Bootstrapping serves as a go-to strategy for many tech startups, yet its application in the realm of biotech remains relatively uncommon.The perceived high stakes in execution, capital demands, timelines, and regulatory hurdles often deter biotech companies.Nonetheless, under favorable circumstances and strategic planning, bootstrapping principles can be judiciously applied, yielding substantial advantages for founders, investors, and employees.This firsthand account delves into a CEO's journey employing these principles at SmartCells, Inc., a company built on MIT-licensed technol. striving to pioneer the world's first glucose-responsive insulin for diabetes.SmartCells navigated a six-year trajectory, securing a modest $10M in equity financing from individual angel investors and an addnl. $10M from non-dilutive government and foundation grants.The journey culminated in Merck and Co.'s acquisition of SmartCells for a remarkable $500M.The narrative then extends to the establishment and funding of Akston Biosciences Corporation, leveraging insights from SmartCells to pioneer a comprehensive protein engineering approach addressing conditions like autoimmunity, diabetes, cancer, infectious diseases, and neurodegenerative disorders.Despite the ambitious scale, Akston still relies on individual angel financing for half of the $90M raised, with the remainder sourced from government grants, foundation support, and revenue generated through licenses and partnerships.The discussion centers on the art of building and motivating a team capable of flourishing in a resource-constrained environment.It delves into strategies for identifying and choosing non-institutional investors and maintaining constructive communication amid the company's growth, even in challenging times.Emphasis is placed on distinguishing frugality from miserliness, emphasizing that a company's fate hinges on judicious spending for maximum impact.The talk also underscores the significance of pivoting and highlights the resilience achieved during macro-environmental downturns, exemplified by SmartCells weathering the 2008-2009 financial crisis and Akston's adaptability in the post-Covid landscape.