May 20, 2002
Volume 80, Number 20
CENEAR 80 20 pp. 32-36
ISSN 0009-2347

Creative chemistry, biology, plus powerful instruments and computers propel Pacific Northwest National Laboratory into proteomics era


"We're not Hanford" is a theme that runs throughout Pacific Northwest National Laboratory (PNNL) as it tries to distinguish itself as a multiprogram, national lab separate from its more famous former plutonium-producing neighbor.

INSTRUMENTATION Researcher sets up experiment on 800-MHz nuclear magnetic resonance spectrometer, one of 15 NMR systems, ranging in power from 300 to 900 MHz, in operation at PNNL.
Lab management may want to clear up any confusion about PNNL's Hanford connection, but the lab does sit on the edge of The Department of Energy's Hanford Reservation on the desert plains of southeastern Washington, near the confluence of the Columbia and Yakima Rivers. And the laboratory came into being in 1965 to provide research support for Hanford's scientists and engineers as they produced plutonium for U.S. nuclear weapons.

Although U.S. weapons plutonium production ended in the late 1980s, the Hanford-PNNL connection remains strong.

About $110 million of the lab's $537 million fiscal 2001 budget is earmarked to aid Hanford, but now PNNL supports the program to clean up the environmental mess left by the bomb makers. The cleanup is expected to cost at least $50 billion and take decades to complete.

The lab still retains a strong defense flavor with nearly half its funding related to national security. But now the focus is mostly on homeland defense and nonproliferation of nuclear, chemical, and biological weapons.

However, PNNL scientists needn't worry about Hanford confusion. They have moved beyond that historical tie.

In fact, over the past two months the lab has announced two big additions that are expected to catapult it along a path it set several years ago into cellular research and proteomics.

In April, PNNL announced the purchase of a $24 million, 8.3-teraflop supercomputer and began installation of one of the world's largest, highest performing nuclear magnetic resonance spectrometers. Both are expected to greatly enhance chemical, biological, and life sciences R&D at the lab, disciplines that managers say will be core
areas of growth for PNNL's future.

The lab is the youngest of DOE's nine national multiprogram labs, a designation that was formalized in 1995. Although now a "national" lab, PNNL has strong regional roots in the Richland, Wash., community, says Lura J. Powell, PNNL director and senior vice president of Battelle Memorial Institute, the nonprofit corporation that has managed PNNL since its birth.

"Before 1965, it was just Hanford out here, and in terms of business, there was not a whole lot else," Powell says. "The Atomic Energy Commission--DOE's predecessor--wanted to encourage economic growth and a diversified economy in the region so if plutonium production pulled out there would be something left, not just the dusty days of the past."

One of Battelle's strong suits, she says, is taking fundamental science and turning it into technologies and products with marketplace potential. That strength has grown at PNNL. And Powell wants it to continue under her leadership.

Powell is a chemist and a former American Chemical Society board member. One of the first women to lead a national, multipurpose DOE lab, Powell came to PNNL two years ago after a 27-year scientific career, most of which was at the Department of Commerce's National Institute of Standards & Technology. During her last five years there, she ran the Advanced Technology Program (ATP) (C&EN, March 13, 2000, page 35).

ATP funds technologies with good commercialization prospects sometime in the future but with very high risks at the moment. Powell oversaw an annual investment portfolio of more than $100 million.

Although liked by scientists, ATP has taken a drubbing from some in Congress who call it "corporate welfare" and want to shut the program down. The fight was particularly intense during Powell's years at ATP, but it helped forge her views of the importance of the government's role in aiding technology transfer from lab to marketplace.

At PNNL, the very relationship between Battelle and DOE encourages commercialization and collaboration with scientists and engineers outside of the lab, she says.

Going back to the original 1965 contract, Battelle was allowed to conduct research for private contractors using DOE facilities, and DOE was able to use Battelle-owned equipment on government jobs. Although PNNL is a DOE lab, the buildings and equipment are jointly owned. Powell estimates that Battelle owns about half the PNNL facilities, which amounts to about 300 acres of land and 1 million sq ft of buildings.

The arrangement gives the lab "scientific leverage," she says, increasing the research power for both DOE and Battelle.

"There is a caveat," she quickly adds. "DOE work always has to come first. We are a national lab. But we have the ability to increase the power of taxpayer dollars for national problems."

Also under the Battelle/DOE contract, once a technology has been developed for its originally funded purpose, Battelle can buy patent protection on that technology and further develop it for new uses.

In those cases, any resulting royalties to Battelle are split between the corporation and the government and reinvested back to the lab. Advocates also note this benefits taxpayers by saving money and society by bringing new products to market. And it helps the lab by generating funds for new equipment, staff, and R&D.

PNNL likes to tout its success in commercializing products. For instance, lab management points to a recognition program run by the Federal Laboratory Consortium, a nationwide organization of 700 federal labs and centers. PNNL has received 51 awards for transferring outstanding technologies since the recognition program began in 1984, the most awards won by any one lab.

Battelle has more than 200 active licenses in place for patented or copyrighted technologies developed by PNNL, and last year it filed more than 100 patent applications for PNNL inventions. Over the past five years, the lab has provided technical assistance to more than 500 companies--mostly in the Northwest--to help them get started or establish new product lines.

For example, lab managers single out a contract and collaboration with Motorola in which the company eventually built its own advanced molecular beam epitaxy deposition and analysis system based on a PNNL design and prototype. PNNL and Motorola continue to jointly use this technology for nanoscale research on semiconductor wafers.

Such collaboration with scientists in industries, universities, and other federal labs greatly strengthens PNNL research, Powell says. "You wrap together different views into a highly leveraged and a very relevant program. Working with a variety of people ensures that your projects are truly relevant and highly important," she continues.

The lab's future, Powell predicts, will be "the interface of life sciences and informational sciences." She intends to accelerate the lab's strong core capability in chemistry and biology by solidly linking it to computational biology.

PNNL largely missed out in playing a big role in the race to map the human genome, she says, but adds that that will not be the case with the next effort--proteomics.

She says PNNL's emphasis on chemical and biological science and its NMR equipment, mass spectrometers, and supercomputers will help push it to the lead in this area. Much of that research will be conducted at the William R. Wiley Environmental Molecular Sciences Laboratory (EMSL), a four-year-old DOE user facility on the PNNL campus.

The facility has a suite of equipment critical to cellular research and proteomics, notes Allison A. Campbell, EMSL deputy director.

Along with 15 NMR units, PNNL has a complement of mass spectrometers, advanced computer systems, and data visualization technologies. By 2003, its new supercomputer should be up and running. It will be geared to problems in molecular science.

EMSL caters to users, Campbell emphasizes. "We help them build equipment and tailor it to their needs. We create a problem-solving environment," she adds. "We know we are distant and it is expensive to get here, so we try to help users solve problems while they are here."

More than half of the 1,400 users never actually come to the lab. They send samples to PNNL and access instruments over the Web through a shared desktop computer system, she says.

"Our scientists and users see each other's cursors and interact through the Web," she notes. NMR-related experimentation usually takes a week or more, she adds, and the remote ability allows researchers to stay at their own institutions while collecting data 24 hours a day.

Powell, the scientist, manager, and consummate PNNL booster, predicts that proteomics research will complement other research done at the lab-- energy production and conservation, global climate change, human health, bioremediation, pathogenesis from biowarfare agents, and more.

And she predicts more growth, more collaborations, and more technologies for DOE and the marketplace, springing from the Washington plains.


Chemistry And Biosciences Are Priorities At PNNL

Construction of what was to become Pacific Northwest National Laboratory (PNNL) began in 1965, shortly after Battelle Memorial Institute, Columbus, Ohio, won an Atomic Energy Commission contract to build and manage a new lab to abut the Hanford Reservation near Richland, Wash.

The prime mission was technological and scientific support for Hanford plutonium production, but the lab also did R&D to develop nuclear power and to study environmental and health effects of radiation.

Since then, the mission has shifted and broadened, the facility has grown, and today PNNL is one of the Department of Energy's nine multiprogram labs.

PNNL has an annual budget of $537 million and a staff of 3,700. About 2,000 staff members are scientists, technicians, or engineers, and more than 1,400 have advanced degrees. Nearly all staff are at the Richland site, but PNNL operates a marine sciences lab in Sequim, Wash., and small facilities in Seattle; Tacoma, Wash.; Portland, Ore.; and Washington, D.C.

Much of its research is in the chemical and biological arena. In 1997, PNNL opened its largest single facility--the William R. Wiley Environmental Molecular Sciences Laboratory. EMSL cost $230 million to build and equip, most of which went for an array of advanced instruments.

EMSL is a DOE user facility with great potential for chemists. It drew 1,400 scientists in 2001 from 200 organizations--886 from universities, 165 from industry, 135 from other federal labs, and 229 from other parts of PNNL. More than half (784) used the facility remotely via the Web and never came to EMSL or Richland.

User access is free to most scientists but requires a peer-reviewed proposal process. Also, results are expected to be shared broadly within the scientific community.

PNNL prides itself on providing technical support to users and on modifying equipment and experiments to their benefit.

Equipment includes a suite of high-performance mass spectrometers and high-field nuclear magnetic resonance facilities, as well as advanced computing facilities including graphics and visualization capabilities.

Last month, PNNL began installation of one of the world's largest, highest performance NMR spectrometers--a first-of-its-kind unit with a 900-MHz, wide-bore system. The NMR has a bore size of 65 mm and a strength of 21.14 tesla.

Also last month, PNNL announced the purchase of a $24 million Hewlett-Packard supercomputer with 8.3 teraflops of performance. The computer will be geared toward solving chemical, biological, and life sciences problems and is intended to accompany EMSL's research activities. It is expected to be operational in 2003 (C&EN, April 29, page 10).


The Hanford Connection

Some $110 million of PNNL's budget supports DOE and its contractors who are working to clean up the Hanford Site. The site contains some of the nation's worst radioactive and chemical contamination, notes John P. LaFemina, director of PNNL environmental programs.

PNNL's science and technology support for the cleanup is focused on four areas: some 50 million gal of chemical and radioactive waste contained in underground tanks, one-third of which are leaking; stored, spent radioactive reactor fuel; plutonium left in closed processing plants; and contaminated groundwater.

The science is interesting, LaFemina says, although the problems are immense. He notes, for example, "If you want to know what is in the tanks or the groundwater, just look at the periodic table."

LaFemina stresses that significant progress has been made to clean up the site and research has played a big part.

Along with providing R&D for the actual cleanup, LaFemina says, PNNL uses its scientific and technological expertise to help DOE and contractors determine what should be cleaned up, when it should be cleaned up, and how it can be cleaned up.

He estimates that about 17% of PNNL's scientific effort is directed to risk analysis to support cleanup decisions. The rest is in hard-core sciences.

"We need to know how to stage the cleanup and how to prioritize work to meet commitments and policy agreements," he says, adding that changes such as DOE's new accelerated cleanup plan will call for significant research modifications, including introduction of breakthrough technologies.

Hanford-related R&D activities appear sprinkled throughout the lab and the site, both fieldwork conducted at Hanford and R&D in PNNL's labs.

Cleanup science also takes some unexpected twists and leads to some unplanned results, LaFemina notes.

Lab scientists discovered an efficient means to retrieve the medical isotope yttrium-90 from purified strontium-90 first obtained from tank waste, LaFemina says. The therapeutic isotope has applications for treatment of many forms of cancer, and the program grew to the point that is now commercialized.

PNNL scientist Mary S. Lipton is using the lab's proteomics facilities to study the microorganism Deinococcus radiondurans, which has the ability to resist the lethal effects of radiation.

So far, PNNL has characterized about 80% of the proteome with the goal of understanding what makes D. radiondurans radiation resistant.

Lipton hopes to couple this research with that of another potentially valuable microbe, Shewanella oneidensis MR-1, which is capable of converting uranium in contaminated groundwater to a form that is insoluble in water. Although S. oneidensis can help precipitate radioactive materials out of groundwater and halt their spread, the microbe is highly sensitive to radiation.

Combining the attributes of these two microbes could have a significant impact on one of the biggest problems facing Hanford: groundwater contamination from the leaking underground tanks.

Groundwater contamination is slowly flowing to the Columbia River and is a top cleanup priority, LaFemina says. However, it is one of many problems in a cleanup that is expected to last decades and cost billions of dollars.


Biodetection Enabling Analyte Delivery System

The Biodetection Enabling Analyte Delivery System (BEADS) is an automated front-end sample preparation device for pathogen detection. The system literally uses a packed bed of beads--tiny glass, polymer, or magnetic spheres--to capture chemical or biological species of interest. BEADS works for liquid, gas, or solid contaminants by suspending them in liquids and placing them in contact with the beads, says Jay W. Grate, PNNL senior chief scientist. The beads are automatically delivered and released for each sample. Bacteria, spores, viruses, or their DNA bind to the beads while other material is washed away. The system concentrates and purifies the protein or DNA from environmental samples for biodetection. BEADS has many applications, such as monitoring air and water contamination and for detecting food contamination or the presence of biowarfare agents.




Solid Oxide Fuel Cells

With four industrial partners sharing costs, the Department of Energy is in the second year of a $500 million, 10-year R&D program to commercialize solid oxide fuel cells. PNNL and DOE's National Energy Technology Lab are coordinating the program.

Solid oxide fuel cells (SOFC), unlike other fuel-cell types, have the advantage of being powered by readily available hydrocarbon fuels such as natural gas, rather than pure hydrogen, says Subhash C. Singhal (right), Battelle fellow and director of PNNL's fuel-cell program.



Their greatest potential is in stationary power generation, particularly distributed generation and industrial settings, such as chemical companies, where the cells' high heat can provide process steam or be coupled to a turbine to generate more electricity. These combos can raise efficiency to 75%, far greater than a coal- or gas-fired power plant, and without the air pollution.

The biggest disadvantage is high cost, says Singhal, who adds that most fuel-cell R&D funding has gone to proton-exchange membranes that are adaptable to smaller applications.

PNNL's SOFC research has focused on a planar design that allows thin cells to be stacked to raise output wattage. More than 30 PNNL researchers take part in the lab's fuel-cell program.

Some of the more interesting SOFC applications being explored, Singhal says, are prototypes to supply electricity to a field soldier or an auxiliary power unit that provides electricity to a motor vehicle and replaces the alternator.

PNNL's partner on the automotive project, Delphi Corp., has installed the first prototype unit (5 kW) in a spare tire well, says staff scientist Jeffry W. Stevenson (left).


Spiders, Fireflies, And Microbes

Spider venom, an enzyme that triggers a firefly's luminescence, and a microbe to spur plant growth are the bases of research projects with a past in Soviet weapons work and a potential future in commercial products.

And they are among 30 PNNL research projects that are part of a Department of Energy program to help former Soviet weapons scientists find new jobs using their research and laboratories to make commercial products rather than weapons.

The goal of the nonproliferation and national security program--Initiatives for Proliferation Prevention (IPP)--is to reduce the global threat of nuclear, biological, and chemical weapons developed in four countries of the former Soviet Union. PNNL's focus is primarily biological, matching the lab's expertise, says Ronald Nesse, senior program manager.

The U.S. lab sits in the middle, searching through and validating the former Soviet research projects while looking for commercial applications and a Western corporate partner.

The program, Nesse says, hopes to stanch the scientific brain drain of weapons scientists and stabilize the research institutes so they can avoid selling their services around the world.

"These institutes," he says, "have unique ways of doing research, which are important to keep alive."

The labs, he says, are isolated physically and intellectually with few ties to the West and have even been cut off from other research programs within the former Soviet Union. With little commercial expertise, much of their research appears truly fundamental.

Consider the fireflies. For 10 years, Soviet scientists physically captured about 100,000 fireflies each summer, says Evguenia I. Rainina, a Russian scientist who is now a PNNL senior research scientist. The scientists extracted the enzyme that triggers luminescence when exposed to bacteria, studied its genome, and eventually engineered it in their labs.

That enzyme is now being used by a Maryland manufacturer that makes biological detection equipment. The enzyme has proven to be quite sensitive, and its use has cut the cost of the company's detectors from $5,000 to $500, Rainina says, opening a broad market for food processors, farms, hospitals, and restaurants.

Then there is spider venom. Soviet researchers found that some peptides and polyamides in arachnids' venom kill insects but have little effect on mammals. The compounds may open a whole new approach for pest control in homes and farms.

And the microbe plant growth stimulator was also developed in Soviet labs. It is being used by a Washington state turf grass seed company, the largest in the nation. Its use is expected to grow enormously.


The Virtual Lung

By wedding the power of supercomputers and nuclear magnetic resonance imaging, PNNL scientists are creating a virtual model of the rat's respiratory system. Ultimately, this will provide a three-dimensional view that allows researchers to see how pollutants enter, travel, and are collected in complex airways.

The model is nearly complete for the rat's nose, sinuses, larynx, and upper lungs, says Kevin R. Minard, senior research scientist. After rats come monkeys and then humans.

The respiratory models provide a unique basis for understanding how poor air quality influences health and how health effects depend on preexisting medical conditions such as asthma; they likely will be useful for developing improved pulmonary drug delivery systems, Minard says.

To validate model predictions, Minard and colleagues currently are working on novel experimental methods that exploit advanced NMR imaging technology for visualizing the dynamics of inhaled gases and for both the distribution and clearance of magnetically labeled particles in living rodents.



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