Examination of Witnesses (Questions 1-19)
DR PETER
NASH, MR
PETER SOUL
AND DR
MANDY BAILEY
WEDNESDAY 22 MAY 2002
Chairman
1. You will no doubt recall, as we all do vividly,
that day however many years ago it was when the Secretary of State
for Health stood up in the House of Commons and said that, in
looking for the cause of the new variant CJD, one could not rule
out that it had been transmitted by the consumption of meat from
animals which had been infected with BSE. In everything we have
learned since then, has that statement been reinforced, diluted,
or has it remained the same? What is now the perception, given
that many of the expectations for the spread of CJD appear not
to have been fulfilled? If you were giving advice to a minister
who had to make that statement now, what would the advice be?
(Dr Nash) I think there are two aspects
to that question. One is the link between BSE in cattle and CJD
in humans, and the second aspect of the question is the consumption
of beef as opposed to other modes of transmission. On the first
of those questions, I would say that, if anything, the evidence
is stronger now than it was then for a link between BSE in cattle
and vCJD in humans. It is true that the evidence is circumstantial,
but it is very strong, and it comes from three sources: first
of all, the different types of infective tissue from BSE and from
vCJD, when strain-typed in mice, give the same signature. Similarly,
when western-blotting or phenotyping of those tissues occurs,
again, the signature is the same. I think what is also interesting
is that when these methods are applied to other forms of CJD,
to sporadic CJD for example, in humans, or indeed when the methods
are applied to scrapie in sheep, they do not give this signature.
So this is quite powerful, albeit circumstantial evidence. Secondly,
experiments have been carried out mainly in other countries on
inoculating three types of monkeys with the material from BSE
in cattle, and they have gone down with TSEs. In the one species
where the brain was examined, it was reported to be extremely
similar to the brain pattern of vCJD. The third type of evidence
is the epidemiological evidence, that the countries which have
had vCJD cases, primarily the UK, Ireland and France, coincide
with the countries where BSE was recognised at an early stage,
or in the case of France as well, of course, where there were
imports of beef from the UK. The evidence is circumstantial, as
I said, but it is very strong. On the second aspect, of whether,
if there is a link, it is caused by the consumption of beef, we
are not necessarily the best Department to ask that question,
I have to say. I think there would be greater expertise and responsibility
within the Department of Health. All I would say is that it is
a plausible explanation that it is the consumption of beef, although
there may be other routes of transmission—medical routes,
for example—which, as I said, others would be expert in.
2. Let us come to BSE. I have been looking back
over the history, and I hope this summary is accurate. The Phillips
Inquiry concluded that BSE probably started spontaneously in a
cow and was spread by rendering. The alternative theory was that
BSE was in sheep but was masked by scrapie, and that a small percentage
of the prions in sheep are in fact BSE prions, and the scrapie
prions are killed by heat and the BSE prions are not. Then there
is a theory that the origin is in other animals, because things
like big cats can develop spongiform encephalopathies spontaneously.
Professor Ebringer argues forcibly that BSE is in fact caused
by auto-immune response to the common organism Acinetobacter and
is not transmissible to humans; that in fact, it resembles multiple
sclerosis in its characteristics. The latest research appears
to tell us that the maternal transmission we all thought we discovered
did not take place at all. One asks oneself why there are so few
cases of new variant CJD—perhaps the oral route is fairly
inefficient as opposed to inoculation to the brain—and with
the species barrier the doses are small. Have we the faintest
idea about the origin of BSE?
(Dr Bailey) Since the Phillips Inquiry, two independent
groups of scientists have looked at this. There has been the Horn
Report, which was published, which has considered the origin,
and then the EU Scientific Steering Committee has also looked
at the scientific evidence relating to the origin. I think the
bottom line is that we really do not absolutely certainly know
the cause, and there are several plausible hypotheses, some of
which, Chairman, you have mentioned yourself. There are some that
are less viable; for example, you mentioned the Ebringer one.
But I think a common agreement is the prion theory. Prions are
associated with the disease, and that is essential in the scientific
opinion, that prions are a part of the thing. One has to differentiate
between the spread of the disease, where again there is very good
agreement that meat and bonemeal was the vector for the disease,
and the origin itself, the first case. There is not absolute agreement
on that.
3. I think it is commonly agreed that meat and
bonemeal was the guilty party, but when you say there is not absolute
agreement on the origin of BSE, you are being more assertive than
perhaps the evidence permits. There just is no agreement. The
simple matter is we do not know.
(Dr Bailey) There is not agreement.
4. So we are in a situation where we are looking
at balance of probabilities in terms of the origin of the disease
in cattle itself, and we are looking at balance of probabilities
in terms of its transmission to humans as well. So we have two
uncertainties, each of which rests upon actuarially the most likely
probability. Is that an accurate assessment?
(Dr Bailey) I think so, yes.
Mr Jack
5. Just to follow up on that, when BSE first
came about and there was a relationship established with CJD—if
I might call it "old" CJD as opposed to the new variant—we
did not seem to be too worried, but then we did become worried
when the new variant arrived and there was the link we have just
discussed with human beings. Have you any idea what caused the
change to come about that we had a new variant of CJD, and given
that CJD seems to be able to change its nature, should we be worried
about that for the future?
(Dr Nash) I think the old, sporadic type of CJD occurs
all over the world, and occurs in older people and, as the name
says, seems to be sporadic; there is no known cause and it seems
to be an inevitable thing. When the new variant CJD came along,
in a sense, there was much greater concern about this because
of the fact that it seems to be linked, as I was saying earlier,
to BSE in cattle, and affects younger people.
6. What caused the old to become the new? Was
there something which changed old CJD into new? I was interested
to know whether that gave us any clue about the whole question
of these transmissible spongiform encephalopathies.
(Mr Soul) I just wanted to pick up on your point saying
that we were not very worried. We were worried, and that is illustrated
by the fact that major surveillance programmes were set up in
a number of different countries to look hard at CJD, and of course,
we found that a new variety of CJD had appeared, and in investigating
that it was quite clear that that was different from the old type
of CJD; it was genuinely a new phenomenon. That is where the link
was then made that the most likely cause of that was in fact a
connection with BSE in cattle. The old type did not change into
the new type; the new type was a genuinely new phenomenon.
Mr Lepper
7. From all that you have said so far, I imagine
that you feel that SEAC was right when it recorded in its minutes
of its meeting of 6 February this year the views of Dr Venters,
published in the British Medical Journal in October last year,
that the causal link between the BSE prion and new variant CJD
is open to question. I assume that you feel that SEAC was right
to be somewhat sceptical of Dr Venters' views.
(Dr Bailey) I think that SEAC were correct in being
somewhat sceptical. This item is really a matter for the Department
of Health though. This was a topic that SEAC considered in providing
advice for the Department of Health.
8. Is there any part of the Government's research
programme that is actually devoted to looking at other possibilities
than the link between the BSE prion and new variant CJD? Has research
got into a kind of rut, or are views such as Dr Venters'—and
there may be others who are questioning—receiving funding
to research?
(Dr Bailey) Yes, the Government has provided funding
in the past for alternative theories. For example, DEFRA, then
MAFF, did provide funding for Professor Ebringer for the auto-immune
theory. The Department has a policy of maintaining an open mind
and funding work in support of alternative theories and hypotheses,
provided that that work is scientifically sound and that it can
demonstrate by the scientific principles used the questions it
is seeking to address. It would be sent for external peer review
to validate those points, but nonetheless, the Department has
a policy of maintaining an open mind in these areas.
9. So we are not in danger of there being a
kind of established orthodoxy which we might come to regret at
a later date because we have overlooked other things?
(Dr Bailey) No, I do not think that is the case.
Chairman
10. You mentioned peer review. This is a new
disease, as you have said. The number of scientists who are experts
in it is presumably limited. One sometimes has the impression
that all the scientists who are working on it are grouped together
under the umbrella of something like SEAC, and it is really quite
difficult to find people who are both expert and independent,
able to bring that sort of peer review to bear. Can you reassure
us that SEAC has not become a closed shop, sharing a particular
view which is difficult to penetrate with alternative concepts?
(Dr Bailey) Again, following up on some of the comments
that were made in the Phillips Inquiry about consulting extensively
the scientific community and not just focusing on one or two individuals,
I think the Department has done this in recent years. If I may
turn again to the comment about the Horn review of the origin
of BSE, the members of that group were certainly not all people
who were TSE scientists. They did have people who had expertise
in other fields—geneticists at Cambridge and people who
had experience in other kinds of neurological disease. That is
one example. Certainly in terms of peer review of project proposals,
our policy again is to consult those individuals who have expertise
that is relevant, and this may not always be TSE expertise. For
example, it may be in the diagnostics area, people who have expertise
in different methodologies, scientific approaches to detecting
things, or people who have experience, for example, in the environmental
area or soil science. We are not just consulting people who have
TSE expertise.
Mr Mitchell
11. You are going to have to help us with the
science. Is it correct that there is a growing belief that there
is a period of susceptibility among young calves, and that BSE
is more likely to be acquired by young calves than by older cows?
(Dr Bailey) The epidemiological evidence, when we
have studied the incidence of individual cases in herds and the
numbers of cases in herds, is that younger animals are more susceptible.
The experimental work to directly test that has not been done,
but DEFRA is currently funding work on age susceptibility and
dose response in sheep, using both BSE and scrapie to challenge
the sheep. So we are actually testing the age susceptibility in
sheep.
12. So we cannot say yet conclusively that there
is a link between the age of a cow and susceptibility?
(Dr Bailey) It has not been shown directly experimentally.
As I said, the epidemiological evidence points in that direction.
13. What impact would it have on the methods
used to deal with the disease if such a link were proved?
(Dr Bailey) I am not sure that it would have any major
effect, given first of all that the disease itself takes a long
time to develop within the animal, and given that the controls
that we have in place provide consumer safety: the feed controls,
which should mean that they can no longer be recycled; the food
controls on meat and bonemeal; the over 30 months scheme—very
few animals throughout the course of the entire epidemic developed
the disease before 30 months—and the removal of specified
risk material. I am not sure that the controls themselves would
necessarily change in any way as a consequence of that.
(Mr Soul) Even if we were absolutely confident that
only calves below six months were susceptible, we could not then
afford to change the control programme because we know that the
risk of cross-contamination in the livestock feed industry is
so huge. If there was any infectivity present in feed for adult
animals, there is a very good chance that calves are going to
get access to that at some stage on some farms.
14. Research is now concentrating on this question
of whether there is a period of susceptibility. What research
has been done?
(Dr Bailey) As I indicated, the research is being
done with sheep actually, looking at different ages of challenge
and also looking at the dose with respect to the different ages.
The reason that we are doing the work primarily with sheep is
because in sheep we believe that, in terms of maintaining scrapie
within the flocks, sheep are exposed by vertical or lateral transmission,
and therefore it is quite important to define this in the case
of sheep.
15. We gather that DEFRA has no plans to undertake
new work on adult cattle. Why is that?
(Dr Bailey) In terms of the age susceptibility question
which you have just mentioned, we are doing work in sheep, and
I know that does not give you a direct answer in cattle, but it
will be very important to establish the principle. The second
reason is that to undertake such an experiment in cattle would
be very expensive and very time-consuming, because clearly you
would have to maintain the cattle for a large number of years,
five to seven years, and we would have to have large numbers of
cattle involved in the experiment in order to do it. Obviously,
resources are not unlimited and we have to consider relative priorities,
and our view is, because we are addressing the issue and doing
work with sheep, which is also answering other questions relevant
to our sheep programme, it is not the highest of our priorities
to do it in cattle.
16. So if you prove the susceptibility period
on sheep, it could also apply to cattle.
(Dr Bailey) It would give an indication. We cannot
make that absolute assumption, but it would give an indication.
17. Does that mean that it is not now possible
to exclude an unmodified scrapie agent as the agent responsible
for BSE?
(Dr Bailey) That was the conclusion of the Horn Committee,
which looked at the origin.
Paddy Tipping
18. You have been telling us helpfully about
age susceptibility and that there is evidence for this, but no
definitive proof. Could you extend the argument and say if there
is evidence on this, when we look at vCJD, is there any evidence
to suggest that that might be a factor there?
(Dr Bailey) Obviously, it is quite possible that it
also applies to new variant CJD, and the evidence is merely looking
at the age profiles of the cases which develop new variant CJD.
In the main, although there has been one case in an elderly man,
they have been young people.
19. So this is again survey work.
(Dr Bailey) Yes.
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