Genetics and tuberculosis. Novartis Foundation Symposium 217: D. J. Chadwick, G. Cardew (Editors) John Wiley and Sons (269 pages), ISBN 0-471-98261-X, £ 57.50, Hardcover

Abstract

worldwide than any other pathogen, and it is estimated that one-third of the world’s population is infected with it. This is despite the availability of a widely used vaccine (BCG) and cheap, effective drug therapy. In November 1997, the Novartis Foundation organised a symposium in Cape Town, South Africa. This meeting brought together 32 researchers from varied backgrounds but with common goals: to improve understanding of the disease and to generate better tools for disease control. The symposium was specifically designed to maximise discussion and interaction between participants. Fifteen were invited to present an up-to-date overview of their field, following which the more interesting or controversial aspects presented were discussed by the whole group. This book is a written record of the proceedings and comprises 15 chapters, one for each presentation, each of which is followed by a transcript of the discussion generated. It also includes two general discussions. As the chairman Douglas Young comments in his introductory remarks, the symposium came at a critical and exciting stage in tuberculosis research. The contents are broader than the title of the book suggests. In addition to topics pertaining to the genetics of both host and microbe, there are chapters on the contrasting epidemiology of tuberculosis in South Africa (this chapter includes a potted history of tuberculosis in Africa) and San Francisco, immune mechanisms of pathogenesis, and novel therapeutic approaches for tuberculosis. These chapters usefully summarise background information, providing the context for the genetic discoveries presented, and generally start from basic principles before moving on to recent research findings. One of the most significant events in the recent history of mycobacterial research was the characterisation of the M. tuberculosis genome; sequencing of the H37Rv strain is essentially complete. In their chapter, S.T.Cole and B.G. Barrell outline the strategies adopted and demonstrate how analysis of the DNA sequence alone can give insight into the biochemistry and metabolism of M. tuberculosis and allows speculation on the evolutionary history of the organism. This knowledge will also enhance our understanding of microbial pathogenicity and lead to the identification of potential novel drug targets (to which a separate chapter is devoted). Broader applications to currently insoluble controversies are also discussed. For example, the organism’s slow growth and ability to remain dormant within the host for many years contribute significantly to the difficulties faced in disease control, including the long chemotherapeutic regimen required for cure, and reactivation of disease in later life or in immunocompromised individuals. One is left with the impression that the potential for genome-based research has instilled new optimism into mycobacterial research. The other major challenge faced by tuberculosis control programmes is the development of drug-resistant organisms. Two chapters are dedicated to mechanisms of antibiotic resistance: Lynn Meisel’s chapter focuses more specifically on the mechanisms of isoniazid action and resistance, while Julian Davies gives an overview of the several genetic mechanisms that can lead to drug resistance. As he points out, these are poorly understood in mycobacterial infections, and different from mechanisms observed in other bacteria. He concludes that there are many unresolved issues and an effective vaccine is the ultimate solution to the problem of tuberculosis. Easier said than done. In his chapter entitled “Vaccines, genes and trials”, Paul Fine gave an overview of the BCG story so far, describing BCG as “an embarrassing public health failure”. Much research effort and many resources are being spent on developing other vaccines (including DNA vaccines, the subject of the final chapter in the book) some of which are now being tested in humans. However, it is clear that it may not be ethical or desirable to stop giving BCG, and the evaluation of new vaccines will not be at all straightforward. The pathogenesis of an infectious disease is determined not only by the microbe, but also by the host’s immune response. On the host genetics side, work in murine models and human studies were described and discussed at this meeting. Richard Bellamy’s chapter includes a clear description of the approaches used to identify human suscepGenetics and tuberculosis. Novartis Foundation Symposium 217: D. J. Chadwick, G. Cardew (Editors)

DOI: 10.1007/s004390050983

Cite this paper

@article{Newport1999GeneticsAT, title={Genetics and tuberculosis. Novartis Foundation Symposium 217: D. J. Chadwick, G. Cardew (Editors) John Wiley and Sons (269 pages), ISBN 0-471-98261-X, £ 57.50, Hardcover}, author={Melanie J. Newport}, journal={Human Genetics}, year={1999}, volume={104}, pages={439-440} }