DOI: 10.1097/01.NT.0000449807.60016.fb

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Issn Print: 1533-7006

Publication Date: 2014/05/01


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BOOKSHELF: Proteins, Prions, and Paradigm Shift — Persistence and a Little Self-Promotion Help Madness and Memory

Christopher M. Filley

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Excerpt

In 1962, the science historian Thomas Kuhn published his influential The Structure of Scientific Revolutions, introducing the idea of the paradigm shift. In contrast to normal science, the paradigm shift introduces a radical change in thinking that challenges widely held scientific assumptions, and then, after validation and acceptance, exerts a lasting change in the field. Stanley Prusiner, MD, a name well known to neurologists and neuroscientists around the world, has written his own book about what he would undoubtedly regard as a paradigm shift of his own making. Whatever the reader concludes, there can be no question that what is described in this book is far indeed from normal science.
Madness and Memory is a personal account of the discovery of prions, packaged with generous autobiographical detail that expands the story to reveal much about the author's background, career, and personality. Prusiner first describes his family, upbringing, and early academic development as a prelude to the grand adventure on which he later embarked to come to his major discovery.
A neurologist with a medical degree from the University of Pennsylvania, he realized early in his training that clinical medicine was not for him, and his decision to embrace laboratory research was pivotal. His boundless enthusiasm for the opportunity offered by bench science led him away from the clinic and toward the investigation of fundamental neurobiology. Still, one finds in his prose the desire for his research to have major implications — as far-reaching as he can imagine — for the understanding and treatment of devastating human diseases he saw as a neurology resident.
The prion, as all neurologists and neuroscientists know, stands for “proteinaceous infectious particle.” The term was introduced in Prusiner's most important paper, a single-authored article in Science that appeared in 1982. Based on his work with the sheep and goat disease scrapie, Prusiner proposed the radically novel idea that the infectious agent in this disease was a particle consisting solely of protein — without the nucleic acid of conventional viruses.
In contrast to the entrenched orthodoxy regarding the structure of infectious organisms, prions were conceptualized as proteins that could transmit disease in the absence of DNA or RNA. The prion was seen as relevant to human disease, most obviously the rapidly progressive dementia Creutzfeldt-Jakob disease (CJD), as well as the cerebellar ataxia of New Guinea cannibals known as kuru. Here is the stuff of paradigm shift, breathtaking in its originality and bound to evoke strong reaction. If the concept of the prion turned out to be true, textbooks would need to be rewritten, lectures thoroughly revised, and ideas about the very nature of life itself revisited.
Just as Kuhn would predict, a robust intellectual dispute immediately erupted between the advocate of the new science and the followers of the existing paradigm. Prusiner recounts in vivid detail the opposition he faced, not only from scientists around the world but in his own department of neurology at the University of California, San Francisco, as well. The animosity he encountered was fierce indeed; he recounts being called “impulsive, presumptuous, reckless, ambitious, aggressive, callous, manipulative, and egotistical.” From his own colleagues he received “negative critiques” arising from “disbelief, disdain, and ignorance.”
Undaunted, Prusiner responded to his detractors with ceaseless energy to pursue his studies and gather the evidence needed for vindication. He reports vigorously rising to the challenges confronting him, resolutely endeavoring with competitive spirit not only to confirm the existence of prions but also to extend his findings to human diseases.
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