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Phage Therapy Principles

Disadvantages of Phage Therapy (and Advantages)"

Due to the personalized nature of this therapy, it is indeed lengthier and thus more expensive to apply than antibiotic treatment. Indeed, it takes time to collect a sample of the patient’s bacteria, cultivate it, and conduct a phagogram (researching the most effective phage). This process already takes 7 to 10 days.

Then, it’s necessary to take a sufficient amount of phages to effectively and properly ‘infect’ the pathogenic bacteria. Treating a urinary infection with phage therapy may require 2 to 3 months to ensure the eradication of the bacteria.

On the other hand, the huge advantage of bacteriophages is that they do not cause serious or lasting side effects, unlike antibiotics. Additionally, if a bacterium becomes resistant to the administered phages, science can recreate a more effective phage based on the patient’s bacteria, ensuring that there is never an absolute therapeutic deadlock.

Finally, the great advantage of phage therapy is that it represents the ultimate solution for patients facing therapeutic dead ends.

Furthermore, another advantage of this therapy is that if a bacterium becomes resistant to the administered phages, science can create a more effective and more tailored phage for the patient’s bacteria, ensuring there are no absolute therapeutic impasses.

And lastly, the huge benefit of phage therapy is that it currently presents the ultimate solution for patients facing therapeutic impasses.

What is Phage Therapy?
Literal definition of phage therapy according to sciencedirect.com:: "Phage Therapy involves the use of bacteriophages-viruses that only attack bacteria and are very host specific - to kill pathogenic microorganisms"

Phage therapy is a therapeutic technique that utilizes the beneficial properties of phages (bacteriophages) to combat bacterial infections. Phages are viruses that infect and destroy bacteria, but do not cause any damage to human or animal cells. That's why this therapy has no recognized side effects after 100 years of use. The process involves finding and identifying the specific viruses suitable for the infection. Then, they need to be applied to the site infected by bacteria (and only bacteria) so they can destroy them. These viruses then multiply and continue to destroy other identical bacteria that they seek out and find. Phage therapy is successfully used in the treatment of antibiotic-resistant bacterial infections, such as, among others, Staphylococcus aureus infections, Pseudomonas aeruginosa infections, Escherichia coli infections, and Klebsiella infections. It is also used in the treatment of gastric issues (gastroenterology) to regulate the microbiota, as well as in ophthalmology to treat eye infections. It's important to note that consultation with a specialized doctor is necessary before resorting to this therapeutic technique. Furthermore, it's crucial to work with qualified professionals who have experience in the use of phages to avoid potential risks and maximize benefits. Over time and with experience, doctors have grown more skilled in how to apply phage therapy.

What are bacteriophages?

Bacteriophages, also known as phages, are viruses that infect bacteria. Phages specifically bind to the surface receptors of bacteria, thereby entering the bacterial cell. Once inside, they multiply and destroy the bacterium in question by making it "explode". The newly replicated phages then go in search of other bacteria to infect and thus destroy. This process continues until the bacterial infection is cured. For each type of bacterium, there is one or more types of phages. But each phage will only attack the bacterium for which it is assigned. This is how bacteriophages can successfully cure a bacterial infection that antibiotics have not managed to cure.

That's why phages can heal us!

There are different types of phages, including lysing phages that destroy bacteria by "lysing" (destroying) them. Lysing phages are the ones used in phage therapy.

Phages are present everywhere in the environment and are very abundant in aquatic ecosystems and soils. They were first discovered at the beginning of the 20th century and have been studied in depth and used since then. Particularly for their therapeutic capacity in phage therapy.

How are phages prepared?

Phages can be prepared artisanally with a bit of scientific knowledge. For example, one can take a sample of water from a stream, sewage, etc., and it will contain phages. This collected water is then centrifuged and decanted in a sterile environment. After that, it is exposed to a culture broth of the bacteria you wish to treat. All that will remain are the phages allocated to destroy this bacterium without the bacterium itself, which will have been destroyed by the phages. However, there may still be bacterial debris left. A bit of chloroform is added to destroy any remaining bacteria without harming the phages. The result is then mixed at high speed to eliminate unwanted cells. This mixture will finally be extremely filtered to eliminate all bacteria (on a membrane with a porosity of less than 0.45 microns), then incubated for 24 hours at 37°C.

Of course, the industrial process is more complex and advanced, but artisanally, it is not difficult to do it in .
Phages are produced in a way that ensures they are safe and effective for patients.

Phage preparation begins with the isolation of phages from different sources, such as soils and primarily waters (especially sewer waters!). The phages are then grown and multiplied using specific bacterial cultures.

This collected water is centrifuged and decanted in a sterile environment. It is then exposed to a culture broth of the bacterium one wishes to treat. All that will remain are the phages allocated to destroy this bacterium without the bacterium, which will have been destroyed by the phages. However, there may still be bacterial debris left. A bit of chloroform is added to destroy any remaining bacteria without harming the phages. The result is then mixed at high speed to eliminate unwanted cells. This mixture will finally be extremely filtered and purified to eliminate all bacteria (on a membrane with a porosity of less than 0.45 microns), then incubated for 24 hours at 37°C.

The quality of the phages is then checked using purity, concentration, and activity tests. The phages are also tested to ensure they do not contain bacteria or harmful contaminants for patients. Phages are then formulated using excipients (like salts, proteins) to stabilize their activity and facilitate their administration. The phages are then packaged in sterile bottles for their use in therapy.

It's important to note that phage preparation is done under strict conditions of hygiene and quality, and it's regulated by health authorities to ensure the effectiveness of the phages used in therapy.

In summary, bacteriophages are prepared in the lab by isolating, cultivating, purifying, and testing phages to ensure they are safe and effective for patients. The phages are then formulated and packaged for their use in therapy. The preparation of phages is carried out under strict hygiene and quality conditions. It is regulated to ensure the safety and effectiveness of the phages used in therapy.

What is the difference between phages and antibiotics?

Phage therapy is a much more personalized therapy than antibiotic therapy and is carried out very differently. It has the huge advantage of having no known side effects in 100 years of practice. To know everything about the differences between phages and antibiotics, read the page dedicated to the Comparison between phages and antibiotics.

How are phages applied to treat patients?

There are many methods of administering phages depending on the illnesses. Even though there are no known side effects of phage therapy (from 100 years of practice), each infected site has its own method of administration (urethral infiltration for urinary infections, mesotherapy for folliculitis, inhalations for lung infections, etc.). You can find all the explanations on how to treat different illnesses with phage therapy on the page "Treatment with phage therapy".

Who discovered phage therapy?

A Franco-Canadian, Félix d'Hérelle, a researcher at the Pasteur Institute, discovered in 1917 that certain samples left on Petri dishes revealed "clear zones", that is, the bacteria disappeared on their own. He had the idea of taking a sample from these clear zones and depositing it on other Petri dishes where the bacteria did not disappear. He then observed the appearance of new clear zones, which meant bacterial destructions. He thus concluded that there was a microorganism that naturally aided in healing. He called them "bacteriophages" (from the Greek Phagos = to eat), so they are "eaters" of bacteria. Then this name was simplified to "PHAGES". He then had the idea to isolate these active bacteriophages (phages) to give them to infected patients and use them for therapeutic purposes. To convince his colleagues of the harmlessness of the prepared phages, he himself swallowed his first phage preparations. He then treated children affected by Shigella (serious infection) and managed to cure them: he had invented phage therapy. He went to Georgia in 1920 to create an world research institute for phage therapy there.

Why are phages not used in the West?

Until 1980, phages were sold in pharmacies and were reimbursed 75% by social security. In 1980, a law was introduced that prohibited treatment with living organisms. This led to the ban on the sale of phages in France and in Western countries. However, at that time, antibiotics were still effective, and antibiotic resistance was not yet a topic of discussion. Phages, being more complicated to use than antibiotics, fell into disuse and disappeared from the Western therapeutic arsenal with little attention.

Today, due to the rapidly increasing problem of antibiotic resistance, the media and scientists are starting to discuss this natural therapeutic solution again. The issue with phages is that they weren't invented but simply taken from nature. As a result, they can't be patented. But, clinical studies cost millions of euros and usually last a decade. No one wants to invest a lot of money into a non-profitable process because it can't be patented. In addition, clinical studies would need to be done for each type of phages for each disease: pseudomonas in the lungs, pseudomonas in the bones, pseudomonas in the sinuses, etc. This multiplies the clinical studies indefinitely. Here's an excerpt from the March 4, 2021 report from the French Parliamentary Office for the Evaluation of Scientific and Technological Choices (full report available by clicking on the following link: https://www.assemblee-nationale.fr/dyn/15/comptes-rendus/ots/l15ots2021101_compte-rendu) :
"A company based in France has started developing phages, Pherecydes Pharma, which will conduct clinical trials. But it must go through all regulatory steps before any market authorization. The National Agency for the Safety of Medicines and Health Products (ANSM) has told us they are absolutely not opposed to phages, but they must comply with the regulatory framework for medicines.

The lack of progress on phages in France is leading some desperate patients to turn to "medical tourism".


I want to point out that one of the barriers for phages is also economic: they can't be patented as such because they come from nature. Furthermore, phage therapy is not a long-term treatment and therefore cannot be profitable like a medicine for a chronic disease. Another barrier is scientific: each phage is very specific, it's difficult to find many similar cases and thus to conduct randomized trials testing their effectiveness and safety. Yet, European and national drug regulations require proof to admit a new drug to the market. We can therefore question the suitability of the legal framework for phages."

Dr. DUBLANCHET, a French expert in phage therapy, has been fighting for more than 20 years to try to bring back phage therapy in Europe :
Alain DUBLANCHET

The american society for Microbology is also a strong advocate for phage therapy:
https://asm.org/Articles/2022/August/Phage-Therapy-Past,-Present-and-Future

Why is phage therapy authorized in Georgia?

Georgia, on the other hand, has never stopped using phage therapy, which has never been banned there. Shortly after the advent of communism, a phage therapy research institute was established in its capital in 1923. It was created by Félix d'Hérelle, the discoverer of phage therapy (French), in collaboration with a Georgian researcher, Giorgi ELIAVA. The institute is named after the Georgian researcher: The Eliava Institute

During the communist era, antibiotics were used less than in the West, and phages continued to be widely adopted, studied, and researched. This has made Georgia the most experienced place in the world (with 100 years of practice) and one of the largest collections of phages in the world (estimated to be over 6000).
To this day, phage therapy is still taught in medical schools in Georgia, which is not the case in the West. Georgian doctors have the knowledge, experience, authorizations, and a significant arsenal of phages to effectively treat patients.