Following in Merck's Footsteps: Classic Scientific Books

Last December, the Merck Index celebrated its 100th birthday. The 2,350 pages of the latest edition, the 11th - with 10,000 entries, 8,000 structures, 62,000 synonyms, and 129 pages of charts and tables - seem a far cry from the original 170 pages published in 1889. The first edition, named for the German company (originally a pharmacy) founded in 1668, was written for the physician, chemist, and pharmacist, listing "whatever chemical products are to-day adjudged as being useful in either medicine or technology." The major selling point of the index - a wealth of information provided conveniently in one volume - hasn't changed. But the new Merck Index (S. Budavari et al., eds., Rahway, N.J., Merck & Co., 1989) serves a far broader audience than did the first edition, reflecting the overlap of biology, chemistry, and medicine, as well as interest from others, such as journalists, investors, and patent attorneys. "Today's society is increasingly more dependent on scientific research and technology. The Merck Index, once used primarily by chemists, now has a broad constituency among other professionals, especially those concerned with environmental safety and health issues," said Patrick P. McCurdy, director of the office of communications of the American Chemical Society, at ACS' Miami meeting last fall. In Volume 10 (published in 1983), the venerable reference book marked a turning point, introducing genetic engineering techniques along with the more traditional organic syntheses. Similarly, the latest edition is also a mix of old and new. Users of the index can still look up the number of drams in a pennyweight or foot-candles in a lux, but they can also consult lists of pesticides, carcinogens, and controlled substances. Although the Merck Index went on-line in 1984, its editors still consider it important to keep the printed version in one volume; thus, they constantly work to prune down the information to be included. The Merck Index is by no means the only scientific book facing the dual challenges of evolution and expansion. Inspired by the centennial of the esteemed index, The Scientist embarked on an examination of other such classics, limiting the fields to those addressed by the Merck. Criteria for inclusion in the "classic" category range from the scientific to the highly unscientific. A quasi-objective analysis was done by consulting library files at General Electric Co.'s Research and Development Center in Schenectady, N.Y., a facility frequented by more than 600 Ph.D.-level scientists. In addition, conversations with scientists in academia and industry yielded some more subjective suggestions for titles to be included. For example, when asked to name their favorite book, a handful of molecular biologists from the State University of New York immediately chorused, "Genes IV" (Benjamin Lewin, Oxford, England, Oxford University, 1990). The book, which is extremely up to date, manages to squeeze a remarkable amount of information on genetics into one volume. Personal reasons why a book should be considered a classic are as individual as scientists themselves. Frank Erk, editor of the Quarterly Review of Biology and professor at the State University of New York at Stony Brook, has an interesting yardstick for measuring the impact of Charles Darwin's works. "Two out of the 51 volumes of the Harvard Classics are Darwin's The Origin of Species and The Voyage of the Beagle," he notes. By contrast, Erk points out, among the other titles in the Harvard series, "only one volume is devoted to the Bible, and three to all of English poetry." (Both volumes were included in the original Harvard Classics edition, edited by Charles Eliot and published by Harvard University, Cambridge, Mass., in 1909). Today's scientists continue to laud Darwin's works for their impeccable reasoning, despite the fact that the author did not know genetics. "It's excellent; it gives a sense of wonder," says Erk of The Origin of Species, which first appeared in 1859, "and if you think it's dull, you're no biologist." By contrast, as an alternative - and more quantifiable - way of determining whether a particular book is to be considered a classic, Dave Shub, head of the Institute for Biotechnology at SUNY-Albany, bases his choices on number of citations in the literature. When The Scientist's lists began to emerge, the books that were included sorted themselves out into three categories - references such as the Merck Index; protocol "cookbooks," because science is, after all, doing; and textbooks so excellent that, even though they were written for students, also become dog-eared by researchers thumbing through them. To the chemist, the Merck Index is but one of several places to look up fundamental yet specific information, such as boiling and melting points. The century-old classic is usually wedged on a shelf along with the CRC (Chemical Rubber Company) Handbook of Chemistry and Physics (R.C. Weast, ed., Boca Raton, Fla., CRC Inc., 1988, 70th ed.) and the Aldrich Catalog/Handbook of Fine Chemicals (Milwaukee, Aldrich Chemical Co., 1990, 25th ed.). These two estimable references are jam-packed with facts, all of which are amazingly easy for the reader to access. A fascinating book for the biologist and physician is Mendelian Inheritance in Man (MIM), a one-of-a-kind compendium of all known human genetic variants by Victor A. McKusick, University Professor of Medical Genetics at Johns Hopkins University. The 4,888 entries in the 1990 ninth edition (Baltimore, Johns Hopkins University) range from familiar genetic diseases, to hemoglobin abnormalities ad infinitum, to such traits as uncombable hair; misshapen toes; pigmented tongue tips; inability to smell skunk and freesia flowers; and missing teeth, lashes, nails, and nasal bones. "It is the single most important book in human genetics, both clinically and scientifically. When a student comes in to talk about a particular disease, it's the first place I turn," says Ben Pierce, of the department of biology at Baylor University in Waco, Texas. Pierce's own book, The Family Genetic Sourcebook (New York, John Wiley & Sons, 1990), is a "McKusick's greatest hits" of sorts, describing 100 of the most interesting traits from the classic title in layman's language. Like the Merck Index, each new edition of MIM reflects technological evolution. The original 1960 version was a catalog of sex-linked traits, whose identification required no technology at all because they are defined by their preponderance in males. In 1962, rare autosomal recessive traits were added, and by 1964, dominant traits were included. Somatic cell hybrids debuted in 1971, and gene sequences in 1983. In 1987 MIM went on-line, a format meant to complement, rather than replace, the book, whose print seems to grow smaller with every edition "Next time we will have to go to two volumes. But we're working to create a new database at Hopkins to combine some things, such as mapping and molecular defects, so it's not duplicative," says Johns Hopkins University Press' Carol Bocchini, editor of MIM. The standard "cookbook" in chemistry is the Handbuch der Organi, an index by Friedric Konrad Beilstein, providing the who, what, where, when, and how of organic syntheses. Known simply as "Beilstein" and first published in 1893, it can be found on most science library shelves. Yet Beilstein's venerable index did not appear in English until 1984; before the English edition appeared, researchers had to struggle through the German. In English, it is known as Beilstein's Handbook of Organic Chemistry (supplementary series 5, New York, Springer-Verlag, 1984-90). Falling somewhere between "reference" and "cookbook" is the Physician's Desk Reference (PDR), now in its 44th edition (Oradell, N.J., Medical Economics Co., 1990), and, like the others, available on-line. The book provides everything you'd want to know about more than 2,000 prescription drugs - indications, dosages, side effects, contraindications, even color photographs. Doctors' offices are littered with old PDRs, and many a physician can be found hunched over the volume between patients' visits. In the fast-paced field of molecular biology, in which researchers' requirements are different from those of chemists, "we don't need lists of data like Merck. We need protocols," says Dave Shub. Here, two classics provide basically the same information - Current Protocols in Molecular Biology, by Fred Ausubel et al. (Brooklyn, N.Y., Greene Publishing Associates, 1989, 3rd ed.; also known among biologists as "The Big Red Book") and Molecular Cloning, by Thomas Maniatas, et al. (Cold Spring Harbor, N.Y., Cold Spring Harbor, 1989, 2nd ed.; also known in biology circles as "Maniatis"). "The Big Red Book" lists seven Harvard Medical School researchers as authors, but a large part of its appeal, Shub says, is reader input in quarterly supplements. The newsletter, instituted in the fall of 1987, is called The Red Book Bulletin. Says editor Sarah Greene of Greene Publishing, "Anyone who has worked with a protocol is invited to send in comments," including readers who have had trouble with a protocol outlined in the book, those who can improve on a protocol that is listed, and readers who have found errata. "The editorial board goes through the comments," Greene explains. "If someone says, `I can do that plasma prep faster than you,' we can't immediately go into the lab and try it, so the newsletter is a mechanism to publish it before it can be tried and put into the red book." Reader participation was slow at first, so Greene threw in an incentive - a T-shirt reading "Never Clone Alone." It's become a status symbol, she says. Meanwhile, "The Big Red Book" itself is constantly evolving. "We strive for half replacement and half new material every year. So 500 pages are added a year, 250 new and 250 replacement. A supplement might consist of a new chapter, or just one page to replace a protocol with a better recipe." The 1989 third edition is three times the size of the first. The three volumes span 1,200 pages; each of the 8,000 subscribers to the book-and-supplement package pays $255. A shortcut in the works is a companion volume listing just summaries. "Once you do something a few times, you don't need all that material. We rewrote all of the boxes of abbreviated steps from the big book into a separate book," says Greene. Molecular Cloning evolved from a collection of protocols from a 1980 Cold Spring Harbor course on eukaryotic genes. After much compiling, discussion, and revision, the 1982 first edition was born. The long-awaited second edition was published in 1989. "Maniatis 1 became a classic by the time it was two years old because of the number of times it was cited. So the second edition was like the Second Coming," says Shub. Both "The Big Red Book" and Maniatis are classics, their editors and users agree, because they are useful to both the experienced and novice cloner. "We include an incredible amount of background, so that anyone can not only perform the protocols, but understand what they're doing. Even cloning has become somewhat automated, from kits. You can follow them [instructions in the kits] blindly and get results, but don't know why you got them. Molecular Cloning goes to great lengths to provide the actual theoretical background," says managing editor Nancy Ford of Cold Spring Harbor Press. The textbooks that come and go are far more numerous than those that stand the tests of time and technology, but a few have emerged as classics. Synthetic chemists own one or both of a venerable pair of advanced texts, both from John Wiley & Sons - Jerry March's Advanced Organic Chemistry, now in its third edition (1985), and Advanced Inorganic Chemistry, by F. Albert Cotten and Geoffrey Wilkinson, which is in its fifth edition (1988). Although intended for students, both books are written on an extremely high level, and even senior scientists do not find them to be condescending. Some books are simply so perfect that they are valued even when they become outdated, like a Beatles record from 1965. Many geneticists revere Alfred Sturtevant and George Beadle's 1936 Principles of Genetics. First published in 1939 by W.B. Saunders in Philadelphia, it was republished in 1962 by Dover, "even though the genetics was out of date, because it was so beautifully written," says Erk. Similarly, many a medical researcher will reach for Bloom and Fawcett: A Textbook of Histology (Philadelphia, W.B. Saunders, 1986, 11th ed.) for its elegant illustrations and clear descriptions, even though the book is out of print. Alex Maximow, originally scheduled to write the book, died in 1928, before he could complete it. William Bloom of the University of Chicago and others took over, and the first edition appeared two years later. By 1962, the eighth edition, Don W. Fawcett from Harvard Medical School joined. Bloom died before the 10th edition was published in 1975. Bloom and Fawcett has smoothly outlived its creators. But Worth Publishers in New York was in a bind when the seemingly irreplaceable Albert Lehninger died a few years ago. The first edition of his classic work, published in 1970, made his name almost synonymous with the book's title, Biochemistry. But his 1982 third edition gradually became outdated, although it was still the first place many a professor would turn to find a clear and concise explanation of a biochemical pathway. After a long search, the publisher found biochemists Michael Cox and David Nelson at the University of Wisconsin, Madison, to revamp Lehninger's text for a fourth edition. Their effort is scheduled to be published next year, says Wendy Schecter, editorial assistant at Worth. And finally there are the new classics, the books that flesh out the marriage of biology and chemistry that has come to predominate the Merck Index in recent years. One such classic is Molecular Biology of the Cell, by Bruce Alberts, et al. (New York, Garland, 1989, 2nd ed.). Written by a half-dozen "who's who" caliber investigators and first published in 1983, this book succeeds, like the other classics, because of a winning combination of thoroughness, timeliness, and lucid explanations. The chapters contributed by the different authors read as if they were penned by one person, a feat lacking in many multiauthored works. How will publishers handle the ever-increasing onslaught of scientific information? Will computers replace books? Most think not, for there is something comforting about a book that you can touch without relying on access to a computer terminal - as the persistence of the Merck Index, PDR, and Mendelian Inheritance in Man in hard copy, despite popular on-line versions, attests. And although computer-only "textbooks" are beginning to appear, researchers are not quite ready to part with their Lewins and Lehningers. Protocol manuals are also likely to co-evolve with their on-line versions, relying on supplements and multivolume sets rather than becoming extinct. Says Cold Spring Harbor Press' Nancy Ford, "The genome project will certainly provide a wealth of information, and more than likely that will best be handled by computer. But in terms of convenience of working at the lab bench, whether or not computerized versions will be a reasonable alternative is hard to know." More practically speaking, a beloved, dog-eared book can still go where a computer cannot - a plane, a hospital bed, a campsite, even a blackout-stricken lab. Like an age-old species that has survived because it has adapted to a variety of niches, classic books will endure. Ricki Lewis teaches biology at the State University of New York, Albany. She hopes that her biology textbook, to be published next year, will become a classic.

Following in Merck's Footsteps: Classic Scientific Books

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