Artistic Beauty, Synthesis, and Front-Row Seats

Like many of my peers, I was first drawn to organic chemistry by the artistic beauty inherent in the synthesis of complex molecules. Once some of the fundamentals have been mastered, the organic chemistry of medicinal compounds takes on an important creative element, which is furthered by the cross-fertilization of ideas that take place at Gordon Conferences.

My Ph.D. adviser at the University of New Hampshire, Robert Lyle, went to the Chemistry of Heterocyclic Compounds GRC every summer. He would regale his graduate students with stories of sitting on the shores of the lakes in New Hampton and drawing molecular structures in the sand. With that inspiration, and following the advice of John Topliss, I applied to and attended my first Medicinal Chemistry GRC in 1975. I was a young scientist at Schering-Plough, following my postdoc years at the University of Michigan and the Squibb Institute for Medical Research. My research had shifted to the investigation of new antiulcer compounds from earlier graduate work on the partial synthesis of the anticancer agent camptothecin and postdoctoral research on molecules that inhibit the biosynthesis of cholesterol.

The Medicinal Chemistry Gordon Conference was well-established by the mid-1970s, and many of the same people attended every year. In fact, the front row of seats at Colby-Sawyer College was unofficially reserved for the conference “elders,” who included Murray Weiner, Nat Sperber, and Jerry Weisbach. I was immediately struck by this assemblage of remarkable people–all leaders in pharmaceutical research from across industry and academia. But a great set of younger scientists was also in attendance: Ray Fuller, who invented serotonin uptake inhibitors; John LaMattina, who went on to become president of R&D at Pfizer; and Peter Gund, who had an illustrious career at Merck in the field of quantitative structure-activity relationships and molecular modeling.

Once I attended, I was hooked, and I participated in the Medicinal Chemistry GRC regularly for several decades. I even made it to the 1981 conference, when I was working for Parke-Davis. I took my two sons to New Hampshire while my wife stayed in Michigan, about to give birth to our daughter. Fortunately, I made it back just in time!

The Medicinal Chemistry meeting opened my eyes to the breadth of research going on at other companies and in academic labs. One of the major strengths of this conference is that it does not focus on a single therapeutic area but instead provides the latest and greatest insights into a wide range of areas and promotes the great discoveries that happen at the interface between therapeutic areas. For example, during the mid-1980s we began a project at Parke-Davis to explore adenosine receptors. In effect, we began with the mechanism and then looked for potent ligands (either antagonists or agonists) of the receptors that we could evaluate to identify a range of therapeutic areas. As it turned out, we found incredibly interesting activities in the areas of pain, hypertension, psychiatric disease, inflammation, and lung disease.

More recently, at Pfizer we have investigated a series of compounds that have the same mechanism of action as Neurontin (gabapentin), a drug that was initially used for epilepsy. Interestingly, these compounds are active in neuropathic pain, anxiety, and a half-dozen other disease areas. As these two examples illustrate, successful pharmaceutical research often happens when scientists apply discovery techniques developed in one area to totally different therapeutic areas. GRC has likewise advanced the field by bringing together scientists from a wide range of research.

Like other Gordon Conferences, Medicinal Chemistry also serves as a leading indicator of research in the field. Annual Reports in Medicinal Chemistry, for which I had the privilege of serving as editor-in-chief for nine years starting in 1990, draws its editors from the Medicinal Chemistry Gordon Conference and begins its planning cycle in September while talks from GRC are still fresh.

By the time I was selected to chair the conference in 1992, the Medicinal Chemistry GRC faced challenges from heavy oversubscription, an overly strong orientation to industrial research, and a lack of diversity. So we worked hard to bring in more women, to invite students, and to keep a focus on unpublished research, including the work of academic scientists. Additional progress was made in subsequent years in bringing greater diversity to Medicinal Chemistry, which has strengthened the conference as well as the field in general.

There is a bright future for medicinal chemistry in the pharmaceutical industry. Drugs will always be needed. While we will continue to see advances in large molecules, proteins, and antibodies, our ability to pay for them is limited. In the future a balance will be struck in the development of large and small molecules. Despite current difficulties in the politics of the pharmaceutical industry, new medicines continue to be important. Medicinal chemistry will be the foundation for future pharmaceutical advances, and the Medicinal Chemistry Gordon Conference will continue to be the premier venue where scientists come together and share advances in the field, just as they have for the last seventy-five years.