Transmissible infectious agents were expected to require DNA or RNA to store and propagate biological information.

By the middle of the twentieth century, DNA and RNA had become central to the understanding of heredity and viruses. Viruses carry genetic instructions in one of those molecules and use a host cell to make more copies. An infectious agent with no DNA or RNA of its own therefore seemed very difficult to explain.

Scrapie, a fatal brain disease of sheep and goats, did not behave like a familiar virus. Researchers could transmit the disease, yet repeated attempts to find a conventional viral genome failed.

In 1982, Stanley Prusiner proposed that the infectious agent was instead a protein. He called it a proteinaceous infectious particle, shortened to prion. The idea was controversial because proteins were not supposed to reproduce biological information by themselves.

The answer lies in shape rather than in a genetic sequence. A normal prion protein made by the host can fold into an abnormal form. That misfolded protein can then make normally folded copies of the same protein adopt the abnormal shape as well. The harmful form therefore spreads from protein to protein.

The host still has DNA encoding the normal prion protein. What the infectious prion lacks is a separate DNA or RNA genome of its own.