Science · Biology

Prions

1982 (named by Stanley Prusiner)

Biology — neurodegenerative disease

A prion is an infectious agent made of protein alone, with no genetic material — a misfolded form of a normal cellular protein that induces its healthy neighbours to misfold in turn, setting off a chain reaction that riddles the brain with holes. Stanley Prusiner coined the name in 1982 and won an unshared Nobel Prize in 1997 for the idea, which was fiercely resisted because it seemed to break the rule that infection requires a nucleic acid. Prion diseases include CJD, kuru, scrapie and BSE.

How to spot them

▸An infectious agent with no DNA or RNA at all
▸A normal brain protein misfolded into a shape that converts others
▸Causes spongiform encephalopathies — brains left full of microscopic holes
▸Kuru, scrapie, BSE, CJD and fatal familial insomnia
▸Survives boiling, formaldehyde, radiation and standard autoclaving

Key facts

Stanley Prusiner coined the name in 1982 from 'proteinaceous infectious particle' and won an unshared Nobel Prize in 1997 (1982)

The 1997 Nobel Prize in Physiology or Medicine; his theory had been ridiculed for a decade.

Kuru, the laughing death of the Fore people of Papua New Guinea, spread by funerary cannibalism

Carleton Gajdusek's work on it won a share of the 1976 Nobel Prize in Physiology or Medicine.

Scrapie, known in British sheep since the eighteenth century, whose victims rub themselves raw against fences

The archetype of this class of disease, and the source of the 'Sc' in PrP-Sc.

The agent behind 'mad cow disease' and the British beef crisis of the 1990s

BSE spread through meat-and-bone meal; its human form, variant CJD, has killed around 180 people in the UK.

The cause of fatal familial insomnia, in which sufferers progressively lose the ability to sleep and die within months

An inherited form, described in an Italian family; the subject of D. T. Max's book The Family That Couldn't Sleep.

An infectious agent containing no nucleic acid whatever, which appeared to break a central rule of biology

Its existence forced a rethink of what 'infectious' can mean.

Chronic wasting disease is its spreading epidemic in North American deer, elk and moose

Now found in wild and farmed cervids across much of the United States, Canada, South Korea and Scandinavia.

Key ideas

The normal protein, PrP-C, is a harmless cell-surface molecule; the rogue form, PrP-Sc, is rich in beta sheet, resists protein-digesting enzymes and acts as a template, recruiting normal molecules into its own conformation.
The same templated-misfolding mechanism is now thought to underlie the spread of amyloid-beta and tau in Alzheimer's and alpha-synuclein in Parkinson's, though these are not transmissible between people in ordinary life.

Quick-fire facts

•The name is a deliberate scrambling of 'proteinaceous infectious particle' — Prusiner said 'proin' sounded wrong.
•Stanley Prusiner's 1997 Nobel Prize in Physiology or Medicine was awarded to him alone.
•Diseases caused: Creutzfeldt–Jakob disease (sporadic, familial, iatrogenic and variant), Gerstmann–Sträussler–Scheinker syndrome, fatal familial insomnia and kuru in humans; scrapie, BSE and chronic wasting disease in animals.
•Sporadic CJD occurs worldwide at about one case per million people per year.
•Carleton Gajdusek shared the 1976 Nobel Prize with Baruch Blumberg for work on kuru and slow viruses.
•They resist standard sterilisation; surgical instruments must be autoclaved at 134°C with sodium hydroxide, or destroyed.
•Some Fore people carry a protective variant of the prion protein gene, an example of natural selection observed in living human populations.
•Yeast has its own harmless versions, such as [PSI+], which behave as protein-based heritable elements.
•Common misconception: they are not viruses and not alive by any usual definition — there is nothing to kill, only a shape to propagate.

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Sources

D. T. Max — The Family That Couldn't Sleep: A Medical Mystery
Stanley B. Prusiner — Novel Proteinaceous Infectious Particles Cause Scrapie (Science, 1982)
Richard Rhodes — Deadly Feasts: Tracking the Secrets of a Terrifying New Plague