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Page 1: The molecular basis of viral replication

T I G - August 1988, Vol. 4, no. 8

In the beginning... The Creation of Life: Past, Future, ,~'.'en by Andrew Scott, BasilBlackwell, 1987. £14.95 kbk (x + 211 pages) ISBN 0 631 14883 3

Interest in the question of the origin of life has very ancient roots in human culture, as is suggested by the rich variety of creation myths preserved in historical records. It is comparatively recently, however, that the problem of life's origins has become a subject of serious scientific interest.

In The Creation of Life, science writer and broadcaster Andrew Scott reviews current explanations of life's origins offered by science. He discusses the main competing theories, pointing out where the major gaps in understanding are, as weIJ ~ experimental work in the field. This discussion is preceded by two chapters providing an elementary intro- duction to the relevant chemistry, biochemistry and molecular biology. The final two chapters are concerned with, respectively, the possibility of life existing elsewhere in the Universe and the prospect of the technological creation of completely novel forms of life. As regards this last chapter, it is not immediately clear how the manufacture of novel organisms by genetic engineer- ing or the construction of serf-replicating, self-programming computers relates to the central theme of the book. Given the rather superficial treatment of the issues raised by this extrapolation of current developments, it would have been preferable to devote the final chapter to an analytic assessment of the state of affairs in the origin of life field.

In broad outline, there are currently three rival programmes, based on the following assumptions: (I) terrestrial life began on Earth from organic starting materials; (2) the first living things on Earth were inorganic crystalline struc- tures capable of serf-replication, organic life having evolved later 'on the hack of these relatively inefficient life forms; and (3) conditions on Earth were never suitable for the generation of living systems and life was brought to our planet from outer space.

The first view represents the domi- nant position. It encompasses many more variations than are discussed by Scott, but the common assumption is that the origin of life was preceded by a long process of organic synthesis on Earth. The possibilities for organic synthesis, however, depend crucially on environ- mental conditions and there is now much controversy about the likely conditions on the early Earth. Even if it is granted that the required organic materials were available, there is as yet no satisfactory account of the origin of replication, nor of the coupling between replication and

metabolism that characterizes life as it is apparent today.

Some, but not all, of these difficulties are avoided by the second view which, although a minority position, has been gaining some ground in recent years. This is the theory, proposed by Cairns- Smith, that certain clay minerals are alive by virtue of their capacity to replicate, mutate and evolve. The ability of clays to catalyse organic synthesis might have led to a situation where certain organic molecules within the crystal organisms began to replicate themselves and did so vastly more efficiently than the crystal structure, leading to autonomous organic life. The most problematic features of this theory are the lack of empirical support, thus far, for the claim that clays do in fact evolve by natural selection and the failure to propose plausible mechan- isrls for the process of 'genetic take- over' by organic life.

The third position does not, in fact, offer an alternative theory of plausible pathways leading to the natural origin of living systems. Its disagreement with the other approaches is on the question of the historical fact of where life began, not how it began. It is not likely to increase its following significantly unless a specific extraterrestrial site (or sites), with well- defined environmental conditions and

book review "2s specific processes leading to life under these conditions, can be proposed.

Are we to agree, then, with Scott's conclusions that the efforts of scientists to explain our origins have so far yielded only 'a few vague and general notions'? This verdict seems unduly harsh. Our understanding of the complexity and interdependence of the processes that maintain the life of the simplest cells has increased enormously over the past few decades. To explain how such finely tuned complexity came into being, we can no longer get away with speculating about the formation of 'naked lumps of protein' (Ernst Haeckel, 1866). Begin- ning with Oparin's pioneering work about 50 years ago, attempts have been made to define historically plausible environ- ments, specific mechanisms of organic synthesis and dynamic transitions to homeostatic systems capable of evolu- tion. These attempts, for all their imperfections, are neither vague nor general. And, incidently, it seems extraordinary that a book about the orig~n of life can be written which does not once mention Oparin.

HARMKE KAMMINGA

Department of History and Philosophy of Science, King's College London, Chelsea Campus, Manresa Road, London SW3 6LX, UK.

Travelling down evolutionary The Molecular Basis of Viral Replication

edited by R. Perez Bercoff, Plenum Press, 1987. $97.50 (xsiii + 579 pages) ISBN 0 306 42619 6

Are the various mechanisms of replica- tion of the many RNA and DNA, doubie- str~mded and single-stranded, nuclear and cytoplasmic animal viruses logically related to each individual virus's niche? Or is a collection of chapters on viral replication necessarily a compendium of the bizarre and unrelated mechanisms of many different evolutionary cul-de-sacs? The strategies of viruses are often so elegant and direct, and yet there is an astonishing array of different types of viruses, and minutiae concerning them! Any volume that attempts to organize, consolidate, interpret or elaborate the available ideas and information is greeted with enthusiasm.

Following a NATO summer school course also entitled 'The Molecular Basis of WLral Repfication' offered in Marathea, Italy, the instructor-authors contributed 'extensive, interpretative reviews of the state of the art in their areas of expertise' to this book. This cogection is therefore neither a symposium volume, being quite general and not exclusively emphasizing the au~ors' research, nor a textbook, due to the somewhat arbitrary nature of some of the topics included and the variable treatments of these topics.

cul-de-sacs The chapters proceed with inexorable

logic. Overviews on viral replication, structure and regulation precede eight chapters on individual classes of RNA viruses, which progress from positive to negative to double-stranded R_HA viruses, and from monopartite to multi- partite genomes within these classes. Two chapters ensue concerning retrovir- uses and hepatitis B (viruses employing both RNA and DNA in the replication of their genome), followed by five chapters on DNA viruses. There are good sub- headings, lots of figures, tables and references, and an excellent index.

At this point, however, the organiza- tion breaks down. In fact, the idiosyncra- tic nature of the individual chapters is both a strength and a weakness of this volume. The best of the 22 chapters accomplish something quite splendid: lucid, organized, personal interpreta- tions of the subjects in question. Of particular charm is the discussion by Morche, Valle and Haenni on trans- lational regulation. If there is an organiz- ing principle in animal virology, it is the common need of all viruses to make viral proteins. Different viruses encode lots of enzymatic functions - polymerases, capping and polyadenylation enzymes, protein kinases, proteases - but not one synthesizes its own protein synthesis machinery. Thus, each virus must produce molecules that resemble cellular nd~As, or are at least recognizable by

Page 2: The molecular basis of viral replication

reviews the eukaryotic ribosome, in order to make viral proteins, and the various mechanisms are discussed quite spirit- edly in this fine chapter. In a scholarly overview of viral replication, Hershey and Taylor provide many interesting comparisons and parallels between animal viruses and bacteriophage. Other excellent chapters provide, in about 20 to 30 pages, lucid discourses on particular viruses, often accompanied by interest- ing speculations by the author and extensive references as current as can be expected for such a volume.

Some of the chapters are nearly unreadable, displaying a wide variety of different defects. Some authors write only for other cognoscenti, referring to arguments rather than clearly making

them, or invoking dogma in their particular field without explanation. Typographical errors abound, and some chapters manifest distracting lapses in English grammar. Other chapters are written in a textbook style useless to another person in the field, for example including tables of facts with no refer- ences. Given the exhaustive treatment of RNA viruses of all sorts, I was disappointed to find no discussions, outside the introduction, of pathogenesis by small RNAs such as hepatitis or viroids (which are, admittedly, plant pathogens). Prions and the basis for their infectivity are also not mentioned, and the effect of viral infection on the host cell is in gener',d given short shrift.

A wealth of information, however, and

T I G - August 1988, Vol. 4, no. 8

a fair dose of wisdom and insight can be found among the highly individualistic chapters of this book. In addition, there are interesting observations such as the finding that the face of Ramses V's mummy bears the marks of smallpox infection. For a textbook in this field, I much prefer Fields's Fundamental Virology, published in 1986. However, I can recommend this book to any virologist, because most will respond as I have, with a mixture of welcome, dismay and simple interest in this collectinn of essays.

KARLA KIRIqEGAAR]D

Department of Molecular, Cellular and Developmental Biolo~, Universi~ of Colorado at Boulder, Boulder, CO 80309-0347, USA.

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Idiosyncratic arcadian celebration Medical and Experimental Mammalian Genetics: A Perspective

edited by V. A. McKusick, T. H. Roder- ick, J. Mori and N. W. Paul, Alan R. L/ss, Inc., 1987. $69.50 (si + 346pages) ISBN 0 8451 1065 9

For a new area of knowledge, dissemi- nation can be of equal importance to discovery. In 1959 Victor McKusick asked the rhetorical question: who would teach the teachers about the importance of genetics and the new discipline of medical genetics? From this question grew the Bar Harbor Short Course in Medical and Experimental Mammalian Genetics. In 27 years, 296 teachers have taught 2299 students in the beautiful surroundings of Bar Harbor and the Arcadia National Park. The graduates from this course have infiltrated every comer of North America and the course has greatly influenced the development of American genetics.

The coarse is designed to provide a firm foundation in the basics of mam- malian genetics and to introduce exciting findings at the forefront of research. The 'book-of-the-course' is a multiauthored volume designed as a celebration of the first 27 years of the course and has the serious aim of giving a perspective on the interrelationship between medical and experimental genetics. Also included in the volume is a brief history of human and mouse genetics and an afterward from Joe Mori representing the sponsors (the philanthropic March of Dimes Birth Defects Foundation).

Despite my respect for the scientific editors and my gratitude to the sponsors, who are one of the major private sponsors of human genetics research, I was disappointed with the book. Accord- ing to the Oxford English Dictionary, a perspective is an impression of relative positions and magnitudes; if this volume is a perspective then it is idiosyncratic. The individual chapters cannot be

faulted; the informatiun is clearly pre- sented, often by a leading expert in the field. Unfortunately the depth of treat- ment is extremely variable and this makes it difficult to discern the intended audience. For example, the book con- tains about one page dedicated to mammalian sex chromosomes and over 50 pages describing mitochundrial gen- etics. Another disappointment is that the book was written in 1984, and four years is a long time in molecular genetics research. I suspect the book was originally intended to celebrate 25 years of Bar Harbor pedagogy rather than the more unusual 27 years. A book specific-

ally designed to cover the same ground as the course would have dated less, would have had an obvious readership and woul~ have a coherence of content and purpose.

In summary, I would suggest that those wishing to gain a basic understand- ing of mammalian genetics should con- vince a charitable body to send them to the Bar Harbor Short Course. The book lacks the breadth and purpose of the course. Nevertheless, it is worth a look- over, while browsing in the library.

P. N. GOODFELLOW

Human Molecular Genetics Laboratory, Imperial Ca~er Rese~ch Fund, PO Box 123, Lincoln's Inn Fields, London WC2A 3PX, UK.

The high life of the lower eukaryotes Gene Structure in Eukaryotic Microbes (Special Publications of the Society for General Microbiology, Vol. 22)

edited by J. R. Kinghorn, IRL Press, 1987. £44.00/$84.00 (kbk), £27.50/ $52.00 (pbk) (xui + 296 pages) ISBN I 85221 041 9

There are many reasons for studying gene expression in lower eukaryotes. They range from scientific interest ('the urge to understand'), via a more clinical angle ('the urge to cure') to more down- to-earth reasons, such as the urge of the researcher to survive, since in many cases lower eukaryotes are the only organisms a university department can afford to study these days. The choice of the organism to be studied is determined by these criteria and the relative ease with which a given organism can be manipulated and adapted to the specific requirements of the research(er). This means that when we talk about 'Gene Structure in Eukaryotic Microbes' we are in fact talking about 'Gene Structure in Yeast and other Fungi'. Volume 22 of the special publications of the Society for

General Microbiology is a clear demon- stration of that fact, since 7 of its 12 chapters deal, in one way or another, with fungal gene expression.

The enormous advantage offered by yeasts, particularly Saccharomyces cere- v/siae, is the possibility of combining genetics and direct biochemical analysis via recombinant DNA techniques. This has resulted in a considerable imbalance in terms of the amount of data collected and resolution of detail of the processes of gene expression, when fungi and the rest of the lower eukaryotic world are compared. The book is an accurate reflection of this imbalance.

Many aspects of the way the genes of yeasts are expressed can now be described in molecular terms. During the long route from gene to protein product, c/s-acting nucleotide sequences instruct certain proteins to (help) perform such diverse tasks as transcription initiation, RNA processing and translation. Surpris- ingly, many of the signals that are used (the TATA box, intron-exon borders and polyadenylation signals) are more or less conserved between lower and higher eukaryotes. Moreover, the basic strat-