Marshall Edgell, Ph.D

Emeritus Kenan Professor of Microbiology at the University of North Carolina and Founder of Innatrix

Dr. Edgell was an independent discoverer of the cleavage properties of restriction enzymes. This discovery, by him and separately by D. Nathans & H. Smith, changed the nature of biological research. Dr. Clyde Hutchison and Dr. Edgell had developed a biological assay in 1970 for small fragments of DNA using limited digestion with pancreatic DNase (Hutchison & Edgell, 1971). That stimulated their labs to try various nucleases under different conditions to determine if DNA could be cut into specific fragments.

Marshall was in the library reading a paper (Schnegg B & Hofschneider PH, 1969) documenting that a mutant of φX174 was subject to the phenomenon of restriction – in contrast to wild-type, which is not subject to restriction. The classic light bulb went on above his head as he reasoned that that meant the phenomenon of restriction must involve sequence-specific cleavage of DNA, since a sequence change was involved in becoming sensitive to the phenomenon of restriction. Within a fairly short time he and Dr. Hutchison proved that was true using a sample of an extract [generously provided by Hamilton Smith] that degraded Hemophillus transforming principle. The team used that extract to cleave C14 thymidine labeled φX174 replicative form (RF) DNA into specific fragments.

Dr. Edgell also was a member of the team that invented site-directed mutagenesis. Site–directed mutagenesis is at the heart of modern molecular biology and our capacity to test hypotheses concerning gene function. Using the assay described above they realized that it should be possible to use their assay for small DNA fragments along with mutant oligonucleotides to effect site-directed mutagenesis [which term they coined]. Michael Smith synthesized the oligonucleotides needed. The team successfully tested the method.

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