Phage Therapy: The Forgotten Cure
Phages are the most common organisms in all of the biosphere. You can find them everywhere; bodies of water, the food we eat, even inside of our bodies. Typically when we hear the word virus we think of a negative thing, maybe a sickness or a vaccine we have to take. But these viruses could be the future of modern medicine.
- What’s Wrong With Antibiotics?
- What are Phages, and What is Their History?
- How Can Phages Solve Antibiotic Resistance?
- How does Phage Therapy Work?
- What are the Problems with Phage Therapy?
- What is Currently Being Done in this Field?
- Key Takeaways
What’s Wrong with Antibiotics?
In the world we live in, antibiotics are used to solve many problems. Although they are frequently effective, they are severely overprescribed and overused. Based on how much we currently rely on antibiotics, our bodies are beginning to develop resistance. If this continues, common colds and small injuries will once again become lethal, and we will once again be unable to perform modern procedures. The more we develop resistance, the more it will be passed on to our offspring until all antibiotics are deemed ineffective and useless.
Superbugs are viruses resistant to multiple types of antibiotics. These used to only occur in hospitals, but now they occur outside as well. Not only this, but there are now bacteria resistant to all antibiotics. These bacteria are called pan-resistant strains, and in 2016 the first one in the US was found in a 70 year old woman. Even drugs specifically designed to overcome drug-resistant organisms had no effect. This woman’s state quickly deteriorated, and the doctors didn’t see any suitable alternative treatments, so she died.
When faced with the growing problem of antibiotic resistance, many healthcare professionals suggested that new antibiotics should be developed. However it can take years to develop an antibiotic, and our DNA is already growing resistant to the current antibiotics, what will stop it from doing this again?
Additionally, not only do antibiotics attack the areas we use them to attack, but they also do damage to nearby cells that help us to function. This is a little known fact, because usually people are only focused on the good parts of antibiotics. Each time we use an antibiotic, we are killing off these good cells.
Many policies are being put in place by the World Health Organization (WHO) as well as other healthcare organizations. These policies include regulating use of antibiotics, spreading awareness about this issue, encouraging patients not to use leftover pills without being advised by a healthcare professional, and many more. Even with these policies in place, the problem continues to grow. We must have an alternative medicine technique in place to treat superbugs and serve as an effective backup plan as resistance develops.
What are Phages, and What is Their History?
Bacteriophages (also known as phages) are viruses that infect bacteria. They are the most common organism on Earth, and they are known for their unique shape. Phages come in different shapes, but the famous shape is the head tail shape (pictured below.) These phages have a large round head on top and legs that resemble those of a spider on the bottom.
Although it is debated when phages were originally discovered, it is agreed that in 1915 bacteriologist Frederick Twort was the first to suggest that these viruses were what killed bacteria. In 1919, Parisian microbiologist Felix d’Herelle first used these viruses as a therapy to treat a young boy with dysentery.
Phage therapy was then “rediscovered” by Western Scientists just before the discovery of antibiotics. However, as soon as these came out, every country who could afford it quickly left phage therapy behind for the new “miracle cure.” The only people who continued to use phages were the former Soviet Union. Many of these countries never stopped using this method, and continue to use it to this day.
How Can Phages Be Used to Solve Antibiotic Resistance?
Many phages can be used to eliminate bacteria in the same situations when antibiotics are typically used. These include E. coli, salmonella, mycobacterium tuberculosis, pseudomonas, listeria, and many more.
Phage treatments are typically a combination of multiple phages that work together. This combination of phages is called a phage cocktail, and this is effective because even if one phage doesn’t work, there are multiple other phages in the cocktail. There are two ways that phages can infect their bacterial hosts: the lytic cycle and the lysogenic cycle.
The lytic cycle works the way most viruses do: phages hijack the bacteria and duplicates itself until the bacteria explodes and dies from the pressure. First, the phage will find the bacteria it’s looking to target and attach itself with its spider like legs. Then, it will inject its DNA into the bacteria. Once the DNA is inside, it will use the bacteria’s resources to make proteins that then assemble to become new phages. This cycle continues until lysis, when the phage expresses genes for proteins that poke holes in the cell wall. The cell then bursts open and the phages are freed from inside to go look for more hosts.
The lysogenic cycle works a little bit differently, one key difference being that the phages don’t kill their host. Some phages only use the lytic cycle, while others have the ability to use either based on the circumstances. This cycle begins with the same attachment and DNA injection as the lytic cycle, but instead of making copies and busting the bacteria, the phage DNA integrates with the bacterial chromosome. This integrated phage DNA is called the prophage, and each time the host divides, the phage DNA will be copied too. However, it is still possible for the phage to become active again and enter the lytic cycle.
Some argue that just as bacteria can become resistant to antibiotics, they can develop resistance to bacteriophages. However, one big difference between antibiotics and phages is that phages are living things. Living things can develop and evolve, so theoretically if the people are developing resistance, the phages can evolve to overcome the resistance. It would take years to develop antibiotics that could overcome the resistance, and humans would still eventually become resistant to that and another antibiotic would be needed. Even then, scientists see phages as a resource that will accompany antibiotics, not be used as a standalone treatment. In the future, phages will be more efficient and effective.
How does Phage Therapy Work?
The first step in this treatment is to identify what type of bacteria is causing the problem. Different phages target different bacteria, so the bacteria cannot be treated effectively if it is unclear what type of bacteria needs to be targeted.
The appropriate type of phage will then be collected, and the next step is to screen the phages in order to see which ones will be most effective. This is done by putting many phages in a dish with a sample of the selected bacteria and seeing which fight it most effectively. Only the best phages will be used on patients, who have far more of the bacteria in their bodies than was used during the screening.
Finally, the best phages are combined to create a phage cocktail and are given to the patient.
What are the Problems with Phage Therapy?
Although there are amazing success stories where bacteriophages save lives and fight superbugs, there are many reasons why people are skeptical. Bacteriophages could be an amazing solution to the problems of modern medicine, but it wouldn’t be fair not to acknowledge the potential downsides as well.
Because they were originally short lived with the release of antibiotics, there is no data in the US to prove the consistency or efficacy of phages, and the data from countries that still use it is very messy and lacking. People won’t want to risk using this unproven treatment when they could use highly consistent antibiotics.
Antibiotics are not only super effective, but also relatively inexpensive. Since they are the current default method and work well in terms of money and treatment, the demand for phage therapy will not be so high.
Typically an infection can be treated with one or two antibiotics, which are mass produced and come straight from the bottle. Phage therapy requires dozens of phage strains, and since phages are living things each one is different.
The process of collecting, sorting, and testing phages requires significantly more work than simply swallowing a few pills, and due to the fact that all phages are different, the FDA (Food and Drug Administration) will probably only approve them in emergency circumstances.
While antibiotics can simply be prescribed and brought home, phage therapy must be performed by a medical professional, and requires special training for how to prescribe and use phages. Based on the inconvenience and little need, physicians may not see a need to learn this.
Finally, since phages only target bacteria and can’t penetrate cells, they cannot be used for any bacteria found inside cells.
What is Currently Being Done in This Field?
Although phage therapy is a relatively small field in the US based on an abundance of antibiotics and other antimicrobials, there are certainly still departments and even entire companies working to make advances in this field.
In terms of colleges and universities, UC San Diego has one of the best phage therapy facilities after having experienced a successful application on a staff member facing imminent death. After psychiatry professor Tom Patterson contracted a rare and deadly superbug on vacation in Egypt, he was brought back home to the university hospital.
There weren’t any bacteriophage resources there at the time, but after multiple antibiotics failed they were cleared for emergency phage therapy by the FDA. Mr. Patterson’s life was saved, and shortly after that the university created the Center for Innovative Phage Applications and Therapeutics.
There are also companies such as PhagoMed, Adaptive Phage Therapeutics, AmpliPhi, and Technophage that are working to develop effective phage cocktails, libraries, and susceptibility tests. They are all working on different projects with the same goal: to increase the efficacy and availability of phage therapy throughout the country.
Key Takeaways
-Phages are viruses that infect bacteria, and they can be used as an alternative to antibiotics to help slow down the growing issue of antibiotic resistance.
-Phages can perform therapy through two different cycles: the lytic cycle and lysogenic cycles. The lytic cycle involves exploding the bacteria, the lysogenic cycle simply injects phage DNA that duplicates.
-The process of choosing phages involves collecting them, bringing them to a phage library, testing each individual phage for efficacy, and mixing the phages into a phage cocktail.
-As with everything, there are some problems that lead to skepticism around phage therapy. These include lack of data to prove phage therapy is effective, small market in comparison to easily accessible antibiotics, and the need for many phages to treat a single infection.
-There are facilities around the country working to increase the efficacy and availability of phage therapy.
Hi, thanks for taking the time to read my article! My name is Raina Bornstein, I’m 14 years old and I love to learn about different kinds of science. I’m particularly passionate about medicine, connectomics, and biotech. I’d love to connect on LinkedIn (linked below), or reach out to me at rainabornstein@gmail.com to talk or collaborate. I can’t wait to hear from you!
