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Viruses Become Medicine as Scientists Study Old Ideas - 2003-09-24

Viruses are best known for causing diseases like SARS and AIDS. But some scientists are re-discovering forgotten ways to use viruses to cure diseases.

Virus researcher Sankar Adhya flips through a stack of small plastic dishes at his laboratory at the National Institutes of Health, just north of Washington, DC. Each dish is covered with a film of bacteria, and each film is riddled with holes a centimeter or two wide. Mr. Adhya says the holes are caused by a virus called a bacteriophage or phage for short.

"Phage infects bacteria and kills them," he said. "Each phage particle will kill a bacterial cell, [it] will disintegrate it. And the new phage particles that are coming out from [the] first infection invade the neighborhood."

In this way, the phage spreads quickly through the neighborhood bacteria. The virus hijacks a bacterium's cell machinery, turning it into a tiny virus factory. Then, the virus disintegrates the bacterium's cell wall, releasing hundreds, or thousands, of new viruses, which then hijack neighboring bacteria, and so on. In a few hours, the viruses have wiped out the whole neighborhood, leaving holes in the bacterial film on Mr. Adhya's dishes.

Virus researcher Carl Merril at the National Institutes of Health says when Canadian scientist Felix d'Herelle discovered bacteriophages in the early 20th century, he saw that these bacteria-hunters had potential.

"D'Herelle did realize that these could be used as an antibiotic," he explained. "He actually published a paper in 1926 where he reported success in treating all sorts of animal diseases using bacterial viruses."

Doctors soon used phage therapy to treat skin infections, stomach illnesses, and many other diseases. But there were problems. Viruses and bacteria were poorly understood at the time. Each type of virus can only infect one type of bacteria. So Mr. Merril says phage therapy often did not work because doctors used the wrong virus. Worse yet, preparations were often contaminated.

"Many of the early preparations may have been as detrimental as the original bacteria were," said Mr. Merril.

When chemical antibiotics became available in the 1940s, phage therapy fell out of favor in much of the world.

But after decades of exposure to antibiotics, more and more bacteria are becoming immune to them. Sandro Sulakvelidze, chief of research at Intralytix, a Maryland-based biotechnology company, says antibiotic resistance threatens to roll back the revolution in medicine that antibiotics have brought about. For example, surgeons need antibiotics to kill germs like Staph. aureus that would otherwise infect patients getting organ transplants, open-heart surgery, or other surgical treatments.

"And so if you are no longer able to suppress those infections, you can have a tremendously successful open hear surgery, but the patient will die because of an untreatable Staph. aureus infection, for example," said Mr. Sulakvelidze.

Mr. Sulakvelidze remembers a time in the mid-1990s when a doctor friend lost a patient to a strain of antibiotic-resistant bacteria.

"He couldn't treat him anymore, and was sort of hopeless at that point," he said. "And without thinking twice, I asked him a very naďve question, I thought. 'How about bacteriophages, so they didn't work either?' And he looked at me, and I realized this is the first time he had heard about therapeutic phage uses to treat human infections."

Mr. Sulakvelidze says he was shocked to discover doctors here had never heard of phage therapy. He thought his question was naďve because phage therapy is still commonly used in his native Georgia. That's because antibiotics reached the Soviet Union much later than in the West. So phage therapy continued, and is still a mainstay of medical treatment in former Soviet countries. Mr. Sulakvelidze says in Georgia today, phage preparations are available alongside antibiotics at the local pharmacy.

One of the major phage research centers is a clinic in Tbilisi, Georgia, founded by one of phage pioneer Felix d'Herelle's co-workers. Virus researcher Betty Kutter at Evergreen State University has sent patients to the Tbilisi clinic to treat infections when antibiotics failed. She says in some ways, phages are better than antibiotics.

"A lot of times, if you take an antibiotic for an infection it kills off all the good bacteria, in your gut, for instance," said Ms. Kutter. "And then you have all sorts of other problems with other bacteria, bad bacteria, that manage to get in there."

She says phages are much more specific. Each type of phage can only attack one type of bacteria. So phages that attack disease-causing bacteria leave good bacteria alone.

They also leave human cells alone. So she says there's no reason to worry that a virus used to treat a disease will actually make you sick.

Sankar Adhya says in the early days, phage therapy was not tested scientifically. And regulatory agencies like the U.S. Food and Drug Administration, or FDA, did not exist. So he says advocates of phage therapy have a lot of work to do to bring it back into the mainstream.

"To make phage therapy acceptable we have to do the basic science, give a scientific face, to convince not only the FDA type of organization, but also the medical doctors around the country," added Mr. Ashya.

Mr. Sulakvelidze's company, Intralytix, is working on viruses that can rid livestock of disease-causing bacteria like Salmonella and E. coli. Another company is developing a gel to treat cuts and burns. Other products are also in the works. Someday soon, this old idea in medicine may be the newest thing in your medicine cabinet.