The chapter opens with Katalin Karikó’s unlikely path to scientific prominence: raised in rural Hungary, she emigrates to the United States after her institute loses funding and eventually lands at the University of Pennsylvania. While the biotech world chases DNA, Karikó commits to the seemingly fragile idea of using mRNA as a temporary medical instruction set for cells. She spends years submitting grant after grant to the NIH, is repeatedly rejected, and is ultimately demoted, leaving her work—and mRNA’s future—apparently stranded.

The narrative jumps to the COVID-19 pandemic, arguing that rules and behavioral interventions produced contested, uneven results, while the world needed a scalable medical solution. mRNA vaccines meet that need with unprecedented speed and broad effectiveness, saving millions of lives. The author uses this contrast to frame invention as a distinct political challenge: some crises cannot be solved mainly by regulating, subsidizing, or building existing things; they require creating something new.

From there, the chapter develops a “politics of invention,” claiming modern liberal goals depend on continual technological progress, while many future problems (decarbonizing aviation and cement, carbon removal, major diseases, rapid pandemic platforms) still require breakthroughs. It argues conservatives often understate government’s role in innovation (citing public support behind technologies and firms like Tesla and SpaceX), and progressives often treat invention as secondary to distribution even though new technology increases what universal programs can deliver.

Returning to mRNA’s origin story, Karikó’s stalled career changes when she meets immunologist Drew Weissman at a Xerox machine in 1997. Together they persist despite grant rejections and early inflammatory failures, eventually finding a way to modify mRNA to avoid triggering dangerous immune responses. Their key paper is rejected by Nature and barely noticed after publication; Karikó later leaves academia, but their work is embraced by private-sector pioneers including Moderna and BioNTech, where Karikó becomes a vice president. When SARS-CoV-2’s genetic sequence is released in January 2020, Moderna designs a vaccine candidate within days, leading to record-speed trials and authorization; Karikó and Weissman later win a Nobel Prize, underscoring how close the breakthrough came to dying from lack of support.

The chapter labels this systemic failure the “Karikó Problem”: American science funding has become biased against young scientists and risky, novel ideas. It links slowing scientific productivity to both the growing “burden of knowledge” and to institutional dysfunction—paperwork, slow reviews, “grantsmanship,” and peer-review incentives that punish highly novel proposals. The author traces how the NIH grew from WWII-era innovation policy into a powerful but increasingly bureaucratic system, shaped by political scrutiny and accountability demands that now consume scientists’ time.

To identify better models, the chapter highlights DARPA’s program-manager-driven approach to ambitious bets and Bell Labs’ long-horizon environment that mixed basic research with practical collaboration. It ends by advocating “metascience”: running policy experiments on science funding itself (simplifying applications, empowering reviewers with “golden tickets,” using lotteries, reducing reporting, funding people rather than projects) and rigorously evaluating outcomes. The goal is a diversified innovation system that takes more risks so future Karikós and life-saving breakthroughs are less likely to be rejected into oblivion.