The findings demonstrate that prions, a class of infectious proteins, can make copies of themselves without the presence of viral DNA or RNA, damage brain tissue, and cause neurological diseases.
The exact function of normal prion protein is unclear. In disease, the malformed protein accumulates in the brain causing dementia. A number of animal species may carry different genes encoding subtly different forms of prion protein, some of which make them more susceptible to developing disease. This can occur spontaneously, or, as in the case of BSE, as a result of being exposed to modified prions from an infected animal.
But reporting in the 30 July 2004 issue of Science (305. 673 - 676 (2004)), nobel laureate Stanley B. Prusiner, and colleagues at the University of California, San Francisco, and Heinrich-Heine Universitat in Germany demonstrate that they have produced a prion protein that can trigger the development of a neurological disorder in mice that is similar to "mad cow" disease.
For the study, Dr. Prusiner and his colleagues produced prion protein fragments in bacteria, folded them into larger protein structures called amyloid fibrils, and then injected them into the brains of susceptible mice.
The mice began exhibiting symptoms of disease in their central nervous systems between 380 and 660 days after they were given the synthetic prion proteins. The amyloid form of the prion protein, which is thought to cause prion disease, was also found in the brains of the diseased mice.
Researchers then administered brain extracts from these animals to another group of mice, which subsequently developed similar symptoms 90 to 150 days later. The disorder seems to be distinct from that caused by other known strains of prions, suggesting that the synthetic prion did not merely activate a pre-existing prion in these mice and that the synthesised prion protein itself is sufficient to make infectious and disease-causing prions.
"The finding represents a renaissance in prion biology," said Prusiner, who originally coined the term 'prion' and was the first to postulate the 'protein-only' hypothesis about infection. "For the first time, we can create prions in a test tube. We now have a tool for exploring the mechanism by which a protein can spontaneously fold into a shape that causes disease."
BSE, a transmissible, neurodegenerative, fatal brain disease of cattle, has been linked to the human disease variant Creutzfeldt-Jakob disease (vCJD). According to the World Health Organisation (WHO), from October 1996 to November 2002, 129 cases of vCJD were reported in the UK, six in France and one each in Canada, Ireland, Italy and the US.
In the early 1990s BSE - bovine spongiform encephalopathy - ravaged the UK beef industry with 37,000 clinical cases of BSE and about 60,000 of the highest risk animals entering the food supply, compared with less than one a year today. In late December 2003, the US identified a BSE infected cow in the state of Washington, leading to a ban from more than 20 countries on imports of US beef.
First identified in 1986, 180,000 cases of BSE have been diagnosed in the UK alone. Only four out of the 25 EU Member States have not yet declared any cases. A number of countries outside Europe have also found cases, making this a global disease. The impact of BSE on European society has been far reaching, with a devastating impact on vCJD patients and their families. Some 146 cases of probable and confirmed vCJD have been reported.
BSE has affected the entire beef food chain, from producer to consumer. Farmers have watched their animals slaughtered in their thousands and seen their livelihoods jeopardised. A European Association of Animal Production report has estimated the cost of BSE to the states of the 15 member EU at more than €90 billion. In addition, the BSE crisis has had a significant impact on public trust in government and governmental scientific advice.