Molecular Biology Watson Pdf Free Download

Four years ago, The FASEB Journal launched a new section called "Milestone Books Review" to celebrate those infrequent books in biology and medicine that possessed truly exceptional suasion and epistemological momentum (1). That criterion meant that it was anticipated that these special reviews would be infrequent. The first review appeared at that time (2), and now the second arrives.

The term "molecular biology" was coined in 1938 (3) by Warren Weaver, then the Director for the Natural Sciences at the Rockefeller Foundation (although I have long wondered if the chemist Linus Pauling or the X-ray crystallographer J. D. Bernai might have at least uttered, if not published, the term even earlier). Molecular biology appears to have been used only once in the title of a textbook before the 1953 arrival of the double helix (4). Genetics textbooks were for the most part slow to take up this new pristine concept (ironically, the very embodiment of genetics), and biochemistry textbooks that were written or revised in the late 1950s/early 1960s also were surprisingly deaf to the sirens' call. A seminal 1959 textbook (5) had chapters by several leaders of nucleic acid structure, including Paul Doty and Alex Rich, as well as major figures in gene action (e.g., David Hogness, Edward Lennox, Cyrus Levinthal, Richard Roberts, and Robley Williams), but the term molecular biology was not to be found. I have written about this exceptional book elsewhere (6).

However, 50 years ago on July 21, 1965, Jim Watson's textbook Molecular Biology of the Gene (hereafter MBoG) went to press, with an initial print run of ∼10,000 (Neil Patterson, publisher, personal communication). It was an immediate hit for three reasons—the author's fame, the dearth of existing textbooks on molecular biology (vide supra), and the book's engaging graphics done by Keith Roberts (who shall reappear). Beyond the burgeoning scientific discipline it embraced, the book also represented a new pedagogical style, to put it mildly.

When I learned that 2015 is the 50th anniversary of the book's publication I got to thinking about my first encounter with it. Like many of us who can still recall where we were and what we were doing when we first saw the book, the sensation was that we had not seen anything like it before. The discovery had been made in 1944 and the structure had been revealed in 1953, yet by my time as an undergraduate (1959–1963), the biology curriculum at Syracuse University had integrated the double helix only marginally. Ironically, at the State University of New York Upstate Medical School, adjacent to the Syracuse University campus, was Martynas Yĉas, one of the members of the "RNA Tie Club," which was a group of RNA/genetic code colleagues organized by Watson and physicist George Gamow in 1954-1955, each member to be issued a necktie bearing the name of their "owned" amino acid (Yĉas got, or perhaps sought, cysteine). Having been told by a faculty member that Yĉas was "the second smartest man in Onondaga County," I went to explore the possibility of working on a project with him in my senior year but could not understand why in the world he was trying to sequence Bence-Jones proteins, which he told me were urine-secreted immunoglobulin light chains that are present in multiple myeloma. Of course, his work was prescient as I realized years later. A general biology course at Syracuse taught by Roger Milkman, who had been a Ph.D. student with the geneticist Paul Levine at Harvard University when MBoG was being written, was memorable for its content and Milkman's pedagogical skills, but DNA was at the rostrum only once, when he told us that the UV inactivation spectrum of a certain trait in a particular organism peaked at λ = 254 nm, a fact that enthralled me; I can still see the spectrum curve that I had copied from the blackboard into my notebook. Later, I took a course that was indeed called "Molecular Biology," but still in hindsight, I can see that Syracuse was slow to modernize the curriculum, although it was quite a strong biology program overall. (As a student, I survived being interviewed by Leo Szilard, who was a member of a U.S. National Institutes of Health training grant site visit committee, and I also got to attend dinner with J. B. S. Haldane after his seminar.) Thus, the way I had responded to MBoG in 1965, my second year of graduate school (I had remained at Syracuse), was rhapsodic. The book threw down the gauntlet: the gene is all and here it is. There had been antecedents in which its author and Francis Crick had proclaimed that the double helix was everything, perhaps Watson more so than Crick as the years went forward, with Crick later turning to cell differentiation and pattern for a while and then histones and DNA (with no success) and later the brain, an endeavor in which one has to admire him for even trying. Since having first arrived at Harvard in the fall of 1956 from Caltech but having spent peripatetic periods of 1954-1955 in Woods Hole (Fig. 1), a "sabbatical" stop back with Crick and trips to Switzerland, Scotland, Israel, Egypt, and Germany, inter alia loci, his DNA-centric position as a junior faculty member rankled many. However irritating Watson's tirades about "old biology" may have been to some, with them being witnessed by senior faculty such as Ernst Mayr, perhaps the greatest biologist in the world at the time, Watson (with his manner aside) was right to a considerable degree. DNA might not be literally superior to everything in biology, but it surely was, to use the current language of our grandchildren, "awesome" and "huge."

The author in 1954, post-double helix, pre-Harvard and pre-textbook, outside the home of Albert Szent-Györgyi on Penzance Point (Woods Hole, MA, USA). The model of DNA, neither as atomically detailed nor as iconic as the one Watson built in 1953, had been assembled by George Gamow. Its hat, eyes and glasses, fish jawbone as mouth, and a pair of sneakers as feet playfully conveyed Gamow's fictional colleague-muse "Mr. Tompkins." Reproduced with permission from the Marine Biological Laboratory Archives/Woods Hole Oceanographic Institution Library from the 2005 exhibit "Science is We—MBL Summer 1954," curated by Ann Weissmann. The photograph was taken by Delbert E. Philpott.

In looking back at MBoG, one can consider several historical contexts. First, despite a dozen antecedent texts with molecular biology as or in the title (a bibliographic search revealed 12 textbooks published in English before 1965 with Molecular Biology as the title, or as part of the title (see ref. 4), there was only one of substance. It was the textbook assigned in the aforementioned molecular biology course that I had taken called Molecular Biology of Bacterial Viruses by Gunter S. Stent (7). Although beautifully written and richly expository, it was curiously understated with regard to the double helix per se, even though it was published a decade later. (That said, it does have a very good final chapter on the discovery of messenger RNA.)

Another dimension of Watson's creation of MBoG is a less widely known part of his post-double helix career. Having pulled off such a remarkable feat with Francis Crick, there soon loomed "career chapter two." RNA was the next quest for him and others, starting in the early 1950s when he was at Caltech but with the different functional roles of RNA having yet to be discovered. Watson and others wondered if the then-envisioned "generic" RNA might have some regular, repeating domain, a 3-dimensional structure similar to DNA, and he had devoted much of his efforts to this research. Early measurements of how much the 260-nm UV absorption of natural RNA increases when heated got him and others excited about a DNA-like structure but it soon became evident that this UV hyperchromicity was attributed to intramolecular folding of RNA, whatever the base sequence and typically involving about two thirds of the chain. Watson and others had of course hoped for a better (i.e., more architecturally appealing) outcome. However, by the time he came to Harvard, a recruitment effort for which the late Paul Doty (8) deserves all the credit, the first cog on the RNA machinery had been discovered—transfer RNA (9–11). In his new Harvard University laboratory, Watson set his sights on the process of RNA synthesis and the most intriguing question of all: what takes information from the gene to protein, and could it be RNA as long suspected? The laboratory was populated by biochemists such as Klaus Weber and Alfred Tissieres and gifted Ph.D. students such as Joan Argetsinger (later Steitz). (For an evocative description of the Watson laboratory at the time and of her own nascent research career, see ref. 12.) The Watson laboratory soon made progress on several fronts, by far the most important of which was the codiscovery of messenger RNA. I set forth this history to convey that when Watson sat down to write MBoG, starting in 1962, he had been at the forefront not only of DNA but of RNA as well, and I contend that this position he held was a key to the excellence of the book, although his bravado was surely another key factor, as we shall see.

Without resorting to archival history (13) in MBoG Watson laid down the au courant DNA story and its readout function in a way that balanced the key facts with a sense of momentum and bravado. Textbooks are always factual by definition, but MBoG was more—it was a call to arms. Students were being beckoned sotto voce (maybe not so sotto): "sign up today!" It is also worth noting, as Watson emphasized in the Preface, that the story of the gene was not to be told without paying tribute to certain aspects of antecedent biochemistry. For many students, MBoG may have been the first time that they had gotten the connection between the ATP and DNA eras. Watson did this because he had seen its necessity from the course he had been teaching; in fact, those lectures formed both the raison d'être and métier of the book.

Most readers immediately were struck by the use of declarative sentences as chapter section headings. This was a totally new style. It had strong appeal to students, viz. "there must be a genuinely true point here because it is stated to be true" (QED). Another striking feature of the book is how the author squeezed in breaking findings, perhaps even calling back a chapter or two to incorporate these new results. For example, 3 days before the final manuscript of MBoG had been sent to the compositor, Paul Doty had communicated to the Proceedings of the National Academy of Sciences a paper from Alex Rich's laboratory that concluded that the ribosome reads mRNA in the 3′ to 5′ direction. Given his very close relationships with both Doty and Rich, it is very likely that Watson was aware of the submitted manuscript. Many authors, just finishing a textbook manuscript, would have felt that the jury was still out; however, Watson stated boldly in the book that the reading direction is 5′ to 3′ and that "this opens the possibility that a ribosome can attach to an incomplete mRNA molecule still in the process of synthesis on its DNA template." This turned out to be the case (in prokaryotes).

Watson's use of declarative sentences as chapter section headings was too good not to be replicated, as success always is. Thus, when he and coauthors launched The Molecular Biology of the Cell in 1983, the declarative section headings were there, as a palimpsest, as were other elements of the bold centrality of the gene, and just as Watson had been keen to include biochemistry in MBoG, Molecular Biology of the Cell also started from the same point of departure (e.g., the importance of weak chemical bonds, etc.) and also extended the graphics of MBoG in extremely engaging ways. One of my favorites was the depiction of a slithering safe cracker in the Introduction, designed to convey a key thermodynamic principle there at the outset. (The able Keith Roberts was on the scene again.) In another book, A Genetic Switch (14), the best "primer" discourse ever on this subject, this style again was carried forward.

In celebrating MBoG, it is only fair to recall that it had some detractors. These were for the most part the standard citizenry who feared that their grip on an earlier edifice (e.g., intermediary metabolism) was being attacked or even overthrown. On his own campus, Watson's world had begun to move in his favor at the time he was writing the book. Because, in part, of key efforts by John Edsall and a fortunate, catalytic relationship between Paul Doty and certain Harvard administrators, notably McGeorge Bundy, a new form of biochemistry (both as curriculum and research) arose that was much more empathic and welcoming of molecular biology. With regard to both this and Harvard BioLabs transformation and MBoG, time soon proved Watson right. His boldness and indeed audacity made MBoG what it was and is: a then-uncommon and later a more frequently seen pedagogical mode of a textbook. The author's intellectual gifts and personal traits both ensured MBoG's success, just as they did in his pursuit of the double helix.

Thus, MBoG is a FASEB Journal milestone book in every dimension of how this honorific section of the journal was conceived. Its author deserves a kudos for his early move and the erudition with which it was done. He will long be remembered for "The Double Helix" (15), but nothing he has written exceeds in lasting value the new-day textbook that he had sat down at his desk to start in 1962 and which took our breath away when it was published 50 years ago this summer.

Judith Nordberg at the University of Massachusetts Medical School's Lamar Soutter Library kindly conducted the textbook search. I am grateful to Richard Burgess (University of Wisconsin) for pointing out Watson's prescient statement in MBoG on the direction of mRNA translation. I thank Gerald Weissmann, Editor-in-Chief of The FASEB Journal, for suggesting the photo in Fig. 1. Book cover image is used with permission.