Love Me Love My Phages

Love Me Love My Phages

Eat Me:

The Soviet method for attacking infection that we can learn from.

By Daria Vaisman

Posted Tuesday, May 30, 2006, at 12:41 PM ET

From: Medical Examiner_Health and medicine explained.

(Illustration Above is stylized Bacteriophage)


In the 1920s and '30s, with diseases like dysentery and cholera running rampant, the discovery of bacteriophages was hailed as a breakthrough. Bacteriophages are viruses found virtually everywhere—from soil to seawater to your intestines—that kill specific, infection-causing bacteria. In the United States, the drug company Eli Lilly marketed phages for abscesses and respiratory infections. (Sinclair Lewis' Pulitzer-winning Arrowsmith is about a doctor who uses phages to prevent a diphtheria epidemic.) But by the 1940s, American scientists stopped working with phages for treatment because they no longer had reason to. Penicillin, discovered by the Scottish bacteriologist Alexander Fleming in 1928, had become widely available thanks to synthetic production and zapped infections without the expertise needed for finicky phages.

But now the equation has changed. Many kinds of bacteria have become antibiotic-resistant—prompting a few Western scientists, and patients, to travel to former Soviet Georgia to give bacteriophages for treatment a try. Phages have been used in the former Soviet Union for decades because scientists there had less access to antibiotics than their American and European counterparts did. Phages were a cheap alternative, and in Soviet clinical trials, they repeatedly stopped infections. Now in a bid for medical tourists, Georgia has opened a center in its capital, Tbilisi, which offers outpatient phage treatment to foreigners. In connection with the Eliava phage research institute, which Stalin helped set up in Tbilisi in 1923, the treatment center offers personalized cures for a host of infections the United States says it can no longer do anything about.

In 2000, the Centers for Disease Control, along with other federal agencies, warned that the world might soon return to a "pre-antibiotic era." Two million people each year now get hospital-borne bacterial infections, 1.4 million of them resistant to antibiotics and 90,000 of them lethal. One example is sepsis, the infection that sickened* Joan Didion's daughter, as Didion relates in The Year of Magical Thinking. New antibiotics are being discovered. But it takes 10 years and at least $800 million to bring an antibiotic to market, according to the Infectious Diseases Society of America. The big advantage that phages offer over antibiotics is that bacterial resistance is less of a problem. Unlike antibiotics, new phage batches can quickly be whipped up to take the place of phages to which bacteria become resistant.

The word phage comes from the Greek "to eat." A phage contains genetic material that gets injected into a virus's host. Whereas "bad" viruses infect healthy cells, phages target specific bacteria that then explode. At Eliava, phages are produced as a liquid that can be drunk or injected intravenously, as pills, or as phage-containing patches for wounds. Though few published articles in Western journals report positive clinical trials—most of the recent long-term research on phages comes out of the Soviet Union—some Western scientists say that phages are safe and that they work. "There is no evidence that phage is harmful in any way," says Nick Mann, a biology professor at the University of Warwick in England and co-director of phage R&D company Novolytics.

So, why do American patients need to go to all the way to Georgia for treatment? For starters, in their natural state phages are hard to patent, the route by which drug companies lock up future profits. The first company to spend millions of dollars to prove that a particular phage is safe could allow its competitors to capitalize on the results. As important is the difficulty of regulation. There are two ways that phages are currently used in the former Soviet Union, and both pose problems from the point of view of the Food and Drug Administration. At the Tbilisi phage center, phages are personalized: You send your bacterial sample to the lab, and it's either matched up with an existing phage or a phage is cultured just for you. In the United States, by contrast, drugs are mass produced, which makes it easier for the FDA to regulate them.

Phages are also sold over-the-counter in Georgia. People take the popular mixture piobacteriophage, for example, to fight off common infections including staph and strep. These phage mixtures are updated regularly so they can attack newly emerging bacterial strains. In the United States, the FDA would want the phages in each new concoction to be gene sequenced, because regulations require every component of a drug to be identified. To do so would entail prohibitively expensive and lengthy clinical trials.

In the early years of phage research in the United States, says former National Institutes of Health scientist Carl Merril, bacteriophages allegedly killed more people than they cured. Phages are culled from dirty, wet places—the first was found in the Ganges River—a recipe for infection unless you know what you're doing. And some kinds of phages—called lysogenic phages—are potentially dangerous, because they sometimes carry genes that cause bacteria to release toxins. So, there is reason for caution.

Despite the caveats, a number of phage biotechnology firms have recently opened up in the United States and also in countries like Canada and Israel. Phage biologists point out we know much more about phage biology now than when the viruses were first discovered. Methods of using phages for treatment, from distillation to identification, have improved significantly since then. Clinicians worldwide also report that patients using phages have had good recovery rates and minor or fleeting side effects. Evergreen State College professor Elizabeth Kutter, who collaborates closely with Eliava researchers in Georgia and heads an international phage conference each year, is working with others to find ways to commercialize phages that could sidestep some of the problems with patenting and regulation. Flu vaccine offers one instructive possibility. Like over-the-counter phages, the vaccine is updated regularly with the most recent strain of flu virus—without requiring FDA approval each time.
 

There are already multiple uses for phages without FDA approval. A promising area is American agriculture and livestock, which is regulated by the less stringent United States Department of Agriculture. Domestic scientists are looking at ways in which phages could kill bacteria before they cause infection (rather than fight an infection after it has begun). Alexander Sulakvelidze, an assistant medical professor at the University of Maryland and a co-founder of the phage R&D company Intralytix, awaits federal approval for a phage-based wash for meat and produce that protects against food poisoning. Vincent Fischetti, a professor at the Rockefeller Institute, is designing a phage-based enzyme solution that can be sprayed into the noses and mouths of hospital and nursing-home patients. Fischetti and researchers in Tbilisi are also experimenting with using phages to detect anthrax and cholera in the case of a terrorist attack.

Using phages to treat infections at home, on the other hand, for the moment seems unlikely. One company recently tried to open a phage center in Tijuana but was deterred by the Mexican government. Phages might be offered someday at clinics on Native American reservations, as a casino-like quirk of legislative autonomy. But for now, U.S. patients at a loss for options may decide that Tbilisi is close enough.

Correction, June 1, 2006: The original sentence stated that Didion's daughter died of sepsis. In fact, she got sick from sepsis but died later from another condition. Click here to return to the corrected sentence.


Love Me Love My Phages