A Pathway for Antibacterial Drug Development (Introduction, draft; March 2016)

Gregory S. BisacchiSyngene International, Ltd.; Bangalore, India

Debate has increasingly intensified during recent years on the question of how, and by whom, new antibacterial drugs will be brought to the market. The medical need of such drugs results from the erosion of efficacy of existing antibacterials due to the inexorable development of resistance to these agents by pathogens. One of the first researchers to describe antimicrobial resistance was Paul Ehrlich who also discovered one of the first small-molecule anti-infectives, salvarsan, introduced in 1910. As a theoretician, Ehrlich proposed the then-new concept of selective action of anti-infective agents, both for biologic agents (polyclonal antisera, introduced in 1890) as well as for small molecules, and popularized the now-clichéd term “magic bullet” to describe such agents. (Ehrlich was undoubtedly alluding to the “free” bullets of popular German folklore, the term “free” used in the sense of “free will”. According to the legend, these specially crafted bullets need not be aimed precisely by the shooter, because once fired, they were free to seek out their intended targets by their own accord.) From the 1940s to the 1980s, the pharmaceutical industry was strategically committed to the field of antibacterial R&D which allowed medical practice to reliably keep pace with bacterial resistance development. This early commitment had been enabled by several unique historical factors. After the 1980s however, industry has largely turned away from the antibacterial field, primarily for economic reasons, and therefore resistant bacterial pathogens have now predictably emerged causing hard-to-treat or completely untreatable infections.

Despite many current global attempts to lure the pharmaceutical industry back to the antibacterial field in a significant way, it may be difficult to do so. Current proposals appear logistically complex, and questions remain regarding how economic incentives may be implemented as motivational tools (and if implemented, whether those incentives will be sufficient). Any new antibacterial project would need to compete for resource against ongoing internal R&D projects or external collaborations.