Issue Date: May 14, 2007
Taking The Familiar Route
Roughly a decade ago, pharmaceutical companies maintained large, in-house natural products programs dedicated to basic research and drug discovery. Recently, many big companies have cut those programs. Merck, Novartis, and Wyeth are among the handful of companies that kept their internal natural products departments. They also outsource services to small biotechnology companies and draw on collaborations with academic researchers.
"Today's natural products research cannot be compared with the situation 10 to 15 years ago," says Frank Petersen, executive director of the natural products unit at Novartis in Switzerland. New separation and analytical systems have reduced research costs and timelines. Microbial genetics and technologies for structure elucidation, screening, and sequencing have opened up new potential. "In our daily work, we learn that nature is still a nonexhausted source for new pharmacophores," he adds.
But Petersen stresses that some of the most exciting and scientifically important research is actually basic research that uses molecules from nature to learn about biological functionality in living systems. "Natural products play an important role as probes" that, for example, are used to help determine whether the specific interaction of a molecule with a target in a model organism triggers the desired change he says.
Sheo B. Singh, director of natural products chemistry at Merck, wholeheartedly agrees. Discovering a drug is a complex process, and discovering the drug lead is just a small part of that process, he says. To find that needle in a haystack requires a significant research effort that includes developing robust biological assays and analytical methods as well as carrying out mechanistic studies.
Merck and Novartis have collaborations on both kinds of research with biotech companies and academic groups. Phil Crews, a chemistry professor who does marine natural products research at the University of California, Santa Cruz, currently collaborates with Novartis.
Crews's work centers around sponges and related microorganisms such as sediment-derived fungi. His students essentially become trained as bioanalytical chemists. They "have no trouble getting jobs," he says. Small biotech firms offer them jobs before they even start writing their doctoral dissertations. Although Crews warns the students that job security with a research start-up can be volatile, most of them take their chances and do well.
Big companies develop relationships with academic labs for the purpose of recruitment as well. For example, the marine natural products work being done in academia is focused on microbes and is closely related to the kind of work that we do here, says Guy Carter, vice president of chemical technologies at Wyeth. Nevertheless, "there are relatively few positions available in industry," he says, "and we don't have much turnover." However, the valuable skill sets gained in natural products work, such as nuclear magnetic resonance or mass spectrometry used to identify unknown compounds, may make a candidate attractive for a job opening in another part of the company or to smaller companies.
Both Petersen and Carter have heard that other large companies are interested in getting back into natural products. Although they believe that there is renewed interest, "it's probably never going to come back to the level it was many years ago," Carter says.
"If positions open up for natural products work, Merck and Novartis hire at B.S., M.S., and Ph.D. levels," Singh says. Merck generally looks for a good background in organic chemistry and biology, with emphasis on isolation and de novo structure elucidation.
Petersen says Novartis wants natural products scientists with knowledge and experience in isolation techniques, bacterial and fungal genetics, general microbiology, strain and media development, and fermentation technology.
Carter says Wyeth hires for natural products work at M.S. and Ph.D. levels. He notes that chemists are generally responsible for purification and structure determination of materials that originate from the microbiology part of the group.
To people debating where to take their careers, several researchers who spoke with C&EN offered the following advice: "Follow your heart." Crews adds, "It took me about 10 years to figure out how to transition from physical organic chemistry to marine natural products research, but that is what my heart told me to do."
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