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NCERT's Biological Classification chapter has a short paragraph on prions: infectious agents "consisting of abnormally folded protein", similar in size to viruses, which cause mad cow disease in cattle and Creutzfeldt-Jakob disease in humans (NCERT Class 11 Biology, Chapter 2). Every other infectious agent in your syllabus carries DNA or RNA. This post covers how Stanley Prusiner showed that this one does not, why other scientists pushed back, and the evidence that changed their minds.
Who is Stanley Prusiner?
His Nobel facts page records that he was born on 28 May 1942 in Des Moines, Iowa, and was at the University of California, San Francisco, when he won the prize. In his Nobel autobiography he says he studied chemistry at the University of Pennsylvania, stayed there for medical school, and spent three years at the US National Institutes of Health, where he learned "developing assays, purifying macromolecules, documenting a discovery by many approaches".
Where did the question come from?
In July 1972 he began a neurology residency at UCSF. Two months later he admitted a patient with progressive memory loss, and was surprised to learn she was dying of a "slow virus" infection called Creutzfeldt-Jakob disease (CJD). Scientists were not even sure a virus caused it. The Nobel press release adds that CJD, kuru and scrapie, a similar disease of sheep, were known to pass on through extracts of diseased brain, and that one theory said the agent lacked nucleic acid, which seemed impossible at the time.
He set up a laboratory to study scrapie in July 1974. The hardest part was measuring the agent at all. The press release explains that in mice each experiment meant waiting about 200 days for symptoms to appear, and that progress sped up when scrapie was moved to hamsters, which fall ill much sooner.
Worked example: why the assay mattered
Here is a rough illustration, not a record of his lab. If each step of a purification needs one infectivity test, and each test in mice takes about 200 days:
5 steps × 200 days = 1,000 days, or 1,000 ÷ 365 ≈ 2.7 years.
Cut the waiting time per test, and the whole project shrinks in proportion. That is why a faster animal model was a breakthrough in itself.
What did the 1982 paper show?
Prusiner's 1982 paper in Science gave "six lines of evidence including sensitivity to proteases" that the scrapie agent contained a protein required for infectivity. On the other side, "five procedures with more specificity for modifying nucleic acids failed to cause inactivation". Because these properties set it apart from viruses, plasmids and viroids, he proposed a new term, "prion", to denote "a small proteinaceous infectious particle which is resistant to inactivation by most procedures that modify nucleic acids".
His autobiography is frank about the reaction. "Virologists were generally incredulous and some investigators working on scrapie and CJD were irate." Around the same time, he writes, HHMI declined to renew his funding and UCSF at first decided not to promote him to tenure, a decision later reversed. He framed the name as a challenge: "Should such a nucleic acid be found, then the word prion would disappear!"
How did one protein cause disease?
The press release sets out the next steps. In 1984 his group and collaborators found that the gene for the prion protein is present in all animals tested, including humans. So the prion protein is one of the body's own proteins. The answer to the puzzle was shape: the protein, PrP, can fold into a normal form, PrPC, and a disease form, PrPSc. The disease form can convert normal protein into more of itself, a chain reaction. It also resists protein-digesting enzymes, solvents and temperatures above 100 °C.
Two more results sealed it. Mutations in the prion gene cause inherited forms of the disease, and mice given mutant genes fell ill. In 1992, mice with the prion gene knocked out were found to be completely resistant to infection, and became susceptible again when the gene was put back.
Common mistakes:
Calling prions viruses. They have no nucleic acid; that is the whole point.
Thinking the prion gene comes from outside. It is the host's own gene; the disease is a change in folding.
Mixing up prions and viroids. NCERT's viroid is free RNA with no protein coat. A prion is protein with no RNA.
Why did it win a Nobel Prize?
The 1997 prize went to Prusiner alone "for his discovery of Prions - a new biological principle of infection", according to the facts page. The press release notes that the scientific community "greeted this discovery with great skepticism".
What can a student take from his way of working?
Follow the result, not the expectation. He expected a small virus; the data kept showing protein and no nucleic acid.
Fix the bottleneck. A faster assay sped up every experiment after it.
Make your claim testable. The word prion invited anyone to disprove it.
If the difference between viruses, viroids and prions keeps slipping, the Fermi Concept Library has every concept in biology with its own lesson, so you can fix one gap and return to the chapter. Our guide to Biological Classification for NEET covers the rest of it.
Next step: make a three-column table of virus, viroid and prion, and write what each contains and one disease it causes.
