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Digging for New Drugs in Lake Soil; Bacteria, Fungi Appear to Hold Medical Promise; Last of Two Parts

Posted on: Monday, 30 May 2005, 15:00 CDT

Last of two parts

Hundreds of feet below the dark, cold surface of Lake Michigan, a war is being a waged. Millions of armed bacteria and fungi are duking it out to the death firing lethal toxins at one another, while parrying oncoming assaults with impenetrable, homemade anti- bacterial shields.

Watching from a distance, Yi-Qiang "Eric" Cheng, a University of Wisconsin-Milwaukee biologist, is taking careful note of the armies and their arsenals. He's investigating their weapons and trying them out in his lab. The hope: He'll find a few that can be used outside of this bacterial barrage, in the arena of human medicine.

Cheng and a graduate student, Melissa Barman, think the soils of the Great Lakes might harbor an untapped pharmacy a trove of new drugs including antibiotics, cancer drugs and fungus fighters.

They say their initial search has proved fruitful: They have identified novel strains of bacteria and fungi that appear to hold medical promise. But with tempered enthusiasm, they added it's still "really too early to say" how lucrative the lakes might be.

Collectively, the Great Lakes represent the largest freshwater body in the world. But, according to Cheng, they have not been systematically scoured for drugs. That is surprising considering almost every other imaginable ecological niche has been searched including rain forest floors, deep ocean vents, volcanic mouths and the Arctic's frozen tundra.

"People have been looking in every conceivable exotic environment," he said. "I figured that since we were here, just a few blocks from Lake Michigan, we should look there."

And mining the lake is neither difficult nor destructive; it requires only a few samples of soil. Once promising microbes are identified, they can be reared and reproduced in the lab.

Their work comes at a time when the need for new anti-bacterial agents is dire: From Russian prisons to American hospital wards, unconquerable strains of bacteria are popping up at increasing rates.

According to the U.S. Centers for Disease Control and Prevention, more than 70% of hospital-acquired infections are resistant to at least one of the drugs commonly used to treat them.

Unfortunately, even if Cheng and Barman do find promising leads, they've got their own battle to fight, especially in the area of new antibiotics. They must get pharmaceutical companies interested in developing their quarry. And they must prove the agents they are identifying are new.

According to Steven Projan, assistant vice president for protein technologies at Wyeth, only seven new anti-bacterials have been approved since 1998. In 2004, of 290 drugs that major pharmaceutical companies were developing, only four were antibiotics.

Cost is a major factor, said Projan. But there's also concern that despite nearly two decades of intensive screening for new antibiotics, few novel agents have been found.

While some say this problem is insurmountable that the millions of bacteria and microbes on the planet share just a few dozen chemical weapons, and no more will be found others say the dearth of new agents is an artifact of the way researchers have been looking for them.

"Soil microbes offer an extraordinarily rich source of active compounds," said Jo Handelsman, a plant pathologist at UW-Madison. "I'm just not convinced we have screened as many environments as we say we have."

The problem is that 99% of the microbes investigated have obstinately refused to release their arsenals of chemicals in a laboratory setting.

Methods used to culture fungi and bacteria have not changed much since the 1940s, Handelsman said. Placed on plastic petri dishes and stored in an incubator or refrigerator, the soil microbes are far removed from the habitats they are adapted to.

In 2003, two researchers from Northeastern University demonstrated that if you place these microbes in a familiar environment, they blossom and show new chemical arsenals.

The problem: If researchers are looking to exploit the weaponry of bacteria and fungi that they've isolated from a deep ocean vent, re-creating that environment in the lab is going to be difficult.

That's the beauty of Cheng's discovery. If he finds his critters don't expose themselves readily in his UWM laboratory, he has only a few blocks to walk to Lake Michigan, grab some soil and water, and refurnish his microbes' home.

But just to be sure he has covered his bases, Cheng also will employ a different way of identifying Lake Michigan's microbes. He'll use a process called metagenomics.

This method will allow Cheng to identify every snippet of DNA in his sample enabling him to see critters that would ordinarily die, or remain invisible, in a laboratory setting.

There are limitations to the technique, he said. For instance, what his computer tells him is a novel species actually might be a loose strand of DNA from another microbe, thereby over-estimating their diversity.

"It's kind of like looking for a needle in a haystack," he said. "But if you don't try, you're not going to find anything."

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SERIES, DAY ONE

There is growing concern among researchers that pharmaceutical products are making their way through wastewater treatment and out into our lakes. To learn more, go online and visit www.jsonline.com/ alive/news/may05/329670.asp

Copyright 2005, Journal Sentinel Inc. All rights reserved. (Note: This notice does not apply to those news items already copyrighted and received through wire services or other media.)

Source: Milwaukee Journal Sentinel

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