Memorandum 15
Submission from the Biotechnology and
Biological Sciences Research Council (BBSRC)
BACKGROUND
1. BBSRC[13]
is the UK's principal funder of basic and strategic bioscience.
To deliver our mission, we support research and postgraduate training
in universities and research centres throughout the UK, including
seven BBSRC-sponsored institutes. We also promote knowledge transfer
from basic research to applications in business, industry and
policy, and foster public engagement in the biosciences.
2. As a major public funder of bioscience,
BBSRC invests over £40 million per annum in research and
training on a wide range of pathogens of plants, animals and humans.
We work with sister research councils such as MRC and NERC where
our research interests are complementary. Over half of BBSRC's
funding for research on plant and animal pathogens is deployed
through key BBSRC-sponsored institutes (see below), with the remainder
going to leading University departments.
In summary BBSRC wishes to make the following
main points to the Committee:
— Excellent basic bioscience research
is essential to combat the threat of dangerous pathogens and to
minimise their economic and social impact. It is not only human
and livestock pathogens that present a risk but also those of
key crops upon which the farming economy and food production depends.
— Most of the UK's capacity to work
on dangerous pathogens of livestock and plants rests in BBSRC-sponsored
institutes. This is particularly the case with animal disease
where the Institute for Animal Health (IAH) is a major international
centre of excellence.
— The BBSRC institutes are a vital
national resource and provide the Government with crucial expertise
and unique facilities not available in universities.
— It is essential that institutes such
as IAH are financially sustainable to maintain investment in skills
and modern well equipped facilities, are able to work with dangerous
pathogens and are well governed.
— The ongoing redevelopment of IAH-Pirbright
as a national centre for surveillance, diagnosis and research
on exotic viral pathogens of animals must continue with all partners
(BBSRC and Defra) committed and sharing the full costs.
3. In making this submission we focus on
the first three points raised by the IUS Committee (current capacity,
state of biosecurity facilities and inspection/licensing). The
remaining points are covered in the joint response from BBSRC,
MRC and NERC via RCUK.
DANGEROUS PATHOGENS[14]
POSE A
SIGNIFICANT ECONOMIC
AND SOCIAL
THREAT
4. Infectious pathogenic organisms pose
a major risk of disease to plants (crops), animals and people,
where the health, economic and social impacts are potentially
huge—for example, the 2001 foot and mouth disease (FMD)
outbreak was estimated to have cost the UK economy around £8
billion.[15]
5. The threat posed by dangerous pathogens
is increasing with growing international movement of people, livestock
and agricultural products. This is compounded by the effects of
climate change that expose the UK to emergent diseases—eg,
the first cases of bluetongue virus in the UK were recorded in
summer 2007. Zoonotic infections,[16]
including major foodborne pathogens, also continue to pose risks
to public health. These include transmissible spongiform encephalopathies
(eg BSE/vCJD), avian influenza, SARS, Salmonella and E.coli
O157.
6. Plant pathogens (fungi, bacteria, viruses
and invertebrates), although not directly a human health issue,
nevertheless have the potential to cause significant economic
and amenity loss. In the 1970s the introduction of Dutch elm disease
changed the face of the UK countryside with the destruction of
millions of trees. Recently Sudden Oak Death has arrived, prompting
concerns that further losses of native trees may occur. It is
only the availability of modern fungicides and other agrochemicals
that prevent significant yield losses of many priority crops due
to pathogens.
7. Despite the UK's phytosanitary regulations
and practices (administered by Defra) several significant plant
diseases pose a threat to the UK. Warmer summers could result
in the emergence of diseases that have not previously thrived
under UK conditions. One example is black stem rust; an aggressive
disease of wheat. In 2007, a particularly virulent strain of this
disease (Ug99) spread to Yemen from East Africa, following the
first discovery in Uganda in 1999. There are now concerns that
it could spread both to Europe and Asia. UK wheat cultivars have
not been bred to resist this disease, and its arrival could result
in significant increases in fungicide use and associated cost
increases to the industry. A precedent for such pandemic expansion
has already occurred with the spread of soybean rust out of Africa
into South America in 2001 (and subsequently the southern USA),
resulting in the need for fungicide treatment on the soybean crop
for the first time.
SCIENCE IS
VITAL TO
COMBAT THE
THREAT OF
DANGEROUS PATHOGENS
8. High quality basic and strategic bioscience
is essential to prevent or treat disease outbreaks. Research provides
an understanding of the infectious organism and its interaction
with the host. This knowledge underpins the development of rapid
and reliable diagnostic tests, and effective vaccines, therapies
or other control strategies. With the support of mathematical
modelling and epidemiological data, scientific research determines
our ability to implement an effective response to dangerous pathogens
and to minimise their impact.
9. Examples of where science has been instrumental
in responding to outbreaks include the recent cases of bluetongue
in the East of England (see Annex 1 for the bluetongue story)
and in the 2007 FMD outbreak, where state-of-the-art genome sequencing
promptly identified the order in which farms became infected (techniques
developed from fundamental genetic research at IAH), and where
rapid diagnosis was provided through the development of a lateral
flow device for the detection of FMD virus particles. Results
were delivered to Defra within one hour of the samples being received
at Pirbright.
OVERARCHING RESPONSIBILITY
FOR BIOSECURITY
10. Where research is undertaken through
BBSRC grants to universities, the university is responsible for
biosecurity. Where the research is undertaken in a BBSRC institute
then health and safety and biosecurity are the responsibility
of the institute Director, who is accountable to Council though
the BBSRC Chief Executive and is responsible to the Chair of the
respective governing body. The Director cannot delegate or devolve
this accountability but may delegate duties and authority to senior
members of the management team. The remainder of this submission
refers mainly to the institutes.
POINTS RAISED
BY THE
IUS COMMITTEE
(a) The current capacity for research
on dangerous pathogenic material in the UK and the capability
to conduct research on the causative agents of disease that may
emerge at a future time
Animal pathogens
11. Capacity for research on dangerous pathogens
of animals is concentrated mainly in the BBSRC-sponsored Institute
for Animal Health and the Veterinary Laboratories Agency. There
is further capacity, though small in comparison to IAH and VLA,
at the Roslin Insititute (work on transmissible spongiform encephalopathies),
Moredun Research Institute (Scottish Government-sponsored) and
a few universities, typically in vet schools.
12. The IAH is a world leading centre[17]
of excellence for research on diseases of farm animals and has
disease containment and other facilities that are unique in the
UK. IAH hosts world, EU and regional reference laboratories for
a number of diseases and its work provides vital support to Defra
through independent scientific and policy advice, disease surveillance,
diagnosis and response to disease outbreaks. The journal Nature
in an editorial in its 20 September 2007 edition stated:
"The IAH is central to Britain's ability
to protect itself against future outbreaks of animal disease,
whether unleashed by natural causes, human error or enemy action.
It also has a vital role in these issues internationally. To fulfil
these roles the institute requires (and indeed has) a world-class
research base that lets it address key scientific questions and
at the same time maintain and develop the techniques needed to
identify and deal with diseases".
13. The ability of IAH-Pirbright to work
with pathogens such as foot and mouth disease virus in large animal
hosts in bio-containment facilities is a major asset and is lacking
in the university sector.
Foodborne zoonoses
14. UK capacity to conduct research on pathogens
responsible for foodborne zoonoses is located mainly in the BBSRC
Institute of Food Research (IFR), IAH and strong university groups
eg Cambridge and Birmingham. IFR currently has the capacity to
conduct research across the full range of foodborne and gut pathogens
and associated toxins, working with organisms at ACDP Hazard Group
1, 2 and 3. IFR has one of the very few facilities within the
UK able to deal with Clostridium botulinum (the causative agent
of botulism) and any associated major outbreak.
Plant pathogens
15. Defra Plant Health Division administers
and issues licences to import, move or keep prohibited plant pathogens
(and invertebrates). Capacity to work on quarantined or licensed
plant pathogens is concentrated in BBSRC institutes such as Rothamsted
Research and the John Innes Centre, or in other PSREs such as
the Scottish Crop Research Institute, Central Science Laboratory
(Defra) and Forest Research. Some universities, especially those
linked to former research institutes, such as Warwick HRI, also
have some capability. The UK commercial sector has limited capability
with the shift of the agrochemical and biotech industries to mainland
Europe and the USA. Syngenta (Jealott's Hill) is the only large
industry research facility remaining.
Future capability?
16. It is not possible to predict the full
range of pathogens that will threaten the UK in the future; eg
avian flu hardly featured in disease strategies a few years ago.
It is clear, however, that climate change and increased mobility
of people, livestock and food products will increase the disease
threats at our borders. The UK must therefore maintain sufficient
flexible research capability to work not only on the pathogens
that we can see pose a potential threat but also on those that
will surprise us.
17. In the field of animal disease research,
IAH is clearly a national centre but its facilities and infrastructure
are in need of replacement (see below on "state of UK facilities"
for more details). The planned redevelopment of IAH-Pirbright
by BBSRC and Defra will result in state-of-the-art containment
facilities due to be commissioned in 2012. But the cost has risen
and it is vital that all partners make the necessary funding commitments
to see the project through.
18. The future capacity for research on
dangerous pathogens of animals needs to be considered more widely
than just BBSRC Institutes. There are benefits to maintaining
the strong linkages between basic and strategic research and wider
diagnostics. We are therefore of the view that there needs to
be an overarching national strategy, involving all associated
public funding bodies (eg Defra, MOD, HEIs and devolved governments),
and considering resources at Veterinary Laboratories Agency (VLA),
Porton Down and the veterinary schools together with those of
BBSRC institutes.
19. The UK's current capacity to work on
zoonotic organisms and emergent plant pathogens is probably adequate.
Facilities for work on insect-transmitted plan diseases, such
as those caused by viruses and phytoplasmas, which are likely
to increase in importance with climate change, are currently limited
to a few Institutes (eg BBSRC-sponsored Rothamsted Research) that
have containment facilities for both insect vectors and microbial
pathogens, and hence are well placed for future eventualities.
There are now concerns however that UK expertise in practical
crop pathology is eroded to the extent that we do not have sufficient
expert capability in place to quickly indentify and deal with
all of the potential plant disease problems that could emerge.
We accept that this is a side issue to containment facilities,
but it is highly relevant to future capability.
(b) The state of biological containment
facilities in the UK
20. We are aware of no specific issues with
the containment facilities necessary to conduct research on foodborne
zoonotic organisms or plant pathogens for which BBSRC is the funder.
In fact BBSRC institutes have some of the best facilities nationally.
The remainder of this section of the submission therefore deals
with the state of biological containment facilities for work on
animal pathogens.
The IAH estate
21. Over the past decade, BBSRC has been
actively restructuring its institutes to maintain crucial capabilities
and secure national facilities to support their long-term sustainability.
22. Given the nature of the work at IAH,
modern facilities and high-level biosecurity must be of the utmost
importance. BBSRC has already recognised the need to modernise
the IAH estate and has set in train a multi-million pound investment
as follows:
Pirbright
23. In 2002 BBSRC Council commissioned a
review[18]
(chaired by Professor Keith Gull) on IAH-Pirbright. The report
found the condition of much of the Pirbright site infrastructure
was unsatisfactory and identified a clear need for urgent investment
in new laboratories and facilities. BBSRC Council quickly took
forward the recommendations from the report, leading to the ongoing
major redevelopment of the Pirbright site in partnership with
Defra following a further review of UK facilities Dr by Richard
Cawthorne, the then Deputy Chief Veterinary Officer.
24. The redevelopment includes the relocation
of the virology work at the VLA from its current location at Weybridge
to the Pirbright site, joining IAH virology research in a new
state-of-the-art laboratory complex. Once the new development
is operational (scheduled for 2012) it will be one of the foremost
facilities in Europe and probably the World.
25. The cost of the project was estimated
in 2003 at £121M to be jointly funded by BBSRC, the DIUS
Large Facilities Capital Fund and Defra. But the cost now looks
certain to rise to accommodate regulatory changes, market conditions
and high inflation for building work. It is vital that the partners
in this ambitious development continue to invest and meet fully
their share of the revised cost of £165 million.
26. Following the foot and mouth outbreak
in summer 2007 the Government commissioned two reports to investigate
any possible link between the outbreak and the Pirbright site,
which is shared by the IAH and Merial Animal Health Ltd. The HSE
was asked to investigate potential breaches of biosecurity and
Professor Brian Spratt was asked to examine more broadly the safety
of UK facilities handling FMD virus.
27. Whilst the CL4 facilities at IAH-Pirbright
met Defra licensing requirements, the HSE report concluded that
it was highly likely that the FMD virus originated from the Merial
or IAH sites at Pirbright, most likely through a drain that was
no longer in good repair, and that the virus was carried off site
by a contractor's vehicles. If this is correct then it is an unfortunate
irony that the presence of contractors on site was part of the
construction of the new high containment laboratories.
28. Professor Spratt in his report underlined
that the redevelopment at IAH-Pirbright should continue as a matter
of urgency—a point clearly endorsed by the Government in
its formal response.[19]
Professor Spratt made two recommendations that are particularly
relevant to the UK's future capability:
— Recommendation 10 urges a re-examination
of the Pirbright development plans to ensure that all safety critical
issues have been addressed.
— Recommendation 12 proposes that given
biosecurity is of utmost importance then there should be a review
of funding, governance and risk management at IAH-Pirbright to
ensure an appropriate focus on biosafety and biosecurity in the
future.
29. BBSRC is pursuing both of these recommendations
with due urgency. The latter review (recommendation 12) is being
chaired by Professor Sir John Beringer (ex ProVC of the University
of Bristol and current member of the Government's Council for
Science and Technology). BBSRC Council has asked Sir John's review
to look at the future of IAH as a whole (not just the Pirbright
site) and he will report in April 2008 on the most appropriate
future governance, funding and risk management arrangements for
this key institute. The IUS Committee may wish to invite Sir John
to give oral evidence in its current inquiry.
Compton
30. The IAH-Compton site, with its focus
on research on endemic diseases of livestock, also requires major
work to bring it to modern standards; some of the buildings are
no longer usable. An estates strategy is being developed to modernise
or replace the Compton research facilities and meet regulatory
needs. Options include redevelopment at Compton or moving to another
site, possibly co-location with Pirbright.
31. Pending the outcome of Sir John Beringer's
review, and if Compton is to be replaced in full, then the necessary
investment could be as high as £220 million over the next
six to seven years. BBSRC would meet 50% of the costs and would
be looking for a substantial contribution from the DIUS Large
Facilities Capital Fund.
(c) Laboratory inspection regimes and
the rationale and practicalities of the licensing system
32. We agree with the recommendations made
recently in the report by Sir Bill Callaghan on the regulatory
framework for animal pathogens.[20]
In BBSRC's view the new single regulatory framework, which is
to be in place by the end of 2008, must address the following:
— There should be a single, independent
regulator for all aspects of work involving animal pathogens.
The regulator needs to be independent of, and separate from any
funder, customer or governor. We endorse the proposal that HSE
takes on this role.
— There should be a single regulatory
framework that is applied consistently and transparently.
It emerged from the Spratt and HSE reports into the first phase
of the 2007 FMD outbreak that the conditions of IAH and Merial's
SAPO 4 licences issued by Defra were different, even though the
two organisations were on the same site, sharing infrastructure
and working with the same viruses, albeit in vastly different
quantities—IAH in millilitre volumes and Merial in thousands
of litres.
The crucial inconsistency was that Merial's SAPO
4 licence allowed the company to discharge live virus material
into a drainage system whereas the IAH licence did not. The drain
was neither designed for live virus nor operated on the basis
that live virus would be entering the system; furthermore the
lease from IAH to Merial prohibited the release of such substances
in to the drain.
There was a lack of transparency because neither
Defra nor Merial informed IAH of the Company's licensing conditions.
Defra took the view that all licensing matters are confidential
between Defra and the licensee, even when there were two parties
operating on the same site and using shared infrastructure. Our
view, reinforced by events subsequent to the FMD outbreak, is
that all aspects of regulation must be transparent and any changes
to a licence for one operator on a site where there are multiple
operations must be consulted upon with all those occupying the
site.
— There must be an expert regulator
that understands the risk and cost benefit balance of
its regulatory impacts and has the capacity and expertise, potentially
international, in biocontainment infrastructure to audit to an
appropriate level containment facilities such as those at IAH.
Again, we would have confidence in HSE being such a regulator.
January 2008
Annex
THE SCIENCE
BEHIND BLUETONGUE
Bluetongue virus (BTV) causes a severe disease
in some ruminants such as sheep and cattle. Biting midges spread
the virus between animals, and sheep are particularly prone where
symptoms include fever, lameness, rapid loss of condition and
muscle wastage. Bluetongue is historically rare in Europe but
over the past eight years it has killed over 1.5 million sheep,
across 12 EU countries. Major outbreaks in the Mediterranean Basin
and Balkans in 1998 were followed by the first cases in northern
Europe in 2006 and the first in the UK in 2007.
Researchers at the IAH-Pirbright laboratory
have long been tracking the progress of bluetongue northwards
and advising that it would eventually reach the UK. Institute
scientists were the first to show that the bluetongue virus could
swap hosts to other species of midge and that infected insects
could be carried long distances on the wind.
In collaboration with the Universities of Cambridge
and Liverpool, IAH scientists developed new mathematical models
that showed the critical role of temperature in the infection
process. Too cold and the virus will not build-up sufficiently
in the midge for effective infection; too hot and the midges might
die before they are able to transmit the virus. Crucially the
work predicted that the UK would be suitable for the establishment
and spread of bluetongue.
The UK farming community was bracing itself
for a bluetongue outbreak in 2007 after IAH scientists in collaboration
with the Met Office used meteorological analysis of the northern
European outbreak in 2006 to show that the temperatures were ideal
for rapid multiplication of the virus in the midges, and easterly
winds in 2007 could easily carry the biting insects to south eastern
England.
IAH is the Bluetongue Reference Laboratory on
behalf of the European Union and the World Organisation for Animal
Health (OIE). As a world centre for bluetongue research IAH has
helped to provide detailed knowledge of the virus and its molecular
structure; knowledge that is essential for rapid and accurate
diagnosis. On the same day in 2007 that IAH confirmed the presence
of bluetongue virus in Suffolk, tests showed that the virus was
of the same serotype as was in Belgium and neighbouring countries,
thus confirming earlier predictions about the spread of the disease.
During the 2007 bluetongue outbreak, IAH has
been able to make a diagnosis within two hours for the antibody
test, and within six hours for the test that detects the bluetongue
virus' genetic material (RNA) on blood samples received from a
farm where bluetongue is suspected. This service is provided seven
days a week. The testing of blood samples taken from animals in
the control zone (in which infected animals have been confirmed)
and in the surrounding protection zone helps to identify whether
the disease is spreading further, and the limits to which it has
spread.
The institute scientists and collaborators are
currently investigating many aspects of bluetongue transmission
and risk in several ongoing projects, using techniques from field
collections and laboratory experiments to computer modelling and
satellite imagery. Recent work has described a novel mechanism
for the virus to conceal itself within host immune cells, which
may offer some insight into the puzzling ability of the virus
to reappear in areas after long periods of absence and without
any apparent reintroduction event.
13 BBSRC, a non-departmental public body, is one of
seven Research Councils supported through the Science and Innovation
Group of the Department for Innovation, Universities and Skills
(DIUS). BBSRC works with partner Research Councils through RCUK. Back
14
We take dangerous pathogens to mean those included in: The
Advisory Committee on Dangerous Pathogens (ACDP) Approved List
of biological agents, for the purposes of the COSHH Regulations
2002 (particularly the Group 3 and Group 4 biological agents);
Specified animal pathogens listed in Part I of the Schedule
to the Specified Animal Pathogens Order 1998; Human and animal
pathogens covered by the Home Office "Pathogens and Toxins
Guidance" (ATCSA 2001 Schedule 5 Order 2007 Notes; and
The Plant Health (England) Order 2005 as amended, and equivalent
regulations. Back
15
Economic costs of the foot and mouth disease outbreak in the
United Kingdom in 2001. D Thompson et al (2002). Rev sci
tech Off int Epiz, 21 (3), 675-687. Back
16
Zoonotic infections are those that can pass from animals/livestock
to people. Back
17
Research within IAH is split over two sites: IAH-Compton-endemic
disease, (eg TB, Salmonella); unique resources for immunology
in cattle (MHC herd) and chicken (for avian flu work). IAH-Pirbright-exotic
viral diseases (eg foot and mouth, bluetongue), world reference
laboratories. Unique facilities in the UK for working with disease
agents in large animals. Back
18
Review of the Institute for Animal Health-Pirbright Laboratory:
http://www.bbsrc.ac.uk/organisation/policies/reviews/operational/0207_iah-pirbright.html Back
19
http://www.defra.gov.uk/animalh/diseases/fmd/investigations/pdf/govstatement_fmd2007.pdf Back
20
http://www.defra.gov.uk/animalh/diseases/fmd/investigations/bill-callaghan.htm Back
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