Later on, because of their structural and genetic simplicity and ease of growth in the lab, Western researchers tapped bacteriophages as model systems to study the molecular basis of genetics, spawning the science of molecular biology. The lab techniques that made the revolution possible were largely advanced through research on phages and their bacterial hosts.
“If you look at the early Nobel Prizes in molecular biology, half of the awards went to researchers using phages,” NIMH’s Merril says. The work also helped researchers understand the shortcomings of phage therapy of the past. Some of the preparations were contaminated. On top of that, early researchers didn’t realize that each phage type is highly specific for a given bacteria species, more finicky than Morris the cat.
Back in the Baltimore lab, Chighladze painstakingly isolates phages from harbor water by culturing them with sundry strains of bacteria. Modern technology can decipher which type of phage kills which type of bacteria. For a broad spectrum assault, purified phages can then be combined in cocktails.
Over time, bacteria naturally develop resistance to phages, as they do to antibiotic drugs. Drug resistance, however, has been accelerated by global misuse of antibiotics. Phages, in contrast, can adapt to keep up with the bacteria, matching their prey mutation for mutation. “It’s a biological arms race,” explains Sulakvelidze, a former Georgian lab director who worked extensively with the Eliava Institute. Back in Tbilisi, phages never fell out of fashion. They’ve been in use in humans for 70 years with claims of miraculous results. Phages offer other advantages over antibiotics. For starters, they don’t harm benevolent bacteria living in symbiosis with human hosts. But even with such positive traits, phages do have their downside.
Rather than kill bacteria, some phages make them even more lethal. This happens, for example, with the bacterium that causes cholera.
In the mid-1980s interest in the West was renewed when British and Polish researchers studied phage success against microbes in animals. But burgeoning cases of antibiotic-resistant bacterial infections really prompted the surge in Western research.
Today Intralytix and Phage Therapeutics, like a handful of other companies, are developing phage catalogs to sequence the genetic code of a select hundred or so of the inestimably large number of species of bacteria-killing viruses found in nature. Although Intralytix has opted to use only naturally occurring species for now, other companies are attempting to genetically engineer phages so that they overcome bacterial resistance.
The first human clinical trials in the United States are slated to begin within a year. Possible applications include impregnating artificial skin or other materials with phages to heal infected wounds, intravenously medicating patients suffering from bacterial infections of the bloodstream, and culturing custom phage therapies from infected patients.
Psychological barriers to phage acceptance remain. “Some people worry about getting treated with a virus,” Merril says, “but they don’t realize that many of today’s leading vaccines are made with live virus.” Yet even Merril doubts phages will ever be a panacea or more than an adjunct to antibiotics.
Whatever the future, phages have already earned a respected place in the annals of medicine. We shall see how much larger their entry becomes.