During his years at Washington University in St. Louis, he also led efforts to develop yeast artificial chromosomes that allowed for the study of large portions of the human genome.

"[3] Upon graduating with his PhD, Olson worked at Dartmouth College as an inorganic chemist but experienced "an early mid-life crisis" and chose to change fields.

[5] In 1979, he accepted a position at Washington University in St. Louis, where he began to work on the development of systematic approaches to the analysis of complex genomes.

He worked with a computer developing algorithms for parallel genome mapping projects through yeast while John Sulston focused on nematode worm, Caenorhabditis elegans.

"[11] In 2003, Olson was elected to the American Academy of Arts and Sciences for "developing technological and experimental innovations critical to genome sequencing.