Book Review

Prion Diseases

N Engl J Med 1997; 337:1017October 2, 1997

Article

Prion Diseases
Edited by John Collinge and Mark S. Palmer. 205 pp., illustrated. New York, Oxford University Press, 1997. $57.50. ISBN: 0-19-854789-7

Not so long ago, even neurologists struggled with the pronunciation of Creutzfeldt–Jakob disease, one of the transmissible spongiform encephalopathies or prion diseases. Now, with the emergence of bovine spongiform encephalopathy, or “mad cow disease,” and the concern that its transmission to humans causes a “new variant” of Creutzfeldt–Jakob disease, prion diseases are front-page news. The increased attention paid to them has advanced the field and led to a number of books on the subject. Prion Diseases, edited by Collinge and Palmer, is one of the best. The fact that eight of the nine contributors are British testifies to the impact of the bovine spongiform encephalopathy epidemic in England.

Astonishing features of prion diseases have received much attention, such as the person-to-person transmission of kuru in New Guinea associated with ritual cannibalistic eating of infected tissue. Equally remarkable is that the agent that transmits these diseases resists heat, ultraviolet radiation, and x-rays and does not evoke an inflammatory response. Landmark experiments by Prusiner (one of the contributors to this book) and colleagues showed that the infectious agent is a proteinase-resistant form (PrP^sc) of a normal cellular prion protein (PrP^c). PrP^sc, which is pathogenic, is believed to be identical to PrP^c except for a difference in conformation. PrP^sc can induce a change in the conformation of the host's normal prion protein into the abnormal one. The continued conversion in conformation is the presumed basis of the “infectivity” of PrP^sc and its puzzling “replicative” nature.

Some scientists remain unconvinced about the absence of nucleic acid in this replicating infectious agent, prompting a speaker at a recent neurovirology symposium to avoid controversy by referring to the transmissible agent as a “thing.” Collinge and Palmer are appropriately decisive and have structured their book around prion protein. Chapters describe the clinical, molecular, and pathological features of the prion diseases in humans and animals, transgenic models of prion diseases, and structural features of prion protein. The editors wisely leave room for changing ideas about these diseases, noting that “understanding of the biology of these conditions is advancing quickly and it is important not to be dogmatic in such definitions [of a prion disease].”

This book succeeds in educating the reader, but the arcane details of “prionology” are at times burdensome, even for the cognoscenti. I appreciate the detailed description of PrP^c mutations in inherited prion diseases in the chapter by Collinge and Palmer, and even the alignments of the amino acids of PrP^c in 11 species of animals (including the greater kudu). Somewhat overwhelming, however, is the complicated terminology in the exhaustive chapter concerning the inoculation of PrP^sc material derived from one animal species into another species that carries a PrP transgene (from yet a different species). One's own brain hurts a bit when one reads about infecting MH2M(MH2M(Sha(Sc237))) prion protein into a host with Tg(MH2M PrP)92.

The book is reasonably up to date, a difficult achievement in such a quickly changing field. There are timely discussions of variants of Creutzfeldt–Jakob disease, but I would have liked a more complete discussion that incorporated recent advances in yeast “prions,” structural studies of prion protein, and public health issues relating to prion diseases. Even so, this book provides abundant food for thought regarding prion diseases, which continue to show us how scientific dogma needs correction.

Raymond P. Roos, M.D.
University of Chicago Medical Center, Chicago, IL 60637