observed. There are many other reasons whywhat little remains of the tropical forestsshould be cherished, but what Plotkinlaments here is that the annihilation ofspecies by the thousand deprives us of untoldopportunities to discover new medicines andother valuable classes of compounds —strong materials, process chemicals andmany more.

He also denounces the profligacy withwhich existing therapeutic resources arebeing degraded: antibiotics are still fed tocattle and federal law is content to allow traceamounts of no fewer than 80 antibiotics toenter the milk that Americans drink. Andfinally, Plotkin notes, a large proportion ofthe most important medicinal substanceswere brought to us by research driven only bycuriosity about the natural world andmocked by Senator William Proxmire andhis allies as a waste of the taxpayers’ money.Let us hope that Plotkin’s voice is heard in thequarters that count, those in which econom-ic and not moral interests prevail. Dr John-son put it pithily: “Sir, I have found you anargument, but I am not obliged to find youan understanding.” ■

Walter Gratzer is at the Randall Centre forMolecular Mechanisms of Cell Function, New Hunt’s House, Guy’s Campus, St Thomas Street, London SE1 1UL, UK.

A function fordysfunctionIon Channels and Diseaseby Frances M. AshcroftAcademic: 1999. 352 pp. £46.95, $75

Thomas J. Jentsch

The importance of many things in our livesbecomes apparent only when we lose them,or when they malfunction. In genetic dis-ease, mutations in a gene may lead to inter-esting and sometimes unexpected insightsinto the physiological importance of theirproduct. Detailed comparison of the proper-ties of both the normal and mutant geneproducts can reveal deep insights into thephysiological role of the protein encoded bythe gene and how it goes awry in disease.

This combination frequently occurs inion-channel diseases (or ‘channelopathies’).Over the past 15 years, genes encoding ionchannels have been isolated at ever-increas-ing rates. Their number exceeds estimatesobtained from biophysical studies, and onemight wonder why there are so many differ-ent channels. In many cases, mutations inion-channel genes, in both humans and ani-mals, have provided clues or answers. Someion-channel genes were even cloned on thebasis of the effects of their disruption. Forexample, positional cloning in the fruitfly

Drosophila led to the isolation of the shakerpotassium channel, and the CFTR chloridechannel was found because its gene is mutat-ed in cystic fibrosis.

The large number of ion-channel dis-eases provides an impressive illustration ofthe many functions of channels. These range from signal transduction to ionichomeostasis, cell-volume regulation, trans-epithelial transport, vesicle acidification andtrafficking, and cytotoxic effects, to namejust a few. As a result, ion-channel diseasesare clinically very diverse, ranging from cystic fibrosis to inherited forms of kidneystones, periodic paralysis, high blood pressure, epilepsy and hyperinsulinaemia.

Ion channels can be studied in great detailusing biophysical methods. One suchmethod is the patch-clamp technique, whichinvestigates the properties of single mol-ecules in real time. The in vitro analysis of channel mutations found in patients has contributed considerably to our understanding of the relationships between channel structure and function. Comparedwith most other genetic diseases, this pro-vides an unrivalled level of understanding ofhow mutations cause disease.

Frances Ashcroft’s book is a fascinatingand accessible account of ion-channel

diseases. But it does not stop there — it is alsoan up-to-date description of the differentclasses of cloned ion channels, their struc-ture and function, and how the disease char-acteristics resulting from their dysfunctionare used to elucidate their physiologicalroles. For completeness, channels not (yet)known to cause human disease are also cov-ered, and the chapter “Ion channels as lethalagents” even discusses the pore-formingpeptides of bacteria and fungi.

Ashcroft begins with a short introduc-tion on the essentials of molecular biology,human genetics, electrophysiology and ion-channel design. Although necessarily super-ficial, this section will be useful for studentsfrom different backgrounds. Beginning withvoltage-dependent sodium channels, theauthor goes on to discuss the different classesof ion channels individually. Only clonedion channels are included, thereby omittingseveral classes of ion channels (such as calcium-activated chloride channels) whosemolecular correlate has not been firmlyestablished.

These chapters begin with a concisedescription of what is known about thestructure and function of the channels, and adiscussion of the key experiments that led tothese insights. The physiological role of the

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236 NATURE | VOL 406 | 20 JULY 2000 | www.nature.com

The Kongo peoples inhabit the River Congoregion in west-central Africa, and are dividedinto many subgroups, all of which have manydifferent cults. Their strong belief in a widespectrum of spiritual forces catalysed thedevelopment of a wealth of sculptural formsdedicated to containing and harnessing theseforces. The statue shown here, called nkisinkonde, represents a power figure generallyassociated with vengeance and aggression, butit could also be involved in the sealing of pactsbetween individuals — each nail or pointdriven into the statue reinforces the pact.Failure to keep the pact would provokeretribution from nkisi nkonde’s particularlyferocious spirit. From Spirits Embodied: Art ofthe Congo by Evan M. Maurer and NiangiBatulukisi (University of Minnesota Press,$34.95, £24.50).

Channelling otherenergies

© 2000 Macmillan Magazines Ltd

channels is then described. These short sec-tions introduce the reader to the cellularphysiology of such diverse systems as the b-cells of the pancreas, photoreceptors, kidneytubules, the neuromuscular junction andeven the complement system.

Ashcroft then discusses diseases that arecaused by mutations in these channels. Themain focus is on human disease, but mousemodels of disease, channel mutations in goats and horses, and in Drosophila and the roundworm Caenorhabditis elegans arealso covered. The perspective is broadened bythe inclusion of such aspects as the modula-tion of inositol phosphate metabolism bylithium in the treatment of manic depression,and a discussion of how glutamate-receptor ion channels are affected by the ingestion of excitotoxins (from shellfish, Nutrasweet or glutamate in the Chinese restaurant syndrome).

Not only are these sections interesting,they are also fun to read. We learn what to pay attention to when preparing a meal fromthe pufferfish Fugu, or how to differentiateclinically between myotonia and para-myotonia (give the patient ice-cream!). Eachchapter is illustrated with useful figures anddiagrams, and remaining problems are high-lighted. For instance, the pathophysiologicalmechanisms underlying some importantchannelopathies (such as cystic fibrosis) arestill not completely understood many yearsafter the gene was identified.

Ion Channels and Disease is a very goodintroduction to the whole field of ion channels, and will be useful for researchers,clinicians and students. Although BertilHille’s Ionic Channels of Excitable Mem-branes (Sinauer, 1992) remains the standardtextbook on the biophysical aspects of ionchannels, and Ion Channels (CambridgeUniversity Press, 1996) by David Aidley andPeter Stanfield is a very good, balancedoverview of the structure and function ofsuch channels, Ashcroft’s book combines ashort review of individual ion-channel classes with an excellent discussion of theirphysiological and pathophysiological roles.It is the favourite of several of my colleagues.Although the book is as up-to-date as it can reasonably be, I hope that frequent neweditions will keep pace with this rapidlydeveloping and fascinating area. ■

Thomas J. Jentsch is in the Zentrum fürMolekulare Neurobiologie, Universität Hamburg,Falkenried 94, D-20246 Hamburg, Germany.

More molecular biologyBiology of Sensory Systemsby C. U. M. SmithWiley, £39.95, $80 (pbk)

Molecular and Cellular Physiology of Neuronsby Gordon L. FainHarvard University Press, $65, £40.50

Conservation gets heavyHotspots: Earth’s BiologicallyRichest and Most EndangeredTerrestrial Ecoregionsby Russell A. Mittermeier, Norman Myers &Cristina Goettsch MittermeierUniversity of Chicago Press: 2000. 432 pp.$65, £45.50

Rory Howlett

Beautifully illustrated, Hotspots representsthe second volume resulting from a three-way collaboration between the non-profitorganization Conservation International,the Mexican conservation organizationAgrupación Sierra Madre and, believe it ornot, Cemex, the world’s third-largest cementcompany. Judging from the book’s weight,one would be forgiven for musing thatCemex contributed more than just cor-porate support to its production. That aside,the company’s environmental credentialsare now no doubt set in concrete.

The first volume in the series, Megadiver-sity: Earth’s Biologically Wealthiest Nations,published in 1997, dealt with the so-called B-17, the 17 biologically richest nations. Thepresent volume focuses on ‘biodiversityhotspots’. The hotspots concept, conceivedof and promulgated by ecologist NormanMyers, is nebulous, but, roughly speaking,highlights the importance of those regions of

the world that have disproportionately highlevels of species richness and, in particular,endemism.

Defining the thresholds of biodiversityand endemism above which a region qualifiesfor ‘hotspot’ status is arbitrary. Indeed, as thefirst chapter makes clear, hotspots have beensubject to ‘reanalysis and reassessment’, withareas being added or removed as criteria forwhat constitutes a hotspot have evolved. Thebasic message, though, is that an estimated60% to 70% of all terrestrial plants and non-fish vertebrates occur within just 1.44% of theEarth’s land surface, providing a rationale forwhat Myers has advocated as a ‘silver bullet’approach to biological conservation.

The following 25 chapters document sep-arate terrestrial ecoregions, each chapterauthored by specialists. The organization isformulaic. Overviews of the regions, theirdiversity of habitats and global importanceare followed by subheaded sections on ‘Flag-ship species’, ‘Threats’ and ‘Conservation’.This makes it easy to access information,despite the absence of an index. For example,the chapter on New Caledonia starts bypointing out that, although the region has aland surface area roughly equivalent only tothat of Wales or New Jersey, it is remarkablyspecies rich, with high levels of endemism. Inthis it is like Madagascar, once also part of theancient continent of Gondwana. Flagshiptaxa include a rainforest-dwelling bird, the

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Feathered flagships: kagus, endemic to thebiodiversity hotspot New Caledonia.

© 2000 Macmillan Magazines Ltd