History
Early attempts at mutagenesis were non-site specific using radiation or chemical mutagens. Analogs of nucleotides and other chemicals were later used to generate localized point mutations, examples of such chemicals are aminopurine, nitrosoguanidine, and bisulfite. Site-directed mutagenesis was achieved in 1973 in the laboratory of Charles Weissmann using N4-hydroxycytidine which induces transition of GC to AT. These methods of mutagenesis however are limited by the kind of mutation they can achieve.
In 1971, Clyde Hutchison and Marshall Edgell showed that it is possible to produce mutants with small fragments of phage ϕX174 and restriction nucleases. Hutchison later produced with his collaborator Michael Smith in 1978 a more flexible approach to site-directed mutagenesis by using oligonucleotides in a primer extension method with DNA polymerase. For his part in the development of this process, Michael Smith later shared the Nobel Prize in Chemistry in October 1993 with Kary B. Mullis, who invented polymerase chain reaction.
Read more about this topic: Site-directed Mutagenesis
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