This directed case study with a lab component tells the story of “Sara,” a college sophomore majoring in biological science. Sara has been awarded an internship in a lab focusing on sequencing gene markers for species identification. On her first day, she learns that the sequencing machine is temporarily out of service, so she is asked to prepare the reaction tube for sequencing the following day using the traditional Sanger method. Sara experiences experimental errors that lead to unexpected results, but her good lab notes allow her to pinpoint the cause. When she runs her prepared reaction tube the following day through the repaired automated sequencing machine she realizes that the invention of Professor Leroy Hood at Caltech and the team of DuPont Research Station has paved the way for second, third, and next generation sequencing (NGS). Central to the case is an activity in which students simulate the synthesizing of new strands of DNA by playing the role of DNA polymerase using the labeled dideoxynucleotide sequencing method.  Originally designed for a first-year medical college general biology class, this case can also be used in high school and college-level biology or biochemistry courses.