Biotech Values

[DewDiligence]

"The bugs bat last!"

http://www.boston.com/news/globe/health_science/articles/2007/06/04/germ_busters

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As Antibiotics Lose Punch, Researchers Use Old Idea to Control Bacteria

By Stephen Smith
June 4, 2007

At this very moment, there's a good chance that germs capable of killing you are hiding out in your nose. They sound like characters straight out of some apocalyptic opera: Streptococcus pneumoniae , Staphylococcus aureus .

Most of the time, they're just along for the ride, causing no real harm. But under the right circumstances -- say, for example, when you're sick with the flu -- they can spawn life-threatening illnesses, everything from pneumonia and meningitis to bouts of flesh-eating bacteria.

There isn't much that doctors and patients can do about those germs until after they turn dangerous. And even then, the best weapons in the medicine cabinet, antibiotics, aren't what they once were.

So now, scientists led by Rockefeller University researcher Vincent Fischetti are developing a way to eliminate lurking bacteria before they can do harm. The approach is one part medical history, one part cutting-edge science.

Nearly 100 years ago, scientists began exploring whether viruses called phages could be used to combat bacterial infections. Researchers knew that in nature, phages had the power to thwart bacteria, so, they figured, maybe phages could work in people, too. But with the discovery of antibiotics, phage research in the United States was put in the drawer labeled, "Good idea, never went anywhere."

Now, Fischetti has resurrected the idea of harnessing nature's own ability to keep bacteria in check -- but with a twist. If his strategy works, it could have implications for everything from reducing earaches in children to limiting deaths in a global flu epidemic. And it could involve something as simple as a squirt up the nose or a gargle in the throat.

Fischetti, who established a biomedical company to further his research, doesn't use the whole phage. Instead, he makes copies of one component, an enzyme, that jabs a hole in the wall of a bacterium, whose harmless contents spew out like champagne from a bottle. It's a lot like using a pin to pop a water balloon.

Unlike antibiotics, which often destroy a broad spectrum of bacteria -- killing the good with the bad -- phage enzymes are much more selective, with each targeting a specific strain of bacterium.

"And they're completely harmless to humans," said Ry Young , a Texas A&M University biologist who studies phages. "They only attack bacteria. You could argue that bacterial phage are our best friend: The enemy of our enemy is our friend."

Researchers familiar with phages and with Fischetti's work said it's conceivable that bacteria could become resistant to the viral components, but several said it was unlikely, in part because phages and bacteria have been engaged in a microscopic tango for 4 billion years.

Still, those scientists do have concerns. For example: If nasty germs are blasted out of our noses and throats, will they be replaced by something even worse?

"Nature abhors a vacuum," said Dr. Paul Sullam , an infectious diseases specialist at the University of California at San Francisco. "If you displace one group of organisms, another one comes along. They could be benign or they could be more virulent. You just don't know.

"The bugs bat last."

Even so, researchers said, the threat from antibiotic-resistant bacteria is so insidious that alternative control methods such as Fischetti's must be explored.

"This is not a far-fetched approach," Sullam said. "There's something evocative about this because of the history of bacteria and phages and images of the pre- antibiotic era. This has definite promise."

To understand the promise, it's important to appreciate the peril.

Researchers have long recognized that all kinds of bacteria coat the inside and outside of humans, our skin, our hair, our intestines. They're there in the millions. Scientists estimate that 40 percent to 50 percent of people, for example, harbor bacteria in their noses that can cause pneumonia and other serious infections.

But those bacteria don't stay there.

"We sneeze, we cough, we kiss, we make love -- all these things exchange saliva one person to the next, and bugs are taking advantage of that," Fischetti said. "If we cut off all of our saliva transmission from individual to individual, these bugs would go away, they couldn't survive.

"But that's not going to happen."

The potentially dangerous germs become troublemakers only when something else goes wrong.

Disease trackers know , for example, that it's not so much the flu virus that kills people as it is complications that ensue -- especially pneumonia. That was the case in 1918, when a flu epidemic swept the globe, said Keith Klugman , an infectious disease specialist at Emory University's Rollins School of Public Health .

There's something about having the flu that, in turn, makes patients susceptible to those germs in the nose. And once they get into the blood and into major organs, they can create havoc.

When antibiotics emerged more than six decades ago, doctors figured the war with bacteria had been won.

"But it turns out that we need to think beyond your routine antibiotic treatments," said Dr. John Powers , an infectious disease specialist at George Washington University School of Medicine . "Because the bacteria have been around millions of years and they're way smarter than us."

Bacteria are becoming resistant to antibiotics faster than new antibiotics can be developed.

That's where Fischetti's phage enzymes come in.

In two studies published in research journals in recent months, Fischetti reported on experiments that dramatically reduced two dangerous types of bacteria from mice.

In one, a phage enzyme was used to wipe out Group B streptococcus , a bacterium common in the birth canal of mothers and responsible for meningitis and other infections in newborns. In the other, mice that got a phage enzyme that targets Streptococcus pneumoniae were much less likely to develop ear infections than mice who weren't exposed to the phage enzyme.

So far, Fischetti's research has been limited to mice. Fischetti said he intends to meet with federal drug regulators this summer to discuss his phage research and predicts that human trials could start within two years.

Drugs that are used to prevent disease, as opposed to treating illnesses, are held to especially rigorous safety standards. While side effects might be tolerated if a pill is treating a severe illness, they're much less acceptable in an agent that's designed to prevent an ailment.

Fischetti said he envisions a time when seniors in nursing homes or children in day-care centers would routinely receive a spray of phage enzymes to wipe out bacteria in their noses.

"We have nothing at this point to control these diseases. Zero," Fischetti said. "This could finally give us something."
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