How did fluorescence-based sequencing improve on radioactive methods?

The transition from radioactive methods to fluorescence-based sequencing was a pivotal advancement for the Human Genome Project, as it enabled the automation necessary to sequence large, complex genomes.1

Previously, sequencing relied on radioactive labeling to detect reaction products, a process that was labor-intensive and difficult to scale. The development of automated sequencing machines that utilized fluorescent dyes instead of radioactive decay allowed for significantly higher throughput. By replacing radioactive detection with fluorescence, scientists could scale up the production of DNA sequences, making the ambitious goal of mapping the entire human genome a realistic endeavor. This shift toward automation was essential for managing the massive volume of data required to decode the human genetic blueprint.12