An alternative treatment for antibiotic-resistant infections that are raising concern nationwide already exists. But there's a big problem. The treatment is not approved for use in the United States.
And it could be a decade or more for the treatment, long used in Russia, former Soviet nations, Eastern Europe and more recently in Asian nations, before it gets regulatory approval for safety and effectiveness.
The treatment method involves bacteriophages -- viruses that kill bacteria -- that are the world's most abundant organisms. Each phage injects DNA into a specific bacterium to replicate itself, killing the bacterium in the process.
Our bodies and our environment are full of phages. Phage experts say creating a treatment involves finding a phage that destroys an infective bacteria such as MRSA, E. coli, salmonella or listeria, or even the bubonic plague, especially infections resistant to antibiotics.
Recently, the U.S. Centers for Disease Control and Prevention sounded a national alarm about "Superbugs" or CRE -- carbapenem-resistant Enterobacteriaceae. The "nightmare bacteria" are becoming untreatable to a point of killing one of every two patients whose infections reach the bloodstream, the CDC states.
For decades, phage has been studied in the United States, including the University of Pittsburgh Bacteriophage Institute. Biologists largely agree that phage treatments exist for antibiotic-resistant infections, although the effectiveness has not been evaluated according to Western research standards. Others contend the evidence is largely anecdotal. It's true that bacteria can develop resistance to specific phages, but phages are so abundant that many can target a specific bacterium and could be used in therapy.
The U.S. Food and Drug Administration requires extensive research and human clinical trials before approving a drug's safety and efficacy. An obstacle to this happening with phages in the United States is the high cost of the research, development and approval process. It can cost up to $1 billion, a prohibitive sum for most pharmaceutical companies, especially for a drug that would work with a single prescription.
A growing number of deaths from resistant infections is raising interest in the potential of phage treatments.
"The time is coming for phages to be used [in the United States], but there is quite a way to go before phages will be in the drug stores," said Revaz Adamia, director of the G. Eliava Institute of Bacteriophages, Microbiology and Virology in Tbilisi, Georgia, considered the home of phage development.
"We've been getting more and more letters from abroad, including the United States, from people interested in phage treatments," he said. "We've had four [MRSA] patients from the U.S., and we cured them. It was absolutely hopeless for them in their native land, and they were desperate."
He said his institute has 1,500 phage treatments and is manufacturing and exporting them, including a shipment of 100,000 doses two weeks ago to China. The institute also has shipped phage treatments to Korea, Czech Republic and former Soviet nations.
"If regulators will not change some rules, it is hard to imagine phages being available for a wider audience," Mr. Adamia said. "The point isn't willingness. The point is regulation, if the West wants to use phages."
The American bias against phage is rooted in medical history, scientific preferences, Cold War distrust and some intellectual pride. Another factor is the American propensity to develop medications based on the profit motive unless the government provides funding to stem an epidemic. So far, scientists say phage treatments won't bring an adequate return on investment.
For 70 years, America has focused on antibiotics -- highly successful treatments that are the drug equivalent of a nuclear bomb. Antibiotics kill large numbers of different types of bacteria, whether they're good, bad or neutral to human health. The Soviets focused on phage, which is a sniper bullet that kills one specific bacterial infection. Different phages are needed for different bacterial infections.
The United States and Soviet Union developed their respective treatments in parallel fashion with little interaction.
Felix d'Herelle discovered the bacteriophage in 1917 and later worked at the Georgian institute founded by Joseph Stalin, who eventually would execute its founding director George Eliava. Phage was heralded in Soviet nations for its success, and d'Herelle was nominated eight times for the Nobel Prize without ever winning it. The plot of Sinclair Lewis' 1925 novel, "Arrowsmith," includes competition between phage scientists, referring to d'Herelle's work.
During World War II, the Eliava Institute pumped out phage treatments for the Soviet Red Army. The United States, meanwhile, used penicillin first formulated in 1928 but not fully developed as a treatment until the early 1940s. The United States produced 2.3 million doses of penicillin drugs for the Normandy invasion.
Eastern Europeans express amazement upon discovering that Americans are dying from infections routinely treated in their homeland with phage. The United States usually has treatments for diseases that kill thousands elsewhere. But Americans also have been reluctant to embrace a treatment that's been described as "Stalin's forgotten cure."
But the emergence of deadly antibiotic-resistant infections has raised the specter of returning to the pre-penicillin eras when few if any treatments existed against infections.
"If we had taken the long distant view in what we are doing clinically over a long period time, we should have tried to broaden our arsenal in dealing with bacterial infections, and it should have included bacterial-based infections," said Graham Hatfull, a biotechnology professor who works with phage and is co-director of Pitt's Bacteriophage Institute. Last year his team published a study about a phage treatment for acne. "Now with bacterial pathogens on an inevitable march toward resistance, we are wishing we had started earlier on phage therapy."
But he and others say phage treatments aren't ready for prime time in the United States. Published research on phage effectiveness is lacking. Bacteria also can incorporate segments of phage DNA to make them even more infectious, which raises added caution.
Mr. Hatfull and Ryland Young, a Texas A&M phage biologist who directs that university's new Center for Phage Technology, say the few overseas studies don't meet Western standards. A phage institute in Hirszfeld, Poland, has published useful studies that show "impressive success rates for infections that have shown resistance to antibiotics," Mr. Young said. "These results suggest that phage therapy should at least be accorded the status of emergency treatment for cases where antibiotic treatments have failed."
Phage clearly infects and kills bacteria, Mr. Hatfull said, "so there is no question they should be used. But it's a matter of utility of using them in a rational and predictable way."
Roger Hendrix, also co-director of the Pitt Bacteriophage Institute and a distinguished professor of biological sciences, is more cautious.
"I don't want to sound like I'm throwing cold water on the whole thing," he said, "I think there's real potential there, but there are hurdles that have to be overcome. I would like to see it work. But so far it hasn't."
Step by step
A clinical trial of a therapeutic bacteriophage preparation -- done at the University College London's UCL Ear Institute and its partner, the Royal National Throat, Nose and Ear Hospital and reported in 2009 -- effectiveness and safety in treating a chronic ear infection, otitis, caused by antibiotic-resistant Pseudomonas aeruglinosa.
With growing confidence that phage treatments work or show promise, the Texas A&M center and Intralytix, a small Baltimore company, have strategies to use phage to kill infectious bacteria on fruits, vegetables, meats and cheese with treatments in the works for veterinary use. This stepped approach eventually could lead to human treatments. That strategy provides time for people to embrace the idea of beneficial viruses in similar fashion to the concept of good bacteria in probiotic supplements that help prevent gastrointestinal infections and aid metabolism.
Co-founder and chief scientist at Intralytix, Alexander Sulakvelidze said the company now has three products to kill dangerous foodborne bacteria, including listeria, E. coli and salmonella.
"I don't see any reason why this will not happen. I think it will happen. It just takes time and money and most drug companies, like us, are small companies and this is expensive," he said. "Big Pharma is cautious, although I clearly see interest among the big players."
The Centers for Disease Control & Prevention and the National Institutes of Health, the nation's major funding source for health research, "would be prudent to invest some money it currently is using for antibiotic research on phage-based therapies," Mr. Young said.
"In our laboratory we have one phage for MRSA that destroys 85 percent of the strains of MRSA that we've encountered. That's a scientifically available fact. There are other phages, and the one wasn't hard to find. I would say it wouldn't take much work to make that 100 percent effective, but there is no use in doing it. What would you do with it? That would be a major undertaking."
On the other hand, he said, a person with antibiotic-resistant MRSA infection can be in a life-threatening situation.
There are signs that phage treatments are drawing interest, even if there's no push to develop phage therapies in the United States.
Dr. Adamia said he recently received a call from the Walter Reed Army Institute of Research inquiring about phage. Last September, Walter Reed researchers published a study showing that a single injection of phage provided mice with partial protection from the bubonic plague.
"Here is the point," he said. "I hope that this will increase. and more and more people will understand that phages are absolutely safe and in many cases help a lot with zero side effects. I'm optimistic that this approach will help a lot of people."
David Templeton: firstname.lastname@example.org or 412-263-1578.