Present at the flood: How structural biology came about, by Richard E. Dickerson

Present at the Flood: How Structural Biology Came About is an essential book for every structural biologist and a must for everyone who reflects on the origins of molecular biology. Present at the Flood, authored by Richard E. Dickerson, enchantingly traces the critical path to the discovery of the underlying atomic structures of proteins and DNA. These discoveries became the foundations of modern molecular biology. Present at the Flood interprets the 30 years that revolutionized structural and molecular biology, from 1933 to 1963, and is dedicated to Francis Crick. Francis also helped Dickerson to unearth some of the unpublished materials that illustrate the true history, such as the draft of the first erroneous DNA model. The moments of critical insight and of erroneous ideas are brilliantly captured by Dickerson, who was himself an essential, key ingredient in the discovery of the first protein structure (he was indeed “present at the flood”), and at the same institution where both the myoglobin and hemoglobin protein structures and the structure of DNA were discovered. These discoveries totally revolutionized biology. They were clearly synergistic with each other in a way that depended on the interplay between the personalities just as much as between structural thinkers. Present at the Flood reflects Dickerson's own total engagement and thrill in the process of discovery. It also reflects his keen recollection of the nuance, the slight remark that triggered a cascade of thought—the essence of some of the most important discoveries in all of biology. Like a detective novel, the book draws the reader into the fabric of discovery. It became a reality after the author presented a course of the same title in 2004 at UCLA. Dickerson retreads the pathway that he and colleagues in structural biology walked, carefully reasoning from the knowledge at the time to retrace the steps and ask precisely how insight came about. The book is very different from, for example, James Watson's personal perspective in The Double Helix; rather, it is a historical analysis of the ideas in the progression to discovery and how personalities augmented or bumped the process forward, backward, or sideways. Thus, he recounts mistakes in the early interpretations of Pauling and Corey and Crick and Watson, and recalls Erwin Chargaff's indignation after the DNA structure was determined. This all makes the historical analysis a personal encounter with the players themselves and a delight to read. Each of the first seven chapters begins with a hand-crafted Dickersonian pun! “In this life one should Perutz high goals, but ultimately settle for what one Kendrew”! Then, there follows a list of key publications, some of which are reprinted at the end. In total, over 40 of the original publications are reprinted, an invaluable record in itself. The text focuses onto Dickerson's interpretation of the meaning of research results, the flash of brilliance, the chance encounter, the stumbles, and communications that became the process of scientific discovery. Dickerson reflects colloquially on personalities, and their quirks that coupled to their contributions. The book reiterates the very words of the cast, including the sometimes sarcastic or even mean-spirited responses to competitors. Thus, the reader comes away knowing a lot about the people involved and the interplay of personality in discovery. Dickerson also questions the missed discoveries that could, or even should, have been made earlier—sometimes errors in logic, and happy accidents. The appendices present an invaluable guide to “Highly Recommended Readings,” and identifies those of key contributions, each with commentary as to why they are important milestones. Appendix 3 reflects on Irving Geis, the first artist and illustrator of the meaning of molecular structure who, with Dickerson, illustrated so many of the discoveries throughout the birth of structural biology and with whom Dickerson had a long very productive interaction. One of their books, The Proteins, coauthored by Dickerson and Geis (published in 1969), represented the first picture “from within” of what structural molecular biology revealed. It was also the beginning of the field of “computer graphic” displays of molecular structures. The Flood is dedicated to Francis H.C. Crick, whose contributions, like Dickerson's, were seminal both to the first discovery of the structure of proteins and to the discovery of the structure of DNA. While Crick worked with Perutz on the hemoglobin structure, Dickerson, in 1957, developed the mathematical basis and the key process to refine the “phases” of myoglobin, and thus, to determine its structure. As Crick realized the structure of DNA with Watson and Franklin's diffraction patterns in 1953, Dickerson, in 1980, was the first to determine the atomic structure of B-form DNA at atomic resolution. He recounts Crick's response on seeing Dickerson's atomic “B-form” structure: “So that's what it looks like!” Books written by investigators who shared in the discovery process often have a special intimacy to their story, and this book certainly is rich in this. Dickerson comments on Max Perutz, “Perutz turned out to be a gifted writer and essayist, which is more than many scientists can say.” Even more could be said of Dickerson's consummate ability to engage his readership! Few writers from the inside have been able to capture and analyze the process of discovery as well as Dickerson; he is scholarly, exact, balanced, and selfless. Dickerson's keen humor and insight draws the reader into the fun and excitement at the birth of molecular biology. Present at the Flood is important for the scientific record, as perhaps the only book that focuses on the discovery of protein structure seen in three-dimensional maps of linked atoms alongside and intertwined with the deduction of the structure of DNA. As such, it is a must for all who may reflect on the impact that structural biology has on molecular and cell biology, genetics, proteomics, biochemistry, or drug discovery. ROBERT M. STROUD Department of Biochemistry, University of California at San Francisco, San Francisco, CA 94143, USA