 In 1946 he became an associate professor (and ultimately full professor) at the University of Utah.In 1958, Emanuel Margoliash joined his lab and they began working on the peptide sequence of the protein cytochrome c; based on comparisons between cytochrome c from different species, Smith and Margoliash performed some of the earliest work in the field of molecular evolution, applying the idea of the molecular clock to the highly conserved cytochrome c sequence.In 1969, he worked with James Bonner to sequence histone H4 in several species, which was also of significant use in evolutionary studies.