Hamilton Othanel Smith (born August 23, 1931 in New York)[1] is an American microbiologist and Nobel laureate.

[2] Smith went on to discover DNA methylases that constitute the other half of the bacterial host restriction and modification systems, as hypothesized by Werner Arber of Switzerland.

[2] 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.

More recently, he has directed a team at the J. Craig Venter Institute that works towards creating a partially synthetic bacterium, Mycoplasma laboratorium.

Smith is scientific director of privately held Synthetic Genomics, which was founded in 2005 by Craig Venter to continue this work.