Professor Peter Smith is the acting chair of the Spongiform Encephalopathy Advisory Committee (SEAC), based at the London School of Hygiene and Tropical Medicine.

What are the different kinds of encephalopathies?
There are a number of different forms of these diseases which affect different animal species. There's a disease called scrapie which affects sheep and has affected sheep for several hundred years. As far as we know we've been eating scrapie infected sheep without harm for all of that period.

There's a disease in humans called CJD which is essentially a disease of old people, a rare disease, affects about one in a million people. We don't know what causes the disease, it may just arise spontaneously through some mutation associated with ageing, but again it's been around for a long time. There are some genetic forms of the disease which are inherited in more or less a Mendelian fashion, which are associated with mutations of the prion protein gene, and that is transmitted within families. And there have been a small number of cases of CJD which have been transmitted through medical procedures, the largest number being through the use of contaminated human growth hormone.

The new diseases in this group are BSE, which was first recognised in the cattle population in 1986, and then variant CJD (vCJD), which we believe is caused by the BSE agent, which was recognised in the human population for the first time in 1995/6. The distinctive feature of vCJD as against CJD is that it affects, so far, predominantly young people.

What is the story of the link between the development of BSE and humans suffering from vCJD?
We don't know where the first case of BSE arose from. There are 2 theories: it could have either arisen spontaneously in a cow or it could have been the scrapie agent in sheep mutating in some way and becoming adapted to cows. That wouldn't have been a problem in itself, but at that time there was a practice of recycling waste parts of cattle and sheep - so-called rendering them - and feeding them back to sheep and cattle as a high protein supplement feed. And in that way an epidemic was propagated before we knew it was going on, because of the long incubation period. So by the time we saw the first case of BSE, in about 1986, there was quite a large epidemic of BSE in the cattle population, affecting probably around a million cattle. Not all of those animals developed BSE, only about 180 000 or so, the remaining number were killed before they showed any signs of BSE and were eaten by the human population. But consumption is the most plausible route for the BSE agent having got into the human population, which, again after an incubation period, manifested itself as this new disease, vCJD.

What evidence is there of the link between BSE and vCJD?
When vCJD was first recognised in the human population in 1996, the evidence actually directly linking it to BSE was circumstantial - although I think many people believed that this was likely to be due to BSE, the evidence for that was more that this was a new disease of the same form as BSE, a BSE-type disease in the human population. It was really in the following year that the evidence that they were caused by the same agent became much firmer, and that was through essentially strain typing studies, where the strain of the agent that was affecting cows was compared with the strain of the agent that was affecting people, and they were found to be identical. And that was really the clinching evidence that these two diseases were caused by agents which were indistinguishable and probably the same.

How do you respond to people who argue that BSE does not directly cause vCJD?
I think there are two questions that people have raised issues about. One is whether BSE was due to the recycling of waste parts of sheep and cattle back to sheep and cattle. The other is whether in fact this disease that we've seen in humans is anything to do with BSE - the alternative is that they've got some other common cause but they're not themselves directly related.

I think the evidence really doesn't support these interpretations. First of all, with respect to the BSE epidemic itself, there was a very sharp fall in the number of cases as soon as controls on feeding were put in place, so I think the evidence that feeding was the main cause of the BSE epidemic is fairly convincing. With regard to this new disease, vCJD, as to whether that's caused by BSE, again I think to my mind the evidence is pretty persuasive that these are caused by the same agent. It's true that we don't know the route by which the agent got into people - the most plausible route is it was through eating contaminated beef products, but we don't have conclusive proof as of yet. However, the biological agents are identical and the temporal sequence the vCJD epidemic following on about ten years later from the BSE epidemic is the sort of thing that we'd expect with this kind of disease.

All of that I think makes a pretty persuasive case that the main determinant of the BSE epidemic was the recycling of waste parts of cattle back to cattle, and the main determinant of the human epidemic is exposure in some way to the BSE agent from infected cattle.

Do we know the exact nature of the infectious agent involved in the diseases?
There is still debate about the nature of the infectious agent. When these were first postulated, unlike bacteria and viruses, it was supposed that these were an infectious agent without any nucleic acid and that sort of went against the tenets of basic biology. As time has gone on I think an increasing number of scientists have become persuaded that indeed this is a protein-only infectious agent, the prion protein, something which every individual produces.

We don't know what the purpose of that normal prion protein is, in fact in experimental studies people have produced mice without a prion protein gene and it doesn't seem to affect those mice very much. But when an abnormal form of the protein is introduced into somebody, it seems that this has a deforming effect on normal prion protein and transforms it into this abnormal form and there's a cascade effect which eventually leads to the build up of this abnormal form in the brain, which leads to disease and shortly thereafter to death. However, there are others who believe there must be some nucleic acid involved somewhere in the process, and that debate continues.

What is the likely scale of a vCJD epidemic?
When the disease was first recognised the first ten cases were reported we had really no idea just how large this epidemic was going to be. We knew that getting on for a million infected cattle had gone into the food chain, so there was the possibility that very large numbers of us had been exposed to this agent. The hope was that there was what is called a large species barrier between cattle and man, such that it would be very difficult for man to become infected with an agent coming directly from cattle. We don't know still exactly how large that species barrier is, and we don't know how large the epidemic is going to be. Since those initial ten cases there have now been a further 80 or so, so the current total is 99 cases. It could be that the eventual epidemic size will be just a few hundred cases, but it could be many thousands.

Our uncertainty is due to two things. One, we don't know what the length of the incubation period is in people, that is the period between infection and when disease occurs. If that's very long, then we could just be seeing the first few cases of what's going to be a very long epidemic. The other uncertainty we have is that we have no test for who's infected, unlike with the AIDS virus where at a very early stage of infection we can test somebody's blood, find out they're infected and they are likely to develop AIDS some time within 10-20 years or so. With this agent we can only really identify those infected either when or just before they develop disease, which restricts us greatly in being able to assess just how many of people in the population are affected.

What are the issues surrounding policy recommendations and taking precautions against transmitting disease?
A number of measures have had to be put in place on a precautionary basis in the face of really enormous uncertainty. For example, there is the worry that once this agent has entered the human population there is no longer a species barrier in terms of transmitting from person to person. So we now lucodeplete, that is, remove the white cells from blood, because of the possibility that there may be individuals who are donating blood who unknowingly are infected with the vCJD agent, and when their blood is transfused to somebody else, they will actually transmit the agent and that person will develop disease. Because we don't know how many people there are who are incubating the disease we just don't know what the magnitude of the problem is. We know it could be very large, or alternatively it could be quite small, and making public health decisions in the face of that enormous uncertainty really does pose many challenges.

How close are we to finding treatment or a cure for vCJD?
I think one has to be fairly pessimistic in the near future about a cure being developed. Firstly, there is a relatively small number of cases of the disease looked at in pharmaceutical company terms, so it's unlikely the pharmaceutical industry is going to invest a lot of research resources, which is where most of our new drug therapies come from, so any research on treatment is mostly being government sponsored.

Also, I think it's perhaps being over-optimistic to imagine that by the time the disease has developed and already quite a lot of damage has been done in the brain that really one's going to find an intervention, a treatment that's going to reverse that damage. I mean, hopefully that may come one day, but that does seem quite a long way off at the moment. Perhaps a bit more hope lies in being able to interfere with the process of the disease at an early stage. There are some animal experiments which have been done in which interventions have been made, giving a drug shortly after we know infection occurs. That has modified the course of that infection, has lengthened it, and that I think is an area where there will be continuing research and will perhaps result in some significant progress.

  < previous   Page 6 of 6

Content last updated: 17/07/2006

Comments