Book Review

Deadly Feasts: Tracking the secrets of a terrifying new plague

N Engl J Med 1997; 337:1016October 2, 1997

Article

Deadly Feasts: Tracking the secrets of a terrifying new plague
By Richard Rhodes. 259 pp. New York, Simon & Schuster, 1997. $24. ISBN: 0-684-82360-8

In the wake of an epidemic of bovine spongiform encephalopathy, or “mad cow disease,” in Great Britain that afflicted nearly a million head of cattle, and the recent emergence there and in France of a new variant of Creutzfeldt–Jakob disease that resembles bovine spongiform encephalopathy biochemically and appears to have been contracted from eating contaminated beef, public interest in the transmissible spongiform encephalopathies, a class of fatal neurodegenerative diseases of humans and animals, is understandably high. After reading several laudatory reviews of Deadly Feasts in the lay press, I approached the book with a mixture of curiosity and skepticism, wondering how a complex and as yet incomplete scientific puzzle could be presented to a worried readership craving definitive answers. What I found was a racy account of clinical and scientific discoveries over the past five decades concerning transmissible spongiform encephalopathies, juxtaposed with an incriminating analysis of the British government's attempt to control the epidemic of bovine spongiform encephalopathy that began in 1985.

Richard Rhodes, a Pulitzer prize–winning author, begins with a lurid depiction of endocannibalism (the ritualistic consumption of deceased family members) among the Stone Age Fore tribes of New Guinea. Carleton Gajdusek, a pediatrician and virologist, and his collaborators demonstrated transmission of kuru to primates, supporting the link between kuru and cannibalism. Gajdusek was awarded the Nobel prize in 1976. Since then, the chief scientific challenge has been to figure out the nature of the infectious agent that causes kuru and other transmissible spongiform encephalopathies. The prion hypothesis proposed in 1982 by Stanley Prusiner, a neurologist and biochemist, dominates the field. According to this hypothesis, the infectious agent is a prion composed largely, if not exclusively, of an abnormal isoform of prion protein, which is encoded by a host gene. The normal isoform of prion protein is converted to the abnormal isoform on exposure to the latter by a cellular process whose precise details are still unknown.

Rhodes takes pains to provide character portraits of the scientists whose work he describes. Without having had the benefit of being acquainted with Prusiner, he lionizes Gajdusek and demonizes Prusiner. One unfortunate consequence of this bias is his championing of Gajdusek's hypothesis about how prions replicate over Prusiner's hypothesis, apparently without understanding important differences between them. Gajdusek's “infectious amyloid” hypothesis involves the “crystallization” of normal prion protein around a “nucleant” of abnormal prion protein. Rhodes takes this idea to an extreme when he compares it to Kurt Vonnegut's “ice-nine” fantasy in Cat's Cradle (New York: Delacorte Press, 1963), making it seem like a passive process. Prusiner's theory of heterodimers, in which a single abnormal molecule of prion protein converts a normal molecule by forming a heterodimer, originated as an explanation for a series of experiments in transgenic animals. Rhodes alludes to one of these experiments but apparently misses the subtler point. This theory provides a conceptual framework for exploring the active cellular and biochemical mechanisms involved in the conversion. Rhodes does not even mention that.

British policy makers charged with managing the epidemic of bovine spongiform encephalopathy are harshly censured and rightly so, in hindsight. The Ministry of Agriculture, Fisheries and Food announced that cattle would be a dead-end host once the source of the infection, ruminant-derived protein supplements, was eliminated. Rhodes attributes this eagerly reached conclusion to strong economic incentives to protect the beef industry, combined with a general lack of foresight. But the ministry's advisory committee relied on what scientists had told them about barriers between species: that their efficacy increases with the divergence of amino acid sequences of prion protein between species. The barrier separating cows and humans was thought to be sufficiently strong to prevent the prions of bovine spongiform encephalopathy from infecting people eating beef. When mounting evidence implicated contaminated beef as the cause of the new variant of Creutzfeldt–Jakob disease, the ad hoc scientific explanation for this unexpectedly tragic turn of events was that bovine spongiform encephalopathy involves a new strain of prions that, for unclear reasons, is particularly infectious and crosses the species barrier with relative ease. Just how easily is not yet known. Because the biology of prion strains is murky, most scientists would have been reluctant to predict this dire outcome. The ministry's policy makers were only too happy to respond to the reluctance with complacency.

One important lesson to be learned from the bovine spongiform encephalopathy epidemic is that scientists and policy makers fulfill different missions. The former are data-oriented and prefer to ignore prophets and prophetesses. The latter, in their capacity as protectors of the public good, need to act as seers erring on the side of caution. Scientists who become policy makers must shift their perspective, and policy makers advised by scientists must understand how scientists think. Deadly Feasts shows the unfortunate consequences of failing to recognize these distinct roles.

Karen K. Hsiao, M.D., Ph.D.
University of Minnesota Medical School, Minneapolis, MN 55455