Local researchers prove that asking good questions is the key to finding answers

by Mike Gibson

They blanket a ridge just south of the main Oak Ridge National Laboratory compound, about one mile from Highway 58—110 huddled acres of bramble and thicket, so much prosaic wood in the rolling foothills of the Cumberland Plateau.

But over the next seven years, this unassuming patch of East Tennessee greenery will be transformed, recast as the site of one of the largest and most visually spectacular research facilities in the world.

Dr. Bill Appleton is the project director for the pending $1.3 billion Spallation Neutron Source, and his eyes fairly shimmer whenever he talks about SNS, the only ripple of emotion visible on his otherwise placid countenance. Once completed, this colossal neutron scattering device will stretch nearly six football fields end to end; the "linac" tunnel that will accelerate the initial pulse of hydrogen ions runs some 1,500 feet, feeding into a narrow, looping channel—the accumulator ring, which gathers and refocuses the beams—nearly as large.

Appleton says the finished product will attract between 1,000 and 2,000 scientists and engineers every year, denizens of big business and academia alike, researchers interested in using this pricey product of space-age necromancy for everything from superconductivity studies to shampoo R & D.

And best of all, Appleton enthuses, the SNS gives the national laboratory a new raison d'�tre in an era when federal funds for scientific research are hard to come by. "The biggest thing for Oak Ridge is that it justifies the continuation of ORNL," he says. "It's an insurance policy for our future."

In a bare hallway of the University of Tennessee's venerable Hesler Biology Building, nearly 30 miles east of Appleton's ORNL office, the telltale kaleidoscopic burble of voices emanates from a third-floor classroom, a sure sign of students at work in lab. Inside, 25 pupils, grouped by twos and threes, work over clear plastic basins of murky water, taping evenly-spaced rows and columns of string across the tops of the bins, makeshift gridworks from which they suspend measuring sticks to chart the depth of the water at each point along the surface.

But a quick survey of these animated laboratory neophytes—none of whom are younger than 25, and all of whom are wearing plastic identification badges bearing the names of far-flung states—reveals that this is hardly a gaggle of bright-eyed freshmen fulfilling a first-year science requirement. These are elementary and high school teachers, herded in from all regions of the country to take part in the university's annual Academy for Teachers of Science and Mathematics.

What do the ungainly efforts of 45 grade-school teachers in a sophomore bio lab have in common with perhaps the most ambitious publicly funded scientific endeavor of the decade? More than you might think. Academy coordinator and UT professor Dr. Kenneth Monty points out that, "The experiments we let these teachers do are relatively unsophisticated, but the principles are the same. The folks at the big labs just happen to have more expensive toys."

According to Monty, the academy will permit these enterprising instructors—most of whom have had little hands-on laboratory experience—to learn what people like Appleton already know: that there's more to science than the study questions in the back of an out-of-date textbook. "What they'll hopefully learn is that science is simply the process of satisfying your curiosity," he says. "Through the academy, we allow our 'students' to live the life of the research folks for a little while."

And the University of Tennessee is an especially apt place for such an effort; Monty notes that we live in an area with more than its fair share of Big Science. The academy syllabus calls for a tour of ORNL, as well as stopovers at nearly every science department on the University's stately Hill. Because the coursework unfolds over barely a month's time, the students won't even begin to explore the region's cache of private researchers, firms drawn like moths to street lamps by the illuminating presence of scientific endeavor.

What kind of research takes place in the halls of academe, corporate labs, and government research strongholds hereabouts? What practical applications might some of these esoteric alchemical processes have? And what stripe of brazen curiosity and unmitigated wonder animates the people who look for answers beneath the lens of a powerful electron microscope or in the vortex of a monolithic neutron scattering chamber? Questions like these can only be answered—just like any research query—by examining the evidence and by studying those who seek.

Though neutron science was born in Oak Ridge, practiced like some strange mystic art in the shrouded inner chambers of the so-called City Behind the Fence since World War II, Appleton explains that the SNS will be bigger, better, capable of producing more neutrons in more intense bursts than any other similar device to date.

Neutron scattering—in essence, the science of making subatomic particles collide at high speeds—is predicated on the fact that neutrons (tiny uncharged particles, one of the building blocks of the atom) are uniquely visible when subjected to the scrutiny of sensitive detection devices. The SNS will accelerate hydrogen ion beams at a target material, causing neutron sprays to careen off the target at the point of collision. "It's much like a beam of light bouncing off an object and into the eye, which digests the information," Appleton explains.

In this instance, the detection instruments are the eye, and they allow researchers to illuminate the character and structure of the target material. The results can yield dividends in any number of fields—enabling the construction of stronger and lighter building materials, casting new light on how some enzymes adversely affect cell chemistry, even revealing the submolecular mechanisms involved in formulating fluids like shampoo or paint.

SNS is hardly the only research project at ORNL; the lab employs more than 1,500 PhDs across more than a dozen areas of study—geneticists unraveling the mysteries of the human genome at the aptly named Mouse House, engineers gearing up for a quantum leap in fuel efficiency at the ORNL propulsion lab, physics doctorates forging heat-resistant ceramic parts at the high temperature materials building...

But SNS has put a new charge of excitement in the air at this multi-faceted research mecca—not to mention new figures in its bottom line, as the SNS funding should increase the lab's total budget by nearly 25 percent. And many of the lab's other divisions are engaged in work that will tie in with spallation's multipurpose mission statement.

ORNL's high-flux isotope reactor (or HIFER, in the vernacular), is a towering cinderblock bunker on one of the lab's sundry satellite compounds, a sullen 30-year-old leviathan redolent of the Atomic Age's foreboding early years. A creaky freight elevator shuttles its denizens to the top-floor control room, a space fraught with wall-mounted dials and buttons and toggle switches and ancient mechanical devices straight out of a '50's flying saucer movie.

And below, separated by tons of concrete and several inches of industrial-strength plexiglass, is the reactor bay, a cavernous room with a maze of yellow rails snaking warily around a luminous blue pool.

Submerged in the pool is the reactor, a 16-by-11-foot cylinder whose sole task is that of splitting enriched uranium atoms. The resulting fission produces sprays of neutrons, which bombard a target element placed at the center of the reactor's keg-like fuel element. The interaction transforms the targets into radioisotopes, highly unstable hyper-elements with various applications in both industry and medicine.

But the HIFER's other mission involves harnessing all of those stray neutrons for secondary analyses; deep in the building's dingy concrete bowels, four colorful dual-cylindered automatons—triple axis spectrometers—surround the reactor pool at equidistant intervals. The spectrometers snare the errant particles, then scatter them off another, smaller target, in much the same fashion (albeit smaller scale) as the SNS.

"Neutron science has taken on a larger share of our work here," says David Glasgow, a researcher in the HIFER's "beam room." HIFER's neutron-scattering capabilities are often employed in forensics, providing for the analysis of microscopic shards of evidence. The HIFER lab reviewed samples from the John F. Kennedy assassination; more recently its researchers scrutinized material samples from a triple homicide at Taco Bell in Clarksville, verifying that a small piece of plastic embedded in the killer's shirt was indeed a souvenir from the crime scene.

"Neutron science is a way of finding the proverbial needle in the haystack," grins Glasgow, one of several HIFER scientists, explaining the appeal of his chosen field. "Neutrons are pretty good things when you get to know them, and we've got plenty of 'em here."

But though ORNL laboratories are full of beatific wonders, paradigms from every spectrum of endeavor, there's a certain antiseptic quality to its carnival array of amazements, as if its horde-like teams of scientists and technicians were a degree or two removed from the subjects under their review.

There's nothing quite like the ivory tower, however, for inducing in researchers that certain mutant strain of enthusiasm that engulfs every fiber of the being. Dr. William Bugg, a long-time member of the UT physics faculty, is the embodiment of every distracted, mono-maniacal professorial stereotype—clad in an evergreen polyester ensemble, with fly-away hair and a piercing voice that gains shrill intensity in proportion to the level of his excitement. ("You can tell those two are in physics," he laughs when he passes a pair of similarly disheveled colleagues. "They look pretty scruffy.")

For the last five years, Bugg has been part of a $600,000, five-professor, four-university project—a very small experiment by the standards of most high-energy physics research. Small, but hardly insignificant; Bugg's work involves creating matter from light, a revolutionary "reversal" of Einstein's famous equation.

"In the early days, they thought in terms of mass being converted to energy," says Bugg, speaking amid a veritable traffic jam of books and boxes in his office on the Hill. "Later, it was pointed out that the process of E=MC-squared could be reversed—that it would be possible to shoot two beams of light at one another and create particles of matter. But for various physical reasons, no one believed we would ever be able to observe this phenomenon."

Using a high-energy particle accelerator from the Stanford Linear Accelerator Center, two high-powered lasers from the Rochester, NY, laser lab, and a calorimeter (for particle detection) engineered at UT, the group began a series of related experiments, colliding electrons and laser beams to create high-voltage electric fields. Gradually, they increased the intensity of the laser beams, fine-tuned the sensitivity of the calorimeters.

And in August 1996, they did the heretofore unthinkable, crossing two high-energy laser beams that would leave behind a submicroscopic wake of electrons and positrons—particles created from pure light.

"We knew in principle we could do it," says Bugg, showing off one of his calorimeters. Layers of heavy metal crowned with a series of comb-like current detectors, it's small—slightly larger than a human hand—but weighing close to 10 pounds and sporting an even heftier $5,000 price tag. "Whether or not our technology would come through—that was another question."

Bugg, who has by now wandered into the basement of the new science and engineering building that houses his office, anticipates the next question, indicating that perhaps he's heard it more than once.

"What's all this good for?" he says with an ironic chuckle, navigating a minefield of cables, giant spools, circuit boards, wood and metal scraps. It's here that he and his associate, Knoxville engineer Steve Berridge, assemble the component parts for their weighty calorimeters.

"The process will be useful for some applications, particularly building bigger and better particle accelerators," he says. "But mostly, it was done to enhance our fundamental knowledge of how matter is made. It will inevitably have some future applications, we just can't predict them right now. Everything turns out to be useful, but never in the way you thought it would be."

If you could throw a stone with centerfielder velocity from the foot of Bugg's building toward the center of campus, it might come close to landing in front of Bruce McKee's streetside office in Walters Life Science at the foot of the Hill. It's doubtful, however, that the offending pebble would even gather notice from the good Dr. McKee, who though somewhat better groomed than Bugg, seems no less distracted, not a whit less consumed.

With fruit flies as his test subjects, McKee's chief pursuit has been the study of meiosis, that divine marvel of reproductive cell division that sees the activated sperm bequeathed with exactly two chromosomes—one x and one y. His research drives at the cardinal question of how cells and genes and DNA strands pull off their singular shell game, and why, in the instance of genetic pathology, the chromosomal tokens get lost in the shuffle.

"We're trying to explore things like, 'Why do those two chromosomes come together?'" posits McKee, a balding 50-ish fellow, his jowls thick with reddish, wiry curls. "What molecules are involved in the process of pairing? What is the mechanism? How does pairing occur? We're using fruit flies, not humans, but the process is more or less universal."

In one of their primary explorations, McKee and his assistants examined mutant x chromosomes that were missing large portions of their characteristic DNA. Without the missing strands, these chromosomes refused to mate with their y counterparts.

McKee narrowed the missing material down to a particular section of the DNA—ribosomal DNA, or RDNA, a substance related to protein synthesis. By replacing a single RDNA insertion, he was able to partially restore pairing; an additional copy increased the capability even further. The experiment is significant in that it lays bare the fundamental mechanism of meiosis, uncovering the specific DNA strands responsible for x and y coupling and making public the previously unknown pairing site of their clandestine subcellular rendezvous.

McKee's work seems tedious, at times even vaguely grotesque; with a powerful microscope, he shows off a sample of his research, a slide exhibiting a smear of mottled red kidney shapes oozing together in amorphous liquid union. The material under surveillance was taken from the insects' reproductive organs. "We have several slides available if you're interested in looking at squashed fly testes," he says with a rare chortle.

But McKee's experiments have powerful if still far-off potential for solving the perplexing enigma of genetic disorders like Down Syndrome, for enabling gene therapy—the still-infant science of repairing or replacing defective genes.

"I've kind of stuck with this area of study ever since my graduate work," says McKee, a transplanted Michigander. "I became fascinated with it and stayed with it. We have enough genetic resources, and I believe if we bring them to bear on the problem for a long enough time, we'll get somewhere. I guess I'm intrigued by the challenge of solving a problem where you feel you're delving into the unknown."

Most scientific findings of any real merit eventually find some practical application, and practical applications eventually find vent in the world of commercial enterprise. Knoxville's CTI, Inc., provides an interesting case study in the evolution of a concept.

CTI's PET scan technology—a diagnostic tool that traces radioactive compounds introduced into the bloodstream—was invented by a group of researchers at Washington University in St. Louis in the mid-1970s. In need of production assistance, they contacted Oak Ridge's EG&G ORTEC, a high-tech firm spun off by Department of Energy scientists, and asked for help in manufacturing PET prototypes.

Almost by default, ORTEC was soon producing all of the PET components. But the involvement was to be short-lived, and when the company's brain trust decided to discontinue the line in the early 1980s, ORTEC engineers Ron Nutt and Terry Douglass purchased the rights to PET and founded their own company, CTI. Today, the firm employs nearly 150 people, most of them stationed at a large, plush headquarters off Pellissippi Parkway.

CTI manufactures two separate PET components: the cyclotron, an enclosed particle acceleration chamber that creates the traceable materials by bombarding a target element with protons, and the PET scanner, a large ring of radiation sensors that tracks and images the compounds after they have been ingested by a human subject. "It's used primarily as a diagnostic tool now," says Ward Digby, a former CTI researcher turned manager of product marketing. "In oncology, it's becoming really hot for detecting tumors."

PET was first used as a research tool, however, particularly for studies of the human brain; after creating a radioactive glucose compound called FDG (the most commonly-used substance in PET scans) with the cyclotron, scientists would inject it into a subject and track brain waves through different stages of thought, the electric impulses made visible via vividly-colored glucose undulations.

Today, however, its greatest promise is in the realm of cancer detection; Digby explains that not only is the FDG compound resistant to metabolic process, but malignant tissues have a voracious appetite for sugar and starch. In x-rays, the glucose-engorged tumors show up like dark, foreboding shadows on a benign field of soft, milky tissues.

But though PET already has many significant real-world applications, Digby says CTI still faces several uphill battles: convincing reticent Medicare bureaucrats that the technology has a favorable cost-to-benefit ratio, adapting the system to detect new types of cancers, and bringing PET's daunting price tag ($1.7 million for the most expensive of three models) in line with the financial limitations of small healthcare providers.

As a result, research is still an indispensable component of CTI's corporate agenda; fully one-third of its employees are engaged in R & D. (Digby shows off one of the research department's niftier turns—an elaborate plastic model of a human brain, with every lobe and fold painstakingly reproduced. "They built it from a scan of one of my buddies back at UCLA," Digby beams.)

"We've been under a lot of pressure—'Can't you just make a cheaper version?'" Digby says. "We could do that, but right now that would mean sacrificing a lot in performance. That's something we're working on pretty diligently."

With a PhD in biomedical physics in tow, Digby entered the CTI fold in 1992, quickly moving from staff scientist to manager of product marketing on the strength of his medical background. "We didn't have any MDs on staff, so I became the resident medical expert," he says.

His own motivations are strangely conflicted, marked at once by a well-grounded pragmatism and a certain child-like curiosity. As an undergraduate, he chose the study of physics as a means of exploring the fundamental underpinnings of existence, of probing the fathomless enigmas of the physical realm. As a working professional, however, he shelved that almost metaphysical sense of inquisitiveness in favor of a more tangible, viable outlet of scientific expression.

"Up to a point, I was fascinated by the basic questions—the basis of why things behave the way they do," says Digby, tall and slim, dark hair speckled lightly with grey. "But then I decided that I didn't want to work somewhere with some particle accelerator and publish a paper every three years, working 20 years on something that doesn't have any immediate application. This field had a real appeal as a way to apply what I knew. Theoretical physics couldn't provide that."

An ardent mid-June sun is bearing down relentlessly from its perch in an expansive blue sky, but inside this classroom in the Nielsen Physics Building, the ambiance is downright cavish—dark, echo-ridden, shot through with a clammy air-conditioned chill. Another group of teachers' academy students are hot on the trail of a new discovery, huddled by twos around diminutive telescope-like instruments—gradings used to divide light rays into their component frequencies.

Their assignment is to determine which portion of the spectrum is emitted by the electrons in a hydrogen atom. With small hand-held bulbs flashing intermittently in the dark, the mostly thirtysomething pupils fidget and giggle and gasp excitedly, occasionally pausing to scribble in black-binder lab books, just like so many of their pubescent charges back home.

With a gentle, almost paternal smile, Monty watches the group take their first tentative steps into the world of light diffraction. For these fledglings, there's little difference between this well-worn field of study and the vast, uncharted hinterlands of high-energy particle acceleration.

"The need to find out 'why' is at the heart of all science, no matter how simple or how complex," Monty says. "There's a real excitement about making a true discovery. It's the kind of thing that always stays with you."