B O O K R E V I E W S

Man, bytes, machine

Artifidal Intelligence and Molecular Biology edited by Laurence Hunter

AAAI Press and MIT Press, 1993. $39.95 pbk (470 pages) ISBN 0 260 58115 9

Artificial intelligence (At) is a branch of computer and cognitive science which aims at creating computer systems that would be considered as intelligent by humans. Founded in 1956, At is now widely used in many areas, such as image processing, natural language understanding, speech recognition, robotics, design and diagnostics. Molecular biology now seems ripe for the application of AI tools. Large-scale sequencing projects will soon crank out the entire genetic message of living organisms, raising the intellectual challenge of making real sense of these data in a wider framework of biological facts and theory. Moreover, the biological sciences are traditionally descriptive. With At methods, such knowledge can be" represented symbolically, at many levels of detail.

Artificial lntellip, ence and Molecular BloioRF stems from the 1990 Spring Symposium on AI and Molecular Biology, which wits sponsored by the American Association for Artificial Intelligence tAAAI). The Ix>ok begins with a brief overview <if life, ;it both molecular and higher levels. Eleven research articles then describe approaches to the analysis of gene sequences, representing and

predicting the structure of proteins, automated and interactive analysis of data, and simulation of biological systems. Each chapter contains a readable introduction to the relevant biological and computational aspects. The emphasis is on representing biological knowledge in computers in such a way that it can be used for solving problems, and on innovative approaches and novel technologies rather than on proven applications.

Many AI methods are influenced by linguistic models. For example, the slightly cryptic phrase 'the old man the boat' can be parsed into a noun-phrase and a verb-phrase. Similarly, within a nudeotide sequence, a gene can be identified by looking for promoter regions, start and stop codons, and perhaps intron splice sites; the coding sequence can then be translated into a predicted amino acid sequence, and so on. In principle, the model can even describe three-dimensional structure. In practice, many of the grammars used are in the familiar form of consensus sequences. The appeal of the linguistic approach is that it provides a rigorous theoretical framework, and that the definition of grammars is particularly easy in Al-programming languages.

Three prototype expert systems for simulating metabolic pathways are impressive. The systems simulated are quite extensive: for example, the complete trp operon is simulated, including components inwilved in transcription, translation and regulation, Enzymes, DNA, substrates, cofactors anti products are represented its abstract objects with their relationships, properties and reactions described in the

knowledge base for the system, gather than attempt quantitative simulation over time from given starting concentrations, reaction rates and stoichiometries, these simulations represent a 'qualitative' biochemistry. Computer-based, systematic construction of metabolic pathways, in which the user can test various preconditions, could prove an instructive tool in teaching biochemistry.

The accumulated information stored in molecular biology databases is a challenge to machine-learning approaches. Neural networks could learn to map between, say, the amino acid sequence of a protein and its three- dimensional structure. However, the key difficulty lies in finding a useful level of abstraction. Many of the programs described are either prototypes that have been tailor-made to address a particular problem, or partly implemented conceptual schemas. The sheer bulk of biological data and knowledge is difficult to manage; thus, one may read that for use with a larger data and knowledge base 'the computational performance of the algorithm would have to be drastically improved, in terms of both conceptual structure and actual implementation'.

All in all, Artificial Intelligence and Molecular Biolopj, is a stimulating volume that illustrates the importance of interaction between different academic disciplines.

Lllsa Hohn

Prolein ~'sil~u Gwup, b311a., D.69012 Heidelt~,tg Germany.

+.Billion dollar bablesP , ,

Guide to Techniques in Mouse Development (Methods in Enzymology, Vol. 225) edited by Paul A. Wasserman and Melvin L. DePampMis

Academic Press, 1993. £46.00/$59,95 pbk (1021 pages) ISBN 0 12 736450 1

ktst winter, the UK Press was agog with the latest in reproductive technology. Two 0articular incidents triggered this interest. The first was the birth of twins to a 59.year-rlld wo,nan after fertilized donor eggs had been transferred to her uterus. This led to ill-judged comment from the Government, and sexist hysteria from the media (alter all, no-one cares when a man even older fathers children through 'natural' means, unless he is a cabinet minister). The second was the suggestion that eggs from aborted foetuses might be used to supplement the limited supply of donated eggs, moving

the Press to enter into uncharacteristic metaphysical speculation about whether a child might suffer from having a mother who 'never existed'. The upshot of all this is that so-called 'designer babies' are once again under discussion (if the British Press can honestly be said to discuss any science issues). Of course, the reproductive techniques that enable otherwise infertile couples to have children have little to do with the genetic analysis of embryos that the term 'designer babies' implies. But these stories sell newspapers, and do, in truth, reflect the wish of most parents to have

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'their' tlal W, and to ensure it is as healthy as possible. The ersatz ouwage of newspaper editors and the bogus concern of the Govemmem over the application of technology hear no relation to this genuine desire that if a genetic del~:t can be prevented, then it should be.

Imagine the outrage if a self-help manual were published that enabled anyone to design their own babies - to get an idea ~f the reaction, one need only think of the scandalized outbursts over lesbian couples who get speml from a willing donor and carry out their own insemination. Well, here is just such a manual. In this book, these very methods are laid out for any old Joe Public to pick up: isolation of oocytes from embryos and from adults; in vitro fertilization; finding new genes that affect the whole range of developmental processes; transferring genes into embryos and manipulating their genetic make-up by knocking out genes. Designer babies to

B O O K R E V I E W S

the max. Mouse babies, of course, but it's all here, and much more besides. We shouldn't forget that human reproductive technology owes its entire existence to decades of curiosity-driven research into mammalian development. In Guide to Techniques in Mouse Development, 56 chapters detail the very latest of this research. These cover almost everything you might want to do to mouse babies (the three notable exceptions are studies involving toxigenics, transferring YACs into mice, and EG cells), and a few things you probably never thought you would want to do (such as quantifying RNA synthesis in early embryos and evaluating the acrosome reaction of sperm). This really is a most comprehensive methods manual. There are a few advanced molecular techniques, but the book is bursting with embryos and ES cells (literally, as it has a plastic loop binding that tends to spring out the pages, or wear away their edges until they fall out).

Of all scientists, biologists have a particularly problematic relationship with methodology. They have an almost my_--~ical faith in 'green fingers', in 'it only works in that lab' and in the importance of 'pedigree'. Those who have mastered certain techniques are the most employable (currently, gene knockouts in ES cells, I believe), rather than those who have the best ideas. Biology is, in fact, almost completely driven by

methods: not that ideas are not important, but there are so many of them, and a,~yone can come up with another half-dozen before coffee. Picking the crucial idea, and testing it thoroughly, is the key tc- becoming the Roquefort among the big cheeses. The myth that those who have worked in cutting-edge labs are better equipped to do cutting- edge work has its roots in the confidence that developing new techniques brings.

So this particular do-it-yourself manual of designer embryos is, like others before it, invaluable. Legal restrictions on human reproductive technology may or may not reflect the genuine interest of government, media and public. Nevertheless, the legal restrictions on animal work, rightly rigorous, are not the major hindrance to progress. In developmental biology, much work is hampered by a lack of technical resources. Really, anyone can do any experiment (if they can't it ain't science), and the relatively limited dissemination of these embryological techniques is currently the biggest obstacle to advancement in many areas. I do worry about printed methods, as they imply that this way js the only way. However, with a few exceptions, the authors of this book seem aware of this trap, pointing out, for example, that 'the~'e are many possible variations... and we do not intend that the methods

should be considered definitive' (Chapter 23) or 'it is by no means the only approach, but it does ~,ork' (Chapter 24).

Despite my comments above, the soft-covered, ring-bound format is very suitable for laboratory use. The figures are of high quality, the authors are authoritative, and I could detect few errors. (The one in the table on p. "xxii, suggesting'that birth takes place less than 19 h after ovulation, will be spotted by any wide-awake biologist.) The only omission that I cared about was in the chapter on gene targetting methods: although it was quite rightly emphasized that probes both 5' and 3' to the gene should be used to conf'u'm targetting, it failed to point out that a large number of apparently homologous recombination events are not targetted, but have picked up flanking homology and integrated elsewhere in the genome.

In conclusion, I have no reservation or hesitation in recommending this book. I am now wondering how I can keep it in my laboratory without chaining it to the bench. I fully expect it will be on permanent loan fcom the moment I end this review.

lanJ.Jackson

Molecular Genetics Section, MRC Human Genetics Unit, Western General Hospital, Ovwe Road, Edinburgb, UK FJt4 2XU.

Protein Ensineerin8- Towards 'Rational Design'?

A Special Issue from Trends in Btotecbnology

The May issue of Trends in Btotechnology is a Special Issue on Protein Engineering - Towards 'Rational Design'? This collection of articles provides an overview of the field, focusing on the current understanding of protein structure-function relationships, the technological approaches enabling their study, and the ways in which improved knowledge is permitting the de novo design or modification of protein characteristics and production.

Topics t o b e c o v e r e d include: . Protein structure analysis and predict ion • Redesign and de novo design • Building structure and function f rom modula r units * Artificial molecular evolut ion • Pept ide and

protein repertoires • Ant ibody design • Engineer ing surface loops • Metal-mediated prote in stabilization • Protein folding and aggregat ion • Engineering for facilitated processing.

C o n t r i b u t i n g a u t h o r s : T. Blundell • A.R. Rees • J.D. Campbel l • E.F. Hounsell • J. Holbrook • F,H. Arnold • M. Uld(m • C. Sander * R. Wetzel • J.M. Thorn ton * W.R. Taylor

Copies of this special issue are priced at individual: £16.00 + VAT'/S25.00, institutions: £33.00 + VAT'/S52.00 Prepayment required. (Enquire for discounts on bulk orders.)

Cheque, E ~ h e q u e or money order made payable to Elsevier. Credit cards accepted. Copies can be ordered Erom:

Elsevier Trends Journals, PO Box 800, Kldlington, Oxford, UK OX5 IDX. Fax: +44 (865) 845300 Tel: +44 (865) 845940

*For EC, non-UK custmners, VAT at appmpiate rate must be added (1993 EC Directive)

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