Dr Moira Bruce is a scientist at the neuropathogenesis unit in Edinburgh. Dr Bruce is an expert in the behaviour of the different strains of encephalopathies. She believes that there may be some kind of viral-type, information carrying agent involved in the disease transmission process, as well as prions.

Could you outline evidence that suggests vCJD is caused by BSE?
When vCJD was recognised there was a suspicion that it might be a transmission of BSE to humans because it was a new disease, it had very different neuropathology and clinical presentation to sporadic CJD. So we tested that by taking a piece of tissue from a vCJD patient and injecting it into mice. We'd previously shown that if you did the same with BSE it produces a very characteristic disease pattern in the mice, based on the length of time that the mice develop disease and the sorts of changes that you see in their brains. And when we did this with vCJD we found exactly the same pattern of disease in the mice as we'd seen with BSE.

Could you explain the prion hypothesis?
We know that in animals that are infected with TSEs (transmissible spongiform encephalopathies) we see accumulations of a modified host protein, PRP, particularly in the brain and sometimes also in the tissues of the immune system, which has changed its shape and aggregated into forms that are really very difficult to remove. The protein-only hypothesis suggests that when introduced into a new host this changed protein with its abnormal shape interacts with the normal protein from the new host and in some way converts it into the abnormal form. This newly converted PRP goes on to change more and more PRP molecules in the host and this causes an amplification of the abnormal form of the protein, which eventually causes disease.

What do you believe to be the problem with the prion-only hypothesis?
If the prion-only hypothesis were true, this would be a new form of infectious agent, quite unlike conventional viruses or bacteria or any other types of micro-organism. We know that there can be many different strains of TSE agent and we've established this over very many years from studies in mice. These strains produce very different types of disease in the mice when they're injected, particularly in terms of the amount of time it takes for the mice to develop the disease and the patterns of damage that you see in the brains of these mice. The conclusions of the studies is that TSE agents contain some form of information which specifies their strain characteristics: we've shown that this information can be retained when, for instance, these strains are passed through mice with different PRP types or even under some circumstances through different host species. Thus, for example, the BSE strain retained its characteristics after being passed through cattle, sheep, goats, cats and humans.

If these agents contain just abnormal PRP and have no other component, then the existence of different strains and the requirement for an informational component that specifies strains means that the protein itself has to carry that information. It's very difficult to envisage how it could do that. Those who support this hypothesis suggest that there are multiple different confirmations (shapes) of the abnormal protein which can be passed on faithfully to new PRP molecules. But this would involve a very faithful reproduction of that shape over very many cycles of reproduction and in that case there would have to be as many confirmations as there are different strains and we've identified 20 different TSE strains in rodents.

What do you believe the nature of the infectious agent to be?
For conventional viruses, where you also see strain variation, the nucleic acid of the virus determines this property. Many years ago Alan Dickinson put forward the vireno theory that suggested that the agent was a hybrid structure consisting of an infection-specific informational molecule, which might be a nucleic acid, which is very closely associated with and protected by a host component, which would be the host PRP. In my opinion the presence of a small nucleic acid within the agent structure should not at the moment be totally ruled out.

Isn't it a problem for the vireno hypothesis that there isn't immune reaction?
If there is a small nucleic acid involved in the agent structure it doesn't necessarily code for a protein and you would only expect to see an immune response if the nucleic acid was producing foreign protein which triggered a response. So I think it's still possible that there's a nucleic acid there, even though there's no immune response to any form of protein.

What are the implications of all this in terms of the disease?
I think there's very convincing evidence that vCJD is caused by the same strain as BSE, but we really don't know exactly what the infectious agents in this whole group of diseases consist of and I think a lot more work has to be done to establish the molecular nature of these agents.

Is the research being done going to lead to treatment?
These diseases are going to be very difficult to treat because they have a very long incubation period during which time infection is accumulating in tissues without any outward sign of infection. By the time symptoms appear there are very widespread degenerative changes in the brain. So it's very difficult to envisage how a treatment might work after a patient is showing symptoms. There are a number of treatments which do reduce susceptibility, but they're most effective around about the time of initial exposure.

What do you think we should learn from this episode?
I think the whole BSE episode and now vCJD has taught us that we have to take TSE seriously. I think for many years we were happy to tolerate scrapie in our sheep, but I think we've come to the stage where really we should make every effort to eradicate scrapie from our sheep flock.

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