The first antibiotics ever cured deadly infections and their initial developers were awarded the Nobel Prize. But these miracle drugs soon exposed their weakness: When antibiotics are overused, they become less effective because the bacteria they are designed to kill develop escape strategies. This flaw has led scientists to look for alternative solutions.
An alternative to antibiotics is phage therapy, which uses viruses to attack bacterial cells. Conceived more than a century ago, phage therapy fell to the wayside as antibiotics came to prominence, but recently, the field has seen a resurgence. In “The Living Medicine: How a Lifesaving Cure Was Nearly Lost — and Why It Will Rescue Us When Antibiotics Fail” (St. Martin’s Press, 2024), science journalist Lina Zeldovich recounts the complicated history of phage therapy and its proponents, while also shedding light on how the treatment could save humanity in the future.
The Phage Whisperer
Biswajit Biswas pulled out a syringe full of phages and injected them into his lab mice, one after the other. The mice weren’t sick, so he wasn’t using the phages as medicine. He simply wanted to know how long the phages would persist inside the mice — an experiment that [Georgy] Eliava and [Felix] d’Herelle had once done to understand how far phages could travel in rodents’ bodies.
About once a day, Biswas would check the mice’s blood to see if phages were still floating around inside them. Usually, most of the phages were lost because they were quickly filtered out by the liver and spleen, but sometimes a tiny fraction survived. Biswas would collect the remaining phages, grow them — and inject them into mice again.
Biswas was working on this unconventional project in the mid-1990s in the lab of Carl Merrill, an NIH scientist and early phage enthusiast who was playing with the idea of using them to treat disease.
His mice blood tests were happening at the same time that [Alexander] Sandro [Sulakvelidze] and [Glenn] Morris were having their first phage talks and putting together their VRE [vancomycin-resistant enterococcus] proposals. Geographically, the two teams weren’t too far from each other. Both were located in Maryland. Both understood phages as medicinal agents that the rest of the medical field considered futile.
However, Merrill approached the problem from a different angle. Instead of treating sick mice with phages, he wanted to know how long live drugs could survive inside an organism. In humans and animals, the liver, spleen and immune system deal with foreign invaders and filter them out quickly.
Merrill wanted to know how long phages could survive before they were swallowed up by the body’s natural defense mechanisms. He also wanted to know if phages could evolve to survive being swallowed. By hand-picking live phages and re-injecting them, Biswas and Merrill hoped to find answers.
“It was a selection process,” Biswas explains. “I was growing phages and injecting them into mice intravenously and inside the abdomen, and the next day, thirteen or eighteen hours later, I would draw the blood of the mice and take those phages and grow them again — one passage after another.” This was a method that d’Herelle had outlined in his book “The Bacteriophage and the Phenomenon of Recovery”, which Eliava translated.