The Unborrowed Vision of Stanley Prusiner

It is a rare treat to get a glimpse into the unrelenting pursuit of truth by a genius. Nobel laureate Dr. Stanley Prusiner, in his biography Madness and Memory: The Discovery of Prion—A New Biological Principle of Disease, provides such a glimpse.

The book recounts Dr. Prusiner’s painstaking struggle to uncover the secrets behind such diseases as scrapie, kuru, Creutzfeld-Jakob Disease, and Mad Cow Disease, which, before his intellectual power was brought to bear on the problem, defied explanation. This chasm in scientific knowledge and the inability to isolate a traditional infectious agent from patients caused scientists to invent tortured concepts like “slow virus” and “unconventional virus.”

The book provides a detailed accounting of the mountains of evidence and data Dr. Prusiner and his associates amassed over decades of work, the inductive leaps that they justifiably made, and the converging evidence that a new infectious agent had been discovered necessitating the creation of a new concept, perfectly designated by the word “prion.”

A prion, or proteinacious infectious particle, unlike all other infecting agents, is exclusively comprised of protein and is devoid of any genetic material yet is able to replicate and cause illness.

While it may seem that Dr. Prusiner proceeding down a relatively straightforward path without many obstacles to surmount, it is far from the truth. It is almost a general, but unfortunate, principle that those who bestow new knowledge on mankind are not greeting with the fanfare that they deserve, but derision, ad hominem attacks, and persecution. Such was clearly the case with Dr. Prusiner and his unborrowed vision that propelled science and human understanding further. As Dr. Prusiner traversed the incalculable distance of an “odyssey” from “heresy to orthodoxy,” he was met with skeptics that ranged from scientific journalists to Nobel-prize winning scientists. (As a student in a virology class I vividly recall my professor expressing open skepticism). But, despite the opposition, Dr. Prusiner’s persisted. He importantly identified that “distorting my understanding to fit other people’s desires was dangerous” and that “for a scientist, the most important trait is intellectual honesty within himself.”

The story of Dr. Prusiner, who eventually was awarded with a well-deserved Nobel Prize in 1997 is instructive and inspirational. It is instructive in that it concretizes how a dogged pursuit of the truth no matter where it led and what scientific dogma it ran contrary to led to an unprecedented breakthrough that caused textbooks to be rewritten. It is inspirational in that it shows how such determination, integrity, and productivity are virtues and lead to the achievement of values.

The best treat of this book is the ability to hear directly from a genius exquisitely conscious of the intellectual process that he exemplified. His description of the Nobel Prize as “a celebration of civilization, of mankind, and of what makes human unique—that is, their intellect, from which springs creativity” perfectly captures how I evaluate this book thatI recommend in the highest possible terms.

Prions, not Zombies, are the Real Brain Eaters

Of all the etiologies of infectious diseases, one of the coolest has to be the prion. Prions are the smallest infectious agents and broke all the paradigm when they were definitively linked to diseases. It was almost heresy to postulate that a proteinaceous infectious particle--devoid of nucleic acid--could cause disease. But today's heresy is tomorrow's Nobel Prize, as Carleton Gajdusek and  Stanley Prusiner showed.

Prions cause disease in a unique way. Though they are definitely transmissible prion diseases they are, in essence, misfolded proteins that cause a cascade of protein misfolding leading to neurologic dysfunction. In some instances, the initial misfolding is the result of a sporadic genetic mutation and in others it is because of introduction of a misfolded protein causing the cascade. It is an impressive process.

Eventually prions, first linked to scrapie in sheep, were linked to human diseases known as the Creutzfeldt-Jakob Diseases (CJD), the most famous of which is new variant CJD (vCJD)--the human form of mad cow disease--as well as the human cannibalism-linked kuru. The story of vCJD is well documented. In short it has to do with changes in industrial farming practices allowing scrapie in sheep to get into cows and then into humans. The human outbreak, which captured headlines in the 1990s, is essentially over as farming practices have changed so as to eliminate exposure to the prion. 

Prions may have slipped from the headlines but research on them continued nonetheless and this week it was announced that a novel prion (alpha-synuclein) was linked to another neurologic disease: Multiple System Atrophy (MSA). Not surprisingly, this discovery came from Dr. Prusiner's lab. 

The biggest implication of this finding is further evidence supporting the hypothesis that other neurodegenerative diseases may have a prion component to their cause. Such an understanding may open up new avenues for treatment and screening for these dreaded diseases.