A black spot of modern biology

Horizon Scientific Press, 1999. $129.99 hbk (218 pages)ISBN 1 898486 07 7It might have seemed to the general public in the early 1900s that the mission of physics was essentially complete. Just a few ‘black spots’ remained to be cleared up, such as the unexplained discrete nature of atomic spectra or the indeterminate phenomenon of radiation, for a coherent picture of the Universe to finally emerge so that physical science would be transformed into a technology dealing with predictable applications.Of course, the deep thinkers thought otherwise. A century later, we now know that they were right and the ‘public’ was wrong. The ‘black spots’ produced concepts and applications that changed not only the face of physics but also our daily lives and the history of humankind in the 20th century. Furthermore, with all due respect to the achievements of physicists, the picture of the Universe remains as cloudy as ever.The prion phenomenon represents a ‘black spot’ on the body of modern biology, and it might have a similar impact. The recent epidemic of ‘mad cow disease’ in the UK and the possibility of the transmission of this incurable and fatal disease to humans have heightened awareness of the medical aspect of this problem. However, prions are able to do even more harm. They challenge the central dogma of molecular genetics, which states that only nucleic acids can transmit genetic information. In the case of prion diseases, no nucleic-acid-containing agent that could be responsible for infection (such as bacteria or virus) has so far been identified. One of the models suggests that the wrongly shaped protein (prion protein) serves as the infectious agent itself because of its ability to convert normal protein into the wrong shape. The 1997 Nobel Prize in Medicine awarded to S. Prusiner, one of the pioneers of prion research, underlines the importance of this emerging field.This new book, edited by the famous prion researcher David A. Harris, serves as a very interesting and detailed introduction to molecular and cellular aspects of prion biology, from structural studies of the prion protein to mechanisms of pathogenesis and the prospects of potential treatments for prion diseases. In vitro cell and animal experimental models of prion conversion and propagation are considered. Human prion diseases and epidemiological aspects of the transmission of ‘mad cow disease’ to humans are discussed. The book has an impressive line-up of contributing authors including such leaders in the prion field as A. Aguzzi, B. Caughey, B. Chesebro, D. Dormont, P. Gambetti, B. Ghetti, R. Glockshuber, C. Weissmann, R. Wickner and others. It should certainly be useful for the wide audience of biologists and physicians who are interested in gaining first-hand exposure to the field.One minor criticism is that the book focuses almost exclusively on one example of a prion, the mammalian PrP. Recent evidence, as Wickner was the first to point out1xWickner, R.B. Science. 1994; 264: 566–569Crossref | PubMedSee all References1, suggests that there is a wider distribution of the prion phenomenon in nature. This gap is filled in part by the chapter written by Masison and colleagues, which summarizes information on yeast and fungal prions. However, further comparisons with other potentially related experimental models would certainly be useful. Cortical inheritance in ciliates is one example of a protein-based hereditary system that exhibits remarkable similarities to prions2xBeisson, J. and Sonneborn, T.M. Proc. Natl. Acad. Sci. U. S. A. 1965; 53: 275–282Crossref | PubMedSee all References, 3xHyver, C. and LeGuyader, H. C. R. Acad. Sci. 1995; 318: 375–380PubMedSee all References. The cytoskeletal structures, in general, possess a clear potential for the ‘template-like’ assembly that could serve as a molecular basis for transmission of structural (as opposed to sequential) information in cell generations. Exploration of such possibilities would be especially useful in the light of recent models suggesting that prion transmission occurs via the process of nucleated polymerization, which possesses remarkable similarities to the assembly of the cytoskeletal structures4xLansbury, P.T. and Caughey, B. Curr. Biol. 1995; 2: 1–5Scopus (117)See all References4. On the other hand, aggregation-related disorders such as Alzheimer’s disease exhibit many similarities to prion diseases and could also be discussed in such a context. This would place the material in a wider evolutionary and medical perspective, and emphasize the potential role of information proteins in heredity and pathogenesis. However, this does not diminish the importance of this book, which reviews one of the most exciting areas of modern biology.