Dr. Hamilton Otaniel Smith is an American microbiologist. He was awarded the Nobel Prize in Physiology or Medicine in 1978 for discovering type II restriction enzymes with Werner Arber and Daniel Nathans as co-recipients.
He later became a leading figure in the nascent field of genomics, when in 1995 he and a team at The Institute for Genomic Research sequenced the first bacterial genome, that of Haemophilus influenza. H. influenza was the same organism in which Smith had discovered restriction enzymes in the late 1960s. He subsequently played a key role in the sequencing of many of the early genomes at The Institute for Genomic Research, and in the sequencing of the human genome at Celera Genomics, which he joined when it was founded in 1998.