Guest editorial – Lawrence J. Marnett, Ph.D. pg. 3
COX-2 was found to be expressed in stimulated inflammatory cells but not in the stomach, whereas COX-1 was found in stomach and many other tissues. This suggested that COX-2 might be the target for the anti-inflammatory action of NSAIDs, whereas COX-1 might be the target for their toxicity. So the race was on to develop a selective COX-2 inhibitor!
Eight years and $200 million later, Monsanto brought Celebrex to market. Celebrex was the biggest drug launch in history, selling approximately $1.5 billon in its first year. Merck marketed Vioxx six months later, and the sales of these two blockbusters grew to nearly $6 billion annually. These selective COX-2 inhibitors appear to have an improved gastrointestinal safety profile for individuals who cannot tolerate non-selective NSAIDs, but their utility for individuals who are not highly sensitive to NSAID toxicity is the subject of considerable debate.
In September 2004, Merck pulled Vioxx off the market after finding that patients in a long-term study who took the drug had an increased risk of heart attack and stroke. Some experts believe all COX-2 inhibitors can cause cardiovascular problems in certain groups of patients. So it will be important to determine the cardiovascular risks of other COX-2 inhibitors and define the patient populations that should or should not be taking these drugs.
Studies of inflammation and treatments for it represent a classic example of the bi-directional translation of scientific discovery, from clinic to bench top and back again. Physicians, molecular biologists, pharmacologists, biochemists, and chemists focus on different aspects of how inflammation arises, what are the important molecular players, how their production can be minimized, and how one can optimize the structure of drugs that do this.
Scientists from all over the world bring their skills to this effort individually or collectively as part of multi-investigator teams. By focusing on the key events in inflammation, scientists can identify the most important studies to be conducted, and they can be assured that the results will have important clinical implications. This makes research in inflammation very exciting because one can see the impact of one’s scientific discoveries on improved human health. Since inflammation contributes to many chronic diseases, this impact is further magnified.
The pace of scientific investigation is accelerating dramatically thanks in part to the development of new tools and technologies, which enable us to plan and conduct experiments that were unthinkable only a few years earlier. Information exchange is nearly immediate via the Internet, so the most exciting findings are communicated rapidly to investigators worldwide. But the basic currency of science remains—the formulation of good ideas and the design of experiments to test them, coupled with the hard work and diligence to complete them.
Good scientists are also good innovators. They not only think about what their experimental results mean but they also ask how they can use the new findings to do something that has never been done before. This means they are frequently traveling in uncharted territory, which is simultaneously terrifying and exhilarating. It is also essential to the translation of good science into better medicine.