Re: How is the 'cow- madness disease' reproducing?

Hi Johannes,

You're right, the transmission of "mad cow disease", or BSE (bovine spongiform encephalopathy) is very mysterious. Here is some history so you can see how we came to know what we know.

BSE is just one of a large family of what are called TSEs (transmissible spongiform encephalopathies). The first of these to be discovered was scrapie, a disease of sheep. Pioneering medical research in Papua New Guinea then revealed that a local disease amongst cannibal tribes named kuru is also a TSE. It was shown that this disease was prevalent amongst those who prepared and ate the brains of their relatives. Similarly, BSE has come about through the use of rendered cattle carcasses as animal feed for other cattle. So we know that the infective agent resides in brain and nervous tissue and can be spread through ingestion.

For a long time, the nature of the agent was mysterious. As you say, it was shown not to be a virus or a bacterium some time ago. The strange thing is that it is resistant to many treatments that normally destroy biological molecules, such as extreme heat, acid or treatment with organic solvents. It is also resistant to UV radiation, which makes it unlikely that nucleic acids (DNA or RNA) are involved.

The key observation came from looking at brain tissue affected by TSEs. These contain "plaques", which are conglomerations of abnormal protein. Analysis of this protein shows that it is a protein normally found in brain and nervous tissue, called PrP (or prion protein), but it has adopted a different structure. So the hypothesis is that TSEs are caused by mutations in PrP that alter its structure. It is then believed that the altered PrP can cause normal PrP to change to the altered form when the two come into contact with each other. Furthermore, the altered structure of "infectious" PrP can make it resistant to the treatments described above-heat, acids, organic solvents. The passage of infective PrP through various tissues in the body to the nervous system has been observed. Also, mice which lack the normal PrP protein cannot be infected with infective PrP. This is good evidence that the normal PrP presents a target for infective PrP. It's also rather intriguing, as these mutant mice appear quite normal, so PrP appears to be non-essential.

However, this is not the whole story. The prion hypothesis has been championed by Stanley Prusiner, but there are those who disagree. For one thing, no-one has been able to observe the transformation of normal PrP to infective PrP by adding the infective PrP to normal PrP in a test tube. For another, the hypothetical structure of infective PrP is unknown. There are people who believe that the infective agent may not be PrP, but something like a viroid-a very small nucleic acid particle that may be difficult to detect. So the argument is far from over!

I recommend a couple of really good resources if you want to know more about this. The first is the book "Deadly Feasts" by Richard Rhodes, which is an excellent summary of the history of TSE research and all the controversies. The second is the Official Mad Cow Disease HomePage. This has all the latest news and research about BSE and other TSEs.

Neil Saunders