2007 marks the 25th anniversary of the publication of Molecular Cloning: A Laboratory Manual. Originally published as a single volume, Molecular Cloning was based on the protocols used during the 1980 Cold Spring Harbor Laboratory course on the Molecular Cloning of Eukaryotic Genes. A set of photocopied protocols was widely distributed in 1981, and over the course of the year, the manual was written. It’s impossible to overstate the impact this manual had on a rapidly expanding field. While it wasn’t the first Molecular Biology laboratory manual ever published (that would be Miller’s Experiments in Molecular Genetics from CSHL Press), Molecular Cloning was the book that really put the techniques into every lab’s hands. It opened a door for many researchers into the world of recombinant DNA technology and played a significant role in spreading these approaches through the scientific community. A look back at the reviews of the various editions gives an interesting picture of how quickly Molecular Cloning became such a laboratory standard.

Reviews for the original edition were overwhelmingly positive. There were certainly a few nitpicks, many typographical errors pointed out, and a few complaints about the exorbitant cost ($40). It’s interesting to note how many reviewers were excited by a compilation of methods that actually worked. As noted in the edition’s Preface, “Although molecular cloning seems straightforward on paper, it is more difficult to put into practice.” Sambrook, Maniatis and Fritsch included only protocols that they themselves had thoroughly tested and used successfully in their own laboratories, which seems to have been something of a departure from what researchers had previously experienced with manuals. As George McCorkle happily proclaims in American Scientist, “In our laboratory, mirabile dictu, the procedures in this manual nearly always work.” George Helmer in Biotechnology attests to the quality of the protocols by noting that in his course, “6 out of 10 groups obtained good yields of DNA on the first try” with the miniprep protocol, and that “the remaining students obtained good yields of DNA on the second try.” In TIBS, Hugh Pelham went so far as to title his TIBS review “Cloning Without Tears.”

The reviews consistently point out one of the book’s great strengths, which continues to this day–the wealth of background material included with the techniques. Even in the first edition, the authors knew that understanding how the techniques worked, and knowing why you were performing a particular step was the key to successful experimentation. In the journal Immunology, A.M. Denman praises the authors for providing the uninitiated with the rationale behind each method. He compares the uneasy approach to reading this manual by members of his field to “a Stone Age savage” reading Roitt’s Essential Immunology, and enthusiastically recommends it to “timorous immunologists who feel like stout Cortez on his peak in Darien.”

The first mention of Molecular Cloning as “The Bible” that I can find comes from a New York Newsday article (complete with cartoons of biologists stirring a witch’s cauldron) from 1984. Waclaw Szybalski is quoted as stating, “We have three or four copies in the lab. It’s our Bible.” Kevin Struhl made the same point in Nature in 1985, that, “This book is omnipresent in Molecular Biology laboratories and is utilized to the point where it is frequently referred to as ‘The Bible’.” As someone who started graduate school in 1987, I can attest to this as countless times my questions were answered by a point to the bookshelf and instructions to “read the bible.”

However, with this great success came almost immediate demands for an updated version. The aforementioned Newsday article talks about the book being woefully out of date upon publication, due to the quick progress in the field. The authors promised a new edition for 1986, which was soon pushed back to 1988. Then the authors realized that the book would be pointless without including even newer developments, like PCR, and the second edition was pushed back to late 1989. At this point, Molecular Cloning went from being Maniatis et al., to being Sambrook et al., to properly reflect Joe’s lead role in writing the manuals (the third edition was written solely by Joe Sambrook and David Russell, and despite this, it is still referred to as “Maniatis”, whereas those who know the herculean efforts put forth by Joe do our best to refer to it as “Sambrook”). In their preface, the authors illustrate the growth in the field since the previous edition in a simple manner–in 1982, there were less than 350 sequences on file in GenBank. By 1989, there were more than 15,000. Which helps explain why Molecular Cloning grew to its now familiar three volume configuration. Stuart Orkin’s review in Nature talks about the excitement for this “long-awaited” new edition felt by “a generation of molecular biologists [who] grew up” with the book.

Also notable in Orkin’s review is that he speculates on future editions, which will have to be “encyclopaedic in scope to fill current gaps and account for future developments.” He suggests (quite presciently) that, “Perhaps a computer-based format will be the final evolution of this literary genre.”

Which brings us to 2001, and the third and latest edition of Molecular Cloning. The book was re-styled and while it’s still at its core a laboratory manual, many of the stylistic techniques from science textbooks were adapted and put into use to help reinforce concepts and understanding of techniques, something vitally important at a stage where so many methods have been automated or can be accomplished by kit without ever making up a single reagent. The book’s Preface discusses the techniques that at the time of the first edition seemed almost “magical” turning into a mature discipline with high reliability. Reviews for this edition re-establish its “primacy as the molecular laboratory manual” (TINS) and “the first port of call when establishing a molecular technique new to a laboratory” (TICB). The reviews are almost wistful in nature, all remarking on the comment in the book’s Preface that this will “almost certainly” be the last print edition of the manual. Science calls it “a last hurrah”.

This edition came with a website, the now defunct MolecularCloning.com. This was a big experiment for Cold Spring Harbor Laboratory Press–we already had online journals, could the book program start to move into this exciting new medium as well? The site reproduced the protocols from Molecular Cloning and provided discussion space for those asking questions or making alterations to techniques. The site was well-received, but ran into a few problems, mainly a lack of a mechanism for continuously adding new updated material. It had taken the authors more than 10 years to compile this new edition, and they didn’t have the time to commit to becoming full-time editors of a large website as well. Another issue was that we never saw much community participation with the forums, something that continues to plague science publishers as they create yet another “myspace for biologists”. The lessons learned from MolecularCloning.com led to CSH Protocols. We realized that if we were going to continuously add new material, we had to think of the project as a journal, and give it a full editorial staff. Moving things out from under the Molecular Cloning name also gave us the freedom to expand our areas of coverage and bring in material from our other manuals, as well as publishing new original articles. Everything that could be found on MolecularCloning.com can now be found on CSH Protocols, plus a whole lot more.

As for this being the last print edition of Molecular Cloning ever, it’s not clear if that prediction will hold true. Despite the growth of electronic media, there’s still a high level of demand for books. Ink on paper is a superb interface, one that has lasted for thousands of years. It’s cheap, durable, high resolution, portable and doesn’t demand a recharged battery. You can take it to the beach, drop it in the bathtub, or spill (some of) your bench solutions on it, and it still keeps working. Not promising anything here, but don’t be surprised if a fourth edition turns up in a few years.

Oh, and one side note–the third edition was the first to feature a sewn binding, one that was designed to be both durable and to lay flat on the benchtop. The plastic comb binding of the first two editions generated more commentary than nearly any other feature. There were those that loved it (Kevin Struhl in the Nature article above), and those that hated it (Karen Armstrong in the Quarterly Review of Biology). Let me assure you that despite what many have claimed, CSHL Press did not feature the spiral binding to deliberately get the book to fall apart forcing you to buy a new copy. The idea was to get the book to lay flat on the bench, and that was what was available at the time. The later sewn binding represents a better solution, although it was not without its critics as well (Adrian Smith in TICB called it “less rugged”). Which I guess just goes to show, even “The Bible” will have its critics.