The decision to pursue particular targets for drug discovery and development can be the difference between success and failure for companies in both the biotechnology and pharmaceutical industries. Pharma and biotech companies make those decisions for often vastly different reasons, even though both are influenced by the underlying biases in their drug discovery research methodologies.

For biotech, which cannot deploy resources on the scale of the pharma powerhouses, the pressure is to make project decisions based on its scientific strengths in order to compete.

The dilemma for biotechnology companies is illustrated by the example of cyclooxygenase-2 (COX-2), an enzyme responsible for the synthesis of prostaglandins involved in inflammation and pain. While aspirin and most non-steroidal antiinflammatory drugs (NSAIDs) inhibit both COX-2 and COX-1, the other isoform of the enzyme, specific COX-2 inhibitors are capable of relieving painful inflammation without the gastrointestinal toxicity associated with inhibition of COX-1.

But while both G.D. Searle & Co.'s Celebrex celecoxib and Merck & Co. Inc.'s Vioxx rofecoxib selective COX-2 inhibitors are being heralded as blockbuster drugs, biotech companies have not pursued COX-2 as a target, raising the question of whether they are missing other potentially profitable opportunities. But if biotech companies have not gone after COX-2, they are competing with pharma in pursuing other targets addressing large markets, such as phosphodiesterase-5 (PDE5), which is the target for Pfizer Inc.'s Viagra sildenafil male erectile dysfunction treatment.

The decisions leading to pursuit of COX-2 as a target by pharma companies on the one hand, and the pursuit of other targets by biotech on the other, are central to the process that will define competition between the industries going forward.

For Searle (Skokie, Ill.) and Merck (Whitehouse Station, N.J.), the COX-2 decision began with having the right people and research teams in place to recognize the opportunity the enzyme presented, and then having the resources to pursue it vigorously.

Philip Needleman, Searle co-president and chief scientist of parent Monsanto Co. (St. Louis, Mo.), had a history of prostaglandin research while an academic at Washington University (St. Louis). Needleman's group was among a handful that conducted early work to identify a second form of cyclooxygenase, COX-2, that represented a specific target expressed in response to inflammatory cytokines, as opposed to COX-1, which is always expressed.

"There were a couple of things that made it easier in a sense for us to embrace the idea of COX-2 as a target," said Peter Isakson, executive director of COX-2 technology at Searle. "The main thing was having Phil at the table as part of the organization. We had some believers internally that there was an alternative form and were experts, who could see a finding immediately and act on it."