Issue 11.10 | October 2003
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How Ravenous Soviet Viruses Will Save the World
They're called phages. And they eat drug-resistant bacteria for breakfast.
By Richard Martin
As a child in the early '70s, alexander Sulakvelidze dreamed of rising to the top of the Soviet scientific establishment. Fascinated by life at the smallest scales, he earned his PhD in microbiology from Tbilisi State Medical University in his hometown, the capital of Soviet Georgia. By the time he was 27, he was deputy director of the Georgian equivalent of the Centers for Disease Control and was collaborating with the Eliava Institute, a local hotbed of research in infectious diseases. He stood at the threshold of a brilliant career.
But when the Berlin Wall fell in 1989, the Soviet Union's formidable scientific infrastructure toppled along with it. By the early '90s, Sulakvelidze found himself laboring in a backwater. Like a Georgian Ginsberg, he watched the best minds of his generation go to waste.
"There was nothing left to do," he recalls. "Good scientists would come to work and spend all day playing cards and chess."
Determined to avoid that fate, he turned to the US. He applied for a National Academy of Sciences research fellowship at the University of Maryland Medical Center under Glenn Morris, one of the world's foremost epidemiologists. He got the nod, and in 1993 Sulakvelidze left Tbilisi for Baltimore.
He arrived to find the hospital in the midst of its own crisis. Enterococcus, a common bacteria that infests the human stomach and intestinal tract, was showing signs of resistance to vancomycin, the antibiotic of last resort. Between mid-'92 and mid-'94, vancomycin-resistant Enterococcus, or VRE, infected 75 patients, killing 6. A random sampling in fall '93 found that 20 percent of patients had VRE in their bloodstream. People were dying, and there was nothing anyone could do about it.
The Georgian microbiologist was nonplussed. Where he came from, infections were treated not only with antibiotics, but with viruses that attack and destroy bacteria. One day, as Morris lamented his inability to fight the outbreak, Sulakvelidze interrupted to ask: "Why don't you try bacteriophages?"
With that question, Sulakvelidze initiated a new phase in the age-old struggle between humans and microbes - one in which scientists are enlisting the power of evolution rather than fighting it.
The cause of the Maryland med center's sudden epidemic was no mystery. Wanton use of antibiotics, both in human patients and animals raised for food, reduces the danger of bacterial infection, but also forces bacteria to adapt at a prodigious rate. The germs that survive breed new generations of superbugs, impervious to even the most powerful medicines.
In an escalating arms race, scientists have scrambled to develop ever more potent drugs - but the bugs are winning. In January 2002, seven people died at a Tokyo hospital when they were infected with a drug-resistant strain of Serratia enterobacteria. The following March, all heart surgery at Scotland's Edinburgh Royal Infirmary was suspended after 13 patients came down with a methicillin-resistant strain of Staphylococcus aureus, the number-one cause of hospital infections. A month later, a 40-year-old diabetic woman in Detroit was found to be suffering from the first known vancomycin-resistant strain of S. aureus. Drug-resistant infections kill 40,000 people each year and account for up to $4 billion in additional treatment costs, according to the National Foundation for Infectious Diseases.
Where this leads is frightening to contemplate. A growing chorus of experts foresee a world in which formerly vanquished illnesses like tuberculosis and pneumonia rage out of control, and immune-compromised patients succumb to once-harmless infections.
"The war against bacteria is not something that can be won by humans," Sulakvelidze says. "If you try to wipe them out, they will always return. Only they will be stronger."
If the problem is classic Darwinian adaptation, the solution might lie in the very same process. Thus, Sulakvelidze, Morris, and others have turned their attention to bacteriophages, which have evolved over eons to destroy bacteria. This approach to fighting infection lets nature do the lab work usually carried out at tremendous expense, and with high failure rates, by the pharmaceutical industry. In contrast to engineered drugs, phages are as numerous and varied as the bacteria they attack. What's more, they evolve along with their prey, matching bacterial adaptation step by step.
The hard part, as Sulakvelidze and Morris have found, isn't harnessing them for medical benefit. Rather, it's bringing a dusty Soviet remedy into the 21st century.
The discovery of phages is lost in murky rivalries and scientific disputes. What's certain is that in 1917 an eccentric French-Canadian scientist named Félix d'Hérelle isolated them and named them bacteriophages - eaters of bacteria. Working independently, George Eliava discovered the minute creatures after collecting specimens from the Mtkvari River, which flows through the Georgian capital of Tbilisi. Eliava, head of the city's Central Bacteriology Laboratory, left a slide of river water containing cholera bacteria under a microscope for three days. When he returned, the germs were gone. Eliava surmised that something had destroyed them, and, like d'Hérelle, he set about isolating the tiny bacteria killers. Eventually, the Georgian struck up a fruitful collaboration with his French colleague. They worked together at the Pasteur Institute in Paris and later at the Institute of Microbiology, founded in Tbilisi in 1923 and later renamed in Eliava's honor.
It was there that a small band of scientists pioneered a new therapy, scrupulously assembling the world's only library of phages and developing cocktails of a dozen or more to treat a variety of bacterial disorders from stomach aches to pneumonia. Phages became part of the standard pharmacopoeia in the USSR, and they even enjoyed a brief heyday in the US, where Eli Lilly had an active phage-production program in the '30s. Soviet medics used the viruses on World War II battlefields, and soldiers with the German general Erwin Rommel carried phage treatments in disease-ridden North Africa.
The embrace of phages in the West didn't last long, though. American reviews of the Soviet research cast doubt on the therapy's efficacy, and when penicillin - widely regarded as a miracle drug - reached hospitals in 1941, Western doctors essentially forgot about phages. They continued to be sold in pharmacies throughout the Soviet Union, but the decline of medical research in the post-Soviet era nearly wiped out their use. By the 1970s, the Eliava Institute had fallen into a desuetude that threatened to bury five decades of research. Like Dark Age monks, the institute's scientists struggled to keep their phage library alive.
Contributing editor Richard Martin (firstname.lastname@example.org) wrote about AIDS vaccines in Wired 11.01.
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