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Science File

The Virus as a Tool of Medicine

U.S. scientists are showing increasing interest in harnessing 'bacteria eaters' to attack and destroy disease-causing microbes.

April 22, 2002|ROSIE MESTEL | TIMES STAFF WRITER

They are many times smaller than a bacterium--yet can easily reduce one to rubble. With steely purpose, they stick to the wall of a bacterial cell and inject their genetic material. Then they use the cell to copy themselves over and over again before crashing out and drifting off to cause more mayhem elsewhere.

Just as there are viruses that infect and cause disease in humans, so there are viruses that infect bacteria.

For decades, researchers in the former Soviet bloc used and studied those viruses--known as bacteriophage, or "bacteria eaters"--in hopes of curing disease. Now, after years of ignoring them, U.S. scientists are showing increasing interest.

The need for new approaches in fighting disease is obvious, says Marissa Miller, who directs the antimicrobial resistance program at the National Institute of Allergy and Infectious Diseases. Overuse of antibiotics has caused drugs to lose a lot of their clout as more and more bugs become resistant.

This is especially a problem in hospitals, where already-sick people can develop complications such as pneumonia and blood infections from bacteria that are resistant to nearly all available drugs.

"In these cases, the therapeutic options are very limited--and usually include drugs that are very toxic," Miller says.

In response to the problem, scientists and companies are exploring avenues such as small, antibacterial proteins, therapies to boost people's immune systems--and bacteriophage.

Some are studying specific molecules that the bacteriophage make, in the hope that they might be developed into drugs. Others envision a time when cocktails of bacteriophage that attack various dangerous bacteria might be swallowed or injected or applied to wounds to kill offending microbes.

"It's an important research area," says scientist Carl Merril, a bacteriophage expert at the National Institutes of Health. "People are going to have to put some work into it, but it'll be a real shame not to develop these agents, because I really think they can save lives."

Most Abundant Life Form on Earth

Bacteriophage--or "phage" for short--are everywhere in nature and are probably big players in the ecology of the microworld. One milliliter of unpolluted water can contain 200 million phage, and there are about 1031--1 with 31 zeroes after it--of them on this planet, making them the Earth's most abundant life form.

They vary enormously. Phage come in a medley of shapes, from simple spheres to rods equipped with elaborate landing gear that give them the look of alien insects. Their genes can be of RNA or DNA. They have different ways of getting into cells and different consequences: some always destroy their hosts while some hang around in cells for long periods without causing harm.

And while some phage have been studied in exquisite detail, some are entirely unknown.

The first phage were independently discovered around 1915 by two scientists, a British bacteriologist, Frederick Twort, and French-Canadian microbiologist Felix d'Herelle, who was working at the Pasteur Institute in Paris.

D'Herelle--who actively pursued the discovery--had cultured stool samples from soldiers suffering from dysentery and had noticed something odd about the bacteria growing in his petri dishes. The lawn of happily growing Shigella microbes had bullet-like holes in them.

The holes were places where phage had infected cells and killed them.

D'Herelle suspected he was dealing with a virus and began a long series of experiments and treatments. His first patient was a 12-year-old child who was gravely ill with dysentery. D'Herelle and colleagues made a phage preparation, swallowed some of it themselves to make sure it wasn't harmful, then treated the child and several others. All of the patients survived.

In subsequent years, D'Herelle experimented with phage to treat diseases in chickens as well as human diseases such as cholera and bubonic plague. He also manufactured commercial products containing different types of phage to treat abscesses, infected wounds, respiratory infections and more.

Products in Wide Use Before World War II

For a while, phage nostrums were everywhere. They were manufactured in the United States before World War II. They were even used during the war by the Germans: vials of phage were found in the medical kits of Rommel's forces in North Africa.

And in the Soviet Union, phage therapy flowered under Joseph Stalin, who helped D'Herelle and scientist Giorgi Eliava set up a huge research institute in Georgia, where tons of phage were manufactured daily. (Eliava was later pronounced a "people's enemy" and executed.)

In the West, however, phage therapy was dropped entirely--in large part because of the discovery of penicillin and other antibiotics.

"The feeling was--why bother with phage therapy or anything else, once we had those miracle drugs?" says Alexander Sulakvelidze, a scientist at the University of Maryland and co-founder of Intralytix, one of several U.S. companies now developing phage therapy.

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