West Recruits Bacteria Assassins 

Half a century ago, antibiotics revolutionized medicine by turning many once-deadly infections like tuberculosis into minor impediments. But overuse is rapidly rendering antibiotics ineffective, and scientists know they need a replacement fast. One of the most promising options is one that's been used in Eastern Europe and Russia for decades: bacteriophage therapy.

The word bacteriophage comes from bacterium, plus the Greek phagein, to eat. Phages, as they're also called, were never thoroughly studied as therapies in the West, mainly because antibiotics proved to be so effective. But with resistance mounting fast, researchers have begun aggressively studying phage therapy, and the first treatment could enter the Western market as soon as 2004.

"The beauty is that the phage will only latch onto and destroy (one) strain of bacteria and leaves all the good bacteria unharmed," said Denise Curnow, CEO of Novolytics, a U.K. company working on a prophylactic to prevent staph infection.

Staph, short for Staphylococcus aureus bacteria, is very common in hospitals. It's carried on the skin and in the nasal passages, and was once a major problem for surgery patients. Antibiotics solved that problem, but antibiotic resistance to those commonly used against staph infection is increasing.

The cream Novolytics is developing would kill staph infection in the nasal passages and prevent its spread. It could also be rubbed on instruments such as catheters to prevent infection. They're beginning the second of the three phases of clinical trials necessary for approval in the United Kingdom, and plan to repeat the process for approval in the United States. Tests so far have been promising, Curnow said. It works, she said, and there are no side effects. They'll have more results by fall, she said.

"I suppose some of the best solutions are the most elegant," she said.

Felix d'Herelle of the Pasteur Institute in France dubbed the bacteria-eaters "bacteriophages" in 1917. They're one of the simplest life forms on earth, with a head made of DNA, and spidery legs that grab bacterium. Phages inject bacteria with their DNA, and the bacteria rapidly make copies of the phage until the bacteria explodes. The explosion launches hundreds of new phage particles into the infected area.

The Republic of Georgia uses phage therapy regularly as a treatment for many types of infections.

"They basically don't cut off feet because of diabetic ulcers in Georgia because their staph phage works so well," said Elizabeth Kutter, referring to the fact that such infections often lead to amputations in the West. Kutter is the director bacteriophage research at Evergreen State College in Olympia, Washington.

Kutter has helped at least two patients with seemingly untreatable infections get well by traveling to the Tblisi clinic in the Republic of Georgia for treatment.

While phage treatments are common and effective there, the Western world requires more rigorous proof that therapies are safe and effective. So companies like Novolytics, Intralytix, Exponential Biotherapies and GangaGen have taken a commercial interest in taking phage treatments through the necessary testing and marketing.

One potential drawback is that phage therapies might be too specific for widespread use against infection, according to Carl Merril, a senior investigator at the National Institutes of Health. For example, one phage might work for one strain of Streptococcus pneumoniae (the most common type of pneumonia) but not for the 27 others.

One solution is to make a "cocktail" treatment containing several phages, but it remains to be seen how useful that approach will be.

The beauty of antibiotics was that any one antibiotic worked for many different types of infection. But it is also turning into their downfall, because they also kill good bacteria that humans need to remain healthy. Moreover, bacteria are good at finding ways to outsmart the drugs.

According to the Centers for Disease Control and Prevention, nearly 2 million people in the United States acquire an infection while in a hospital every year, and 90,000 of them die. More than 70 percent of the bacteria that cause these infections are resistant to at least one of the antibiotics commonly used to treat them.

Phage therapies are at the opposite end of the spectrum. They kill the bacteria they're meant to almost without fail, and bacteria don't become resistant nearly as often. However, Merril cautioned, "Given the narrow host range of phage, you can't use it like penicillin."

Still, Kutter and others believe phage therapy is the greatest hope against antibiotic resistance. Kutter will host the 15th annual bacteriophage conference from July 23-27 at Evergreen, and expects about 100 researchers from 13 countries.