try all your existing viruses against them and recombine existing viruses. Afterwards you can see whether any of your mixes produce non-zero effects. Once you have a virus with non-zero effects you can in-vitro allow evolution to optimize the virus to be effective against the strain you are targeting.
Viruses fought various organisms over billions of years and no bacteria evolved to have virus proof coating.
There’s no good reason to think that the arms race between viruses and bacteria will suddenly be decided in favor of bacteria just because we humans produce more viruses.
Phage therapy is very different then antibiotics because you can’t evolve antibiotics the way you can evolve viruses in labs.
So phage therapy won’t have the weakness of antibiotics (some things are resistant) because it isn’t using one existing general attack, but instead creates a new set of specialized attacks/tactics.
Yes. It’s a toolkit that allow more targeted attacks on bacteria then antibiotics provide. This means that you get the benefits of a more targeted intervention but you regulation that allows you to provide more targeted interventions and the analytics to target your interventions.
Seems unlikely as phages can evolve just as fast.