The Importance of Being Unreasonable: Building a Company on the Frontiers of Science and Medicine

In 2002, John Maraganore left the leadership of an established biotech company with an ambition many thought implausible. Small RNA molecules had been found to stop cells making specific proteins by destroying messenger RNAs. It was one of biology's most exciting recent discoveries. But it seemed unlikely that this RNA interference (RNAi) could ever be applied therapeutically. The molecules were hard to work with and there was no technology for delivering them where they would be needed. Skeptics were plentiful and success unlikely. Nevertheless, Maraganore joined a group of visionary scientists in Cambridge MA to become the founding CEO of Alnylam Pharmaceuticals, intent on creating RNAi-based medicines.

The Importance of Being Unreasonable is Maraganore's inside account of the two-decade pursuit of an unproven idea and its culmination in creating an entirely new class of medicines capable of silencing disease-causing genes.

Along the way, Alnylam faced seemingly intractable scientific problems in chemistry and drug delivery as well as huge challenges in clinical development, financing, and commercialization. Maraganore describes exhilarating breakthroughs and devastating failures, fierce competitors and indispensable collaborators, and bold strategic bets and times of peril for the company's survival. Yet the conviction that transformative science demanded rigorous evidence as well as the willingness to flout conventional wisdom resulted in the development and global deployment of five RNAi-based therapeutics before Maraganore stepped down in 2021.

Part scientific adventure, part company-building story, and part reflection on scientific leadership, this book offers a rare view of the biotechnology industry from the inside. Maraganore shows how company culture, resilience, calculated risk, and an unwavering focus on patients can turn scientific possibilities into medicines, and how progress often depends on people unreasonable enough to persist when others say it cannot be done.