The history of prion disease

Where does the story start?

With sheep, and then with a village. Scrapie, a disease of sheep, had been recognised for centuries. The human illness that came to be called Creutzfeldt-Jakob disease was described in the 1920s, in patients who declined and died within a few months of the first symptoms, and for decades afterwards it remained very rare and little studied. Cases in families were noticed early, without anyone being able to explain them.

What changed the picture?

Kuru. From the early 1950s Australian patrol officers in the eastern highlands of Papua New Guinea reported an unexplained fatal brain illness among the Fore people. Arthur Carey asked for a medical diagnosis in 1951, John McArthur described it in 1953, and the first medical publications came from Carleton Gajdusek and Vincent Zigas in 1957. The disease had spread through the region over the preceding decades and was tied to funeral practices in which the dead were eaten, which had largely stopped in the north by the 1950s.

In July 1959 Gajdusek received a letter from William Hadlow pointing out how closely kuru resembled scrapie in sheep, with the implication that it might be transmissible in a laboratory. Neuropathological study of kuru brains was published the same year. By 1965 inoculation experiments in chimpanzees had produced neurological disease. Gajdusek was awarded a Nobel Prize in 1976, and CJD was shown to be transmissible in the laboratory in the years around then.

The practical point from kuru is how long these illnesses can stay silent. Two brothers from one village developed kuru 21 and 27 years after they could have been exposed. Kuru has the fuller account.

When did anyone work out what the agent was?

Through the 1970s and 1980s. The agent did not behave like a virus or a bacterium, and the explanation that held up was that a protein itself, folded into the wrong shape, was the infectious material. Stanley Prusiner received a Nobel Prize in 1997 for the work on prions. What is a prion explains the idea in plain terms.

The gene came next. Once PRNP, the gene for prion protein, was identified, the inherited forms could be explained and named: familial CJD, Gerstmann-Straussler-Scheinker disease and fatal familial insomnia.

What about mad cow disease?

Bovine spongiform encephalopathy was first identified in cattle in the mid 1980s and caused a large UK outbreak in the late 1980s and 1990s affecting millions of cattle, after cattle had been fed meat and bone meal from other cattle. The first North American case was reported in 1993 in a cow imported into Canada from the UK. Chronic wasting disease in deer and elk had been recognised in Colorado in the late 1960s.

Variant CJD, the human disease linked to eating beef from cattle with BSE, was first reported in the UK in 1996. In total 233 people worldwide have been reported with it since then, and it affects a much younger age group than classic CJD, with an average age of 28 against 68. Variant CJD covers it, and how common is prion disease has the current numbers.

What came out of all this?

Surveillance, and the diagnostic tests in use today. Countries set up national CJD surveillance after the BSE years, which is the reason reasonably reliable case numbers exist at all for such a rare group of diseases. Most research effort now sits on the inherited forms, where treatment might be given before symptoms begin.

Nothing on this page describes a particular person. Questions about a diagnosis or about a family history belong with a neurologist and a genetic counsellor.