1997 Nobel Prize in Physiology or Medicine
Reason for Award
for the discovery of Prions – a new biological principle of infection
Laureates
United States of America
Explanation
Our bodies are built from tiny parts called proteins. A protein works when it is folded into a precise shape, like a neat piece of origami. Sometimes a protein can fold the wrong way; when this misshapen protein bumps into normal ones it can teach them the bad folding, spreading the mistake. This troublesome particle is called a “prion.” When prions pile up in the brain they make it look like a sponge full of holes, causing disease in cows, sheep, and people. Dr. Stanley Prusiner showed that such diseases are not caused by bacteria or viruses but by the protein itself. Because of his work, medicines and foods are checked more carefully, giving us better protection for our health.
Related Keywords
Prion
A pathogen believed to consist solely of protein. It propagates by converting the normal protein PrP^C into the abnormal conformation PrP^Sc, creating a chain reaction. Because it lacks nucleic acids it challenged conventional biology. It is the causative agent of transmissible spongiform encephalopathies such as BSE and CJD, and is highly resistant to heat and proteases.
Transmissible Spongiform Encephalopathy (TSE)
A group of neurodegenerative diseases in which the brain develops sponge-like vacuoles. It includes scrapie, BSE, and Creutzfeldt–Jakob disease. They have long incubation periods, progress rapidly once symptoms appear, and are fatal. Pathology shows PrP^Sc accumulation, gliosis, and neuronal loss. No effective cure exists, so early diagnosis and infection control are critical.
Protein conformational change
Proteins adopt various folded states depending on sequence and environment. In prion disease the α-helix-rich PrP^C converts into β-sheet-rich PrP^Sc, effecting an amplification analogous to self-replication. Misfolding triggers amyloid fibril formation and compromises neuronal function.
Bovine Spongiform Encephalopathy (BSE)
A TSE occurring in cattle that caused a major outbreak in the 1990s, affecting food safety worldwide. Spread via contaminated feed and can cause variant CJD in humans. Based on prion theory, bans on meat-and-bone meal and screening tests were introduced internationally.
Protease resistance
PrP^Sc retains a 27–30 kDa C-terminal core even after digestion with proteinase K. This property allows detection of the abnormal form by Western blot and serves as a standard marker in diagnosis and research.
Species barrier
The phenomenon whereby prion transmission between different species is inefficient. Amino-acid differences in PrP and conformational compatibility create the barrier. BSE displays a relatively low species barrier, and cases of human infection have been reported.
RT-QuIC
Abbreviation for Real-Time Quaking-Induced Conversion. A highly sensitive diagnostic assay that uses trace PrP^Sc as a seed to convert recombinant PrP under shaking, with fluorescence readout. Enables in-vivo diagnosis from cerebrospinal fluid or skin samples.
Amyloid fibril
A fibrillar aggregate composed of stacked β-sheet layers. Formed by prions and Alzheimer’s Aβ, causing cellular toxicity and tissue damage. The cross-β architecture is confirmed by X-ray diffraction and cryo-electron microscopy.
Creutzfeldt–Jakob disease (CJD)
A human TSE with sporadic, genetic, iatrogenic, and variant (vCJD) subtypes. Characterized by rapidly progressive dementia, ataxia, and myoclonus, leading to death within months. Definitive diagnosis requires brain tissue; clinically RT-QuIC and MRI findings are used.
Protein-only hypothesis
The proposal that prion infectivity resides solely in the abnormal protein conformation without requiring nucleic acid. Named and advocated by Prusiner, supported by knockout mice and in-vitro amplification experiments. It added a new paradigm for biological information transfer.