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1/22/2020 12:12:56 PM
Posted: 10/12/2007 10:44:44 AM EST
In the Battle Against Cancer, Researchers Find Hope in a Toxic Wasteland
Key for the Next Generation of Breast Cancer Drugs?

Posted: 2007-10-10 17:13:18
BUTTE, Mont. - Death sits on the east side of this city, a 40-billion-gallon pit filled with corrosive water the color of a scab. On the opposite side sits the small laboratory of Don and Andrea Stierle, whose stacks of plastic petri dishes are smeared with organisms pulled from the pit. Early tests indicate that some of those organisms may help produce the next generation of cancer drugs.

From death's soup, the Stierles hope to coax life.

"I love the idea of looking at toxic waste and finding something of value," said Ms. Stierle, 52, a chemistry researcher at Montana Tech of the University of Montana.

For decades, scientists assumed that nothing could live in the Berkeley Pit, a hole 1,780 feet deep and a mile and a half wide that was one of the world's largest copper mines until 1982, when the Atlantic Richfield Company suspended work there. The pit filled with water that turned as acidic as vinegar, laced with high concentrations of arsenic, aluminum, cadmium and zinc.

Today it is one of the harshest environments in the country. When residents speak of the pit, they often recall the day in 1995 when hundreds of geese landed on the water and promptly died.

"It's definitely an eerie place," said Russ Forba, who directs the cleanup of the pit, now a Superfund site, for the federal Environmental Protection Agency.

But the pit itself is far from dead. Over the last decade, Mr. Stierle said, the couple have found 142 organisms living in it and have "isolated 80 chemical compounds that exist nowhere else."

In two papers published recently in peer-reviewed organic chemistry journals, the Stierles reported finding two compounds that showed initial success in killing breast and ovarian cancer cells in lines maintained by the National Institutes of Health.

"In this test we're just really knocking the snot out of ovarian cancer," Ms. Stierle said, reviewing her findings. But she was quick to describe the tests as very early-stage experiments. Even if these initial results were independently replicated, she said, it would be years before any drugs could be manufactured.

"Someone in my field looks at that and says, 'Oh, that looks juicy,'" said John Beutler, a staff scientist in the molecular targets development program at the National Cancer Institute.

The Stierles won widespread recognition in the scientific community in the mid-1990s for discovering a fungus, native to mountaintops in the Pacific Northwest, that produces taxol, which is commonly used to fight breast and ovarian cancer. The fungus was found next to yew trees, which had long been the primary source of taxol.

The couple's results were published in the journal Science, and they were awarded 11 United States and international patents for their discovery of taxol in the fungus and for developing methods to isolate and grow it.

Then the financing they had for their taxol research from Cytoclonal Pharmaceutics came to an end. The Stierles needed something new to study, quickly. They turned to the Berkeley Pit, about a mile from their house. They persuaded the Montana Bureau of Mines and Geology to allow its Berkeley Pit coordinator to take water samples that they could use to collect microbes.

"It sure saved us a lot of money on gas," Mr. Stierle said.

Mr. Stierle is a tenured professor at Montana Tech, but his wife gets paid only for teaching an occasional class or if there is a grant to finance her research. From 1996 to 2001 they applied for dozens of grants, but received only rejection letters. So they financed their own research, using personal savings and $12,000 in annual patent royalty payments. In 2001, they won a six-year, $800,000 grant from the United States Geological Survey.

"Their work is considered a very high-risk approach," said Matthew D. Kane, a program director at the National Science Foundation. "It takes a long time to get funding, and some luck to find active compounds."

Unlike scientists at large research universities, who commonly teach only one class a year and employ graduate students to run their laboratories, Mr. Stierle teaches four classes each semester at a college with 2,000 undergraduates and no major research presence.

"They're finding lots of really neat stuff using people who don't even have their bachelor's degrees," said Nicholas Oberlies, who directs the natural products laboratory at RTI International, a large nonprofit research center in North Carolina.

Meanwhile, the Stierles said, they have turned down job offers from major universities that would have tripled their salaries.

"We love Montana, and we love what we do," said Ms. Stierle, who often wears a T-shirt that reads "I Dig Science!" around her office. "And then I look at my investment portfolio and think, 'Oh my God, what was I thinking?'"

In return, the Stierles said, they get to witness an unfolding story of strange little creatures struggling mightily to survive. Microbes react to harsh conditions in the Berkeley Pit by switching on genes that otherwise lay dormant or by evolving through mutation and natural selection, Mr. Stierle said. Either way, they produce new chemical compounds, which the Stierles hope may benefit human health.

The couple have become intimately acquainted with the personalities of these new microorganisms. The pit's strain of mycobacterium is a slimy, obstinate fungus that smells bad and is difficult to cultivate in a laboratory. But it has shown initial success in fighting some pathogens, Ms. Stierle said.

Then there is Penicillium rubrum, which is fuzzy and green like bread mold. "It's sweet, it grows, and this little guy produces large amounts of interesting compounds," she said. "It's one of the loveliest microbes we've ever worked with."

Among scientists familiar with their work, the Stierles' talent for making discoveries in such Spartan conditions generates a kind of awe.

"They have that special ability of groundbreaking researchers to ask the obvious questions, which makes all the rest of us think, 'God, I wish I would have thought of that,'" said Kyle Strode, a chemistry professor at Carroll College in Helena, Mont., who describes himself as a friendly competitor with the Stierles.

The couple said they were negotiating privately with a pharmaceutical company to test some of the compounds they have discovered and possibly turn them into drugs. As they wait, they open another Mason jar filled with murky pit water, draw a sample and return to work.

"The pit very easily could have been a complete waste of time," Mr. Stierle said. "We just had luck and worked our butts off. We take that first walk into the dark."
Link Posted: 10/12/2007 10:46:18 AM EST
That's an amazing story and really puts an exclamation point on how opportunistic life is on Earth and how life will thrive no matter the conditions.
Link Posted: 10/12/2007 10:47:19 AM EST
I hope every time I read these things that someone will come up with a cure for it, but I think they'd much prefer treating it than curing it.
Link Posted: 10/12/2007 10:47:19 AM EST
No kiddin!?!?!?

I've been to the Berkeley Pit and wondered how bad it would suck to fall in there. Maybe I should have been taking a soak in there...
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