The phone rang in my San Diego home, and on the other end was John Finn. "Hello Mark?", he said. "How are you doing?"
It had been eight years or more since I had spoken to him. We had worked together in herbicide discovery at American Cyanamid in Princeton, New Jersey. He had been a good collaborator with me. We had begun our careers in the early eighties and had experienced a special time by any measure as the Ag Division exploded in growth. When we arrived, the top selling product of the division was an organophosphate insecticide, terbuphos, with annual sales of around $90 million. Before the end of the 80's, the sales would measure in the hundreds of millions from fifteen new products, most significantly imidazolinone herbicides. We rode a veritable tsunami of commercial success, and the leadership ploughed some of the profits back into "ARD", the Ag Research Division.
Our personal contributions towards the commercial successes were somewhat modest. I was the first plant biochemist hired, and my contribution was to help explain the mechanism of action of the herbicides. This was worked out fairly close to my hiring by others, but I did my part in developing enzyme assays as screens to support discovery research. John worked initially on filling out the patent space for the imidazolinones, always in search of new products. One part of his work helped focus attention on the last imidazolinone to be commercialized. But his main contribution as far as I was concerned was his innovation in bringing tools and approaches to research, especially chromatography and combinatorial chemistry.
At one point, I had collaborated with John to produce large arrays of compounds without purification. The idea we tested was to improve the standard output in synthetic chemistry resulted, about one compound per week per chemist. This output came from a chemist conceiving an end product, then working the steps to the product and finally purifying the product. Our idea was that most such products are useful only as information to direct the next iteration and that the majority effort of purification was a waste for something not actually thought to be useful. If the assays could tolerate crude preparations, such as they tolerated in natural product research, why not make an array of crude preparations, then see if the information is useful enough for the next iteration? John's try at this resulted in hundreds of compounds per week and a significantly larger chemical space explored.
Anyway, John and I developed a common sense of efficiency and drive. When he left the company, I co-wrote a scathing condemnation of chemistry management. It was my distress about his departure, but it was also my distress about the gap in innovation I felt with his absence. Fortunately, the letter was received positively, and the innovation John provided was seen as important to continue; John went on with two other companies, and I lost track of him.
I consider the discipline of small molecule drug discovery from the perspective of a biochemist and a capitalist. Maybe the order should be reversed because for me, the goal of attaining a commercial success is paramount. I can only enjoy the journey if the chance of success exists. Without the chance the activity is a bit sterile and academic. If there is no point to the work, then almost any scientific endeavor is equivalent and difficult to prioritize. I guess the premise of drug discovery is the promise of a product; if the research does not have the promise, then the work is hollow. Perhaps this judgement is too harsh, but there it is.
