This year's Harvey W. Wiley award goes to a medicinal chemist who at one time wanted to be a concert oboe player. The award, AOAC's top scientific honor, is given annually for career achievements in analytical methodology.

Richard B. van Breemen is a natural products specialist at the University of Illinois, College of Pharmacy, in Chicago, who uses advanced mass spectrometry to trace the active ingredients of dietary supplements from the health food store to the bloodstream.

Technically, van Breemen is a professor of medicinal chemistry and pharmacognosy, a field that turns out to be a good springboard for a wide-ranging interest in mass spectrometry.

"When Professor van Breemen joined this university, we had one working mass spectrometer," department head Judy L. Bolton told AOAC in nominating him for the award. "Today, we have 10 mass spectrometers in his laboratory alone. . . He has been instrumental in developing LC/MS/MS assays for the quantitative analysis of a wide variety of natural products and biomolecules."

For example, she said, van Breemen has worked with methods related to determining carotenoid bioavailability, and for the quantitative analysis of isoflavones and triterpene glycosides in human blood and urine. He's also worked in drug discovery, developing new high-throughput assays based on pulsed ultrafiltration MS--a process that replaces the conventional HPLC column with an ultrafiltration chamber. "These assays have the exceptional potential to enhance the efficiency of drug discovery from natural product sources as well as expedite early drug development studies such as metabolism and toxicity testing," Bolton wrote.

• The first use of continuous-flow fast atom bombardment for LC/MS and LC/MS/MS analysis of chlorophylls
• Similar work with beta-carotene, lycopene, and lutein
• The first use of electrospray LC/MS in carotenoid analysis
• Pioneering work in atmospheric pressure chemical ionization LC/MS for carotenoid analysis
• Novel applications of LC/MS and LC/MS/MS to oligonucleotides, ginsenosides, retinoids, betulinic acid, and resveratrol

In this role, he helps head up an NIH-funded center for dietary supplement research. "At our Botanical Center, we look at the safety and efficacy of dietary supplements used by women, in particular supplements that might be used for the relief of menopausal symptoms," he says.

The studies involve such products as red clover extract, black cohosh, and hops. In addition to helping standardize these products by measuring their active ingredients, van Breemen works on clinical trials studying blood levels of these chemicals and their metabolites. "Our work spans [the range] from raw material to clinical trials," he says. "It's fun because I'm able to take LC/MS through all the stages."

Like many top researchers, van Breemen came to his specialty in a roundabout manner. In high school, he'd studied oboe with the intention of becoming a professional performer. In fact, he chose his undergraduate institution, Oberlin College, because it offered the opportunity to pursue both that and his other great love, science.

But by the start of his freshman year, he'd decided that the oboe would be a hobby, not a vocation. The decision came about when he went to a music clinic where there were several dozen other oboists. "I realized that at least 30 were better than I was," he says. "Then I looked at the job market. How many great orchestra positions become available in a lifetime? I decided I'd be more happy and successful as a scientist."

Initially, he decided to major in physics. But chemistry was more fun. The turning point came when one of his professors complained about the quality of chemistry education in high schools of that era. "I learned that I'd been taught some 19th century science," he says.

Learning about the modern field was eye opening. "I became very interested in chemistry."

Science ran in his family. His father, Verne van Breemen ("My grandparents loved Jules Verne") had done pioneering biological work in electron microscopy in the 1940s and 50s, back when the first pictures of subcellular organelles were being obtained. "[They were] things we didn't even know existed, so we didn't know yet what they did," he says. "It's fun to go to the literature and look up my father's name. People are still citing him."

His maternal grandfather was also a researcher. Recipient of the first Ph.D. in physiology awarded in the state of Iowa, he stayed on at the University of Iowa, rising to head the physiology department prior to his retirement in the 1960s.

All of this gave van Breemen an interest in the life sciences to match his interest in chemistry. As a result, he pursued toxicology and pharmacology in graduate school. Analytical chemistry and mass spectrometry, in particular, helped tie it all together.

His dissertation research concerned how certain classes of drug metabolites might be toxic or even carcinogenic. But his committee chairman was also studying natural products as cancer chemopreventatives, and soon enough, van Breemen was doing the same. "Research on cancer prevention was simply not popular when I was a graduate student," he says, "But this attitude has been changing."

Today, in his NIH-funded program, he says, "We screen botanical extracts and other sources of natural products to find potential drugs that might prevent cancer rather than treat it after it happens."

One is lycopene, a tomato ingredient that has received media attention as a possible inhibitor of prostate cancer. One recently completed study involved looking at cancer patients to see if lycopene supplementation actually increases the levels of lycopene in blood and prostate tissue. It also looked for biomarkers that might show beneficial effects. "Now we're looking at the same biomarkers in healthy men taking lycopene supplements," he says.

He's also been working to develop assays for the standardization of botanical dietary supplements, including serving since 2003 as a member of AOAC's Core Advisory Group for its Official Methods^SM program for dietary supplements. Occasionally, he has also helped look for adulterants, such as pharmaceutical agents. "We've published a few papers in that area," he says. "We are great advocates of carrying out analytical chemistry to verify safety, purity, and standardization."

His tool of choice has been mass spectrometry. "It wasn't long ago, if you look back in the analytical literature, that there really was very little analysis carried out on these supplements," he says. "[And] even when analysis was carried out, virtually nobody was using LC/MS. This whole field really began in earnest in the 1980s."

One of the things he finds interesting about mass spectrometry is the way new methodologies reignite the field every few decades.

"In the 1930s," he says, "people were saying, 'Don't do mass spectrometry because we know all the elements and their isotopes, and there's no other thing that can be done.'" But then the military wanted to standardize aviation fuel mixtures for World War II, and chemists discovered that mass spectrometry didn't require breaking chemicals down to component elements: it could also be done with small organic molecules.

Within a few years, all the oil companies were doing such analyses, and soon enough, they were standard in chemistry departments, worldwide. "Then in the 60s and 70s, they started saying it wasn't worth studying mass spectrometry because everything's been done that can be done."

Needless to say, that proved to be another false prediction. Electrospray and matrix-assisted laser desorption ionization soon allowed mass spectrometers to handle not just small molecules, but large ones, too.

"Every generation, some teachers tell students to abandon the field," van Breemen says, "and they've always been wrong. I think mass spectrometry becomes more exciting every year."

He adds: "I teach my students never to say something cannot be done."

The result is that colleagues frequently contact him with their analytical problem children: compounds on which a postdoc might have been working unsuccessfully for a year or two. "Sometimes we'll take samples that others have worked on for months or longer and solve [them] in a couple of hours," he says. "We pride ourselves in analyzing things where others have given up."

He does this without attempting to develop new instruments. "I like to use existing tools in ways others haven't thought of," he says. For example: "Many researchers new to mass spectrometry think in terms only of positive ions. [But] the universe contains negative ions, too."

Also, there are novel ways of fragmenting molecules. And it's possible to do multiple stages of tandem mass spectrometry. "Not just MS/MS but MS to the third or the fourth [degree]."

Meanwhile, he continues to play the oboe with his children, whose instruments include clarinet and flute. "I can play duets with them and trio music. They all play."

He doesn’t say whether they, too, might become award-winning scientists. But in a family that includes a Wiley winner and a Verne [after Jules], anything is possible.

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