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Enemies of Our Enemies: Our Viral Friends

Can you successfully use the concept ‘enemy of our enemy is our friend’ in medical treatment? Specifically, could you use viruses to treat an incurable infection?

Born with genetic disease cystic fibrosis, Isabelle Holdaway had to deal with lung infections and breathing problems all her life. Because of persistent infections, by her fifteenth birthday, her lungs had lost more than two-thirds of their functions. As a last resort, her doctors decided to transplant her lungs even though they feared infection might spread through her entire body after the surgery. And unfortunately, that’s exactly what happened. As the infection spread beyond her surgical wound, the doctors told her mother, Jo Holdaway, that her daughter's infection couldn’t be treated and that Isabelle’s chance of survival was less than one percent. 

Desperate for a miracle, Jo decided to look into alternative treatment options for her daughter. She knew her daughter's infection was caused by bacteria, microscopic single-celled organisms. To treat bacterial diseases, we commonly take antibiotics, but because the infectious bacteria in Isabelle had developed antibiotic resistance, antibiotics would be ineffective on her.  

During her search, however, she got to know about bacteriophages. Phage in bacteriophage comes from Greek ‘phagein’ which means ‘to devour’, so the term bacteriophage literally means bacteria eater.  Scientists use the term bacteriophages to describe a group of viruses that infect bacteria and destroys the bacterial host in the process of making identical copies of themselves (check out this cool video to know more about bacteriophages!). Yes, even bacteria are not immune to viral infections! Jo wondered if the doctors could use bacteriophages to kill the bacteria that threatened her daughter’s life.  
Bacteriophages attached to a bacterial cell (Courtesy: Wikipedia)
Instead of shaking their heads, her daughter's doctors decided to give it a try. After all, treating infections using bacteriophages actually was not uncommon in the early twentieth century. Before the discovery of antibiotics, bacteriophages were often used to treat various bacterial diseases in both humans and animals. The complications that arose from those treatments and the lack of controlled studies eventually halted medical research in that field. However, there has been a resurgence of interest in bacteriophages because worldwide, antibiotic resistance has increased significantly. Isabelle’s doctors found a few research papers where intravenous bacteriophages had been used to treat bacterial infections, but not on the bacterial type that infected Isabelle. So the team of researchers and doctors had to find bacteriophages that could specifically target and kill that particular bacterial type. 

As described in their paper, Dedrick and her colleagues took bacterial samples from Isabelle and grew bacterial colonies on plates that provided necessary nutrients for the bacteria. The researchers then used these plates to screen for suitable bacteriophages: if a virus succeeds in killing off the bacteria, then the bacterial colonies would disappear, very much like nail polish remover removing ink stains. The researchers had over 10,000 potential candidates because the bacteriophage database they used had that many viruses!

Three bacteriophages emerged from their screening though—these viruses had varying levels of success in eliminating the bacterial colonies. After genetically tweaking these viruses to make them perfect killers, the researcher decided to use a cocktail of all three viruses on Isabelle. They felt this mix of bacteriophages would be more effective in eliminating the infectious bacteria. 

For the next eight months, Isabelle received an injection of the viral mix in every 12 hours. Isabelle’s body tolerated the treatment well, and her condition continued to improve as the treatment progressed. Her surgical wounds and skins lesions from infection began to heal. Her liver function improved, and she began to gain weight (she was just skin and bones when the treatment began). Serum from her blood showed no bacteria since the start of her treatment.

Right now, it's unknown whether similar treatment could be effective on patients infected with antibiotic-resistant bacteria. For the Holdaway family, however, Isabelle’s recovery is nothing short of a miracle. According to Jo, Isabelle, now 17, is doing what a normal teenager would do. Isabelle is full of energy, eating well, and arguing with her sister again.

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