The discovery of new antibiotics is a path well-trod, yet few of those who embark on the journey ever reach the end. For most, novel antibiotics are never more than the tight line drawn across the blue sky at the horizon, never closer, never further away. And, I am an optimist who holds discovery as a tenet of faith.
In a world where the urgency for new antibiotics increases by the day, most sensible pharmaceutical companies have withdrawn from the field or offer “me-too” analogues of known actives. Discovery is an orphan left on the world’s doorstep. There are many sound reasons that bring us to this modern-day conundrum: lack of investment, low financial returns, weak IP protection, litigation, regulatory control, a patent system that gives equal weight to the discoverer of true novelty versus me-too imitation, our belief system that finding in nature does not merit ownership ……and so the list expands.
To those crestfallen researchers who see these mountains as obstacles, I would say that never in the history of antibiotics has the world been so rosy with opportunity. Indeed, like almost every discovery over the last 80 years, it is our evolving understanding of microbes that will push innovation into the future. We have ended the era of “chase the active” bioassay-driven discovery and entered a new era where our understanding of talented microbes as a whole is the best option in town. In this realm we can see all, but as yet we know so very little. Each microbe, with up to and quite often over 50 biosynthetic gene clusters, gives rise to over 100 secondary metabolites and importantly we know the pharmacology of only a handful.
In my presentation, I intend to support this view by detailing a 25-year odyssey of discovery at Microbial Screening Technologies in Sydney. Over 500,000 microbes were isolated across Australia and screened for antibiotic activity. Along the way, there were wins, losses, draws, things we needed to develop and stuff jettisoned to approach journey’s end.