Hamilton Smith

Type II restriction enzymes are proteins that recognize specific short DNA sequences—typically 4 to 8 base pairs—and cleave the DNA at or near that recognition site. Smith discovered the first one, called HindII, in the bacterium Haemophilus influenzae in 1970. Unlike type I enzymes, which cut randomly far from their recognition sequence, type II enzymes cut at defined positions, making them precision tools for DNA manipulation.

Type II restriction enzymes function as molecular scissors that cut DNA at predictable locations, enabling scientists to isolate, recombine, and manipulate specific genes. Daniel Nathans, Smith's colleague at Johns Hopkins, used Smith's HindII enzyme to create the first restriction map of the SV40 tumor virus genome. This combination of cutting and mapping became the foundation of recombinant DNA technology, gene cloning, and the entire field of genetic engineering.

Smith shared the 1978 Nobel Prize in Physiology or Medicine with Swiss microbiologist Werner Arber and American biologist Daniel Nathans, both also at Johns Hopkins. Arber had predicted the existence of restriction enzymes through genetic experiments in the 1960s, Smith biochemically isolated the first type II enzyme, and Nathans demonstrated their practical use in mapping DNA.

Smith became a leading figure in genomics, joining the Institute for Genomic Research (TIGR) and collaborating with Craig Venter on several landmark genome-sequencing projects. He contributed to the sequencing of the first free-living organism, Haemophilus influenzae, in 1995, and later worked on the Human Genome Project at Celera Genomics. He remains a professor emeritus at Johns Hopkins University.