Neurotoxins in neurobiology: Their actions and applications

110 structures, let alone the mechanisms and chemical transformations. Perhaps biochemists should do more than pay lip service to the ideas that biochemistry aims to study the chemistry of life processes. But equally those running chemistry courses for biology majors could perhaps do better in terms of understanding. This book will not bridge this gap. The text is divided into three sections each of 3 or 4 chapters. The titles of these Parts are mostly journalese: I is 'The Changing Tradition' and has chapters on bonding, catalysis, spectroscopy and geometry/crystals. Part II is entitled 'New Products, New Functions' and has chapters on molecular recognition, plastics that conduct electricity, superconductivity, and the colloids (from thixotropic paints to membranes and liposomes to liquid crystals). Part IIl is 'Chemistry as a Process' and goes from prebiotic synthesis, through crystal growth and fractals, to the environment (greenhouse effect, ozone layer, acid rain) and this latter is a rather well balanced account. The range of topics covered will be seen from this brief outline. The flavour of the text can perhaps be appreciated from subtitles to chapters. Inevitably, spectroscopy is "watching atoms dance", but in fact the description of the background is dealt with in an approachable way that students may well find helpful. The same might be said of the first chapter (on chemical bonds): it is not rigorous but is approachable. There is quite a lot of biochemistry but on the whole it is probably better done in some of our modern biochemistry texts. Bali's text, however, is sometimes better at explaining why things might be the way they are. I would like to give a couple of examples of what 1 see as the gap in perception - - between how chemists see things and how biochemists see them. In chapter 2, about catalysis, the initial treatment is good, clear and helpful. Then it is said that 'homogeneous catalysts are potentially capable of more delicate tasks than most heterogeneous varieties'. The gap in understanding that I see is that arguments about whether catalysts are heterogeneous or homogeneous is rather irrelevant. What is important is the understanding that the active site is a surface or cleft in a protein and that catalysis and specificity can be explained quite well in chemical terms on the basis of the groups present, etc. Indeed, the author remarks, a few pages further on, that it is "unclear whether [enzymes] should be thought of as homogeneous or heterogeneous catalysts". Who cares? A separate point is that it is said that the synthesis of proteins and DNA molecules are "well beyond the capabilities of organic chemists" (p 76). This is only partly true: smallish molecules can certainly be manufactured and biochemists are surely greatly indebted to the organic chemists for providing the wherewithal to make gene machines work so that we can have oligos to order. But here again is the difference in perception. If biochemists want to make large proteins and DNA molecules they use the techniques of molecular biology and use organisms and enzymes to do the chemistry for them. Why feel handicapped if you cannot do it in the traditional organic laboratory? As I have indicated this is an interesting read and different people will find different things interesting, amusing, exciting or controversial. The somewhat idiosyncratic diagrams are mostly clear, but I did not think the colour plates in a separate section added very much. E J Wood

Monoclonal Antibodies: The Second Generation E d i t e d by H Zola. pp 224. Bios Scientific, Oxford. 1994. £49/$99 ISBN 1 - 8 7 2 7 4 8 - 7 8 - 3 Monoclonal antibodies are in the main produced by mouse hybridoma technology and in fact the technique has been very successful. Monoclonal antibodies have revolutionised diag-

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nostic techniques as well as many other areas of biology, including immunology itself. The next revolution (or the "second generation" of the title) is going to be in the application of molecular biology techniques to engineer the next generation of antibodies, over the next decade. This small but authoritative book gives a flavour of what is to come in this exciting area. It is up to date and covers a wide area. The initial parts of chapters are suitable for undergraduate updating and postgraduates and researchers will find individual chapters helpful in getting into new areas. Not many of them are going to buy the book at £49, however. Chapter I gives a general introduction and chapter 2 describes how to make 'conventional' mouse monoclonals. (The first half of the book actually contains quite a lot of experimental details and recipes, incidentally: the second half does not). This second chapter assumes an overall familiarity with the technique and the authors give their own favoured protocols. When it is wished to use monoclonal antibodies for therapeutic purposes (eg targetting drugs to human cells) there are obvious disadvantages in having to use mouse antibodies. However, the only method presently available for producing human antibodies is by the immortalisation of human antibodysecreting cells with EBV. Chapter 3 gives many examples (in brief) of the use of this procedure and also gives some experimental details. But, of course, since knowledge of the antibody genes is extensive, the obvious next step is to engineer antibodies and essentially the second half of the book goes into the various ways of doing this. Chapter 4 is on antibody reconstruction by genetic engineering techniques. Chapter 5 gives details of preliminary clinical use of antibodies, which the Editor admits is limited at present. Chapter 6 is on phage display libraries, chapter 7 on libraries of artificial antibodies, e.g. by isolation of V genes from lymphocytes, amplification by PCR and expression in E coli. However, a problem is that such expressed polypeptides need to be renatured in vitro, and chapter 8 is about expressing antibody genes in mammalian cells such as transiently in COS cells or the transfection of myeloma cells. Finally chapter 9 takes us into single-chain Fvs and the ideas - - many now successful - - of engineering the binding parts of antibody molecules in a variety of ways. Much of this is biotechnology and certainly looks set to revolutionise the diagnostic industry (once again). We've come a long way since the original publication of K6hler and Milstein in 1975! B N Dodd

Neurotoxins in Neurobiology: Their Actions and Applications E d i t e d by K F T i p t o n a n d F Dajas. pp 196. Ellis H o r w o o d Series in N e u r o s c i e n c e , Chichester. 1994 ISBN 0 - 1 3 - 6 1 4 9 9 1 - X Natural toxins are produced by a variety of terrestrial and marine organisms. This book, edited by Professors Tipton and Dajas, is a compilation of chapters that illustrate the enormous variety of toxins and their applications for studying the operation of the nervous system. The book is divided into three parts: I Toxin Diversity, II Toxins, and llI Nerve function and Neurotoxins. We learn that the neurotoxins act on (1) ion channels (K +, Ca-'+, Na +) (ii) Neurotransmitter receptors (Acetyl choline receptors, G A B A , Adrenoreceptors, Glutamatergic receptors, or (iii) enzymatic mechanisms (phospholipases, acetyl cholinesterases). It is now established that spider venom can be obtained in 'pure' form and some progress has been made in the amino acid sequence of the peptide toxins of the tarantula. The toxins from marine

111 organisms affecting the cholinergic nervous system act either antagonistically or synergistically to acetyl choline and some assay methods are described for the isolation of the toxins. Methods of assay of K ÷ channel, anticholinesterase and muscuranic toxins are explained comprehensively. The most interesting section is that which describes the action of toxins on neurotransmitter release. Tetanus toxin from Clostridium tetani is a potent neurotoxin responsible for causing the tetanic syndrome in humans. The nucleotide sequence of its gene has been determined and the primary structure of the gene product characterized. The expression of specific fragments of the toxin gene in E coli has also been achieved. Focal injection of tetanus toxin into the rat hippocampus has enabled scientists to use this toxin as a tool to produce neurodegeneration in the rat brain. Ruthenium red, an inorganic dye, is neurotoxic and experiments in vitro, with synaptosomes and in neuromuscular preparations have shown that the dye exerts its effects on synaptic neurotrans3+ mission. By interfering with Ca- , alteration in motor behaviour and paralysis result. The last chapter (also the lengthiest one) is by Professor Tipton. l-methyl-4-phenyl-l,2,3,6-tetra hydropyridine (MPTP), a contaminant of a synthetic pethidine analogue that had been sold as a street drug, produces a condition resembling idiopathic Parkinsons disease. Tipton's and others' work led to the understanding of the mechanisms by which MPTP causes selective destruction of nigro-striatal dopaminergic neurons. Neuroscientists will find this book very useful. C V Anand

Human Biology By C Starr a n d B McMillan. pp 527 + appendices. W a d s w o r t h Publishing, B e l m o n t , C A . 1995. £21.95 ISBN 0 - 5 3 4 - 2 0 2 0 8 - X One has come to expect N American college-level texts to be lavish - - and this one is no exception - - but this should not disguise the immense amount of thought and care that goes into this production. An overall concept, a large panel of reviewers, art and design directors, et al, all combined, authors hope, to produce a text that is clear, logical, engaging and respectful of the intelligence of students. The treatment is full colour with end-of-chapter review questions, critical thinking questions ("you decide"), self-quizzes, and key terms and a short reading list. Inevitably there always seem to be lots of pictures of athletes and a heavy emphasis on not smoking (or perhaps I am getting a little old and cynical). On the whole I felt that this presentation was very successful. The text is easy to read, the diagrams 'flow' very well and everything is in its place on carefully designed pages. In addition, many ethical issues are raised that will surely engage young people in a human biology context (drug taking, anabolic steroids, contraception, safe sex, abortion, withdrawal of life support systems). Most of the issues seem to be dealt with in considerable depth and the authors write with authority on the varied issues. Is there anything missing? I felt sometimes that, despite the depth of treatment, the element of uncertainty in science was sometimes lacking. Students don't like uncertainty and controversy (two sides of a story to learn instead of one for an exam), but science thrives on it and much of the work that scientists do is driven by a desire to clarify uncertainty and controversy. Here facts are facts: things are not much in dispute; they are presented with authority in full colour. Where there are questions they are questions of morality and ethics based on scientific facts. The book is divided into four major sections. The first short section is Foundation which includes simple chemistry and cell biology. Section two is on Body System and Function and is basically on human anatomy and physiology, with some bio-

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chemistry, development (embryology), immunology, with a final section on sexually transmitted diseases. Section three is on inheritance, genetics and DNA, with final chapters on cancer and on biotechnology (including gene therapy). The fourth section is on Evolution and Ecology. The book closes with a set of Appendices and an extensive glossary. At chapter ends there are very short reading lists (this is 'extra reading': everything you could possibly want is in the text already?), many with 1993 and 1994 dates, the exception being the main reference to a biochemistry text - - Lehinger's Principles of 1982! The authors clearly know their audience: thousands of college students in N America, many of them on the premed track. In the UK it would certainly be highly recommendable to new preclinical medics who do not have a high school Biology qualification. It would also be a good high school Biology text in its own right. I enjoyed reading the text and found few errors and little to quibble with. (I guess the pictures on p 248 of how to do drug abuse in various ways will be old-hat to students). The story of haemoglobin electrophoresis on p 412 is wrong (it's not done by SDS-PAGE), and the view presented of cholera treatment on p 36 is very naive: antibiotics are largely a waste of money, but in contrast glucose/NaCI rehydration therapy is very cheap and effective. Overall this is a very attractive and up-to-date production. It will also engage young people for the issues it covers (in a straightforward factual way) and it is environmentally correct. It will not tell them much about how science is done but hopefully it will attract at least some of them to a scientific career. E J Wood

Advances in Nutrition and Cancer Advances in Experimental Medicine and Biology Vol 248 E d i t e d by V Z a p p i a , M Salvatore a n d F D R a g i o n e . pp 169. P l e n u m Press, New York. 1993. $65 ISBN 0-306-44670-7 This volume contains the scientific contributions presented at an International Symposium held in Naples, Italy, in 1992. It is divided into three parts: Molecular Basis of Malignant Transformation, Epidemiological Studies: Risk Factors, and Diet and Clinical Research and Perspectives. The first part has five chapters. They contain information about Growth Factor Requirements for Cell Proliferation and highlight the multistep process involving the activation of cellular proto-oncogenes and inactivation of tumour suppressor genes. A protocol for the purification and characterisation of mammalian 5'-deoxy-5'-methyl thioadenosine phosphorylase is presented. The use of transgenic mice as a powerful tool to investigate in vivo oncogenic action during transformation is also presented in this section. The second part has five chapters. These chapters describe a longitudinal study of food intake and alcohol intake in two rural Italian cohorts. It has been shown that those who drank highest amount of alcohol and ate least amount of other foods had the highest incidence of all cancers and, surprisingly, quite a low rate of stomach cancer when compared to the group whose consumption of alcohol was not so high. Other chapters in this section have some interesting findings on diet and precancerous lesions, dietary prevention of chronic diseases and dietary fibres and prevention of cardiovascular disease. The third part focuses on clinical research pertaining to diet and large bowel cancer, nutritional etiology of breast cancer, diet and gastric cancer, diet and coeliac disease. Perhaps the most interesting aspect is the 'protective' nature of the Mediterranean diet on cancer risks. C V Anand