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Survival of the fittest Combinatorial Libraries: Synthesis, Screening and Application Potential

edited by Riccardo Cortese, de Gruyter, 1995. DMl38.00 (232 page)

ZSBN 3 11 014395 X

Creating your own biologically active molecule from scratch is a highly demanding procedure. If you are lucky: structures &on1 related compounds may be used as a template to start out horn. Systematic alterations followed by testing of individual mutants may eventually lead to the molecule you were looking for.

If, as is most often the case, there is no a priori knowledge of structure-activity relationships between, for instance, a ligand and receptor. the only practical approach is to test a multitude of compounds for the desired activity. Methods for the generation and systematic screening of immense molecular diversities have recently been developed. The common underlying principle of these techniques is based on the generation of expansive collections of very large numbers of moleculrs (peptides, oligonucleotides or proteins), one or several of which may possess the desired characteristics. Screening and selection isolates the molecules with the desired properties from these combinatorial libraries.

Three basic formats can be distinguished. Synthetic peptidr libraries, which may consist of large collections of chemically prepared peptide-chains. either in solution or on beads. Systematic screening identifies the peptide with the desired characteristics. Nucleic acid libraries are constructed from collections of RNA or DNA oligonucleotides; as random oligonucleotides can assume a large number of tertiary structures, some of them may possess desirable binding or catalytic activity agamst a target molecule. Rounds of selection and PCR amplification yields a pool of molecules rnriched in the desired properties. In a molecular biology approach, peptides or whole protein domains are presented on the surface of filamentous phage particles containing in their phage coat the genetic information encoding the presented structures. Phage particles selected for binding to an epitope are propagated in Exhericilia roli

bacteria. With all these techniques, the structure of the tested compound is typically not

A golden thread The Thread of Life: the Story of Genes and Genetic Engineering

by Susan Aldridge, Catnbrid~r Cbtiversiry Press, 1996. LK,4 16.95

(vii + 258pages) ZSBN 0 522 46542 7

This is just the book to throw at introduction to genetics, including your Auntie Madge if she starts applications and implications, for asking you to explain what DNA is anyone developing an interest in and whether the scientific the subject. This may include community is capable of cloning a A-level students, undergraduates human being yet. I would wanting a very basic introduction recommend it as an invaluable before embarking upon a

determined until its biological relevance has been established.

Combinatoral library technology is still at a very early stage of development and thus the relative merits of the different approaches are assessed mostly at a theoretical level. Riccardo Cortese’s volume does present ample examples of all the variants of combinatorial library technology, written by scientists who are among the best in their area of research. Applications discussed range from selecting antifungal peptides, thrombin-binding DNA oligonucleotides, antibody epitopes, MHC binding motifs and complete high-affinity antibodies. In each case, the theoretical background, advantages and disadvantages, experimental set-up and results are extensively discussed.

The volume does not provide you with any practical protocols on how to actually perEorm your experiments, which is rather a pity because success in these types of experiments tends to be highly dependent on tiny details that are easily overlooked by someone not an expert in the field. You will have to work your way through the long lists of references to find these details.

In conclusion, while not providing you with the protocols to start doing your own selections right away, this book will give you a pretty good insight into the possibilities of combinatorial library technolou.

John de Kruif

Department of Immunology, HP F03.821,

Utrecht University, PO Box 85500,

3508GA Utrecht. The Netherlands.

related course, or even the general public.

Susan Aldridge guides her audience through a complex subject with skill, making the basic concepts accessible without compromising accuracy. She provides a historical backdrop for the important discoveries and also tackles the ethical implications of

applying new technologies developed from them. Her illustrations are clear and aid explanations of difficult points, but unfortunately lack the innovative style of the text. The book is well structured, dividing the subject matter into manageable chunks with intriguing sub-headings to

TlElTECHJANUARY1997P/OL15)

40

book reviews

retain the reader’s interest. This is also achieved by a host of real-life examples, which not only simplify explanation but also act as a constant reminder of the relevance to everyday life of the subject being handled.

The first section of the book answers the question ‘what is DNA?‘. It starts with a full description of the structure of DNA and relates this to its function via the Central Dogma, pointing out some important exceptions to the rule such as retroviruses and prions. It then puts DNA back into the context of the genome, explaining where DNA is located, how it is packaged and expressed and how genome mapping works. Attention is also drawn to the C-value paradox and the fluidity of the genome. Finally. the author tackles the question of where DNA may have come from in the first place

and how it has evolved since then. The next two sections are

concerned with genetic engineering and biotechnology. The former discusses engineering genes: how this can be done, what effects this might have and whether we should be allowed to do it. It covers such areas as DNA fingerprinting, the creation of transgenic animals and the potential of gene therapy. The latter section discusses biotechnology and how it can be utilized in areas as diverse as medicine, the food industry, crop breeding and environmental clean-up programs. In this part of the book there is an emphasis on assessing the acceptability of these ideas to the general public and how controls may be implemented, including a section on patent protection.

The final section briefly assesses whether a full knowledge of

Technology evolution Immunoassay Automation: An Updated Guide to Systems

edited by Dafzipi Chats, Academic Press, f 995. US$59.95 (3 12 pages)

ISBN 0 12 167640 4

The book is an update of the practical guide published in 1992 and provides the reader with a comprehensive review of the new generation of immunoassay systems that have been introduced since the original publication. As Daniel Chan indicates in his introductory chapters, the clinical laboratory environment is changing as a result of pressures on healthcare expenditure, the maturing of the market sector and advances in infomration technology. This has resulted in the evolution of

integrated systems that incorporate the features of different immunoassay systems.

Unlike the previous book, the update does not contain the useful general sections on the important factors to consider when evaluating the technical, clinical, operational and economic performance of an automated immunoassay system. Someone new to the area would be well advised to read the update in conjunction with the original publication. The individual chapters do, however. provide a

molecular genetics can possibly lead us to a comprehensive understanding of nature. It discusses the reductionist view whereby DNA is central to unlocking the elusive secrets of nature. These are countered with some controversial theories such as chaos theory which may have important implications on the matter.

Overall, Susan Aldridge has succeeded in the ambitious task of giving a comprehensive introduction to a fascinating area. She has related subjects of general interest such as gene therapy down to their molecular roots in a way that even Auntie Madge can understand.

Cindy Macpherson Department of Genetics, University of

Cambridge, Downing Street, Cambrtdge, UK CB2 3EH.

(Email: cmp@mole.bio.cam.ac.uk)

comprehensive review of the detailed technical features of each of the systems described. The sections give sufficient detail on the technology and its performance to allow meaningful comparisons. To the target audience in the clinical laboratory considering the purchase of a new automated system or those in the industry attempting to keep up with the developments in the area, the review is a useful reference book.

The final three chapters on technologies that may have application are a little incongruous with the rest of the book. In the opinion of the reviewer, these do not provide a comprehensive review of the new technologies that are most likely to have a major impact on the area of future automated immunoassay systems.

Keith May Unipath Ltd, Norse Road, Bedford,

UK MK41 OQG.

Publishers Please send book details of interest to biotechnologists to W3TECH Book Reviews, ETJ,

68 Hills Road, Cambridge,UK CBZ 1LA.

lBTECHJANUARY1997 (VOL15)