Examination of Witnesses (Questions 260
- 279)
MONDAY 15 OCTOBER 2007
PROFESSOR DOUGLAS
YOUNG AND
PROFESSOR GLYN
HEWINSON
Q260 Mr Drew: That is now clear-cut,
you can determine that this animal is infected as against this
animal has been vaccinated?
Professor Hewinson: You can do
that. Real progress has been made from sequencing the genomes
of BCG which is the lead candidate vaccine and M. bovis.
What is less clear is whether you can differentiate between animals
that are vaccinated and are constantly exposed to infection compared
with animals which are infected. Those trials are ongoing at the
moment in a natural transmission experiment so we should know
the answer to that within the year. The other advance, I should
say, is that it has been shown that it is possible to improve
BCG in cattle so there are vaccines which are looking more effective
in experimental situations than BCG in cattle. That gives us hope.
Professor Young: I think another
way that is useful to bring in at this stage is when we say, "Do
you have a vaccine or do you not have a vaccine?" It is not
going to be a tool which gives 100%, this disease just disappears
so it is going to reduce the amount of disease the animal gets,
it will increase their resistance and then becomes more of a policy
issue how much reduction of disease makes it really worthwhile
as a control tool. I think that is quite important.
Q261 Mr Drew: Given the response
to James Gray earlier, you are on the more optimistic side of
the continuum. To what extent is it possible to predict that you
could in all but name eradicate bovine TB in the same way, as
I said that we have eradicated TB amongst the developed world
or is there always going to be some legacy bovine TB which we
have to learn to live with? It is one of those questions, "Are
you beating your wife" type of thing, but give us a hunch.
Professor Young: I would imagine
it should be easier to eliminate bovine TB than it is to eliminate
human TB. I would caution that although you think you have eliminated
human TB I would be cautious about that. I do not think it is
going to be a vaccine on its own, it will be a vaccine as part
of a combination of policies. The fact that you can take infected
animals and you can kill them is a hugely powerful tool compared
with humans.
Q262 Mr Drew: Sticking with cattle
for one last question, one of the things I have never quite understood
is that when you get a breakdown, unless it is a huge breakdown,
there are always cattle which do not succumb to bovine TB. They
often get slaughtered, or have been, because we take the decision
that it is easier to take the whole herd out or a significant
number. I realise that from policy terms that has begun to become
less of a way forward. To what extent have you thought about using
the natural resistance of some cattle as the way to which you
might be able to develop a vaccine. In other words, you have got
the BCG, you take an animal which has been in direct contact with
bovine TB which clearly has not over time succumbed to that TB,
so it must have some level of resistance, is this understood in
any way or is this something which has been studied or something
which is a missed opportunity?
Professor Young: It is quite difficult
to study, you are looking at the same animals—
Q263 Mr Drew: I understand you are
dealing with an animal, there may be ageing and it may subsequently
develop TB.
Professor Young: There is a certain
degree of random effects, it depends how many bacteria that particular
animal happened to breathe in. Where it is clearest to my mind
that there is a difference is when you look at very different
breeds of cattle. When we look at this project that we are doing
in Ethiopia, we are looking at cattle that come from very different
lineages, very different genetic backgrounds, and they do seem
to have a difference and we are very interested in that scientifically.
Q264 Mr Drew: You say you are very
interested in that, are you researching that? Are you looking
at how the vaccine may work with different species of cattle,
may work with cattle which has been directly impacted on by a
breakdown? Is this something which is going on?
Professor Young: This is something
which is going on in this case out in Ethiopia because we can
see it, it is a much more extreme situation there. With cattle
we can use modern and genetic tools to map it. We know the sequence
of the cattle genome and we are trying to then say, "Can
we associate those differences in susceptibility to differences
in the genetics of those animals".
Q265 Mr Drew: Does this fit with
what you said earlier, this is the idea of a vaccine almost plus
natural resistance as being the best way that we will fight bovine
TB? I am not saying is it 70:30 or 60:40, I am just saying if
you add the two things together—
Professor Young: That particular
tool of trying to breed your cattle to take out enhanced resistance
in the national herd is not something I am an expert on.
Q266 Mr Drew: That is what we are
doing with sheep after all, with scrapie. We are trying to breed
the national flock which is scrapie resistant and breed the scrapie
out.
Professor Young: If you can do
that without losing other traits about milk yield and other factors
about the cattle, that might be interesting. From my point of
view, I would see it more as a fundamental understanding of the
disease.
Professor Hewinson: Even in the
Ethiopian situation which we have been looking at, the animals
which seem to be more resistant, only produce one or two litres
of milk whereas even a sick Holstein Friesian produces 20 litres
of milk, so even though they are more resistant in terms of production
it would be very dangerous.
Q267 Mr Drew: Let me be clear on
this. Are you saying there is almost an economic argument about
the degree to which we might look at a different type of animal,
obviously an animal that is resistant to TB but would also be
boosted by a vaccination against TB, that might have adverse consequences
on its ability to produce as much milk?
Professor Hewinson: With any breeding
programme, if you are just breeding purely for resistance, you
stand the chance of breeding out other production phenotypes.
You have to take that into account, I think.
Q268 Mr Drew: If we can move on to
vaccines for badgers and, as I say, I have seen the badger vaccine
trial site. I am eternally grateful for being given permission
to go and have a word with the lady who is overseeing it there.
Again, the issue is, having got I think two years' results—tell
me if I am wrong but I think we have got something like two years
of results—to what extent can we now pressurise for earlier
answers to some of the key questions about, "Does the BCG
vaccine have any benefit in terms of the resistance it could give
badgers against succumbing to bovine TB?" You might also
want to add on what links you have got internationally, although
we are going to come on to that and I know this is not just a
national experiment. I will not go too far as we are going to
look at that in a bit more detail later. Professor Young?
Professor Young: The primary purpose
of the badger vaccine experiment was to get information about
the safety of BCG. If we are going to use BCG in badgers we need
to license it and to license it we would need to have clear data
that it was not going to make the disease worse in the wild badger
population. Also, the licensing authority would look at efficacy
data in an experimental setting. The primary read-out from the
badger vaccine trial is safety and we have very promising results
on that. Since we are doing a trial, we can try and get some indication
of efficacy at the same time. It is too early in the trial, we
did the first vaccination in—
Professor Hewinson: —2006.
Professor Young: We were supposed
to be trapping and revaccinating at the present time but we have
been put on hold, as you know, because foot and mouth closed down
the batch where we would have picked up some data in revaccinating.
We will not get it this year.
Q269 Mr Drew: You are saying at the
moment that you are not able to vaccinate.
Professor Young: Because of foot
and mouth we have not been able to trap this season and that puts
us back. June is our next time.
Q270 Mr Drew: I think we will be
writing to the powers that be to say, "Are there special
exemptions which could be allowed" because one of the problems
with bovine TB is that we lost out in terms of the original ISG
trials because we were affected by foot and mouth then and I think
we are not happy that we are going to see slippage again. Everyone
will say it is a good thing, so I think we have made advances.
Professor Young: That is my understanding,
that the trapping has been cancelled this season.
Professor Hewinson: Also that
was in sensitivity to the landowners wishes who did not want workers
going on to their land while the foot and mouth was an issue.
Mr Drew: I understand that. I understand
we have to have special clearance. Some would argue that foot
and mouth is sadly affecting rather a small area, bovine TB affects
rather a large number even though economically both are, sadly,
very dangerous to the livestock.
Mr Gray: They are different areas, Chairman.
Q271 Mr Drew: As I say, completely
different areas. We are going to look at the international work
in a minute but the parallels with what was learned from Ireland,
is that something which has been integral to the work that the
badger vaccine trial site has been doing, presumably drawn on
that experience, although there are those who criticise the way
the science was conducted?
Professor Hewinson: Do you mean
in terms of what Ireland have been doing on vaccinations?
Q272 Mr Drew: Yes, the work they
have been doing on vaccinations but also, of course, in the sense
that came on the back of their attempting to look at the culling
strategy, so I will be interested to know to what extent the science
is helpful rather than being very different.
Professor Hewinson: In terms of
the vaccine development, we have been working very closely with
the Republic of Ireland in terms of badger vaccine work, indeed
we have had workers working in their laboratories and their workers
have come over to ours. Essentially we have developed the immunology
for badgers which the Irish are using to look at the vaccination
of badgers with the BCG. In Ireland they are allowed to experimentally
infect badgers with Mycobacterium bovis, they have now developed
those infection models which allows you to look at how well BCG
protects badgers. They have shown that both injectable BCG and
oral BCG, given in a formulation that has been developed by New
Zealand—and I am sure we will come back to talk about that
later—gives good protection against experimental challenge.
Where we differ is that we are pursuing an injectable vaccine
as the first phase of our vaccine strategy because that is the
quickest to license and will be the quickest way to get vaccination
out into the field. Ireland are looking at oral vaccination, they
are planning an oral vaccine trial now, but that formulation is
not manufactured by any manufacturer so it is not made to good
laboratory practice. Even if the product looks promising they
will have to do another trial based on the safety type approach
that we have been doing with injectable vaccines.
Q273 Mr Drew: Can I ask one final
question. Given the importance of the work at the badger vaccine
trial site, because we all know that a cattle vaccine has got
some downsides, not the least of which is whether we can retain
our TB-free status as a nation within the EU, why has this not
been replicated in other parts of the country? It would be useful
perhaps to do some comparisons. Here we are, again, trying to
pursue the whole of a hunch in one part of the country which may
have quirky badgers, let alone quirky results from that experimentation,
is that not a weakness of this? If someone was to come and say,
"Here are two more areas" you would bite their hands
off, would you not?
Professor Young: We would go and
do it. There was a lot of uncertainty about going forward with
a badger vaccine in the first place, so if you go back a few years
we had the Krebs Report which saw badger vaccination as a second-best
strategy. If you cull the badgers that gets rid of them 100%,
if you vaccinate them you may just reduce the amount of disease.
For a long time it was not our mainstream policy. Since the ISG
proved that badgers were contributing to the bovine TB problem
and showed that culling has downsides then I think we have ramped
up the badger vaccine programme significantly. That we should
be ramping it up more, which is what you are suggesting, would
be something we can take on board. I think within a year, we have
said in the document by 2010, we would hope we would have a licensed
vaccine but I think a year from the badger vaccine trial we will
begin to get a feeling for are we moving in a positive direction.
If we are moving in a positive direction we would be strongly
counselling to expand that type of study.
Q274 Mr Drew: That information will
be shared with appropriate parties? One of the things which impressed
me about the badger vaccine trial was the degree to which the
scientists were willing and able to talk to the farmers—partly
to keep them on board—about whether they thought what they
were doing was of value.
Professor Young: I think we do
chime with the public, people like the idea of vaccinating.
Q275 Mrs Moon: I would just like
to clarify a few things for myself. You have talked about the
trapping having stopped which means whatever results you are going
to have are going to be delayed another year because of foot and
mouth. You have also said, yes, it would be helpful to have other
areas where you are also carrying out trials so you could have
comparison studies. Can I clarify who would need to agree to those
other areas, and I assume we would also need funding for those
areas?
Professor Young: A fairly substantial
amount of funding to run and you would then have a local team.
I do not know whether you would run out of the number of people
who were very close to CSL on these, how many experts there are
available who could run those trials in the same way.
Q276 Mrs Moon: Do we have the experts
to run those trials or not? Would it be realistic to say let us
have, even if not two, one other trial area so we can compare
the results? Do we have the experts even if we have the money?
Professor Hewinson: What I was
going to say is that this trial is not really to do with working
out how efficacious BCG is, it is about licensing BCG that you
could then take into the field. There are two philosophies: do
you do a lot of field trials that may or may not give you statistically
significant data that you might have to wait a long time to get
both in terms of how effective the vaccine is in badgers and then
how effective it is at stopping TB breakdowns in cattle or do
you focus your efforts in licensing the vaccine by showing that
it has a protective effect in the experimental situation and that
it is safe in the environment and then just rolling that vaccine
out and monitoring how effectively it works. There are two different
philosophies.
Q277 Mrs Moon: Is BCG the only vaccine
that has been trialled? Has anything else been trialled with badgers
or just the BCG?
Professor Young: Just BCG.
Professor Hewinson: Just BCG.
Q278 Mrs Moon: We have just got BCG.
Can I clarify in terms of the licensing route, which is the one
you are following, is it sufficient in a licensing regime to have
one trial? Is that going to be satisfactory? In the longer term
are you going to come up against a lobby which says, "Hang
on, the science is not good enough because it has only been focused
around one trial"?
Professor Hewinson: I think those
are two different things. You have got the licensing issue where
if you show that the vaccine is safe experimentally and safe in
the environment in the natural situation, and you show that the
vaccine can do what it says on the bottle experimentally, then
you can get a licence to use that vaccine. How you then use it
and how you apply it and how effective it is is the second question.
Q279 Mrs Moon: My question was, is
one trial enough for those two routes?
Professor Hewinson: I do not think
this trial is going to give you strong enough statistics in order
to tell you how effective the vaccine is. It will be good enough
for licensing but it will not allow you to tell how effective
a vaccine will be used in the field. To do that you would either
need to do further trials or you would need to roll that vaccine
out, it may be in specific areas, and see how effective it is,
so monitor it as you use it.
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