Chapter 1: Introduction to Phage Therapy

Phage therapy is gaining traction as a promising alternative in the battle against antibiotic resistance. With rising concerns about superbugs, drug manufacturers are increasingly investing in this innovative approach.

Steffanie Strathdee, a leading researcher in phage therapy, has witnessed its effectiveness firsthand. One compelling case is that of Joel Grimwood, whose condition was dire due to a bacterial infection that was unresponsive to antibiotics. Grimwood's heart implant became a breeding ground for Staphylococcus aureus, leading to severe complications. After four hospitals refused to perform a transplant due to the infection, his doctors decided to employ phages—viruses that specifically target bacteria.

A mere week into the treatment, Grimwood reported a remarkable improvement, feeling revitalized as the phages began to combat the bacteria. “It was as if it devoured the bacteria,” he described. By the end of the month, he successfully received a heart transplant.

Grimwood's story is one of around 50 documented cases in the U.S. where patients have received targeted phage infusions. Research centers, particularly at the University of California, San Diego, are optimistic that phage therapy can bridge the gaps left by antibiotic-resistant bacteria. Phages are viewed as precision tools—biodegradable "smart bombs" programmed to attack harmful bacteria without disturbing the beneficial microbes in the body. “Maintaining the microbiome is crucial,” emphasizes Strathdee.

Pharmaceutical companies are paying attention. BiomX Inc. is utilizing phages to address bacterial strains associated with ulcerative colitis, collaborating with Johnson & Johnson's Janssen Pharmaceuticals to develop treatments for inflammatory bowel diseases. Additionally, Janssen is working with Locus Biosciences to engineer phages capable of targeting respiratory and other organ infections. The U.S. National Institutes of Health is also funding various phage research initiatives, including a successful three-phage cocktail that treated a drug-resistant infection in a teenager with cystic fibrosis.

While many of these advancements are still years away from reaching the market, there is optimism that synthetic biology will accelerate the discovery and commercialization of beneficial phages. “Once significant investments come in, the advancements in this field will be astonishing,” states Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases.

Chapter 2: Historical Context of Phage Therapy

The concept of utilizing antibacterial viruses isn't new; it dates back a century and thrived in the Soviet Union. However, with the rise of antibiotics, its use dwindled in the West. Now, as bacteria become more resistant due to the overuse of antibiotics in healthcare and agriculture, the urgency for alternatives has intensified. According to the Centers for Disease Control and Prevention, an antibiotic-resistant infection claims a life in the U.S. approximately every 15 minutes.

Researchers are also investigating other beneficial properties of phages, such as their capacity to reduce bacterial virulence and reverse drug resistance. Tom Patterson, a psychiatry professor at UCSD, exemplifies this potential. After falling critically ill in 2016, he became the first U.S. patient to receive this therapy for a systemic superbug. His wife, Strathdee, suggested phage treatment as a last resort. Miraculously, just days into the intravenous therapy, Patterson showed signs of recovery, eventually responding to a common acne medication after the phages disrupted the bacteria's resistance mechanisms.

Pharmaceutical companies continue to explore phage genetics, yet the quest for viruses that can effectively target specific bacteria remains challenging. Martha Clokie, a phage researcher at the University of Leicester, has dedicated years to discovering phages effective against Clostridioides difficile, a bacterium responsible for numerous deaths in the U.S. each year. Her findings from the estuarine soils of southeast England are now being tested in animal models, with new phages also being utilized against salmonella. "Every new phage discovered reveals unexpected possibilities," Clokie notes.

The first video titled "A new weapon in the fight against superbugs | David Brenner" discusses the potential of phage therapy as a revolutionary approach to combat antibiotic-resistant bacteria.

The second video, "Factory farms, antibiotics and superbugs: Lance Price at TEDxManhattan," highlights the impact of antibiotic use in agriculture and its contribution to the rise of superbugs.