Present at the Flood: How Structural Molecular Biology Came About

This book chronicles a revolution in molecular biology--the crucial 30 years (roughly between 1933 and 1963) during which our ideas about proteins and nucleic acids changed from those of formless, functionless organic chemicals into precisely structured molecular machines with specific biological purpose. Proteins evolved from being colloidal micelles or globules with no specific structure (or even sequence) into quite precisely structured molecular catalysts, carrier proteins, and information-sensing agents. Indeed, the very idea that the amino acids of a protein were linked in a specific order in long linear chains was not accepted initially. During this same time period, DNA changed from being a sterile repeating polymer of no particular function (the tetranucleotide hypothesis) into a double helix that serves as the archive of genetic information. Without this revolution, molecular biology would not exist today, and biochemistry itself would still be a collection of recipes and unconnected empirical observations about a cellular slime known vaguely as "protoplasm."

The book is unique in that it tells this story in its authors' own words, as found in reprints of 42 key scientific papers. It is organized into nine chapters:

1. Introduction (goals and methodology of the book)
2. Your Cells Are Not Micelles! (the demolition of the colloid theory of proteins)
3. Workers of the World, Cast Off Your Chains! (cyclol rings vs. polypeptide chains)
4. The Folding and Coiling of Polypeptide Chains (a-helices, ß-sheets, etc.)
5. The Race for the DNA Double Helix (including various triple-helix blunders)
6. How to Solve a Protein Structure (Max Perutz and isomorphous replacement)
7. High-Resolution Protein Structure Analysis (myoglobin and hemoglobin)
8. The Knowledge Explosion (early protein workshops and what came next)
9. Epilogue (what has happened to all the pioneers)

Chapters 2-7 are each followed by reprints of original papers (203 pages in all) that are discussed in the chapter. Each chapter begins with a list of the key publications (including the reprints) relevant to the topic at hand. The chapters themselves are commentaries that place the papers in context and provide explanatory diagrams. A chapter concludes with a reference list of other important papers that were not reprinted, a set of study questions, and the reprinted papers themselves. Answers to study questions appear at the end of the book.

Present at the Flood will be of interest to biochemistry and molecular biology graduate students, to scientists actively engaged in the field, and to anyone who is curious to know where this field that we call "molecular biology" came from.