Molecular pathology techniques are rooted in fundamental molecular biology discoveries of the 1940s to 1980s.4 The clinical laboratory application of molecular biology techniques would not be possible without the discovery by Griffith and Avery that nucleic acid is the genetic material. The foundation of work by Chargaff and Franklin was capitalized on by Watson and Crick, who elucidated the structure of DNA. Understanding DNA structure is seminal to understanding nucleic acid hybridization, which is central to almost all molecular methods used in the clinical molecular laboratory. Additionally, work by Nirenberg (unraveling the genetic code); Wilcox, Smith, Nathans, and others (use of restriction endonucleases for DNA manipulation); Baltimore and Temin (discovery of RNA-dependent DNA polymerase or reverse transcriptase); Britten and Davis (hybridization kinetics); Kornberg and Okazaki (work on DNA polymerases and DNA replication, respectively); Southern (development of solid-phase nucleic acid hybridization, or the Southern blot); Sanger, Maxam, and Gilbert (development of DNA sequencing); Mullis (discovery of PCR for in vitro nucleic acid amplification); and their scientific collaborators and competitors led to a refined understanding of how DNA may be manipulated in vitro for research and ultimately diagnostic purposes.
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