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Restriction Enzymes: A History

Subject Area(s):  BiotechnologyMolecular BiologyGeneticsHistory of Science

By Wil A.M. Loenen, Leiden University Medical Center

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Funding for Restriction Enzymes: A History is made possible by the Genentech Center for the History of Molecular Biology and Biotechnology at Cold Spring Harbor Laboratory. This title is freely available to read online at, or click here to download it in PDF format. The book is also available to order in print format below.

© 2019 • 346 pages, illustrated (38 color and 26 B&W), index
Hardcover •
ISBN  978-1-621821-05-2

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  •     Description    
  •     Contents    
  •     Reviews    


Restriction enzymes cleave DNA at specific recognition sites and have many uses in molecular biology, genetics, and biotechnology. More than 4000 restriction enzymes are known today, of which more than 621 are commercially available, justifying their description by Nobel Prize winner Richard Roberts as “the workhorses of molecular biology.”

This book by Wil Loenen is the first full-length history of these invaluable tools, from their recognition in the 1950s to the flowering of their development in the 1970s and 1980s to their ubiquitous availability today. Loenen has worked with restriction enzymes throughout her career as a research scientist and came to know many of the leaders in this field personally and professionally. She is the author of several authoritative and widely appreciated reviews of the enzymes’ biology. This book was written with the close assistance of several of the field’s pioneers, including Rich Roberts, Stuart Linn, Tom Bickle, Steve Halford, and the late Joe Bertani. The seed for the book was sown at a retirement party for Noreen Murray, to whom the book is dedicated, and its roots lie in a remarkable 2013 conference at Cold Spring Harbor Laboratory that celebrated the people and events that were vital to the field’s development.

Funding for the book was made possible by the Genentech Center for the History of Molecular Biology and Biotechnology at Cold Spring Harbor Laboratory. A companion website to the book ( includes an electronic version of the text and ancillary material that is freely accessible to readers.


1. Discovery of a Barrier to Infection and Host-Controlled Variation: 1952–1953
2. Host-Controlled Variation Is Methylation and Restriction of DNA: The 1960s
3. The Discovery of Type II Restriction Enzymes: The 1970s
4. Expansion and Cloning Restriction Enzymes: The 1970s and Early 1980s
5. The First Decade after the Discovery of EcoRI: Biochemistry and Sequence Analysis during the 1970s and Early 1980s
6. Variety in Mechanisms and Structures of Restriction Enzymes: ∼1982–1993
7. Crystal Structures of Type II Restriction Enzymes and Discovery of the Common Core of the Catalytic Domain: ∼1993−2004
8. Improved Detection Methods, Single-Molecule Studies, and Whole-Genome Analyses Result in Novel Insights in Structures, Functions, and Applications of Type I, II, III, and IV Restriction Enzymes: ∼2004–2016
Summary and Conclusions
Appendix A: The History of Restriction Enzymes October 19–21, 2013 Meeting Program
Appendix B: Modern-Day Applications of Restriction Enzymes
About the Author


review:  “The author, active in the field for 40 years, gives an authoritative, clearly written...narrative. ...The text is produced to a very high standard...This is a permanent resource for advanced students and professionals. Selected portions make excellent supplemental reading for advanced undergraduates.”