Does chemistry have a future in therapeutic innovations?

With the intensive development of biopharmaceuticals during the last two decades, policy makers have tended to consider that drugs based on small molecules made by chemists will disappear by 2030. This is a misleading idea for several reasons, which are discussed in the present Essay. In fact, the key question is the appraisal of the real position of chemical-based drugs in the panel of drugs that will be used in the future for treating different diseases ranging from viral, bacterial, and parasitic infections, to cancers, central nervous systems disorders, neurodegenerative diseases, immunological disorders, and diseases induced by aging. It is important to assess the role and future position of medicinal chemistry in the design of new therapeutic agents, in order to reach a reasonable balance between small molecules and biopharmaceuticals. The equilibrium between these two types of drugs will in fact depend on several factors, including the necessity of having highly efficient drugs for the treatment of diseases and health disorders at a minimal cost. The challenge is to cure the largest possible number of patients at a cost that is compatible with the foreseen limits of national health budgets in 2030. As a start, we can consider the historical evolution of the use of chemicals as therapeutic tools. With the early development of analytical chemistry and extraction methods during the first half of the 19th century, chemists and pharmacists were able to extract the active substances from plants that were used in traditional medicine. Quinine was extracted and identified by Pelletier and Caventou in 1820 and can be considered the first milestone of alkaloid pharmacology. The development of organic synthesis in the middle of the same century made it tempting to prepare alkaloids by total synthesis. The attempt of Perkin to prepare quinine from aniline was a “successful failure”: he obtained mauveine, the famous dye that would be known as Perkin s mauve. At the beginning of the 20th century extractive and synthetic chemistry, in association with the emerging field of biochemistry, formed the origin of modern pharmacology with the lock-and-key concept introduced by H. E. Fischer in 1894 and the notion of receptors formulated by P. Ehrlich in 1906. The chemistry–biochemistry tandem was the scientific base of the “business model” of all pharmaceutical companies for nearly a century. We all have in mind the names of the giants in Europe and in the USA that dominated the drug industry with a strong connection between chemistry and pharmacology. In Europe, Bayer, ICI, and Rh ne–Poulenc were classical examples of these pharmaceutical companies based on chemicals. In the 1980s, this industrial paradigm changed under the pressure of the evolution of scientific domains and economic parameters. In a non-exhaustive fashion, some of these parameters will be considered in the following sections.