The West's new prospectors seek microbes

  • NASA scientist Jack Farmer collects bits of stone from hot pool

    Michael Milstein
 

Note: This article is a sidebar to this issue's feature story, A park boss goes to bat for the land.

Karl O. Stetter and his team ignore the fresh tracks of a grizzly on their way to hot springs in Yellowstone National Park. Once there, an electronic monitor reveals the pH of the soil is roughly equivalent to sulfuric acid, caustic enough to dissolve the fabric of a backpack left on the ground.

Which is exactly why Stetter, a professor of microbiology in Germany, has come here. He is searching for the most resilient life on the planet.

"Many people might say leave this place to Dante, it's like hell," said Stetter, who works with a U.S. biotechnology company. "But to me, it's heaven."

Stetter is one of a growing number of molecular biologists searching Yellowstone's hot springs for organisms that persist where other life cannot. The same stamina that lets the microbes survive acid pools makes them hugely profitable to industry.

The corporate quest for valuable products of nature is well-established in tropical nations, where rainforests may hold the makings of wonder drugs. But it's a new and puzzling concept for the United States. More than a dozen biotechnology companies - including such industry leaders as New England BioLabs and Roche Molecular Systems - are collecting lucrative life in Yellowstone and at least two have proposed deals to cut the National Park Service in on revenue generated by their discoveries. But park managers say strict laws against the exploitation of park life bar them from making such deals, though they have not barred the collecting that raised the question to begin with. One thing is clear: Public understanding has not yet caught up with "bio-prospecting."

Solving the problems raised by bio-prospecting was the goal of a delegation from Yellowstone that in January visited Costa Rica, a Central American nation that courts bio-prospecting as a way to make nature pay for its own preservation.

"We need to find a way to take advantage of the values that our national parks protect without undermining the missions of the parks and selling them out," said Michael A. Soukup, the National Park Service's associate director for natural resources and science.

Technology complicates the quandary. Companies now pluck valuable DNA straight from nature's soup and patent those one-of-a-kind genes. No one knows or seeks to know from what organism they came, and that raises a question as fundamental to environmental protection as genes are to life itself: If genes hold the blueprint of life, are genes the commodity, or is the commodity life itself?

So-called "products of nature" cannot be patented. But their various components, including genes, can be. So genes - free for the taking - are the green vein that bio-prospectors seek.

Some believe Yellowstone may be the place to take a stand against the commercialization of life, the notion that nothing without a price tag has value. If patenting life is an egregious excess, as it is to Jonathan King, Massachusetts Institute of Technology professor of molecular biology, then patenting life from a national park is "doubly egregious," he says.

"Privatizing life in a place like Yellowstone is like privatizing the sky - it's a misappropriation of the common heritage of all," says King, a director of the Council for Responsible Genetics, which opposes all patenting of genetic material. "We didn't save Yellowstone to make a profit. We saved it because it has a greater value."

When Congress set aside Yellowstone as America's first national park in 1872, it was thought nothing could live in the boiling water of its hottest hot pools. A microbiologist named Thomas Brock, now retired from the University of Wisconsin, was the first to look closely. In Yellowstone in the 1960s, he found tiny organisms thriving in water hot enough to scald human skin, beyond the supposed upper-temperature limit of life. Among the bacteria he discovered was one shaped like a cigar. He named it Thermus aquaticus and deposited a sample in a national warehouse of cell cultures.

Which is where a biotech company found it and employed one of its enzymes to drive what's called the polymerase chain reaction, or PCR, the genetic photocopier that makes DNA fingerprinting possible (HCN, 12/27/93). PCR requires heating, a step that destroyed enzymes from room-temperature microbes, but not those designed to work in the heat of hot springs. The Yellowstone enzyme now earns more than $100 million a year for Hoffmann-LaRoche, the Swiss drug giant that today owns the patent on it.

It's unlikely that Yellowstone will ever earn more than fame for its contribution to PCR. But many park managers contend it's only right for the public - by way of the government - to reap some return for future discoveries in a refuge the public has paid to protect for more than a century.

"It's great to see this sort of benefit come from the parks," said National Park Service Director Roger Kennedy. "But we're also talking about compensating the taxpayers who have paid to protect Yellowstone all these years."

Modern genetic screening, made possible by PCR, lets scientists sift through Yellowstone's springs with far greater efficiency than Brock ever could. When they scan for fragments of raw DNA, more than 99.9 percent of the genes they come up with fail to match any known species of microorganism. This means that 99.9 percent of the microscopic life out there is unknown. That easily overwhelms the roughly 4,000 known species of microbes, which were identified mainly in laboratories.

Indiana University researchers studying a remote Yellowstone pool say two species of microbes taken from it appear to more closely resemble the first life on Earth than anything else alive today.

"We are only beginning to understand the diversity of life that exists in these habitats," said David Ward, a professor of microbiology at Montana State University who works in Yellowstone and has a consulting agreement with Stratagene, a California biotech company.

Wherever microbes live - which is just about everywhere - they carry out life's basic functions with a toolbox of enzymes encoded in their spiral strands of DNA. Evolution has molded enzymes to catalyze virtually every biochemical reaction known, and far more efficiently than human-engineered industrial chemicals ever could.

Now the biotech industry wants to substitute environmentally kind enzymes for chemicals that often cast off toxic byproducts. J.K. Research, a small Montana company, has identified an enzyme from Yellowstone that can strip paint off old military airplanes without harsh chemicals. Enzymes called proteases that break down proteins inside living cells are giants of the $25 billion detergent market because they also break down protein stains in dirty clothes.

The more trying the surroundings, typically, the sturdier the inhabitants. Proteases from hot springs in places like Yellowstone will not disintegrate in the hot water of washing machines. Microbes already toil for industry, gobbling polluting sulfur out of coal before it is burned, for instance.

It used to be hard to locate utilitarian enzymes since most bacteria are too finicky to keep alive in laboratories. Today there is no need to coddle the organisms; instead, researchers go straight for their DNA codes, reeling in codes for an enzyme that may aid manufacture of a new antibiotic, or another that breaks down fats in diet food. An enzyme from an ice-dwelling microbe might work to tenderize meat even while it's stacked in the refrigerated cases of grocery stores.

It's a simple matter to patent DNA patterns for useful enzymes and plug them into lab-friendly microbes, which then churn out the enzymes as dairy cows do milk.

"We believe the future is really in accessing genes as a raw material directly from the government," said Jay M. Short, chief technology officer of Recombinant BioCatalysis Inc., a biotech company that counts Stetter as a founder. The company employs robots that work around the clock scrutinizing samples from places like Yellowstone for genetic fingerprints of valuable enzymes.

To find as many as possible, RBI needs genetic diversity; to obtain it, the company has signed agreements under which it pays for access to geysers and hot springs in Iceland and a range of tropical habitats in Costa Rica.

In Yellowstone, where RBI also collects, access currently requires only a free research permit. That doesn't sit right with Eric Mathur, director of RBI's Center for Molecular Diversity. "We're going to make money on Yellowstone enzymes soon and I want to give them royalties. Right now, they won't take it. That's the opposite of everybody else."

Siphoning a little hot-spring water laced with microbes probably no more violates rules that protect park wildlife than does slapping a mosquito on your arm. But Yellowstone Superintendent Michael Finley worries that letting companies take jarfuls of water could bring lumber companies wanting trees to uncover genes that could boost productivity on private tree farms.

"People will get the idea we're auctioning off what the park is supposed to preserve," he said.

Park personnel are giving their regulations a fresh look, however, and a report is expected out on the conference in Costa Rica. For more information, call the Yellowstone Center for Resources, 307/344-2203.

Michael Milstein reports from Cody, Wyoming, for the Billings Gazette.