Examination of Witnesses (Questions 1-19)
26 MAY 2004
PROFESSOR DOUG
YOUNG, MR
ALICK SIMMONS
AND DR
CHRIS CHEESEMAN
Chairman: Can I welcome to the Committee
Professor Doug Young, Fleming Professor of Medical Microbiology
at Imperial College of Medicine, and Defra's bovine TB vaccine
adviser. He is accompanied by Mr Alick Simmons, Head of the Veterinary
Endemic and Zoonoses Division, Department for Environment, Food
and Rural Affairs, and Dr Chris Cheeseman, the Team Leader, Woodchester
Park badger establishment, Central Science Laboratory. The reason
we are here today is because I think we feel, probably like everybody
else connected with bovine TB, a deep sense of frustration that
we still seem to be no nearer cracking this problem of having
a strategy that will deal with the spread of TB and against a
background where farmers in those areas where TB is effectively
rampant are deeply troubled and frightened and those who are bordering
on areas where currently TB has yet to spread are also very frightened
indeed about the consequences to their businesses and lots has
been done but nothing has actually seemingly delivered a solution.
One of the main things that we would be grateful if you as experts
in the field would concentrate on in responding to the questions
that we will ask is to update us on some of the latest work that
has been going on and try to help us forward on the agenda that
says if Krebs et al is Plan A and it does not work, what
is going to be Plan B? I would like to start our questioning this
afternoon by inviting Diana Organ to make some comments about
Somerset.
Q1 Diana Organ: The map of bovine TB
incidence in Great Britain in 1997 and again in 2002 is deeply
depressing in that there has been huge growth in the incidence
of the disease. One thing that I noted from the map is that there
seems to be something happening in Somerset. It has a grassland
economy and has dairy and beef cattle in quite substantial numbers.
Whereas in my area, in Gloucestershire, it is getting worse and
worse and worse, there seems to be something positive occurring
in Somerset. Has anybody looked at what is happening in Somerset?
Have there been studies about the husbandry there or about the
badger population there, something that might give us a clue to
help with our policy?
Mr Simmons: Mr Chairman, perhaps
it might be better if I started off here. I happen to live in
Somerset and my previous post was Divisional Veterinary Manager
for Somerset and Dorset, so I happen to know the area quite well.
As Mrs Organ says, there is foci of infection in West Somerset
and also a patch along the edge of the Mendips where it borders
with what used to be the county of Avon and there is also a small
patch of disease along the Polden Hills, but as I am sure you
know from the geography of Somerset, there are large tracts of
Somerset which have got very low lying areas as well. Whilst I
could not be certain about this, I believe one of the reasons
for it is that the type of agricultural system and the habitat
for wildlife on the Somerset Levels and Moors is very different
from the areas I have just mentioned and also very different from
most of Gloucestershire where the habitat for badgers and the
type of grazing for cattle is very different.
Q2 Diana Organ: So it is a geographic
reason; it is to do with the badger habitat rather than the practices
of the dairy or beef farmers. That is why we do not have incidence
of TB so prolifically there as we have in other parts of the West
Country?
Dr Cheeseman: In terms of badger
habitat the Somerset Levels is not very good habitat. There are
badgers there but it is not prime habitat, so I would expect the
badger density in that part of the world to be lower than it is
on the Quantocks or the Mendips and certainly it is a lot lower
than it is in the Cotswolds. My colleague is right about the farming
practice, there is a different type of farming on the Levels and
it is a fairly unique system in a way. I would guess that there
are a lot of variables which are different in that part of the
world. One of the things that intrigues us about this problem
is that there are some parts of the country where the disease
is notably absent in both badgers and cattle and there are some
parts of the country where the disease seems to be absent in badgers
although it is present in cattle and there are anomalies like
this which give us hope for understanding it better. We do not
fully understand why this is the case at the moment, but if we
could get to the bottom of that we may be nearer a solution.
Q3 Diana Organ: You said there are some
places where there is incidence of the disease in cattle but not
in the badger. Could you tell me where that might be?
Dr Cheeseman: I cannot specifically
tell you.
Q4 Diana Organ: I wonder if we could
have a note about that because that is quite interesting. We have
got the disease exhibiting in cattle and we have to look at why
it is being transmitted to cattle and how, but it is not in the
natural wildlife of the badgers.
Dr Cheeseman: That is true. Historically
Somerset was a county where the prevalence of disease in badgers
has been extremely low. I think that picture has changed in the
last few years in that on the edges of Exmoor there is now a disease
problem in both badgers and cattle where there was not perhaps
10 or 15 years ago. There is something different there and it
could be a genetic immunity in the badgers possibly. There are
a number of possible reasons that we simply do not know.
Chairman: If you look at the Sanger Institute
website, when they were doing their work on genomics in this area
I was pulled up somewhat short where they said, "It is more
likely that man gave Tuberculosis to cattle", so it is in
fact all down to us. I hope nobody is suggesting that we get culled
in this particular operation.
Q5 Mr Drew: Given all the negatives that
we started with in regard to this particular issue, can you give
us some positive news? You have to advise the Minister and he
is sat behind you and he will be listening. Can you give us some
positive news on what has been learned that can begin to help
us deal with the key issues of transmission and eventually causation
and can help us move forward? It may be that each one of you will
want to say a bit about your area. I think we want to move away—that
is the whole point of today—from some of the stereotypical
positions that people traditionally take up on these areas.
Dr Cheeseman: I will try and start
to answer that question with a little bit of positive news. I
have talked to this Committee before about husbandry and the fact
that I feel that the farming industry perhaps could do more to
reduce the risks. We published a study very recently where we
found that badgers do indeed frequent farm buildings to find food
and, not surprisingly, it is more often in dry weather when their
natural food supplies are not available. The most recent work
has demonstrated that the frequency of visits by badgers to buildings
and cattle feed supplies is much greater than we ever really thought.
These are high risk situations around the farms and it is often
fairly simple to prevent badgers gaining access to these places.
I would say there is a little glimmer of hope in that we might
persuade the industry, although I am not quite sure how, that
it certainly needs to be taken much more seriously by farmers.
Some farmers are good on their bio-security and husbandry but
others are not, you see plenty of scruffy farms around. There
is a lot that could be done to reduce the risk of badgers getting
into these buildings and gaining access to the cattle feed and
leaving their excretory products there, which are an extremely
high risk to the cattle. I would say there is a glimmer of hope
on improvements in farm husbandry that could contribute to a reduction
in the risk.
Q6 Chairman: You have not got any hard
and fast evidence to say that given the state of bovine TB you
can expect an X% reduction if you followed your line of thinking.
Dr Cheeseman: That is perfectly
true, Chairman, and I will put my hands up and admit that is a
weakness. A lot of the advice that we give the farmers is really
down to common sense. Certainly, if I was a farmer I would shut
doors and I would keep feed stores closed to wildlife because
it makes sense. I cannot say to a farmer that if he takes these
measures he will reduce his risks by 50%. You can understand that
to do that we would have to mount a trial along the lines of the
culling trial to establish what the actual risks are and by how
much we might expect to reduce them. To get that information would
be another huge trial. What we are doing at the moment is basing
our advice on our scientific studies of badger behaviour. We have
mounting evidence that this is a serious problem and it really
does need to be taken much more seriously by the industry.
Q7 Mr Drew: I would just like to hear
from the other two participants about what they could give us
as positive news that could move us in a direction that we might
want to go.
Professor Young: At the time of
the Krebs Report Plan B was a vaccine and people have been working
very hard in laboratories on vaccines. Vaccines for TB have proven
extremely difficult. We do not have a good vaccine for the human
disease. It is very challenging. It is right at the edge of our
scientific understanding to work out how to make a vaccine. What
progress there has been we can split into two: we can think of
vaccines in badgers and we can think of vaccines in cattle. In
badgers what has been shown recently in the Republic of Ireland
is that the BCG vaccine, which is the vaccine that we use in humans,
has a protective effect against TB challenge in badgers in captivity
and that is positive progress. To know whether that is really
going to be a useful weapon in controlling the spread of TB in
badgers is several steps down the road, but we are on a forward
projectary with that. On the other side would be cattle. In the
past we have tried BCG vaccination in cattle and that has not
been sufficient to control the disease. There is a glimmer of
interest at what has generally been tried, which is BCG in fully
grown cattle and there is some evidence that perhaps if we use
BCG in neonatal cattle, so cattle in the first few days of life,
which is the way that we use it predominantly for humans, there
might be some use of BCG as a cattle vaccine. People have been
working very hard to make new improved vaccines both in human
and against animal TB and again in the laboratory and in experimental
situations we do have vaccination protocols which are better than
BCG now. These generally involve BCG with something on top of
that in addition, but again the story stops there. At the moment
it is like the badgers, inside our experimental systems we are
saying we are making progress, we can see something that means
we might be moving in a forward direction, but we need to try
those in field settings and see whether they really have got a
significant impact on the real disease situation. For both of
them I can say that things have been positive in the lab at the
experiment level. We are now at the stage of trying these out
in the real world.
Q8 Mr Wiggin: I am very curious about
this because I think you said BCG in adult cattle was not effective.
Professor Young: There has been
a series of trials and, a little bit like the human trials, in
some of them it has looked reasonably effective, we have maybe
got a 60 or 70% reduction in disease, but in other ones it has
been completely ineffective.
Q9 Mr Wiggin: Does that mean that you
take the adult cow, you vaccinate it and then it still develops
the disease?
Professor Young: You would then
look again a year or so later. So you would vaccinate half your
cows and not the other half and then you count who gets the disease
over the next couple of years and they still got diseased.
Q10 Mr Wiggin: Obviously cattle all have
passports now. The potential to track cattle, particularly ones
that are not for export—and I think that is the area where
we are vulnerable—is much easier now than it has been before.
What I was wondering is two-fold. First of all, if you are a farmer
who is worried how can you get your herd into a trial? Potentially
the protocols, BCG plus, may well be the solutions that they need.
How can I get my cow in there? Secondly, what sort of financial
advantage is there to any company developing these vaccines to
make sure that we can buy them over the counter, or will be able
to support them financially? Finally, what support would you expect
from the Government?
Professor Young: I will start
with the first one which was your idea of farmer Smith who wants
to get his cattle into a trial. Really in the short term I do
not think farmer Smith is going to be involved. Those previous
trials on BCG have been mainly carried out in places where you
do not have a test and slaughter policy. Although it looks very
bad to us in terms of the amount of bovine TB we have got in this
country, the actual number of cattle coming down with disease
is pretty small when you are thinking about doing a clinical trial
to see whether that vaccine is going to work or not. One of the
problems about moving these forward into any kind of trial is
to find a situation where we have a high enough incidence that
within a reasonably short period of time, with a manageable number
of animals, we would really be able to see whether the vaccine
works or not. One of the issues that we are wrestling with at
the moment is how we can move it forward realistically to find
out whether these vaccines are working in a real life situation
and it is going to have to be some kind of focused situation where
you either accumulate reactor cattle in one place or you go to
some part of the world where you do not have a test and slaughter
policy, but there are difficulties in doing that trial.
Q11 Chairman: Can you just explain to
me as a humble observer the scene? You said a moment ago that
to crack TB in people was very difficult, it was right at the
limits of our science. Searching for this vaccine is a bit like
looking for the Holy Grail. People have been talking about it
just over the horizon for as long as I can remember this problem
being here. Why is it so difficult? Is it that you do not know
the science or you have not got enough money to crack the problem
or something else?
Professor Young: Robert Koch was
the person who discovered mycobacterial tuberculosis and the first
thing he did was to make a vaccine. So he discovered a vaccine
very quickly and that proved not to work. It is more than 100
years ago we have been failing to make vaccines. We have still
failed to make them in humans. The BCG vaccine we have used will
control certain forms of the disease in humans but it is not controlling
the real problem of TB in humans. It is the science of it we do
not understand, it is very complicated and this little bacterium
interacts with our immune system and it seems to understand our
immune system rather better than we do. We do not understand fully
the immune response. We cannot identify which particular part
of our immune system it is that would control this bacterium,
we still have not cracked that for humans or for cattle.
Q12 Chairman: Just take me forward a
little bit. You keep saying it is too difficult, we might never
ever understand it. If we look at the genes sequencing exercise
that has been carried out and having read all this wonderful stuff
about it, it sounded as though you were beginning, as far as M.bovis
was concerned, to have some understanding of it. How far down
the track has this exercise taken us and how much further down
the track have we got to go?
Professor Young: You keep going
down until you have got 4,000 genes. One of these 4,000 might
be the magic bullet that we want to hit. Over the last five or
ten years, more in the context of human TB vaccine development,
people have tested literally hundreds of vaccine candidates based
on using these genetic tools. What we have done is tested on small
animals, on mice and guinea pigs, we have got various candidates
that work. What we have now moved to in the human field is very
much like the situation I explained in badgers and cattle where
we are now moving the best of those candidates into human clinical
trials and those are extremely expensive. The latest funding in
this area was $100 million from the Gates Foundation just to move
some of these candidates into human trials. We do not know if
they are going to work in humans.
Q13 Chairman: Let us hope heroically
that one of these is a winner. How long would it be before you
would be confident as a scientist to say "That's the one.
We can use it in cattle successfully"?
Professor Young: Your first clinical
trial to see whether your vaccine works or not is going to be
a period of two to three years just to give the animals time to
develop the disease. So for each run through of your test candidate
you are talking now about a three to five year time-frame by the
time you have done all of that. If the first one that I took was
brilliantly successful then in five years' time I would be telling
you "Okay, we now look like we can move this into larger
scale trials".
Q14 Chairman: How long from the largest
scale trial—
Professor Young: —before
you would have a commercially viable vaccine that you would be
making money with? You would need to think another five years
as you scaled up these things. So you are still talking ten years
as the optimistic scenario.
Mr Wiggin: Is there a market even?
Q15 Chairman: You talked about $100 million
from the Gates Foundation. What kind of sums of money are we talking
about to complete the process you have just described?
Professor Young: I do not know.
In humans we would talk about things like half a billion dollars,
that sort of amount would be realistic for making a vaccine candidate,
but the safety issues and testing are probably more expensive
in humans.
Q16 Chairman: You are telling us from
the scientific standpoint that we are looking at possibly up to
eight years from now and possibly half a billion dollars to get
to the stage where you might have a potential winner. So we are
looking at 2013 as a possible date, are we not?
Professor Young: Yes.
Q17 Paddy Tipping: This is in humans?
Professor Young: Yes. These are
the numbers that we use in the human field. I do not know whether
Defra could help me with any realistic numbers for cattle.
Mr Simmons: The properties of
a vaccine for cattle I would venture to say would probably be
expected to be less rigorous than the properties for a human vaccine.
What we are looking for with a cattle vaccine is something that
reduces pathology or, if we are lucky, eliminates it and also
reduces transmission between cattle. A number of the vaccines
that are used and already licensed for veterinary medicine at
the moment do not have a desperately high efficacy but they still
work in a flock or a herd situation. I would also suggest that
the property of the vaccine will dictate the policy rather than
the other way round.
Q18 Mr Breed: Mr Simmons, in the information
that Diana referred to earlier it appears that in the south-west
in 1992 about 1.8% of the herds registered for testing reactors
were found and in 2002 this had gone up to 6%, so over three times
the number, during which time of course we have had the celebrated
trials and then we had the Godfray report followed by some changes
to the badger culling trial. Bearing in mind what has just been
said about the rising cost of compensation which is now reaching
astronomic sums, how much higher is it going to get before you
in Defra actually call it a day on trials and everything else
and actually start to tackle the major problem?
Mr Simmons: The strategy document
which we are consulting on at the moment sets out a variety of
ways forward and seeks views from a variety of stakeholders, and
we have been through a series of regional meetings where we have
been asking the very sort of questions you have just asked and
the intention is to try and reach some sort of consensus on a
way forward. We have done predictions which show that if the most
recent rate of increase was to continue then we would be in very
deep trouble indeed simply because the disease would be probably
in most cattle herds within the country, but I think that tends
to take no account of the biological factors, the geographical
factors and the husbandry factors that clearly do limit spread
in the same way that I was explaining how I feel that spread has
been limited within Somerset. We will reach a period when the
increase will tend to level out or even start to reverse and I
would say there is the faintest glimmer of that at the moment.
Q19 Mr Breed: On the map that we have
in front of us it would be easier to demonstrate those areas that
do not have it rather than those areas that do.[1]
Forgive my suspicious mind, but the figures stop in 2002. When
are we going to see 2003 figures bearing in mind we are in 2004?
Mr Simmons: The 2003 figures are
on the web but they are not mapped yet.
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