Phage Therapy — The War Against Superbugs
The way out of possibly one of the biggest epidemics ever
The Story of a Survivor
Imagine you’re a kid born with cystic fibrosis (a lung disorder that causes sticky mucus production) and grow up constantly fearing death.
Then, imagine you’re told that your lungs have been infected by the bacteria Mycobacterium abscessus, a relative of tuberculosis. To treat the infection you’ve been taking strong antibiotics almost your entire life. Then, at the age of 16, you have a double-lung transplant (both lungs transplanted), hoping it would cure you of both the infection and cystic fibrosis.
However, you’re told that the drug you were given to prevent rejection of the transplanted lungs by your body, has allowed the deadly bacteria to come back. And the worst part? The bacteria can’t be killed by any of the antibiotics you took before.
Well, you might have to imagine this. But for 17-year old Isabelle Cornell-Holdaway, this was the unfortunate truth. After her condition continued to worsen because of the bacteria, her doctors told her that she had less than a 1% chance of survival.
For patients with re-growth of Mycobacterium after transplant, in our experience, have all gone and died — Helen Spencer, Isabelle’s Doctor
Then, Isabelle’s mother, Jo, discovered phage therapy. She contacted researchers at Harvard, who agreed to help her. Isabelle’s body was injected with phages designed to attack and kill the bacterial colony. Within weeks, Jo noticed a difference in Isabelle’s healths, and Isabelle quickly recovered and was soon out of the hospital.
Now, Isabelle is learning how to drive and is performing outstandingly well in school. For her, life has returned to almost normal.
This story shows that phage therapy is not some crazy, unproven science. It has worked numerous times and is our way out of the return of an era when a simple cut could kill you with bacterial infections.
Superbugs
Before we begin, if you haven’t read my previous article on superbugs, go check it out first. It’ll be much more difficult for you to understand this article if you don’t know what superbugs are and what the big problem is.
What is phage therapy?!?!
Phage therapy involves using bacteriophages (that’s where ‘phage’ comes from), a type of virus, to kill bacterial infections.
Now you may be thinking, “But doesn’t injecting a bunch of viruses into a patient’s body lead to viral infections?” In this case, it doesn’t.
This is because viruses are like guided missiles. They target certain types of cells, and will only attack those cells. Bacteriophages are specific to bacterial cells. This means they will hunt bacteria like a pack of wolves, but leave human cells alone.
So what can we do with them?
How is this more useful than antibiotics?
1. Because of their specificity, bacteriophages only kill the bad bacteria.
When a person takes antibiotics, they don’t only kill the infectious bacteria in their body. Antibiotics instead behave like a bomb, killing everything they come across. This includes the ‘good’ bacteria that are important to your body, assisting in processes such as digestion.
Bacteriophages, on the other hand, are, as I mentioned, like guided missiles. They are not only specific to bacterial cells, but each different type of bacteriophage is specific to one bacterial strain. This means that one bacteriophage will only target the type of bacteria it was designed to attack, and leave all others alone.
2. Bacteria are not resistant to bacteriophages.
In the case of antibiotics, bacteria are the only ones mutating and evolving. This allows the bacteria to become resistant to the antibiotics since the medications don’t change in any way.
Bacteriophages, however, mutate and evolve at even faster rates than bacteria. This means it is very difficult for bacteria to effectively develop resistance to specific bacteriophages since the viruses would just evolve into a strain that the bacteria isn’t resistant to.
3. We can make antibiotics more effective.
Bacteriophages don’t have to kill the bacteria. They can be engineered to disrupt genes responsible for antibiotic resistance. By doing this, we can make the antibiotics effective once again, allowing us to continue using them to fight against bacterial infections.
When first treating infections, we can put the bacteria in a catch-22, where we administer antibiotics, but also bacteriophages that prevent resistance development, allowing full eradication of the bacteria.
Challenges
Even with all the benefits, phage therapy isn’t perfect. There are many challenges that we must overcome to reach a point where phage therapy can be widely used.
1. We need to develop a library of phages
The specificity of phages also brings with it a huge problem. Since we can’t use one phage on multiple bacteria, we must develop an easily-accessible library of phages designed to target every type of bacteria that can be a danger to humans.
This is super expensive and requires a lot of work to accomplish. There are millions of different types of virulent bacterial species out there, all of which would require specific phages. After determining which phages are required, we have to develop these libraries in multiple locations to make the phages easily accessible everywhere around the world.
2. We must genetically engineer the phages to achieve the exact function we want
When we need to use the phage to restrict the development of antibiotic resistance, especially, we would have to genetically engineer the phages to target specific genes. This leads to even more difficult since we also have to figure out which genes to target, and how to disrupt them.
3. The body doesn’t like them
Even though bacteriophages do not attack human cells, they are still considered foreign entities. Therefore, when they are released into the bloodstream, they are quickly removed/killed, while the body also develops immunity to those phages. This means one specific phage can only be used once, to avoid an immune reaction.
4. We can’t predict the behaviour of phages
Even if we genetically engineer phages, we can’t ensure they will behave the way we want. There’s a possibility they won’t kill the bacteria.
But an even worse possibility is the fact that the phages could help the bacteria to develop resistance. Sometimes, instead of immediately killing the bacteria, phages can incorporate their DNA into the bacterial DNA, and enter a rest phase.
Later, they can be triggered to develop more viruses that escape, killing the bacteria in the process. When they do this, they can take some sections of the bacterial DNA with them. When they infect the next virus, this DNA can be incorporated into the new bacteria’s DNA, in a process known as transduction.
If the gene the virus takes with itself happens to be a resistance gene, the process of transduction could lead to other bacteria developing antibiotic resistance, which essentially reverses the entire point of phage therapy.
5. Research is super slow
You might be surprised to find out that phage therapy isn’t something new. The idea of phage therapy was proposed even earlier than the development of antibiotics.
So what went wrong? Why have we still not developed it?
Because of the advent of antibiotics. When they were discovered, all research into phage therapy in the West was quickly halted, since it was considered to be useless.
Scientists in the Soviet Union did continue to experiment with the method, and even had some success. However, due to poor methods of reporting on the data, all the information is essentially unusable today.
This means, when research did start up again, we were back at square one. We had to start everything anew, from optimizing methods of introducing phages into the patient’s body to engineering the phages to achieve desired functions.
And even now, our research is moving at a snail’s pace, due to the lack of funds and interest in the field. Pharmaceutical companies, especially, are unwilling to invest money into this research, due to the greater economic prospects in developing new antibiotics.
So where does that leave us?
We still have a far way to go. We have yet to perfect phage therapy for consumer usage and have yet to deal with the many challenges associated with it.
To move forward at a quick enough rate, however, we will need governments, scientists, and pharmaceutical companies to come together and research. Without that, we might truly be screwed.
What did you learn?
- Superbugs can’t be killed by antibiotics
- Phages are viruses that only target bacteria
- There are many advantages to phage therapy, including specificity
- There are also a few disadvantages, such as increased costs, as well as the requirement of a phage library
- We need to invest more money, time, and energy into researching it
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