UK researchers have made a major advance in understanding how the brain protein involved in bovine spongiform encephalopathy (BSE) in cattle and Creutzfeldt-Jakob Disease (CJD) in humans causes so much damage, according to research published in Science magazine. This advance will help the European Parliament, which is next month due to debate a joint resolution from its Agriculture and Environment Committees, insisting that preventative health and consumer protection measures must be given priority in all measures to tackle BSE. The Council of Ministers is expected to reach a common position at its meeting on 14 June 1999. Prion diseases, such as BSE and scrapie in animals, and CJD in humans all involve conversion of a normal cell protein, known as the prion protein or PrP, into an abnormal or rogue form. This rogue PrP is thought to be the infectious "prion" which causes these diseases. It replicates by converting normal PrP into more rogue PrP, setting off a chain reaction which leads to its progressive accumulation and brain damage. The difference between the normal and rogue forms of PrP is known to relate to their shape. Until now, just how the conversion from normal to abnormal PrP takes place has remained a mystery. Now researchers have managed to capture this remarkable and unprecedented change in a test tube, as explained by Professor John Collinge, Imperial College School of Medicine and Director of the Medical Research Council Prion Unit, who led the research team: "There are two major building blocks from which proteins are constructed, known as alpha helices and beta sheets. Normal PrP is nearly all alpha structure, while the rogue form is largely beta. Using a genetically-engineered form of normal soluble prion protein, we have managed to capture, for the first time, the moment when the change occurs. "We now know that the conversion involves breaking a single bond in the molecule using conditions, which exist normally within cells. This remarkable property of prion protein is unprecedented, as no other protein has yet been shown to be able to exist in two such entirely unrelated shapes," continued Professor Collinge. In addition, this protein, when placed in concentrations of salt seen normally in the brain, forms clumped, aggregated material indistinguishable from the rogue form that accumulates in the brain in BSE and CJD. For the first time, this provides an explanation of how these prions replicate. This research, funded jointly by the Wellcome Trust, the world's largest medical research charity, and the Medical Research Council (MRC), represents a major advance in understanding the key events in prion disease. Armed with this new information, it should be possible to make antibodies which detect beta-PrP specifically, offering the opportunity of new diagnostic tests for prion disease in humans and animals. Knowing how the switch from normal to rogue occurs could help researchers develop new drugs. It may in the future be possible to use beta-PrP to develop new strategies for therapies and prevention of prion disease. "Understanding how to inter-convert the prion protein between its alpha and beta forms opens up new research directions to understand CJD and BSE," said Professor Collinge. "While this leads to the possibility of developing much better diagnostic tests, our eventual goal of an effective treatment for these devastating brain diseases still remains an enormous challenge." Professor Collinge was working in collaboration with Dr Tony Clarke of the University of Bristol and the MRC Prion Unit, Dr John Waltho at Sheffield University and Professor Helen Saibil at Birkbeck College.