William Pierce Jr., Ph.D., laughs as he relates one of his favorite stories. It's about the time he was showing a television reporter a new lab instrument that had just been purchased with funds from the WHAS Crusade for Children.

"It was an atomic absorption spectrometer," Pierce recalls. "When I said that, the guy looked up from his notepad and said, 'Uh, yeah.' And when it was shown on the news that night, the little blurb at the bottom of the TV screen said 'medical machine.' "

While the general public might not be able to even pronounce the instruments' names, hundreds of physicians and researchers in the region rely heavily upon Pierce's lineup of "medical machines" to help them do everything from study the structure of proteins to detect harmful lead levels in babies.

Pierce and his staff operate UofL's Biomolecular Mass Spectrometry Core Lab, housed in two unimposing rooms on the 13th floor of the Research Tower in the heart of the Health Sciences Campus.

The mass spectrometers contained there don't look like much -- mainly, big tan boxes hooked up to computer terminals -- but their capabilities and significance to research are incalculable.

Mass spectrometry involves the separation of matter according to its atomic and molecular mass. Most often used for analyzing organic compounds, it is considered one of the most versatile and sensitive analytical methods available today.

"This is the workhorse of biomedical studies," says Russell Prough, Ph.D, associate vice president for health affairs/research and vice dean for research in the School of Medicine.

Prough, who specializes in biochemistry, says he has a high regard for Pierce and for his work. The two have collaborated often over the past 15 years, co-publishing five papers during that time.

"Many people in the medical school have used Bill's unique analytical skills to do a number of things, and he's a big factor behind a number of grants for others and for himself," Prough says. "He's helped set up the infrastructure for research here."

Jon Klein, M.D., Ph.D., and David Gozal, M.D., are just two UofL researchers who rely on the mass spectrometry lab. Both nationally recognized researchers are engaged in proteomics studies, which examine how proteins affect the function of the body's cells, organs and tissues.

"When researchers get to a point where they've separated all these interesting biomolecules," Pierce says, "they turn them over to us and we can tell them what they're looking at."

Lab growth

Pierce, a professor of pharmacology and toxicology with a joint appointment in chemistry, is noted across campus for teaming up on projects. But he developed the mass spectrometry lab into a significant research center with another goal in mind-to aid his own studies into estrogens and osteoporosis.

"In order to do the work I wanted to do I needed to be able to study the structure of certain molecules," Pierce explains.

A UofL graduate, Pierce earned his bachelor's degree in chemistry in 1977 and a Ph.D. in pharmacology and toxicology four years later. He followed that up with postdoctoral work at Stanford -- "I worked in the lab that got the Nobel Prize for Viagra, but I had nothing to do with that," he recalls with a laugh -- then was a candidate for posts at the National Institutes of Health and the Centers for Disease Control before returning to his alma mater in 1982 as a research associate.

Pierce has made his mark on the university in the years since. Among other honors, he is a 2002 Distinguished Service Award recipient and vice chair of the Faculty Senate.

Along the way, he also managed to teach himself mass spectrometry.

When Pierce joined UofL, Harrell Hurst, Ph.D., had just set up a mass spectrometry lab. However, it was used mainly to examine drug overdoses and poisonings. None of its machines was capable of studying the big molecules that intrigued Pierce.

In the mid-90s, he set out to do something about that.

"I needed to get a new one of these instruments, and the only way to justify it was to write a grant discussing how it would help a lot of people," he recalls.

His first request went to the NIH in 1997 for a $282,000 HPLC-electrospray mass spectrometer, which among other things can determine the molecular weight of proteins and peptides up to 100 kDaltons.

While that proposal was under review Pierce learned of a new "crackerjack" version of the instrument, quickly added a $25,000 supplement to his proposal along with a request to switch to the new machine -- and got it.

That was just the start.

Today the lab contains four spectrometers, all of which are used for related types of work, but each has a different complementary capability.

The atomic absorption spectrometer, for instance ("that's the medical machine," Pierce jokes), is used to analyze inorganic metals. Its main purpose is to test children for lead poisoning.

In addition to that and the HPLC-electrospray, the lab also houses a $275,000 MALDI-TOF (matrix-assisted laser desorption ionization-time of flight) mass spectrometer and, the latest addition, a $600,000 hybrid quadrupole time-of-flight mass spectrometer.

This machine, added earlier this year, helps researchers identify unknown molecules, then analyzes their structure and tells how much is there.

"Once you do that you can perform comparative experiments, like contrasting a situation in which you didn't do anything to one where you applied a hormone," Pierce explains. "This will allow you to analyze both cases and then begin to understand the function of that hormone.

"Although I get excited about my spectrometers, they won't do everything," he cautions. "But much of what they won't do you can deduce from complementary studies across Jackson Street at the cancer center, where they now have the big nuclear magnetic resonance instruments.

"NMR spectrometry gives you a whole different set of information about molecules than mass spectrometry and vice versa, so they need us and we need them."

The grant artist

His success as a collaborator in grant applications has given Pierce high visibility on campus. During the course of a year he might participate in 30 or 40 submitted proposals -- "I didn't say I get 30 or 40 of them funded," he notes -- so he has the process down to a fine art.

For instance, to persuade the Crusade for Children to finance the $50,000 atomic absorption spectrometer Pierce enlisted the aid of pediatrics professor George Rodgers, M.D., Ph.D. They promised that, in return, the lab would develop a new technique for detecting lead poisoning in children using just one drop of blood and costing only $25.

"Before this, it took a tablespoon of blood -- you'll pay hell getting that from a wiggling baby -- and it cost $60 to send it off to Atlanta or somewhere else for testing," Pierce explains.

"We also promised the Crusade that if the patient can't pay we won't turn them away. We'll run the analysis and worry about what we can get compensated for later."

Today, the lab analyzes several thousand samples each year.

"You can get it done for free at the county health clinic," Pierce says, "but to be honest they're just swamped. So they're glad for us to do this."

Along with teaming up with the right people and making deals to get the job done, Pierce says he always tries to show that the instruments he wants funded can be used by many different researchers for many different purposes. He also assures the grantor that his lab will assist in a certain number of promising research projects at no charge, hoping that at some point the investigative team can secure funding and give the mass spectrometry lab a piece of the action.

Pierce is constantly scouting for new projects in which his lab can participate by attending seminars and sitting down with colleagues over coffee to learn how his lab might assist in their studies.

Education is another key element in getting grants funded, Pierce says. When possible, he includes a component in his grant requests promising to promote each instrument's capabilities and its value to research through seminars and meetings with students and potential users.

Even more important, Pierce says, is a show of support from the university's leadership.

"The biggest reason these grants get funded is that the NIH or whomever we're approaching for funding sees a working lab that has solid institutional backing. UofL supports these very strongly," Pierce notes. "I can't overemphasize that."

Key to this support, Pierce says, are Prough; Joel Kaplan, M.D., dean of the medical school; Nancy Martin, UofL's vice president for research; and David Hein, Ph.D., chair of pharmacology.

'We make collaboration work'

Upon meeting Pierce for the first time, you might not guess that he's in such a serious business. He talks about his work in simple terms, joking and peppering his explanations with amusing anecdotes to help drive his point home.

In fact, Pierce bears a remarkable likeness to the late Jerry Garcia of the Grateful Dead. And he would probably consider that a compliment.

A self-described guitar-playing former hippie, Pierce jokes that he got into pharmacology "because I was a child of the '60s and I just wondered how all that stuff worked."

Even today, Pierce says that in times of duress, "I head out to the woods to swim, read, play my guitar and forget all about this place for a bit."

Another holdover from the '60s is Pierce's focus on sharing. Collaboration is the key to research, he believes, and he practices what he preaches.

He stops often when describing his work to give credit to Jian Cai, Ph.D., the lab's technical director, and Ned Smith, its manager.

And while conducting a tour he stops to chat with each student and research assistant, then brags to his visitor about what he or she does and how well they do it.

That attitude extends to the researchers and physicians that he works with campus-wide and beyond.

Currently his group collaborates with more than 50 people on the health sciences and Belknap campuses at UofL, another dozen or so at UK and with researchers at Eli Lilly in Indianapolis.

"This isn't so much a tribute to what our lab does as it is the realization that this is the way research is now done," Pierce explains.

"It used to be that everyone got his or her individual grants and worked in these little monolithic labs. That just won't work anymore."

When you're asking for an instrument that might cost $1 million, Pierce advises, you need to show how it can be used for more than just one study.

"So we make collaboration work. Collaboration to me is more of a mindset than anything else," he adds.

"It's what we can do together. And in my humble opinion, that's what the university has to do.

"To compete with the larger research universities we not only have to do what we said we would in the Challenge for Excellence, which is identify areas where we're pretty darned good already and then become excellent in them, but we also have to look for every possible opportunity to collaborate.

"Then we can synergistically feed off one another."