Professor Roy Anderson is an epidemiologist at Imperial College School of Medicine, and an expert on the vCJD epidemic.

Could you explain the different kinds of CJD and what causes them?
The groups of agents which CJD belongs to are called the TSE, transmissible spongiform encephalopathies. These are very severe diseases which are almost a challenge to one of the central dogmas in biological science, which is that a living organism (an agent) has its informational coding, which is its genetic code, in one or other of 2 molecules called DNA or RNA. The TSE are diseases caused by an agent called a prion protein which is essentially a replicating protein and it has no informational coding molecules such as DNA or RNA. So it's an extremely unusual infectious agent, almost invariably fatal as far as we know.

There are quite a number of these TSE: there are agents which cause disease in animals, such as cows with BSE; elk in North America with a wasting syndrome disease; and a thing called scrapie which is in sheep flocks. Then the human ones are various: there is a thing called kuru, which occurred only in Papua New Guinea in one small tribal grouping and there is CJD, classical CJD, which occurs in the elderly. The new form that we're very concerned with at the moment is vCJD, which is very tightly, or closely related to the BSE agent.

So it's a broad class of lethal diseases, typically very rare in the world's population, and their primary pathology is to create a spongiform appearance in the brain and essentially the destruction of the brain and motorneuron function. Mortality is virtually inevitable in the current state of therapies and diagnostic methods.

What is the story of vCJD in Britain?
BSE, or Mad Cow Disease, is one of the class of these TSE. So the concern when Mad Cow Disease first arose in the cattle herd in GB was that this infectious agent might transmit from some animal product into humans. The government body SEAC (Spongiform Encephalopathy Advisory Committee) detected some cases of a disease called CJD in people much, much younger than was typical, in the age range of 15 -35 and a suspicion arose that they may indeed have been the transmission of mad cow disease to humans. Subsequently a variety of scientific approaches strengthened that hypothesis in the spring of 1996 the then Minister of Health Stephen Dorrell made an announcement to the House of Commons that these new cases of vCJD were probably associated with exposure to the Mad Cow Disease agent, the bovine songiform encephalopathy. That was the beginning of the story which then became in the public and government's attention.

Could you describe the experimental work that has suggested BSE and vCJD are the same thing?
The scientific evidence that BSE is the causative agent of vCJD in humans is diverse. First of all, there is the epidemiological inference that humans were exposed to a lot of this Mad Cow Disease agent, particularly prior to 1989. All these diseases have one characteristic which is a very long incubation period, which is the time from infection to when symptoms of disease appear. And therefore if you had a lot of exposure prior to 1989, you would expect quite a number of years before you detected the first cases in humans.

Then there's a more important body of evidence which is experimental science. Now, in an ideal world what you'd do to prove the hypothesis would be to give the agent to the host species in a controlled and defined way and then monitor what happened in the particular exposed host. Well, clearly you can't do that with humans, so you use a variety of other methods.

One of them is to use a primate model such a marmoset or a monkey, and either inject or feed the host species, experimental species, with the bovine agent and then monitor the behaviour of the infected group and the control group to see what disease emerges. Now, the trouble with that is that it requires a very long time period, so if you expose a marmoset or a primate, a monkey to the agent, you might have to wait 5-7 years before you see disease. So an alternative approach is to use mice, which have a much shorter life expectancy, and we know from a variety of scientific studies that some of these TSEs, such as scrapie, do actually as it were, establish in mice and cause a disease which is very similar to scrapie. And also you can nowadays use a particular method which is called transgenic biology, where you insert a gene into a mouse which mimics or is an exact copy of the human gene. So knowing that there's an abnormal prion protein, you can put the human prion gene into the mouse, expose the mouse to BSE agent and then look at the type of pathology or disease that develops.

And what transpired was that the major classifying approach to the disease to start with was on straight pathology, that was if you take a cross-section of the brain of the diseased animal, you look at the pattern of the spongiform appearance of the brain and each of the TSEs induces a slightly different pattern. Subsequently there are more advanced methods which are called immino chemistry, where you're staining to look for the presence of the abnormal protein, and that is the method that is very much in favour at the moment.

Do you believe the infectious agent in BSE/ vCJD is a viral or a protein-only agent?
There's been much discussion over many, many years about what the spongiform encephalopathies are. When I was a student they were referred to as the slow virus diseases because it was thought that the destruction was due to a virus which hadn't been detected at present and it took a very long time to cause this pathology. Stan Prousner in the US was the main scientist, along with a body of other scientists who pointed out that these abnormal proteins could in a classical experimental sense transmit disease. Yet there still persisted views that something else was involved - a virus, bacterium, some abnormal chemical or whatever.

Well, experimentation, increasingly refined over the years, has demonstrated that if you take an inoculating sort of quantity of an abnormal protein, you treat it in ways that would kill all known living organisms that are based on DNA or RNA, such as viruses and bacteria, treat it in a way you kill all of that, you're left with this extraordinarily resistant protein only and when you give that via the oral route, or indeed inject it directly into the brain, it causes the disease that we see in patients and indeed in animals.

What is the likely extent of a vCJD epidemic?
When first encouraged to take an interest into what the future might hold for the vCJD epidemic, my initial reaction was that this was really an impossible scientific problem because there were too many unknowns. But we adopted an approach where we took the early number of cases, which were very small, we looked at their age distribution, particularly they were distributed to younger people, we took what we knew about past exposure to the BSE epidemic, which you could call the risk function over time, and we simulated millions and millions of scenarios, changing the values of the unknowns, drawing them off a distribution in a big computer and then created a cloud of possibilities into the future. As expected, the range of possibilities is from a few hundred to over 100 000 cases and developing over a very, very long time period. If the incubation period is short in humans, say it was 8 years, then we may have seen the worst of the epidemic in the next few years. If it's much longer, it could even be 20-30 years, because one characteristic of these agent is when they cross species barriers the incubation period tends to lengthen, and this is cross from cows to humans. If it's much longer, say 20-30 years, then the epidemic could be very large.

Now, just recently an important hint - it's not hard evidence - has emerged to give us at least some minimum bound on the incubation period. This was a cluster of vCJD cases in Leicestershire, for which, given detailed investigations of when individuals were exposed to a common source of food from a set of butchers, the minimum bound on the incubation period may be somewhere in the region of say 12-15 years. Now, they may be the early incubators, so that says to me at this current point in time, although the evidence is weak, that the incubation period is likely to be quite long, and so that's not particularly good news at the moment.

What do you think the government has learnt from this experience?
There are good and bad things that have come out of this experience. The bad things are well documented - exposure of the human community to a very dangerous agent. The good things are perhaps less widely experienced. One of the most important, actually, is I think government has learnt the lesson that openness in scientific advice to the government is an important component. So scientific advisory committees are now encouraged to have public meetings, they are encouraged to have representatives who are not scientists, but are representing the public or consumer interests. Secondly, the government is more organised in the way it receives scientific advice, and it's also very conscious of the fact that absence of evidence of risk is not absence of risk, and that's really important.

Do you think a treatment for the diseases will be found?
Progress in research is always slow, particularly towards therapies, but there's been good progress recently on diagnostic methods and good progress in developing ideas of possible therapeutic lines of attack, in other words, thinking about ways that the agent causes the cascade of conversion of normal protein to abnormal - are there scientific ways of stopping that, or slowing it down? So I'm an optimist in the longer term that we will have some therapeutic options. They may not be cures, but they could be slowing progression to disease or alleviating symptoms. But, as always in science, it's going to be a long time and science is very unpredictable process, you can't say progress is linear in a particular direction, it goes in bumps and starts, depending on people, opportunities and odd ideas that emerge.

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