The Chemical Educator, Vol. 9, No.2, Media Reviews, © 2003 The Chemical Educator


Media Review

Introduction to Bioinformatics. By Arthur M. Lesk. Oxford University Press: Oxford, 2002. 320 pp, paperback, 246mm ´ 189 mm. £23.99. ISBN 0-19-925196-7.

Bioinformatics is an expanding field of science with a very broad definition. Its name will be familiar to most scientists, but, when asked, few would be able to give a precise definition of what areas bioinformatics covers. To put it most simply, bioinformatics can be defined as an interdisciplinary field that “marries” biology and computer science.

Readers of this book will find good coverage of mainstream topics in bioinformatics. This includes information retrieval from databases, sequence comparison, phylogenetic inference methods, and protein structure prediction and modeling. As the title implies, the text is aimed at readers with little or no prior knowledge of bioinformatics. In addition, it assumes very little previous knowledge of biology or computer science. It introduces the principal concepts in bioinformatics, its applications and how it may be applied effectively.

This book is most suitable for readers who are developing an interest in genetics and proteomics. This would include undergraduates who have done some basic molecular biology at the university level. Alternatively, any computer scientist with an enthusiasm for applying their computer knowledge to solve biological problems would find this book useful.

In the first chapter, readers are eased into the world of bioinformatics through an introduction to its main components. This includes the concept of the central dogma (DNA ® RNA ®Protein), databases, computer science, and the World Wide Web as a valuable resource for information and tools. This is followed by a series of examples to illustrate the objective of bioinformatics. From an early stage, the author makes it clear that the book is not targeted mainly at those who seek to learn more about the programming aspects of bioinformatics. Even so, the chapter does contain some snippets of PERL that should wet the appetite of those who are particularly code savvy.

The field of bioinformatics developed from the realization that the genetic make-up of living organisms is much too large to be examined manually. Even the genome of one of the simplest organisms, the bacteria Mycoplasma genitalium, consists of over half a million base pairs. In the second chapter, the author provides the reader with an appreciation of both prokaryotic and eukaryotic genomes. This chapter not only introduces important concepts in genetics, but also makes the reader aware of the wealth of information “hidden” in the genomes, from the world’s most studied worm, the nematode, Caenorhabditis elegans, to us, Homo sapiens. The chapter concludes by illustrating the genetic diversity in genomes and how these can be exploited to infer both inter and intra specie relationships.

Having completed the first two chapters, readers would have been introduced to the basic concepts underlying bioinformatics and have an appreciation of how it applies to real-life problems. The final three chapters of the book appropriately begin to explore bioinformatics more deeply. The first of these chapters relates to databases and data mining. An important aspect of bioinformatics is the ability to harness all the information available in the most efficient manner. Considering the enormity of public databases available, the author does a good job in providing coverage of all major databases. The use of the databases is illustrated by real examples with URLs, keywords, and accession number used in each example clearly shown. This would assist readers in familiarizing themselves with the use of some of the major databases when following the examples through while using the internet.

The final two chapters highlight the more technical aspects of bioinformatics, namely, the computational and mathematical aspects and their significance within practical biology. The topic of the fourth chapter is sequence analysis and phylogenetic analysis. For the typical biology student, this chapter will be comparatively more challenging to grasp as the concepts become more abstract. Nevertheless, these concepts are essential as they demonstrate the theory underlying bioinformatics. Lesk sensibly begins with the introduction of the dot plot before introducing the dynamic programming algorithm and more advance techniques of multiple sequence alignment using BLAST and Hidden Markov Models. Throughout, mathematical and computational concepts are kept to an absolute minimum. Readers with interests in their implementation are directed to further reading material. Similarly, in the introduction to phylogenetic analysis, the author does well to avoid much of the statistical appreciation required in this field. Even so, the chapter will still provide the reader with some background to the basic methods in phylogenetic analysis.

The final chapter of the book arguably contains the most advanced topic. Research in proteins and proteomics predominates over genetics in this postgenomic era. Topics covered include prediction of protein properties such as hydrophobicity, structural classification, secondary structure, and tertiary structure. The chapter not only introduces these concepts but goes into some detail in explaining how they work. For example, Lesk provides a succinct introduction to neural networks and explains how this artificial intelligence method is applied in secondary structure prediction.

Throughout the book, there are sets of problems at the end of each chapter to reinforce the concepts presented. The problems are stimulating and provide the reader with conceptual, mathematical, algorithmic, and programming exercises. In addition, there are a number of innovative “weblems”—problems to be carried out through the use of the Internet—in each chapter. These should particularly encourage readers to apply their newly gained knowledge in familiarizing themselves with the increasingly important resources on the Internet. The book has a companion Web site that provides supplementary material such as figures in high resolution and source code for some example programs used in the book.

By the end of the book, undergraduate or graduate students studying bioinformatics for the first time should be well equipped to apply their knowledge to practical situations. Lecturers or tutors teaching from this book will appreciate the wealth of examples and problems that may be used as illustrate and reinforce the concepts in bioinformatics. Furthermore, researchers who are exposed to bioinformatics for the first time will certainly find this book useful as reference material. In particular, references to different databases and resources available to the public on the World Wide Web will save the reader lots of time in finding an appropriate database to use in his or her research.

Lesk’s writing style is lucid and concise. Students in particular will welcome the ability of this author to cover such a diverse topic in a mere 283 pages. The book is easy to read, with refreshing examples throughout the text relating to everyday life outside of biology and computer science. For instance, I quote “Whales, like Australians, are mammals that have adopted an aquatic lifestyle. But what—in the case of the whales—are their closest land-based relatives?”. The book overall does a very good job in what it sets out to achieve as stated in the title. I would certainly recommend this to anyone who has a curiosity in finding out what bioinformatics is all about.

Jason Wong

Physical and Theoretical Chemistry Laboratory, Oxford University, U.K.,

S1430-4171(04)02777-4, 10.1333/s00897040777a

Chemical Structure, Spatial Arrangement: The Early History of Stereochemistry, 1874–1914. By Peter J. Ramberg. Ashgate Publishing Co.: Burlington, VT, 2003. Figures, tables. xxiv + 399 pp, 16.0 ´ 23.9 cm., hardbound. $99.95. ISBN 0-754-60397-0.

Today the structure of molecules and ions—how atoms are arranged in space, how they are linked to each other, and how much freedom of movement within the species they possess—is taken for granted. For example, in 1996 Robert F. Curl, Jr., Harold W. Kroto, and Richard E. Smalley were awarded the Nobel Prize in Chemistry “for their discovery of fullerenes,” those elemental forms of carbon possessing a soccer ball shape. Even the public at large is well aware of DNA, the three-dimensional helical molecule considered to bear the secret of life, largely because the 50th anniversary of the discovery of its structure was celebrated last year [1].

For more than a century chemists have known that certain substances consist of either left-handed or right-handed molecules, and chemists can now produce pure enantiomers rather than the equimolar mixtures of mirror-image species to which they were previously restricted in their laboratory syntheses. The life process is stereospecific, and with the advent of chiral synthesis chemists can now synthesize many biologically active substances with important medical applications. Chemists and molecular biologists routinely think in three dimensions and even design new molecules at their desks.

Yet this was not always so. As late as 1870, chemists did not possess the conceptual tools to picture or model three-dimensional molecules. Furthermore, even at the end of the 19th century Wilhelm Ostwald remained skeptical about the actual existence of atoms themselves.

In 1872 Johannes Wislicenus declared that “structural formulas did not represent the arrangement of atoms in molecules,” but three years later he was convinced that such formulas could designate the spatial characteristics of molecules (p 1). Two intervening events served to change his mind. In September 1874 the 22-year-old Dutch chemist Jacobus Henricus van ’t Hoff [2, 3] published his 11-page paper in Dutch, later translated into English as “A Suggestion Looking to the Extension in Space of the Structural Formulas at Present Used in Chemistry and a Note upon the Relation between the Optical Activity and the Chemical Constitution of Organic Compounds.” This short but influential booklet, which is considered to mark the founding of stereochemistry, antedated Joseph Achille Le Bel’s similar but independently conceived proposal of the asymmetric carbon atom by only two months. The two classics explained the existence of organic optical isomers by postulating that the carbon atom possesses a tetrahedral configuration [4]. According to Peter J. Ramberg,

Wislicenus’ personal conversion exemplifies a general transformation in the meaning of structural formulas during the last quarter of the nineteenth century. The origins and reasons for this transformation from the concept of the “chemical structure” of a molecule and the “spatial arrangement” of atoms in a molecule, the last major stage in the development of traditional nineteenth-century chemistry, is the subject of this book (p 1) [5].

Ramberg’s book is the third volume in the series, “Science, Technology and Culture, 1700–1945,” edited by David M. Knight of the University of Durham and Trevor H. Levere of the University of Toronto and focused on “the social, cultural, industrial and economic contexts of science and technology from the ‘scientific revolution’ up to the Second World War.” The series also provides an outlet for such studies as well as for new research on the history of science within this period. Ramberg admits that the study of stereochemistry “requires a great deal of technical knowledge—chemical formulas, nomenclature, and laboratory practice—to decipher the arguments, and some of those technical details have been included here,” but he states, “I have done my best to introduce these details on a level suitable for nonchemists to understand” (p 9). However, I think that the audience for his book will probably be limited to chemists and historians of chemistry and of science.

The author, Assistant Professor of History of Science at Truman State University, Kirksville, MO, is ideally qualified to write such a study. After receiving his bachelor’s degree from the University of Minnesota (1984), where he pursued undergraduate research in organic electrochemistry, Ramberg entered Indiana University, where he earned an M.S. degree in organic chemistry (1987), an M.A. degree in history and philosophy of science (1989), and a Ph.D. degree in the history of science with a dissertation on “Theory and Methodology in the Early History of Stereochemistry, 1874–1900” (1993), the subject of the book under review here. He taught organic chemistry at the Johns Hopkins University, North Dakota State University, and Ohio University and was wissenschafttlicher Mitarbeiter with Ursula Klein’s new group in the history and philosophy of chemistry at the Max-Planck-Institut für Wissenschaftsgeschichte, Berlin (1999–2000), where he completed the research for, and writing of, the book. He has authored a number of articles on the history of stereochemistry as well as stereochemists who figure prominently in the book, and he organized the 125th Anniversary of the Tetrahedral Carbon Atom Symposium at the 218th National Meeting of the American Chemical Society (New Orleans, LA, August 1999).

Each chapter of the book is prefaced by one or more pertinent quotations by chemists contributing to the subject matter of that chapter. The title for Chapter 1, “Introduction: ‘Van ’t Hoff’s Gold Mines’” (10 pp, the shortest chapter), is taken from a characterization of Van ’t Hoff’s theory as “gold mines that have gone entirely unnoticed” [6]. Ramberg outlines the book’s contents and states:

The small amount of existing secondary literature on the early history of stereochemistry has centered on the co-discovery of the tetrahedral carbon atom, and for the most part has assumed that the importance of the discovery lay in its contribution to modern chemistry, not in its own nineteenth-century context. One of the purposes of this book is to draw together the existing fragmentary accounts of stereochemistry into a more comprehensive narrative of the events surrounding the adoption of stereochemical principles as a natural, but not necessarily inevitable, outgrowth of traditional nineteenth-century chemistry (pp 3, 4) [7].

In my opinion Ramberg has succeeded admirably in accomplishing this goal.

Chapter 2, “The Historical Development of Organic Chemistry to 1874” (42 pp), deals with the intellectual, practical, and institutional background of organic chemistry during the 1860s, largely a synthesis of the existing historical literature on the origins of structural theory. Chapter 3, “The Tetrahedral Carbon Atom, 1874–1877” (34 pp), details the immediate context surrounding Van’t Hoff’s and Le Bel’s proposals and delineates the principal differences between the two. Because the subsequent development of stereochemistry resulted almost entirely from Van’t Hoff’s ideas rather than from Le Bel’s, the remainder of Ramberg’s book focuses on the consequences of Van ’t Hoff’s concepts. Also, because few chemists were fluent in Dutch, and because most of them learned of Van ’t Hoff’s proposals from either the French version (1875) [8] or the German version (1877) [9], the chapter closely examines the evolution from the Dutch pamphlet to the German version. Since before the late 1890s stereochemistry was not practiced outside Germany, Ramberg emphasizes the contributions of German chemists.

Chapter 4, “Initial Reception of the Tetrahedron, 1874–1887” (23 pp), explores the reception of Van ’t Hoff’s theory during the crucial period 1874–1887 and shows that, contrary to the widespread assumption based on Hermann Kolbe’s famous—or infamous—criticism, the chemical community was much more receptive than commonly believed. Chapter 5, “Johannes Wislicenus and Molecular Dynamics” (45 pp), discusses the paramount importance of Johannes Wislicenus, whose work on lactic acid directly inspired Van ’t Hoff’s theory and whose vigorous defense of it, leads Ramberg to consider him as “Van ’t Hoff’s bulldog” [10].

Chapter 6, “Victor Meyer: The New Science of Stereochemistry” (36 pp), deals at length with Victor Meyer, who coined the adjective “stereochemisch” and noun “Stereochemie.” Together with his assistant Karl Auwers, Meyer determined that the isomeric benzildioximes were structurally identical, and the two proposed a novel but incorrect stereochemical explanation to differentiate them. Chapter 7, “Arthur Hantzsch: The Stereochemistry of Nitrogen” (49 pp, the longest chapter), examines the alternative spatial theory for the benzildioximes, proposed by Alfred Werner in his doctoral dissertation and based on a tetrahedral configuration for the nitrogen atom [11]. Although Werner’s mentor Hantzsch gave him complete credit for the concept, Hantzsch, who wrote Grundriss der Stereochemie (1892), the first stereochemical monograph not written by Van ’t Hoff, deserves credit for defending the theory and establishing the evidence in its favor. Ramberg points out that although recognized primarily as Werner’s Doktorvater, Hantzsch was one of the most innovative organic chemists of the time, and he supplemented chemical measurements with extensive physical measurements.

Chapter 8, “Emil Fischer and Carbohydrate Chemistry, 1884–1891” (34 pp), considers Fischer’s application of Van’t Hoff’s tetrahedral hypothesis to his investigations of the sugars, especially his proposal for the configuration of glucose (1891). Ramberg sees the origins of Fischer’s famous “lock and key” hypothesis (1894) in his previous work on carbohydrates. Chapter 9, “Alfred Werner and Coordination Chemistry, 1893–1914” (43 pp), examines in detail Werner’s Habilitationsschrift [12], his coordination theory [13], his controversy with Sophus Mads Jørgensen, and his two decade-long tour de force of synthesizing the compounds needed to prove unequivocally his coordination theory. In so doing, Werner “single-handedly reorganized inorganic chemistry, largely along explicitly spatial principles, as fundamentally as the structure theory had reorganized organic chemistry” (p 7).

In Chapter 10, “Conclusion” (30 pp), Ramberg summarizes some of the general characteristics of the development of stereochemical theory discussed in the preceding chapters. He broadens his treatment and goes beyond stereochemistry itself to survey the development of 19th-century chemistry and discusses a number of wider issues concerning the general character of scientific change, including the nature of chemistry, mechanism and physicalism in chemical theory, methods and methodology in organic chemistry, generational dynamics, and research groups and schools.

Six appendices present historical documents, all of which appear here in English translation for the first time: 1. Tjaden Modderman’s letter to neighbors of Van ’t Hoff’s parents (October 17, 1874); 2. Van ’t Hoff’s preface to his La Chimie dans l’espace (1875); 3. Letters of Felix Hermann (November 9, 1875) and Johannes Wislicenus (November 10, 1875) to Van ’t Hoff; 4. Wislicenus’ foreword to the 1st edition of Van ’t Hoff’s Die Lagerung der Atome im Raume (1877); 5. Two letters from Victor Meyer to Adolf von Baeyer concerning the strain theory (October 5 and 18, 1885); and 6. A “translation” of Van’t Hoff’s sign notation for compounds with multiple asymmetric carbon atoms into modern Fischer projections.

Considering the length and detail of the book, the number of errors, most of which involve misspellings of names, is not excessive: “Herman” for “Hermann” (Kolbe, p 5), “Chapter 4” for “Chapter 5” (p 6, line 6), “alternate” for “alternative” (p 6), “Ramsey” for “Ramsay” (pp 8, 316), “Practises” for “Practices” (p 37), “Marcelin” for “Marcellin” (Berthelot, pp 78, 90, 395), “Douglas” for “Dean Stanley” (Tarbell, pp 141, 394), “Kaufmann’s” for “Kauffman’s” (p 194, the many other occurrences of my name in the book are spelled correctly), “Benzophenone” for “Benzophenonen” (p 210), “asymmetrischer Hydrazon” for “asymmetrischen “Hydrazonen” (pp 211, 217), “Habilitationsschrifft” for “Habilitationsschrift” (p 280),“George” for “Georg” (Lunge, p 294), “societé” for “société” (p 372), “Vierteljahrschrift” for “Vierteljahrsschrift” (p 373), “Züricher” for “Zürcher” (p 373), “p-Tolylphenylketon” for “p-Tolylphenylketons” (pp 206, 374, 377), “Karbocyklischen” for “karbocyklischen” (p 374), “asymmetrische” for “asymmetrischer” (p 375), “Stereochemische Isomerie” for “stereochemische Isomerie” (p 375), “stereoisomerie” for “Stereoisomerie” (p 376), “asymmetrischer” for “asymmetrischen (pp 211, 376), “Hydrazon” for “Hydrazonen” (pp 211, 376), and “Russel” for “Russell” (McCormmach, p 388).

Alfred Werner was not a coauthor on Arthur Hantzsch’s articles in Berichte 1890, 23, 2325–32 (pp 206, 377) or Berichte 1890, 23, 2322–25 (p 377); his lecture, “Untersuchungen über anorganische Konstitutions- und Konfigurations-Fragen,” was held on November 3, 1906 but published in Berichte in 1907 not 1906 (p 382); his article, “Valenzlehre,” was published in 1915 not 1913 (p 382); and the pages for his Chemiker-Zeitung obituary of Sophus Mads Jørgensen are 557–564 not 557–559.

Ramberg has made extensive use of the primary and secondary literature as well as of archives in Germany, Switzerland, and the United States. In addition to notes and references cited at the bottoms of individual pages, his book includes a 21-page bibliography of books and articles with items as recent as 2001. The 103 numbered figures, some of which consist of multiple parts, include structural formulas, reaction schemes, tables, and templates, many of which are reproduced from the original publications. The name (two 2-column pages) and subject indexes (two 2-column pages) are not very detailed for a work of this length. Portraits of the principal chemists involved in the story and photographs of historical molecular models would have been desirable but would undoubtedly have added to the price of the volume.

I am pleased to recommend this book, and I agree wholeheartedly with Trevor H. Levere, who in his Series Editor’s Preface states, “Here is rich material for the history, philosophy, and social study of chemistry” (p xxii).

References and Notes

1.       Kauffman, G. B. DNA Structure: Happy 50th Birthday! Chem. Educator 2003, 8, 219–230; DOI 10.1333/s00897030695a.

2.       In contrast to the familiar American and German spelling “van’t Hoff,” Ramberg consistently uses Dutch spelling rules, according to which a space is required between the “van” and “’t” portions of Van ’t Hoff’s name, and the “V” is capitalized when no first name or initials are present. Otherwise, the lower case “v” is used, for example, “J. H. van ’t Hoff” but “Van ’t Hoff.”

3.       Ramberg, P. J.; Somsen, G. E. The Young J. H. van ’t Hoff: the background to the publication of his 1874 pamphlet on the Tetrahedral Carbon Atom, Together with a New English Translation. Ann. Sci. 2001, 58, 51–74.

4.       Kauffman, G. B. Jacobus Henricus Van’t Hoff. In Macmillan Encyclopedia of Chemistry; Lagowski, J. J., Ed.; Macmillan Reference USA: New York, 1997; Vol. 4, pp 1482–1483.

5.       Aside from my longtime interest in stereochemistry, this volume is of special interest to me because the author asked me to read the chapter on Alfred Werner (Chapter 9).

6.       Meyer, V.; Auwers, K. Weitere Untersuchungen über die Isomerie der Benzildioxime. Ber. 1888, 21, 3510–3529, 3513.

7.       For example, O. B. Ramsay’s Stereochemistry; Heyden: London, Philadelphia, Rheine, 1981, the previously most comprehensive treatment of the subject, was written primarily as a textbook.

8.       van ’t Hoff, J. H. La chimie dans l’espace; Bazendijk: Rotterdam, 1875.

9.       van ’t Hoff, J. H. Die Lagerung der Atome im Raume; Hermann, F., Transl.; F. Vieweg: Braunschweig, 1877.

10.     Because of his fervent championing of Charles Darwin’s theory of evolution, Thomas H. Huxley has been called “Darwin’s bulldog.”

11.     Hantzsch, A.; Werner, A. Über räumliche Anordnung der Atome in stickstoffhaltigen Molekülen. Ber. 1890, 23, 11–30. For a discussion and annotated English translation see Kauffman, G. B. Foundation of Nitrogen Stereochemistry: Alfred Werner’s Inaugural Dissertation. J. Chem. Educ. 1966, 43, 155–165. Also see Kauffman, G. B. Stereochemistry of Trivalent Nitrogen Compounds: Alfred Werner and the Controversy over the Structure of Oximes. Ambix 1972, 19, 129–144.

12.     Werner, A. Beiträge zur Theorie der Affinität und Valenz. Vierteljahrsschrift Zürcher Naturforsch. Ges. 1891, 36, 129–216. For a discussion and annotated English translation see Kauffman, G. B. Alfred Werner’s Habilitationsschrift. Chymia 1967, 12, 183–216.

13.     Werner, A. Beitrag zur Konstitution anorganischer Verbindungen. Z. anorg. Chem. 1893, 3, 267–330. For a discussion and annotated English translation see Kauffman, G. B. Classics in Coordination Chemistry, Part 1: The Selected Papers of Alfred Werner; Dover Publications: New York, 1968; pp 5–88.

George B. Kauffman

California State University, Fresno,

S1430-4171(04)02778-3, 10.1333/s00897040778a